Microbial production of carotenes in literature.
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Barely three months into the new year and we are happy to announce a monumental milestone reached - 150 million downloads.
\n\nThis achievement solidifies IntechOpen’s place as a pioneer in Open Access publishing and the home to some of the most relevant scientific research available through Open Access.
\n\nWe are so proud to have worked with so many bright minds throughout the years who have helped us spread knowledge through the power of Open Access and we look forward to continuing to support some of the greatest thinkers of our day.
\n\nThank you for making IntechOpen your place of learning, sharing, and discovery, and here’s to 150 million more!
\n\n\n\n\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:"8385",leadTitle:null,fullTitle:"Nanocrystalline Materials",title:"Nanocrystalline Materials",subtitle:null,reviewType:"peer-reviewed",abstract:'The term "nanocrystalline materials" relates to the sizes of structural elements. The range of application of these materials is huge, such as more efficient catalysts, films, magnetic materials, protective coatings, and biological and biomaterials. Many compounds and elements, if made on the nanoscale, behave quite differently from how they would have in their conventional state. The overall purpose of this book, "Nanocrystalline Materials", is to provide present selected advanced topics on nanocrystals, allowing the book to be a good resource for scholars and students of material science, nanotechnology, and physical chemistry.',isbn:"978-1-78985-594-4",printIsbn:"978-1-78985-593-7",pdfIsbn:"978-1-83880-274-5",doi:"10.5772/intechopen.78515",price:119,priceEur:129,priceUsd:155,slug:"nanocrystalline-materials",numberOfPages:130,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"cf72d957868565da82cc4ad919e6c4d7",bookSignature:"Behrooz Movahedi",publishedDate:"February 5th 2020",coverURL:"https://cdn.intechopen.com/books/images_new/8385.jpg",numberOfDownloads:5674,numberOfWosCitations:3,numberOfCrossrefCitations:16,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:41,numberOfDimensionsCitationsByBook:0,hasAltmetrics:0,numberOfTotalCitations:60,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"February 6th 2019",dateEndSecondStepPublish:"March 27th 2019",dateEndThirdStepPublish:"May 26th 2019",dateEndFourthStepPublish:"August 14th 2019",dateEndFifthStepPublish:"October 13th 2019",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6,7",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"150371",title:"Prof.",name:"Behrooz",middleName:null,surname:"Movahedi",slug:"behrooz-movahedi",fullName:"Behrooz Movahedi",profilePictureURL:"https://mts.intechopen.com/storage/users/150371/images/system/150371.jpg",biography:"Dr. Behrooz Movahedi obtained his Ph.D degree in Materials Engineering at Isfahan University of Technology (IUT) in Iran in 2010. During this period, while on a sabbatical leave he visited the School of Materials Science and Engineering in Nanyang Technological University (NTU) in Singapore. After that he joined the Department of Nanotechnology Engineering in the University of Isfahan (UI) as an Associate Professor. Recently, he is the head of the Nanotechnology Engineering Department in Faculty of Advanced Sciences and Technologies. Dr. Behrooz Movahedi has over 10 years of experience in the nanotechnology, amorphous materials, optical ceramics and advanced thermal spray coatings for environmental and industrial applications. He was invited as a reviewer in some potential ISI journals such as Materials & Design, Journal of Alloys and Compounds, Surface and coatings Technology, Applied Surface Science, Materials Science & Engineering B, Ceramics International, Journal of Materials Engineering and Performance.",institutionString:"University of Isfahan",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"1",institution:null}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"208",title:"Material Science",slug:"nanotechnology-and-nanomaterials-material-science"}],chapters:[{id:"70447",title:"Introductory Chapter: Nanocrystalline Materials",doi:"10.5772/intechopen.90255",slug:"introductory-chapter-nanocrystalline-materials",totalDownloads:749,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:null,signatures:"Behrooz Movahedi",downloadPdfUrl:"/chapter/pdf-download/70447",previewPdfUrl:"/chapter/pdf-preview/70447",authors:[{id:"92198",title:"Dr.",name:"Behrooz",surname:"Movahedi",slug:"behrooz-movahedi",fullName:"Behrooz Movahedi"}],corrections:null},{id:"67576",title:"Silicon Nanocrystals and Amorphous Nanoclusters in SiOx and SiNx: Atomic, Electronic Structure, and Memristor Effects",doi:"10.5772/intechopen.86508",slug:"silicon-nanocrystals-and-amorphous-nanoclusters-in-sio-sub-x-sub-and-sin-sub-x-sub-atomic-electronic",totalDownloads:914,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Semiconductor nanocrystals in dielectric films are interesting from fundamental aspect, because quantum-size effects in them appear even at room temperature, so such objects can be called as “quantum dots”. Silicon nanocrystals and amorphous silicon nanoclusters in substoichiometric SiOx and SiNx films are traps for electrons and holes that apply in nonvolatile memory devices. In this chapter the formation of silicon nanocrystals and silicon amorphous nanoclusters in SiOx and SiNx films was studied using structural and optical methods. The phonon confinement model was refined to obtain sizes of silicon nanocrystals from analysis of Raman scattering data. Structural models that lead to nanoscale potential fluctuation in amorphous SiOx and SiNx are considered. A new structural model which is intermediate between random mixture and random bonding models is proposed. Memristor effects in SiOx films are discussed.",signatures:"Vladimir Volodin, Vladimir Gritsenko, Andrei Gismatulin and Albert Chin",downloadPdfUrl:"/chapter/pdf-download/67576",previewPdfUrl:"/chapter/pdf-preview/67576",authors:[{id:"295149",title:"Prof.",name:"Vladimir",surname:"Volodin",slug:"vladimir-volodin",fullName:"Vladimir Volodin"},{id:"299276",title:"Prof.",name:"Vladimir",surname:"Gritsenko",slug:"vladimir-gritsenko",fullName:"Vladimir Gritsenko"},{id:"317682",title:"Dr.",name:"Andrei",surname:"Gismatulin",slug:"andrei-gismatulin",fullName:"Andrei Gismatulin"},{id:"317683",title:"Dr.",name:"Albert",surname:"Chin",slug:"albert-chin",fullName:"Albert Chin"}],corrections:null},{id:"68155",title:"Ferrite-Based Nanoparticles Synthesized from Natural Iron Sand as the Fe3+ Ion Source",doi:"10.5772/intechopen.88027",slug:"ferrite-based-nanoparticles-synthesized-from-natural-iron-sand-as-the-fe-sup-3-sup-ion-source",totalDownloads:1136,totalCrossrefCites:0,totalDimensionsCites:2,hasAltmetrics:0,abstract:"Ferrite-based nanoparticles, namely, bismuth ferrite (BiFeO3) and calcium ferrite (CaFe4O7), have been synthesized via sol-gel and chemically dissolved method, respectively, employing hematite (α-Fe2O3) as the Fe3+ ion source. Firstly, α-Fe2O3 nanoparticles were prepared from natural iron sand containing mostly magnetite (Fe3O4) phase through coprecipitation technique continued by sintering process at 800°C for 2 h. Higher BiFeO3 phase content was achieved after Bi-Fe gel being annealed at 650°C for 1 h in air atmosphere. Furthermore, major phase of CaFe4O7 was formed with molar ratio of Fe3+/Ca2+ = 6 and sintering temperature of 800°C for 3 h. Interestingly, the powders with dominant CaFe4O7 phase, known as calcium biferrite, exhibit higher ferromagnetism at room temperature. The magnetic properties of the calcium biferrite are comparable to those of barium hexaferrite which can be applied for radar-absorbing material. Meanwhile, BiFeO3 powders also show weak room temperature ferromagnetism. It has also demonstrated that Ni doping in the bismuth ferrite (BiFe1−xNixO3 with x = 0.1) nanoparticles results in enhancement of the magnetic properties. Moreover, a ferroelectric hysteresis loop and a trend of frequency dependence of the dielectric constant have been observed, which were enhanced by Pb doping (Bi1−yPbyFeO3 with y = 0.1). These results suggest a multiferroic behavior in the BiFeO3 nanoparticles.",signatures:"Malik Anjelh Baqiya, Retno Asih, Muhammad Ghufron, Mastuki, Dwi Yuli Retnowati, Triwikantoro and Darminto",downloadPdfUrl:"/chapter/pdf-download/68155",previewPdfUrl:"/chapter/pdf-preview/68155",authors:[{id:"192041",title:"Prof.",name:"D",surname:"Darminto",slug:"d-darminto",fullName:"D Darminto"},{id:"192812",title:"Dr.",name:"Malik",surname:"Baqiya",slug:"malik-baqiya",fullName:"Malik Baqiya"},{id:"195349",title:"Dr.",name:"T.",surname:"Triwikantoro",slug:"t.-triwikantoro",fullName:"T. Triwikantoro"},{id:"299625",title:"Dr.",name:"Retno",surname:"Asih",slug:"retno-asih",fullName:"Retno Asih"},{id:"299626",title:"Mr.",name:"Muhammad",surname:"Gufron",slug:"muhammad-gufron",fullName:"Muhammad Gufron"},{id:"299627",title:"Ms.",name:"Dwi Yuli",surname:"Retnowati",slug:"dwi-yuli-retnowati",fullName:"Dwi Yuli Retnowati"},{id:"306331",title:"MSc.",name:"M",surname:"Mastuki",slug:"m-mastuki",fullName:"M Mastuki"}],corrections:null},{id:"67838",title:"Surface Plasmons in Oxide Semiconductor Nanoparticles: Effect of Size and Carrier Density",doi:"10.5772/intechopen.86999",slug:"surface-plasmons-in-oxide-semiconductor-nanoparticles-effect-of-size-and-carrier-density",totalDownloads:836,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Oxide semiconductors have received much attention for potential use in optoelectronic applications such as transparent electrodes, transistors, and emitting devices. Recently, new functionalities of oxide semiconductors have been discovered such as localized surface plasmon resonances (LSPRs), which show high-efficiency plasmon excitations in the infrared (IR) range using different structures such as nanorods, nanoparticles (NPs), and nanodots. In this chapter, we introduce optical properties of carrier- and size-dependent LSPRs in oxide semiconductor NPs based on In2O3: Sn (ITO). In particular, systematic examinations of carrier- and size-dependent LSPRs reveal the damping mechanisms on LSPR excitations of ITO NPs, which play an important role in determining excitation efficiency of LSPRs. Additionally, the control of carrier and size in the ITO NPs contribute toward improving solar-thermal shielding in the IR range. The high IR reflectance of assembled films of ITO NPs is due to three-dimensional plasmon coupling between the NPs, which is related to electron carriers and particle size of ITO NPs. This chapter provides new information concerning structural design when fabricating thermal-shielding materials based on LSPRs in oxide semiconductor NPs.",signatures:"Hiroaki Matsui",downloadPdfUrl:"/chapter/pdf-download/67838",previewPdfUrl:"/chapter/pdf-preview/67838",authors:[{id:"7227",title:"Dr.",name:"Hiroaki",surname:"Matsui",slug:"hiroaki-matsui",fullName:"Hiroaki Matsui"}],corrections:null},{id:"68946",title:"A Facile Method for Formulation of Atenolol Nanocrystal Drug with Enhanced Bioavailability",doi:"10.5772/intechopen.88191",slug:"a-facile-method-for-formulation-of-atenolol-nanocrystal-drug-with-enhanced-bioavailability",totalDownloads:733,totalCrossrefCites:1,totalDimensionsCites:2,hasAltmetrics:0,abstract:"Atenolol is a commonly used antihypertensive drug of class III BCS category. The objective of the present study is to enhance the permeability of atenolol by using a suitable technique which is economical and devoid of using any organic solvents. The nanocrystal technology by high pressure homogenization was chosen for this purpose, which is less expensive and simple method. In this technique, no organic solvent was used. The study was further aimed to characterize prepared nanocrystals in solid state by Fourier-transform infrared spectroscopy (FTIR), powder X-ray diffraction (PXRD) patterns, particle size, zeta potential, % yield, and drug permeation study through isolated goat’s intestine. An in vivo study was carried out to determine the pharmacokinetic property in comparison to pure drug powder using rats as experimental animals. The formulation design was optimized by a 3(2) factorial design. In these designs, two factors, namely surfactant amount (X1) and speed of homogenizer (X2), were evaluated on three dependent variables, namely particle size (Y1), zeta potential (Y2), and production yield (Y3).",signatures:"Luis Castañeda",downloadPdfUrl:"/chapter/pdf-download/68946",previewPdfUrl:"/chapter/pdf-preview/68946",authors:[{id:"294990",title:"Prof.",name:"Luis",surname:"Castañeda",slug:"luis-castaneda",fullName:"Luis Castañeda"}],corrections:null},{id:"68817",title:"Production, Processes and Modification of Nanocrystalline Cellulose from Agro-Waste: A Review",doi:"10.5772/intechopen.87001",slug:"production-processes-and-modification-of-nanocrystalline-cellulose-from-agro-waste-a-review",totalDownloads:1306,totalCrossrefCites:13,totalDimensionsCites:35,hasAltmetrics:1,abstract:"Nanocrystalline cellulose is a renewable nanomaterial that has gained huge attention for its use in various applications from advanced biomedical material to food packaging material due to its exceptional physical and biological properties, such as high crystallinity degree, large specific surface area, high aspect ratio, high thermal resistance, good mechanical properties, abundance of surface hydroxyl groups, low toxicity, biodegradability, and biocompatibility. However, they still have drawbacks: (1) sources of raw materials and its utilization in the production of nanocomposites and (2) high chemical and energy consumption regarding the isolation of macro-sized fibers to nano-sized fibers. The incorporation of hydrophilic nanocrystalline cellulose within hydrophobic polymer limits the dispersion of nano-sized fibers, thus resulting in low mechanical properties of nanocomposites. Hence, surface modification on nano-sized fiber could be a solution to this problem. This review focuses on the advanced developments in pretreatment, nanocrystalline production and modifications, and its application in food packaging, biomedical materials, pharmaceutical, substitution biomaterials, drug excipient, drug delivery automotive, and nanopaper applications.",signatures:"R.A. Ilyas, S.M. Sapuan, R. Ibrahim, M.S.N. Atikah, A. Atiqah, M.N.M. Ansari and M.N.F. 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D in Physics in 2012 from Indian Institute of Technology Guwahati, India. Presently, he is associated with the Faculty of Science, Sri Sri University, India as an Assistant Professor in Physics. Prior to joining the current\naffiliation, he was a postdoctoral fellow at different renowned institutions, Kobe University Japan, S. N. Bose National Centre for Basic Sciences, India and Cardiff University, United Kingdom. He was awarded prestigious JSPS postdoctoral fellowship based on his research contribution on semiconducting nanowires. He has published more than 32 research articles including 1 review article in high profile international journals and 3 book chapters to his credit. 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Hodges",dateSubmitted:"June 21st 2018",dateReviewed:"October 22nd 2018",datePrePublished:"December 31st 2018",datePublished:"February 19th 2020",book:{id:"8295",title:"Landscape Reclamation",subtitle:"Rising From What's Left",fullTitle:"Landscape Reclamation - Rising From What's Left",slug:"landscape-reclamation-rising-from-what-s-left",publishedDate:"February 19th 2020",bookSignature:"Luis Loures",coverURL:"https://cdn.intechopen.com/books/images_new/8295.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"108118",title:"Dr.",name:"Luis",middleName:null,surname:"Loures",slug:"luis-loures",fullName:"Luis Loures"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"264298",title:"Dr.",name:"Jason",middleName:null,surname:"Gordon",fullName:"Jason Gordon",slug:"jason-gordon",email:"jason.gordon@uga.edu",position:null,institution:{name:"University of Georgia",institutionURL:null,country:{name:"United States of America"}}}]}},chapter:{id:"65057",slug:"public-perceptions-of-values-associated-with-wildfire-protection-at-the-wildland-urban-interface-a-s",signatures:"Jason Gordon, Adam S. Willcox, A.E. Luloff, James C. Finley and Donald G. Hodges",dateSubmitted:"June 21st 2018",dateReviewed:"October 22nd 2018",datePrePublished:"December 31st 2018",datePublished:"February 19th 2020",book:{id:"8295",title:"Landscape Reclamation",subtitle:"Rising From What's Left",fullTitle:"Landscape Reclamation - Rising From What's Left",slug:"landscape-reclamation-rising-from-what-s-left",publishedDate:"February 19th 2020",bookSignature:"Luis Loures",coverURL:"https://cdn.intechopen.com/books/images_new/8295.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"108118",title:"Dr.",name:"Luis",middleName:null,surname:"Loures",slug:"luis-loures",fullName:"Luis Loures"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"264298",title:"Dr.",name:"Jason",middleName:null,surname:"Gordon",fullName:"Jason Gordon",slug:"jason-gordon",email:"jason.gordon@uga.edu",position:null,institution:{name:"University of Georgia",institutionURL:null,country:{name:"United States of America"}}}]},book:{id:"8295",title:"Landscape Reclamation",subtitle:"Rising From What's Left",fullTitle:"Landscape Reclamation - Rising From What's Left",slug:"landscape-reclamation-rising-from-what-s-left",publishedDate:"February 19th 2020",bookSignature:"Luis Loures",coverURL:"https://cdn.intechopen.com/books/images_new/8295.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"108118",title:"Dr.",name:"Luis",middleName:null,surname:"Loures",slug:"luis-loures",fullName:"Luis Loures"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}}},ofsBook:{item:{type:"book",id:"11999",leadTitle:null,title:"Earthquakes - Recent Advances, New Perspectives and Applications",subtitle:null,reviewType:"peer-reviewed",abstract:"
\r\n\tThe evaluation of the seismic hazard of a particular site represents the principal input data needed to develop the seismic code regulations and to perform structural building design worldwide. Being the actual trend of automatization of structural designs using various available software, it is imperative that structural engineers also study the estimation of earthquake ground motions and the associated risk of their designs, and seismologists envision in their research interests the structural analysis of buildings as well. Merging these technical fields would result in a new educational curriculum that would fulfill the actual research trends and demand practices. This book will address the recent advances, new perspectives, and applications of seismic hazard and risk evaluation based on the following topics: Tectonics, seismicity evaluation, ground motion prediction equations GMPEs, seismic hazard probabilistic methods, and site effects evaluation, including but not limited to inversion analysis on strong motion data and geophysical prospecting; development of structural fragility curves and seismic risk estimation.
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Dr. Salazar is a member of the Seismological Society of America (SSA) and Earthquake Engineering Research Institute (EERI).",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"236461",title:"Dr.",name:"Walter",middleName:null,surname:"Salazar",slug:"walter-salazar",fullName:"Walter Salazar",profilePictureURL:"https://mts.intechopen.com/storage/users/236461/images/system/236461.jpg",biography:"Dr. Walter Salazar is a structural civil engineer who obtained a doctoral degree in Engineering Seismology from the Interdisciplinary Graduate School of Science and Engineering, Tokyo Institute of Technology, Japan, in 2004. Dr. Salazar has been active in site-effects and seismic hazard research, producing several peer-reviewed maps for El Salvador, Jamaica, and the Eastern Caribbean. He has published sixty articles in peer-reviewed journals, books, and international conferences. 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From chapter submission and review to approval and revision, copyediting and design, until final publication, I work closely with authors and editors to ensure a simple and easy publishing process. I maintain constant and effective communication with authors, editors and reviewers, which allows for a level of personal support that enables contributors to fully commit and concentrate on the chapters they are writing, editing, or reviewing. I assist authors in the preparation of their full chapter submissions and track important deadlines and ensure they are met. I help to coordinate internal processes such as linguistic review, and monitor the technical aspects of the process. As an ASM I am also involved in the acquisition of editors. 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The vivid color of carotenoids contributes to the beauty of many flowers, fruits and animals. For example, the loveliness of yellow marigolds comes mainly from lutein, a yellow carotene; the redness of watermelons and tomatoes is because they are rich in lycopene, a red carotene; and the scarlet plumage of flamingos stems from another red carotenoid, astaxanthin. The beautiful colors of plants are also responsible for attracting insects and animals for their pollination and seed dispersal [1]. The carotenoid color originates in the structure of multiple conjugated double bonds. This unique structure enables two essential features of carotenoids: the light-harvesting capability and a powerful anti-oxidant effect by the quenching of free radicals, singlet oxygen and reactive oxygen species. In photosynthetic organisms, carotenoids are indispensable for photosynthesis and photo-protection [2]. In non-photosynthetic organisms including animals, the anti-oxidant activity not only protects cells from oxidative damages (e.g., oxidative DNA damage [3]) but can provide additional benefits for humans such as anti-inflammatory and anti-cancer effect [4]. In addition, carotenoids play an important health role as pro-vitamin A compounds. About 30–50 carotenoids are believed to have vitamin A activity including two well-known compounds: β-carotene and α-carotene [2].
Vitamin A includes retinol, retinal and retinoic acid, which are all apocarotenoids. Apocarotenoids are a group of oxidative products of carotenoids. While carotenoids contribute to the visual beauty of flowers and fruits, apocarotenoids are famous for the pleasant aromas and give rise to fragrance and palatable flavors of many flowers and fruits (such as rose, violet, tomato and raspberry) [5, 6, 7]. These apocarotenoid aromas, in a similar manner to the colored carotenoids, attract pollinators and promote plant-insect interactions [8]. In addition, some apocarotenoids act as hormones. For example, the plant growth hormone, abscisic acid, has multiple functions in plant development processes including bud dormancy and response to environmental stress and plant pathogens [5]. Strigolactones are another important subclass of apocarotenoids, functioning as shoot-branching inhibitors and promoting the formation of symbiotic association between plants and fungi [9, 10].
Due to the color, aroma, remarkable nutrition and health benefits, carotenoids and apocarotenoids have been widely used in food, feed, nutritional, pharmaceutical and personal care industries. The market demands for carotenoids and apocarotenoids are rising rapidly as increasing clinical research studies report various health and pharmaceutical benefits [11, 12, 13]. The global carotenoid market is projected to reach 1.53 billion USD by 2021 [14]. The regular uptake of food with a high content of carotenoids (e.g., β-carotene) or retinoids is vital to alleviate vitamin A deficiency. Vitamin A deficiency can lead to severe aftermath including blindness, decreased immune function and even death [15]. Lutein and zeaxanthin are critical for eye health by preventing age-related macular degeneration [16]. Astaxanthin has even more benefits such as potent anti-oxidant activities, promoting immune response, reducing eye fatigue, enhancing muscle performance and so on [11]. Because of low exceptional fragrance property, α-ionone and β-ionone are widely used in cosmetics such as perfumes [17]. Crocin is another valuable apocarotenoid and is responsible for the red pigmentation of saffron, a high-value spice with retail prices ranging between 2000 and 7000 euros/kg [18].
Despite carotenoids and apocarotenoids being widely distributed in nature, their cellular contents are extremely low. For example, 100 tons of raspberries, or 20 hectares of agricultural area, could only yield 1 g of α-ionone [19]. Similarly, it requires the manual harvest of stigmas from as many as 110,000–170,000 flowers to obtain 1 kg of saffron [20], justifying the high cost of these molecules. Chemically synthetized carotenoids, despite being less expensive, have been reported to have hazardous effects to human health and are increasingly unpopular with consumers [19]. Currently, microbial-derived commercial carotenoids are those derived from native producer strains which have not been genetically engineered but in some cases have undergone classical mutagenesis followed by selection to screen for improved production characteristics. These include the β-carotene production strains of the microalga
To date, 1117 natural carotenoids and apocarotenoids have been reported, which consist of C30, C40, C45 and C50 carotenoids [22]. Among them, C40 carotenoids and their derived apocarotenoids are the most abundant with 1093 different structures. In this chapter, I will cover only a few of the commercially interesting C40 carotenoids and apocarotenoids that will illustrate the challenges and potentials of this biosynthetic alternative supply chain.
To understand how carotenoids and apocarotenoids can be produced in microbes, it is essential to elucidate the biosynthetic enzymes which constitute these metabolic pathways.
Carotenoids are a subclass of terpenoids (or isoprenoids); thus, as other terpenoids, they share the common C5 building blocks, isopentenyl pyrophosphate (IPP) and its isomer dimethylallyl pyrophosphate (DMAPP). In nature, there exist two independent biosynthetic pathways to produce IPP/DMAPP: the mevalonate (MVA) pathway [23] and the 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway, also referred to as the 1-deoxy-D-xylulose 5-phosphate (DXP) or the non-MVA pathway [24].
The MEP pathway starts from the condensation of pyruvate and glyceraldehyde-3-phosphate, which are catalyzed by DXP synthase (
Biosynthetic pathway of terpenoid precursors. Carotenoids are a subclass of terpenoids. In nature, two major biosynthetic pathways of terpenoids exist, one is the 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway, and the other is the mevalonate (MVA) pathway. Abbreviations:
In the MVA pathway, two molecules of acetyl-CoA are condensed into one molecule of acetoacetyl-CoA by acetyl-CoA acetyltransferase (
Most bacteria including cyanobacteria use exclusively the MEP pathway, whereas most eukaryotes and archaea possess only the MVA pathway. Interestingly, plants have both pathways: the MVA pathway located in the plant cytoplasm and the MEP pathway located in plastids. This is consistent with the hypothesis that chloroplasts originate from cyanobacteria endosymbionts [25]. Both pathways have been engineered to produce terpenoids including carotenoids. The MEP pathway has a higher theoretical yield than the MVA pathway [26] due to its adoption of a variety of cofactors (ATP, NADPH, CTP and flavodoxin, etc.) whereas the MVA pathway mainly uses ATP. However, in practice, it is easier to manipulate the MVA pathway and its theoretical yield has been achieved for certain products [27, 28, 29, 30]. In contrast, the practical yield of the MEP pathway is often limited by the low activity of ispG and ispH enzymes and their special requirement of iron-sulfur cofactors. To the best of my knowledge, the highest reported yields of terpenoids synthesized by the MEP pathway in literature are less than 20% of its theoretical yield [30].
The two pathway metabolites IPP and DMAPP are condensed to give geranyl diphosphate (GPP, C10) or farnesyl diphosphate (FPP, C15), catalyzed by GPP synthase (
Biochemical pathway of carotenoids and apocarotenoids.
As a colorless carotene, phytoene is the common precursor to all the C40 carotenoids (Figure 2). It exhibits excellent anti-UV activity [33] and is clinically proved to have activities of skin whitening and wrinkle reduction [34]. Hence, there are increasing cosmetic products developed based on phytoene. Phytoene is an intermediate carotenoid in plants and exists only as a minor product; hence, it is expensive to extract phytoene from plant materials. Consequently, it is promising to engineer microbes to produce higher concentrations of phytoene and more importantly, to produce it at high purity without other carotenoids. By deleting the
Lycopene, a red color pigment most commonly associated with tomatoes, belongs to one of the top six commercial carotenoids. It is produced from the dehydrogenation of phytoene catalyzed by different types of phytoene desaturases (
Moving further along the carotenoid biosynthetic pathway, lycopene is usually cyclized into β-carotene or α-carotene by a lycopene cyclase (Figure 2). Both α- and β-carotenes are yellow pigments; β-carotene is more commonly marketed, being one of the most important commercial carotenoids. As mentioned earlier, β-carotene is a direct precursor of vitamin A (Figure 2). It has been widely used as a colorant, nutritional supplement, animal feed and in pharmaceutical and personal care industries. Chemically synthesized β-carotene is less popular among consumers than that extracted from natural sources or so-called ‘bio-based’ sources. At the same time, naturally derived β-carotene has gradually taken over the market. Currently, β-carotene is produced mainly in the microalga
No. | Hosts | Carotenes | Titer (mg/L) | Content (mg/g DCW) | Culture conditions | References |
---|---|---|---|---|---|---|
1 | Phytoene | 50 | 35 | 1–2 days, in flasks | [35] | |
2 | Lycopene | 224 | 34.5 | 1–2 days, in flasks | [48] | |
3 | Lycopene | / | 20 | 1–2 days, in flasks | [40] | |
4 | Lycopene | 1500 | 35 | 2 days, in bioreactors | [19] | |
5 | Lycopene | 1350 | 32 | 2 days, in bioreactors | [39] | |
6 | Lycopene | 1610 | 24.4 | 5–6 days, in bioreactors | [41] | |
7 | Lycopene | 1650 | 54.6 | 5–6 days, in bioreactors | [49] | |
8 | Lycopene | / | 16 | 7–8 days, in flasks | [42] | |
9 | Lycopene | 213 | 21.1 | 10 days, in bioreactors | [43] | |
10 | β-Carotene | 5600 | / | 7 days, in bioreactors | [50] | |
11 | β-Carotene | 2100 | 60 | 3–4 days, in bioreactors | [45] | |
12 | β-Carotene | 3200 | / | 2–3 days, in bioreactors | [44] | |
13 | β-Carotene | 6500 | 90 | 5–6 days, in bioreactors | [47] | |
14 | β-Carotene | 4000 | 50 | 10–11 days, in bioreactors | [46] |
Microbial production of carotenes in literature.
The modification of carotenes by enzymes such as hydroxylases and ketolases leads to the synthesis of xanthophylls (Figure 2). Due to the polarity introduced by oxygen, xanthophylls have different physical properties and physiological activities. For example, unlike carotenes, most xanthophylls do not possess provitamin A activity but do have higher anti-oxidant activities. The reason is that, in addition to the polyene structure, the functional groups of xanthophylls such as keto groups in the β-ionone rings can also quench singlet oxygen resides [31].
Among various xanthophylls, astaxanthin is the most important commercial product. Astaxanthin is a red pigment with numerous health benefits. As a potent anti-oxidant, astaxanthin protects the tissue against UV-light damage [51, 52, 53] and exhibits anti-cancer activity [54, 55] and anti-inflammatory properties [56]. In double-blind, randomized controlled trials, astaxanthin lowered oxidative stress in obese subjects and improved cognition and promoted proliferation of nerve stem cells [57]. Astaxanthin also improves integrated immune response [58], reveals anti-aging effects by protecting red blood cells in both aging and young people [59, 60] and relieves eye fatigue especially beneficial for persons spending too much time on the computer and smartphones [61]. In addition, astaxanthin supplement can prevent atherosclerotic cardiovascular disease [62, 63] and diabetes [64, 65]. More importantly, besides all these benefits, astaxanthin is clinically proven to be safe for human and animals. Therefore, astaxanthin has been widely used in fish feeding, food, nutritional, medicinal and cosmetic industries. The current global annual market of astaxanthin is around 250 tons worth $447 million [66], and it is growing rapidly. Synthetic astaxanthin, like β-carotene, is less popular with consumers and yields a mixture of three isomers, RR, RS and SS, at the ratio of 1:2:1 and appears to be less available for assimilation than the natural forms. Astaxanthin produced by the microalga
Due to the wide application of astaxanthin, many researchers have been working hard to engineer microbes to produce high titer and yield of astaxanthin. It is not trivial to optimize the biotransformation of β-carotene to astaxanthin as the biosynthetic pathway is rather complex with many intermediates and a complex network of enzymatic reactions [67]. By screening different β-carotene hydroxylases and ketolases, there has been success to improve astaxanthin production from sub-milligram to milligram per gram DCW [67, 68]. Further optimization of the metabolic pathway leading to astaxanthin synthesis has led to improved yields which are now promising for commercialization. For example, Zhou et al. developed a
No. | Hosts | Carotenoids | Titer (mg/L) | Content (mg/g DCW) | Culture conditions | References |
---|---|---|---|---|---|---|
1 | Astaxanthin | / | 4.7 | 3–4 days in flasks | [72] | |
2 | Astaxanthin | / | 0.029 | 5 days in flasks | [73] | |
3 | Astaxanthin | / | 2.64 | 2 days in flasks | [74] | |
4 | Astaxanthin | / | 0.31 | 2 days in flasks | [68] | |
5 | Astaxanthin | 2.1 | 1.41 | 2 days in flasks | [75] | |
7 | Astaxanthin | 2.9 | 1.99 | 2 days in flasks | [67] | |
8 | Astaxanthin | / | 1.6 | 2 days in flasks | [76] | |
9 | Astaxanthin | 1.6 | 0.29 | 3 days in flasks | [77] | |
10 | Astaxanthin | / | 9.0 | 8 days in flasks | [78] | |
11 | Astaxanthin | 561 | 5.0 | 4–5 days in bioreactors | [79] | |
12 | Astaxanthin | 47.2 | 8.1 | 3–4 days in flasks | [69] | |
13 | Astaxanthin | / | 9.90 | 3 days in bioreactors | [70] | |
14 | Astaxanthin | 54.6 | 3.5 | 3–4 days in plates | [66] | |
15 | Astaxanthin | 320 | 15.0 | 2 days in bioreactors | [71] | |
16 | Zeaxanthin | 10.8 | 0.5 | 7.5 days in flasks | [80] | |
17 | Zeaxanthin | / | 11.9 | 2 days in bioreactors | [81] | |
18 | Zeaxanthin | 722 | 23.2 | 2.5 days in bioreactors | [82] |
Microbial production of astaxanthin and zeaxanthin in literature.
Zeaxanthin is another important xanthophyll with high commercial values. Lutein, an isomer of zeaxanthin, is typically found in plants (such as corn), whereas zeaxanthin is present in cyanobacteria and some non-photosynthetic bacteria [2]. Although both lutein and zeaxanthin are used as colorants and potentially in pharmaceutical and nutraceutical industries, the demand for alternative sources of zeaxanthin is more urgent than lutein. Till now,
As shown in Figure 2, carotenoids can be further converted into apocarotenoids by CCDs or other oxygenases. Here, three apocarotenoids of high commercial values are highlighted here. Retinol, or vitamin A, is one of the most important apocarotenoids to humans. Retinol exhibits an essential function in vision, bone development and also promotes skin health as an anti-oxidant [83]. The other two are aromatic molecules, α-ionone, which naturally exists in raspberry, and β-ionone, which is found in many flowers, for example, rose, osmanthus and violet [84]. The chemical synthesis of these three molecules is not very difficult and contributes significantly to the current market share. However, consumers prefer natural derivatives and are willing to pay higher prices for natural ingredients [19]. As mentioned in the introduction, the extremely low concentrations in natural plant materials make their extraction an extremely expensive process. Consequently, the fermentation of engineered microbes is a promising alternative route.
As an important nutritional compound and an active cosmetic ingredient, retinol market size is estimated at 1.6 billion dollars [85]. Jang et al. pioneered retinol production in metabolically engineered
A ‘plug-n-play’ platform for biosynthesis of apocarotenoids. Adapted from author’ s paper [
Both α-ionone and β-ionone have exceptional aroma activities as their odor threshold is at the sub-ppb range [7, 87]. Hence, they have been widely used as fragrance molecules in cosmetics and perfumes. As consumers prefer natural ingredients, the market demand for natural ionone is increasing dramatically. In addition, there is a chiral center for α-ionone. Natural α-ionone from plants (such as raspberry) is (R)-(+)-(E)-alpha-ionone. In contrast, synthetic α-ionone has two isomers (R and S). The R-enantiomer has a unique and strong floral flavor and aroma, described as a violet-like, fruit-like or raspberry-like flavor, while the S-enantiomer is woody or β-ionone like. Lashbrooke et al. did a proof-of-principle production of α-ionone at about 300 ng/L [88]. By coupling the modular metabolic engineering approach and enzyme engineering methods (N-terminal truncation and protein fusion), we developed an
No. | Hosts | Apocarotenoids | Titer (mg/L) | Specific titer (mg/g DCW) | Culture conditions | References |
---|---|---|---|---|---|---|
1 | Retinol | 54 | 6.3 | 2–3 days in flasks | [85] | |
2 | Retinol | 76 | 9.8 | 2–3 days in flasks | [86] | |
3 | Retinol | 28 | 10.0 | 2 days in flasks | [19] | |
4 | β-Ionone | 0.22 | / | 2–3 days in flasks | [87] | |
5 | β-Ionone | 6 | 1.0 | 2–3 days in bioreactors | [90] | |
6 | β-Ionone | 500 | 16.0 | 2 days in bioreactors | [19] | |
7 | α-Ionone | 340 ng/L | / | 2 days in flasks | [88] | |
8 | α-Ionone | 480 | 7.0 | 2 days in bioreactors | [19] |
Microbial production of retinol, α- and β-ionones in literature.
Although several groups have attempted to produce β-ionone using yeast or
In general, the chief challenge for commercializing microbial production of chemicals is relatively high cost. The cost depends mainly on titer, rate (or productivity) and yield (or ‘TRY’) [91]. Hence, researchers are inventing and exploring different approaches to engineer microbes to obtain TRY figures of merit. Until then, it would not be cost effective or competitive to other sources (such as chemical synthesis). The good news is that carotenoids and apocarotenoids are high-value specialty chemicals; thus, their requirements for commercialization are less stringent as compared to fuels and commodity chemicals. For example, the current processes of β-carotene production in microalga
Amid diverse natural products, carotenoids and apocarotenoids are particularly interesting. This is not only due to their bright color and pleasant fragrances but also their light-harvesting capability, the electron/energy transferring ability, the potent anti-oxidant properties, the hormone function, vitamin A activity and numerous other health benefits to both human and other life forms on the Earth. Increasingly, clinical studies have supported the concept that the regular uptake of carotenoids can prevent many serious diseases. The list of benefits and applications keeps growing and with the market for commercial exploitation it can be confidently expected to increase. In light of this and the extremely low levels found in plant materials, it is urgent to find solutions enabling these valuable molecules to be supplied in a sustainable and cost-effective manner. In the past decade, the metabolic engineering of microorganisms has progressed remarkably for the production of carotenoids and apocarotenoids. Some of these processes are being commercialized already but the scope to further extend this family of molecules is high, adding an increasingly solicited pipeline of natural products to compete with chemical synthesis.
This work was supported by the research funding of Biotransformation Innovation Platform (BioTrans), Agency for Science, Technology and Research (A*STAR), Singapore. The author appreciates Dr. Nic Lindley, Ms. Sudha Devi Manbahal Shukal and Ms. Chin Chin Lim in BioTrans for invaluable advice.
The physiological and pharmacological applications of Ketamine’s evolved historically. In the mid-1950s, it was initially introduced as an anesthetic agent, and it was short-acting with better post-operational effects compared to phencyclidine. Phencyclidine by itself is linked to multiple undesirable effects, including severe and prolonged post-surgery hallucinations, agitation, and delirium that made it undesirable for human use [1, 2]. Functionally, ketamine is a safer derivative of phencyclidine [3]. Both are psychoactive arylcyclohexamines agents, a unified feature of these compounds is their molecular antagonism of the N-methyl-d-aspartate (NMDA) receptor [4]. Ketamine lacks the complete unconsciousness state and is characterized by catatonia, catalepsy, and amnesia [3]. However, ketamine still retains some adverse events, such as abuse potentials and dissociative effects, and neurotoxicity when administered through the spinal cord.
In the seventies, the Food and Drug Administration (FDA) approved ketamine, and it became commercially available as a rapid and short-acting anesthetic agent [3]. Among other anesthetics, ketamine is characterized by a more significant safety, which makes it advantageous compared to other anesthetics. On the level of circuitry, as an agent, it does not elevate the blood pressure. Additionally, physiologically, it is not linked to respiratory depression in both intravenous doses of 1–2 mg/kg or intramuscular doses of 4–11 mg/kg [3, 5]. At subanesthetic doses, ketamine exhibited an analgesic effect and can be clinically used in numerous conditions associated with pain in a mechanism similar to opioids but with less respiratory depressive effects [3]. Overall, high-priced patient-monitoring tools and equipment are not necessary for clinical applications of ketamine. Thus, it is a good anesthetic of choice, especially in the middle- and low-income countries. Due to the fact ketamine, clinical applications were indispensable. It has been listed on the World Health Organization (WHO) Essential Medicines List since 1985 [6]. Also, ketamine was reported sedation in individuals with severe behavioral disturbances in clinical settings. In some cases, agitated patients may require police interference to handle them, and in comparison, to the standard sedative induction protocol, ketamine was found to be effective in parenteral relatively low doses (about 5 mg/kg) [7].
The chronic use of ketamine is linked to abuse liabilities and issues with the urinary tract system [8]. The illicit use of ketamine is well-acknowledged. However, ketamine overdose is not a common event. According to the recommendations of the WHO Expert Committee on Drug Dependence in 2016, ketamine should not be listed in the international drug control conventions [6].
In general, multiple uncovered potential novel uses of ketamine were identified including the neuroprotective effect of ketamine and its use in the management of epilepsy, chronic pain, migraine, inflammation, and tumors. Interestingly, in the past few years (the 2000s), ketamine has progressively received increased attention, and there has been significant research into the potential use of ketamine as an expeditiously acting treatment for MDD, treatment-resistant depression (TRD), and suicidality [6, 9]. Intranasal (S)-ketamine has recently been approved for depression by the FDA [10]. However, it is currently too expensive for the widespread use and is unlikely to be cost-effective for the management of TRD in the United States unless its price falls by more than 40% [11].
The chemical basis of ketamine is a similar composition of a racemic mixture, in a ratio of 1:1. This mixture is composed of arketamine (R-ketamine) and esketamine (S-ketamine) [12]. Functionally, these enantiomers are different. In the mid-eighties, white and his colleagues [13] conducted the first comparative study to examine the clinical differences between ketamine isomers using the electroencephalographic monitoring of brain activity in healthy volunteers. They observed that the arketamine exhibited less hypnotic and analgesic effects compared to the esketamine. The arketamine was associated with a faster recovery rate, regarded as the reduced central nervous system depressant effects [13]. Subsequent studies reported more functional and pharmacological differences. For example, the esketamine has greater potency toward the NMDA receptors (as an antagonist), and thus it is pharmacologically more active than the R-ketamine. Additionally, the arketamine exhibits higher potency toward the μ-opioid receptor (an agonist) [14].
In clinical settings, the esketamine was found to be as twice as potent in anesthetic effect compared to the racemic mixture and as threefold potent compared to arketamine [3, 14]. Furthermore, esketamine is described as the less psychotomimetic and the greater analgesic enantiomer. In comparison to arketamine the esketamine is linked to reduced clinically significant side effects such as drowsiness, fatigue, and altered cognitive function [14]. In another clinical study, they examined the recovery effects of both isomers. One hour following the intravenous administration of ketamine isomers, individuals who received the esketamine exhibited better concentration and memory retention [15]. Accordingly, in analgesic and anesthetic applications, esketamine is more favored [14].
Besides, they exhibit neuroprotective differences. In primary cultured rat hippocampal neurons, the esketamine exerts neuroprotective effects. It prevents the release of arachidonic acid and modulates axonal outgrowth measured by the expression of microtubule-associated protein at different time points [16].
Interestingly, even if the potency is comparable among the isomers, the molecular mechanism may differ. In guinea pig histamine-mediated preconstricted strips, both isomers were found to mediate spasmolytic effects. Even though their potency was similar, the mechanism was quite different. The esketamine exerts more effects through adrenaline signaling, whereas arketamine spasmolytic modulation was through calcium signaling [17].
Preclinical evidence using various depression animal models suggests the potential antidepressant advantages of arketamine over esketamine. Despite the lower affinity of arketamine, NMDA receptors exhibited superior potency and more prolonged antidepressant effects than esketamine. For that reason, other molecular targets may play an essential role in mediating ketamine antidepressant effects [10, 18]. Importantly, arketamine also has fewer side effects than either (R, S)-ketamine or esketamine as it may not induce psychotomimetic side effects or exhibit abuse potential in rodents and monkeys [11, 14, 19].
A previous report examined the enantiomers’ molecular targets selectivity and potency. Their impact on multiple neurotransmitter systems revealed that both isomers have similar effects. They increased the release of serotonin, dopamine, and noradrenaline neurotransmitters. The magnitude of their effects was quite different [18]. Arketamine showed a significant impact on the release of serotonin than esketamine. At the same time, esketamine increases dopamine release more than arketamine [19]. Table 1 summarizes the main differences between ketamine isomers.
Esketamine | Arketamine | References | |
---|---|---|---|
Potency | This isomer is considered as functionally more potent than the racemic mixture (2× more than the racemic mixture, and 3× more than R-ketamine) | This isomer is a less active one. | [3, 14] |
NMDAR antagonizing affinity | Greater affinity | Lower affinity | [20] |
μ-Opioid receptor agonism Affinity | Greater affinity | Lower affinity | [20, 21] |
Side effects (psychotomimetic, drowsiness, lethargy, and cognitive impairment, and abuse liabilities) | More side effects | less side effects | [12] |
The main differences between ketamine isomers.
Major depressive disorder (MDD) places a considerable burden on the community [22]. Among mood disorders, MDD is a common one, and it is considered one of the debilitating psychiatric disorders. Commonly prescribed antidepressants are of limited efficacy and take weeks to months to yield full therapeutic effects [21]. Most existing treatments have been found by serendipity. However, there are several limitations. First, the response to antidepressants is relatively heterogeneous; in fact, a considerable number of patients do not respond well to the treatment, the TRD [23]. An additional challenge is to distinguish TRD from inadequately treated depression [24]. Furthermore, differences are exhibited in patients’ pharmacokinetic and pharmacodynamics characteristics, which could be a key reason for the discrepancy in sex-related efficacy [25]. Moreover, most drugs are intolerable [26, 27], frequent, and enduring [28]. For these reasons, there is a need to identify and develop effective and ideal antidepressant agents.
Recently, Ketamine gained a lot of attention in its fast-onset and effectiveness when applied to depressed patients. Overall, the ketamine efficacy was successfully recorded in severely depressed patients using different validated rating scales [14]. In early 2000, Berman and his colleagues recorded the fast, moderately persistent, and robust pharmacological effects in depressed patients [29]. The double-blinded trial showed that depressed patients were significantly improved 3 days following the ketamine administration, which opened a new avenue in the management of MDD. Over the last 20 years, studies have indicated the antidepressant properties of ketamine. As an antidepressant agent, it functions in quite different mechanisms and onset than conventional antidepressant agents. Of particular interest, it brings an antidepressant effect in patients with refractory depression [30].
The central nervous system pharmacological targets of ketamine are diverse and ubiquitous. One of the main pharmacological targets for ketamine is the excitatory NMDA receptors. It is believed that ketamine mediates the anesthetic and analgesic effects through the direct noncompetitive NMDA receptors antagonist. It stimulates glutamate release in preclinical [31], and clinical studies [32]. The in vivo magnetic resonance spectroscopy clinical studies indicated that the metabolism of the 13-C-glutamate is elevated in cortical brain regions [33, 34].
Additionally, ketamine act—in lower affinity—molecularly at the inhibitory receptor the γ-aminobutyric acid (GABA) [35]. In fact, a previous report suggested the deficit of both GABAergic and glutamatergic is a unified pathological feature of MDD [36].
The AMPA receptor is another target for ketamine. Functional activation of AMPA receptors is essential for recruiting multiple pathways in modulating ketamine-induced antidepressant effects [37]. Preclinical evidence has found that the activation of AMPA receptor is critical for mediating rapid and sustained ketamine-induced antidepressant effects [38]. Ketamine was reported to elevate the hippocampal expression of AMPA receptor subunits, the glutamate receptor (GluA)1 and 2 subunits [39]. A previous study indicated that the AMPA-mediated Ketamine-induced antidepressant effects involve the glycogen synthase kinase-3 [40]. Electrophysiological studies indicate that AMPA signaling is essential for mediating the ketamine-induced antidepressant effects [38, 41]. A meta-analysis study based on in vivo and ex vivo studies indicated that ketamine elevates the level of dopamine in different brain regions relevant to the pathology of depression, including the frontal cortex, striatum, and nucleus accumbens [42].
Another molecular target for ketamine is opioid signaling. Ketamine was reported to be a weak agonist to opioid receptors isoforms, including the mu, delta, and kappa. Studies indicated that the involvement of the opioid receptor is essential for ketamine-induced antidepressant effects [14, 43].
Additionally, in a double-blind clinical study using suicidality-specific rating scales, naltrexone—an opioid receptor antagonist—was found to weaken the anti-suicidality effects of ketamine. Indicating that opioid receptor activation plays a major role in the anti-suicidality effects of ketamine [43].
The dopaminergic, cholinergic, serotonergic, and opioid, receptors are implicated in ketamine-induced antidepressant effects [44]. Furthermore, ketamine acts on the hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. Moreover, ketamine provides anti-inflammatory activities. It decreases the production of proinflammatory cytokines including the nuclear factor κB, the tumor necrosis factor-α, the interleukin 6 (IL-6), and the inducible nitric oxide synthase [3].
Another molecular target for ketamine is the glucocorticoids pathway. The administration of ketamine was found to stimulate the release of glucocorticoid downstream component, the Serum glucocorticoid kinase 1 (SGK1). Indicating that the pharmacological function of ketamine may recruit the glucocorticoid receptor pathway [45]. Table 2 describes the primary molecular targets for ketamine-mediated antidepressants effects.
The pathway | Description of the action | The mechanism of actions | References |
---|---|---|---|
NMDAR | The disinhibition hypothesis | At subanesthetic doses, ketamine inhibits NMDARs on GABAergic interneurons | [29, 46] |
Leading to alteration in the disinhibition and the overall feedback and feed-forward mechanisms. | [47] | ||
Another consequence, changing the postsynaptic AMPARs activations. | [32, 37] | ||
Direct inhibition of extra-synaptic NMDARs | Ketamine directly prevents the extra-synaptic GluN2B. Leading to precluding the glutamate-induced activation of glutamatergic receptors. Overall, this would alter protein synthesis | [37] | |
Blocking spontaneous NMDAR activation) | On principal cells—at rest—ketamine directly inhibits NMDARs | [32] | |
Preventing the tonic activation leading to activation of other pathways such as eEF2 and BDNF signaling | [46] | ||
AMPA receptor | The activation of AMPA receptor | ketamine-induced antidepressant effects are linked to the functional activation of AMPA receptors | [37] |
Preclinical evidence has found that AMPA receptor activation is critical for mediating rapid and sustained ketamine-induced antidepressant effects | [38] | ||
BDNF | The activation of BDNF | Ketamine-induced behavioral antidepressant effects are mediated through BDNF release in hippocampal primary neuronal cultures | [48] |
Ketamine-induced cellular effects through BDNF release in rats. | [49] | ||
In a clinical setting, the level of plasma BDNF in treatment-resistant depressed patients correlates with the infused level of ketamine. | [50] | ||
eEF2 | The inhibition of eEF2 | The ketamine glutamatergic-mediated mechanisms reduce eEF2 kinase activation, leading to alterations in synaptic plasticity | [32] |
Monoamines | Increases monoamines levels | Ketamine prevents serotonin reuptake | [29] |
Ketamine prevents dopamine reuptake | [51] | ||
Ketamine prevents norepinephrine reuptake | |||
Opioid system | Opioid agonism | Weak agonistic effects are mediated toward multiple isoforms of opioid receptors, including the mu, delta, and kappa | [14] |
Multiple studies indicated that activation of the opioid receptor is essential for ketamine-induced antidepressant effects | [51] |
The main molecular targets for ketamine-mediated antidepressants effects.
NMDAR, N-methyl-D’aspartate receptor; AMPAR, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors; mTORC1, mechanistic target of rapamycin complex 1; eEF2, eukaryotic elongation factor 2; BDNF, brain-derived neurotrophic factor.
The prevalence of depression is almost twice as high among women as men [46, 47, 48]. The clinical symptoms are also more prolonged and severe in women, with a high rate of recurrence compared to men [49]. Additionally, exposure to psychosocial stress is a significant risk factor for stress-related disorders, including depression. Most importantly, the physiological responses to stress are sexually dimorphic [50, 51, 52].
One possible explanation for sexually dimorphic stress responses is the locus coeruleus, a brain stem nucleus responsible for most of the noradrenergic system [53]. Triggering the locus coeruleus is a critical component of stress responses. A previous report demonstrated that neuronal populations within the locus coeruleus are substantially sensitive to the corticotropin-releasing factor in female rats compared to males [54]. We previously reported considerable evidence indicating that sexual dimorphism is a confounding factor facing a complete understanding of pathological mechanisms involved in depression and in finding an effective treatment [55].
Multiple studies have reported that ketamine-induced antidepressant effects are exerted in a sexually dimorphic manner. For instance, in a transgenic animal model, the intraperitoneal injection of ketamine exhibited sexually dimorphic molecular changes. It was found to elevate the mRNA level of Bdnf in females [56]. In another example, ketamine exhibited neurobehavioral and neurochemical alterations in a sex-dependent manner. A single sub-anesthetic ketamine dose was found to alter the 5-hydroxyindoleacetic acid to the 5-hydroxytryptamine ratio in the prefrontal cortex of female rats in 24 h post ketamine injection. While performing the forced-swim test in a behavioral setting, female rats exhibited more sensitivity to lower doses of ketamine than male rats [57]. Indicating the profound effects of hormones over the ketamine-mediated antidepressant effects. In line with this, another report found that ketamine-induced antidepressant effects were not observed in ovariectomized rats. Additionally, these effects were functionally observable following the administration of both estrogen and progesterone [58].
Interestingly, the sub-anesthetic ketamine dose was found to exhibit pharmacological dissociative effects in a sexually dimorphic manner. Whereas female rats were more sensitive and developed more significant ataxia in comparison to male rats. Besides, the magnitude of head weaving in female rats during their diestrus phase was more significant compared to females in their other stages of the estrous cycle [59]. Also, pharmacokinetics profiling of ketamine in rats indicated that both ketamine and ketamine-metabolites were presented in higher plasma concentrations in female rats than in males, suggesting the rate of hepatic clearance and metabolism might be affected by female hormones [60].
The effect of ketamine on neuroplasticity markers was examined at the proteomic level in the different brain regions following multiple ketamine bolus doses. Different bolus doses were found to induce the protein expression of c-Fos in the amygdala of female rats, not the male rats. Also, in the prefrontal cortex, this expression was modulated by the estrous cycle [61]. The administration of ketamine in female mice exposed to chronic unpredictable mild stress was reported to be mediated via the extracellular-signal-regulated kinase and glucose transporter 3 (ERK/GLUT3) signaling pathway [62].
The glucose transporter 3 (GLUT3) was found to be essential for modulating neuronal circuitry and metabolic functions [63]. This isoform of glucose transporters is predominantly expressed in neuronal populations [64]. Additionally, glut3 heterozygous mice exhibited seizures, cognitive impairments, and altered sociability behaviors in a sex-dependent manner [65].
On the other hand, ERK signaling is a crucial modulator of physiological roles affected by gender. For instance, a previous report indicated that the ERK pathway regulates the hypothalamic-pituitary-gonadal axis, and the functional maturation of the female reproduction system in pituitary-targeted ERK knockout mice is altered [66]. In line with this, in a model of psychiatric disorders, the neonatal ventral hippocampal lesion, a validated animal model of schizophrenia, the ERK signaling was reported to function in a sex-dependent manner. In the report, the content, and the phosphorylation level of different components of the ERK signaling was found to be sexually dimorphic [67].
The whole gender-related variable psychological, neurobehavioral, and molecular effects in clinical and preclinical studies are not a characteristic of ketamine alone. Other antidepressants function in a sexual-dimorphism manner. For example, males reported better outcomes than depressed females in response to tricyclic antidepressants, classical antidepressant agents. On the other hand, females exhibited better responses to selective serotonin reuptake inhibitors [68]. Indicating the significant role of gender and the hormonal system in the pathology of depression.
Whether a depression model is environmental [55], pharmacological, or genetic, organizational, and activational hormonal effects cannot be overlooked. The organizational and activational hypothesis was introduced in the late 1950s [69]. This hypothesis suggests that sex hormones regulate the central nervous system’s organization, development, and function. Organizational effects refer to the effect of steroid hormones on the brain during early developmental stages. At the same time, activational effects are lifelong hormonal effects [70].
A review conducted by Arnold [71] proposed a framework for the organizational and activational hypothesis. In his report, this hypothesis’s fundamentals include prenatal masculinization, where the prenatal exposure of female guinea pigs to testosterone alters their behavior later on. These females behaved like a male guinea pig. These changes were permanent, which could be mediated by the hormonal effect on neuronal development (the organizational effect), and that indicates the central nervous system’s vulnerability during this critical period of development. Overall, this framework supports the notion that steroid hormones’ cellular, molecular, and behavioral effects vary [71]. Extensive reports reviewed this hypothesis [71, 72, 73]. However, steroidal hormones’ activational versus organizational effects have not yet been clearly characterized [74].
Further investigation into sexual dimorphism in the neurobiology of depression is quite essential. This knowledge could potentially improve the diagnosis and treatment of depression and provide a basis for sex-based interventions. These interventions could take into account the pharmacodynamic and pharmacokinetic differences between men and women. It can further consider molecular targets for each gender.
This can be achieved if sex-oriented research on the mechanism of depression in both sexes is conducted at clinical and pre-clinical levels. Despite their limitations, animal models provide a wealth of knowledge on depression neurobiology. This chapter aimed to review existing pre-clinical research on sex differences in the neurobiology of depression and, therefore, to highlight the unmet need to investigate depression with respect to gender as a variable and, most importantly, encourage researchers to establish disease-based studies.
The authors declare that there is no conflict of interest.
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Urban tunnels are often made in soils with very low values of overburden. Risks of collapse and large deformations at the surface are high; thus negative impact on old buildings are likely to occur if appropriate measures are not taken in advance, when designing and constructing the tunnel. For deep tunnels with high overburden and low rock mass properties, squeezing conditions and excessive loads around the excavation can jeopardize the stability of the tunnel, leading to extensive collapse. The aim of the chapter is to give details on advance computational modelling and analytical methodologies, which can be used in order to design shallow and deep tunnels and to present real case studies from around the world, from very shallow tunnels in India with only 4.5 m overburden to a deep tunnel in Venezuela with extreme squeezing conditions under 1300 m overburden.",book:{id:"7690",slug:"tunnel-engineering-selected-topics",title:"Tunnel Engineering",fullTitle:"Tunnel Engineering - Selected Topics"},signatures:"Spiros Massinas",authors:[{id:"295762",title:"Dr.",name:"Spiros",middleName:null,surname:"Massinas",slug:"spiros-massinas",fullName:"Spiros Massinas"}]},{id:"68157",title:"Introductory Chapter: Textile Manufacturing Processes",slug:"introductory-chapter-textile-manufacturing-processes",totalDownloads:4470,totalCrossrefCites:14,totalDimensionsCites:25,abstract:null,book:{id:"8892",slug:"textile-manufacturing-processes",title:"Textile Manufacturing Processes",fullTitle:"Textile Manufacturing Processes"},signatures:"Faheem Uddin",authors:[{id:"228107",title:"Prof.",name:"Faheem",middleName:null,surname:"Uddin",slug:"faheem-uddin",fullName:"Faheem Uddin"}]},{id:"66828",title:"Breathing Monitoring and Pattern Recognition with Wearable Sensors",slug:"breathing-monitoring-and-pattern-recognition-with-wearable-sensors",totalDownloads:3097,totalCrossrefCites:12,totalDimensionsCites:15,abstract:"This chapter introduces the anatomy and physiology of the respiratory system, and the reasons for measuring breathing events, particularly, using wearable sensors. Respiratory monitoring is vital including detection of sleep apnea and measurement of respiratory rate. The automatic detection of breathing patterns is equally important in other respiratory rehabilitation therapies, for example, magnetic resonance exams for respiratory triggered imaging, and synchronized functional electrical stimulation. In this context, the goal of many research groups is to create wearable devices able to monitor breathing activity continuously, under natural physiological conditions in different environments. Therefore, wearable sensors that have been used recently as well as the main signal processing methods for breathing analysis are discussed. The following sensor technologies are presented: acoustic, resistive, inductive, humidity, acceleration, pressure, electromyography, impedance, and infrared. New technologies open the door to future methods of noninvasive breathing analysis using wearable sensors associated with machine learning techniques for pattern detection.",book:{id:"7654",slug:"wearable-devices-the-big-wave-of-innovation",title:"Wearable Devices",fullTitle:"Wearable Devices - the Big Wave of Innovation"},signatures:"Taisa Daiana da Costa, Maria de Fatima Fernandes Vara, Camila Santos Cristino, Tyene Zoraski Zanella, Guilherme Nunes Nogueira Neto and Percy Nohama",authors:[{id:"192464",title:"Ph.D.",name:"Percy",middleName:null,surname:"Nohama",slug:"percy-nohama",fullName:"Percy Nohama"},{id:"285706",title:"MSc.",name:"Taísa Daiana",middleName:null,surname:"Da Costa",slug:"taisa-daiana-da-costa",fullName:"Taísa Daiana Da Costa"},{id:"285707",title:"MSc.",name:"Maria de Fatima Fernandes",middleName:null,surname:"Vara",slug:"maria-de-fatima-fernandes-vara",fullName:"Maria de Fatima Fernandes Vara"},{id:"285708",title:"BSc.",name:"Camila Santos",middleName:null,surname:"Cristino",slug:"camila-santos-cristino",fullName:"Camila Santos Cristino"},{id:"285709",title:"Prof.",name:"Guilherme Nunes",middleName:null,surname:"Nogueira Neto",slug:"guilherme-nunes-nogueira-neto",fullName:"Guilherme Nunes Nogueira Neto"},{id:"293109",title:"BSc.",name:"Tyene",middleName:null,surname:"Zoraski Zanella",slug:"tyene-zoraski-zanella",fullName:"Tyene Zoraski Zanella"}]},{id:"41411",title:"Textile Dyes: Dyeing Process and Environmental Impact",slug:"textile-dyes-dyeing-process-and-environmental-impact",totalDownloads:20666,totalCrossrefCites:101,totalDimensionsCites:317,abstract:null,book:{id:"3137",slug:"eco-friendly-textile-dyeing-and-finishing",title:"Eco-Friendly Textile Dyeing and Finishing",fullTitle:"Eco-Friendly Textile Dyeing and Finishing"},signatures:"Farah Maria Drumond Chequer, Gisele Augusto Rodrigues de Oliveira, Elisa Raquel Anastácio Ferraz, Juliano Carvalho Cardoso, Maria Valnice Boldrin Zanoni and Danielle Palma de Oliveira",authors:[{id:"49040",title:"Prof.",name:"Danielle",middleName:null,surname:"Palma De Oliveira",slug:"danielle-palma-de-oliveira",fullName:"Danielle Palma De Oliveira"},{id:"149074",title:"Prof.",name:"Maria Valnice",middleName:null,surname:"Zanoni",slug:"maria-valnice-zanoni",fullName:"Maria Valnice Zanoni"},{id:"153502",title:"Ph.D.",name:"Farah",middleName:null,surname:"Chequer",slug:"farah-chequer",fullName:"Farah Chequer"},{id:"153504",title:"MSc.",name:"Gisele",middleName:null,surname:"Oliveira",slug:"gisele-oliveira",fullName:"Gisele Oliveira"},{id:"163377",title:"Dr.",name:"Juliano",middleName:null,surname:"Cardoso",slug:"juliano-cardoso",fullName:"Juliano Cardoso"},{id:"163393",title:"Dr.",name:"Elisa",middleName:null,surname:"Ferraz",slug:"elisa-ferraz",fullName:"Elisa Ferraz"}]},{id:"70242",title:"Advancements in the Fenton Process for Wastewater Treatment",slug:"advancements-in-the-fenton-process-for-wastewater-treatment",totalDownloads:1975,totalCrossrefCites:12,totalDimensionsCites:26,abstract:"Fenton is considered to be one of the most effective advanced treatment processes in the removal of many hazardous organic pollutants from refractory/toxic wastewater. It has many advantages, but drawbacks are significant such as a strong acid environment, the cost of reagents consumption, and the large production of ferric sludge, which limits Fenton’s further application. The development of Fenton applications is mainly achieved by improving oxidation efficiency and reducing sludge production. This chapter presents a review on fundamentals and applications of conventional Fenton, leading advanced technologies in the Fenton process, and reuse methods of iron containing sludge to synthetic and real wastewaters are discussed. Finally, future trends and some guidelines for Fenton processes are given.",book:{id:"9415",slug:"advanced-oxidation-processes-applications-trends-and-prospects",title:"Advanced Oxidation Processes",fullTitle:"Advanced Oxidation Processes - Applications, Trends, and Prospects"},signatures:"Min Xu, Changyong Wu and Yuexi Zhou",authors:[{id:"307479",title:"Dr.",name:"Changyong",middleName:null,surname:"Wu",slug:"changyong-wu",fullName:"Changyong Wu"},{id:"307546",title:"Prof.",name:"Yuexi",middleName:null,surname:"Zhou",slug:"yuexi-zhou",fullName:"Yuexi Zhou"},{id:"311139",title:"Dr.",name:"Min",middleName:null,surname:"Xu",slug:"min-xu",fullName:"Min Xu"}]}],onlineFirstChaptersFilter:{topicId:"24",limit:6,offset:0},onlineFirstChaptersCollection:[{id:"82676",title:"Electrospinning of Fiber Matrices from Polyhydroxybutyrate for the Controlled Release Drug Delivery Systems",slug:"electrospinning-of-fiber-matrices-from-polyhydroxybutyrate-for-the-controlled-release-drug-delivery-",totalDownloads:11,totalDimensionsCites:0,doi:"10.5772/intechopen.105786",abstract:"The submission provides an overview of current state of the problem and authors’ experimental data on manufacturing nonwoven fibrous matrices for the controlled release drug delivery systems (CRDDS). The choice of ultrathin fibers as effective carriers is determined by their characteristics and functional behavior, for example, such as a high specific surface area, anisotropy of some physicochemical characteristics, spatial limitations of segmental mobility that are inherent in nanosized objects, controlled biodegradation, and controlled diffusion transport. The structural-dynamic approach to the study of the morphology and diffusion properties of biopolymer fibers based on polyhydroxybutyrate (PHB) is considered from several angles. In the submission, the electrospinning (ES) application to reach specific characteristics of materials for controlled release drug delivery is discussed.",book:{id:"11127",title:"Electrospinning - Material Technology of the Future",coverURL:"https://cdn.intechopen.com/books/images_new/11127.jpg"},signatures:"Anatoly A. Olkhov, Svetlana G. Karpova, Anna V. Bychkova, Alexandre A. Vetcher and Alexey L. Iordanskii"},{id:"82600",title:"Impact of the Spreading of Sludge from Wastewater Treatment Plants on the Transfer and Bio-Availability of Trace Metal Elements in the Soil-Plant System",slug:"impact-of-the-spreading-of-sludge-from-wastewater-treatment-plants-on-the-transfer-and-bio-availabil",totalDownloads:12,totalDimensionsCites:0,doi:"10.5772/intechopen.103745",abstract:"The spreading of sludge from sewage treatment plants increased the production of durum wheat and rapeseed. Their richness in nitrogen, phosphorus, and potassium gives them a beneficial effect on crops. However, the application of the sludge can induce increases in the concentration of metals in plant tissues. This increase can generate disturbances at the level of the cell and organelles, such as mitochondria and chloroplasts, which can be altered. Repeated applications of the sludge on the same site tend to increase the accumulation of heavy metals in the soil, so that an cause toxicities for soil microorganisms, animals, and humans, via the food chain. However, it is important to specify that these nuisances mainly concerned industrial sludge, but the use of this sludge is strictly prohibited. In addition, the high doses used in our field experiments are significantly higher than those authorized in agricultural practice. Finally, the risk assessment by calculating both the level of consumer exposure and the number of years for soil saturation shows that the use of urban sludge is safe, especially in the short and medium-term. Nevertheless, the quality of the sludge to be spread must be constantly monitored.",book:{id:"11173",title:"Wastewater Treatment",coverURL:"https://cdn.intechopen.com/books/images_new/11173.jpg"},signatures:"Najla Lassoued and Bilal Essaid"},{id:"81249",title:"Electrospun Polymeric Substrates for Tissue Engineering: Viewpoints on Fabrication, Application, and Challenges",slug:"electrospun-polymeric-substrates-for-tissue-engineering-viewpoints-on-fabrication-application-and-ch",totalDownloads:8,totalDimensionsCites:0,doi:"10.5772/intechopen.102596",abstract:"Electrospinning is the technique for producing nonwoven fibrous structures, to mimic the fabrication and function of the native extracellular matrix (ECM) in tissue. Prepared fibrous with this method can act as potential polymeric substrates for proliferation and differentiation of stem cells (with the cellular growth pattern similar to damaged tissue cells) and facilitation of artificial tissue remodeling. Moreover, such substrates can improve biological functions, and lead to a decrease in organ transplantation. In this chapter, we focus on the fundamental parameters and principles of the electrospinning technique to generate natural ECM-like substrates, in terms of structural and functional complexity. In the following, the application of these substrates in regenerating various tissues and the role of polymers (synthetic/natural) in the formation of such substrates is evaluated. Finally, challenges of this technique (such as cellular infiltration and inadequate mechanical strength) and solutions to overcome these limitations are studied.",book:{id:"11127",title:"Electrospinning - Material Technology of the Future",coverURL:"https://cdn.intechopen.com/books/images_new/11127.jpg"},signatures:"Azadeh Izadyari Aghmiuni, Arezoo Ghadi, Elmira Azmoun, Niloufar Kalantari, Iman Mohammadi and Hossein Hemati Kordmahaleh"},{id:"82145",title:"Slope Casting Process: A Review",slug:"slope-casting-process-a-review",totalDownloads:8,totalDimensionsCites:0,doi:"10.5772/intechopen.102742",abstract:"Semi solid processing is a near net shape casting process and one of the promising techniques to obtain dendritic free structure of metals. Semi solid casting gives numerous advantages than solid processing and liquid processing. Semi solid casting process gives, Laminar flow filling of die without turbulence, Lower metal temperature, Less shrinkage, Less porosity, Higher mechanical properties. Semi solid casting process is industrially successful, producing a variety of products with good quality. Slope Casting process is a simple technique to produce semi solid feed-stoke with globular microstructure and dendrite free structure castings. Slope casting process depends on different process parameters like slope length, slope angle, pouring temperature etc. The present study mainly focuses on review of various explorations made by researchers with different process parameters of the Slope casting process and explain the mechanisms that lead to microstructural changes which leads to good mechanical properties.",book:{id:"11119",title:"Casting Processes",coverURL:"https://cdn.intechopen.com/books/images_new/11119.jpg"},signatures:"Mukkollu Sambasiva Rao and Amitesh Kumar"},{id:"81861",title:"Emerging Human Coronaviruses (SARS-CoV-2) in the Environment Associated with Outbreaks Viral Pandemics",slug:"emerging-human-coronaviruses-sars-cov-2-in-the-environment-associated-with-outbreaks-viral-pandemics",totalDownloads:19,totalDimensionsCites:0,doi:"10.5772/intechopen.103886",abstract:"In December 2019, there was a cluster of pneumonia cases in Wuhan, a city of about 11 million people in Hubei Province. The World Health Organization (WHO), qualified CoVid-19 as an emerging infectious disease on March 11, 2020, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which spreads around the world. Coronaviruses are also included in the list of viruses likely to be found in raw sewage, as are other viruses belonging to the Picornaviridae family. SRAS-CoV-2 has been detected in wastewater worldwide such as the USA, France, Netherlands, Australia, and Italy according to the National Research Institute for Public Health and the Environment. In addition, the SARS-CoV-2 could infect many animals since it has been noticed in pigs, domestic and wild birds, bats, rodents, dogs, cats, tigers, cattle. Therefore, the SARS-CoV-2 molecular characterization in the environment, particularly in wastewater and animals, appeared to be a novel approach to monitor the outbreaks of viral pandemics. This review will be focused on the description of some virological characteristics of these emerging viruses, the different human and zoonotic coronaviruses, the sources of contamination of wastewater by coronaviruses and their potential procedures of disinfection from wastewater.",book:{id:"11173",title:"Wastewater Treatment",coverURL:"https://cdn.intechopen.com/books/images_new/11173.jpg"},signatures:"Chourouk Ibrahim, Salah Hammami, Eya Ghanmi and Abdennaceur Hassen"},{id:"81797",title:"Study of Change Surface Aerator to Submerged Nonporous Aerator in Biological Pond in an Industrial Wastewater Treatment in Daura Refinery",slug:"study-of-change-surface-aerator-to-submerged-nonporous-aerator-in-biological-pond-in-an-industrial-w",totalDownloads:11,totalDimensionsCites:0,doi:"10.5772/intechopen.104860",abstract:"Daura refinery, with a capacity of 140,000 barrel per stream day as a refining capacity, wastewater discharged from refining and treatment processing units, polluted water as foul water, drainages, oil spills, blowdown of boilers and cooling towers, and many other polluted water sources, aims to remove pollutants and reject clean water to the river; wastewater treatment system takes place in this treatment process. Wastewater treatment system suffers from many problems and specifically biological stage; at this stage, activated sludge with bacteria, should be supplied with oxygen, aeration system done by surface aerators with four surface fans; these fans suffer from high vibration, loss support, and in consequence, lack in oxygen supply to aerobic bacteria less than 4 ppm. The nonporous aerator is suggested as an oxygen source for the biological pool. The pilot plant builds the aim to study the ability to apply the new aeration system at the biological pool, pilot plant build with 1 cubic meter capacity tank and continuous overflow of wastewater of 10 liters.min−1, air injected with the pressure of (0.5–0.75) bar(g), and airflow of (7.6–9.7) liter.min−1 respectively. Oxygen concentration was recorded as (3.4–6.0) ppm; in terms of consumption power, changing the aeration system reduces it to less than 20%.",book:{id:"11173",title:"Wastewater Treatment",coverURL:"https://cdn.intechopen.com/books/images_new/11173.jpg"},signatures:"Omar M. 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She is currently an Adjunct Professor at Feevale University in Medicine and Biomedicine courses and a permanent professor of the Academic Master\\'s Degree in Virology. She has experience in the field of Microbiology, with an emphasis on Bacteriology, working mainly on the following topics: bacteriophages, bacterial resistance, clinical microbiology and food microbiology.",institutionString:null,institution:{name:"Universidade Feevale",country:{name:"Brazil"}}},{id:"229220",title:"Dr.",name:"Amjad",middleName:"Islam",surname:"Aqib",slug:"amjad-aqib",fullName:"Amjad Aqib",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229220/images/system/229220.png",biography:"Dr. Amjad Islam Aqib obtained a DVM and MSc (Hons) from University of Agriculture Faisalabad (UAF), Pakistan, and a PhD from the University of Veterinary and Animal Sciences Lahore, Pakistan. Dr. Aqib joined the Department of Clinical Medicine and Surgery at UAF for one year as an assistant professor where he developed a research laboratory designated for pathogenic bacteria. Since 2018, he has been Assistant Professor/Officer in-charge, Department of Medicine, Manager Research Operations and Development-ORIC, and President One Health Club at Cholistan University of Veterinary and Animal Sciences, Bahawalpur, Pakistan. He has nearly 100 publications to his credit. His research interests include epidemiological patterns and molecular analysis of antimicrobial resistance and modulation and vaccine development against animal pathogens of public health concern.",institutionString:"Cholistan University of Veterinary and Animal Sciences",institution:{name:"University of Agriculture Faisalabad",country:{name:"Pakistan"}}},{id:"333753",title:"Dr.",name:"Rais",middleName:null,surname:"Ahmed",slug:"rais-ahmed",fullName:"Rais Ahmed",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/333753/images/20168_n.jpg",biography:null,institutionString:null,institution:{name:"University of Agriculture Faisalabad",country:{name:"Pakistan"}}},{id:"62900",title:"Prof.",name:"Fethi",middleName:null,surname:"Derbel",slug:"fethi-derbel",fullName:"Fethi Derbel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/62900/images/system/62900.jpeg",biography:"Professor Fethi Derbel was born in 1960 in Tunisia. He received his medical degree from the Sousse Faculty of Medicine at Sousse, University of Sousse, Tunisia. He completed his surgical residency in General Surgery at the University Hospital Farhat Hached of Sousse and was a member of the Unit of Liver Transplantation in the University of Rennes, France. He then worked in the Department of Surgery at the Sahloul University Hospital in Sousse. Professor Derbel is presently working at the Clinique les Oliviers, Sousse, Tunisia. His hospital activities are mostly concerned with laparoscopic, colorectal, pancreatic, hepatobiliary, and gastric surgery. He is also very interested in hernia surgery and performs ventral hernia repairs and inguinal hernia repairs. He has been a member of the GREPA and Tunisian Hernia Society (THS). During his residency, he managed patients suffering from diabetic foot, and he was very interested in this pathology. For this reason, he decided to coordinate a book project dealing with the diabetic foot. Professor Derbel has published many articles in journals and collaborates intensively with IntechOpen Access Publisher as an editor.",institutionString:"Clinique les Oliviers",institution:null},{id:"300144",title:"Dr.",name:"Meriem",middleName:null,surname:"Braiki",slug:"meriem-braiki",fullName:"Meriem Braiki",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/300144/images/system/300144.jpg",biography:"Dr. Meriem Braiki is a specialist in pediatric surgeon from Tunisia. She was born in 1985. She received her medical degree from the University of Medicine at Sousse, Tunisia. She achieved her surgical residency training periods in Pediatric Surgery departments at University Hospitals in Monastir, Tunis and France.\r\nShe is currently working at the Pediatric surgery department, Sidi Bouzid Hospital, Tunisia. Her hospital activities are mostly concerned with laparoscopic, parietal, urological and digestive surgery. She has published several articles in diffrent journals.",institutionString:"Sidi Bouzid Regional Hospital",institution:null},{id:"229481",title:"Dr.",name:"Erika M.",middleName:"Martins",surname:"de Carvalho",slug:"erika-m.-de-carvalho",fullName:"Erika M. de Carvalho",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229481/images/6397_n.jpg",biography:null,institutionString:null,institution:{name:"Oswaldo Cruz Foundation",country:{name:"Brazil"}}},{id:"186537",title:"Prof.",name:"Tonay",middleName:null,surname:"Inceboz",slug:"tonay-inceboz",fullName:"Tonay Inceboz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/186537/images/system/186537.jfif",biography:"I was graduated from Ege University of Medical Faculty (Turkey) in 1988 and completed his Med. PhD degree in Medical Parasitology at the same university. I became an Associate Professor in 2008 and Professor in 2014. I am currently working as a Professor at the Department of Medical Parasitology at Dokuz Eylul University, Izmir, Turkey.\n\nI have given many lectures, presentations in different academic meetings. I have more than 60 articles in peer-reviewed journals, 18 book chapters, 1 book editorship.\n\nMy research interests are Echinococcus granulosus, Echinococcus multilocularis (diagnosis, life cycle, in vitro and in vivo cultivation), and Trichomonas vaginalis (diagnosis, PCR, and in vitro cultivation).",institutionString:"Dokuz Eylül University",institution:{name:"Dokuz Eylül University",country:{name:"Turkey"}}},{id:"71812",title:"Prof.",name:"Hanem Fathy",middleName:"Fathy",surname:"Khater",slug:"hanem-fathy-khater",fullName:"Hanem Fathy Khater",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/71812/images/1167_n.jpg",biography:"Prof. Khater is a Professor of Parasitology at Benha University, Egypt. She studied for her doctoral degree, at the Department of Entomology, College of Agriculture, Food and Natural Resources, University of Missouri, Columbia, USA. She has completed her Ph.D. degrees in Parasitology in Egypt, from where she got the award for “the best scientific Ph.D. dissertation”. She worked at the School of Biological Sciences, Bristol, England, the UK in controlling insects of medical and veterinary importance as a grant from Newton Mosharafa, the British Council. Her research is focused on searching of pesticides against mosquitoes, house flies, lice, green bottle fly, camel nasal botfly, soft and hard ticks, mites, and the diamondback moth as well as control of several parasites using safe and natural materials to avoid drug resistances and environmental contamination.",institutionString:null,institution:{name:"Banha University",country:{name:"Egypt"}}},{id:"99780",title:"Prof.",name:"Omolade",middleName:"Olayinka",surname:"Okwa",slug:"omolade-okwa",fullName:"Omolade Okwa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/99780/images/system/99780.jpg",biography:"Omolade Olayinka Okwa is presently a Professor of Parasitology at Lagos State University, Nigeria. She has a PhD in Parasitology (1997), an MSc in Cellular Parasitology (1992), and a BSc (Hons) Zoology (1990) all from the University of Ibadan, Nigeria. She teaches parasitology at the undergraduate and postgraduate levels. She was a recipient of a Commonwealth fellowship supported by British Council tenable at the Centre for Entomology and Parasitology (CAEP), Keele University, United Kingdom between 2004 and 2005. She was awarded an Honorary Visiting Research Fellow at the same university from 2005 to 2007. \nShe has been an external examiner to the Department of Veterinary Microbiology and Parasitology, University of Ibadan, MSc programme between 2010 and 2012. She is a member of the Nigerian Society of Experimental Biology (NISEB), Parasitology and Public Health Society of Nigeria (PPSN), Science Association of Nigeria (SAN), Zoological Society of Nigeria (ZSN), and is Vice Chairperson of the Organisation of Women in Science (OWSG), LASU chapter. She served as Head of Department of Zoology and Environmental Biology, Lagos State University from 2007 to 2010 and 2014 to 2016. She is a reviewer for several local and international journals such as Unilag Journal of Science, Libyan Journal of Medicine, Journal of Medicine and Medical Sciences, and Annual Research and Review in Science. \nShe has authored 45 scientific research publications in local and international journals, 8 scientific reviews, 4 books, and 3 book chapters, which includes the books “Malaria Parasites” and “Malaria” which are IntechOpen access publications.",institutionString:"Lagos State University",institution:{name:"Lagos State University",country:{name:"Nigeria"}}},{id:"273100",title:"Dr.",name:"Vijay",middleName:null,surname:"Gayam",slug:"vijay-gayam",fullName:"Vijay Gayam",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/273100/images/system/273100.jpeg",biography:"Dr. Vijay Bhaskar Reddy Gayam is currently practicing as an internist at Interfaith Medical Center in Brooklyn, New York, USA. He is also a Clinical Assistant Professor at the SUNY Downstate University Hospital and Adjunct Professor of Medicine at the American University of Antigua. He is a holder of an M.B.B.S. degree bestowed to him by Osmania Medical College and received his M.D. at Interfaith Medical Center. His career goals thus far have heavily focused on direct patient care, medical education, and clinical research. He currently serves in two leadership capacities; Assistant Program Director of Medicine at Interfaith Medical Center and as a Councilor for the American\r\nFederation for Medical Research. As a true academician and researcher, he has more than 50 papers indexed in international peer-reviewed journals. He has also presented numerous papers in multiple national and international scientific conferences. His areas of research interest include general internal medicine, gastroenterology and hepatology. He serves as an editor, editorial board member and reviewer for multiple international journals. His research on Hepatitis C has been very successful and has led to multiple research awards, including the 'Equity in Prevention and Treatment Award” from the New York Department of Health Viral Hepatitis Symposium (2018) and the 'Presidential Poster Award” awarded to him by the American College of Gastroenterology (2018). He was also awarded 'Outstanding Clinician in General Medicine” by Venus International Foundation for his extensive research expertise and services, perform over and above the standard expected in the advancement of healthcare, patient safety and quality of care.",institutionString:"Interfaith Medical Center",institution:{name:"Interfaith Medical Center",country:{name:"United States of America"}}},{id:"93517",title:"Dr.",name:"Clement",middleName:"Adebajo",surname:"Meseko",slug:"clement-meseko",fullName:"Clement Meseko",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/93517/images/system/93517.jpg",biography:"Dr. Clement Meseko obtained DVM and PhD degree in Veterinary Medicine and Virology respectively. He has worked for over 20 years in both private and public sectors including the academia, contributing to knowledge and control of infectious disease. Through the application of epidemiological skill, classical and molecular virological skills, he investigates viruses of economic and public health importance for the mitigation of the negative impact on people, animal and the environment in the context of Onehealth. \r\nDr. Meseko’s field experience on animal and zoonotic diseases and pathogen dynamics at the human-animal interface over the years shaped his carrier in research and scientific inquiries. He has been part of the investigation of Highly Pathogenic Avian Influenza incursions in sub Saharan Africa and monitors swine Influenza (Pandemic influenza Virus) agro-ecology and potential for interspecies transmission. He has authored and reviewed a number of journal articles and book chapters.",institutionString:"National Veterinary Research Institute",institution:{name:"National Veterinary Research Institute",country:{name:"Nigeria"}}},{id:"158026",title:"Prof.",name:"Shailendra K.",middleName:null,surname:"Saxena",slug:"shailendra-k.-saxena",fullName:"Shailendra K. Saxena",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRET3QAO/Profile_Picture_2022-05-10T10:10:26.jpeg",biography:"Professor Dr. Shailendra K. Saxena is a vice dean and professor at King George's Medical University, Lucknow, India. His research interests involve understanding the molecular mechanisms of host defense during human viral infections and developing new predictive, preventive, and therapeutic strategies for them using Japanese encephalitis virus (JEV), HIV, and emerging viruses as a model via stem cell and cell culture technologies. His research work has been published in various high-impact factor journals (Science, PNAS, Nature Medicine) with a high number of citations. He has received many awards and honors in India and abroad including various Young Scientist Awards, BBSRC India Partnering Award, and Dr. JC Bose National Award of Department of Biotechnology, Min. of Science and Technology, Govt. of India. Dr. Saxena is a fellow of various international societies/academies including the Royal College of Pathologists, United Kingdom; Royal Society of Medicine, London; Royal Society of Biology, United Kingdom; Royal Society of Chemistry, London; and Academy of Translational Medicine Professionals, Austria. He was named a Global Leader in Science by The Scientist. He is also an international opinion leader/expert in vaccination for Japanese encephalitis by IPIC (UK).",institutionString:"King George's Medical University",institution:{name:"King George's Medical University",country:{name:"India"}}},{id:"94928",title:"Dr.",name:"Takuo",middleName:null,surname:"Mizukami",slug:"takuo-mizukami",fullName:"Takuo Mizukami",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94928/images/6402_n.jpg",biography:null,institutionString:null,institution:{name:"National Institute of Infectious Diseases",country:{name:"Japan"}}},{id:"233433",title:"Dr.",name:"Yulia",middleName:null,surname:"Desheva",slug:"yulia-desheva",fullName:"Yulia Desheva",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/233433/images/system/233433.png",biography:"Dr. Yulia Desheva is a leading researcher at the Institute of Experimental Medicine, St. Petersburg, Russia. She is a professor in the Stomatology Faculty, St. Petersburg State University. She has expertise in the development and evaluation of a wide range of live mucosal vaccines against influenza and bacterial complications. Her research interests include immunity against influenza and COVID-19 and the development of immunization schemes for high-risk individuals.",institutionString:'Federal State Budgetary Scientific Institution "Institute of Experimental Medicine"',institution:null},{id:"238958",title:"Mr.",name:"Atamjit",middleName:null,surname:"Singh",slug:"atamjit-singh",fullName:"Atamjit Singh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/238958/images/6575_n.jpg",biography:null,institutionString:null,institution:null},{id:"252058",title:"M.Sc.",name:"Juan",middleName:null,surname:"Sulca",slug:"juan-sulca",fullName:"Juan Sulca",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/252058/images/12834_n.jpg",biography:null,institutionString:null,institution:null},{id:"191392",title:"Dr.",name:"Marimuthu",middleName:null,surname:"Govindarajan",slug:"marimuthu-govindarajan",fullName:"Marimuthu Govindarajan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/191392/images/5828_n.jpg",biography:"Dr. M. Govindarajan completed his BSc degree in Zoology at Government Arts College (Autonomous), Kumbakonam, and MSc, MPhil, and PhD degrees at Annamalai University, Annamalai Nagar, Tamil Nadu, India. He is serving as an assistant professor at the Department of Zoology, Annamalai University. His research interests include isolation, identification, and characterization of biologically active molecules from plants and microbes. He has identified more than 20 pure compounds with high mosquitocidal activity and also conducted high-quality research on photochemistry and nanosynthesis. He has published more than 150 studies in journals with impact factor and 2 books in Lambert Academic Publishing, Germany. He serves as an editorial board member in various national and international scientific journals.",institutionString:null,institution:null},{id:"274660",title:"Dr.",name:"Damodar",middleName:null,surname:"Paudel",slug:"damodar-paudel",fullName:"Damodar Paudel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/274660/images/8176_n.jpg",biography:"I am DrDamodar Paudel,currently working as consultant Physician in Nepal police Hospital.",institutionString:null,institution:null},{id:"241562",title:"Dr.",name:"Melvin",middleName:null,surname:"Sanicas",slug:"melvin-sanicas",fullName:"Melvin Sanicas",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/241562/images/6699_n.jpg",biography:null,institutionString:null,institution:null},{id:"322007",title:"Dr.",name:"Maria Elizbeth",middleName:null,surname:"Alvarez-Sánchez",slug:"maria-elizbeth-alvarez-sanchez",fullName:"Maria Elizbeth Alvarez-Sánchez",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Universidad Autónoma de la Ciudad de México",country:{name:"Mexico"}}},{id:"337443",title:"Dr.",name:"Juan",middleName:null,surname:"A. Gonzalez-Sanchez",slug:"juan-a.-gonzalez-sanchez",fullName:"Juan A. Gonzalez-Sanchez",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Puerto Rico System",country:{name:"United States of America"}}},{id:"337446",title:"Dr.",name:"Maria",middleName:null,surname:"Zavala-Colon",slug:"maria-zavala-colon",fullName:"Maria Zavala-Colon",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Puerto Rico, Medical Sciences Campus",country:{name:"United States of America"}}},{id:"338856",title:"Mrs.",name:"Nur Alvira",middleName:null,surname:"Pascawati",slug:"nur-alvira-pascawati",fullName:"Nur Alvira Pascawati",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Universitas Respati Yogyakarta",country:{name:"Indonesia"}}}]}},subseries:{item:{id:"4",type:"subseries",title:"Fungal Infectious Diseases",keywords:"Emerging Fungal Pathogens, Invasive Infections, Epidemiology, Cell Membrane, Fungal Virulence, Diagnosis, Treatment",scope:"Fungi are ubiquitous and there are almost no non-pathogenic fungi. Fungal infectious illness prevalence and prognosis are determined by the exposure between fungi and host, host immunological state, fungal virulence, and early and accurate diagnosis and treatment. \r\nPatients with both congenital and acquired immunodeficiency are more likely to be infected with opportunistic mycosis. Fungal infectious disease outbreaks are common during the post- disaster rebuilding era, which is characterised by high population density, migration, and poor health and medical conditions.\r\nSystemic or local fungal infection is mainly associated with the fungi directly inhaled or inoculated in the environment during the disaster. The most common fungal infection pathways are human to human (anthropophilic), animal to human (zoophilic), and environment to human (soilophile). Diseases are common as a result of widespread exposure to pathogenic fungus dispersed into the environment. \r\nFungi that are both common and emerging are intertwined. In Southeast Asia, for example, Talaromyces marneffei is an important pathogenic thermally dimorphic fungus that causes systemic mycosis. Widespread fungal infections with complicated and variable clinical manifestations, such as Candida auris infection resistant to several antifungal medicines, Covid-19 associated with Trichoderma, and terbinafine resistant dermatophytosis in India, are among the most serious disorders. \r\nInappropriate local or systemic use of glucocorticoids, as well as their immunosuppressive effects, may lead to changes in fungal infection spectrum and clinical characteristics. Hematogenous candidiasis is a worrisome issue that affects people all over the world, particularly ICU patients. CARD9 deficiency and fungal infection have been major issues in recent years. Invasive aspergillosis is associated with a significant death rate. Special attention should be given to endemic fungal infections, identification of important clinical fungal infections advanced in yeasts, filamentous fungal infections, skin mycobiome and fungal genomes, and immunity to fungal infections.\r\nIn addition, endemic fungal diseases or uncommon fungal infections caused by Mucor irregularis, dermatophytosis, Malassezia, cryptococcosis, chromoblastomycosis, coccidiosis, blastomycosis, histoplasmosis, sporotrichosis, and other fungi, should be monitored. \r\nThis topic includes the research progress on the etiology and pathogenesis of fungal infections, new methods of isolation and identification, rapid detection, drug sensitivity testing, new antifungal drugs, schemes and case series reports. It will provide significant opportunities and support for scientists, clinical doctors, mycologists, antifungal drug researchers, public health practitioners, and epidemiologists from all over the world to share new research, ideas and solutions to promote the development and progress of medical mycology.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/4.jpg",hasOnlineFirst:!0,hasPublishedBooks:!1,annualVolume:11400,editor:{id:"174134",title:"Dr.",name:"Yuping",middleName:null,surname:"Ran",slug:"yuping-ran",fullName:"Yuping Ran",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bS9d6QAC/Profile_Picture_1630330675373",biography:"Dr. Yuping Ran, Professor, Department of Dermatology, West China Hospital, Sichuan University, Chengdu, China. Completed the Course Medical Mycology, the Centraalbureau voor Schimmelcultures (CBS), Fungal Biodiversity Centre, Netherlands (2006). International Union of Microbiological Societies (IUMS) Fellow, and International Emerging Infectious Diseases (IEID) Fellow, Centers for Diseases Control and Prevention (CDC), Atlanta, USA. Diploma of Dermatological Scientist, Japanese Society for Investigative Dermatology. Ph.D. of Juntendo University, Japan. Bachelor’s and Master’s degree, Medicine, West China University of Medical Sciences. Chair of Sichuan Medical Association Dermatology Committee. General Secretary of The 19th Annual Meeting of Chinese Society of Dermatology and the Asia Pacific Society for Medical Mycology (2013). In charge of the Annual Medical Mycology Course over 20-years authorized by National Continue Medical Education Committee of China. Member of the board of directors of the Asia-Pacific Society for Medical Mycology (APSMM). Associate editor of Mycopathologia. Vice-chief of the editorial board of Chinses Journal of Mycology, China. 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