Various advanced oxidation processes.
\\n\\n
Released this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\\n\\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\\n"}]',published:!0,mainMedia:{caption:"Highly Cited",originalUrl:"/media/original/117"}},components:[{type:"htmlEditorComponent",content:'IntechOpen is proud to announce that 191 of our authors have made the Clarivate™ Highly Cited Researchers List for 2020, ranking them among the top 1% most-cited.
\n\nThroughout the years, the list has named a total of 261 IntechOpen authors as Highly Cited. Of those researchers, 69 have been featured on the list multiple times.
\n\n\n\nReleased this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\n\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\n'}],latestNews:[{slug:"intechopen-supports-asapbio-s-new-initiative-publish-your-reviews-20220729",title:"IntechOpen Supports ASAPbio’s New Initiative Publish Your Reviews"},{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"}]},book:{item:{type:"book",id:"974",leadTitle:null,fullTitle:"Mesotheliomas - Synonyms and Definition, Epidemiology, Etiology, Pathogenesis, Cyto-Histopathological Features, Clinic, Diagnosis, Treatment, Prognosis",title:"Mesotheliomas",subtitle:"Synonyms and Definition, Epidemiology, Etiology, Pathogenesis, Cyto-Histopathological Features, Clinic, Diagnosis, Treatment, Prognosis",reviewType:"peer-reviewed",abstract:"Mesotheliomas are mysterious mesothelial tumors in that they are relatively rare, difficult to diagnose, with a large number of synonyms, and the etiology and pathogenesis of the disease are still not fully disclosed. This problem attracts the attention of various specialists in the field of medicine and biology every year. In recent years there has been a significant increase of mesothelioma morbidity in most of the countries, due to the further industrialization of society. In this regard, this book has been published with the participation of an international group of experts with rich experience from around the world . The book consists of 14 chapters containing the most advanced achievements of all aspects of the various types of mesotheliomas, both in humans and domestic animals, at a high methodological level. This book is intended for biologists and all health care workers, mostly oncologists of different profiles, as well as students of medical educational institutions engaged or even just interested in the problems of mesotheliomas.",isbn:null,printIsbn:"978-953-307-845-8",pdfIsbn:"978-953-51-6715-0",doi:"10.5772/1480",price:119,priceEur:129,priceUsd:155,slug:"mesotheliomas-synonyms-and-definition-epidemiology-etiology-pathogenesis-cyto-histopathological-features-clinic-diagnosis-treatment-prognosis",numberOfPages:258,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"75d66c9a37715a7b43ddaf0ea3e46a63",bookSignature:"Alexander Zubritsky",publishedDate:"February 3rd 2012",coverURL:"https://cdn.intechopen.com/books/images_new/974.jpg",numberOfDownloads:40858,numberOfWosCitations:3,numberOfCrossrefCitations:0,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:4,numberOfDimensionsCitationsByBook:0,hasAltmetrics:0,numberOfTotalCitations:7,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"March 22nd 2011",dateEndSecondStepPublish:"April 19th 2011",dateEndThirdStepPublish:"August 24th 2011",dateEndFourthStepPublish:"September 23rd 2011",dateEndFifthStepPublish:"January 21st 2012",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"84298",title:"Dr",name:"Alexander",middleName:"N",surname:"Zubritsky",slug:"alexander-zubritsky",fullName:"Alexander Zubritsky",profilePictureURL:"https://mts.intechopen.com/storage/users/84298/images/809_n.jpg",biography:'Alexander Nickolaevich Zubritsky is a pathologist of the highest category (2011), a member of the European Society of Pathology (1989), International Union Against Tuberculosis and Lung Disease (1990), European Section, International Society for Heart Research (1992), International Society on Diagnostic Quantitative Pathology (1994), New York Academy of Sciences (1995), Academic Board of the Atlantic-Euro-Mediterranean Academy of Medical Sciences (2008).\n He was born on March 14, 1949 (Pisces, year of the Bull) in Severo-Kurilsk, Sakhalin Region in the family of a military therapist. At age 15, worked as a hospital attendant in a pathology department of a hospital in Sverdlovsk (Yekaterinburg) and studied at night school for working youth. In 1974 he graduated the curative and preventative faculty of the Sverdlovsk Medical Institute. In 1974-1975 was an internship in pathological anatomy at the basis of Sverdlovsk Regional Clinical Hospital. In 1977 enrolled in correspondence postgraduate study at the Institute of Human Morphology in Moscow on a specialty “pathological anatomy” under the direction of the Hero of Socialist Labor, Lenin Prize laureate, Academician of AMS USSR Prof. A.I.Strukov. In 1990, he defended his thesis “Quantitative analysis of pathomorphological changes in the right ventricle of the heart in group of patients with chronic nonspecific pulmonary disease” in the I.M.Sechenov Moscow Medical Academy.\nIn 1990 he became a finalist of the Marvin I. Dunn Award for the best presentation in Cardiology at the meeting of the American College of Chest Physicians in Toronto. In 1993 in Innsbruck is awarded by the “Pathology Research and Practice” for the best reply under the heading “Expert Quiz”. He is a winner of the International Peace Prize for 2003 (UCC). In 2004 was awarded a gold medal \\"Scientist of 2004\\" (IBC). In 2005 he was awarded the World Medal of Freedom in pathological anatomy and in the same year was awarded the title \\"Man of Achievement\\" for his outstanding contributions to pathological anatomy of cor pulmonale (ABI). He is a winner of the encyclopedia “Best People of Russia” with the presentation of his commemorative medal (2006). In 2007 he was awarded the medal \\"Gold Medal for Russia\\" (ABI).\nAuthor of the 4 rationalisation proposals and 195 published works as sole author.\nPublications about the editor: Great Minds of the 21st Century (ABI, 2005), Who\\\'s Who in America (Marquis Who’s Who, 2005), Best People of Russia (Spets-Adres, 2006), Who\\\'s Who: World Edition (Astreya, 2011), etc.\nNow the editor is unemployed pensioner.',institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"1",institution:null}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"1093",title:"Thoracic Oncology",slug:"thoracic-oncology"}],chapters:[{id:"27664",title:"Molecular Pathogenesis of Malignant Pleural Mesothelioma",doi:"10.5772/33418",slug:"molecular-pathogenesis-of-malignant-pleural-mesothelioma",totalDownloads:2427,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:null,signatures:"Philip A. 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Glazzard and Samuel Stones",coverURL:"https://cdn.intechopen.com/books/images_new/10228.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"294281",title:"Prof.",name:"Jonathan",middleName:null,surname:"Glazzard",slug:"jonathan-glazzard",fullName:"Jonathan Glazzard"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}}},ofsBook:{item:{type:"book",id:"11695",leadTitle:null,title:"Biomechanical and Mechanobiological Analysis of Bone Mineral Density",subtitle:null,reviewType:"peer-reviewed",abstract:"\r\n\tBone mineral density (BMD) measures the percentage of inorganic minerals in the bones. BMD represents one of the most informative assessments of bone quality and strength in biomechanical and clinical studies. BMD depends on several factors, such as age, sex, disease, genetics, lifestyle as well as bone mechanobiology (cellular activities and bone remodeling process), which directly affect bone mass and density. Low BMD is directly associated with osteoporosis and a high risk of bone fracture.
\r\n\r\n\tThere are several techniques for measuring and qualifying BMD, such as single and dual-energy photon absorptiometry, quantitative computed tomography, and magnetic resonance imaging. Each has advantages and limitations, depending on the objective of the analysis and the bone site to be examined. Modeling and simulation are also widely used to understand and study the variation and evolution of BMD, mechanical behavior, and the risk of bone fracture.
\r\n\r\n\tThis book aims to represent a collection of original research works, literature reviews, and technical notes related to topics that deal with bone mineral density:
\r\n\t- BMD measurement technology
\r\n\t- Osteoporosis and fracture risk
\r\n\t- Bone growth and remodeling
\r\n\t
\r\n\tThe submission is also open to any other original study related to these research topics.
Water pollution is one the fundamental problems that have got the serious concerns of the researchers. Water poluution arises due to a number of reasons including domestic, industrial, agricultural, scinec and technology. The contribution of industrial sector in water pollution is significant. A number of industries like textile industry, leather industry, food industry, pharmaceutical industry, printing industries etc. release their wastewater to the environment. These wastewater of these industries contain a variety of organic and inorganic pollutants. Hence, the wastewater released from these induries cause water pollution. The water pollution due to dyes is very serious issue. The textile industry is the main industry that releases the dyes contaminated wastewater to the environment. Textile industry uses a huge amount of dyes annualy. It is estimated that about 700000 tons of the various dyes are produced annualy around the world. These dyes have been classifies as azo dyes, basic dyes, direct dyes, vat dyes, reactive dyes etc. More than 15% of the globally produced dyes are released to the environment in wastewater from textile and other industries. These dyes released in aqueous system are highly toxic and carcinogeneic in nature. These dyes badly affect the living organisms. Dyes are highly colored substances that impart intense color to the aqueous body when dyes contaminated wastewater is released into it. Due to intense color of aqueous body, the sunlight is inhibited by penetration into the interior of the aqueous body. As a result of non-penetration of sunlight, the aqueous ecosysytem is badly affected by dyes [1, 2, 3, 4, 5, 6].
A varities of protocols have been attempeted for the removal of dyes from aqueous body. Techniques like biological degradation technique, membrane filteration technique, adsorption atechniques, sedimentation technique, physical coagulation technique and chemical coagulation technique has been attempted for the elimination of dyes from aqueous medium. However, these techniques are not successful in the removal of dyes. As these techniques do not degrade the dyes molecules, therefore, these techniques fail to remove the dyes from aqueous medium. These techniques only transform the dyes pollutants from one form to another form. Furthermore, these techniques give rise secondary pollution [7, 8, 9, 10]. Hence, there is an urgent need to develop effective techniques for the removal of these dyes and other organic pollutants from aqueous medium.
The advanced oxidation processes are considered as effective alternative technique for the removal of dyes from aqueous medium. Advanced oxidation processes are chemical processes which are based on production of hydroxyl radicals. These hydroxyl radicals are highly reactive spectices. These species take part in complete degradation of organic pollutants molecules. The advanced oxidation processes include heterogeneous photocatalysis, electrochemical oxidation and Fenon reactions. Table 1 shows various advanced oxidation proceses. The advanced oxidation processes have many advantages compared to conventional techniques as follows [11, 12, 13].
The pollutants molecules are directly converted to simple inorganic molecules like water and carbon dioxide by advanced oxidation processes.
The advanced oxidation processes can degradade a wide range of organic pollutant with out any selectivity.
There is no formation of hazardous products in advanced oxidation process as the organic pollutants are converted into simple inorganic molecules like water and carbon dioxide.
No | AOP | Oxidatant | Benifits | Drawbacks |
---|---|---|---|---|
1 | Fenton’s reaction | ·O2− ·OH | No formation of bromate. No off-gas treatment. Less energy-intensive than ozone and UV alone. | Maintenance costs. Works in low pH only. Requirement of Iron extraction system. |
2 | Photocatalyst | UV ·O2− ·OH ·HO2 | Low energy requirement than other AOPs. No formation of bromate. Use of solar irradiation. No off-gas treatment. | Requirement of pre-treatment. Loss of catalytic activity with time. Sensitivity to pH. |
3 | H2O2/O3 | UV O3 ·O2− ·OH | Higher generation of OH. More effective than O3 or UV alone. Supplementary disinfectant. | Requirement of high cost and energy. Formation of bromate. Inhibition to penetration of UV light due to turbidity. Contamination due to failure of the UV lamp. |
4 | O3 | O3 ·OH | The established technique for the treatment of wastewater. Supplementary disinfectant. | Requirement ozone off-gas treatment. |
5 | Electron beam | eaq H2O2 ·OH ·H | No formation of bromate. Minimal effect of turbidity. No off-gas treatment. Can help in disinfection. | Requirement of skilled professionals. Not scalable for practical application. Energy and cost intensive. |
6 | Cavitation | ·H ·OH | Less energy consumption. No formation of bromate. Low maintenance cost. No off-gas treatment. | Not scalable for practical application. Efficiency is low. |
7 | O3/UV | O3 UV ·O2− ·OH | Higher production of OH than H2O2/UV. More effective than UV or O3 alone. | Inhibition to penetration of UV light due to turbidity. Contamination due to failure of UV lamp. Formation of bromate. Comparatively costly. |
8 | H2O2/UV | H2O2 UV ·O2− ·OH | No formation of bromate. No off-gas treatment is required. Can oxidize more MTBE compared to H2O2 or UV alone. | Inhibition to penetration of UV light due to turbidity. Contamination due to failure of the UV lamp. Absorption of UV by interfering compounds. |
Various advanced oxidation processes.
Due to the above mentioned merits of advanced oxidation processes, the advanced oxidation processes have got considerable interest of the scientists. The photocatalysis using heterogeneous metal oxide semicondutors as photocatalyst in the presence of ultra violet or visible light is one of the techniques of advanced oxidation proesses. The photocatalytic treatment of organic pollutants has got significant attention of the researchers recently. The photocatalytic technique doesnot need any extra ordinary energy requirement. Furthermore, there is no formation of hazardous by-products in photocatalysis. A large number of reports are available of photocatalytic degradation of dyes in aqueous medium. Figure 1 shows the total number of photocatalytic reports for various dyes reported during 2000–2017. Figure 2 shows the total number, percentage and number of reports under visible and ultra violet radiation for various dyes.
Number of publications on photocatalytic treatment of wastewater. This figure is reproduced with permission from Environ. Sci. Technol. 2019, 53, 2937−2947 Copyright 2019 American Chemical Society.
Classification of available photocatalytic reports on photo catalytic degradation of various dyes.
The data given in Figure 2 shows that researchers have studidied the tiazine dyes mostly. The xanthenes dyes are at second position in the mostly investigated dyes in the subject of photocatalytic degradation.
The applications and fundamentals of photocatalysis developed tremendously during the last four decades. Photocatalysis can be defined as a reaction induced by irradiation of light in the presence of a substance called a catalyst. The photocatalytic reactions are initiated by the absorption of light having energy greater than or equal to the band gap energy of the photocatalyst. The energy difference between the highest filled energy level (valence band) and lowest vacant energy level (conduction band) of photocatalytic substance is called band gap energy of the cited substance [14, 15]. The absorption of light causes the excitation of electrons from the highest filled energy level (valence band) to the lowest vacant energy level (conduction band) of the photocatalyst. This photoinduced excitation creates a positive hole (h+) in the valence band and electrons (e−) in conduction band of the substance. After formation of positive holes and electrons, two types of processes may proceed further.
The positive holes and electron recombine, and energy is released in the form of heat.
The positive holes and electrons take part in reactions and initiates a series of redox reactions called photocatalytic reactions.
Hence, for photocatalytic reactions, process 1 mentioned above (recombination of positive holes and electrons) must be prevented to favor the photocatalytic reactions. The goal of photocatalysis is to initiate reactions of positive holes and electrons with the reductants and oxidants to produce oxidized and reduced products, respectively [16].
Presently, photocatalysis is used in several emerging fields like photodegradation of aqueous organic pollutants, production of hydrogen by water splitting, treatment of gaseous environmental pollutants like NOx, treatment of halogenated hydrocarbon, inactivation of microorganisms, treatment of pesticides and organohalide compounds, oxidation of micropollutants and many more [17, 18, 19, 20, 21].
Generally, the semiconductor metal oxides are used as photocatalysts in photocatalysis. Fujishima et al., the pioneer of photocatalysis, employed titanium dioxide (TiO2) as a catalyst for the production of hydrogen gas by splitting water for the first time [22]. Water can not be decomposed by visible light because it is transparent to it. Water can only be decomposed if it is irradiated with light having a wavelength less than 190 nm. Fujishima and co-workers electrochemically decomposed water using TiO2 electrode. They reported that water can be electrochemically decomposed if a potential difference of 1.23 V is applied between anode and cathode. The potential difference of 1.23 V is equivalent to the energy of photons having wavelength about 1000 nm. Water can be electrochemically decomposed under any one of the following conditions.
The production of oxygen takes place at a potential which is more negative as compared to potential at which production of hydrogen takes place under normal conditions.
The production of hydrogen takes place at potential which is more positive as compared to potential at which production of oxygen takes place under normal conditions.
The potential at which production of oxygen takes place is made more negative and the potential at which production of hydrogen takes place is made more positive.
Fujishima and co-workers used TiO2 electrode for electrothermal decomposition of water. They investigated the current–voltage curves under light condition and dark condition. They found that anodic current flowed under the irradiation of light having wavelength less than 415 nm. The energy of these radiation is equivalent to 3.0 eV. This energy is equal to the band gap of TiO2. On the basis of these observations, it was suggested that irradiation of light produced holes in the valence band of TiO2. Similarly, the production of oxygen at −0.5 V was also confirmed by various electrochemical measurement. They constructed an electrochemical cell. The TiO2 was used as electrode which was connected to a Pt electrode. The irradiation of surface of TiO2 electrode caused a current to flow from Pt electrode to TiO2 electrode. The flow of current from Pt electrode to TiO2 electrode suggested that production of oxygen takes place TiO2 electrode by oxidation reaction and production of hydrogen takes place at Pt electrode by reduction reaction. It was suggested irradiation caused decomposition of water in the absence of any external potential. The decomposition of water took place according to following reactions.
Production of hole and electron by excitation of TiO2
Production of oxygen by oxidation reaction at TiO2
Production of hydrogen by reduction at Pt
The net decomposition reaction is
Since the work of Fujishima et al., TiO2 gained the attention of many researchers and presently it is the most used substance in the field of photocatalysis.
Titanium dioxide (TiO2) exists in three crystalline phases: Brookite, Anatase, and Rutile phase. The Brookite phase of titanium dioxide is unstable and therefore it is not used in photocatalytic applications. Anatase and Rutile phases of titanium dioxide are thermodynamically stable phases. The rutile phase is mostly used in photocatalytic applications due to its easy preparation and higher catalytic performance. Studies have shown that mixed phases of titanium dioxide are used as catalysts for higher photocatalytic performances. It is believed that mixed phases titanium dioxide exhibits higher catalytic performance due to the movement of photoinduced electrons from Rutile to Anatase phase of titanium dioxide. This movement of electrons prevents the recombination of positive holes and electrons and ultimately enhances the photocatalytic performance [23, 24, 25]. However, it has also been shown that electrons move from Anatase to Rutile phase in mixed-phase photocatalysts [26]. The band gap energy of the anatase and rutile phase of titanium dioxide is 3.2 eV and 3.0 eV, respectively. Irradiation of titanium dioxide with photons havening energy equal to or greater than 3.2 eV results in the excitation of an electron from the valence band to the conduction band. This excitation results in the formation of an electron–hole pair. These photo-induced charges move to the surface of titanium dioxide and promote a series of redox reactions. The positive holes lead to the formation of vacancies in titanium dioxide as well as excite the reduced species. The photoinduced electrons produce O2• free radicals. These free radicals are highly reactive and unstable species, so they react further [27, 28]. This whole process can be summarized as follows.
Production of positive hole and electron by excitation of TiO2
Recombination of positive hole and electron
Production of OH radical by oxidation of water by reaction with positive hole
Reduction of oxygen by reaction with electron
Production of OH radical by reaction of super oxide anion with water
Reaction of OH radicals with reactants
The mechanism given above has been proposed based on electron spin resonance (ESR) and spin trapping studies. However, Ângelo [29] reported 82% conversion of NO for a feed containing 75% NO and 25% RH with −20°C as dew point; the same work indicates that the water-adsorbed monolayer is reached for a relative humidity of 25%. If OH• were the main species in the conversion of NO, then the conversion of NO for dry feed would be much smaller. Hence, this study questions Eq. (3) in the above mechanism or otherwise the role of OH• radicals in photocatalysis. Montoya et al., [30] reported against the formation of OH• radicals by direct reaction of positive holes with water. They proposed a direct–indirect model (D-I) for titanium dioxide catalyzed reactions. The proposed mechanism is given and explained in Figure 3. They proposed two mechanisms for the transfer of interfacial charges.
In the case of stronger electronic interaction, there is a direct transfer (DT) of the photo-induced positive holes for the reactions with adsorbed species.
In the case of weaker interaction, there is an indirect transfer (IT) of the photo-induced positive holes. The transfer of positive holes takes place in two steps. In the first step, the positive holes are trapped by lattice oxygen of TiO2 and generate lattice oxygen radicals. In the second step, the trapped holes are transferred to the adsorbed reactants through tunneling.
Graphical representation of direct–indirect mechanism; a) direct transfer of positive holes, b) indirect transfer of positive holes.
Although titanium dioxide has been used successfully as a photocatalyst for several reactions. However, its wide band gap (3.2 eV) limits its photocatalytic applications. Due to its wide band gap, titanium dioxide can be used as a photocatalyst under ultraviolet radiation only. The best photocatalyst is one that can be used under visible light as well as ultraviolet light because the sunlight is mainly composed of visible light. Being longer wavelength, the visible light can not excite electrons from the valence band to the conduction band of the titanium dioxide. The photocatalytic performance of titanium dioxide can be improved in two ways.
By prevention of recombination of photoinduced positive holes and electrons
By narrowing the band gap of the TiO2
The prevention of recombination of photoinduced positive holes and electrons will permit the occurrence of redox reactions of the positive holes and electrons. These redox reactions will generate hydroxyl radicals and ultimately the photocatalytic performance will be enhanced.
The narrowing of band gap will allow the absorption of visible light by photocatalyst, so the photocatalyst will absorb a wide range of the solar spectrum. The solar spectrum consists of 47% infrared, 46% visible, and 4–5% ultraviolet light. Hence the absorption of visible light will also improve the photocatalytic performance. It has been reported that recombination of the photoinduced positive holes and electrons has a significant contribution to the photocatalytic performance of the catalysts. Most of the researchers work to develop methods and techniques to prevent the recombination of these positive holes and electrons [31, 32, 33]. The researchers have proposed that crystal structure significantly affects the photocatalytic performance of the photocatalyst as it plays a significant role in the recombination of positive holes and electrons. Hence, attempts have been made for modifications in the crystal structure to improve the photocatalytic performance of titanium dioxide.
Furthermore, the low photo conversion efficiency of the TiO2 is also a challenge for the researchers. It has been reported that loss of efficiency is associated with each photo catalytic step. Due to loss of efficiency at each step, the observed photo catalytic efficiency with TiO2 reported in literature is very low. This low photo catalytic efficiency of TiO2 is the critical drawback associated with TiO2 catalyzed treatment. Hence, the photocatalytic efficiency is expected to be low compared to other advanced oxidation processes. However, the TiO2 has the ability to absorb less energetic photons. This characteristic of TiO2 enable the researcher to develop TiO2 based photo catalysts that can absorb light in visible region. The presence of hydrogen peroxide is not needed in visible light photocatalysis. The presenece of hydrogen peroxide is needed in other advanced oxidation processes.
Various structural modifications in the crystal structure of titanium dioxide have been proposed for the improvement of its photocatalytic performance. All these modifications enhance the photocatalytic performance by decreasing the rate of recombination of positive holes and electrons. These modifications allow the absorption of visible light as well. Two types of structural modifications are commonly used for enhancement in the photocatalytic performance of titanium dioxide. These modifications are doping of titanium dioxide with metals or nonmetals and formation of heterojunctions with other semiconductors.
Doping is the addition of elements (impurities) into the inner structure of titanium dioxide. The doping of elements causes a red shift in the absorption of light. It also causes the prevention of recombination of photo-induced positive holes and electrons. Hence, doping improves the photocatalytic performance by absorbing of wide range of radiations and separation of charge carriers. Silver (Ag) is one of the elements used for doping of titanium dioxide. The silver (Ag) doping is used for improvement of photocatalytic performance of titanium dioxide towards photo degradation of organic pollutants [34, 35, 36]. Saeed et al., [37] have reported the improvement in photocatalytic performance of titanium dioxide for photodegradation of methylene blue and rhodamine B dyes by incorporation of silver (Ag) in the structure of titanium dioxide. They investigated the effect of silver (Ag) on the photocatalytic performance of titanium dioxide using 2, 4, 6, and 8% loading of Ag on titanium dioxide. They reported 65, 84, 97, and 78% photodegradation of methylene blue over 2, 4, 6, and 8% Ag-TiO2 as a catalyst, respectively. It was found that doping of Ag enhanced the photocatalytic performance of titanium dioxide significantly. Figure 4 shows the comparison of photocatalytic activity of TiO2 and 6% Ag-TiO2 for photodegradation of methylene blue and rhodamine B. The data given in Figure 4 was obtained by performing degradation experiments with 0.1 g of Ag-TiO2. A 50 mL solution of methylene blue and/or rhodamine B having concentration of 100 mg/L was used asmodel solution separately for degradation study.
Comparison of photocatalytic performance of TiO2 and Ag-TiO2 towards photodegradation of methylene blue dye (a) and rhodamine B dye (b) [
It was found that higher loading of Ag decreased the photocatalytic performance of titanium dioxide. Higher loading of Ag blocks the active sites of the catalyst, therefore the photocatalytic performance decreased [38].
Similarly, Ag-TiO2 with 1, 3, 5, 7, and 10% Ag have been also reported for photodegradation of methylene blue and methyl orange dyes [39]. In this study, the Ag-TiO2 loaded with 5% Ag showed the highest photocatalytic performance for photodegradation of dyes. it was reported that doping of silver generates the surface defects by the creation of oxygen vacancies and Ti (III) sites in the structure of TiO2. The formation of Ti (III) has been proposed by the flow of electrons from Ag to Ti (IV). The generation of oxygen vacancies leads to the formation of defect energy levels below the conduction band of TiO2. Also, the incorporation of Ag narrows the band gap of titanium dioxide due to the formation of Ag 4 d states. These modifications favor the excitation of electrons from the valence band to the conduction band under visible light irradiations. The photogenerated positive holes and electrons flow to the surface of titanium dioxide. The positive holes initiate oxidation by reaction with H2O or OH ions and generate reactive hydroxyl radicals (OH•). Similarly, the photogenerated electrons initiate reduction by reaction with adsorbed oxygen and give rise to super oxide anion radicals. The photo-generated positive holes are trapped by Ag as well and produce Ag (II). The Ag (II) also initiate oxidation reactions by reaction with H2O or OH ions and ultimately produce hydroxyl radicals (OH•). Similarly, the Ag (I) traps the photo-generated electrons and produces Ag (0) and then these trapped electrons are transferred to oxygen or Ti (IV). Hence, the recombination of positive holes and electrons is decreased and ultimately the photocatalytic performance is increased [40, 41, 42, 43, 44]. Chemical reactions 11 to 18 explain the whole mechanism.
Similarly, other elements can also be used for doping TiO2. Doping of nitrogen is also one of the most studied approaches for the enhancement of photocatalytic performance of titanium dioxide. The doping of nitrogen has been used to extend the absorption of light towards the visible wavelength side. Some of the others have reported that doping of nitrogen results in narrowing of the band gap of titanium dioxide. Some researchers have argued the interaction between valance band, conduction band, and energy states of doping element cause the narrowing of band gap [13, 45, 46]. Di Valentin and co-workers [47] have reported the density functional theory (DFT) study for the evaluation of the photocatalytic performance of N-doped-TiO2. They predicted that nitrogen atoms occupy either interstitial or substitutional sites in the lattice of titanium dioxide. As a result, localized energy states are generated. In the case of the interstitial position of nitrogen, discrete energy states are formed above the valence band. In the case of the substitutional position of nitrogen atoms, energy levels are formed in extension to the valence band. In the same way, the doping of other elements like carbon can also improve the catalytic performance of titanium dioxide by narrowing its band gap [48]. It has also been reported that modifications in the (101) plane of titanium dioxide take place with doping of elements. The modifications resulted from the doping of elements enhance the movement of photo-generated electrons to other places within the structure. This flow of electrons to other places increases the lifetime of photo-induced charge carriers and ultimately causes an improvement in photocatalytic performance [49].
Although the doping of elements in the lattice of titanium dioxide has been used for enhancement in the photocatalytic performance of titanium dioxide, however, these dopants may also decrease the photocatalytic performance as these dopants can promote the recombination of photogenerated positive holes and electron. Therefore, the doping of elements in high concentrations must be avoided [50].
The photo catalytic performance of TiO2 can be enhanced by doping of iron as well. The doping ot TiO2 with iron produces mixed oxides as well as mixture composed of mixed oxides and simple oxides. The Fe (III) and Ti (IV) have almost similar radii, therefore, Fe(III) occupies the substitutional positions. The presence of Fe (III) decrease the rate of recombination of positive holes and electrons by separating them and hence ultimately increases the catalytic performance. The Fe(III) traps the positive hole and produces Fe(IV). Then, the Fe (IV) reacts with hydroxyl ions and produce the hydroxyl radicals and O2− [51, 52]. The doping of TiO2 with Fe shifts the light absorption ability towards visible light region. Under irradiation by visible light, excitation takes place (Fe(III)/Fe(IV) to conduction band of TiO2. By irradiation, the Fe(III) changes to Fe(IV) by absorption of visible radiation because the t2g level of d orbital of Fe(III) is above the valence band of TiO2. The electron released from Fe(III) is shifted to conduction band of TiO2. The shifted electron produces hydroxyl radicals by further reactions.
A heterojunction is an interface that occurs between two layers or regions of dissimilar crystalline semiconductors. As stated in an earlier section that titanium dioxide is very important in photocatalysis. However, two factors limit the photocatalytic activity of titanium dioxide. These factors include the wide band gap and fast recombination of positive holes and electrons. The formation of heterojunction of titanium dioxide with other semiconductor metals oxide is also an attempt to improve the photocatalytic performance by separation of positive holes and electrons and narrowing the band gap. The synthesis of heterojunction or composite of titanium dioxide with other semiconductors has gained much attention [53]. The formation of heterojunction shifts the absorption capacity of titanium dioxide towards the visible wavelength side and thus improves the catalytic performance. Different semiconductor metal oxides can be used for the formation of heterojunction. Zinc oxide (ZnO) is one of the semiconductors that can be used for the formation of heterojunction of titanium dioxide. The zinc oxide has band gap similar to titanium dioxide and it possesses good catalytic activity. Therefore, the TiO2-ZnO heterojunction is expected to show good photocatalytic performance under visible light irradiation [54, 55, 56]. Saeed and his coworkers [57] have reported the synthesis of ZnO-TiO2 heterojunction as an efficient photocatalyst for the photodegradation of methyl orange. They found that photodegradation of methyl orange was 98% with ZnO-TiO2 catalyst. The photocatalytic performance was much higher than the photocatalytic performance of ZnO and TiO2 alone having 75 and 60% activity, respectively. Figure 5 shows the comparison of photocatalytic performance of ZnO-TiO2 heterojunction with pure semiconductor ZnO and TiO2. The data given in Figure 5 was obtained by performing degradation experiments with 50 mg of ZnO or TiO2 or ZnO-TiO2. A 50 mL solution of methyl orange having concentration of 100 mg/L was used asmodel solution for degradation study.
Comparison of photo catalytic performance of ZnO-TiO2, ZnO and TiO2 towards photodegradation of methyl orange [
The ZnO-TiO2 exhibited higher photocatalytic performance due to the synergistic effect between zinc oxide and titanium dioxide. This synergetic effect arises due to the formation of heterojunction. When ZnO-TiO2 heterojunction is irradiated with light, positive holes and electrons are formed in valence band and conduction band respectively. The positive hole flows from the titanium dioxide valence band to the zinc oxide valence band. At the same time, the electrons flow from the zinc oxide conduction band to the titanium dioxide conduction band. This flow of positive holes and electrons has been explained in Figure 6. The flow of positive holes and electrons separates the positive holes and electrons from one another. As a result, the recombination of positive holes and electrons is suppressed. Therefore, these positive holes and electrons take proceed the redox reactions. Hence, the photocatalytic performance is increased.
Process of separation of positive holes and electrons for the improvement of photocatalytic performance towards photodegradation of methyl orange [
Similarly, heterojunctions of titanium dioxide with other semiconductors have also been reported. For example, Abd-Rabboh and his co-workers [53] have reported the synthesis of BiVO4-TiO2 heterojunction as an effective photocatalyst for photodegradation of rhodamine B dye. They reported the heterojunction between BiVO4 and TiO2 for the production of hydrogen gas and photo degradation of rhodamine B dye. it was found that formation of heterojunction shifted that absorption of radiation by TiO2 towards visible light region. The prepared heterojunction was tested as catalysts for degradation of rhodamine B dye. It was found that BiVO4-TiO2 heterojunction showed a photo catalytic performance of ten times greater than bare TiO2. The rate constant for photodegradation of rhodamine B were 0.021 and 0.0023 per minute with BiVO4-TiO2 and TiO2 as catalyst respectively. Mousavi and Ghasemi [58] have reported TiO2-CoTiO3 heterojunction as photocatalyst for photodegradation of different dyes. They reported 99% photodegradation of methyl orange, methylene blue, and rhodamine b dye over TiO2-CoTiO3 heterojunction as photocatalyst under visible light irradiation. Another research group [59] has used TiO2-Ti3C2 heterojunction as a catalyst for photodegradation of methyl orange with 99% performance under sunlight irradiation. CuO-TiO2 heterojunction has also been reported for photodegradation of phenol with excellent photocatalytic performance [60]. Hence, it is concluded that the formation of heterojunction for titanium dioxide with other semiconductor metal oxide enhanced the photocatalytic performance of titanium dioxide.
Although a lot of literature is available on photocatalytic degradation of dyes and other organic pollutants in the presence of TiO2 based photocatalysts, a summary is given in Table 2.
No | Catalyst | Substrate | Comments | Reference |
---|---|---|---|---|
1 | TiO2-SiO2 | Acid Orange 7 (AO7) | TiO2-SiO2 was 12.3 and 2.3 times efficient than TiO2 and P-25 | [61] |
2 | TiO2-zeolite | C.I. Basic Violet 10 | Photodegradation followed 1st order kinetics | [62] |
3 | TiO2-zeolite | Methyl Orange (MO) | TiO2-zeolite exhibited higher performance irrespective of concentration of MO | [63] |
4 | TiO2 Degussa P-25 | Malachite Green (MG) | 99.9% degradation achieved with 0.5 g/L catalyst, Catalytic performance was higher at pH higher than ZPC pH | [64] |
5 | TiO2-graphitic carbon (TiO2-GC) | Rhodamine B | TiO2-GC-950 showed rate of 0.012 per min compared to rate of 0.006 per min with TiO2 | [65] |
6 | TiO2-graphitic carbon (TiO2-GC) | Phenol | TiO2-GC-950 showed rate of 0.012 per min compared to rate of 0.008 per min with TiO2 | [65] |
7 | TiO2 Degussa P-25 | Triphenylmethane dye | Degussa P-25 was much active than than other TiO2 | [66] |
8 | TiO2 Degussa | C.I. Reactive Red | Formation of electrons and holes by irradiation were confirmed by persulfate ions and ethaol | [67] |
9 | TiO2 nanoparticles | Reactive Red | Optimum pH 3, increase in dye concentration decreased color removal | [68] |
10 | TiO2-glass photoreactor | Methyl Red | TiO2-glass photoreactor showed lower catalytic performance than TiO2, because immobilization reduced active surface area | [69] |
11 | TiO2-Carbon | Phenol | Both TiO2-Carbon catalysts with pellet and powder carbon showed good performance | [70] |
12 | TiO2 Degussa | Phenol | TiO2 combined with hydrogen peroxide and ultra violet light showed good catalytic performance | [71] |
13 | TiO2 prepared by sol–gel method | Phenol | The operating conditions significantly affected the catalytic activity | [72] |
14 | Commercial TiO2 | Bisphenol A (BPA) | Complete degradation achieved after 20 h under UV irradiation | [73] |
15 | TiO2-MWCNTs | 2,4-dinitrophenol | 0.05% MWCNTs:TiO2 was best combination | [74] |
16 | TiO2-Activated carbon | 2,4-dichlorophenol (DCP) | Improved catalytic performance was due to synergistic effect | [75] |
17 | Cerium-doped TiO2 | Phenol | The optimum doping was found as 0.4 wt % | [76] |
18 | Iron-doped TiO2 | Methylene blue | The optimum doping was found as 0.1 mole % | [77] |
19 | Vanadium-doped TiO2 | 2,4-dichlorophenol and Methylene Blue | The optimum doping was found as 1 mole % | [78] |
20 | Bismuth-doped TiO2 | Methylene blue | The optimum doping was found as 0.05 mole % | [79] |
A summary of photocatalytic degradation of pollutant in the presence of TiO2 based photocatalysts.
Water pollution is one the fundamental problems that have got the serious concerns of the researchers. Water poluution arises due to a number of reasons including domestic, industrial, agricultural, scinec and technology. The textile industry is the main industry that releases the dyes contaminated wastewater to the environment. A varities of protocols have been attempeted for the removal of dyes from aqueous body. Photocatalysis plays a significant role in various applications. Semiconductor metal oxides are used as photocatalysts in photocatalysis. Titanium dioxide is one of the metal oxides that has been used widely in photocatalytic applications. The titanium dioxide can be used as a photocatalyst under irradiation of ultraviolet light. The photocatalytic applications of titanium dioxide are limited by (i) wide band gap (ii) fast recombination of positive holes and electrons and (iii) activation under ultraviolet light only. Various modifications in the structure of titanium dioxide have been suggested to overcome the cited limitations. The doping of other elements in the structure of titanium dioxide and the formation of heterojunctions between titanium dioxide and other semiconductor metal oxides have been reported as effective attempts to enhance the photocatalytic performance of titanium dioxide.
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].
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].
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].
(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.
Renin-Angiotensin System.
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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Aalborg University has Two Satellite Campuses, one in Copenhagen (Aalborg University Copenhagen) and the other in Esbjerg (Aalborg University Esbjerg).\n· He is a member of prestigious IEEE (Institute of Electrical and Electronics Engineers), and IAENG (International Association of Engineers) organizations. \n· He is the chief Editor of the Journal of Software Engineering.\n· He is the member of the Editorial Board of International Journal of Computer Science and Software Technology (IJCSST) and International Journal of Computer Engineering and Information Technology. \n· He is also the Editor of Communication in Computer and Information Science CCIS-20 by Springer.\n· Reviewer For Many Conferences\nHe is the lead person in making collaboration agreements between Aalborg University and many universities of Pakistan, for which the MOU’s (Memorandum of Understanding) have been signed.\nProfessor Akbar is working in Academia since 1990, he started his career as a Lab demonstrator/TA at the University of Sussex. After finishing his P. hD degree in 1992, he served in the Industry as a Scientific Officer and continued his academic career as a visiting scholar for a number of educational institutions. In 1996 he joined National University of Science & Technology Pakistan (NUST) as an Associate Professor; NUST is one of the top few universities in Pakistan. In 1999 he joined an International Company Lineo Inc, Canada as Manager Compiler Group, where he headed the group for developing Compiler Tool Chain and Porting of Operating Systems for the BLACKfin processor. The processor development was a joint venture by Intel and Analog Devices. In 2002 Lineo Inc., was taken over by another company, so he joined Aalborg University Denmark as an Assistant Professor.\nProfessor Akbar has truly a multi-disciplined career and he continued his legacy and making progress in many areas of his interests both in teaching and research. 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Advances in aeronautical engineering have enabled next-generation aircraft to operate well beyond the natural limits of human endurance. Although the demand for unmanned systems is increasing exponentially, continued use of manned aircraft is still desirable within civilian and military operations for various safety and security reasons. With the continued presence of pilots in cockpits, future aircraft designers will require a basic understanding of the unique physiological factors affecting human performance in this domain. Given knowledge of human limitations, strategies for real-time on board monitoring of the “human system” may be employed to increase the safety of the pilot and aircraft.",book:{id:"6399",slug:"aircraft-technology",title:"Aircraft Technology",fullTitle:"Aircraft Technology"},signatures:"Douglas Summerfield, David Raslau, Bruce Johnson and Lawrence\nSteinkraus",authors:[{id:"161053",title:"Dr.",name:"Bruce",middleName:null,surname:"Johnson",slug:"bruce-johnson",fullName:"Bruce Johnson"},{id:"216519",title:"Dr.",name:"Douglas",middleName:null,surname:"Summerfield",slug:"douglas-summerfield",fullName:"Douglas Summerfield"},{id:"231816",title:"Dr.",name:"David",middleName:null,surname:"Raslau",slug:"david-raslau",fullName:"David Raslau"},{id:"231819",title:"Dr.",name:"Lawrence",middleName:null,surname:"Steinkraus",slug:"lawrence-steinkraus",fullName:"Lawrence Steinkraus"}]},{id:"69603",title:"Introduction to Satellite Attitude Control",slug:"introduction-to-satellite-attitude-control",totalDownloads:1381,totalCrossrefCites:1,totalDimensionsCites:1,abstract:"This chapter will introduce the space environment satellites must operate in, the motion they make in orbit, and their orientation while in orbit. The forces acting on the spacecraft will be considered, along with the implications of conservation of energy. The fundamentals of orbital mechanics will be presented, so common orbits can be visualized and discussed in terms of the six classical orbital elements. Perturbations impacting the orbit are covered for a better understanding of how orbits change over time. The inertial frame of reference will be defined and then transformed into body coordinates of the satellite using the direction cosine matrix and quaternions to describe the attitude of the spacecraft. A variety of modern attitude control techniques will be developed in the following chapters.",book:{id:"7761",slug:"advances-in-spacecraft-attitude-control",title:"Advances in Spacecraft Attitude Control",fullTitle:"Advances in Spacecraft Attitude Control"},signatures:"Henry Travis",authors:[{id:"290765",title:"Mr.",name:"Henry",middleName:null,surname:"Travis",slug:"henry-travis",fullName:"Henry Travis"}]},{id:"56312",title:"Design and Development of Aerial Robotic Systems for Sampling Operations in Industrial Environment",slug:"design-and-development-of-aerial-robotic-systems-for-sampling-operations-in-industrial-environment",totalDownloads:1480,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"This chapter describes the development of an autonomous fluid sampling system for outdoor facilities, and the localization solution to be used. The automated sampling system will be based on collaborative robotics, with a team of a UAV and a UGV platform travelling through a plant to collect water samples. The architecture of the system is described, as well as the hardware present in the UAV and the different software frameworks used. A visual simultaneous localization and mapping (SLAM) technique is proposed to deal with the localization problem, based on authors’ previous works, including several innovations: a new method to initialize the scale using unreliable global positioning system (GPS) measurements, integration of attitude and heading reference system (AHRS) measurements into the recursive state estimation, and a new technique to track features during the delayed feature initialization process. These procedures greatly enhance the robustness and usability of the SLAM technique as they remove the requirement of assisted scale initialization, and they reduce the computational effort to initialize features. To conclude, results from experiments performed with simulated data and real data captured with a prototype UAV are presented and discussed.",book:{id:"5847",slug:"aerial-robots-aerodynamics-control-and-applications",title:"Aerial Robots",fullTitle:"Aerial Robots - Aerodynamics, Control and Applications"},signatures:"Rodrigo Munguia, Edmundo Guerra, Sarquis Urzua, Yolanda Bolea\nand Antoni Grau",authors:[{id:"13038",title:"Prof.",name:"Antoni",middleName:null,surname:"Grau",slug:"antoni-grau",fullName:"Antoni Grau"},{id:"18024",title:"Dr.",name:"Yolanda",middleName:null,surname:"Bolea",slug:"yolanda-bolea",fullName:"Yolanda Bolea"},{id:"163432",title:"Dr.",name:"Rodrigo",middleName:null,surname:"Munguia",slug:"rodrigo-munguia",fullName:"Rodrigo Munguia"},{id:"165970",title:"Ph.D. Student",name:"Edmundo",middleName:null,surname:"Guerra",slug:"edmundo-guerra",fullName:"Edmundo Guerra"},{id:"201103",title:"Mr.",name:"Sarquis",middleName:null,surname:"Urzua",slug:"sarquis-urzua",fullName:"Sarquis Urzua"}]},{id:"61403",title:"Aircraft Gas-Turbine Engine with Coolant Injection for Effective Thrust Augmentation as Controlled Object",slug:"aircraft-gas-turbine-engine-with-coolant-injection-for-effective-thrust-augmentation-as-controlled-o",totalDownloads:1435,totalCrossrefCites:4,totalDimensionsCites:5,abstract:"This chapter deals with some intensive methods regarding aircraft gas-turbine-engine performance enhancement, which are suitable alternatives for the most common temporarily thrust increasing method—the afterburning. Coolant injection method, into the compressor or into the combustor, realizes the desired thrust increase for a short period, when the flight conditions or other aircraft necessities require this. Both methods were studied from aircraft engine’s point of view, considering it as controlled object. New engine’s mathematical model was built up, following the thermo- and gas-dynamics changes and some quality studies were performed, based on engine’s time behavior simulations; some control options and schemes were also studied. Quantitative studies were based on the model of an existing turbo-engine; mathematical model’s coefficients are both experimentally determined (in the Aerospace Engineering Division labs) as well as estimated based on graphic-analytic methods. This approach and the presented methods could be applied to any other turbo-jet engine and used even in the stage of pre-design of a new engine, to estimate its stability and quality.",book:{id:"6399",slug:"aircraft-technology",title:"Aircraft Technology",fullTitle:"Aircraft Technology"},signatures:"Alexandru Nicolae Tudosie",authors:[{id:"30042",title:"Dr.",name:"Alexandru Nicolae",middleName:"Nicolae",surname:"Tudosie",slug:"alexandru-nicolae-tudosie",fullName:"Alexandru Nicolae Tudosie"}]}],onlineFirstChaptersFilter:{topicId:"111",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:90,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:107,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:33,numberOfPublishedChapters:330,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:14,numberOfPublishedChapters:145,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:9,numberOfPublishedChapters:139,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:122,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:112,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:21,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:10,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:"2753-6580",doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}},{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}}]},series:{item:{id:"14",title:"Artificial Intelligence",doi:"10.5772/intechopen.79920",issn:"2633-1403",scope:"Artificial Intelligence (AI) is a rapidly developing multidisciplinary research area that aims to solve increasingly complex problems. In today's highly integrated world, AI promises to become a robust and powerful means for obtaining solutions to previously unsolvable problems. This Series is intended for researchers and students alike interested in this fascinating field and its many applications.",coverUrl:"https://cdn.intechopen.com/series/covers/14.jpg",latestPublicationDate:"July 5th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:9,editor:{id:"218714",title:"Prof.",name:"Andries",middleName:null,surname:"Engelbrecht",slug:"andries-engelbrecht",fullName:"Andries Engelbrecht",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRNR8QAO/Profile_Picture_1622640468300",biography:"Andries Engelbrecht received the Masters and PhD degrees in Computer Science from the University of Stellenbosch, South Africa, in 1994 and 1999 respectively. He is currently appointed as the Voigt Chair in Data Science in the Department of Industrial Engineering, with a joint appointment as Professor in the Computer Science Division, Stellenbosch University. Prior to his appointment at Stellenbosch University, he has been at the University of Pretoria, Department of Computer Science (1998-2018), where he was appointed as South Africa Research Chair in Artifical Intelligence (2007-2018), the head of the Department of Computer Science (2008-2017), and Director of the Institute for Big Data and Data Science (2017-2018). In addition to a number of research articles, he has written two books, Computational Intelligence: An Introduction and Fundamentals of Computational Swarm Intelligence.",institutionString:null,institution:{name:"Stellenbosch University",institutionURL:null,country:{name:"South Africa"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:6,paginationItems:[{id:"22",title:"Applied Intelligence",coverUrl:"https://cdn.intechopen.com/series_topics/covers/22.jpg",isOpenForSubmission:!0,editor:{id:"27170",title:"Prof.",name:"Carlos",middleName:"M.",surname:"Travieso-Gonzalez",slug:"carlos-travieso-gonzalez",fullName:"Carlos Travieso-Gonzalez",profilePictureURL:"https://mts.intechopen.com/storage/users/27170/images/system/27170.jpeg",biography:"Carlos M. Travieso-González received his MSc degree in Telecommunication Engineering at Polytechnic University of Catalonia (UPC), Spain in 1997, and his Ph.D. degree in 2002 at the University of Las Palmas de Gran Canaria (ULPGC-Spain). He is a full professor of signal processing and pattern recognition and is head of the Signals and Communications Department at ULPGC, teaching from 2001 on subjects on signal processing and learning theory. His research lines are biometrics, biomedical signals and images, data mining, classification system, signal and image processing, machine learning, and environmental intelligence. He has researched in 52 international and Spanish research projects, some of them as head researcher. He is co-author of 4 books, co-editor of 27 proceedings books, guest editor for 8 JCR-ISI international journals, and up to 24 book chapters. He has over 450 papers published in international journals and conferences (81 of them indexed on JCR – ISI - Web of Science). He has published seven patents in the Spanish Patent and Trademark Office. He has been a supervisor on 8 Ph.D. theses (11 more are under supervision), and 130 master theses. He is the founder of The IEEE IWOBI conference series and the president of its Steering Committee, as well as the founder of both the InnoEducaTIC and APPIS conference series. He is an evaluator of project proposals for the European Union (H2020), Medical Research Council (MRC, UK), Spanish Government (ANECA, Spain), Research National Agency (ANR, France), DAAD (Germany), Argentinian Government, and the Colombian Institutions. He has been a reviewer in different indexed international journals (<70) and conferences (<250) since 2001. He has been a member of the IASTED Technical Committee on Image Processing from 2007 and a member of the IASTED Technical Committee on Artificial Intelligence and Expert Systems from 2011. \n\nHe has held the general chair position for the following: ACM-APPIS (2020, 2021), IEEE-IWOBI (2019, 2020 and 2020), A PPIS (2018, 2019), IEEE-IWOBI (2014, 2015, 2017, 2018), InnoEducaTIC (2014, 2017), IEEE-INES (2013), NoLISP (2011), JRBP (2012), and IEEE-ICCST (2005)\n\nHe is an associate editor of the Computational Intelligence and Neuroscience Journal (Hindawi – Q2 JCR-ISI). He was vice dean from 2004 to 2010 in the Higher Technical School of Telecommunication Engineers at ULPGC and the vice dean of Graduate and Postgraduate Studies from March 2013 to November 2017. He won the “Catedra Telefonica” Awards in Modality of Knowledge Transfer, 2017, 2018, and 2019 editions, and awards in Modality of COVID Research in 2020.\n\nPublic References:\nResearcher ID http://www.researcherid.com/rid/N-5967-2014\nORCID https://orcid.org/0000-0002-4621-2768 \nScopus Author ID https://www.scopus.com/authid/detail.uri?authorId=6602376272\nScholar Google https://scholar.google.es/citations?user=G1ks9nIAAAAJ&hl=en \nResearchGate https://www.researchgate.net/profile/Carlos_Travieso",institutionString:null,institution:{name:"University of Las Palmas de Gran Canaria",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null},{id:"23",title:"Computational Neuroscience",coverUrl:"https://cdn.intechopen.com/series_topics/covers/23.jpg",isOpenForSubmission:!0,editor:{id:"14004",title:"Dr.",name:"Magnus",middleName:null,surname:"Johnsson",slug:"magnus-johnsson",fullName:"Magnus Johnsson",profilePictureURL:"https://mts.intechopen.com/storage/users/14004/images/system/14004.png",biography:"Dr Magnus Johnsson is a cross-disciplinary scientist, lecturer, scientific editor and AI/machine learning consultant from Sweden. \n\nHe is currently at Malmö University in Sweden, but also held positions at Lund University in Sweden and at Moscow Engineering Physics Institute. \nHe holds editorial positions at several international scientific journals and has served as a scientific editor for books and special journal issues. \nHis research interests are wide and include, but are not limited to, autonomous systems, computer modeling, artificial neural networks, artificial intelligence, cognitive neuroscience, cognitive robotics, cognitive architectures, cognitive aids and the philosophy of mind. \n\nDr. Johnsson has experience from working in the industry and he has a keen interest in the application of neural networks and artificial intelligence to fields like industry, finance, and medicine. \n\nWeb page: www.magnusjohnsson.se",institutionString:null,institution:{name:"Malmö University",institutionURL:null,country:{name:"Sweden"}}},editorTwo:null,editorThree:null},{id:"24",title:"Computer Vision",coverUrl:"https://cdn.intechopen.com/series_topics/covers/24.jpg",isOpenForSubmission:!0,editor:{id:"294154",title:"Prof.",name:"George",middleName:null,surname:"Papakostas",slug:"george-papakostas",fullName:"George Papakostas",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002hYaGbQAK/Profile_Picture_1624519712088",biography:"George A. Papakostas has received a diploma in Electrical and Computer Engineering in 1999 and the M.Sc. and Ph.D. degrees in Electrical and Computer Engineering in 2002 and 2007, respectively, from the Democritus University of Thrace (DUTH), Greece. Dr. Papakostas serves as a Tenured Full Professor at the Department of Computer Science, International Hellenic University, Greece. Dr. Papakostas has 10 years of experience in large-scale systems design as a senior software engineer and technical manager, and 20 years of research experience in the field of Artificial Intelligence. Currently, he is the Head of the “Visual Computing” division of HUman-MAchines INteraction Laboratory (HUMAIN-Lab) and the Director of the MPhil program “Advanced Technologies in Informatics and Computers” hosted by the Department of Computer Science, International Hellenic University. He has (co)authored more than 150 publications in indexed journals, international conferences and book chapters, 1 book (in Greek), 3 edited books, and 5 journal special issues. His publications have more than 2100 citations with h-index 27 (GoogleScholar). His research interests include computer/machine vision, machine learning, pattern recognition, computational intelligence. \nDr. Papakostas served as a reviewer in numerous journals, as a program\ncommittee member in international conferences and he is a member of the IAENG, MIR Labs, EUCogIII, INSTICC and the Technical Chamber of Greece (TEE).",institutionString:null,institution:{name:"International Hellenic University",institutionURL:null,country:{name:"Greece"}}},editorTwo:null,editorThree:null},{id:"25",title:"Evolutionary Computation",coverUrl:"https://cdn.intechopen.com/series_topics/covers/25.jpg",isOpenForSubmission:!0,editor:{id:"136112",title:"Dr.",name:"Sebastian",middleName:null,surname:"Ventura Soto",slug:"sebastian-ventura-soto",fullName:"Sebastian Ventura Soto",profilePictureURL:"https://mts.intechopen.com/storage/users/136112/images/system/136112.png",biography:"Sebastian Ventura is a Spanish researcher, a full professor with the Department of Computer Science and Numerical Analysis, University of Córdoba. Dr Ventura also holds the positions of Affiliated Professor at Virginia Commonwealth University (Richmond, USA) and Distinguished Adjunct Professor at King Abdulaziz University (Jeddah, Saudi Arabia). Additionally, he is deputy director of the Andalusian Research Institute in Data Science and Computational Intelligence (DaSCI) and heads the Knowledge Discovery and Intelligent Systems Research Laboratory. He has published more than ten books and over 300 articles in journals and scientific conferences. Currently, his work has received over 18,000 citations according to Google Scholar, including more than 2200 citations in 2020. In the last five years, he has published more than 60 papers in international journals indexed in the JCR (around 70% of them belonging to first quartile journals) and he has edited some Springer books “Supervised Descriptive Pattern Mining” (2018), “Multiple Instance Learning - Foundations and Algorithms” (2016), and “Pattern Mining with Evolutionary Algorithms” (2016). He has also been involved in more than 20 research projects supported by the Spanish and Andalusian governments and the European Union. He currently belongs to the editorial board of PeerJ Computer Science, Information Fusion and Engineering Applications of Artificial Intelligence journals, being also associate editor of Applied Computational Intelligence and Soft Computing and IEEE Transactions on Cybernetics. Finally, he is editor-in-chief of Progress in Artificial Intelligence. He is a Senior Member of the IEEE Computer, the IEEE Computational Intelligence, and the IEEE Systems, Man, and Cybernetics Societies, and the Association of Computing Machinery (ACM). Finally, his main research interests include data science, computational intelligence, and their applications.",institutionString:null,institution:{name:"University of Córdoba",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null},{id:"26",title:"Machine Learning and Data Mining",coverUrl:"https://cdn.intechopen.com/series_topics/covers/26.jpg",isOpenForSubmission:!0,editor:{id:"24555",title:"Dr.",name:"Marco Antonio",middleName:null,surname:"Aceves Fernandez",slug:"marco-antonio-aceves-fernandez",fullName:"Marco Antonio Aceves Fernandez",profilePictureURL:"https://mts.intechopen.com/storage/users/24555/images/system/24555.jpg",biography:"Dr. Marco Antonio Aceves Fernandez obtained his B.Sc. (Eng.) in Telematics from the Universidad de Colima, Mexico. He obtained both his M.Sc. and Ph.D. from the University of Liverpool, England, in the field of Intelligent Systems. He is a full professor at the Universidad Autonoma de Queretaro, Mexico, and a member of the National System of Researchers (SNI) since 2009. Dr. Aceves Fernandez has published more than 80 research papers as well as a number of book chapters and congress papers. He has contributed in more than 20 funded research projects, both academic and industrial, in the area of artificial intelligence, ranging from environmental, biomedical, automotive, aviation, consumer, and robotics to other applications. He is also a honorary president at the National Association of Embedded Systems (AMESE), a senior member of the IEEE, and a board member of many institutions. His research interests include intelligent and embedded systems.",institutionString:"Universidad Autonoma de Queretaro",institution:{name:"Autonomous University of Queretaro",institutionURL:null,country:{name:"Mexico"}}},editorTwo:null,editorThree:null},{id:"27",title:"Multi-Agent Systems",coverUrl:"https://cdn.intechopen.com/series_topics/covers/27.jpg",isOpenForSubmission:!0,editor:{id:"148497",title:"Dr.",name:"Mehmet",middleName:"Emin",surname:"Aydin",slug:"mehmet-aydin",fullName:"Mehmet Aydin",profilePictureURL:"https://mts.intechopen.com/storage/users/148497/images/system/148497.jpg",biography:"Dr. Mehmet Emin Aydin is a Senior Lecturer with the Department of Computer Science and Creative Technology, the University of the West of England, Bristol, UK. His research interests include swarm intelligence, parallel and distributed metaheuristics, machine learning, intelligent agents and multi-agent systems, resource planning, scheduling and optimization, combinatorial optimization. Dr. Aydin is currently a Fellow of Higher Education Academy, UK, a member of EPSRC College, a senior member of IEEE and a senior member of ACM. In addition to being a member of advisory committees of many international conferences, he is an Editorial Board Member of various peer-reviewed international journals. He has served as guest editor for a number of special issues of peer-reviewed international journals.",institutionString:null,institution:{name:"University of the West of England",institutionURL:null,country:{name:"United Kingdom"}}},editorTwo:null,editorThree:null}]},overviewPageOFChapters:{paginationCount:20,paginationItems:[{id:"82526",title:"Deep Multiagent Reinforcement Learning Methods Addressing the Scalability Challenge",doi:"10.5772/intechopen.105627",signatures:"Theocharis Kravaris and George A. Vouros",slug:"deep-multiagent-reinforcement-learning-methods-addressing-the-scalability-challenge",totalDownloads:19,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Multi-Agent Technologies and Machine Learning",coverURL:"https://cdn.intechopen.com/books/images_new/11445.jpg",subseries:{id:"27",title:"Multi-Agent Systems"}}},{id:"82196",title:"Multi-Features Assisted Age Invariant Face Recognition and Retrieval Using CNN with Scale Invariant Heat Kernel Signature",doi:"10.5772/intechopen.104944",signatures:"Kamarajugadda Kishore Kumar and Movva Pavani",slug:"multi-features-assisted-age-invariant-face-recognition-and-retrieval-using-cnn-with-scale-invariant-",totalDownloads:14,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Pattern Recognition - New Insights",coverURL:"https://cdn.intechopen.com/books/images_new/11442.jpg",subseries:{id:"26",title:"Machine Learning and Data Mining"}}},{id:"82063",title:"Evaluating Similarities and Differences between Machine Learning and Traditional Statistical Modeling in Healthcare Analytics",doi:"10.5772/intechopen.105116",signatures:"Michele Bennett, Ewa J. 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He is an academic staff member of the Department of Reproduction and Artificial Insemination, Selçuk University, Turkey. He manages several studies on sperms and embryos and is an editorial board member for several international journals. His studies include sperm cryobiology, in vitro fertilization, and embryo production in animals.",institutionString:"Selçuk University, Faculty of Veterinary Medicine",institution:null},{id:"90846",title:"Prof.",name:"Yusuf",middleName:null,surname:"Bozkurt",slug:"yusuf-bozkurt",fullName:"Yusuf Bozkurt",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/90846/images/system/90846.jpg",biography:"Yusuf Bozkurt has a BSc, MSc, and Ph.D. from Ankara University, Turkey. He is currently a Professor of Biotechnology of Reproduction in the field of Aquaculture, İskenderun Technical University, Turkey. His research interests include reproductive biology and biotechnology with an emphasis on cryo-conservation. He is on the editorial board of several international peer-reviewed journals and has published many papers. Additionally, he has participated in many international and national congresses, seminars, and workshops with oral and poster presentations. He is an active member of many local and international organizations.",institutionString:"İskenderun Technical University",institution:{name:"İskenderun Technical University",country:{name:"Turkey"}}},{id:"61139",title:"Dr.",name:"Sergey",middleName:null,surname:"Tkachev",slug:"sergey-tkachev",fullName:"Sergey Tkachev",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/61139/images/system/61139.png",biography:"Dr. Sergey Tkachev is a senior research scientist at the Institute of Fundamental Medicine and Biology, Kazan Federal University, Russia, and at the Institute of Chemical Biology and Fundamental Medicine SB RAS, Novosibirsk, Russia. He received his Ph.D. in Molecular Biology with his thesis “Genetic variability of the tick-borne encephalitis virus in natural foci of Novosibirsk city and its suburbs.” His primary field is molecular virology with research emphasis on vector-borne viruses, especially tick-borne encephalitis virus, Kemerovo virus and Omsk hemorrhagic fever virus, rabies virus, molecular genetics, biology, and epidemiology of virus pathogens.",institutionString:"Russian Academy of Sciences",institution:{name:"Russian Academy of Sciences",country:{name:"Russia"}}},{id:"310962",title:"Dr.",name:"Amlan",middleName:"Kumar",surname:"Patra",slug:"amlan-patra",fullName:"Amlan Patra",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/310962/images/system/310962.jpg",biography:"Amlan K. Patra, FRSB, obtained a Ph.D. in Animal Nutrition from Indian Veterinary Research Institute, India, in 2002. He is currently an associate professor at West Bengal University of Animal and Fishery Sciences. He has more than twenty years of research and teaching experience. He held previous positions at the American Institute for Goat Research, The Ohio State University, Columbus, USA, and Free University of Berlin, Germany. His research focuses on animal nutrition, particularly ruminants and poultry nutrition, gastrointestinal electrophysiology, meta-analysis and modeling in nutrition, and livestock–environment interaction. He has authored around 175 articles in journals, book chapters, and proceedings. Dr. Patra serves on the editorial boards of several reputed journals.",institutionString:null,institution:{name:"West Bengal University of Animal and Fishery Sciences",country:{name:"India"}}},{id:"53998",title:"Prof.",name:"László",middleName:null,surname:"Babinszky",slug:"laszlo-babinszky",fullName:"László Babinszky",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/53998/images/system/53998.png",biography:"László Babinszky is Professor Emeritus, Department of Animal Nutrition Physiology, University of Debrecen, Hungary. He has also worked in the Department of Animal Nutrition, University of Wageningen, Netherlands; the Institute for Livestock Feeding and Nutrition (IVVO), Lelystad, Netherlands; the Agricultural University of Vienna (BOKU); the Institute for Animal Breeding and Nutrition, Austria; and the Oscar Kellner Research Institute for Animal Nutrition, Rostock, Germany. In 1992, Dr. Babinszky obtained a Ph.D. in Animal Nutrition from the University of Wageningen. His main research areas are swine and poultry nutrition. He has authored more than 300 publications (papers, book chapters) and edited four books and fourteen international conference proceedings.",institutionString:"University of Debrecen",institution:{name:"University of Debrecen",country:{name:"Hungary"}}},{id:"201830",title:"Dr.",name:"Fernando",middleName:"Sanchez",surname:"Davila",slug:"fernando-davila",fullName:"Fernando Davila",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/201830/images/5017_n.jpg",biography:"I am a professor at UANL since 1988. My research lines are the development of reproductive techniques in small ruminants. We also conducted research on sexual and social behavior in males.\nI am Mexican and study my professional career as an engineer in agriculture and animal science at UANL. Then take a masters degree in science in Germany (Animal breeding). Take a doctorate in animal science at the UANL.",institutionString:null,institution:{name:"Universidad Autónoma de Nuevo León",country:{name:"Mexico"}}},{id:"309250",title:"Dr.",name:"Miguel",middleName:null,surname:"Quaresma",slug:"miguel-quaresma",fullName:"Miguel Quaresma",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/309250/images/9059_n.jpg",biography:"Miguel Nuno Pinheiro Quaresma was born on May 26, 1974 in Dili, Timor Island. He is married with two children: a boy and a girl, and he is a resident in Vila Real, Portugal. He graduated in Veterinary Medicine in August 1998 and obtained his Ph.D. degree in Veterinary Sciences -Clinical Area in February 2015, both from the University of Trás-os-Montes e Alto Douro. He is currently enrolled in the Alternative Residency of the European College of Animal Reproduction. He works as a Senior Clinician at the Veterinary Teaching Hospital of UTAD (HVUTAD) with a role in clinical activity in the area of livestock and equine species as well as to support teaching and research in related areas. He teaches as an Invited Professor in Reproduction Medicine I and II of the Master\\'s in Veterinary Medicine degree at UTAD. Currently, he holds the position of Chairman of the Portuguese Buiatrics Association. He is a member of the Consultive Group on Production Animals of the OMV. He has 19 publications in indexed international journals (ISIS), as well as over 60 publications and oral presentations in both Portuguese and international journals and congresses.",institutionString:"University of Trás-os-Montes and Alto Douro",institution:{name:"University of Trás-os-Montes and Alto Douro",country:{name:"Portugal"}}},{id:"38652",title:"Prof.",name:"Rita",middleName:null,surname:"Payan-Carreira",slug:"rita-payan-carreira",fullName:"Rita Payan-Carreira",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRiFPQA0/Profile_Picture_1614601496313",biography:"Rita Payan Carreira earned her Veterinary Degree from the Faculty of Veterinary Medicine in Lisbon, Portugal, in 1985. She obtained her Ph.D. in Veterinary Sciences from the University of Trás-os-Montes e Alto Douro, Portugal. After almost 32 years of teaching at the University of Trás-os-Montes and Alto Douro, she recently moved to the University of Évora, Department of Veterinary Medicine, where she teaches in the field of Animal Reproduction and Clinics. Her primary research areas include the molecular markers of the endometrial cycle and the embryo–maternal interaction, including oxidative stress and the reproductive physiology and disorders of sexual development, besides the molecular determinants of male and female fertility. She often supervises students preparing their master's or doctoral theses. She is also a frequent referee for various journals.",institutionString:null,institution:{name:"University of Évora",country:{name:"Portugal"}}},{id:"283019",title:"Dr.",name:"Oudessa",middleName:null,surname:"Kerro Dego",slug:"oudessa-kerro-dego",fullName:"Oudessa Kerro Dego",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/283019/images/system/283019.png",biography:"Dr. Kerro Dego is a veterinary microbiologist with training in veterinary medicine, microbiology, and anatomic pathology. Dr. Kerro Dego is an assistant professor of dairy health in the department of animal science, the University of Tennessee, Institute of Agriculture, Knoxville, Tennessee. He received his D.V.M. (1997), M.S. (2002), and Ph.D. (2008) degrees in Veterinary Medicine, Animal Pathology and Veterinary Microbiology from College of Veterinary Medicine, Addis Ababa University, Ethiopia; College of Veterinary Medicine, Utrecht University, the Netherlands and Western College of Veterinary Medicine, University of Saskatchewan, Canada respectively. He did his Postdoctoral training in microbial pathogenesis (2009 - 2015) in the Department of Animal Science, the University of Tennessee, Institute of Agriculture, Knoxville, Tennessee. Dr. Kerro Dego’s research focuses on the prevention and control of infectious diseases of farm animals, particularly mastitis, improving dairy food safety, and mitigation of antimicrobial resistance. Dr. Kerro Dego has extensive experience in studying the pathogenesis of bacterial infections, identification of virulence factors, and vaccine development and efficacy testing against major bacterial mastitis pathogens. Dr. Kerro Dego conducted numerous controlled experimental and field vaccine efficacy studies, vaccination, and evaluation of immunological responses in several species of animals, including rodents (mice) and large animals (bovine and ovine).",institutionString:"University of Tennessee at Knoxville",institution:{name:"University of Tennessee at Knoxville",country:{name:"United States of America"}}},{id:"251314",title:"Dr.",name:"Juan Carlos",middleName:null,surname:"Gardón Poggi",slug:"juan-carlos-gardon-poggi",fullName:"Juan Carlos Gardón Poggi",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/251314/images/system/251314.jpeg",biography:"Juan Carlos Gardón Poggi received University degree from the Faculty of Agrarian Science in Argentina, in 1983. Also he received Masters Degree and PhD from Córdoba University, Spain. He is currently a Professor at the Catholic University of Valencia San Vicente Mártir, at the Department of Medicine and Animal Surgery. He teaches diverse courses in the field of Animal Reproduction and he is the Director of the Veterinary Farm. He also participates in academic postgraduate activities at the Veterinary Faculty of Murcia University, Spain. His research areas include animal physiology, physiology and biotechnology of reproduction either in males or females, the study of gametes under in vitro conditions and the use of ultrasound as a complement to physiological studies and development of applied biotechnologies. Routinely, he supervises students preparing their doctoral, master thesis or final degree projects.",institutionString:null,institution:{name:"Valencia Catholic University Saint Vincent Martyr",country:{name:"Spain"}}},{id:"309529",title:"Dr.",name:"Albert",middleName:null,surname:"Rizvanov",slug:"albert-rizvanov",fullName:"Albert Rizvanov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/309529/images/9189_n.jpg",biography:'Albert A. Rizvanov is a Professor and Director of the Center for Precision and Regenerative Medicine at the Institute of Fundamental Medicine and Biology, Kazan Federal University (KFU), Russia. He is the Head of the Center of Excellence “Regenerative Medicine” and Vice-Director of Strategic Academic Unit \\"Translational 7P Medicine\\". Albert completed his Ph.D. at the University of Nevada, Reno, USA and Dr.Sci. at KFU. He is a corresponding member of the Tatarstan Academy of Sciences, Russian Federation. Albert is an author of more than 300 peer-reviewed journal articles and 22 patents. He has supervised 11 Ph.D. and 2 Dr.Sci. dissertations. Albert is the Head of the Dissertation Committee on Biochemistry, Microbiology, and Genetics at KFU.\nORCID https://orcid.org/0000-0002-9427-5739\nWebsite https://kpfu.ru/Albert.Rizvanov?p_lang=2',institutionString:"Kazan Federal University",institution:{name:"Kazan Federal University",country:{name:"Russia"}}},{id:"210551",title:"Dr.",name:"Arbab",middleName:null,surname:"Sikandar",slug:"arbab-sikandar",fullName:"Arbab Sikandar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/210551/images/system/210551.jpg",biography:"Dr. Arbab Sikandar, PhD, M. Phil, DVM was born on April 05, 1981. He is currently working at the College of Veterinary & Animal Sciences as an Assistant Professor. He previously worked as a lecturer at the same University. \nHe is a Member/Secretory of Ethics committee (No. CVAS-9377 dated 18-04-18), Member of the QEC committee CVAS, Jhang (Regr/Gen/69/873, dated 26-10-2017), Member, Board of studies of Department of Basic Sciences (No. CVAS. 2851 Dated. 12-04-13, and No. CVAS, 9024 dated 20/11/17), Member of Academic Committee, CVAS, Jhang (No. CVAS/2004, Dated, 25-08-12), Member of the technical committee (No. CVAS/ 4085, dated 20,03, 2010 till 2016).\n\nDr. Arbab Sikandar contributed in five days hands-on-training on Histopathology at the Department of Pathology, UVAS from 12-16 June 2017. He received a Certificate of appreciation for contributions for Popularization of Science and Technology in the Society on 17-11-15. He was the resource person in the lecture series- ‘scientific writing’ at the Department of Anatomy and Histology, UVAS, Lahore on 29th October 2015. He won a full fellowship as a principal candidate for the year 2015 in the field of Agriculture, EICA, Egypt with ref. to the Notification No. 12(11) ACS/Egypt/2014 from 10 July 2015 to 25th September 2015.; he received a grant of Rs. 55000/- as research incentives from Director, Advanced Studies and Research, UVAS, Lahore upon publications of research papers in IF Journals (DR/215, dated 19-5-2014.. He obtained his PhD by winning a HEC Pakistan indigenous Scholarship, ‘Ph.D. fellowship for 5000 scholars – Phase II’ (2av1-147), 17-6/HEC/HRD/IS-II/12, November 15, 2012. \n\nDr. Sikandar is a member of numerous societies: Registered Veterinary Medical Practitioner (life member) and Registered Veterinary Medical Faculty of Pakistan Veterinary Medical Council. The Registration code of PVMC is RVMP/4298 and RVMF/ 0102.; Life member of the University of Veterinary and Animal Sciences, Lahore, Alumni Association with S# 664, dated: 6-4-12. ; Member 'Vets Care Organization Pakistan” with Reference No. VCO-605-149, dated 05-04-06. :Member 'Vet Crescent” (Society of Animal Health and Production), UVAS, Lahore.",institutionString:"University of Veterinary & Animal Science",institution:{name:"University of Veterinary and Animal Sciences",country:{name:"Pakistan"}}},{id:"311663",title:"Dr.",name:"Prasanna",middleName:null,surname:"Pal",slug:"prasanna-pal",fullName:"Prasanna Pal",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/311663/images/13261_n.jpg",biography:null,institutionString:null,institution:{name:"National Dairy Research Institute",country:{name:"India"}}},{id:"202192",title:"Dr.",name:"Catrin",middleName:null,surname:"Rutland",slug:"catrin-rutland",fullName:"Catrin Rutland",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/202192/images/system/202192.png",biography:"Catrin Rutland is an Associate Professor of Anatomy and Developmental Genetics at the University of Nottingham, UK. She obtained a BSc from the University of Derby, England, a master’s degree from Technische Universität München, Germany, and a Ph.D. from the University of Nottingham. She undertook a post-doctoral research fellowship in the School of Medicine before accepting tenure in Veterinary Medicine and Science. Dr. Rutland also obtained an MMedSci (Medical Education) and a Postgraduate Certificate in Higher Education (PGCHE). She is the author of more than sixty peer-reviewed journal articles, twelve books/book chapters, and more than 100 research abstracts in cardiovascular biology and oncology. She is a board member of the European Association of Veterinary Anatomists, Fellow of the Anatomical Society, and Senior Fellow of the Higher Education Academy. Dr. Rutland has also written popular science books for the public. https://orcid.org/0000-0002-2009-4898. www.nottingham.ac.uk/vet/people/catrin.rutland",institutionString:null,institution:{name:"University of Nottingham",country:{name:"United Kingdom"}}},{id:"283315",title:"Prof.",name:"Samir",middleName:null,surname:"El-Gendy",slug:"samir-el-gendy",fullName:"Samir El-Gendy",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRduYQAS/Profile_Picture_1606215849748",biography:"Samir El-Gendy is a Professor of anatomy and embryology at the faculty of veterinary medicine, Alexandria University, Egypt. Samir obtained his PhD in veterinary science in 2007 from the faculty of veterinary medicine, Alexandria University and has been a professor since 2017. Samir is an author on 24 articles at Scopus and 12 articles within local journals and 2 books/book chapters. His research focuses on applied anatomy, imaging techniques and computed tomography. Samir worked as a member of different local projects on E-learning and he is a board member of the African Association of Veterinary Anatomists and of anatomy societies and as an associated author at local and international journals. Orcid: https://orcid.org/0000-0002-6180-389X",institutionString:null,institution:{name:"Alexandria University",country:{name:"Egypt"}}},{id:"246149",title:"Dr.",name:"Valentina",middleName:null,surname:"Kubale",slug:"valentina-kubale",fullName:"Valentina Kubale",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/246149/images/system/246149.jpg",biography:"Valentina Kubale is Associate Professor of Veterinary Medicine at the Veterinary Faculty, University of Ljubljana, Slovenia. Since graduating from the Veterinary faculty she obtained her PhD in 2007, performed collaboration with the Department of Pharmacology, University of Copenhagen, Denmark. She continued as a post-doctoral fellow at the University of Copenhagen with a Lundbeck foundation fellowship. She is the editor of three books and author/coauthor of 23 articles in peer-reviewed scientific journals, 16 book chapters, and 68 communications at scientific congresses. Since 2008 she has been the Editor Assistant for the Slovenian Veterinary Research journal. She is a member of Slovenian Biochemical Society, The Endocrine Society, European Association of Veterinary Anatomists and Society for Laboratory Animals, where she is board member.",institutionString:"University of Ljubljana",institution:{name:"University of Ljubljana",country:{name:"Slovenia"}}},{id:"258334",title:"Dr.",name:"Carlos Eduardo",middleName:null,surname:"Fonseca-Alves",slug:"carlos-eduardo-fonseca-alves",fullName:"Carlos Eduardo Fonseca-Alves",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/258334/images/system/258334.jpg",biography:"Dr. Fonseca-Alves earned his DVM from Federal University of Goias – UFG in 2008. He completed an internship in small animal internal medicine at UPIS university in 2011, earned his MSc in 2013 and PhD in 2015 both in Veterinary Medicine at Sao Paulo State University – UNESP. Dr. Fonseca-Alves currently serves as an Assistant Professor at Paulista University – UNIP teaching small animal internal medicine.",institutionString:null,institution:{name:"Universidade Paulista",country:{name:"Brazil"}}},{id:"245306",title:"Dr.",name:"María Luz",middleName:null,surname:"Garcia Pardo",slug:"maria-luz-garcia-pardo",fullName:"María Luz Garcia Pardo",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/245306/images/system/245306.png",biography:"María de la Luz García Pardo is an agricultural engineer from Universitat Politècnica de València, Spain. She has a Ph.D. in Animal Genetics. Currently, she is a lecturer at the Agrofood Technology Department of Miguel Hernández University, Spain. Her research is focused on genetics and reproduction in rabbits. The major goal of her research is the genetics of litter size through novel methods such as selection by the environmental sensibility of litter size, with forays into the field of animal welfare by analysing the impact on the susceptibility to diseases and stress of the does. Details of her publications can be found at https://orcid.org/0000-0001-9504-8290.",institutionString:null,institution:{name:"Miguel Hernandez University",country:{name:"Spain"}}},{id:"350704",title:"M.Sc.",name:"Camila",middleName:"Silva Costa",surname:"Ferreira",slug:"camila-ferreira",fullName:"Camila Ferreira",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/350704/images/17280_n.jpg",biography:"Graduated in Veterinary Medicine at the Fluminense Federal University, specialist in Equine Reproduction at the Brazilian Veterinary Institute (IBVET) and Master in Clinical Veterinary Medicine and Animal Reproduction at the Fluminense Federal University. She has experience in analyzing zootechnical indices in dairy cattle and organizing events related to Veterinary Medicine through extension grants. I have experience in the field of diagnostic imaging and animal reproduction in veterinary medicine through monitoring and scientific initiation scholarships. I worked at the Equus Central Reproduction Equine located in Santo Antônio de Jesus – BA in the 2016/2017 breeding season. I am currently a doctoral student with a scholarship from CAPES of the Postgraduate Program in Veterinary Medicine (Pathology and Clinical Sciences) at the Federal Rural University of Rio de Janeiro (UFRRJ) with a research project with an emphasis on equine endometritis.",institutionString:null,institution:null},{id:"41319",title:"Prof.",name:"Lung-Kwang",middleName:null,surname:"Pan",slug:"lung-kwang-pan",fullName:"Lung-Kwang Pan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/41319/images/84_n.jpg",biography:null,institutionString:null,institution:null},{id:"125292",title:"Dr.",name:"Katy",middleName:null,surname:"Satué Ambrojo",slug:"katy-satue-ambrojo",fullName:"Katy Satué Ambrojo",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/125292/images/system/125292.jpeg",biography:"Katy Satué Ambrojo received her Veterinary Medicine degree, Master degree in Equine Technology and doctorate in Veterinary Medicine from the Faculty of Veterinary, CEU-Cardenal Herrera University in Valencia, Spain.Dr. Satué is accredited as a Private University Doctor Professor, Doctor Assistant, and Contracted Doctor by AVAP (Agència Valenciana d'Avaluació i Prospectiva) and currently, as a full professor by ANECA (since January 2022). To date, Katy has taught 22 years in the Department of Animal Medicine and Surgery at the CEU-Cardenal Herrera University in undergraduate courses in Veterinary Medicine (General Pathology, integrated into the Applied Basis of Veterinary Medicine module of the 2nd year, Clinical Equine I of 3rd year, and Equine Clinic II of 4th year). Dr. Satué research activity is in the field of Endocrinology, Hematology, Biochemistry, and Immunology in the Spanish Purebred mare. She has directed 5 Doctoral Theses and 5 Diplomas of Advanced Studies, and participated in 11 research projects as a collaborating researcher. She has written 2 books and 14 book chapters in international publishers related to the area, and 68 scientific publications in international journals. Dr. Satué has attended 63 congresses, participating with 132 communications in international congresses and 19 in national congresses related to the area. Dr. Satué is a scientific reviewer for various prestigious international journals such as Animals, American Journal of Obstetrics and Gynecology, Veterinary Clinical Pathology, Journal of Equine Veterinary Science, Reproduction in Domestic Animals, Research Veterinary Science, Brazilian Journal of Medical and Biological Research, Livestock Production Science and Theriogenology, among others. Since 2014 she has been responsible for the Clinical Analysis Laboratory of the CEU-Cardenal Herrera University Veterinary Clinical Hospital.",institutionString:null,institution:null},{id:"201721",title:"Dr.",name:"Beatrice",middleName:null,surname:"Funiciello",slug:"beatrice-funiciello",fullName:"Beatrice Funiciello",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/201721/images/11089_n.jpg",biography:"Graduated from the University of Milan in 2011, my post-graduate education included CertAVP modules mainly on equines (dermatology and internal medicine) and a few on small animal (dermatology and anaesthesia) at the University of Liverpool. After a general CertAVP (2015) I gained the designated Certificate in Veterinary Dermatology (2017) after taking the synoptic examination and then applied for the RCVS ADvanced Practitioner status. After that, I completed the Postgraduate Diploma in Veterinary Professional Studies at the University of Liverpool (2018). My main area of work is cross-species veterinary dermatology.",institutionString:null,institution:null},{id:"291226",title:"Dr.",name:"Monica",middleName:null,surname:"Cassel",slug:"monica-cassel",fullName:"Monica Cassel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/291226/images/8232_n.jpg",biography:'Degree in Biological Sciences at the Federal University of Mato Grosso with scholarship for Scientific Initiation by FAPEMAT (2008/1) and CNPq (2008/2-2009/2): Project \\"Histological evidence of reproductive activity in lizards of the Manso region, Chapada dos Guimarães, Mato Grosso, Brazil\\". Master\\\'s degree in Ecology and Biodiversity Conservation at Federal University of Mato Grosso with a scholarship by CAPES/REUNI program: Project \\"Reproductive biology of Melanorivulus punctatus\\". PhD\\\'s degree in Science (Cell and Tissue Biology Area) \n at University of Sao Paulo with scholarship granted by FAPESP; Project \\"Development of morphofunctional changes in ovary of Astyanax altiparanae Garutti & Britski, 2000 (Teleostei, Characidae)\\". She has experience in Reproduction of vertebrates and Morphology, with emphasis in Cellular Biology and Histology. She is currently a teacher in the medium / technical level courses at IFMT-Alta Floresta, as well as in the Bachelor\\\'s degree in Animal Science and in the Bachelor\\\'s degree in Business.',institutionString:null,institution:null},{id:"442807",title:"Dr.",name:"Busani",middleName:null,surname:"Moyo",slug:"busani-moyo",fullName:"Busani Moyo",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Gwanda State University",country:{name:"Zimbabwe"}}},{id:"439435",title:"Dr.",name:"Feda S.",middleName:null,surname:"Aljaser",slug:"feda-s.-aljaser",fullName:"Feda S. 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