The comparison between ACE and ACE2 is given in Table 1 [22, 23, 24, 25, 26].
\\n\\n
These books synthesize perspectives of renowned scientists from the world’s most prestigious institutions - from Fukushima Renewable Energy Institute in Japan to Stanford University in the United States, including Columbia University (US), University of Sidney (AU), University of Miami (USA), Cardiff University (UK), and many others.
\\n\\nThis collaboration embodied the true essence of Open Access by simplifying the approach to OA publishing for Academic editors and authors who contributed their research and allowed the new research to be made available free and open to anyone anywhere in the world.
\\n\\nTo celebrate the 50 books published, we have gathered them at one location - just one click away, so that you can easily browse the subjects of your interest, download the content directly, share it or read online.
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IntechOpen and Knowledge Unlatched formed a partnership to support researchers working in engineering sciences by enabling an easier approach to publishing Open Access content. Using the Knowledge Unlatched crowdfunding model to raise the publishing costs through libraries around the world, Open Access Publishing Fee (OAPF) was not required from the authors.
\n\nInitially, the partnership supported engineering research, but it soon grew to include physical and life sciences, attracting more researchers to the advantages of Open Access publishing.
\n\n\n\nThese books synthesize perspectives of renowned scientists from the world’s most prestigious institutions - from Fukushima Renewable Energy Institute in Japan to Stanford University in the United States, including Columbia University (US), University of Sidney (AU), University of Miami (USA), Cardiff University (UK), and many others.
\n\nThis collaboration embodied the true essence of Open Access by simplifying the approach to OA publishing for Academic editors and authors who contributed their research and allowed the new research to be made available free and open to anyone anywhere in the world.
\n\nTo celebrate the 50 books published, we have gathered them at one location - just one click away, so that you can easily browse the subjects of your interest, download the content directly, share it or read online.
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Frank",slug:"craig-l.-frank",email:"frank@fordham.edu",position:null,institution:{name:"Fordham University",institutionURL:null,country:{name:"United States of America"}}}]},book:{id:"11032",title:"Bats",subtitle:"Disease-Prone but Beneficial",fullTitle:"Bats - Disease-Prone but Beneficial",slug:"bats-disease-prone-but-beneficial",publishedDate:"April 20th 2022",bookSignature:"Heimo Mikkola",coverURL:"https://cdn.intechopen.com/books/images_new/11032.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"144330",title:"Dr.",name:"Heimo",middleName:"Juhani",surname:"Mikkola",slug:"heimo-mikkola",fullName:"Heimo Mikkola"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}}},ofsBook:{item:{type:"book",id:"9985",leadTitle:null,title:"Geostatistics",subtitle:null,reviewType:"peer-reviewed",abstract:"
\r\n\tGeostatistical modeling too often falls into the trap of "button pushing" on commercial software without an understanding of the basic underlying principles. After more than 30 years of teaching earth modeling classes, it is clear that the base knowledge of geostatistical principles has grown amongst earth modelers, yet, there remains a great deal more to learn. Many modelers today have become lost in software products and rely too heavily on embedded defaults, or suggestions from colleagues.
\r\n\r\n\tThis book is intended to be a companion to modelers interested in knowing the practical meaning of what is behind the buttons they are pushing. It is not a textbook on the mathematics of geostatistics or the evolution of its theory. It is a guide to help make practical decisions and simply explain the “why” and “how” of what works and what does not. Further, it will attempt to answer questions where difficult choices and resulting implications are not clear; e.g. What variogram model should I use? What simulation algorithm is best? How many realizations should I run? After a review of basic principles and common pitfalls, case study examples will be drawn from both conventional and unconventional reservoirs. The case studies will be followed by a constructive review from a panel of experts geostatisticians articulating both strong and weak points of the models, and offer suggestions. Finally, the impact of high-performance computing, machine learning, data analytics (big and small), Python, and R will be discussed with a view towards successful earth modeling for the next decade.
",isbn:"978-1-83968-502-6",printIsbn:"978-1-83968-501-9",pdfIsbn:"978-1-83968-503-3",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!0,isSalesforceBook:!1,isNomenclature:!1,hash:"423cb3896195a618c4acb493ce4fd23d",bookSignature:"Prof. Jeffrey M. Yarus, Dr. Marko Maucec, Dr. Timothy C. Coburn and Associate Prof. Michael Pyrcz",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/9985.jpg",keywords:"Variograms Kriging, Conditional Simulation, Nugget Effect, Nested Models, Clastic Hydrocarbon Reservoirs, Carbonate Hydrocarbon Reservoirs, Geothermal, Solar, Soil, Nitrates, Machine Learning, Advanced Data Analytics",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"August 25th 2021",dateEndSecondStepPublish:"November 1st 2022",dateEndThirdStepPublish:"December 31st 2022",dateEndFourthStepPublish:"March 21st 2023",dateEndFifthStepPublish:"May 20th 2023",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"4 months",secondStepPassed:!1,areRegistrationsClosed:!1,currentStepOfPublishingProcess:2,editedByType:null,kuFlag:!1,biosketch:"Professor at the Case Western Reserve University with more than 42 years of industry experience, one of the creators of the Earth Modeling software in 2006 that is a core module on the DecisionSpace Geoscience Suite even today.",coeditorOneBiosketch:"Dr. Maucec is a Petroleum Engineering Consultant with Reservoir Description and Simulation Department at Saudi Aramco in Saudi Arabia. He has authored more than 80 peer-reviewed and professional conference papers, co-authored a reference book on Intelligent Digital Oil & gas Fields, and is an inventor on 30 US patents and patent applications. Formerly, he has worked internationally with Halliburton/Landmark, Shell International E&P, and in nuclear research and industry.",coeditorTwoBiosketch:"Dr. Tim Coburn is a Professor of Systems Engineering at Colorado State University (CSU) and Research Associate in the CSU Energy Institute. He also held professional externships at Sandia National Laboratory, the US Geological Survey, and the Kansas Geological Survey, and is active in numerous geoscience, engineering, and energy-related professional organizations.",coeditorThreeBiosketch:"Michael is an Associate Professor in the Department of Petroleum and Geosystems Engineering at the University of Texas at Austin. Michael has written over 60 peer-reviewed publications, a Python package, and a textbook on spatial data analytics with Oxford University Press. He is currently an associate editor with Computers and Geosciences, and on the editorial board member for Mathematical Geosciences. Previously, he conducted a great impact and led the research with Chevron’s technology company.",coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"78011",title:"Prof.",name:"Jeffrey M.",middleName:null,surname:"Yarus",slug:"jeffrey-m.-yarus",fullName:"Jeffrey M. Yarus",profilePictureURL:"https://mts.intechopen.com/storage/users/78011/images/system/78011.jpg",biography:"Jeffrey Yarus is a Professor at the Case Western Reserve University and a retired Halliburton Technology Fellow for Landmark with over 42 years of industry experience. Jeffrey’s specific areas of thought leadership include Earth Modeling and Geostatistics, and he is the technical lead and a Senior Manager of DecisionSpace Earth and Reservoir Modeling software.\r\nEarly in his career, Dr. Yarus enjoyed the opportunity to work with a number of Major Oil Companies and Technology Service Companies including Amoco, Marathon, Beicip-Franlab, and Roxar. In 2001, Yarus and a business partner were responsible for funding their own research and consulting company – Quantitative Geosciences (QGSI) – specializing in applied Earth Modeling. The QGSI staff along with Dr. Yarus joined Landmark Graphics Corporation in 2006 to build an Earth Modeling software product; today a core module on the DecisionSpace Geoscience Suite.\r\nDr. Yarus earned his Ph.D. and master’s degree in Geology from the University of South Carolina and his bachelor’s degree in Geology from the College of Wooster. Yarus served as a Chair of a number of AAPG’s committees including the Computer Applications, Publications, and Reservoir Development Committees. He has authored many papers and abstracts on reservoir modeling and Geostatistics including AAPG volumes on Stochastic Modeling and Geostatistics, the chapter on Reservoir Characterization and Geostatistics and the recent SPE Petroleum Engineering Handbook, Volume 6.\r\nAn acknowledged lecturer and author in the industry, Dr. Yarus earned the distinction of 12-year Adjunct Faculty Member for the University of Houston Department Of Petroleum Engineering. He is one of the senior editors of the Stochastic Modeling volumes in AAPG’s Computer Applications Series. In 2016, Dr. Yarus received the prestigious, George Matheron Lecturer Award from the International Association of Mathematical Geosciences.",institutionString:"Case Western Reserve University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Case Western Reserve University",institutionURL:null,country:{name:"United States of America"}}}],coeditorOne:{id:"429659",title:"Dr.",name:"Marko",middleName:null,surname:"Maucec",slug:"marko-maucec",fullName:"Marko Maucec",profilePictureURL:"https://mts.intechopen.com/storage/users/429659/images/system/429659.jpg",biography:"Marko Maucec is a Petroleum Engineering Consultant with Reservoir Description and Simulation Department at Saudi Aramco, Dhahran, Saudi Arabia. His main responsibilities cover the development and implementation of methods for uncertainty quantification, dynamic model inversion with assisted history matching, production optimization, and data- and physics-driven predictive modeling into reservoir simulation practices. Formerly, Maucec has worked internationally with Halliburton/Landmark, Shell International E&P, and in nuclear research and industry. He has authored more than 80 peer-reviewed and professional conference papers, co-authored a reference book on Intelligent Digital Oil & gas Fields, and is an inventor on 30 US patents and patent applications. Maucec holds Ph.D. and MSc degrees in Nuclear Engineering and BSc degree in Electrical Engineering. 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Previously, Coburn served as Founding Director, School of Energy Economics, Policy and Commerce at The University of Tulsa, and Founding Director, School of Information Technology and Computing, Abilene Christian University. Prior to his academic career, Coburn worked in various administrative and technical positions in the data science arena at Marathon Oil Company, Phillips Petroleum Company, and the National Renewable Energy Laboratory. He also held professional externships at Sandia National Laboratory, the US Geological Survey, and the Kansas Geological Survey, and is active in numerous geoscience, engineering, and energy-related professional organizations. He currently serves on the lectures committee of the International Association of Mathematical Geoscientists (IAMG), the education advisory committee of the Professional Petroleum Data Management (PPDM) Association, and the energy statistics committee of the American Statistical Association (ASA). Coburn is the author of numerous technical and professional publications, and, with Jeffrey Yarus, is co-editor of two prior texts on spatial data analysis: Geographic Information Systems in Petroleum Exploration and Development and Stochastic Modeling and Geostatistics, Vol. 2.",institutionString:"Colorado State University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Colorado State University",institutionURL:null,country:{name:"United States of America"}}},coeditorThree:{id:"437107",title:"Associate Prof.",name:"Michael",middleName:null,surname:"Pyrcz",slug:"michael-pyrcz",fullName:"Michael Pyrcz",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003FVU4kQAH/Profile_Picture_1640088624476",biography:"Michael is an Associate Professor in the Department of Petroleum and Geosystems Engineering, Cockrell School of Engineering and the Department of Geological Sciences and Bureau of Economic Geology, Jackson School of Geosciences at The University of Texas at Austin where he teaches and conducts research on subsurface data analytics, geostatistics and machine learning. In addition, Michael accepted the role of Principal Investigator in the College of Natural Sciences, The University of Texas at Austin, of the freshman research initiative in energy data analytics and teaches widely in the energy industry. Before joining The University of Texas at Austin, Michael conducted and led research on reservoir data analytics and modeling for 13 years with Chevron’s technology company. He was an enterprise-wide subject matter expert, advising and mentoring on workflow development and best practice. Michael has written over 60 peer-reviewed publications, a Python package and a textbook on spatial data analytics with Oxford University Press. He is currently an associate editor with Computers and Geosciences, and on the editorial board member for Mathematical Geosciences. For more information see www.michaelpyrcz.com, and his course lectures at https://www.youtube.com/GeostatsGuyLectures, along with the demonstration numerical workflows at https://github.com/GeostatsGuy and contributions to outreach through social media at https://twitter.com/GeostatsGuy.",institutionString:"The University of Texas at Austin",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"The University of Texas at Austin",institutionURL:null,country:{name:"United States of America"}}},coeditorFour:null,coeditorFive:null,topics:[{id:"10",title:"Earth and Planetary Sciences",slug:"earth-and-planetary-sciences"}],chapters:null,productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"429341",firstName:"Paula",lastName:"Gavran",middleName:null,title:"Ms.",imageUrl:"//cdnintech.com/web/frontend/www/assets/author.svg",email:"paula@intechopen.com",biography:null}},relatedBooks:[{type:"book",id:"5962",title:"Estuary",subtitle:null,isOpenForSubmission:!1,hash:"43058846a64b270e9167d478e966161a",slug:"estuary",bookSignature:"William Froneman",coverURL:"https://cdn.intechopen.com/books/images_new/5962.jpg",editedByType:"Edited by",editors:[{id:"109336",title:"Prof.",name:"William",surname:"Froneman",slug:"william-froneman",fullName:"William Froneman"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1591",title:"Infrared Spectroscopy",subtitle:"Materials Science, Engineering and Technology",isOpenForSubmission:!1,hash:"99b4b7b71a8caeb693ed762b40b017f4",slug:"infrared-spectroscopy-materials-science-engineering-and-technology",bookSignature:"Theophile Theophanides",coverURL:"https://cdn.intechopen.com/books/images_new/1591.jpg",editedByType:"Edited by",editors:[{id:"37194",title:"Dr.",name:"Theophile",surname:"Theophanides",slug:"theophile-theophanides",fullName:"Theophile Theophanides"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3161",title:"Frontiers in Guided Wave Optics and Optoelectronics",subtitle:null,isOpenForSubmission:!1,hash:"deb44e9c99f82bbce1083abea743146c",slug:"frontiers-in-guided-wave-optics-and-optoelectronics",bookSignature:"Bishnu Pal",coverURL:"https://cdn.intechopen.com/books/images_new/3161.jpg",editedByType:"Edited by",editors:[{id:"4782",title:"Prof.",name:"Bishnu",surname:"Pal",slug:"bishnu-pal",fullName:"Bishnu Pal"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3092",title:"Anopheles mosquitoes",subtitle:"New insights into malaria vectors",isOpenForSubmission:!1,hash:"c9e622485316d5e296288bf24d2b0d64",slug:"anopheles-mosquitoes-new-insights-into-malaria-vectors",bookSignature:"Sylvie Manguin",coverURL:"https://cdn.intechopen.com/books/images_new/3092.jpg",editedByType:"Edited by",editors:[{id:"50017",title:"Prof.",name:"Sylvie",surname:"Manguin",slug:"sylvie-manguin",fullName:"Sylvie Manguin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"371",title:"Abiotic Stress in Plants",subtitle:"Mechanisms and Adaptations",isOpenForSubmission:!1,hash:"588466f487e307619849d72389178a74",slug:"abiotic-stress-in-plants-mechanisms-and-adaptations",bookSignature:"Arun Shanker and B. 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Compared with many other inorganic pigments, TiO2 has the advantages of high stability, being non-toxic, and low cost. TiO2 have three polymorphs: anatase, rutile and brookite, but only anatase and rutile crystal forms have been useful as pigment. Both anatase and rutile crystals have very high refractive indices, and their particles can scatter visible light almost completely [1]. The optimum particle size of TiO2 for pigment applications is around 250 nm. In the early application of TiO2 as pigment, it was found that paint faded more rapidly than others when painted films were exposed to the Sun and ultraviolet (UV) light. Coating with inorganic compounds such as alumina or silica suppressed the catalytic activity on the surface and improve the weather resistance, leading titanium dioxide in wide applications as white pigment. Global titanium dioxide pigment sales were about 6 million tons in 2017 and the growth trend of global titanium dioxide pigment sales is continuing over the recent years [2].
In the 60s of the last century, scientists studied the photo-induced phenomena on the solids of TiO2 and ZnO under UV light irradiation [3, 4, 5]. In the early 1970s, research on photocatalysis by TiO2 got wide attention due to the historic discovery of the electrochemical water splitting by use of TiO2 [6]. In the 1990s, photocatalytic research of TiO2 had made progress in the practical applications of TiO2 in the decomposition of harmful organic materials [7, 8]. A function of super hydrophilicity of TiO2 was also discovered [9]. Since the beginning of this century, nano-structured TiO2 has attracted extensive interests. When the particle sizes of TiO2 are reduced down to the nano-meter scale (generally in 1–100 nm), the surface characteristics and surface areas of TiO2 have changed dramatically. The new or enhanced physical and chemical properties of nano-structured TiO2 begin to emerge. The photocatalytic property of nano-structured TiO2 has been greatly enhanced because of the changes in the surface characteristics and surface areas. Quantum effects of nano-structured TiO2 can also have a role to play, affecting its photocatalytic, optical or electronic properties. As the results of academic and industrial research in recent years, enormous progresses have been made in the preparation, characterization, and scientific understandings of nano-structured TiO2. Nano-structured TiO2 have begun to find applications in a wide range of areas including electronic materials, energy, environment, health & medicine, sensors, catalysts, etc.
TiO2 pigment is industrially produced from titanium containing ores by using a Chloride or Sulfate process [1, 10]. Nano-structured TiO2 are made in the different ways, depending on the material characteristics required for the specific applications. A number of innovative fabrication methods of nano-structured TiO2 materials have been developed and are used for different applications. These methods can be broadly classified as the liquid phase or the gas phase methods. Nano-particles, nano-wires, nano-tubes, two or three-dimensional nano-structured TiO2 materials can also be fabricated for different applications [11, 12, 13, 14, 15, 16, 17, 18].
This chapter will discuss and highlight the recent development of applications of titanium dioxide as pigment and as functional materials in the areas of energy, environment, catalyst, and biomedicine.
The main use of titanium dioxide is white pigment, because it absorbs almost no incident light in the visible region of the spectrum (380–700 nm). Titanium dioxide has a strong light scattering power, and scatters incident light in three ways: surface reflection, refraction and diffraction in the crystal [1]. When the refractive index difference between titanium dioxide and medium increases, the reflected light increases and complies with Eq. (1):
np and nm are the refractive index of pigment and medium, respectively [1]. Titanium dioxide has a high refractive index (refractive index of rutile and anatase titanium dioxide is 2.70 and 2.55 respectively) [19]. These high refractive index values enable the rutile and anatase TiO2 pigments to have much greater hiding power in coatings or in plastics, making TiO2 to be a much better pigment than the other chemical substances. Therefore, under the same conditions, only less titanium dioxide is needed to form a coating, which is white and opaque. Studies have shown that the optical properties of titanium dioxide pigments are related to their particle size, and the optimum of particle size of pigmentary titanium dioxide is around 250 nm [1].
Pigmentary TiO2 is inert, non-toxic, stable and less costly. Over 50 percent of all TiO2 pigment produced is consumed by the coatings industry, and approximately a quarter by the paper industry. Eleven per cent goes into plastics; remaining a few percent into inks and other end-uses [20]. Titanium dioxide particles optimized with particle size and surface treatments have excellent hiding power, brightness, and other important features such as resistance to chemical degradation. Rutile pigment is more resistant to UV light than anatase, and is preferred for paints, plastics, especially for the applications in outdoor conditions. Anatase pigment is less abrasive and is used mainly in indoor paints and in paper manufacture. TiO2 is surface treated with one or more inorganic oxides such as alumina, silica, zirconia or a combination of these inorganic oxides, and organic compounds such as polyhydric alcohol to have the required properties of dispersion, photoactivity, and opacity required for a specific application [21].
In coating applications, a relatively high quantity of TiO2 pigment must be used to achieve desirable hiding effect on the coating subtracts, because coatings of titanium dioxide are usually in the form of very thin layers. The pigment volume concentration (PVC) is practically used to specify the amount of TiO2 in a coating. Different types of paints containing TiO2 pigment will have different levels of PVC, depending on different coating applications. TiO2 coatings are used to cover a wide range of surfaces, including indoor and outdoor building, wood products, metal objects, domestic and industrial equipment [21].
In plastics applications, titanium dioxide pigment is used to opacify plastic materials. In some applications, TiO2 is used to improve photodurability. The requirements for TiO2 in plastics are good dispersibility in a polymer system and good heat stability. Hydrophobic organic surface treatments on the pigments are utilized to facilitate their dispersion in the viscous molten plastic resin. These are often silicone oils and other organic compounds for specialized uses. In many plastics applications, a blue undertone is also desirable to mask an intrinsic yellowness in the color of the resin or a slight degradation that occurs during the high-temperature processing. For this reason, plastics pigments often have a smaller crystal size than those for coatings applications [19].
The amount of titanium dioxide used in paper industry is the third largest after coating and plastic industries [20]. Although other white pigments can be used in paper industry, the production of high quality papers must use titanium dioxide as pigment. Titanium dioxide imparts desirable brightness and opacity to high-quality papers. Papers containing titanium dioxide pigment have high strength and have appearance to be white, shiny, thin and smooth. Because photochemical stability is not as critical in paper as in paint, both anatase and rutile pigments are widely be used in paper industry.
In inks applications, performance requirements for TiO2 pigment are different from coatings, plastics and paper. Inks are usually applied to produce a much thinner film on a surface than a general coating. It is very important to choose titanium dioxide particles with good shape, suitable size and size-distribution, smooth surface and non-angular. The type of TiO2 can also affect the rheology, abrasiveness, gloss and redispersibility for ink products and applications.
TiO2 is also widely used as a pigment for coloring of different products in pharmaceuticals and cosmetics industries. The characteristics of titanium dioxide provide interesting colors and allow new properties to pharmaceuticals with very small amounts of pigments. There are many products in this field that contain titanium dioxide, including: shampoos, creams, sunscreens, toothpaste, etc. [10].
With the special physical and chemical properties, nano-structured titanium dioxide has shown a number of promising application prospects in energy generation and storage. These include: solar cells, hydrogen production, and lithium battery [22, 23, 24].
The solar energy is a clean, abundant and renewable energy [25]. The current technology for the conversion of sunlight to electrical power is predominately silicon-based solid state solar cells. In recent years, the new semiconducting material-based solar cells have emerged to offer the possible alternative photovoltaic technology with prospect of cheap fabrication and flexibility [26, 27, 28]. Nano-structured TiO2 has been the main semiconducting material for this new generation of solar cells. In this technology, an electron sensitizer absorbing in the visible is used to inject charge carriers across the semiconductor-electrolyte junction into TiO2 to enhance the conversion efficiency from solar energy, because TiO2 with its band gap of 3.2 electronvolt (eV) absorbs only the ultraviolet part of the solar energy. This type of solar cells is therefore called dye-sensitized solar cells (DSSCs). The dye-sensitized solar cells (DSSCs) have exhibited high performance and have the potential to be low-cost [29, 30, 31, 32, 33].
Figure 1 illustrates the working principle of a dye-sensitized solar cell. The dye-sensitized solar cell consists of two electrodes, a dye-sensitized nano-structured TiO2 mesoporous layer, and a liquid electrolyte containing redox system (
Working principle of a dye-sensitized solar cell.
The nano-structured TiO2 mesoporous layer in a dye-sensitized solar cell has a much larger surface area available for the dye-chemisorptions. The kinetic processes occurring in a dye-sensitized solar cell have been profoundly changed as a result of using nano-structured TiO2. Solar energy-to-electricity conversion efficiencies of DSSCs have been increased. The record for the highest certified single cell and DSSCs module efficiencies are 11.9% and 8.8%, respectively [34].
More recently, TiO2 is used in a new type of solar device so-called pervoskite solar cells. As in DSSCs, TiO2 is used as a mesoporous layer. However, instead of using organic dye in DSSCs, organic lead complex (for example, CH3NH2PbI3) is used to inject electrons into the conduction band of TiO2. In a short period of the recent few years, the reported efficiency of pervoskite solar cells was 9.7% initially, and then 12.0% [35, 36]. Further progress was made with efficiencies above 15.0% [37]. The record for the highest certified single cell and minimodule efficiencies are 20.9% and 16.0%, respectively [34].
In 1972, Fujishima and Honda discovered the phenomenon of photocatalytic splitting of water on a TiO2 electrode under UV light [6, 38, 39]. Compared with other photocatalysts, TiO2 is much more promising as it is stable, non-corrosive, environmentally friendly, abundant and cost effective. Figure 2 illustrates the mechanism of the photocatalytic hydrogen production by TiO2 semiconducting materials. When excited by photons which have energy equal to or higher than their band gap (
Illustration of mechanism of photocatalytic hydrogen production by TiO2.
The photo-generated (e−) and (h+) in TiO2 can recombine, releasing energy in the form of heat or photons. The photo-generated (e−) and (h+) that migrate to the surface of TiO2 without recombination can reduce and oxidize H2O molecules adsorbed on the surface of TiO2 to generate H2 and O2.
As can be seen in Figure 2, the conduction band level of TiO2 is more negative than the hydrogen production level (
Despite many advantages of using TiO2 for photocatalytic hydrogen production, the efficiency using solar energy for water-splitting by TiO2 is still low, and is currently not been used for industrial scale of hydrogen production. The low energy conversion efficiency of TiO2 in water-splitting is believed to be caused by the wasteful recombination of electron/hole pairs, backward reaction of combining hydrogen and oxygen into water, and limitations for TiO2 to utilize visible light due to its large band gap. Research has been carried out to produce nano-structured TiO2 with a narrower band gap in order to utilize visible-light energy more efficiently. Progresses have been made in modifying the band gap of nano-structured TiO2 by means of metal loading, ion doping, metal ion-implantation, dye sensitization and composite TiO2. Noble metals, such as Pt, Au, Pd, and Ag, have been reported to be very effective in enhancing TiO2 photocatalysis [40, 41, 42, 43]. Carbon-doped nano-structured TiO2 have showed much more efficient water splitting under visible-light illumination [44]. A study using a dye sensitizer for photocatalytic hydrogen production was investigated [45]. A visible light absorber, C3N4, has been coupled to many wide-band gap semiconductors to improve solar harvesting. A 50 wt % C3N4/TiO2 junction was found to double H2 evolution compared to pure C3N4 under visible irradiation [46].
Lithium-ion batteries are a type of rechargeable batteries commonly used in consumer electronics. Lithium ion battery system and technology has been a revolutionary change in the field of power supply battery. Anode materials based on titanium oxides are the promising candidates as alternative materials to carbonaceous anodes due to advantages in terms of cost, safety and toxicity [47, 48]. TiO2 also exhibits excellent structural stability, high discharge voltage plateau (more than 1.7 V versus Li+/Li), and excellent cycling stability [49, 50].
Typically the Li+ insertion–extraction reaction for TiO2 polymorphs occurs according to reaction (3):
x can range between 0 and 1, depending strongly on the polymorph, particle size, and morphology of TiO2. The maximum theoretical capacity is 335 mAh g−1 which corresponds to x = 1. This makes TiO2 a highly competitive alternative to graphite anodes having a theoretical capacity of 372 mAh g−1 [51, 52, 53]. However, TiO2 has limitations, such as low capacity, low electrical conductivity, and poor rate capability. Strategies have been developed to address the issues of TiO2-based anodes. These include the use of multi-dimensional nanostructured TiO2, composite and coating materials, and element doping.
One dimensional anatase TiO2 nanofiber anodes were used as an anode active material in Li ion batteries and exhibited a high lithium storage capacity, a stable cycle life, and good rate capability [54]. Two dimensional TiO2 nanosheets have been shown to exhibit the superior capacities, improved cycling stability and rate capabilities, owing to unique exposed facets, shortened path, and reserved porous structures [55, 56, 57]. Nanostructured TiO2 is a low voltage insertion host for Li and a fast Li insertion/extraction host [58, 59]. These characteristics provide nanostructured TiO2 a potential anode material for high-power Li-ion batteries. Studies on the use of nanostructured TiO2 as anode with LiCoO2 cathode demonstrated specific capacity of 169 mAh g−1 [60]. Xu, et al. investigated electrochemical performance of TiO2-coated LiCoO2 and LiMn2O4 in different potential regions [61]. Mechanically blended composite of nanosized TiO2 and carbon nanotubes (CNTs) has been used as potential anode materials for Li-ion batteries. It was found that the TiO2/CNTs nanocomposites exhibited an improved cycling stability and higher reversible capacity than CNTs [62, 63]. Metal oxide coatings containing TiO2 can efficiently improve the capacitive performance of the materials through synergistic effects in an electrode system [64, 65, 66, 67].
Excitation of TiO2 with UV light with energy greater than the band gap (>3.2 eV) promotes electrons from valence band into the conduction band and generates electron/hole pairs [68, 69]. Figure 3 illustrates the mechanism of generating reactive radicals from TiO2 under irradiation of UV light. The conduction band electrons e− can reduce molecular oxygen to generate (O2•−) superoxide radicals, and valance band holes h+ is positive enough to generate (OH•) radicals from H2O or OH− on TiO2 surface. OH• radicals have the strongest oxidation potential. Superoxide radicals (O2•−) have moderate oxidation potentials, but their diffusion distances can reach up to hundreds of micrometers [70]. Both radicals are very reactive, and they attack the organic matter present or near the surface of TiO2 to degrade toxic and bio-resistant compounds or species into CO2, H2O, etc. [69, 71].
Mechanism of generating reactive radicals (OH•) and superoxide (O2•−) from TiO2 under irradiation of UV light.
The generation of reactive radicals (OH•) and (O2•−) is affected by the crystalline state, and properties such as surface area and particle size. Although anatase and rutile have the similar band gaps, anatase has shown to have more rapid rate in photo-degradation of organic or bio-resistant compound than rutile [72, 73]. Therefore, nano-structured anatase TiO2 is often used as a catalyst in photo-degradation applications.
One application, which is commercially successful, is the nano-structured TiO2 material for self-clean and antibacterial uses [68, 74, 75]. Many nano-structured TiO2 material based products have been used as construction materials [76, 77, 78, 79, 80, 81, 82]. Self-clean application is based on the actions of sunlight, rainwater, and photocatalytic properties of TiO2. Under the irradiation of sunlight, adsorbed organic materials like oil can be decomposed by hydroxyl radicals on the surface of TiO2. Because of the hydrophilic property of TiO2 surface, contaminates and dust can be washed away off by rainwater. Tiles containing nano-structured TiO2 have been used to construct photocatalytic surface to decompose bacteria and viruses on the surface or bacteria floating in the air as they come in contact with surface.
Studies have shown that the photocatalytic properties of TiO2 can sometimes be enhanced by doping TiO2 with different elements. For example, TiO2 nano-particles containing Ag+ have been widely used in antibacterial plastics and coatings [83, 84, 85]. Fe or Sb-doped TiO2 have been used to make coatings with high antibacterial property [79, 80].
Nano-structured self-clean glass is now an important commercial product. Pilkington Glass has developed the first self-cleaning windows. The window glass is coated with a very thin and transparent TiO2 layer to have the properties of photocatalysis and hydrophilicity on the glass surface. Photocatalysis of TiO2 break down the organic dirt adsorbed onto the window in sunlight, and the decomposed organic species is washed away efficiently by rain or other water in the form of thin layer instead of droplets [86].
Another important application of nano-structured TiO2 is in the water-treatment, utilizing its photocatalytic properties [87, 88, 89, 90, 91, 92]. Research of using nano-structured TiO2 for water-treatment has been very active in recent years. TiO2 has been used in the photocatalytic decomposition of organic dyes in waste water, and organic pollutants such as pesticides, dyes and pharmaceuticals in other contaminated water [93, 94]. The photocatalytic decomposition of organic matters in water are all based on the mechanism of the generation of highly reactive radicals (OH•) and superoxide ions (O2•−) in TiO2 under UV irradiation, as illustrated in Figure 3. TiO2 has been considered to be the best choice to be used as photo-catalysts, as TiO2 is chemically inert, and cheap to manufacture and to apply.
The complete separation and recycling of TiO2 fine particles is important for the practical applications. A number of innovative methods have been developed for this purpose. For example, fixing TiO2 nano-particles on supports such as glass plates, aluminum sheets, and activated carbon are investigated to recycle the catalyst [95], or developing TiO2 catalyst system which can be separated from reaction liquid by applying external magnetic field [96, 97].
Because TiO2 and many other semiconductors have the large band gaps, the application of photocatalytic water treatment using TiO2 is limited by its relatively low efficiency. To improve photocatalytic efficiency of TiO2 for water treatment, as well as other photocatalytic applications, Enormous research has been carried out to extend the photocatalytic response of TiO2 into the visible range [98]. One of the strategies for improving photocatalytic efficiency for water treatment is to modify the band gap of TiO2 by incorporation of other ions into TiO2 structure, through metal and non-metal doping, metal implantation, noble metal loading, and others [99, 100, 101, 102, 103, 104].
TiO2-based composite materials have been widely used as catalysts [105, 106, 107]. TiO2 is used as support in commercial V2O5-WO3/TiO2 catalysts for the selective catalytic reduction (SCR) of NOx. In SCR technology, highly undesirable NOx acid gas emissions from various industrial sources are reduced to harmless N2 and H2O. The V2O5-WO3/TiO2 catalysts are widely used in commercial applications because of their excellent thermal stability and lower oxidation activity for the conversion of SO2 to SO3 [108, 109]. The V2O5-WO3/TiO2 catalysts have become the most widely used industrial catalysts for these SCR applications since the introduction of this technology in the early of 1970s [110].
TiO2 has the potential to induce the reductive chemical transformation. The reductive photocatalysis of ethyne and ethene have been reported [111, 112, 113]. TiO2 have been used as a useful catalyst for the reduction of carbonyl compounds such as aldehydes or ketones, nitro compounds, imines and for the some of the chemical transformations involving redox processes. Photocatalysis on TiO2 is a light-driven redox reaction. Redox reactions can be induced by electrons (e−) generated in conduction band (CB) and holes (h+) simultaneously generated in valance band (VB) under the irradiation of light. The electrons in the conduction band are readily available for transferring while the holes in the valence band are open for donations [114]. The photocatalytic reduction of an electron acceptor can be carried out in the presence of a large excess amount of electron donors such as alcohols or amines, which are used to scavenge (h+). Oxygen (O2) is a competitive electron acceptor, and can influence the reduction reaction. Therefore, the reductive chemical transformation should be generally performed in an O2 free environment. Under these conditions, a photocatalytic reduction proceeds through transferring electrons (e−) in CB or trapped at surface defects of TiO2 into the organic molecules adsorbed on TiO2 surface. The photocatalytic reduction of aldehydes, nitro compounds, and imines have been reported. Aromatic aldehydes and ketones were reduced to the corresponding alcohols using TiO2 as a photocatalyst [115, 116]. Aromatic and aliphatic nitro compounds were reduced to corresponding amines using TiO2 as catalyst [117]. The direct reduction of imines to corresponding secondary amines was studied [118].
The sunlight reaching the earth’s surface contains UV, visible and infrared wavelength. The Sun releases ultraviolet (UV) radiation in three different wavelengths, and all are harmful in different ways. These wavelengths in sunlight are called UVA (315–400 nm), UVB (280–315 nm) and UVC (100–280 nm) [119]. Because the earth’s atmosphere blocks most UVC rays, UVC does not generally reach the earth’s surface to a significant degree. Therefore, they are not thought to be important contributors to the biological effects on human skin [120]. UVA wavelength penetrates more deeply into the skin causing photo-aging and the formation of skin cancer. UVB is shorter, and damages the surface of the skin. The damage from UVB can cause sunburn and cancer [121, 122, 123, 124].
TiO2 is a semiconducting material with very high refractive index. The high refractive index is what allows the substance to scatter visible light. The current method of preventive treatment again harmful UV radiation involves suspending a substance that either absorbs or scatters UV radiation in a thick emulsion, called sunscreen. Titanium dioxide (TiO2) is an ingredient in sunscreens where its loading is frequently 2–15%. Sunscreen typically contain chemical filters that are organic compounds that absorb strongly the UV (most often UVB) and physical filters such as TiO2 and ZnO that block UVA and UVB sunlight through absorption, reflection and scattering.
In biomedicine, TiO2 nanoparticles with their extraordinary stability, exceptional photo-reactivity, and biocompatibility have a special place in biomedical solutions. The therapeutic potential of TiO2 lies in the ability of these particles in response to light to produce reactive oxygen species (ROS). Production of ROS is the main factor in causing detrimental effects on cells. This effect was first applied by Cai
In both photodynamic therapy (PDT) and sonodynamic therapy (SDT), nano-structured titanium dioxide is used as an agent to produce reactive oxygen species (ROS). Photodynamic therapy (PDT) is an anti-tumor method in which photosensitive agent is applied and target area is illuminated for the activation of the agent. TiO2 is normally a photocatalyst that produces oxidizing radicals by reacting with water during UV exposure and can damage nearby cells [127, 128]. Titanium dioxide and zinc oxide are two of the most effective photosensitizers for PDT applications. In sonodynamic therapy, TiO2 acts as a sonocatalyst. Studies have shown that TiO2 particles can promote the production of hydroxyl (OH•) radicals by ultrasound irradiation even in dark conditions [129, 130]. Ultrasound technology has been already used for some cancer therapies, either by generating localized heating using high intensity ultrasound or by activating a drug release using low intensity ultrasound. Ultrasound can penetrate inches below the skin. Therefore, it can be used to activate TiO2 nanoparticles deep below the skin surface.
TiO2 has been considered to be a good material for the design of drug carriers, for the reasons that the shape and size of TiO2 nanoparticles can be engineered to control their electronic and chemical properties, and the surface of TiO2 nanoparticles can be functionalized with various drug molecules [131, 132]. These capabilities bring new opportunities for more efficient site-selective chemistry of TiO2, and form the vehicles for drug delivery applications.
Titanium dioxide is a stable, non-toxic inorganic material with very high refractive index, and can scatter visible light almost completely. The particle sizes for pigmentary TiO2 are generally engineered to be around 250 nm to have optimized light scattering property. After coating with inorganic compounds such as alumina or silica, the catalytic activity on the surface of TiO2 particles is suppressed and the weather resistance is improved. Because of the superior optical properties and chemical stability, TiO2 has been developed and used as white pigment over several decades. Pigmentary titanium dioxide has excellent ability to impart brightness and opacity. Titanium dioxide has now been a well established inorganic white pigment and is widely applied in the coatings, plastics, paper manufacturing, and in many common products. Global sales of titanium dioxide pigment were about 6 million tons in 2017 and the growth trend of global titanium dioxide pigment sales is continuing over the recent years.
Titanium dioxide is also a semiconducting material which is characterized by a filled valence band and an empty conduction band. When excited by photons which have energy equal to or higher than their band gap, electrons (e−) in valence band of TiO2 are promoted to the conduction band and holes (h+) are created in the valence band of TiO2. Because of the discovery of photocatalytic properties of titanium dioxide, and the ability to engineer TiO2 nanomaterials for controlling their electronic and chemical properties, the applications of titanium dioxide as functional materials have become the focus of enormous research and development in the recent years. The applications of nano-structured TiO2 can now be found in a wide range of areas including electronic materials, energy, environment, health & medicine, and catalysts. A number of materials containing nano-structured TiO2 have become the important commercial products. Further research is continuing to modify the electronic and chemical properties, as well as surface characteristics of TiO2 for the creation of more efficient TiO2 functional materials in more specific application areas.
This work was financially supported by the Pangang Group under a Basic Research Grant.
The authors declare no conflict of interest.
The last two decades have seen epidemic outbreaks by novel viruses including SARS, MERS, and influenza which shared certain commonalities such as a likely zoonotic origin, high mortality rates, and less available therapeutic methods to counteract them. The COVID-19 pandemic shows no signs of slowing down with affecting 223 countries, with 224,811,910 cases, and 4,633,797 death tolls till date [1]. With what history on earlier pandemics has made us understand and with the rapidly mutating nature of the SARS-CoV-2 virus, it is not unreasonable to say that the pandemic is here to stay, and the world must learn to co-exist with it. The first reported case of COVID-19 was found in Wuhan, China in December 2019. By March 2020, the disease had spread across the globe and had become a public health emergency. The WHO declared a pandemic state to the disease spread on March 11, 2020 [2]. With more than a year since the declaration of the pandemic, the scientific community has yet not developed a definitive anti-viral drug to combat the disease spread. Even though the advent of vaccination has set the pace in favour of global health, we have a long way to go to eradicate if at all suppress the disease spread.
SARS-CoV-2 is highly virulent and highly contagious with the R0 value of 3.77 [3]. Though it predominantly affects the respiratory system, other organ systems like the gastrointestinal system, heart, kidney, and central nervous system are also targeted by the virus. Fever, chills, cough, shortness of breath or breathing difficulty, sore throat, nasal congestion, diarrhoea, nausea, vomiting, generalised body aches are some of the common symptoms noted in patients infected with COVID-19 [4].
Neurological manifestations of COVID-19 include non-specific symptoms like headache, dizziness, fatigue, and myopathy and more specific symptoms like anosmia, ageusia, impaired consciousness, stroke, meningitis, acute transverse myelitis, and Guillian-Barre syndrome [5, 6]. More than one third of the individuals with COVID-19 were found to present with neurological symptoms [7, 8]. The presence of viral RNA in cerebrospinal fluid and the brain was observed in COVID-19 patients [9]. Preliminary
Coronaviruses are the largest among RNA viruses. They have a crown-like spikes on their surface and hence the name. SARS-CoV-2 is the latest/seventh coronavirus to become pathogenic to humans. It belongs to the Coronaviridae family which includes four genera; α−, β−, γ−, and δ-CoV. Out of these human pathogens include HCoV- 229E, HCoV- NL63 [α − CoV] and OC43, and HKU1 [β − CoV] that in most cases cause mild self-limiting respiratory disease. γ − and δ-CoV strains mainly affect avian species [13]. SARS-CoV and MERS-CoV, causatives of SARS and MERS, are beta coronaviruses that caused up to 9.6% and 34.3% mortality rates which were responsible for earlier pandemics that resulted in a death toll of 812 and 866, respectively [14]. SARS-CoV-2 is more similar to SARS-CoV and MERS-CoV while being far more pathogenic and transmissible than the earlier known coronaviruses.
SARS-CoV-2 is a beta coronavirus that is positive-sense single-stranded RNA virus with 29–30 kb in size. It has four structural proteins and 16 non-structural proteins. Nucleocapsid protein [N], membrane protein [M], spike protein [S], and envelope protein [E] are the four structural proteins (Figure 1) . The capsid of the genome is formed by N protein and the genome is further surrounded by an envelope that is made up of M, E, and S proteins. Like other coronaviruses, SARS-CoV-2 has enveloped with a crown-like spikes on its surface. It is the spike protein that is responsible for the variations in host specificity and tissue tropism of the different coronavirus. Spike protein is a type-I membrane glycoprotein and has two functional subunits S1 and S2 with different functional domains in the amino and carboxy terminal. S1 subunit contains the receptor-binding domain [RBD] and binds with the receptor in the host cells. S2 subunit fuses the membranes of the host cells and the virus. The entry of the virus into the host cell involves binding of the S protein [S1 subunit] to a specific cell receptor followed by priming of the S protein by proteases in the host cell. This leads to the fusion of the spike protein to the cell membrane which is mediated by the S2 subunit [15]. The specific cell receptor through which SARS-CoV-2 enters the host cell is the ACE2 receptor and the protease in the host cell that processes the spike protein to reveal the fusion peptide between S1 and S2 subunits facilitating its entry, is a TMPRSS2 serine protease, member of the hepsin/TMPRSS subfamily [16]. Another protein named furin or paired basic amino acid cleaving enzyme [PACE], a member of the subtilisin-like proprotein convertase family, mediates proteolytic cut of the S protein at S1-S2 boundary, is required for TMPRSS2 processing of S protein. Both TMPRSS2 and furin are essential for the entry of SARS-CoV-2 into the cell. The furin cleavage site in the S protein of SARS-CoV-2 is not found in SARS-CoV and other beta coronaviruses [17].
(a) Structure of ACE2 and SARS-CoV-2; (b) Interaction of spike protein and ACE2; (c) Shedding of ACE2 and entry of SARS-CoV-2 into the cell.
ACE2 is a cell surface protein, a metalloproteinase and an ectoenzyme which is an obligatory receptor for SARS-CoV and SARS-CoV-2. The affinity of SARS-CoV-2 to ACE2 is ten times higher than that of SARS-CoV which partly explains its higher pathogenicity [18]. It was discovered in 2000 by two independent groups of researchers while searching for human ACE homologues [19, 20]. The gene for ACE2 in humans is located in Xp22 and has 18 exons, a majority of which are similar to the exons of the ACE gene [21]. Despite ACE2 exhibiting 42% sequence identify and 61% sequence similarity with ACE, the two enzymes show enormous variations (Table 1) [27].
ACE | ACE2 | |
---|---|---|
Forms | Exists as a 2-domain somatic form and a one domain testicular form | Exists as a single form |
Structure | Transmembrane ectoenzyme with two active sites | Transmembrane ectoenzyme with one active site |
Enzymatic action | Removes C-terminal dipeptide – peptidyl-dipeptidase | Removes single amino acid from C-terminus – carboxypeptidase |
Substrate specificity | Converts Ang I to Ang II | Converts Ang I to Ang (1-9) |
Does not cleave Ang II | Converts Ang II to Ang (1-7) | |
Converts Ang (1-9) to Ang (1-7) | Does not cleave Ang (1-9) | |
Converts Ang (1-7) to Ang (1-5) | Does not cleave Ang (1-7) | |
Does not cleave Ang A | Converts Ang A to Alamandine | |
Hydrolyses bradykinin | Does not cleave bradykinin | |
Does not cleave des-Arg9-bradykinin | Hydrolyses des-Arg9-bradykinin | |
Action on amyloid protein | Hydrolyses Aβ-43 to Aβ41 | Hydrolyses Aβ43 to Aβ42 |
Hydrolyses Aβ-42 to Aβ40 | Does not cleave Aβ-42 | |
Localisation within cells | Equal distribution between apical and basolateral membranes | Localised on the apical membrane |
Transports intestinal amino acids | No | Transports intestinal neutral amino acids |
Shedding into plasma | Unidentified. May involve metalloproteinase and A Disintegrin | By A Disintegrin and Metalloprotease 17 (ADAM 17) |
Response to ACE inhibitor | Inhibited | Resistant, gets upregulated |
Acts as a receptor to virus | No | Receptor for SARS-CoV and SARS-CoV-2 |
Since the 20 years of its discovery, ACE2 was found to have a multitude of physiological and pathological functions based on its three fundamental actions viz. negative regulation of renin-angiotensin system [RAS], facilitation of amino acid transport in the intestine, and surface receptor for SARS-CoV and SARS-CoV-2. ACE2 is mainly expressed in the lungs, intestine, liver, heart, kidneys, testes, and brain. In the brain, it is expressed in neurons, astrocytes and oligodendrocytes, and in ventricles, substantia nigra, hypothalamus, hippocampus, middle temporal gyrus, posterior cingulate cortex, nuclei in pons—the nucleus of tractus solitarius and pre-Bötzinger complex and olfactory bulb [21, 28]. ACE2 expression is higher in astrocytes, astrocytic foot processes, pericytes, and endothelial cells which form the key components of the blood–brain barrier [29]. In the olfactory epithelium, its expression is higher in the supporting sustentacular cells than in olfactory sensory neurons [30]. The sites of ACE2 expression are given in Table 2 [31].
Vascular system | Endothelial cells, vascular smooth muscle cells, and migratory angiogenic cells |
Heart | Cardiomyocytes, endothelial cells, pericytes, and epicardial adipose cells, and cardiofibroblasts |
Skin | sebaceous gland cells and basal epidermal layer |
Kidneys | glomerular endothelial cells, proximal tubule epithelial cells, bladder urothelial cells, luminal surface of tubular epithelial cells, and podocytes |
Reproductive system | Ovary, oocyte, uterus, vagina, and placenta of the female reproductive system Adult Leydig cells and cells in the seminiferous ducts in the testis of the male reproductive system |
Liver | Perinuclear hepatocytes, cholangiocytes, epithelial cells of the bile duct |
Gut | Stratified epithelial cells of oesophagus, stomach, Intestinal epithelial cells, enterocytes of small intestine, absorptive enterocytes from the ileum, colon and rectum, and endothelial cells |
Pancreas | Acinar cells and duct cells of the exocrine gland and alpha, beta, delta, and PP cells of islets of Langerhans |
Thyroid | Glandular cells |
Oral cavity | Tongue, buccal mucosa, gingiva, leucocytes within the oral mucosa, non-keratinising squamous epithelium of the oral cavity – basal layer |
Upper airway | Ciliated epithelial cells, goblet cells |
Lungs | Pulmonary vasculature, type I and II alveolar epithelial cells, bronchiolar epithelial cells |
Eyes | Pigmented epithelial cells, photoreceptor cells, Müller glial cells |
Central nervous system | Neurons, astrocytes, and oligodendrocytes, and in ventricles, substantia nigra, hypothalamus, hippocampus, middle temporal gyrus, posterior cingulate cortex, nuclei in pons – nucleus of tractus solitarius and pre-Bötzinger complex and olfactory bulb and cerebral vasculature and components of blood–brain barrier (astrocytes, astrocytic foot processes, pericytes, and endothelial cells) |
Sites of ACE2 expression.
ACE2 is a type 1 integral membrane protein that includes a short cytoplasmic C-terminus, a transmembrane region, collectrin, and N-terminal ectodomain. Zinc-binding motifs, HEMGH forms the active site of the enzyme. N-terminal domain has a claw-shaped protease domain which is the binding site of receptor-binding domain [RBD] of SARS-CoV and SARS-CoV-2. N terminus is homologous to ACE and is a carboxypeptidase that metabolises peptides like angiotensin II, kinins, apelin-13, apelin-36, neurotensin 1–13, kinetensin, and morphins, and C terminus is homologous to collectrin which is involved in the trafficking of neutral amino acid transporter [B[o]AT1] in the intestinal epithelium [32].
Both ACE and ACE2 play a major role in maintaining renin-angiotensin system [RAS] homeostasis. ACE2 acts like a negative regulator of ACE in RAS. RAS involves a variety of proteins and enzymes. Angiotensinogen is an inactive precursor that gets cleaved by renin to form angiotensin I. ACE acts on angiotensin I to convert into angiotensin II [Ang II] while ACE2 converts Ang II to Ang [1-7]. Ang [1-7] then binds to Mas receptors and causes attenuation of the signal cascade that was activated by Ang II (Figure 2). Thus, ACE2 not only inactivates Ang II but also generates the antagonistic peptide Ang [1-7] [33]. Ang [1-7] can also be formed from Ang I by neutral endopeptidases and neprilysin, but the most effective pathway of Ang [1-7] generation is through ACE2 [34]. The conversion of Ang II to Ang [1-7] by ACE2 is 70 folds more efficient than the conversion of Ang I to Ang [1-9] by ACE2. Thus, under physiological conditions, ACE2 mainly forms Ang [1-7] than Ang [1-9] [34].
Renin-Angiotensin System.
While Ang II, which acts via angiotensin 1/AT1 [primary mediator] and angiotensin 2/AT2 receptors is a potent vasoconstrictor, a pro-fibrotic, and a pro-inflammatory agent, Ang [1-7] acts via Mas receptors and has vasodilator, anti-apoptotic and anti-proliferative effect. Mas receptors are G protein-coupled receptors and in the brain, they are highly expressed in the dentate gyrus of the hippocampus, a site-specific for adult neurogenesis and in blood vessels [35]. The ACE2/Ang [1-7]/Mas receptor axis of the RAS is considered to be the protective arm of the renin-angiotensin system. A balance in ACE/ACE2 is critical which implies a balance between the pro-inflammatory pro-oxidative arm and the anti-inflammatory and anti-oxidative arm of RAS. An increase in ACE/ACE2 ratio was observed in many pathological conditions including cardiovascular pathology, renal dysfunction, pulmonary hypertension, in cigarette smokers, and Alzheimer’s disease [36, 37, 38, 39]. SARS-CoV-2 which enters the host cells via ACE2 also causes downregulation of ACE2 and the major targets of SARS-CoV-2 are those which express higher levels of ACE2 [26]. The fibrotic and inflammatory processes observed in various organs in COVID-19 patients could be attributed to the dysregulation of ACE2 and subsequently, RAS which is observed in endocrine, paracrine, and intracrine levels in several organs [40]. Dysregulation of RAS in the brain is associated with neuroinflammation and neurodegeneration [41].
The old dogma that the production of functional neurons does not occur in adult life was refuted when Altman and Das published evidence to support the continuation of neurogenesis in adult life in rodents [42]. Neurogenesis refers to the process of the generation of new neurons from neural stem cells. This process which plays a major role in brain development in embryonic life ceases to exist shortly after birth in the majority of brain areas except two. The subgranular zone [SGZ] of the dentate gyrus of the hippocampus and subventricular zone [SVZ], lining the lateral wall of the lateral ventricles are the two areas where neurogenesis persists well into adult life albeit declining slightly with ageing (Figure 3) [43, 44]. There is a complex microenvironment that nourishes and supports the neural progenitor cells and their progeny which is called the ‘neurogenic niche’. There are various trophic factors, blood vessels, supporting glial cells, and hormones in the neurogenic niche that help to control and enhance neurogenesis [45]. The newborn neurons mature and get integrated into neural circuits and are involved in a variety of functions including learning and memory like temporal and pattern separation, high-resolution memory, synaptic plasticity, fear conditioning and emotions, and olfaction [46]. Incidentally altered neurogenesis is implicated in several neuropsychiatric diseases like Alzheimer’s disease, Parkinson’s disease, depression, Huntington’s disease, and stroke, epilepsy, and demyelinating disease [46, 47].
Coronal section of the brain showing the sites of adult neurogenesis.
The process of adult neurogenesis occurs in stages viz. maintenance of neural stem/progenitor cells [NPC] and proliferation of NPC, fate specification/commitment, differentiation, maturation, survival of immature neurons, and integration into neural circuitry. The defining abilities of NPC are self-replication and multipotency, that is, the ability to differentiate into multiple lineages of cells and in this case neurons, astrocytes, and oligodendrocytes [48]. There are different types of neural progenitor cells in SGZ and SVZ. Type-1 cells in SGZ, B-cells in SVZ, and radial glia-like cells in SGZ and SVZ are largely quiescent cells, which are similar to radial glia cells found during embryonic development and have a morphology similar to mature astrocytes. Type-2 cells in SGZ and C-cells in SVZ are small roundish cells that are highly proliferative, and they give rise to type-3 cells in SGZ and A-cells in SVZ which represent committed neuroblasts. The type-1/B-cells are multipotent and have unlimited self-renewal capacity which get activated by various factors and multiply to form highly proliferative transient intermediate progenitor cells [TIP] in the SGZ. In SVZ, the transit-amplifying cells [TAC] [type-2/C-cells] has the ability to differentiate into neurons. These divide to form neuroblasts or immature neurons [type-3/A-cells] which proceed to neuronal differentiation and forms newborn neurons that mature and get integrated into neural circuitry in the brain. It is pertinent to know that many of the newborn neurons perish and only 15–30% of immature neurons survive the maturation process. There are various factors that regulate this step and thereby the process of adult neurogenesis [49, 50, 51].
In SGZ, the NPCs form granule cells which are the principal excitatory cells of the dentate gyrus. Their axons form the mossy fibres extending to the CA3 region and their dendrites are in the molecular layer which receives connections from the entorhinal cortex. Immature neurons that are less than a week-old start to have neurite outgrowth and by one- or two-weeks axons can be observed in the hilus, and dendrites start to extend to the molecular layer without spines which being developed by around the 16th day. By 17 days, functional connections are formed by the axons [mossy fibres] with the CA3 pyramidal neurons [52]. They release glutamate as the neurotransmitter. After around 1 week of birth, the newborn granule cells receive GABAergic inputs and after 2 weeks receive glutamatergic inputs [53]. These immature neurons exhibit enhanced excitability by virtue of high input resistance and subthreshold calcium ion conductance which enables them to develop action potential with less excitatory currents. They also have a low threshold for induction of LTP [long-term potentiation] [54, 55]. Between 3 weeks and 2 months, there occurs a gradual increase in spine formation, dendritic arborisation and connection, boutons on CA3 neurons, and maturation of mossy fibres. By less than 2 months, the newborn neurons become functionally indistinguishable from fully mature granule cells [52].
In SVZ, restricted neural progenitor cells migrate along scaffolds maintained by specialised astrocytes via the rostral migratory stream [RMS] to reach the olfactory bulb. By 15–30 days, they differentiate into two types of interneurons, GABAergic granule neurons [95%] and GABA or dopaminergic periglomerular neurons [5%]. The newborn GABAergic granule neurons can become cells with dendrites that do not cross beyond the mitral cell layer and those with non-spiny dendrites that extend till the external plexiform layer. These interneurons mature and get integrated into olfactory network and start responding to olfactory signals [52].
There are various factors that regulate neurogenesis. These include intrinsic niche-derived intrinsic mechanisms and extrinsic systemic factors. The intrinsic factors that regulate adult neurogenesis are given in Table 3. There are extrinsic environmental cues and systemic factors that can positively and negatively affect adult neurogenesis like physical exercise, dietary intake, olfactory/hippocampal-dependent learning, environmental enrichment, ageing, stress, alcohol abuse, and certain inflammatory conditions [46, 56, 57, 58, 59].
Intrinsic factors | Examples |
---|---|
Neurotrophic factors | brain-derived neurotrophic factor (BDNF), insulin-like growth factor-1 (IGF-1), nerve growth factor (NGF), glia-derived nerve factor (GDNF), fibroblast growth factor 2 (FGF-2), epidermal growth factor (EGF) |
Morphogens | Notch, sonic hedgehog (Shh), wingless ligands (Wnts), and bone morphogenic proteins (BMPs). |
Inflammatory cytokines | tissue necrosis factors α (TNFα), interleukin-6 (IL-6) and IL-1β IL-4 and IL-10 |
Neurotransmitters | gamma-aminobutyric acid (GABA), glutamate, dopamine, serotonin, norepinephrine, acetylcholine |
Hormones | Glucocorticoids, sex hormones, leptin, incretin |
Epigenetic factors | methyl-CpG-binding domain protein 1 (Mbd1), MYST family histone acetyltransferase Querkopf (Qkf), mixed-lineage leukaemia 1 (Mll1), polycomb complex protein (Bmi-1), histone deacetylase 2 (HDAC2), and microRNAs (miR124, 137, 184, 185, and 491-3p) |
Transcriptional factors | sex-determining region Y-box 2 (Sox2), Orphan nuclear receptor TLX, forkhead box O proteins (FoxOs), prospero homeobox 1 (Prox1), neurogenic differentiation1 (NeuroD1), Kruppel-like factor 9, cyclic AMP response element-binding protein (CREB), paired box protein (Pax6), and neurogenin 2 (Neurog2) |
List of intrinsic factors that affect adult neurogenesis.
There are different ways that are the possible pathway for the entry of SARS-CoV-2 into the brain. Some of the ways include olfactory transmucosal invasion, hematogenous dissemination, and neuronal retrograde dissemination [5]. The olfactory sensory neurons of the olfactory mucosa are bipolar neurons. The axons of the olfactory sensory neurons along the apical side project into the nasal cavity while that on the basal side merge into filia and protrudes into the olfactory bulb through the cribriform plate. Thus, the olfactory sensory neurons are in direct contact with the cerebrospinal fluid [60]. In the olfactory mucosa, ACE2 receptors are mainly found in the non-neuronal cells, sustentacular cells while their expression in the olfactory sensory neurons is less [30]. The blood vessels lining the olfactory mucosa express both ACE2 and TMPRSS2 protease receptors which help in the invasion of the SARS-CoV-2 virus and facilitate binding, replication, and accumulation of the virus [61, 62]. Studies have found that SARS-CoV-2 enters CNS through this neural-mucosal interface by infection of the olfactory neurons or by diffusion through channels formed by olfactory ensheathing cells in the olfactory mucosa [60, 63]. Following the olfactory transmucosal invasion, the virus passes along the olfactory tract via axonal transport, trans-synaptic transport, or microfusion to different areas of the brain linked with the olfactory tract [60, 64].
Recent studies have observed that SARS-CoV-2 RNA was found in brain regions that are not directly connected to olfactory mucosa like the cerebellum which shows that other forms/routes of viral entry into the brain are at play. Neuronal retrograde dissemination is the one where the virus may breach peripheral nerve terminals and take a trans-synaptic route to reach CNS. For instance, SARS-CoV-2 may invade peripheral chemoreceptors and may reach the cardiorespiratory centre in the brain stem [65] or through the gut-brain axis where the virus may enter the brain through enteric nerves [66]. In case of hematogenous dissemination, the virus after infecting the airways may breach the epithelial barrier and enter the bloodstream. Through systemic circulation, the virus may reach the cerebral circulation and could infect endothelial cells of blood–brain barrier or epithelial cells of the blood CSF barrier to reach the brain or via circumventricular organs which lack the blood–brain barrier [5]. Trojan horse mechanism is another way by which SARS-CoV-2 could reach the brain parenchyma. It is the process in which the virus infects leucocytes which get activated and disseminate to other tissues and cross blood–brain barrier [67].
Once SARS-CoV-2 enters the brain, it enters and infects the neurons, glial cells, and endothelial cells through ACE2 and replicates which leads to cell death. It causes damage to the blood–brain barrier which will increase its permeability and cause oedema, intracerebral bleeding, and neuronal death. The infected neurons can release inflammatory mediators that can activate other immune cells like mast cells, neurons, microglia, astrocytes, endothelial cells, and pericytes [68, 69].
Earlier studies show that survivors of critical illness have higher risk of developing neuropsychiatric consequences after discharge from the hospital. The prevalence of symptoms of depression, anxiety, and post-traumatic stress was found to be 29% [28, 29, 30, 31, 32, 33, 34], 34% [30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42], and 34% [27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50] in survivors of critical illness, respectively [70, 71, 72]. Impairment in memory, attention, and concentration was observed in SARS survivors 1 year after recovery [73]. Based on the knowledge from earlier infections by coronaviruses, SARS, and MERS, an increased risk of neuropsychiatric disorders like depression, anxiety, post-traumatic stress disorder, are possible in a long-term follow-up of patients recovered from COVID-19 [12].
Neuropsychiatric disorders that display impaired adult neurogenesis include major depressive disorder, Alzheimer’s disease, Parkinson’s disease, schizophrenia, and post-traumatic stress disorder. All of these correlate well with the reduction in hippocampal volume, cognitive deficits, and mood dysregulation [74]. A recent 3-month prospective study by Yiping Lu et al. conducted in COVID-19 recovered patients found that there was grey matter enlargement in olfactory cortices and hippocampus bilaterally [75]. Yiping Lu et al. also found that the grey matter volume of the hippocampus was negatively related to loss of smell during the disease phase [75]. Anosmia over a course of time in upper respiratory tract infections was found to be associated with a decrease in the grey matter volume [GMV] of the central olfactory system due to loss of stimulation while enlargement of GMV is observed during recovery [76]. Functional compensation in the form of enlarged neurons and an increase in the dendritic spine and compensatory enhanced neurogenesis are believed to be the reason behind GMV enlargement during recovery [77]. Loss of memory that persisted 3 months after the active infection in COVID-19 recovered patients was found to be negatively related to hippocampal grey matter volume [75]. Memory acquisition depends on newborn neurons and impairment in the acquisition of memory occurs due to inhibition of adult neurogenesis in the hippocampus [78, 79].
Anosmia is regarded as the key feature of COVID-19 which either occurs as an only symptom or in association with other signs and symptoms [80, 81]. Earlier studies show that any impairment in olfactory neurogenesis is associated with anosmia since neurogenesis in the olfactory epithelium and olfactory bulb is essential for the sense of smell [82, 83]. Dysfunction or atrophy of the olfactory bulb was observed in COVID-19 patients by recent studies done using brain imaging reports [84, 85]. Pathogenic changes in COVID-19 seem to cause loss of dopaminergic neurons, defects in the dopamine system, and exacerbate the clinical features of Parkinson’s disease [PD] [86, 87]. Anosmia is an important premotor symptom of PD which is not directly related to the neurodegenerative process in substantia nigra but appears to be related to defective adult neurogenesis [88, 89].
Understanding the process of adult neurogenesis in COVID-19 may reveal a critical role of the regenerative capacity of NPCs in combating the neuropsychiatric consequence of COVID-19. There are no studies or evidence to link COVID-19 with adult neurogenesis yet. Based on the factors like the presentation of neuropsychiatric symptoms in COVID-19, the occurrence of symptoms like anosmia, memory and cognitive deficits in COVID-19, the neuro-invasive potential of SARS-CoV-2, ACE2 expression in sites of adult neurogenesis, increased levels of pro-inflammatory cytokines like IL-6, Il-1β which inhibit adult neurogenesis and impact of earlier coronavirus infections, it might not be far-fetched to say that COVID-19 could have a possible impact on adult neurogenesis. There is a severe scarcity in research analysing the effect of SARS-CoV-2 infection on adult neurogenesis. The current chapter, which is speculative and based on a thorough literature search, discusses the possible changes in adult neurogenesis in COVID-19 emphasising the role of ACE2. If proven to be true in the future, the findings in this article will help in achieving early intervention to address the neuropsychiatric long-term consequence of COVID-19.
SARS-CoV-2 entry into the cell through ACE2 is followed by the downregulation of ACE2. A decrease in ACE2 will lead to dysregulation of RAS and various other complications. A recent study has found that ACE2 is expressed in young neurons and in human-induced pluripotent stem cell-derived neural progenitor cells [90]. ACE2 is found to have various neuroprotective functions. It converts neurotoxic amyloid protein Aβ into neuroprotective one in transgenic mice [91]. ACE2 activator, diminazene increased CREB, BDNF, glutamate, and nicotinic receptor and decreased the levels of apoptotic and inflammatory proteins in the AD model of D-galactose-ovariectomized rats [92]. All these factors play a major role in adult neurogenesis. ACE2 deficiency in mice was found to be accompanied by significantly impaired learning and memory [93]. Exercise-induced neurogenesis in the dentate gyrus was abolished in ACE2 deficient mice. Ang II, Ang [1-7], and Mas receptors were not found to be responsible and hence the mediator of this effect is not identified yet [94].
ACE2 expression is stronger in the enterocytes of the small intestine and colon, which is even higher than in the lungs. Neural ganglia cells in the colon of the enteric nervous system also express ACE2 receptors. Intestinal ACE2 plays a major role in the transport of neutral amino acids via B0AT1, neutral amino acid transporter. ACE2/B0AT1 complex regulates the composition and function of gut microbiota. ACE2 knockout animals showed lower levels of serum neutral amino acid levels like tryptophan, and impaired gut microbiota composition along with reduced expression of small intestinal antimicrobial peptides [95]. Enteric infection is an important presentation of COVID-19. Faeces of COVID-19 patients were found to have Viral mRNA [96, 97]. SARS-CoV-2 entry via the enteric route into host cell leads to ACE2 shedding due to S priming which may lead to gut microbiota dysbiosis [98]. Depletion of gut microbiota by prolonged antibiotic treatment resulted in impairment in cognitive function and hippocampal neurogenesis in adult mice [99]. The existence of a strong link between gut microbiota and the development of mental disorders, depression, and anxiety which are associated with impaired adult neurogenesis has been explored in recent studies [100].
Neuroinflammation directly impairs adult hippocampal neurogenesis. Pro-inflammatory cytokine IL-1β, IL-6, IFN-α causes a reduction in neural cell proliferation and suppresses adult hippocampal neurogenesis [101, 102, 103]. SARS-CoV-2 entry into the brain triggers an immune response by activating microglia, astrocytes, and other immune cells. This leads to increased production of cytokines in the brain. Cytokine storm which is a deadly hyperinflammatory response is considered to be a hallmark feature of COVID-19 pathogenesis [104]. Hypercytokinemia of IL-6, IL-10, and TNF-α was observed in COVID-19 patients. Increased levels of IL-6 correlate with mortality and the need for ventilator support [105, 106].
Thus, there are different possible mechanisms through which SARS-CoV-2 affects adult neurogenesis via ACE2. This chapter, however, will focus on the role of ACE2 in possible alterations in adult neurogenesis in COVID-19 via neurotransmitters.
Neurotransmitter signalling is found to play a major role in the formation of new neurons in addition to its clear and indisputable role in communication between neurons. Starting from embryogenesis, neurotransmitters are involved in neuronal proliferation. In adult neurogenesis, they influence various steps including proliferation, differentiation, and migration. In addition to the direct action of neurotransmitters on adult neurogenesis, they also influence other factors that regulate neurogenesis like neurotrophic factors and growth factors [107].
Serotonin is a crucial monoaminergic neurotransmitter that acts as a mood stabiliser and is associated with feelings of happiness, well-being, and contentedness. In the brain, it is synthesised by the Raphe nuclei neurons in the brain stem from tryptophan using neuron-specific tryptophan hydroxylase 2 enzymes. Vesicular monoamine transporter 2 [VMAT] packs the synthesised serotonin into vesicles. Serotonin transporters [SERT] re-uptake serotonin back to presynaptic neurons after its release, thereby regulating its extracellular levels [108]. The serotonergic fibres from raphe nuclei have projections throughout the brain and especially to the granule cells and interneurons of the dentate gyrus of the hippocampus. Serotonin is known to play a major regulatory role in adult hippocampal neurogenesis. Selective serotonin reuptake inhibitors [SRRI] are commonly used antidepressants that act by increasing serotonin levels in the brain causes clinical improvement associated with an increase in adult hippocampal neurogenesis characterised by increased neuronal proliferation and number of newborn neurons [109]. Malberg et al. in 2000 were the first to show that chronic treatment with fluoxetine improved adult hippocampal neurogenesis [109]. In the dentate gyrus, serotonin is known to promote neuronal development and its depletion was found to cause reduced dendritic spine density of granule cells [110, 111, 112, 113]. Chronic treatment with SSRI, fluoxetine was found to increase the survival of newborn neurons in the dentate gyrus [109, 114]. In stress models like inescapable stress, cold restraint stress in the animal model, fluoxetine administration was found to exhibit neurogenic and neuroprotective roles in the hippocampus [114, 115]. Accelerated synaptogenesis and increased long-term potentiation [LTP] in the hippocampus were also observed by long-term treatment by fluoxetine [116].
Recent studies have found that ACE2 plays a major role in the biosynthesis of serotonin [5HT]. The precursor for 5HT is an essential amino acid, tryptophan which can cross the blood–brain barrier and whose intestinal absorption was found to be reduced by 70% in case of ACE2 deficiency. Thus, ACE2 has an indirect modulatory role in 5HT synthesis in the brain [117]. There are recent studies that show that 5HT synthesis in the brain is dependent on ACE2, which acts by modulating 5HT metabolism and ACE2 deficiency leads to decreased serum tryptophan levels and decreased serotonin levels in the brain [94].
Dopamine is involved in executive functions, volition, motor control, motivation, pleasure/reward, and attention/concentration [118]. The role and mechanism of action of dopamine in adult neurogenesis are not elucidated fully. Dopamine was found to modulate cell proliferation in the embryonic brain [119]. Hippocampus and sub-ventricular zone [SVZ] which are the neurogenic niche containing neural stem cells receive dopaminergic projections from the substantia nigra and ventral tegmental area. Dopamine receptors are also widely expressed in these two areas and play a regulatory role in adult neurogenesis and neural plasticity [120, 121]. Earlier studies show that depletion of dopamine in the rat model reduces both proliferation and survival of neural precursor cells in the sub-granular zone [SGZ] of the dentate gyrus [122, 123]. Dopaminergic denervation in substantia nigra caused a significant reduction in the proliferation of neural stem cells in SGZ and SVZ which was reversed by D2 receptor stimulation in rodents [123]. In humans, post-mortem studies have revealed that the number of neural precursor cells in SGZ and SVZ was reduced in patients with Parkinson’s disease [124]. Dopamine was also found to increase the type 2A early progenitor cell in the hippocampus of rodents via D1 like receptors [118]. Dopamine receptor agonist pramipexole increases the proliferation and survival of newborn neurons in SVZ, olfactory bulb [119].
RAS plays a major role in dopaminergic vulnerability through AT1 receptors. Dysregulation of RAS due to the downregulation of ACE2 induced by SARS-CoV-2 may increase the vulnerability of dopaminergic neurons and subsequently dopamine levels [125]. Interactions between dopamine and angiotensin receptors that are counterregulatory in nature are observed in substantia nigra and striatum [125]. The gene for ACE2 was found to coexpress and coregulate with that of dopa decarboxylase [DDC] in non-neuronal cells, which is a major enzyme of dopamine, serotonin, and histamine biosynthesis. DDC converts L-3,4-dihydroxyphenylalanine [L-DOPA] into dopamine which subsequently forms norepinephrine and epinephrine and L-5-hydroxytryptophan into serotonin. This coexpression and coregulation link between the genes for ACE2 and DDC gives rise to the possibility of a functional link between the actions of ACE2 and DDC [i.e.,] in the synthesis of Ang [1-7] and dopamine and serotonin mediated by ACE2 and DDC, respectively [126]. Following the infusion of Ang [1-7] in the hypothalamus of rats, brain dopamine levels increased which emphasises the link between ACE2 and DDC. SARS-CoV-2 induced downregulation of ACE2 could cause the decreased synthesis of serotonin and dopamine [94, 127].
The SARS-CoV-2 infection has been found to cause loss of dopaminergic neurons and deficits in the dopamine system [86, 128]. ACE2 expression is high in dopaminergic neurons and the downregulation of ACE2 by SARS-CoV-2 may cause depletion of dopaminergic neurons and dopamine levels. This is evident from the worsening of symptoms observed in COVID-19 patients with Parkinson’s disease [PD], requiring increased dopamine replacement therapy [129]. ACE2 deletion in the knockout mouse model caused a significant reduction in dopamine D1 mRNA expression in substantia nigra [130].
Norepinephrine is an important catecholamine that is involved in alertness, arousal, sleep–wake cycle, memory storage, and emotions. It modulates various functions of the hippocampus like learning, memory, and mood. Noradrenergic axon terminals arising from the locus coeruleus densely innervate the neurogenic niche in the adult hippocampus [131]. Norepinephrine along with the other monoaminergic neurotransmitters plays a major role in adult neurogenesis. Norepinephrine was found to activate the stem cells and neural precursor cells via β3-adrenergic receptors where non-proliferating latent precursor cells develop the ability to respond to mitogens and generate neurospheres. It also increases the proliferation of early progenitor cells in the adult hippocampus via β2-adrenergic receptors [132, 133]. Depletion of norepinephrine significantly decreased the proliferation of progenitor cells of granule cells in the hippocampus [134]. Antidepressants that selectively increase norepinephrine were found to increase adult hippocampal neurogenesis [132].
Downregulation of ACE2 by SARS-CoV-2 may affect the activity of DDC due to the coexpression and coregulation between the genes for ACE2 and DDC. This could lead to a decrease in the biosynthesis of dopamine and subsequently norepinephrine [126].
Glutamate is the predominant excitatory neurotransmitter of the CNS. It plays a vital role in both embryonic brain development and adult neurogenesis. Its extracellular levels are especially higher in the neurogenic niche when compared to other areas of the brain [135, 136]. It has trophic effects on the developing neurons before synapse formation like proliferation, migration, and maturation. It causes an increase in the proliferation of neural progenitor cells [NPC]. The NPCs express NMDA metabotropic glutamate receptors, stimulation of which caused increased intracellular calcium and activation of NeuroD1, proneural gene [137]. Glutamate signalling plays a positive role in maintaining the proliferation of NPCs and the survival rates of newborn neurons [137, 138].
Gamma-aminobutyric acid [GABA] is a principal inhibitory neurotransmitter in the CNS. It is produced from glutamate by the action of the enzymes glutamate decarboxylase GAD65 and GAD67 [139]. Dysfunction in the GABAergic system is implicated in major depressive disorder and anxiety [140]. However, in the developing brain, GABA exerts an excitatory effect, that is, GABA is excitatory in immature neurons. Tonic discharge from GABAergic neurons is necessary for maintaining the quiescent state of NPCs. The absence of GABAergic excitability will cause impairment in neuronal maturation and synapse formation while an excess of it over newborn neurons will lead to seizures [141]. In SGZ, GABA mediates depolarisation of progenitor cells which is involved in the incorporation of AMPA receptors in immature granule cells, which is critical for learning and formation of memory [142]. It has a negative influence on neuroblasts. It inhibits the proliferation and migration of neuroblasts. It also inhibits the proliferation of NPCs [143, 144, 145]. It also promotes the differentiation of hippocampal NPCs. GABAA receptor agonist, phenobarbital caused a reduction in NPC proliferation and increase in differentiation which resulted in an increased number of newborn neurons [146]. Thus, it plays crucial role in different stages of adult neurogenesis. GABA and glutamate signalling play a major role in adult neurogenesis. Selective activation of the receptor subtypes of GABA and glutamate expressed in NPCs plays a pivotal role in self-replication and fate commitment of the developing neurons into a particular progeny [147].
A recent study has found ACE2 to be located mainly in excitatory neurons of the brain and to a lesser extent in inhibitory neurons like GABAergic neurons [148]. This indicates that SARS-CoV-2 once enters the brain has the potential to access the glutamatergic and GABAergic neurons. The consequence of this is not known however, viral entry may trigger apoptotic pathways and cause excitatory-inhibitory imbalance, and lead to neuronal death [149]. Cytokine release from infected neurons and other activated microglia and astrocytes may also cause a decrease in glutamate and GABA [150]. These effects are implicated along with impaired adult neurogenesis in neurodegenerative diseases like Parkinson’s disease and Alzheimer’s disease. Seizure is one of the neurological symptoms in COVID-19 patients, in which an increase in glutamate levels and decrease in GABA levels in the cerebral cortex and hippocampus is an implicated mechanism [151]. This further emphasises the possible impact of SARS-CoV-2 on glutamate and GABA.
Thus, SARS-CoV-2 induced downregulation of ACE2 in COVID-19 is potentially detrimental to adult neurogenesis. ACE2 deficiency affects the levels and actions of the neurotransmitters serotonin, dopamine, norepinephrine, GABA, and glutamate which play crucial roles in adult neurogenesis.
SARS-CoV-2 has been found to have a high affinity to ACE2 receptors. Such high affinity has been linked to affect neurogenesis through a variety of mechanisms. The present chapter has clearly postulated the link between this deadly virus and its effect on monoaminergic neurotransmitters as well as GABA and glutamate which play a major role in adult neurogenesis. As ACE2 receptors are expressed in the hippocampus, decreased neurogenesis in this region could be one of the major factors behind the neuropsychiatric disorders associated with patients affected with COVID-19. Awareness and early intervention to prevent and treat long-term psychiatric consequences of COVID-19 are crucial. We should be aware of the possibility that in the long term, COVID-19 may be associated with cognitive and psychiatric disorders in those who recovered. Despite having a mild course of disease in children and adolescents, immunological response to the infection in this population may affect synaptic pruning which may lead to various issues that may not be immediately apparent. Insights into the various machinations of adult neurogenesis in COVID-19 can be used to engineer the process to help with the pathological changes in the brain inflicted by the disease.
The authors would like to thank the Deanship of Scientific Research, Majmaah University for the support of this chapter.
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Almost all the parts of this plant, that are, fruit, leaves, flower bud, trunk, and pseudo-stem, can be utilized. This chapter deals with the fiber extracted from the pseudo-stem of the banana plant. It discusses the production of banana pseudo-stem fiber, which includes plantation and harvesting; extraction of banana pseudo-stem fiber; retting; and degumming of the fiber. It also deals with the characteristics of the banana pseudo-stem fiber, such as morphological, physical and mechanical, durability, degradability, thermal, chemical, and antibacterial properties. Several potential applications of this fiber are also mentioned, such as the use of this fiber to fabricate rope, place mats, paper cardboard, string thread, tea bags, high-quality textile materials, absorbent, polymer/fiber composites, etc.",book:{id:"7544",slug:"banana-nutrition-function-and-processing-kinetics",title:"Banana Nutrition",fullTitle:"Banana Nutrition - Function and Processing Kinetics"},signatures:"Asmanto Subagyo and Achmad Chafidz",authors:[{id:"257742",title:"M.Sc.",name:"Achmad",middleName:null,surname:"Chafidz",slug:"achmad-chafidz",fullName:"Achmad Chafidz"},{id:"268400",title:"Mr.",name:"Asmanto",middleName:null,surname:"Subagyo",slug:"asmanto-subagyo",fullName:"Asmanto Subagyo"}]},{id:"69568",title:"Water Quality Parameters",slug:"water-quality-parameters",totalDownloads:9909,totalCrossrefCites:12,totalDimensionsCites:32,abstract:"Since the industrial revolution in the late eighteenth century, the world has discovered new sources of pollution nearly every day. So, air and water can potentially become polluted everywhere. Little is known about changes in pollution rates. The increase in water-related diseases provides a real assessment of the degree of pollution in the environment. This chapter summarizes water quality parameters from an ecological perspective not only for humans but also for other living things. According to its quality, water can be classified into four types. Those four water quality types are discussed through an extensive review of their important common attributes including physical, chemical, and biological parameters. These water quality parameters are reviewed in terms of definition, sources, impacts, effects, and measuring methods.",book:{id:"7718",slug:"water-quality-science-assessments-and-policy",title:"Water Quality",fullTitle:"Water Quality - Science, Assessments and Policy"},signatures:"Nayla Hassan Omer",authors:null},{id:"40180",title:"Plant Tissue Culture: Current Status and Opportunities",slug:"plant-tissue-culture-current-status-and-opportunities",totalDownloads:66452,totalCrossrefCites:43,totalDimensionsCites:89,abstract:null,book:{id:"3568",slug:"recent-advances-in-plant-in-vitro-culture",title:"Recent Advances in Plant in vitro Culture",fullTitle:"Recent Advances in Plant in vitro Culture"},signatures:"Altaf Hussain, Iqbal Ahmed Qarshi, Hummera Nazir and Ikram Ullah",authors:[{id:"147617",title:"Dr.",name:"Altaf",middleName:null,surname:"Hussain",slug:"altaf-hussain",fullName:"Altaf Hussain"}]},{id:"66996",title:"Ethiopian Common Medicinal Plants: Their Parts and Uses in Traditional Medicine - Ecology and Quality Control",slug:"ethiopian-common-medicinal-plants-their-parts-and-uses-in-traditional-medicine-ecology-and-quality-c",totalDownloads:4059,totalCrossrefCites:6,totalDimensionsCites:10,abstract:"The main purpose of this review is to document medicinal plants used for traditional treatments with their parts, use, ecology, and quality control. Accordingly, 80 medicinal plant species were reviewed; leaves and roots are the main parts of the plants used for preparation of traditional medicines. The local practitioners provided various traditional medications to their patients’ diseases such as stomachaches, asthma, dysentery, malaria, evil eyes, cancer, skin diseases, and headaches. The uses of medicinal plants for human and animal treatments are practiced from time immemorial. Stream/riverbanks, cultivated lands, disturbed sites, bushlands, forested areas and their margins, woodlands, grasslands, and home gardens are major habitats of medicinal plants. Generally, medicinal plants used for traditional medicine play a significant role in the healthcare of the majority of the people in Ethiopia. The major threats to medicinal plants are habitat destruction, urbanization, agricultural expansion, investment, road construction, and deforestation. Because of these, medicinal plants are being declined and lost with their habitats. Community- and research-based conservation mechanisms could be an appropriate approach for mitigating the problems pertinent to the loss of medicinal plants and their habitats and for documenting medicinal plants. Chromatography; electrophoretic, macroscopic, and microscopic techniques; and pharmaceutical practice are mainly used for quality control of herbal medicines.",book:{id:"8502",slug:"plant-science-structure-anatomy-and-physiology-in-plants-cultured-in-vivo-and-in-vitro",title:"Plant Science",fullTitle:"Plant Science - Structure, Anatomy and Physiology in Plants Cultured in Vivo and in Vitro"},signatures:"Admasu Moges and Yohannes Moges",authors:[{id:"249746",title:"Ph.D.",name:"Admasu",middleName:null,surname:"Moges",slug:"admasu-moges",fullName:"Admasu Moges"},{id:"297761",title:"MSc.",name:"Yohannes",middleName:null,surname:"Moges",slug:"yohannes-moges",fullName:"Yohannes Moges"}]},{id:"29764",title:"Underlying Causes of Paresthesia",slug:"underlying-causes-of-paresthesia",totalDownloads:192987,totalCrossrefCites:3,totalDimensionsCites:7,abstract:null,book:{id:"1069",slug:"paresthesia",title:"Paresthesia",fullTitle:"Paresthesia"},signatures:"Mahdi Sharif-Alhoseini, Vafa Rahimi-Movaghar and Alexander R. Vaccaro",authors:[{id:"91165",title:"Prof.",name:"Vafa",middleName:null,surname:"Rahimi-Movaghar",slug:"vafa-rahimi-movaghar",fullName:"Vafa Rahimi-Movaghar"}]}],onlineFirstChaptersFilter:{topicId:"2",limit:6,offset:0},onlineFirstChaptersCollection:[{id:"82195",title:"Endoplasmic Reticulum: A Hub in Lipid Homeostasis",slug:"endoplasmic-reticulum-a-hub-in-lipid-homeostasis",totalDownloads:0,totalDimensionsCites:null,doi:"10.5772/intechopen.105450",abstract:"Endoplasmic Reticulum (ER) is the largest and one of the most complex cellular structures, indicating its widespread importance and variety of functions, including synthesis of membrane and secreted proteins, protein folding, calcium storage, and membrane lipid biogenesis. Moreover, the ER is implicated in cholesterol, plasmalogen, phospholipid, and sphingomyelin biosynthesis. Furthermore, the ER is in contact with most cellular organelles, such as mitochondria, peroxisomes, Golgi apparatus, lipid droplets, plasma membrane, etc. Peroxisomes are synthesized from a specific ER section, and they are related to very-long-chain fatty acid metabolism. Similarly, lipid droplets are vital structures in lipid homeostasis that are formed from the ER membrane. Additionally, there is a specific region between the ER-mitochondria interface called Mitochondria-Associated Membranes (MAMs). This small cytosolic gap plays a key role in several crucial mechanisms from autophagosome synthesis to phospholipid transfer. Due to the importance of the ER in a variety of biological processes, alterations in its functionality have relevant implications for multiple diseases. Nowadays, a plethora of pathologies like non-alcoholic steatohepatitis (NASH), cancer, and neurological alterations have been associated with ER malfunctions.",book:{id:"11674",title:"Updates on Endoplasmic Reticulum",coverURL:"https://cdn.intechopen.com/books/images_new/11674.jpg"},signatures:"Raúl Ventura and María Isabel Hernández-Alvarez"},{id:"82438",title:"Mosquito Excito-Repellency: Effects on Behavior and the Development of Insecticide Resistance",slug:"mosquito-excito-repellency-effects-on-behavior-and-the-development-of-insecticide-resistance",totalDownloads:0,totalDimensionsCites:0,doi:"10.5772/intechopen.105755",abstract:"Mosquito’s resistance to avoiding insecticide-treated surfaces (“excito-repellency”) has two effects: irritation from direct contact with a treated area and repellency as an avoidance response to contact with treated surfaces. Nowadays, this behavior appears to reduce the success of mosquito control programs, particularly those based on insecticide-driven strategies. Different systems have been designed to assess the excito-repellency, evaluating numerous insecticides’ irritants, deterrents, and toxic properties at different concentrations. The information provides valuable insights regarding the patterns of mosquito behavior based on their physiological conditions, such as the age of the mosquitoes and the duration of the tests. However, the physiological processes resulting from chemical stimulus contact “chemoreception”) are still poorly explored and understood. This review provides an overview of insecticide effects on mosquito behavior and describes the mechanisms involved in chemical stimuli uptake, translation, and recognition.",book:{id:"11379",title:"Mosquito Research - Recent Advances in Pathogen Interactions, Immunity, and Vector Control Strategies",coverURL:"https://cdn.intechopen.com/books/images_new/11379.jpg"},signatures:"Yamili J. Contreras-Perera, Abdiel Martin-Park, Henry Puerta-Guardo, Azael Che-Mendoza, Silvia Pérez-Carrillo, Irám P. Rodrígez-Sánchez, Pablo Manrique-Saide and Adriana E. Flores"},{id:"82307",title:"The Impact of Heavy Metals on the Chicken Gut Microbiota and their Health and Diseases",slug:"the-impact-of-heavy-metals-on-the-chicken-gut-microbiota-and-their-health-and-diseases",totalDownloads:2,totalDimensionsCites:0,doi:"10.5772/intechopen.105581",abstract:"It is important to consider the health and well-being of birds in various production methods. The microbial makeup and function of a bird’s gastrointestinal (GIT) system may vary based on the bird’s food, breed, age, and other environmental conditions. Gut flora play a critical role in maintaining intestinal homeostasis. Environmental exposure to contaminants such as heavy metals (HMs) has been linked to a wide range of disorders, including the development of dysbiosis in the gut, according to many studies. Changes in the gut microbiota caused by HMs are a major factor in the onset and progression of these illnesses. The microbiota in the gut is thought to be the first line of defense against HMs. Thus, HMs exposure modifies the gut microbiota composition and metabolic profile, affecting HMs uptake and metabolism by altering pH, oxidative balance, and concentrations of detoxifying enzymes or proteins involved in HM metabolism. This chapter will focus on the exposure of chicken to HMs from their feed or water and how these HMs affect the immune system resulting in various diseases.",book:{id:"11345",title:"Broiler Industry",coverURL:"https://cdn.intechopen.com/books/images_new/11345.jpg"},signatures:"Selina Acheampong"},{id:"82436",title:"Heavy Metal Residues in Milk and Milk Products and Their Detection Method",slug:"heavy-metal-residues-in-milk-and-milk-products-and-their-detection-method",totalDownloads:2,totalDimensionsCites:0,doi:"10.5772/intechopen.105004",abstract:"Milk and milk products are an essential part of the human daily diet, and their consumption is steadily increasing. Milk is regarded as a complete food because it contains all of the macronutrients including protein, carbohydrates, fat and vitamins. Milk also has a high concentration of mineral elements (metals) such as sodium, potassium, iron, calcium, magnesium, selenium, copper and zinc. They are critical for proper body growth and maintenance but excess in these metals, particularly, heavy metals cause disturbances and pathological conditions. People nowadays are concerned about food safety issues involving microbial, chemical and physical hazards. Heavy metal residues such as cadmium (Cd), lead (Pb), arsenic (As) and mercury (Hg) pose a chemical hazard. These are the main contaminants. Heavy metals are any metallic chemical elements with a relatively high density (5 g/cc) whose levels must be monitored. Atomic absorption spectroscopy can be used to estimate the heavy metal contamination in milk and milk products.",book:{id:"11741",title:"Trends and Innovations in Food Science",coverURL:"https://cdn.intechopen.com/books/images_new/11741.jpg"},signatures:"Ankur Aggarwal, Tarun Verma and Sumangal Ghosh"},{id:"82362",title:"Studies on the Short-Term Effects of the Cease of Pesticides Use on Vineyard Microbiome",slug:"studies-on-the-short-term-effects-of-the-cease-of-pesticides-use-on-vineyard-microbiome",totalDownloads:0,totalDimensionsCites:0,doi:"10.5772/intechopen.105706",abstract:"In this chapter, an overview of the impact of phytosanitary treatments on the vineyard microbiome is provided, together with the results of the research we conducted. The studied plant material consisted of grapevine from the cultivars Sauvignon blanc and Cabernet Sauvignon, cultivated within the plantation of the Research Station for Viticulture and Enology from Murfatlar, Romania. For each cultivar, a treated plot and an untreated plot were established. For each of those, the phyllosphere microbiota was quantified using the epifluorescence microscopy method, followed by automated image analysis using CellC software. At the same time, the soil fungal diversity was evaluated in three stages during the year 2021, using microscopic morphological criteria. The results give useful information regarding the phytosanitary state of the studied plant, as well as the short-term effects produced by the ceasing of pesticide application on the grapevine microbiota.",book:{id:"11663",title:"Vegetation Dynamics, Changing Ecosystems and Human Responsibility",coverURL:"https://cdn.intechopen.com/books/images_new/11663.jpg"},signatures:"Simona Ghiță, Mihaela Hnatiuc, Aurora Ranca, Victoria Artem and Mădălina-Andreea Ciocan"},{id:"82423",title:"Removal of Divalent Nickel from Aqueous Solution Using Blue Green Marine Algae: Adsorption Modelling and Applicability of Various Isotherm Models",slug:"removal-of-divalent-nickel-from-aqueous-solution-using-blue-green-marine-algae-adsorption-modelling-",totalDownloads:1,totalDimensionsCites:0,doi:"10.5772/intechopen.103940",abstract:"The adsorption of Ni(II) onto blue green marine algae (BGMA) in batch conditions is being investigated. The highest adsorption capacity of BGMA was found to be 42.056 mg/g under ideal testing conditions, where the initial Ni(II) metal ion concentration was adjusted from 25 ppm to 250 ppm. The optimal pH, biomass loading, and agitation rate for maximum Cu(II) ion removal have been determined to be 6, 2 g and 120 rpm, respectively. For the equilibrium condition, 24 hours of contact time is allowed. At room temperature, all of the experiments are conducted. The isotherm has a L shape, based on the equilibrium experimental data. It indicates that there is no considerable competition for active sites between the solvent and Ni(II). There is no strong competition between the solvent and Ni(II) for the active sites of BGMA, indicating that there is no strong competition between the two. It also suggests that the BGMA’s Ni sorption ability is restricted (II). The experimental data is validated using multiple isotherm models, and the mechanism of adsorption is then discovered, as well as the process design parameters. The Fritz-Schlunder-V isotherm model is particularly relevant in defining the mechanism of Ni(II) adsorption under the conditions used in this study, according to modelling studies. 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He is also a faculty member in the Molecular Oncology Program. He obtained his MSc and Ph.D. at Oregon State University and Texas Tech University, respectively. He pursued his postdoctoral studies at Rutgers University Medical School and the National Institutes of Health (NIH/NIDDK), USA. His research focuses on biochemistry, biophysics, genetics, molecular biology, and molecular medicine with specialization in the fields of drug design, protein structure-function, protein folding, prions, microRNA, pseudogenes, molecular cancer, epigenetics, metabolites, proteomics, genomics, protein expression, and characterization by spectroscopic and calorimetric methods.",institutionString:"University of Health Sciences",institution:null},{id:"180528",title:"Dr.",name:"Hiroyuki",middleName:null,surname:"Kagechika",slug:"hiroyuki-kagechika",fullName:"Hiroyuki Kagechika",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/180528/images/system/180528.jpg",biography:"Hiroyuki Kagechika received his bachelor’s degree and Ph.D. in Pharmaceutical Sciences from the University of Tokyo, Japan, where he served as an associate professor until 2004. He is currently a professor at the Institute of Biomaterials and Bioengineering (IBB), Tokyo Medical and Dental University (TMDU). From 2010 to 2012, he was the dean of the Graduate School of Biomedical Science. Since 2012, he has served as the vice dean of the Graduate School of Medical and Dental Sciences. He has been the director of the IBB since 2020. Dr. Kagechika’s major research interests are the medicinal chemistry of retinoids, vitamins D/K, and nuclear receptors. He has developed various compounds including a drug for acute promyelocytic leukemia.",institutionString:"Tokyo Medical and Dental University",institution:{name:"Tokyo Medical and Dental University",country:{name:"Japan"}}},{id:"94311",title:"Prof.",name:"Martins",middleName:"Ochubiojo",surname:"Ochubiojo Emeje",slug:"martins-ochubiojo-emeje",fullName:"Martins Ochubiojo Emeje",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94311/images/system/94311.jpeg",biography:"Martins Emeje obtained a BPharm with distinction from Ahmadu Bello University, Nigeria, and an MPharm and Ph.D. from the University of Nigeria (UNN), where he received the best Ph.D. award and was enlisted as UNN’s “Face of Research.” He established the first nanomedicine center in Nigeria and was the pioneer head of the intellectual property and technology transfer as well as the technology innovation and support center. Prof. Emeje’s several international fellowships include the prestigious Raman fellowship. He has published more than 150 articles and patents. He is also the head of R&D at NIPRD and holds a visiting professor position at Nnamdi Azikiwe University, Nigeria. He has a postgraduate certificate in Project Management from Walden University, Minnesota, as well as a professional teaching certificate and a World Bank certification in Public Procurement. Prof. Emeje was a national chairman of academic pharmacists in Nigeria and the 2021 winner of the May & Baker Nigeria Plc–sponsored prize for professional service in research and innovation.",institutionString:"National Institute for Pharmaceutical Research and Development",institution:{name:"National Institute for Pharmaceutical Research and Development",country:{name:"Nigeria"}}},{id:"268659",title:"Ms.",name:"Xianquan",middleName:null,surname:"Zhan",slug:"xianquan-zhan",fullName:"Xianquan Zhan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/268659/images/8143_n.jpg",biography:"Dr. Zhan received his undergraduate and graduate training in the fields of preventive medicine and epidemiology and statistics at the West China University of Medical Sciences in China during 1989 to 1999. He received his post-doctoral training in oncology and cancer proteomics for two years at the Cancer Research Institute of Human Medical University in China. In 2001, he went to the University of Tennessee Health Science Center (UTHSC) in USA, where he was a post-doctoral researcher and focused on mass spectrometry and cancer proteomics. Then, he was appointed as an Assistant Professor of Neurology, UTHSC in 2005. He moved to the Cleveland Clinic in USA as a Project Scientist/Staff in 2006 where he focused on the studies of eye disease proteomics and biomarkers. He returned to UTHSC as an Assistant Professor of Neurology in the end of 2007, engaging in proteomics and biomarker studies of lung diseases and brain tumors, and initiating the studies of predictive, preventive, and personalized medicine (PPPM) in cancer. In 2010, he was promoted to Associate Professor of Neurology, UTHSC. Currently, he is a Professor at Xiangya Hospital of Central South University in China, Fellow of Royal Society of Medicine (FRSM), the European EPMA National Representative in China, Regular Member of American Association for the Advancement of Science (AAAS), European Cooperation of Science and Technology (e-COST) grant evaluator, Associate Editors of BMC Genomics, BMC Medical Genomics, EPMA Journal, and Frontiers in Endocrinology, Executive Editor-in-Chief of Med One. He has\npublished 116 peer-reviewed research articles, 16 book chapters, 2 books, and 2 US patents. His current main research interest focuses on the studies of cancer proteomics and biomarkers, and the use of modern omics techniques and systems biology for PPPM in cancer, and on the development and use of 2DE-LC/MS for the large-scale study of human proteoforms.",institutionString:null,institution:{name:"Xiangya Hospital Central South University",country:{name:"China"}}},{id:"40482",title:null,name:"Rizwan",middleName:null,surname:"Ahmad",slug:"rizwan-ahmad",fullName:"Rizwan Ahmad",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/40482/images/system/40482.jpeg",biography:"Dr. Rizwan Ahmad is a University Professor and Coordinator, Quality and Development, College of Medicine, Imam Abdulrahman bin Faisal University, Saudi Arabia. Previously, he was Associate Professor of Human Function, Oman Medical College, Oman, and SBS University, Dehradun. Dr. Ahmad completed his education at Aligarh Muslim University, Aligarh. He has published several articles in peer-reviewed journals, chapters, and edited books. His area of specialization is free radical biochemistry and autoimmune diseases.",institutionString:"Imam Abdulrahman Bin Faisal University",institution:{name:"Imam Abdulrahman Bin Faisal University",country:{name:"Saudi Arabia"}}},{id:"41865",title:"Prof.",name:"Farid A.",middleName:null,surname:"Badria",slug:"farid-a.-badria",fullName:"Farid A. Badria",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/41865/images/system/41865.jpg",biography:"Farid A. Badria, Ph.D., is the recipient of several awards, including The World Academy of Sciences (TWAS) Prize for Public Understanding of Science; the World Intellectual Property Organization (WIPO) Gold Medal for best invention; Outstanding Arab Scholar, Kuwait; and the Khwarizmi International Award, Iran. He has 250 publications, 12 books, 20 patents, and several marketed pharmaceutical products to his credit. He continues to lead research projects on developing new therapies for liver, skin disorders, and cancer. Dr. Badria was listed among the world’s top 2% of scientists in medicinal and biomolecular chemistry in 2019 and 2020. He is a member of the Arab Development Fund, Kuwait; International Cell Research Organization–United Nations Educational, Scientific and Cultural Organization (ICRO–UNESCO), Chile; and UNESCO Biotechnology France",institutionString:"Mansoura University",institution:{name:"Mansoura University",country:{name:"Egypt"}}},{id:"329385",title:"Dr.",name:"Rajesh K.",middleName:"Kumar",surname:"Singh",slug:"rajesh-k.-singh",fullName:"Rajesh K. Singh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329385/images/system/329385.png",biography:"Dr. Singh received a BPharm (2003) and MPharm (2005) from Panjab University, Chandigarh, India, and a Ph.D. (2013) from Punjab Technical University (PTU), Jalandhar, India. He has more than sixteen years of teaching experience and has supervised numerous postgraduate and Ph.D. students. He has to his credit more than seventy papers in SCI- and SCOPUS-indexed journals, fifty-five conference proceedings, four books, six Best Paper Awards, and five projects from different government agencies. He is currently an editorial board member of eight international journals and a reviewer for more than fifty scientific journals. He received Top Reviewer and Excellent Peer Reviewer Awards from Publons in 2016 and 2017, respectively. He is also on the panel of The International Reviewer for reviewing research proposals for grants from the Royal Society. He also serves as a Publons Academy mentor and Bentham brand ambassador.",institutionString:"Punjab Technical University",institution:{name:"Punjab Technical University",country:{name:"India"}}},{id:"142388",title:"Dr.",name:"Thiago",middleName:"Gomes",surname:"Gomes Heck",slug:"thiago-gomes-heck",fullName:"Thiago Gomes Heck",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/142388/images/7259_n.jpg",biography:null,institutionString:null,institution:{name:"Universidade Regional do Noroeste do Estado do Rio Grande do Sul",country:{name:"Brazil"}}},{id:"336273",title:"Assistant Prof.",name:"Janja",middleName:null,surname:"Zupan",slug:"janja-zupan",fullName:"Janja Zupan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/336273/images/14853_n.jpeg",biography:"Janja Zupan graduated in 2005 at the Department of Clinical Biochemistry (superviser prof. dr. Janja Marc) in the field of genetics of osteoporosis. Since November 2009 she is working as a Teaching Assistant at the Faculty of Pharmacy, Department of Clinical Biochemistry. In 2011 she completed part of her research and PhD work at Institute of Genetics and Molecular Medicine, University of Edinburgh. She finished her PhD entitled The influence of the proinflammatory cytokines on the RANK/RANKL/OPG in bone tissue of osteoporotic and osteoarthritic patients in 2012. From 2014-2016 she worked at the Institute of Biomedical Sciences, University of Aberdeen as a postdoctoral research fellow on UK Arthritis research project where she gained knowledge in mesenchymal stem cells and regenerative medicine. She returned back to University of Ljubljana, Faculty of Pharmacy in 2016. She is currently leading project entitled Mesenchymal stem cells-the keepers of tissue endogenous regenerative capacity facing up to aging of the musculoskeletal system funded by Slovenian Research Agency.",institutionString:null,institution:{name:"University of Ljubljana",country:{name:"Slovenia"}}},{id:"357453",title:"Dr.",name:"Radheshyam",middleName:null,surname:"Maurya",slug:"radheshyam-maurya",fullName:"Radheshyam Maurya",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/357453/images/16535_n.jpg",biography:null,institutionString:null,institution:{name:"University of Hyderabad",country:{name:"India"}}},{id:"418340",title:"Dr.",name:"Jyotirmoi",middleName:null,surname:"Aich",slug:"jyotirmoi-aich",fullName:"Jyotirmoi Aich",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000038Ugi5QAC/Profile_Picture_2022-04-15T07:48:28.png",biography:"Biotechnologist with 15 years of research including 6 years of teaching experience. Demonstrated record of scientific achievements through consistent publication record (H index = 13, with 874 citations) in high impact journals such as Nature Communications, Oncotarget, Annals of Oncology, PNAS, and AJRCCM, etc. Strong research professional with a post-doctorate from ACTREC where I gained experimental oncology experience in clinical settings and a doctorate from IGIB where I gained expertise in asthma pathophysiology. A well-trained biotechnologist with diverse experience on the bench across different research themes ranging from asthma to cancer and other infectious diseases. An individual with a strong commitment and innovative mindset. Have the ability to work on diverse projects such as regenerative and molecular medicine with an overall mindset of improving healthcare.",institutionString:"DY Patil Deemed to Be University",institution:null},{id:"349288",title:"Prof.",name:"Soumya",middleName:null,surname:"Basu",slug:"soumya-basu",fullName:"Soumya Basu",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000035QxIDQA0/Profile_Picture_2022-04-15T07:47:01.jpg",biography:"Soumya Basu, Ph.D., is currently working as an Associate Professor at Dr. D. Y. Patil Biotechnology and Bioinformatics Institute, Dr. D. Y. Patil Vidyapeeth, Pune, Maharashtra, India. With 16+ years of trans-disciplinary research experience in Drug Design, development, and pre-clinical validation; 20+ research article publications in journals of repute, 9+ years of teaching experience, trained with cross-disciplinary education, Dr. Basu is a life-long learner and always thrives for new challenges.\r\nHer research area is the design and synthesis of small molecule partial agonists of PPAR-γ in lung cancer. She is also using artificial intelligence and deep learning methods to understand the exosomal miRNA’s role in cancer metastasis. Dr. Basu is the recipient of many awards including the Early Career Research Award from the Department of Science and Technology, Govt. of India. She is a reviewer of many journals like Molecular Biology Reports, Frontiers in Oncology, RSC Advances, PLOS ONE, Journal of Biomolecular Structure & Dynamics, Journal of Molecular Graphics and Modelling, etc. She has edited and authored/co-authored 21 journal papers, 3 book chapters, and 15 abstracts. She is a Board of Studies member at her university. She is a life member of 'The Cytometry Society”-in India and 'All India Cell Biology Society”- in India.",institutionString:"Dr. D.Y. Patil Vidyapeeth, Pune",institution:{name:"Dr. D.Y. Patil Vidyapeeth, Pune",country:{name:"India"}}},{id:"354817",title:"Dr.",name:"Anubhab",middleName:null,surname:"Mukherjee",slug:"anubhab-mukherjee",fullName:"Anubhab Mukherjee",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0033Y0000365PbRQAU/ProfilePicture%202022-04-15%2005%3A11%3A18.480",biography:"A former member of Laboratory of Nanomedicine, Brigham and Women’s Hospital, Harvard University, Boston, USA, Dr. Anubhab Mukherjee is an ardent votary of science who strives to make an impact in the lives of those afflicted with cancer and other chronic/acute ailments. He completed his Ph.D. from CSIR-Indian Institute of Chemical Technology, Hyderabad, India, having been skilled with RNAi, liposomal drug delivery, preclinical cell and animal studies. He pursued post-doctoral research at College of Pharmacy, Health Science Center, Texas A & M University and was involved in another postdoctoral research at Department of Translational Neurosciences and Neurotherapeutics, John Wayne Cancer Institute, Santa Monica, California. In 2015, he worked in Harvard-MIT Health Sciences & Technology as a visiting scientist. He has substantial experience in nanotechnology-based formulation development and successfully served various Indian organizations to develop pharmaceuticals and nutraceutical products. He is an inventor in many US patents and an author in many peer-reviewed articles, book chapters and books published in various media of international repute. Dr. Mukherjee is currently serving as Principal Scientist, R&D at Esperer Onco Nutrition (EON) Pvt. Ltd. and heads the Hyderabad R&D center of the organization.",institutionString:"Esperer Onco Nutrition Pvt Ltd.",institution:null},{id:"319365",title:"Assistant Prof.",name:"Manash K.",middleName:null,surname:"Paul",slug:"manash-k.-paul",fullName:"Manash K. Paul",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/319365/images/system/319365.png",biography:"Manash K. Paul is a Principal Investigator and Scientist at the University of California Los Angeles. He has contributed significantly to the fields of stem cell biology, regenerative medicine, and lung cancer. His research focuses on various signaling processes involved in maintaining stem cell homeostasis during the injury-repair process, deciphering lung stem cell niche, pulmonary disease modeling, immuno-oncology, and drug discovery. He is currently investigating the role of extracellular vesicles in premalignant lung cell migration and detecting the metastatic phenotype of lung cancer via machine-learning-based analyses of exosomal signatures. Dr. Paul has published in more than fifty peer-reviewed international journals and is highly cited. He is the recipient of many awards, including the UCLA Vice Chancellor’s award, a senior member of the Institute of Electrical and Electronics Engineers (IEEE), and an editorial board member for several international journals.",institutionString:"University of California Los Angeles",institution:{name:"University of California Los Angeles",country:{name:"United States of America"}}},{id:"311457",title:"Dr.",name:"Júlia",middleName:null,surname:"Scherer Santos",slug:"julia-scherer-santos",fullName:"Júlia Scherer Santos",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/311457/images/system/311457.jpg",biography:"Dr. Júlia Scherer Santos works in the areas of cosmetology, nanotechnology, pharmaceutical technology, beauty, and aesthetics. Dr. Santos also has experience as a professor of graduate courses. Graduated in Pharmacy, specialization in Cosmetology and Cosmeceuticals applied to aesthetics, specialization in Aesthetic and Cosmetic Health, and a doctorate in Pharmaceutical Nanotechnology. Teaching experience in Pharmacy and Aesthetics and Cosmetics courses. She works mainly on the following subjects: nanotechnology, cosmetology, pharmaceutical technology, aesthetics.",institutionString:"Universidade Federal de Juiz de Fora",institution:{name:"Universidade Federal de Juiz de Fora",country:{name:"Brazil"}}},{id:"219081",title:"Dr.",name:"Abdulsamed",middleName:null,surname:"Kükürt",slug:"abdulsamed-kukurt",fullName:"Abdulsamed Kükürt",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/219081/images/system/219081.png",biography:"Dr. Kükürt graduated from Uludağ University in Turkey. He started his academic career as a Research Assistant in the Department of Biochemistry at Kafkas University. In 2019, he completed his Ph.D. program in the Department of Biochemistry at the Institute of Health Sciences. He is currently working at the Department of Biochemistry, Kafkas University. He has 27 published research articles in academic journals, 11 book chapters, and 37 papers. He took part in 10 academic projects. He served as a reviewer for many articles. He still serves as a member of the review board in many academic journals.",institutionString:"Kafkas University",institution:{name:"Kafkas University",country:{name:"Turkey"}}},{id:"178366",title:"Dr.",name:"Volkan",middleName:null,surname:"Gelen",slug:"volkan-gelen",fullName:"Volkan Gelen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/178366/images/system/178366.jpg",biography:"Volkan Gelen is a Physiology specialist who received his veterinary degree from Kafkas University in 2011. Between 2011-2015, he worked as an assistant at Atatürk University, Faculty of Veterinary Medicine, Department of Physiology. In 2016, he joined Kafkas University, Faculty of Veterinary Medicine, Department of Physiology as an assistant professor. Dr. Gelen has been engaged in various academic activities at Kafkas University since 2016. There he completed 5 projects and has 3 ongoing projects. He has 60 articles published in scientific journals and 20 poster presentations in scientific congresses. His research interests include physiology, endocrine system, cancer, diabetes, cardiovascular system diseases, and isolated organ bath system studies.",institutionString:"Kafkas University",institution:{name:"Kafkas University",country:{name:"Turkey"}}},{id:"418963",title:"Dr.",name:"Augustine Ododo",middleName:"Augustine",surname:"Osagie",slug:"augustine-ododo-osagie",fullName:"Augustine Ododo Osagie",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/418963/images/16900_n.jpg",biography:"Born into the family of Osagie, a prince of the Benin Kingdom. I am currently an academic in the Department of Medical Biochemistry, University of Benin. Part of the duties are to teach undergraduate students and conduct academic research.",institutionString:null,institution:{name:"University of Benin",country:{name:"Nigeria"}}},{id:"192992",title:"Prof.",name:"Shagufta",middleName:null,surname:"Perveen",slug:"shagufta-perveen",fullName:"Shagufta Perveen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/192992/images/system/192992.png",biography:"Prof. Shagufta Perveen is a Distinguish Professor in the Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. Dr. Perveen has acted as the principal investigator of major research projects funded by the research unit of King Saud University. She has more than ninety original research papers in peer-reviewed journals of international repute to her credit. She is a fellow member of the Royal Society of Chemistry UK and the American Chemical Society of the United States.",institutionString:"King Saud University",institution:{name:"King Saud University",country:{name:"Saudi Arabia"}}},{id:"49848",title:"Dr.",name:"Wen-Long",middleName:null,surname:"Hu",slug:"wen-long-hu",fullName:"Wen-Long Hu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49848/images/system/49848.jpg",biography:"Wen-Long Hu is Chief of the Division of Acupuncture, Department of Chinese Medicine at Kaohsiung Chang Gung Memorial Hospital, as well as an adjunct associate professor at Fooyin University and Kaohsiung Medical University. Wen-Long is President of Taiwan Traditional Chinese Medicine Medical Association. He has 28 years of experience in clinical practice in laser acupuncture therapy and 34 years in acupuncture. He is an invited speaker for lectures and workshops in laser acupuncture at many symposiums held by medical associations. He owns the patent for herbal preparation and producing, and for the supercritical fluid-treated needle. Dr. Hu has published three books, 12 book chapters, and more than 30 papers in reputed journals, besides serving as an editorial board member of repute.",institutionString:"Kaohsiung Chang Gung Memorial Hospital",institution:{name:"Kaohsiung Chang Gung Memorial Hospital",country:{name:"Taiwan"}}},{id:"298472",title:"Prof.",name:"Andrey V.",middleName:null,surname:"Grechko",slug:"andrey-v.-grechko",fullName:"Andrey V. Grechko",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/298472/images/system/298472.png",biography:"Andrey Vyacheslavovich Grechko, Ph.D., Professor, is a Corresponding Member of the Russian Academy of Sciences. He graduated from the Semashko Moscow Medical Institute (Semashko National Research Institute of Public Health) with a degree in Medicine (1998), the Clinical Department of Dermatovenerology (2000), and received a second higher education in Psychology (2009). Professor A.V. Grechko held the position of Сhief Physician of the Central Clinical Hospital in Moscow. He worked as a professor at the faculty and was engaged in scientific research at the Medical University. Starting in 2013, he has been the initiator of the creation of the Federal Scientific and Clinical Center for Intensive Care and Rehabilitology, Moscow, Russian Federation, where he also serves as Director since 2015. He has many years of experience in research and teaching in various fields of medicine, is an author/co-author of more than 200 scientific publications, 13 patents, 15 medical books/chapters, including Chapter in Book «Metabolomics», IntechOpen, 2020 «Metabolomic Discovery of Microbiota Dysfunction as the Cause of Pathology».",institutionString:"Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology",institution:null},{id:"199461",title:"Prof.",name:"Natalia V.",middleName:null,surname:"Beloborodova",slug:"natalia-v.-beloborodova",fullName:"Natalia V. Beloborodova",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/199461/images/system/199461.jpg",biography:'Natalia Vladimirovna Beloborodova was educated at the Pirogov Russian National Research Medical University, with a degree in pediatrics in 1980, a Ph.D. in 1987, and a specialization in Clinical Microbiology from First Moscow State Medical University in 2004. She has been a Professor since 1996. Currently, she is the Head of the Laboratory of Metabolism, a division of the Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology, Moscow, Russian Federation. N.V. Beloborodova has many years of clinical experience in the field of intensive care and surgery. She studies infectious complications and sepsis. She initiated a series of interdisciplinary clinical and experimental studies based on the concept of integrating human metabolism and its microbiota. Her scientific achievements are widely known: she is the recipient of the Marie E. Coates Award \\"Best lecturer-scientist\\" Gustafsson Fund, Karolinska Institutes, Stockholm, Sweden, and the International Sepsis Forum Award, Pasteur Institute, Paris, France (2014), etc. Professor N.V. Beloborodova wrote 210 papers, five books, 10 chapters and has edited four books.',institutionString:"Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology",institution:null},{id:"354260",title:"Ph.D.",name:"Tércio Elyan",middleName:"Azevedo",surname:"Azevedo Martins",slug:"tercio-elyan-azevedo-martins",fullName:"Tércio Elyan Azevedo Martins",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/354260/images/16241_n.jpg",biography:"Graduated in Pharmacy from the Federal University of Ceará with the modality in Industrial Pharmacy, Specialist in Production and Control of Medicines from the University of São Paulo (USP), Master in Pharmaceuticals and Medicines from the University of São Paulo (USP) and Doctor of Science in the program of Pharmaceuticals and Medicines by the University of São Paulo. Professor at Universidade Paulista (UNIP) in the areas of chemistry, cosmetology and trichology. Assistant Coordinator of the Higher Course in Aesthetic and Cosmetic Technology at Universidade Paulista Campus Chácara Santo Antônio. Experience in the Pharmacy area, with emphasis on Pharmacotechnics, Pharmaceutical Technology, Research and Development of Cosmetics, acting mainly on topics such as cosmetology, antioxidant activity, aesthetics, photoprotection, cyclodextrin and thermal analysis.",institutionString:null,institution:{name:"University of Sao Paulo",country:{name:"Brazil"}}},{id:"334285",title:"Ph.D. Student",name:"Sameer",middleName:"Kumar",surname:"Jagirdar",slug:"sameer-jagirdar",fullName:"Sameer Jagirdar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/334285/images/14691_n.jpg",biography:"I\\'m a graduate student at the center for biosystems science and engineering at the Indian Institute of Science, Bangalore, India. I am interested in studying host-pathogen interactions at the biomaterial interface.",institutionString:null,institution:{name:"Indian Institute of Science Bangalore",country:{name:"India"}}},{id:"329248",title:"Dr.",name:"Md. Faheem",middleName:null,surname:"Haider",slug:"md.-faheem-haider",fullName:"Md. Faheem Haider",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329248/images/system/329248.jpg",biography:"Dr. Md. Faheem Haider completed his BPharm in 2012 at Integral University, Lucknow, India. In 2014, he completed his MPharm with specialization in Pharmaceutics at Babasaheb Bhimrao Ambedkar University, Lucknow, India. He received his Ph.D. degree from Jamia Hamdard University, New Delhi, India, in 2018. He was selected for the GPAT six times and his best All India Rank was 34. Currently, he is an assistant professor at Integral University. Previously he was an assistant professor at IIMT University, Meerut, India. He has experience teaching DPharm, Pharm.D, BPharm, and MPharm students. He has more than five publications in reputed journals to his credit. Dr. Faheem’s research area is the development and characterization of nanoformulation for the delivery of drugs to various organs.",institutionString:"Integral University",institution:{name:"Integral University",country:{name:"India"}}},{id:"329795",title:"Dr.",name:"Mohd Aftab",middleName:"Aftab",surname:"Siddiqui",slug:"mohd-aftab-siddiqui",fullName:"Mohd Aftab Siddiqui",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329795/images/15648_n.jpg",biography:"Dr. Mohd Aftab Siddiqui is currently working as Assistant Professor in the Faculty of Pharmacy, Integral University, Lucknow for the last 6 years. He has completed his Doctor in Philosophy (Pharmacology) in 2020 from Integral University, Lucknow. He completed his Bachelor in Pharmacy in 2013 and Master in Pharmacy (Pharmacology) in 2015 from Integral University, Lucknow. He is the gold medalist in Bachelor and Master degree. He qualified GPAT -2013, GPAT -2014, and GPAT 2015. His area of research is Pharmacological screening of herbal drugs/ natural products in liver and cardiac diseases. He has guided many M. Pharm. research projects. He has many national and international publications.",institutionString:"Integral University",institution:null},{id:"333824",title:"Dr.",name:"Ahmad Farouk",middleName:null,surname:"Musa",slug:"ahmad-farouk-musa",fullName:"Ahmad Farouk Musa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/333824/images/22684_n.jpg",biography:"Dato’ Dr Ahmad Farouk Musa\nMD, MMED (Surgery) (Mal), Fellowship in Cardiothoracic Surgery (Monash Health, Aust), Graduate Certificate in Higher Education (Aust), Academy of Medicine (Mal)\n\n\n\nDato’ Dr Ahmad Farouk Musa obtained his Doctor of Medicine from USM in 1992. He then obtained his Master of Medicine in Surgery from the same university in the year 2000 before subspecialising in Cardiothoracic Surgery at Institut Jantung Negara (IJN), Kuala Lumpur from 2002 until 2005. He then completed his Fellowship in Cardiothoracic Surgery at Monash Health, Melbourne, Australia in 2008. He has served in the Malaysian army as a Medical Officer with the rank of Captain upon completing his Internship before joining USM as a trainee lecturer. He is now serving as an academic and researcher at Monash University Malaysia. He is a life-member of the Malaysian Association of Thoracic & Cardiovascular Surgery (MATCVS) and a committee member of the MATCVS Database. He is also a life-member of the College of Surgeons, Academy of Medicine of Malaysia; a life-member of Malaysian Medical Association (MMA), and a life-member of Islamic Medical Association of Malaysia (IMAM). Recently he was appointed as an Interim Chairperson of Examination & Assessment Subcommittee of the UiTM-IJN Cardiothoracic Surgery Postgraduate Program. As an academic, he has published numerous research papers and book chapters. He has also been appointed to review many scientific manuscripts by established journals such as the British Medical Journal (BMJ). He has presented his research works at numerous local and international conferences such as the European Association for Cardiothoracic Surgery (EACTS) and the European Society of Cardiovascular Surgery (ESCVS), to name a few. He has also won many awards for his research presentations at meetings and conferences like the prestigious International Invention, Innovation & Technology Exhibition (ITEX); Design, Research and Innovation Exhibition, the National Conference on Medical Sciences and the Annual Scientific Meetings of the Malaysian Association for Thoracic and Cardiovascular Surgery. He was awarded the Darjah Setia Pangkuan Negeri (DSPN) by the Governor of Penang in July, 2015.",institutionString:null,institution:{name:"Monash University Malaysia",country:{name:"Malaysia"}}},{id:"30568",title:"Prof.",name:"Madhu",middleName:null,surname:"Khullar",slug:"madhu-khullar",fullName:"Madhu Khullar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/30568/images/system/30568.jpg",biography:"Dr. Madhu Khullar is a Professor of Experimental Medicine and Biotechnology at the Post Graduate Institute of Medical Education and Research, Chandigarh, India. She completed her Post Doctorate in hypertension research at the Henry Ford Hospital, Detroit, USA in 1985. She is an editor and reviewer of several international journals, and a fellow and member of several cardiovascular research societies. Dr. Khullar has a keen research interest in genetics of hypertension, and is currently studying pharmacogenetics of hypertension.",institutionString:"Post Graduate Institute of Medical Education and Research",institution:{name:"Post Graduate Institute of Medical Education and Research",country:{name:"India"}}},{id:"223233",title:"Prof.",name:"Xianquan",middleName:null,surname:"Zhan",slug:"xianquan-zhan",fullName:"Xianquan Zhan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/223233/images/system/223233.png",biography:"Xianquan Zhan received his MD and Ph.D. in Preventive Medicine at West China University of Medical Sciences. He received his post-doctoral training in oncology and cancer proteomics at the Central South University, China, and the University of Tennessee Health Science Center (UTHSC), USA. He worked at UTHSC and the Cleveland Clinic in 2001–2012 and achieved the rank of associate professor at UTHSC. Currently, he is a full professor at Central South University and Shandong First Medical University, and an advisor to MS/PhD students and postdoctoral fellows. He is also a fellow of the Royal Society of Medicine and European Association for Predictive Preventive Personalized Medicine (EPMA), a national representative of EPMA, and a member of the American Society of Clinical Oncology (ASCO) and the American Association for the Advancement of Sciences (AAAS). He is also the editor in chief of International Journal of Chronic Diseases & Therapy, an associate editor of EPMA Journal, Frontiers in Endocrinology, and BMC Medical Genomics, and a guest editor of Mass Spectrometry Reviews, Frontiers in Endocrinology, EPMA Journal, and Oxidative Medicine and Cellular Longevity. He has published more than 148 articles, 28 book chapters, 6 books, and 2 US patents in the field of clinical proteomics and biomarkers.",institutionString:"Shandong First Medical University",institution:{name:"Affiliated Hospital of Shandong Academy of Medical Sciences",country:{name:"China"}}},{id:"297507",title:"Dr.",name:"Charles",middleName:"Elias",surname:"Assmann",slug:"charles-assmann",fullName:"Charles Assmann",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/297507/images/system/297507.jpg",biography:"Charles Elias Assmann is a biologist from Federal University of Santa Maria (UFSM, Brazil), who spent some time abroad at the Ludwig-Maximilians-Universität München (LMU, Germany). He has Masters Degree in Biochemistry (UFSM), and is currently a PhD student at Biochemistry at the Department of Biochemistry and Molecular Biology of the UFSM. His areas of expertise include: Biochemistry, Molecular Biology, Enzymology, Genetics and Toxicology. He is currently working on the following subjects: Aluminium toxicity, Neuroinflammation, Oxidative stress and Purinergic system. Since 2011 he has presented more than 80 abstracts in scientific proceedings of national and international meetings. Since 2014, he has published more than 20 peer reviewed papers (including 4 reviews, 3 in Portuguese) and 2 book chapters. He has also been a reviewer of international journals and ad hoc reviewer of scientific committees from Brazilian Universities.",institutionString:"Universidade Federal de Santa Maria",institution:{name:"Universidade Federal de Santa Maria",country:{name:"Brazil"}}}]}},subseries:{item:{id:"14",type:"subseries",title:"Cell and Molecular Biology",keywords:"Omics (Transcriptomics; Proteomics; Metabolomics), Molecular Biology, Cell Biology, Signal Transduction and Regulation, Cell Growth and Differentiation, Apoptosis, Necroptosis, Ferroptosis, Autophagy, Cell Cycle, Macromolecules and Complexes, Gene Expression",scope:"The Cell and Molecular Biology topic within the IntechOpen Biochemistry Series aims to rapidly publish contributions on all aspects of cell and molecular biology, including aspects related to biochemical and genetic research (not only in humans but all living beings). 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Her research interests include archaea metabolism, enzymes purification and characterization, gene regulation, carotenoids and bioplastics production, antioxidant\ncompounds, waste water treatments, and brines bioremediation.\nRosa María’s other roles include editorial board member for several journals related\nto biochemistry, reviewer for more than 60 journals (biochemistry, molecular biology, biotechnology, chemistry and microbiology) and president of several organizing committees in international meetings related to the N-cycle or respiratory processes.",institutionString:null,institution:{name:"University of Alicante",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null,series:{id:"11",title:"Biochemistry",doi:"10.5772/intechopen.72877",issn:"2632-0983"},editorialBoard:[{id:"79367",title:"Dr.",name:"Ana Isabel",middleName:null,surname:"Flores",slug:"ana-isabel-flores",fullName:"Ana Isabel Flores",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRpIOQA0/Profile_Picture_1632418099564",institutionString:null,institution:{name:"Hospital Universitario 12 De Octubre",institutionURL:null,country:{name:"Spain"}}},{id:"328234",title:"Ph.D.",name:"Christian",middleName:null,surname:"Palavecino",slug:"christian-palavecino",fullName:"Christian Palavecino",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000030DhEhQAK/Profile_Picture_1628835318625",institutionString:null,institution:{name:"Central University of Chile",institutionURL:null,country:{name:"Chile"}}},{id:"186585",title:"Dr.",name:"Francisco Javier",middleName:null,surname:"Martin-Romero",slug:"francisco-javier-martin-romero",fullName:"Francisco Javier Martin-Romero",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSB3HQAW/Profile_Picture_1631258137641",institutionString:null,institution:{name:"University of Extremadura",institutionURL:null,country:{name:"Spain"}}}]},onlineFirstChapters:{paginationCount:34,paginationItems:[{id:"81595",title:"Prosthetic Concepts in Dental Implantology",doi:"10.5772/intechopen.104725",signatures:"Ivica Pelivan",slug:"prosthetic-concepts-in-dental-implantology",totalDownloads:23,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Current Concepts in Dental Implantology - 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Thus proteomics, an area of research that detects all protein forms expressed in an organism, including splice isoforms and post-translational modifications, is more suitable than genomics for a comprehensive understanding of the biochemical processes that govern life. The most common proteomics applications are currently in the clinical field for the identification, in a variety of biological matrices, of biomarkers for diagnosis and therapeutic intervention of disorders. From the comparison of proteomic profiles of control and disease or different physiological states, which may emerge, changes in protein expression can provide new insights into the roles played by some proteins in human pathologies. Understanding how proteins function and interact with each other is another goal of proteomics that makes this approach even more intriguing. Specialized technology and expertise are required to assess the proteome of any biological sample. Currently, proteomics relies mainly on mass spectrometry (MS) combined with electrophoretic (1 or 2-DE-MS) and/or chromatographic techniques (LC-MS/MS). MS is an excellent tool that has gained popularity in proteomics because of its ability to gather a complex body of information such as cataloging protein expression, identifying protein modification sites, and defining protein interactions. 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