Distribution of Nd, Pr, Fe, and B in the one-shot recovery process.
\\n\\n
These books synthesize perspectives of renowned scientists from the world’s most prestigious institutions - from Fukushima Renewable Energy Institute in Japan to Stanford University in the United States, including Columbia University (US), University of Sidney (AU), University of Miami (USA), Cardiff University (UK), and many others.
\\n\\nThis collaboration embodied the true essence of Open Access by simplifying the approach to OA publishing for Academic editors and authors who contributed their research and allowed the new research to be made available free and open to anyone anywhere in the world.
\\n\\nTo celebrate the 50 books published, we have gathered them at one location - just one click away, so that you can easily browse the subjects of your interest, download the content directly, share it or read online.
\\n\\n\\n\\n\\n"}]',published:!0,mainMedia:null},components:[{type:"htmlEditorComponent",content:'
IntechOpen and Knowledge Unlatched formed a partnership to support researchers working in engineering sciences by enabling an easier approach to publishing Open Access content. Using the Knowledge Unlatched crowdfunding model to raise the publishing costs through libraries around the world, Open Access Publishing Fee (OAPF) was not required from the authors.
\n\nInitially, the partnership supported engineering research, but it soon grew to include physical and life sciences, attracting more researchers to the advantages of Open Access publishing.
\n\n\n\nThese books synthesize perspectives of renowned scientists from the world’s most prestigious institutions - from Fukushima Renewable Energy Institute in Japan to Stanford University in the United States, including Columbia University (US), University of Sidney (AU), University of Miami (USA), Cardiff University (UK), and many others.
\n\nThis collaboration embodied the true essence of Open Access by simplifying the approach to OA publishing for Academic editors and authors who contributed their research and allowed the new research to be made available free and open to anyone anywhere in the world.
\n\nTo celebrate the 50 books published, we have gathered them at one location - just one click away, so that you can easily browse the subjects of your interest, download the content directly, share it or read online.
\n\n\n\n\n'}],latestNews:[{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"},{slug:"introducing-intechopen-book-series-a-new-publishing-format-for-oa-books-20210915",title:"Introducing IntechOpen Book Series - A New Publishing Format for OA Books"}]},book:{item:{type:"book",id:"4648",leadTitle:null,fullTitle:"Concepts, Compounds and the Alternatives of Antibacterials",title:"Concepts, Compounds and the Alternatives of Antibacterials",subtitle:null,reviewType:"peer-reviewed",abstract:"This edition is intended to provide better understanding of antibacterial drugs and their mechanism, the role of a few metal drug complexes as antibacterials, cross-checking of a few compounds and biomaterials against drug-resistant bacterial strains as well as a few alternative approaches using medicinal plant based formulations in the control of antibiotic-resistant bacteria. The information in this book provides clues for upcoming trends in treating antibiotic resistance problems with which one can explore new approaches in the treatment of common infections with drug-resistant strains.",isbn:null,printIsbn:"978-953-51-2232-6",pdfIsbn:"978-953-51-5417-4",doi:"10.5772/59522",price:119,priceEur:129,priceUsd:155,slug:"concepts-compounds-and-the-alternatives-of-antibacterials",numberOfPages:210,isOpenForSubmission:!1,isInWos:1,isInBkci:!1,hash:"ba284c040146d00fdd709cabc4c8cb5a",bookSignature:"Varaprasad Bobbarala",publishedDate:"December 9th 2015",coverURL:"https://cdn.intechopen.com/books/images_new/4648.jpg",numberOfDownloads:19519,numberOfWosCitations:50,numberOfCrossrefCitations:38,numberOfCrossrefCitationsByBook:1,numberOfDimensionsCitations:92,numberOfDimensionsCitationsByBook:3,hasAltmetrics:1,numberOfTotalCitations:180,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"October 20th 2014",dateEndSecondStepPublish:"November 10th 2014",dateEndThirdStepPublish:"February 14th 2015",dateEndFourthStepPublish:"May 15th 2015",dateEndFifthStepPublish:"June 14th 2015",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"90574",title:"Dr.",name:"Varaprasad",middleName:null,surname:"Bobbarala",slug:"varaprasad-bobbarala",fullName:"Varaprasad Bobbarala",profilePictureURL:"https://mts.intechopen.com/storage/users/90574/images/868_n.jpg",biography:"Dr. Varaprasad Bobbarala received his Ph.D. in Faculty of Science from Andhra University in 2008 under the direction of Professor K. Chandrasekhara Naidu and Professor G. Seshagiri Rao. Specialized in Biochemistry, Medicinal chemistry and Microbiology. He has published over 90 original research articles, reviews, book chapters, and edited three books. He is currently Editor In-Chief of International Journal of Bioassays (ISSN: 2278-778X), Associate Editor and member of the editorial boards as well as the reviewer of dozens of high-impact international periodicals. Dr. B. Varaprasad, previously served as the Chief Scientist of Research and Development (R & D) at Krisani Innovations Pvt. Ltd., before his current role as the Chief Scientist and Technical Director of Research and Development of Adhya Biosciences Pvt. Ltd., India. He is actively engaged in scientific research in the areas of Antimicrobial Resistance, Drug Discovery, Isolation of Bio-active metabolites and bio-efficacy studies.",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"3",institution:null}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"897",title:"Pharmaceutical Microbiology",slug:"pharmaceutical-microbiology"}],chapters:[{id:"48837",title:"Antibacterial Drugs — From Basic Concepts to Complex Therapeutic Mechanisms of Polymer Systems",doi:"10.5772/60755",slug:"antibacterial-drugs-from-basic-concepts-to-complex-therapeutic-mechanisms-of-polymer-systems",totalDownloads:3311,totalCrossrefCites:2,totalDimensionsCites:10,hasAltmetrics:0,abstract:"Infections caused by diverse bacteria represent a major problem that threats the health of humans. This stimulates the scientists to find new solutions for treating these diseases by clarifying the interactions of antibacterial compounds with the biological medium. In this context, the chapter presents some basic concepts regarding the antibacterial drugs. The synthesis routes of novel compounds and specific design techniques with polymer materials are described in correlation with the in vitro and in vivo activity of antibacterial substances. Essential data about the mechanism of action, selected in vivo efficacy and mechanisms of resistance to the most used antibacterial drugs are reviewed.",signatures:"Andreea Irina Barzic and Silvia Ioan",downloadPdfUrl:"/chapter/pdf-download/48837",previewPdfUrl:"/chapter/pdf-preview/48837",authors:[{id:"93800",title:"Dr.",name:"Silvia",surname:"Ioan",slug:"silvia-ioan",fullName:"Silvia Ioan"}],corrections:null},{id:"49219",title:"Perception and Resistance Mechanism of some Metal-drug Complexes and Their Roles as Antibacterial",doi:"10.5772/61033",slug:"perception-and-resistance-mechanism-of-some-metal-drug-complexes-and-their-roles-as-antibacterial",totalDownloads:1614,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Metal-based drugs have undergone much development and application for therapeutic and diagnostic purposes for many decades since the huge success of cisplatin and other successful metal-drug complexes in the clinical stages. Furthermore, this metal-based drug has come up with a lot of signs of resistance and side-effects in their uses. This review points to some of the resistance natures and mechanisms of previously synthesized complexes in the field of chemistry.",signatures:"Joshua A. Obaleye, Nzikahyel Simon, Olufunso O. Abosede, Mercy\nO. Bamigboye, Abiodun A. Ajibola, Uche B. Eke and Elizabeth A.\nBalogun",downloadPdfUrl:"/chapter/pdf-download/49219",previewPdfUrl:"/chapter/pdf-preview/49219",authors:[{id:"99498",title:"Prof.",name:"Joshua",surname:"Obaleye",slug:"joshua-obaleye",fullName:"Joshua Obaleye"}],corrections:null},{id:"49473",title:"Quinolone Compounds with Activity Against Multidrug- Resistant Gram-Positive Microorganisms",doi:"10.5772/60948",slug:"quinolone-compounds-with-activity-against-multidrug-resistant-gram-positive-microorganisms",totalDownloads:1731,totalCrossrefCites:2,totalDimensionsCites:2,hasAltmetrics:0,abstract:"The emergence of resistance to antimicrobial agents is a global public health problem. Some microorganisms may develop resistance to a single antimicrobial agent (or related class of agent), while others develop resistance to several antimicrobial agents or classes. These organisms are often referred to as multidrug-resistant or MDR strains. Identification of new molecules that show activity against multidrug-resistant microorganisms and its development on a new antimicrobial drug, would be an important step in the fight against antimicrobial resistance. This paper presents experimental data regarding the synthesis of several quinolones. The novel compounds having quinolone structure were synthesized by Gould-Jacobs method. Their structure has been determined and confirmed by the following physicochemical methods: elemental analysis, IR spectral analysis, H-NMR, C-NMR, UV, thin layer chromatography. The new compounds have been evaluated for „in vitro” activity by determining minimum inhibitory concentration against a variety of bacteria Some of new quinolones, which showed a good activity, have been tested against 30 strains of methicillin resistant Staphylococcus aureus isolated in the Microbiology Laboratory of INBI Prof. “Dr. Matei Bals” during 2012 The minimum inhibitory concentration (MIC) of the isolates have been determined by agar plate Mueller Hinton (bioMerieux) dilution method using the reference strain Staphylococcus aureus ATCC 29213. The 30 strains of isolated have been also tested for susceptibility to ciprofloxacin, levofloxacin and imipenem by Etest method. Base on the “in vitro” studies, the quinolone FPQ-30 appears to be an promising compound, all strains isolates were inhibited at a concentration of 8 μg/ml.",signatures:"Pintilie Lucia",downloadPdfUrl:"/chapter/pdf-download/49473",previewPdfUrl:"/chapter/pdf-preview/49473",authors:[{id:"94504",title:"Dr.",name:"Lucia",surname:"Pintilie",slug:"lucia-pintilie",fullName:"Lucia Pintilie"}],corrections:null},{id:"49246",title:"Chitosan as a Biomaterial — Structure, Properties, and Electrospun Nanofibers",doi:"10.5772/61300",slug:"chitosan-as-a-biomaterial-structure-properties-and-electrospun-nanofibers",totalDownloads:4618,totalCrossrefCites:24,totalDimensionsCites:55,hasAltmetrics:0,abstract:"Chitosan is a polysaccharide derived from chitin; chitin is the second most abundant polysaccharide in the world, after cellulose. Chitosan is biocompatible, biodegradable and non-toxic, so that it can be usedin medicalapplications such as antimicrobial and wound healing biomaterials. It also used as chelating agent due to its ability to bind with cholesterol, fats, proteins and metal ions.",signatures:"H. M. Ibrahim and E.M.R. El- Zairy",downloadPdfUrl:"/chapter/pdf-download/49246",previewPdfUrl:"/chapter/pdf-preview/49246",authors:[{id:"90645",title:"Dr.",name:"Hassan",surname:"Ibrahim",slug:"hassan-ibrahim",fullName:"Hassan Ibrahim"},{id:"175694",title:"Dr.",name:"Enas",surname:"El- Zairy",slug:"enas-el-zairy",fullName:"Enas El- Zairy"}],corrections:null},{id:"48931",title:"Nisin",doi:"10.5772/60932",slug:"nisin",totalDownloads:2991,totalCrossrefCites:7,totalDimensionsCites:11,hasAltmetrics:0,abstract:"Antimicrobial peptides (AMPs) are small cationic peptides which protect their hosts against bacteria, protozoa, viruses, and fungi. Bacterial AMPs are called bacteriocins, and are produced by both Gram-positive and Gram-negative bacteria. Because of their high potency and specificity, bacteriocins are considered as promising antimicrobial agents for different applications, including food preservation and infection treatment; specially the ones produced by acid lactic bacteria species (Gram-positive). Nisin is the most intensively studied and used bacteriocin, it is found commercially available and its use is regulated in over 50 countries. Therefore, special attention is given to this bacteriocin.",signatures:"Angela Faustino Jozala, Letícia Celia de Lencastre Novaes and\nAdalberto Pessoa Junior",downloadPdfUrl:"/chapter/pdf-download/48931",previewPdfUrl:"/chapter/pdf-preview/48931",authors:[{id:"82505",title:"Prof.",name:"Adalberto",surname:"Pessoa Jr.",slug:"adalberto-pessoa-jr.",fullName:"Adalberto Pessoa Jr."},{id:"84924",title:"Dr.",name:"Letícia",surname:"De Lencastre Novaes",slug:"leticia-de-lencastre-novaes",fullName:"Letícia De Lencastre Novaes"},{id:"174371",title:"Dr.",name:"Angela",surname:"Jozala",slug:"angela-jozala",fullName:"Angela Jozala"}],corrections:null},{id:"48961",title:"Natural Products as Antibacterial Agents — Antibacterial Potential and Safety of Post-distillation and Waste Material from Thymus vulgaris L., Lamiaceae",doi:"10.5772/60869",slug:"natural-products-as-antibacterial-agents-antibacterial-potential-and-safety-of-post-distillation-and",totalDownloads:2633,totalCrossrefCites:3,totalDimensionsCites:13,hasAltmetrics:1,abstract:"Medicinal plants have a long tradition of use in folk and conventional medicine. In recent years numerous studies confirm various bioactivities of natural products, among them antibacterial activity. Natural antibacterial agents such are essential oils and isolated compounds now represent a notable source for pharmaceutical and food industry and are widely used in cosmetology. They meet standards of 'green consumerism' together with excellent antibacterial activity. Aromatic plants such is Thymus vulgaris L. are the major sources of essential oils. Thyme essential oil, as well as dominant compounds thymol and carvacrol are generally recognised as safe and have been registered by European Commission for use as flavouring agents in foodstuffs. However, essential oil is present in very low amount (0,8-2,6%) in thyme leaves. Thus, the majority of plant material remains unused after the isolation. Nowadays, the biological potential of various plant waste materials are in focus of numerous studies. These investigations also include the antimicrobial activity considering the fact that waste material extracts represent the valuable source of different phenolic compounds. Regarding all this, the aim of the present study was to determine antibacterial potential of chemically characterised extracts obtained from waste material remaining after the preparation of drug (stems) and isolation of thyme essential oil (deodorised leaves, postdistillation decoction) on selected bacterial strains. Also, in order to determine safety of waste extracts their cytotoxicity was investigated. All extracts were prepared with maceration using 45% or 75% ethanol (EtOH) for 24 h at room temperature (1:10 w/v). Total phenolic compounds and flavonoids were determined spectrophotometrically. Extracts were chemically characterized by HPLC/DAD analysis. Antibacerial testing was done with broth dilution method against several bacterial strains (Staphylococcus aureus, Bacillus cereus, Salmonella infantis, Escherichia coli and Campylobacter jejuni). Cytotoxicity and cytoprotection studies were performed by XTT assay. Result of HPLC analysis showed that investigated extracts, especially those obtained from deodorised leaves represent a valuable source of rosmarinic acid and luteolin 7-O-glucuronide. Antibacterial testing indicated that all waste material extracts, except the extract T2, possess similar or even stronger bacteriostatic activity than T1. No cytotoxicity nor cytoprotection were determined. In conclusion, results of this study confirmed antibacterial potential investigated thyme extracts. High concentrations of rosmarinic acid and luteolin 7-O-glucuronide, which both have numerous pharmacological activities, were determined. This indicates that thyme postdistillation waste material extracts could be used for isolation of dominant compounds or as addities in pharmaceutical and food industry.",signatures:"Neda Gavarić, Jasna Kovač, Nadine Kretschmer, Nebojša Kladar,\nSonja Smole Možina, Franz Bucar, Rudolf Bauer and Biljana Božin",downloadPdfUrl:"/chapter/pdf-download/48961",previewPdfUrl:"/chapter/pdf-preview/48961",authors:[{id:"78766",title:"Dr.",name:"Biljana",surname:"Bozin",slug:"biljana-bozin",fullName:"Biljana Bozin"},{id:"174457",title:"Dr.",name:"Neda",surname:"Gavarić",slug:"neda-gavaric",fullName:"Neda Gavarić"},{id:"174458",title:"MSc.",name:"Nebojša",surname:"Kladar",slug:"nebojsa-kladar",fullName:"Nebojša Kladar"},{id:"174460",title:"MSc.",name:"Jasna",surname:"Kovač",slug:"jasna-kovac",fullName:"Jasna Kovač"},{id:"174461",title:"Dr.",name:"Aleksandra",surname:"Mišan",slug:"aleksandra-misan",fullName:"Aleksandra Mišan"},{id:"174462",title:"Prof.",name:"Sonja",surname:"Smole Možina",slug:"sonja-smole-mozina",fullName:"Sonja Smole Možina"},{id:"174463",title:"Prof.",name:"Franz",surname:"Bucar",slug:"franz-bucar",fullName:"Franz Bucar"}],corrections:null},{id:"49693",title:"Phytopharmaceutical Studies of Selected Medicinal Plants Subjected to Abiotic Elicitation (Stress) in Industrial Area",doi:"10.5772/61891",slug:"phytopharmaceutical-studies-of-selected-medicinal-plants-subjected-to-abiotic-elicitation-stress-in-",totalDownloads:2622,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Plants are a source of large amount of drugs comprising antispasmodics, emetic, Anti-cancer, anti microbial and anticancer activities etc. A large number of the plants are claimed to possess the antibiotic properties in the traditional system and today they are extensively used by the people and the metal Components in the plants grown in polluted area seemingly increase the concentration of phytochemicals. Recent times the flora and fauna of any region is directly or indirectly exposed to the all types pollutants which may result into adverse effects rarely the metal pollutants may trigger the production of phytochemicals. The present study deals with Industrial pollution of the area selected for study, metal up take, and their effect on phytochemical, antimicrobial and anticancer activities that explore the research on five medicinal plants namely Adhatoda vasica, Eucalyptus globulus, Hyptis suaveolens, Ricinus communis and Tinospora cordifolia that thrive well and grow luxuriantly in industrial polluted area and the same five plants from natural area of Visakhapatnam District. The aim of this study is to analyze the effect of Metal elements on phytochemical productivity and antimicrobial and anticancer activity of these medicinal plants. Metal analysis is done ICP-MS (PerkinElmer Sciex Instrument, model ELAN DRC II, USA). Alkaloids, flavanoids, terpenoids and phenols screening is done in solvents Hexane, Chloroform and methanol and checked for antimicrobial activity and anti-cancer activity of Eucalyptus globulus and Tinospora cordifolia were determined by XTT assay on MCF-7 cell lines. The results are discussed in comparison of Natural with pollutant grown plants. The plants that showed better production of phytochemicals due to the presence of metal elements could be recommended to phytopharmaceutical industries as they comparatively showed better production of phytochemicals further proposing a definite way to eliminate toxic metals from them.",signatures:"Sr. Prema Kumari Jonnada, Louis Jesudas and Varaprasad\nBobbarala",downloadPdfUrl:"/chapter/pdf-download/49693",previewPdfUrl:"/chapter/pdf-preview/49693",authors:[{id:"90574",title:"Dr.",name:"Varaprasad",surname:"Bobbarala",slug:"varaprasad-bobbarala",fullName:"Varaprasad Bobbarala"},{id:"176247",title:"Dr.",name:"Prema Kumari",surname:"Jonnada",slug:"prema-kumari-jonnada",fullName:"Prema Kumari Jonnada"},{id:"176248",title:"Prof.",name:"Louis",surname:"Jesudas",slug:"louis-jesudas",fullName:"Louis Jesudas"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"2129",title:"A Search for Antibacterial Agents",subtitle:null,isOpenForSubmission:!1,hash:"1567c6402f459b018a6aabfd620aa3f7",slug:"a-search-for-antibacterial-agents",bookSignature:"Varaprasad Bobbarala",coverURL:"https://cdn.intechopen.com/books/images_new/2129.jpg",editedByType:"Edited by",editors:[{id:"90574",title:"Dr.",name:"Varaprasad",surname:"Bobbarala",slug:"varaprasad-bobbarala",fullName:"Varaprasad Bobbarala"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1406",title:"Antimicrobial Agents",subtitle:null,isOpenForSubmission:!1,hash:"716194563847e4c8e0f4a7c07ff858ed",slug:"antimicrobial-agents",bookSignature:"Varaprasad Bobbarala",coverURL:"https://cdn.intechopen.com/books/images_new/1406.jpg",editedByType:"Edited by",editors:[{id:"90574",title:"Dr.",name:"Varaprasad",surname:"Bobbarala",slug:"varaprasad-bobbarala",fullName:"Varaprasad Bobbarala"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8427",title:"Antimicrobials, Antibiotic Resistance, Antibiofilm Strategies and Activity Methods",subtitle:null,isOpenForSubmission:!1,hash:"0fdedc9bf6c23241235a0ae011c0304c",slug:"antimicrobials-antibiotic-resistance-antibiofilm-strategies-and-activity-methods",bookSignature:"Sahra Kırmusaoğlu",coverURL:"https://cdn.intechopen.com/books/images_new/8427.jpg",editedByType:"Edited by",editors:[{id:"179460",title:"Associate Prof.",name:"Sahra",surname:"Kırmusaoğlu",slug:"sahra-kirmusaoglu",fullName:"Sahra Kırmusaoğlu"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6978",title:"Antimicrobial Resistance",subtitle:"A Global Threat",isOpenForSubmission:!1,hash:"949e88946357845e5843b4d7fbc1701f",slug:"antimicrobial-resistance-a-global-threat",bookSignature:"Yashwant Kumar",coverURL:"https://cdn.intechopen.com/books/images_new/6978.jpg",editedByType:"Edited by",editors:[{id:"79718",title:"Dr.",name:"Yashwant",surname:"Kumar",slug:"yashwant-kumar",fullName:"Yashwant Kumar"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"4759",title:"Antimicrobial Resistance",subtitle:"An Open Challenge",isOpenForSubmission:!1,hash:"04be7bb9b8da174cdb838a38c75236b4",slug:"antimicrobial-resistance-an-open-challenge",bookSignature:"Maria Cristina Ossiprandi",coverURL:"https://cdn.intechopen.com/books/images_new/4759.jpg",editedByType:"Edited by",editors:[{id:"80691",title:"Prof.",name:"Maria Cristina",surname:"Ossiprandi",slug:"maria-cristina-ossiprandi",fullName:"Maria Cristina Ossiprandi"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9521",title:"Antimicrobial Resistance",subtitle:"A One Health Perspective",isOpenForSubmission:!1,hash:"30949e78832e1afba5606634b52056ab",slug:"antimicrobial-resistance-a-one-health-perspective",bookSignature:"Mihai Mareș, Swee Hua Erin Lim, Kok-Song Lai and Romeo-Teodor Cristina",coverURL:"https://cdn.intechopen.com/books/images_new/9521.jpg",editedByType:"Edited by",editors:[{id:"88785",title:"Prof.",name:"Mihai",surname:"Mares",slug:"mihai-mares",fullName:"Mihai Mares"}],equalEditorOne:{id:"190224",title:"Dr.",name:"Swee Hua Erin",middleName:null,surname:"Lim",slug:"swee-hua-erin-lim",fullName:"Swee Hua Erin Lim",profilePictureURL:"https://mts.intechopen.com/storage/users/190224/images/system/190224.png",biography:"Dr. Erin Lim is presently working as an Assistant Professor in the Division of Health Sciences, Abu Dhabi Women\\'s College, Higher Colleges of Technology in Abu Dhabi, United Arab Emirates and is affiliated as an Associate Professor to Perdana University-Royal College of Surgeons in Ireland, Selangor, Malaysia. She obtained her Ph.D. from Universiti Putra Malaysia in 2010 with a National Science Fellowship awarded from the Ministry of Science, Technology and Innovation Malaysia and has been actively involved in research ever since. Her main research interests include analysis of carriage and transmission of multidrug resistant bacteria in non-conventional settings, besides an interest in natural products for antimicrobial testing. She is heavily involved in the elucidation of mechanisms of reversal of resistance in bacteria in addition to investigating the immunological analyses of diseases, development of vaccination and treatment models in animals. She hopes her work will support the discovery of therapeutics in the clinical setting and assist in the combat against the burden of antibiotic resistance.",institutionString:"Higher Colleges of Technology",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Perdana University",institutionURL:null,country:{name:"Malaysia"}}},equalEditorTwo:{id:"221544",title:"Dr.",name:"Kok-Song",middleName:null,surname:"Lai",slug:"kok-song-lai",fullName:"Kok-Song Lai",profilePictureURL:"https://mts.intechopen.com/storage/users/221544/images/system/221544.jpeg",biography:"Dr. Lai Kok Song is an Assistant Professor in the Division of Health Sciences, Abu Dhabi Women\\'s College, Higher Colleges of Technology in Abu Dhabi, United Arab Emirates. He obtained his Ph.D. in Biological Sciences from Nara Institute of Science and Technology, Japan in 2012. Prior to his academic appointment, Dr. Lai worked as a Senior Scientist at the Ministry of Science, Technology and Innovation, Malaysia. His current research areas include antimicrobial resistance and plant-pathogen interaction. His particular interest lies in the study of the antimicrobial mechanism via membrane disruption of essential oils against multi-drug resistance bacteria through various biochemical, molecular and proteomic approaches. 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Oxygen free radicals or, more generally, reactive oxygen species (ROS) are products of normal cellular metabolism. They are well recognized for playing a contradictory dual role in living systems, sometimes deleterious sometimes beneficial, depending on cell type, genetic background and levels and types of species involved. Beneficial effects of ROS occur at low/moderate concentrations and involve modulation of signaling pathways and gene expression regulation. The harmful effect of free radicals is termed oxidative stress and can result in damage to cellular lipids, proteins and DNA. The balance between benign and deleterious effects of ROS is a decisive factor of living organisms and is controlled by mechanisms called redox regulation. This process protects cells from oxidative stress and maintains the redox homeostasis by modulating the redox state
ROS are a group of chemically reactive molecules derived from partial reduction of molecular oxygen, comprising a family of radical and non-radical species. A radical species is a free electron-containing species, including superoxide anion (O2•ˉ) and its conjugated acid hydroperoxyl radical (HO2•ˉ), hydroxyl (•OH), carbonate (CO3•ˉ), peroxyl (RO2•) and the alkoxyl radical (RO•). Non-radical species, such as H2O2, hydrogen chloride (HOCl), fatty acid hydroperoxides (FaOOH), reactive aldehydes and singlet oxygen, can be readily reduced into free electron-containing species [18]. The reactivity of the different ROS with other compounds is variable and depends on their processing into more reactive ROS and the diffusion capability. It was shown that O2•ˉ and H2O2 do not exhibit strong reactivity with other bio-molecules, because they are more stable and can diffuse away from their sites of formation. Additionally, H2O2 can diffuse through membranes into the extracellular space. In the other hand, •OH radical is highly reactive and probably accounts for most of the oxidative damage attributed to ROS. It half-live time is very short, approximately 10-9s, so •OH produced
These reactive species are generated partly as by-products of cellular metabolism mainly during mitochondrial electron transport. Evidences implicating mitochondria as the principal source of ROS were based on the fact that isolated mitochondria can produce O2•ˉ through (1) auto-oxidation of the flavin component of complex I (NADH hydrogenase) and/or (2) auto-oxidation of the ubisemiquinone at complex III. During the process of cellular respiration, electron transfer occurs from NADH and FADH through complexes in the mitochondrial membrane, leading to a proton gradient, which is necessary for ATP production. Oxygen is involved as an electron acceptor at the end of the electron transfer in respiration chain. The electron transfer in respiratory chain is not completely efficient due electrons leakage from electron transport chain [20]. Approximately 1-3% of the total oxygen consumed in aerobic metabolism produces O2•ˉ instead of contributing to the reduction of oxygen to water [18] Direct or indirect damage to mitochondria can lead to electrons leak from electron transport chain, including oxidative modification of mitochondrial membrane lipids (e. g. cardiolipin), resulting in mitochondrial outer membrane permeabilization. So O2•ˉ is continuously generated mainly at complex I and complex III due to transfer of electrons to molecular oxygen. Superoxide radical that is produced by complex I is released into the mitochondrial matrix, whereas complex III forms O2∙- both in the matrix and the inner mitochondrial space [21].
Another major source of ROS is NADPH oxidases, a family of membrane-bound enzymes that catalyze controlled production of O2•ˉ by coupling NADPH-derived electrons to oxygen. The NADPH oxidase complex consist of a membrane heterodimeric flavocytochrome (cytochrome B559) comprising two subunits, gp91phox and p22phox, and four cytosolic proteins, p47phox, p67phox, p40phox and the small guanosine triphosphate (GTP)-binding protein Rac (1 and 2) that form a functional complex at the membrane [22,23].
Superoxide can be also produced in the cell through one-electron transfer reactions catalyzed by a number of enzymes including monoamine oxidase, xantina oxidase, cyclooxygenases, lipoxygenases and components of the cytochrome P450 system. Peroxisomes are known to produce H2O2, but not O2•ˉ, under physiologic conditions [24]. Exposition to chemotherapeutic drugs and UV irradiation also increases the amount of ROS in intracellular milieu [25,26].
Redox homeostasis is determined by the balance between ROS production and detoxification rates by various antioxidants systems. To maintain intracellular free radicals from many sources under tight control, cells have developed a series of defense mechanisms against ROS-induced oxidative stress. The maintenance of intracellular redox state is essential for regulation of signal transduction because alterations in ROS levels can modify proteins conformation and consequently their functions. Enzymatic anti-oxidant defenses include superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GPx) and catalase (CAT). Non-enzymatic antioxidants systems are represented by ascorbic acid (Vitamin C), carotenoids, flavonoids, glutathione (GSH), α-tocopherol (Vitamin E), thioredoxin and other antioxidants. Superoxide dismutase converts O2•ˉ in the lesser reactive species H2O2 [18,27]. There are three different SODs, which are involved in superoxide neutralization depending on the site of superoxide production or diffusion. Cu,Zn-SOD-1 is located in the cytoplasm, MnSOD-2 in mitochondria and Cu,Zn-SOD3 in the extracellular space [28]. When H2O2 is present in peroxisomes, it is decomposed to H2O and O2 by catalase. In the cytoplasm, glutathione peroxidase catalyzes the reduction of H2O2 into H2O via oxidation of glutathione [29, 30, 31].
The tripeptide glutathione is the abundant low-molecular-weight thiol antioxidant, constituting with thioredoxin, the major redox buffer of the mammalian cells. Glutathione is present in reduced (GSH) and in oxidized (GSSH) forms and the reduced form of glutathione is 10- to 100-fold higher than the oxidized form. Glutathione couple (2GSH/GSSG couple) is the main responsible for the cellular redox homeostasis and therefore is a representative indicator of oxidative stress [17]. Because cellular glutathione concentration is ~500- to 1000-fold higher than the other redox regulating proteins, changes in the ratio of reduced to oxidized glutathione reflect directly intracellular redox alterations [29]. The GSH/GSSG ratio is normally tightly regulated. Increased ROS levels result in an elevation of GSSH content, which is reduced to GSH by the NADPH-dependent glutathione reductase as well as thioredoxin/glutaredoxin systems. So, even in the presence of oxidative stress, the redox homeostasis can be maintained by increasing glutathione reductase activity or via elimination of GSSG from cells. Glutathione decreases intracellular ROS levels by acting as cofactor of several detoxifying enzymes against oxidative stress, e.g, glutathione peroxidase and glutathione transferase; participating in amino acid transport through the plasma membrane; regenerating vitamin C and E back to their active forms [32]. Glutathione also modulates the activity of thiol-dependent enzymes that contain cysteine residues sensitive to redox changes [33].The enzyme γ-glutamylcysteine synthase (γ-GCS), involved in GSH synthesis, is regulated by ROS levels. Oxidizing conditions that result in GSH depletion promote a conformation change in γ-GCS, increasing its activity and GSH synthesis, while physiological GSH concentrations reduces GSH synthesis through feedback inhibition mechanisms [33].
Peroxiredoxins (Prxs) are also considered important cell redox state-regulating enzymes. Prxs are a family of peroxidases that also reduce H2O2 and alkyl hydroperoxides to the corresponding water or alcohol. At least six isoforms of human Prxs (Prx1-6) were located in different subcellular compartments, particularly in mitochondria (Prxs3 and 5). Prxs are maintained in the reduced form by the thioredoxin /thioredoxin reductase system that in conjunction with the GSH/GR system maintains the cellular thiol-disulfide redox status in the cell [34].
The thioredoxin system comprises thioredoxin (Trx), thioredoxin reductase (TrxR) and NADPH. Trxs are small redox active proteins (about 12kDa) with a disulfide active site (Trx-S2) that is reduced to a dithiol (Trx-(SH)2) by thioredoxin reductase (TrxR) using NADPH as electron donor. Mammalian Trx and TrxR are expressed as isoforms either in the cytosol and in the nucleus (Trx1 and TrxR1) or in mitochondria (Trx2 and TrxR2); in addition, there are testis-specific Trx/TrxR system (Trx3 and TrxR3). Unlike Trx, which is reduced by its own reductase, glutaredoxins (Grxs) are coupled to GSH/GR. There are four Grx isoforms in humans, Grx1, Grx-3 and Grx5 primarily cytosolic and Grx2 displays different splice variants, which are located in mitochondria and nucleus [35].
There is a body of evidence showing the involvement of ROS in regulation of innumerous signaling pathways that control important biological processes, including migration, differentiation, proliferation, apoptosis, stress adaptation and gene expression. ROS can modulate multiple transduction signals by activation of growth factor receptors (e.g. the c-MET, EGF and PDGF receptor), activation of early growth-related genes such as c-fos and c-jun, alterations in the activities of protein kinases, oxidative inactivation of phosphatases and activation of transcription factors [36]. In the other hand, increased ROS levels in tumor cells is influenced by numerous factors such as disrupted signaling pathways, altered expression of transcription factors, deregulation of antioxidant enzymes, mitochondrial dysfunction, aberrant cancer cell metabolism, alteration in proliferation and the acquisition of the metastatic phenotype [9, 37].
Redox regulation of signaling pathways occurs through modifications of redox-reactive cysteine residues on proteins, which depend on redox status of the cell and the concentration of ROS. Oxidation of these residues forms reactive sulfenic acid (-SOH) that can form disulfide bonds with nearby cysteine (-S-S-) or undergo further oxidation to sulfinic (-SO2H) or sulfonic (-SO3H) acid. These alterations induced by ROS modify the structure and activity of proteins, regulating their functions. These redox modifications are reversible by antioxidants systems, including thioredoxin and peroxiredoxin, contributing to the modulation of signal transduction [8].
Since ROS can act as signaling molecules it is reasonable to think that depending on cell context ROS could participate in development of innumerous pathologies including cancer. There is accumulating evidence supporting this view. Levels of ROS are increased in many tumors and murine and human tumor cells lines, contributing to neoplastic transformation and tumor progression [13, 38, 39, 40]. By regulating signal transduction pathways, ROS is involved in the acquisition of cancer hallmarks including self-sufficiency in growth signals, insensitivity to growth inhibitory (anti-growth) signals, evasion of programmed cell death (apoptosis), limitless replicative potential, sustained angiogenesis, tissue invasion and metastasis, altered metabolism and inflammation [40, 41]. The accumulation of ROS participates in the tumor development of many types of cancer including melanoma, leukemia, gastric, prostate, breast and colon cancer [39, 42, 43, 44, 45].
One of the signaling pathways regulated by ROS that is implicated in oncogenic transformation is the mitogen-activated protein kinase (MAPK) cascade that consists of four major MAPKs: the extracellular signal-related kinases (ERK 1/2), the c-Jun N-terminal kinases (JNK), the p38 kinase (p38) and the big MAP kinase 1 (BMK1/Erk5). The apoptosis signal-regulated kinase 1 (ASK1), which regulates the JNK and p38 MAPK pathways, is activated under stress conditions by dissociation of the redox protein thioredoxin. ASK1 is activated when ROS oxidize two cysteine residues in the redox center of thioredoxin, inducing formation of an intramolecular disulfide bond and triggering this dissociation from ASK1 [8]. Activated p38 negatively regulates the malignant transformation induced by oncogenic H-Ras by inhibition of ERK pathway, induction of premature senescence or by cell cycle arrest triggered by p53 [46]. In fact, it was shown that p38 specifically impairs the malignant transformation induced by oncogenes that increase ROS levels (including Ras) by triggering apoptosis and decreasing the accumulation of ROS [47]. MAPK pathways are also activated by the direct inhibition of MAPK phosphatases by ROS. Downregulation of mitogen-activated protein kinase phosphatase (MKP)-3, a negative regulator of ERK1/2, was associated with ubiquitination/proteosome degradation mediated by high intracellular ROS accumulation such as hydrogen peroxide. The aberrant ERK activation contributes to tumorigenicity and chemoresistance of human ovarian cancer cells [48].
Another signaling pathway that contributes to malignant phenotype acquisition, participating in cell survival and proliferation, is the phosphoinositide 3-kinase (PI3K) pathway. Activation of this signal transduction is regulated by the phosphatase and tensin homology (PTEN) phosphatase. It was found that PI3K pathway is reversible regulated by the redox status of the cell by inactivation of PTEN through oxidation of the cysteine located in its catalytic domain [8].
ROS have also been implicated at all stages of the carcinogenic process since are capable of modulating gene expression through oxidative DNA damage and epigenetic alterations [38, 50]. ROS-induced DNA damage includes single- or double-stranded DNA breaks, purine, pyrimidine or deoxyribose modifications and DNA cross-links. DNA damage can result in arrest or induction of transcription, induction of signal transduction pathways, replication errors and genomic instability, all of which are associated with tumorigenesis [19, 51]. The most extensively studied DNA lesion is 8-OH-G, a potential biomarker of carcinogenesis [50]. This oxidative DNA lesion was shown to interfere in the binding of methyl binding proteins to 5-methylcytosines [52], and 8-OH-G located adjacent to the target cytosine can affect the affinity of DNA for DNMT3A [53]. These data indicate that 8-OH-G may play a role in the formation of aberrant DNA methylation patterns during tumor formation. Increased Dnmt1 and global DNA methylation levels were observed in murine melanocytes submitted to sustained stress condition associated with malignant transformation [38]. Increased ROS levels can also induce the recruitment of DNMT1 to damaged chromatin where, together with DNMT3B and members of the Polycomb repressive complex 4, they form a silencing complex in GC-rich areas that might explain cancer-specific aberrant DNA methylation and transcriptional repression [54]. Oxidative stress associated with inflammation also triggers redox signaling through inactivation of HDACs. The reduction of HDAC activity is associated with posttranslational modifications, such as carbonylation [55]. Together, these data suggest a connection among oxidative stress, DNA damage, epigenetic alterations and malignant transformation.
Chronic stress conditions in tumor cells are triggered by an imbalance between ROS production and the ability of cells to scavenge these species. Many studies have shown the increase in Nox expression and activity in transformed cell lines [9, 56, 57]. It was shown that constitutively activated isoform of p21Ras, H-Rasv12, in NIH-3T3 fibroblasts improved increased superoxide anion production by Nox1, and was functionally required for oncogenic Ras transformation [58]. Mitochondria dysfunction can lead to oxidative stress, which could be also implicated in cancer development. Besides defects in mitochondrial electron transport chain and prolonged hypoxia and glucose deprivation, disrupted cell signal transduction can also increase mitochondrial-derived ROS in cancer cells. In turn, alteration in mitochondrial bioenergetics modulates signal transduction. It was demonstrated that increased ROS production derived from mitochondria is induced by oncogenic K-Ras and is required to maintain anchorage-independent cell grow and proliferation [59].
Increased ROS levels in malignant cells can arise also from the alteration or inactivation of the antioxidant defense system. Low activities of CuZn-SOD, Mn-SOD, CAT and GPxs have been reported in a variety of transformed and malignant cells compared with their normal counterparts [19]. Decreased activity and expression of Mn-SOD was reported in melanoma, colorectal, prostatic and pancreatic carcinomas [19].
However, it is important to note that only under a mild elevation in intracellular O2•ˉ and H2O2 signaling pathways stimulate proliferation. In the other hand, if the concentration of ROS in the cells is so high these effects can be completely reversed resulting in oxidative stress and death. In this way, cancer cells must render the intracellular milieu pro-oxidant, where ROS has a pro-life role [60], which is supported by the fact that MnSOD acts like a tumor suppressor gene. Many authors have shown the suppression of malignant phenotype after MnSOD re-expression [61, 62, 63]. In addition, intracellular O2∙- has the ability to regulate apoptosis sensitivity to a variety of apoptotic stimulus [12,13]. The inhibitory effect of O2∙- on cell death signaling can be attributed to caspase proteases, mediators of apoptotic signaling, inactivation by oxidative modifications [60] and by the increased expression of Bcl-2, which is associated with a pro-oxidant milieu [64].
Cutaneous melanoma is a highly malignant tumor derived from pigment-producing melanocytes in the epidermis of the skin. Melanocytes are responsible for the synthesis of melanin in melanosomes, which in turn, is transferred to neighboring keratinocytes where it can protect DNA from UV radiation damage. Melanocytic transformation is triggered by sequential accumulation of genetic and epigenetic alterations that driven modifications in several genes and signaling transduction pathways leading to abnormal proliferation of melanocytes.
Melanoma is one of the most aggressive tumors with a high frequency of metastasis. The incidence and mortality rates of malignant melanoma have increased in the past few decades particularly in Europe and the United States. Although, the etiology of melanoma is not completely known, several molecular and cellular mechanisms have been shown to contribute to melanoma genesis. Chronic stress exposures induced, for example, by solar UV and inflammation are among risk factors for melanoma development [65,66].
Many authors have shown increased ROS levels in melanoma cells through multiple mechanisms [9, 12, 57]. It was also demonstrated that the ability of melanocytes and melanoma cells to respond to oxidative stress is different. While melanocytes have the capability of suppressing increased ROS levels, melanoma cells are unable to do that [67]. This redox imbalance has a central role in melanoma genesis. One of the reasons is that melanoma cells show decreased antioxidant capability characterized by reduced catalase, glutathione-S-transferase and MnSOD enzymatic activity and low levels of glutathione [68, 69], characterizing an aberrant redox state. Moreover, melanoma cells have constitutive abnormalities in their melanosomes [70]. More importantly, it was found that melanoma cells have increased superoxide anion and decreased hydrogen peroxide levels leading to an establishment of a pro-oxidant intracellular milieu and the activation of redox-sensitive transcription factors that enhance the aggressiveness seen in melanoma cells characterized by high proliferative rate and drug resistance [60].
Besides genetic alterations found in melanoma caused by UV, the involvement of ROS in epigenetic alterations was also described in melanoma cells. Increased Dnmt1 and global DNA methylation levels was observed in murine melanocytes submitted to sustained stress condition associated with malignant transformation [38]. The treatment of cells with superoxide anion scavenger abrogated the increase of both Dnmt1 and global DNA methylation level (unpublished results).
Circumstantial and direct evidences show ultraviolet radiation (UVR) as major environmental risk factor for melanoma formation. One of the evidences is the fact that melanoma incidence is higher in population with light skin types [71]. Skin types depend on melanin production and there are two types of melanin, eumelanin and pheomelanin. People with light skin have more pheomelanin than eumelanin and it has been shown that eumelanin confers more protection against malignant melanoma [72, 73]. Melanin is an important chromophore in the skin which is able to absorb UVR, visible light and scavenge molecular oxygen and hydroxyl radicals, protecting DNA from adducts formation and breaks [4]. In addition, melanoma from sun-exposed areas has different gene mutations than melanoma from unexposed skin areas, suggesting the existence of a particular pathway in melanoma genesis associated with UV radiation [65].
Ultraviolet radiation is subdivided into long wavelength UVA, shorter UVB and shortest UVC. UVC is normally absorbed by ozone at atmosphere and generally does not reach human skin. UVB is absorbed by cells located at outermost layer of epidermis and can be directly absorbed by keratinocytes DNA, causing its damage by producing photoproducts such as cyclobutane pyrimidine dimmers [74]. Additionally, UVB can affect DNA indirectly through oxidative stress generation [75]. In other way, UVA radiation can penetrate deeper into skin and, in addition to be absorbed by keratinocytes, is also absorbed by melanocytes, dermal fibroblasts and other cell types [76]. UVA comprises the majority of UV radiation that reaches earth’s surface (95%) and is poorly directly absorbed by DNA, but can indirectly affect DNA by causing reactive oxygen species (ROS) increase and oxidative stress [77]. Oxidative stress can lead to single and double strand DNA breaks, DNA adducts formation, as well lipids and protein peroxidation.
The specific contribution of UVB and UVA radiation to melanocytes malignant transformation is questionable because the majority of
When compared to UVB, there are fewer studies showing long-wave UVA radiation role in skin cancer, including melanoma. Recent study in mice did not show an induction of melanoma by a single UVA dose [84]. Nevertheless, there are circumstantial evidences suggesting UVA role in melanoma formation once it gets through clothes in greater quantities than UVB and it comprises the majority of UV radiation. Moreover, UVA, like mentioned before, can penetrate deeper into skin than UVB. It has been shown that high UVA dose causes loss of reduced glutathione and reduces plasma membrane stability in human melanocytes [85]. Glutathione is an important cell antioxidant and loss of its reduced state may reflect the oxidative pressure within this melanocytes as well the plasma membrane stability, once oxidative stress can cause lipid peroxidation. In opposite way to this effect of UVA on melanocytes, this has only been shown before in keratinocytes after UVB irradiation [85]. In addition, a recent work showed an alternative role of melanin in mitochondrial DNA damage only during UVA irradiation, not UVB, providing evidences for dual role of melanin as both protector and damage agent [86]. The accumulation of mitochondrial DNA (mtDNA) mutations, through oxidative stress mechanisms, has been proposed to contribute to carcinogenic and aging process in many tissues, including skin [76, 86].
Regarding the link between UV radiation and oxidative stress in melanoma, it is important to mention the fact that both UVA and UVB irradiation can induce nitric oxide synthases (NOS) expression at skin [87, 88, 89]. Warren and colleagues showed, for example, that an intradermal injection of L-NAME (NOS inhibitor) prevented erythema caused by UV radiation exposition in rats [87]. In addition, nitric oxide in combination with superoxide anion can form peroxynitrite, which leads to lipids and proteins peroxidation. Additionally, peroxynitrite might oxidize tetrahydrobiopterin (BH4) NO syntases’ cofactor, what could cause NOS uncoupling. A critical aspect of NOS function is the requirement for the cofactor BH4, its absence destabilize NOS, which becomes “uncoupled”. Uncoupled NOS produces superoxide anion instead of nitric oxide [12]. NOS-dependent superoxide formation has central role in the pathology of vascular diseases like diabetes, hypertension and atherosclerosis, but less is known about this phenomenon in cancer [90, 91]. Nevertheless, results from our group showed for the first time the involvement of the uncoupled eNOS in the generation of superoxide in melanoma genesis [12].
As showed, a potential causative role of ultraviolet radiation in oxidative stress and melanoma genesis has been investigated; however, more studies are necessary to fully understand this association.
The exposure of skin to UV irradiation results in increased blood flow, infiltration by macrophages and neutrophils, as well higher levels of nitric oxide and prostaglandins [87, 92]. This phenomenon is clinically observed as inflammation. Other UV-induced mediators such as tumor necrosis factor (TNF) and interleukin-1α (IL-1α) also contribute to inflammation. The recruited inflammatory cells produce ROS that, like mentioned before, drive damage to lipids, proteins and DNA. This damage could lead to genetic and epigenetic alterations and contribute to cancer development [38, 93, 94]. ROS and NO can be associated with all steps of tumor progression, causing oncogene activation, tumor suppressor inhibition through mutations or aberrant epigenetic modifications, angiogenesis, local invasion and metastasis [95].
Another feature of UV radiation is the fact that it can cause local and systemic immunosuppression on skin. The precise mechanism is not fully elucidated, but DNA damage is regarded as fundamental inciting event, which leads to depletion of Langerhans cells from epidermis, interfering with antigen recognition [96, 97]. It was observed that immunosuppression induced by UVA radiation diminishes immune surveillance and allows cutaneous melanoma development in transgenic mice [84]. Some additional evidences suggest that NO might be involved in passing a “migration signal” to the Langerhans cells that stimulates them to migrate and leave epidermis [98]. In this way, nitrosative stress could be involved both in inflammation and immunosuppression mechanisms linked with carcinogenesis.
Melanoma cells spontaneously generate ROS and present alteration in NOX expression. NOX family, that comprises
There are few studies about NOX role in melanoma and more studies in this area may elucidate how NADPH oxidases might regulate specific signaling pathways during melanocyte malignant transformation and melanoma progression.
Recently, the role of mitochondrial functions, such as redox regulation and oxidative phosphorylation in melanoma progression has become to be elucidated. It was shown that dysfunctional mitochondria affect melanoma cell survival and death and drug resistance [101]. Tumor cells normally produce ATP via glucose metabolism with concomitantly decrease in ATP production by oxidative phosphorylation [102]. Unlike most tumor cells, melanoma cells rely more on oxidative phosphorylation than glycolysis to produce ATP. Compared with solid tumor xenografts, human melanoma xenografts have one of the highest rates of oxygen consumption, a surrogate marker of oxidative phosphorylation [101, 103]. Moreover, non-glycolytic metabolic sources, such as the Krebs cycle, occur more frequently in melanoma cells compared with melanocytes [104]. It was also shown that a particular group of patients with advanced melanoma utilize oxidative phosphorylation for energy production in addition to glycolysis [105]. Consequently, the mitochondria of melanoma cells generate high levels of ROS. These features make mitochondria a potential chemotherapy target in melanoma. In fact, it was shown that the drug Elesclomol, that alter redox balance and induce oxidative stress, lead to melanoma cells apoptosis by inhibiting oxidative phosphorylation through down regulation of proteins from electron respiratory chain. In addition, it was also demonstrated that melanoma cells with high levels of lactate dehydrogenase (LDH) (***--q), with characterizes ATP production mainly by glucose metabolism, are more resistant to Elesclomol [101]. Analysis of patients with normal lactate LDH versus patients with high serum LDH levels showed that the increase in LDH levels is a prognostic factor for metastatic melanoma [106].
In normal melanocytes, melanin is generated from the successive oxidation of tyrosine by tyrosinase in sub organelles called melanosomes to protect DNA, including mitochondrial DNA, from UV radiation-induced damage [86]. Moreover, melanin neutralizes the inflammatory response to radiation and acts like an antioxidant, suppressing superoxide anion, singlet oxygen and hydrogen peroxide [107]. However, in melanoma cells, melanogenesis itself is a source of ROS and oxidative stress because of malformed melanosomes and melanin synthesis disruption [108]. Therefore, depending on the melanin type and redox intracellular state, melanin can play a dual role, both as a photoprotector and as a photosensitizer [86]. In melanoma cells, melanosomes are poorly compartmentalized, with malformed or twinned membranes, occlusions within the melanin and evident fragments outside of melanosome [109]. The structural differences between melanosomes from melanocyte and melanoma cells are significant, as melanosomal compartmentalization protects the cell from the highly reactive small-molecules catechols that are generated as by products during melanogenesis [108]. Ultrastructural studies of human melanosomes also indicate that melanocytes generally have fewer melanosomes than malignant melanoma [110]. Melanin deregulation renders it a pro-oxidant with ability to increase ROS levels and damage DNA [111]. In addition, melanin exposition to radiation also renders it pro-oxidant [107]. It is important to note that disturbed melanin synthesis and chronic oxidative stress are present in dysplastic nevi, indicating that the switch of melanin to a pro-oxidant state occurs early in melanoma development [112].
Melanins are naturally associated with a number of metal ions and have the capability to accumulate metals. However, oxidized melanin has high affinity for metal ions
Melanin synthesis is regulated mainly by the alpha-melanocyte stimulating hormones (α-MSH), which bind to the melanocortin 1 receptor (MC-1R) and activate the cAMP pathway, which in turn, triggers its downstream effector molecules Protein Kinase A (PKA) and cAMP-Responsive Element Binding (CREB) transcription factors to up-regulate the expression of microphtalmia-associated transcription factor (MITF). MITF induces the transcription of tyrosinase, the rate-limiting enzyme in the synthesis of melanin [116]. Recently, it was shown that melanin synthesis is regulated by Nox4-induced ROS in a feedback mechanism regulated by MITF signaling pathway in melanoma cells [37]. The expression of Nox4 and ROS production was increased by α-MSH and was dependent of MITF signaling. Expression silencing of Nox4 gene increased melanin formation through MITF and tyrosinase activation upregulation, unraveling a novel negative regulatory mechanism of pigmentation in melanoma cells. This could be an adaptive mechanism of melanoma cells submitted to chronic stress condition to maintain redox homeostasis: decreasing oxidative stress by inhibiting the synthesis of pro-oxidant melanin.
There is a lot of evidence showing the involvement of inducible nitric oxide synthase (iNOS) in melanoma development. Its strong association with poor patient survival seems to indicate that iNOS is a molecular marker of poor prognosis or a putative target for therapy. All these studies show the role of nitric oxide, a free radical produced by NOS, in proliferation and apoptosis [118, 119]. Recently, the role of NO derived from eNOS in melanoma induced by chronic stress was shown [117]. In fact, eNOS-/- mice are resistant to tumor development [120, 121]. However, NOS can be also a source of superoxide anion [10, 11].
It has been extensively demonstrated that uncoupled NOS can generate superoxide, which has a central role in the pathogenesis of vascular diseases, such as diabetes, hypertension and atherosclerosis. NOS are homodimeric oxidoreductases that catalyze NO production from L-arginine guanidine nitrogen using molecular oxygen. The NOS reductase domain generates electron that flow from NADPH through FAD and FMN flavins and are transferred to the oxidase domain of the other monomer in which L-arginine oxidation occurs at the heme group in the active site. A critical aspect of NOS function is the requirement of the cofactor tetrahydrobiopterin (BH4). In its absence, NOS dimerization is lost and NOS catalytic activity becomes uncoupled. In this state, NADPH oxidation and molecular oxygen reduction are uncoupled from L-arginine hydroxylation and nitric oxide (NO) formation. However, electron transfer from NADPH to molecular oxygen is not inhibited, resulting in superoxide production [10, 11].
An
The appropriate proceeding of tumor cells exposed to ROS is associated with activation of different signaling pathways that in turn regulate transcriptional changes that allow cells to respond and adapt to oxidative stress for maintenance of homeostasis. These alterations are regulated by redox sensors such as apurinic/apyrimidinic endonuclease (APE-1/Ref-1). APE/Ref-1 is a point of convergence for various redox-sensitive signals as well as being important in DNA repair. Many studies demonstrated that many survival, proliferation and anti-apoptotic signaling pathways are activated by APE/Ref-1–mediated transcription factors, such as AP-1, NF-κB, HIF-1α and p53, whose regulation occurs in both a redox-dependent and a redox-independent manner [36]. Elevated APE/Ref-1 was associated with decreased intracellular ROS levels as well as reduced oxidative DNA-damage lesions. However, the prolonged activation of APE/Ref-1 induced by a sustained stress condition, switches the cellular signaling to proliferation and apoptosis resistance. It was shown that increased expression of APE/Ref-1 and increased ROS levels play a role in malignant transformation by increasing anchorage-independent growth and colony formation [123]. Moreover, knockdown of APE/Ref-1 was shown to efficiently induce apoptosis, sensitization, or both to chemical treatments [124]. It is also well documented that elevated APE/Ref-1 is associated with chemo- and radio-resistance in a number of cellular systems. Recently, this group also suggested that APE/Ref-1 is involved in the regulation of metastasis produced by melanoma cells [125]. These studies suggested that, as an adaptive response induced by APE/Ref-1, this transcription factor besides efficiently repairs oxidative DNA damage, also regulates redox-sensitive signaling such as AP-1 and NF-κB, which are involved in melanoma genesis. In fact, it was demonstrated the increased expression of APE/Ref-1 in melanoma specimens and cells, which is predominantly found in the nucleus and contributed to the binding and activation of AP-1 and NF-κB [123, 124]. Therefore, all these properties make APE/Ref-1 a promise target for melanoma therapy.
A signaling pathway disrupted in melanoma cells that is redox-sensitive is the Ras/BRAF/MEK/ERK [126]. We have observed that activation of Ras-ERK signal transduction in melan-a melanocytes during loss of integrin-mediated cell-matrix contact is regulated and regulates superoxide anion levels which is associated with global DNA hypermethylation (unpublished results). This aberrant signaling seems to have a significant impact in melanoma genesis since the malignant transformation was drastically compromised when melan-a melanocytes were pre-treated with superoxide scavenger.
Another pathway involved in melanoma progression that is responsive to alterations in redox homeostasis is p38 signal pathway. In melanocytes exposed to oxidative stress and UV-irradiation, p38 is activated and induces the expression of p16INK4A, which in turn decreases ROS levels [127]. It can be a mechanism by which the tumor suppressor gene p16INK4A protects melanocytes against malignant transformation. According to this point, it was shown by many authors that induction of apoptosis in melanoma cells is dependent on p38 activation [128, 129].
Many cancer types have some imbalance in physiologic antioxidant levels compared with the cell of origin like was mentioned before in this chapter [130]. Moreover, levels of anti-oxidant enzymes and non-enzymatic antioxidants such as catalase, MnSOD, glutathione (GSH), vitamins E, C and A are all typically decreased in tumors [131]. Although mutations in MnSOD gene have been demonstrated in some melanomas, the other antioxidant enzymes were found with high activity in this type of cancer cells [61, 131].
The redox imbalance found in melanoma cells is implicated in the malignant phenotype of these cells, characterized by abnormal proliferation, apoptosis resistance and metastasis capability through regulation of key signaling pathways. These observations support the notion that melanoma could be targeted using antioxidant therapy.
One of antioxidants, approved by Food and Drug Administration (FDA) and used to treat pulmonary fibrosis, is N-acetylcysteine (NAC) [132]. Studies in mouse showed that orally administrated NAC reduced UV-induced squamous carcinoma [133]. Moreover, Cotter and colleagues showed that NAC protects melanocytes from oxidative stress and delays UV-induced melanoma growth in mice [134]. In addition, other studies observed that topical NAC reduced UV-mediated GSH depletion and peroxide induction in normal human skin [135, 136]. The antioxidant vitamin E delays or reduces UV-induced skin carcinogenesis in mice, through reduction in DNA damage, immunosuppression or both [137]. Other epidemiologic studies showed that increased vitamins D and C intakes have some influence in melanoma prevention [14].
As mentioned above, the redox transcription factor sensor APE/Ref-1 has a potential as a target for the development of a new chemopreventive agent against cancer. Using docking-and-scoring technology and virtual screening, resveratrol was found to dock in one of the two drug-treatable pockets located in the redox domain of APE/Ref-1 [124]. The inhibitory effects of resveratrol on APE/Ref-1 occurred mostly through its redox-regulating functions and might be the principal role on its pharmacological activities, which are implicated in the reduced AP-1 and NF-κB activities in many human cancers [138]. In studies using human melanoma cells, resveratrol was shown to inhibit, in a dose-dependent manner, the APE1/Ref-1-mediated DNA-binding of AP-1. Resveratrol was also shown to inhibit APE1/Ref-1 endonuclease activity and render melanoma cells more sensitive to treatment with the alkylating agent dacarbazine [124]. More recently, a small molecule called E3330 was developed and showed strong inhibition of APE/Ref-1
Although promising, treatment of melanoma with antioxidants has not yet achieved the desired results. One hypothesis is that antioxidants can be used as chemopreventive drugs, since the main role of ROS seems to be in the early progression of melanoma, when the tumor is fully installed.
Melanocytes are naturally exposed to oxidative stress due to UV, UV-associated inflammation and metal ions accumulation. However, melanocytes have a great capability to regulate their redox homeostasis due increased antioxidant activity and redox buffer characteristic of melanin. The disruption of redox regulation in melanocytes is not clear, but seems to be a consequence of many factors, including decreased of antioxidant enzymes expression and activity as MnSOD and glutathione levels, the switch of melanin to a pro-oxidant molecule and disturbance of signaling pathways that control melanocytes proliferation. Therefore, increased ROS levels found in melanoma cells are not a simple consequence of altered metabolism, but instead seem to have a central role in melanocyte malignant transformation and in abilities acquired during tumor progression as chemoresistance. The establishment of a pro-oxidant microenvironment also contributes to melanoma progression, implicating inflammatory cells as essential sources of ROS. Many mechanisms are associated with ROS accumulation in melanoma cells, including mitochondria dysfunction, increased NADPH oxidase activity and NOS uncoupling. ROS are implicated in regulating several biological processes by acting downstream important signaling pathways. Moreover, ROS regulate gene expression by genetic and epigenetic alterations. Although ROS are implicated in all stages of melanocyte malignant transformation, the uses of antioxidants as therapeutic strategies have not been successful. However, its use as a chemopreventive strategy has been shown to be efficient. Hence, efforts should be concentrated in the studies of the use of antioxidants as chemopreventive drugs for melanoma.
This work was supported by FAPESP (2011/12306-1 to MGJ and 2008/50366-3 to FM) and CAPES (2867/10 to FHMM).
Rare earths (RE) are widely consumed in polish, catalysts, rare earth magnets, and so on [1]. Due to the skewed distribution of production countries for RE, many countries depend on the imports from other countries. For example, in Japan, the amount of import of RE metals reached 6479 tons in 2014. The import price, severely depending on international markets, fluctuates widely. Japan is promoting the provisions such as development of alternative materials and the recycle of rare earths. Because the demand of NdFeB magnets has been growing rapidly in recent years because of their use in motors of electric vehicles, wind turbines, etc., the recycling of RE elements extracted from used magnets has become an important research area [2, 3, 4, 5].
There are two main classes of recycling of RE: dry and wet processes. As for the dry process, the recovery of Nd metal has been demonstrated [6] by employing Mg acting as an extraction medium, which forms a low-viscosity liquid alloy with Nd. It has been reported that RE can be separated by a selective reduction and a distillation [7]. The large difference of vapor pressure between RECl2 and RECl3 is skillfully utilized, and the selection efficiency is highly improved. Recently, the difference of oxygen affinity between RE and transition metals has also received attention in that this difference is used as a RE separation. For example, the mixture with flux FeO·B2O3 is a promising method for high purity and high extraction ratio of RE oxide [8]. Thermal isolation of RE oxides from NdFeB magnets using carbon as a reducing agent has been reported [9]. However, many attempts based on the dry process proposed so far are still at the initial laboratory stage.
Development of ore dressing technologies has promoted wet process methods [10, 11], which have already been applied to recycling the sludge of in-plant scrap. After the acid leaching of scrap using HCl, HNO3, and H2SO4, and the filtration of insoluble material mainly containing Fe, acid solution is reacted with oxalic or carbonic acid to form a precipitate containing RE elements. The calcined precipitate becomes RE oxides, which can be returned to the initial manufacturing process of NdFeB magnet. The roasting of NdFeB magnet [12, 13, 14] as a pretreatment improves the selectivity between rare earths and Fe, but the recovery ratio of RE is usually rather low with acid (especially HCl) leaching at room temperature. Nearly 100% recovery is achieved [12, 13] when HCl solution is heated to 80–180°C. In the acid leaching method for sludge [15], it is also necessary to heat the acid solution up to 80°C. We have recently proposed a pretreatment of corrosion [16] before the HCl leaching and the oxalic acid precipitation. In this method, the recovery ratio of Nd reaches 97% even when a room temperature process is used.
From the standpoint of sustainability and ecology, the main issue of the wet process is the discharge of waste acid solution. The recyclability of waste acid crucially depends on the efficient extraction of the constituent elements of the magnet from the used acid. One of the promising methods for Fe extraction involves a reaction with an ionic liquid [12, 17, 18, 19, 20], which often possesses a high selectivity between rare earths and Fe. Trihexyl(tetradecyl)phosphonium chloride (Cyphos® IL101) is a well-characterized ionic liquid that can extract Fe3+ ions in HCl solution with no extraction of trivalent rare earth ions [12, 18]. A possible closed-loop acid process for roasted NdFeB magnet has also been proposed, and the elemental technologies are well investigated [12]. However, an actual demonstration with reuse of waste acid solution has not been performed.
In this study, we introduce the full recovery of rare earth from NdFeB magnet using a wet process with the pretreatment of corrosion but without a closed-loop acid process. After that we describe the detailed experimental results of multiple rare earth extraction in a closed-loop acid process [21].
We used two kinds of commercial NdFeB magnets (Niroku seisakusyo). The elemental component of one magnet (denoted as magnet (1)) according to the manufacturer is Nd:Fe:B:the other elements (Dy et al.) = 28:66:1:5 in wt%. The composition of the other magnet (denoted as magnet (2)) was checked by an energy-dispersive X-ray spectrometer equipped in a field emission scanning electron microscope (JEOL, JSM-7100F) and determined to be Nd1.6Pr0.6Fe14B. Figure 1(a) shows the process flow without a closed-loop acid process. A demagnetized and pulverized NdFeB magnet (1), weighing approximately 0.5 g, was immersed in 3% NaCl solution (300 mL) for 1 week. An air pump provided constant air flow to the solution to accelerate the corrosion. The corroded sample was leached into HCl solution (100 mL) ranging from 0.1 to 0.3 mol/L, at room temperature. The insoluble material was calcined at 800°C for 5 h to obtain α-Fe2O3. The solution after removal of the insoluble was reacted with 0.26 g oxalic acid. The precipitate after the reaction was also calcined at 800°C for 5 h to obtain cubic Mn2O3-type Nd2O3 (c-Nd2O3).
(a) Procedures for rare earth recovery from NdFeB magnet (1) without closed-loop acid process. (b) Procedures for rare earth recovery from NdFeB magnet (2) with closed-loop acid process. S, L, and IL denote the solid, liquid, and ionic liquid, respectively. In procedure (b), elements expected to be present in the solid or solution are denoted.
To examine the feasibility of closed-loop acid process, the process flow was modified as shown in Figure 1(b). In this case, the corroded sample was leached in HCl solution (100 mL) with 0.2 mol/L or 0.5 mol/L for 1–2 h. After removal of the insoluble material, the solution was reacted with ionic liquid Cyphos® IL101 (HCl:ionic liquid = 4:1 in volume ratio), purchased from Sigma-Aldrich. The salting-out agent 10 mol/L NH4Cl was added to the solution. The mixture underwent magnetic stirring at 750 rpm and 60°C for 10 min. Then, it was centrifuged at 2500 rpm for 10 min and split into each component. The HCl solution was reacted with oxalic acid.
Several samples, calcined at 800°C for 5 h in the air, were evaluated using a powder X-ray diffractometer (Shimadzu, XRD-7000 L) with Cu-Kα radiation. We employed an inductively coupled plasma atomic emission spectrometer (Shimadzu, ICPE-9000) to analyze the concentrations of Nd, Pr, Fe, and B dissolved in HCl or NaCl solution. The concentrations were determined by the working curves of standard Nd, Pr, Fe, and B liquids.
The XRD pattern of corroded magnet (1) is shown in Figure 2, in which the XRD pattern of magnet (1) itself is also displayed. The main phase of magnet (1) is Nd2Fe14B with additional minor phase of NdFe4B4. The XRD pattern of Nd2Fe14B completely disappears in the corroded magnet, partially containing the XRD pattern of γ-FeOOH denoted by the filled triangles. In order to investigate the origin of the rest of the diffraction peaks (open circles) in the corroded sample, we have corroded NdFeB magnet (1) by hydrogenating it at 600°C for 12 h under a high pressure of hydrogen. The hydrogenated sample [22], as shown in the bottom pattern of Figure 2, shows the decomposition into Nd hydride (NdH2 + x) and α-Fe. Therefore, in each compound, the corrosion process would independently occur. The XRD pattern of corroded sample after the hydrogenation almost coincides with that of directly corroded magnet (1). Considering that α-Fe corroded into the Fe hydroxide (γ-FeOOH), a Nd hydroxide is probably responsible for the rest of the diffraction peaks (open circles) in the corroded sample. We note here that the NaCl concentration is not optimized. We simply suppose the sea water which is an abundant resource. The preliminary result using more concentrated NaCl solution (10%) also leads to the same results.
XRD patterns of corroded magnet, corroded sample after hydrogenation, and hydrogenated magnet. The employed magnet is magnet (1). The origin of each pattern is shifted by an integer value for clarity. Based partly on Ref. [
We checked the XRD pattern of insoluble material after HCl leaching of the corroded sample as shown in Figure 3(a). The diffraction peaks match well with those of the XRD pattern of γ-FeOOH, which transforms into α-Fe2O3 through the calcination (see Figure 3(b)). Figure 3(a) supports that the Nd hydroxide would be selectively dissolved into HCl solution, in which Nd ions are generated. The oxalic acid precipitation was performed to recover Nd. The precipitate has been calcined and evaluated by XRD pattern, which is displayed in Figure 3(b) with the simulated pattern of c-Nd2O3. The XRD patterns are well matched between the calcined precipitate and c-Nd2O3, suggesting the successful recovery of Nd in the form of Nd oxide.
(a) XRD patterns of corroded magnet (1) and insoluble material after HCl (0.1 mol/L, 30 min) leaching and γ-FeOOH. (b) XRD patterns of insoluble material and oxalic acid precipitate in HCl solution. They were calcined in the air. The simulation patterns of α-Fe2O3 and c-Nd2O3 are also shown. The HCl concentration is 0.2 mol/L, and the leaching time is 2 h. The origin of each pattern in (a) and (b) is shifted by an integer value for clarity. Based partly on Ref. [
Figure 4 shows the leaching time dependences of effective recovery ratio
Leaching time dependences of effective recovery ratio of Nd. The examined HCl solutions are 0.1, 0.2, and 0.3 mol/L. Based partly on Ref. [
For each HCl concentration,
Next, we show the experimental results of rare earth extraction using the closed-loop acid process. The starting magnet is magnet (2) with the mass of approximately 0.5 g. The distribution of constituent elements in our method mentioned above is partially unknown. Thus, a one-shot extraction with 0.2 mol/L HCl and 0.26 g oxalic acid but with no use of ionic liquid was performed. Table 1 shows the distribution of each ion in the NaCl solution after removal of the corroded sample and in the HCl solution after removal of precipitates produced by the reaction with oxalic acid. In the NaCl solution, only B is detected. A sufficient amount of oxalic acid can efficiently separate rare earths. A large amount of Fe stays in the HCl solution. The expected ion concentrations of the completely dissolved 0.5 g magnet are 1041 mg/L for Nd, 381 mg/L for Pr, 3527 mg/L for Fe, and 49 mg/L for B, respectively. The summation of the B concentrations in the two states listed in Table 1 is not far from 49 mg/L. Then, approximately 30% of B can be separated by the NaCl solution, and the remaining B stays in the HCl solution. Approximately 60% of the Fe ions are contained in the insoluble material obtained after HCl leaching. The recovery ratio of Nd (Pr) is 99% (97%).
Solution | Nd (mg/L) | Pr (mg/L) | Fe (mg/L) | B (mg/L) |
---|---|---|---|---|
NaCl after removal of corroded magnet | ND | ND | ND | 12.3 |
HCl after removal of oxalic acid precipitates | 10.6 | 13.0 | 1480 | 28.6 |
Distribution of Nd, Pr, Fe, and B in the one-shot recovery process.
ND means not detected. Based on Ref. [21].
Following the results of Ref. [12] which reported that salting-out agent NH4Cl plays an essential role in full extraction of Fe by an ionic liquid, the dependence of extraction efficiency on NH4Cl concentration was determined. Without NH4Cl, the extraction efficiency of Fe is only 40%, increasing to 75% with 5 mol/L NH4Cl and 95% for 10 mol/L NH4Cl. In this experiment, we also found that B is fully extracted by the ionic liquid. We speculate that Cyphos® IL101 represented by C38H68ClP transforms into C38H68FeCl4, after the incorporation of Fe3+ ions. Thus, the extraction efficiency of Fe severely depends on the Cl concentration, and the salting-out agent NH4Cl is necessary to provide enough Cl ions.
The preliminary experiment for a closed-loop process of HCl solution was performed using 0.5 mol/L HCl to reduce the experimental time. The oxalic acid mass was maintained at 0.26 g. Hereafter, the HCl solutions after removal of insoluble material in the acid leaching, after Fe extraction by the ionic liquid, and after removal of rare earths by oxalic acid precipitation are denoted state [I], [II], and [III], respectively (see also Figure 1(b)). Table 2 shows the Nd, Pr, and Fe concentrations of these states during each cycle. In the first cycle, approximately 24% of rare earths are extracted together with Fe by the ionic liquid. Only Nd and Pr are separated by the reaction with the oxalic acid. In state [I] during the second cycle, the concentrations of Nd and Pr are approximately one-quarter of those during the first cycle, which means an immediate precipitation due to excess oxalic acid in the previous cycle.
Cycle | State of solution | Nd (mg/L) | Pr (mg/L) | Fe (mg/L) |
---|---|---|---|---|
First | [I] | 929 | 346 | 2320 |
[II] | 707 | 264 | 105 | |
[III] | 16.9 | 17.4 | 109 | |
Second | [I] | 218 | 94 | 2770 |
[II] | 231 | 99 | 132 | |
[III] | ND | ND | 134 |
Distribution of Nd, Pr, and Fe in the preliminary experiment of a closed loop for HCl solution.
The notations of solutions are defined in Figure 1(b). ND means not detected. Based partly on Ref. [21].
The preliminary experiment suggested that the weight of oxalic acid needs to be adjusted. The weight of oxalic acid for a 0.5 g magnet, reproducing the initial concentrations of Nd and Pr in state [I] in the second cycle, has been searched as shown in Figure 5. The vertical axis shows the difference in Nd (Pr) ion concentration in state [I] between the first and second cycles, which is denoted as ▵c. A positive value for ▵c indicates a poor precipitation efficiency, and a negative value indicates an excess oxalic acid. For each element, ▵c linearly decreases with increasing weight of oxalic acid. A weight of 0.1675 g oxalic acid can reproduce the initial Nd (Pr) ion concentration of state [I] in the second cycle. The chemical equation for oxalic acid precipitation is.
A plot of Δc vs. the weight of oxalic acid. Δc represents the difference in Nd (Pr) ion concentration after HCl leaching of corroded magnet between the first and second cycles. Based partly on Ref. [
If the starting magnet weight is 0.5 g, the ideal amount of oxalic acid is 0.1335 g. However, as shown in Figure 5, Nd and Pr would not fully precipitate for 0.1335 g of oxalic acid. To achieve sufficient precipitation, the amount of oxalic acid that is consumed must be 1.3 times larger.
From the preliminary experiments for the closed-loop process of HCl solution, we have obtained the conditions of 10 mol/L NH4Cl and 0.1675 g oxalic acid for the recycling of 0.5 g magnet. Table 3 shows the results of a demonstration of triple rare earth extraction from 0.5 g magnet with the closed loop of HCl solution. The HCl concentration was 0.5 mol/L to expedite the experiment. The concentrations of Nd and Pr ions are measured in states [I], [II], and [III]. In each cycle, 10–15% of Nd and Pr ions are extracted together with Fe ions by the ionic liquid, as in the preliminary experiment (see Table 2). Contrary to our expectation, 30–35% of Nd and Pr ions remain in solution after the oxalic acid precipitation. However, these ions apparently do not contribute to the rare earth concentrations of state [I] in the next cycle; the concentrations of Nd and Pr ions in state [I] are the same as those during the previous cycle. The recovery ratio of each element, calculated by eliminating the amount of element extracted by the ionic liquid, is approximately 50% in all cycles. Figure 6 shows the XRD pattern of calcined insoluble material after HCl leaching in the second cycle. The simulated patterns of Nd0.73Pr0.27FeO3 and α-Fe2O3 are also exhibited. Elemental Nd (Pr) is partially recovered together with Fe. The XRD pattern in Figure 6 supports the idea that the Nd and Pr elements, which are present in the same concentration as the ions in state [III], would enter insoluble material in state [I] in the next cycle.
Cycle | State of solution | Nd (mg/L) | Pr (mg/L) | Recovery ratio of Nd (%) | Recovery ratio of Pr (%) |
---|---|---|---|---|---|
First | [I] | 971 | 370 | 50 | 47 |
[II] | 818 | 311 | |||
[III] | 328 | 136 | |||
Second | [I] | 980 | 406 | 49 | 50 |
[II] | 836 | 357 | |||
[III] | 352 | 156 | |||
Third | [I] | 919 | 410 | 61 | 56 |
[II] | 842 | 360 | |||
[III] | 280 | 130 |
The distribution of Nd and Pr and the recovery ratio of each element in a triple rare earth extraction.
The notations of the solutions are defined in Figure 1(b). Based partly on Ref. [21].
XRD pattern of calcined insoluble material after HCl leaching in the second extraction. The simulated Nd0.73Pr0.27FeO3 and α-Fe2O3 patterns are also shown. The origin of each pattern is shifted by an integer value for clarity. Based partly on Ref. [
In our method, Cyphos® IL101 is rather expensive, and the regeneration of the ionic liquid by stripping Fe3+ is required to reduce the cost. We examined two stripping methods. The first one is the stripping using NaOH solution. After the reaction of the ionic liquid containing Fe3+ ions with NaOH solution, Fe(OH)3 is expected to be precipitated, and Fe2O3 would be obtained after the calcination. The ionic liquid was reacted with NaOH solution (1 mol/L) with a volume ratio of Cyphos® IL101:NaOH solution = 1:2.The calcined precipitate was checked by the XRD pattern, and it is shown in Figure 7(a). The obtained pattern is in good agreement with the XRD pattern of NaFeO2. The recovery ratio of Fe is estimated to be 17%. The second method is the employment of ammonia solution, for which 100% stripping of Fe3+ has been already reported [23]. We roughly followed the reported recipe [23]. The yellow-colored ionic liquid containing Fe3+, which was obtained in the actual process flow, was reacted with the ammonia solution (approximately 3 wt.%) with a volume ratio of Cyphos® IL101:ammonia solution = 1:10. The precipitate at the interface between the liquids was collected using a cellulose filter and calcined together with the filter in the air. Figure 7(b) shows the XRD pattern of the calcined sample recovered from used Cyphos® IL101. The figure also displays the simulated patterns of α-Fe2O3, Fe3PO7, and C. The experimental XRD pattern closely matches the superposition of simulated patterns. The sources of P and C atom contamination would be Cyphos® IL101 containing P and the cellulose filter, respectively. Despite the contamination due to our insufficient filtration technique, Fe can be stripped. Furthermore, the yellow-colored ionic liquid once again became transparent after Fe3+ stripping, which means the ionic liquid is regenerated.
(a) XRD pattern of the calcined sample recovered from used Cyphos® IL101 reacted with NaOH solution. The simulated NaFeO2 pattern is also presented. The origin of each pattern is shifted by an integer value for clarity. (b) XRD pattern of calcined sample recovered from used Cyphos® IL101 reacted with ammonia solution. The simulated α-Fe2O3, Fe3PO7, and C patterns are also presented. The origin of each pattern is shifted by an integer value for clarity. (Based partly on Ref. [
Focusing on the one-shot recovery processes, a comparison between our method and other methods [12, 13, 14, 15] based on the acid leaching mentioned in Introduction is shown in Table 4. The number of steps in the recovery processes and the rare earth recovery ratio of each method are similar. The roasting used in Refs. [12, 13, 14] would have a cost disadvantage. Although Ref. [15] does not employ roasting, HNO3 has a disadvantage because waste discharge containing nitrate salt is severely controlled by law for environmental reasons. The acid leaching process in our method and in Ref. [14] is performed at room temperature, which means that these are safe processes. Since B is harmful, its separation is highly desired. Our method has achieved 30% B separation, whereas the other methods do not report a clear B separation. If a closed-loop acid process with a high recovery ratio of rare earths is realized, our method is promising because each step except Fe extraction by ionic liquid is performed at room temperature. This condition and the rather simple procedures lead to a safe and low-cost recovery process. In addition, the peculiar feature of B separation in our method is environmentally friendly.
Items | Our method [16] | [12] | [13] | [14] | [15] |
---|---|---|---|---|---|
Pretreatment | Corrosion at RT | Roast at 950°C | Roast at 500–1000°C | Roast at 750°C | Sludge |
Acid | HCl | HCl | HCl | H2SO4 | HNO3 |
Acid leaching temperature | RT | 80°C | 180°C | RT | 80°C |
B separation | 30% | Not separated | Not separated | Not separated | Not separated |
Recovery ratio of rare earths (%) | 97 | 100 | 100 | 100 | 94 |
Comparison between our method and other methods based on acid leaching in a one-shot recovery process.
RT means room temperature. Based partly on Ref. [21].
Rare earth extraction methods based on acid leaching are entering the stage of practical use. To address the issue of rather low selectivity between rare earths and Fe at the room temperature acid-process, we have proposed the pretreatment of corrosion. Our method has improved the selectivity, and rare earth recovery ratio, in one-shot extraction, reaches to almost 100% even at room temperature. For sustainability and environmental considerations, the recyclability of waste acid solution is one of the central issues in rare earth recycling, and this has not been well investigated. In this work, we have experimentally determined the recovery ratio of rare earth elements in our method with the closed-loop acid process. This ratio is approximately 50%, reduced from almost full recovery in a one-shot extraction. Although the recovery ratio is rather low at the present stage, our encouraging result should lead to rapid advancement of the study of recycling using a closed-loop acid process.
The demonstration of closed-loop process for HCl solution indicates that the precipitation by oxalic acid is not sufficient, although the amount of oxalic acid is larger than the ideal amount calculated using the chemical formula of precipitation. To increase the recovery ratios of rare earth elements, if the amount of oxalic acid is increased, it will result in a reduced recovery ratio in the second cycle, as deduced from Table 2. Thus, a trade-off between the number of rare earth extractions and the recovery ratio of rare earths might exist for the present precipitation condition. The main cause of the reduced recovery ratio is the insufficient ionization of oxalic acid. The degree of ionization of oxalic acid strongly depends on the pH of the solution. The ionization concentration generally increases with increasing pH, and the full ionization of oxalic acid with an ideal weight of 0.1335 g would be realized. Another issue to be considered is the partial rare earth extraction by the ionic liquid. If the oxalic acid precipitation process is performed before the process of Fe3+ extraction by the ionic liquid, only rare earth elements would be separated due to the high selectivity between rare earths and Fe under oxalic acid precipitation. Thus, the issue would be resolved by reversing the sequence of the two processes. As shown in Figure 6, unassigned peaks of material other than α-Fe2O3 and Nd0.73Pr0.27FeO3 are present in the XRD spectrum. In our study, complete separation of the ionic liquid from the HCl solution is difficult, which results in contamination of the calcined sample. Further improvement of the separation technique is needed to obtain a pure calcined sample.
This research was supported by the Matching Planner Program of the Japan Science and Technology Agency (JST). J.K. is grateful for the support provided by the Comprehensive Research Organization of Fukuoka Institute of Technology.
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Conditions of UHF excitation and propagation of the bulk, surface, and Lamb plate acoustic waves have been established and studied experimentally. Frequency dependencies of the impedance and quality factor have been studied to obtain a number of piezoelectric layered structure parameters as electromechanical coupling coefficient, equivalent circuit parameters, etc. Results of 2D finite element modeling of a given piezoelectric layered structure have been compared with the experimental ones obtained for the real high-overtone bulk acoustic resonator. An origin of high-overtone bulk acoustic resonator’s spurious resonant peaks has been studied. Results on UHF acoustic attenuation of IIa-type synthetic single crystalline diamond have been presented and discussed in terms of Akhiezer and Landau–Rumer mechanisms of phonon–phonon interaction. Identification and classification of Lamb waves belonging to several branches as well as dispersive curves of phase velocities have been executed. 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Blank",authors:[{id:"181306",title:"Prof.",name:"Boris",middleName:null,surname:"Sorokin",slug:"boris-sorokin",fullName:"Boris Sorokin"},{id:"185347",title:"Dr.",name:"Gennadiy",middleName:null,surname:"Kvashnin",slug:"gennadiy-kvashnin",fullName:"Gennadiy Kvashnin"},{id:"185348",title:"Dr.",name:"Arsenii",middleName:null,surname:"Telichko",slug:"arsenii-telichko",fullName:"Arsenii Telichko"},{id:"185349",title:"Dr.",name:"Sergey",middleName:null,surname:"Burkov",slug:"sergey-burkov",fullName:"Sergey Burkov"},{id:"185350",title:"Prof.",name:"Vladimir",middleName:null,surname:"Blank",slug:"vladimir-blank",fullName:"Vladimir Blank"}]}],mostDownloadedChaptersLast30Days:[{id:"51560",title:"Piezoelectric Energy Harvesting",slug:"piezoelectric-energy-harvesting",totalDownloads:2912,totalCrossrefCites:3,totalDimensionsCites:6,abstract:"The piezoelectric material selection and the circuit design in vibrational energy harvesting are discussed. The performances of the energy-harvesting unimorph devices that captured frequencies of 60 Hz by using piezoelectric PZT-based and BT-based ceramics were evaluated. Output voltages and power from the devices depend on the amplitude and the frequency of the oscillations, and depend on the load resistance. Generally, PZT-based ceramics are superior for piezoelectric energy-harvesting applications. The figures of merit of the materials are discussed in order to provide the guidelines of the piezoelectric material selections. Piezoelectric voltage coefficient, g31, is considered to be good parameter to predict the maximum voltages. On the other hand, d31g31/tanδ, k312Qm and d31g31 are close to the behavior of the maximum power. Combination of the piezoelectric unimorph and power management circuit produced the constant voltage output, which would be used as the power sources.",book:{id:"5215",slug:"piezoelectric-materials",title:"Piezoelectric Materials",fullTitle:"Piezoelectric Materials"},signatures:"Hiroshi Maiwa",authors:[{id:"27242",title:"Prof.",name:"Hiroshi",middleName:null,surname:"Maiwa",slug:"hiroshi-maiwa",fullName:"Hiroshi Maiwa"}]},{id:"43265",title:"The Application of Piezoelectric Materials in Machining Processes",slug:"the-application-of-piezoelectric-materials-in-machining-processes",totalDownloads:4528,totalCrossrefCites:0,totalDimensionsCites:0,abstract:null,book:{id:"3272",slug:"piezoelectric-materials-and-devices-practice-and-applications",title:"Piezoelectric Materials and Devices",fullTitle:"Piezoelectric Materials and Devices - Practice and Applications"},signatures:"Saeed Assarzadeh and Majid Ghoreishi",authors:[{id:"162546",title:"Dr.",name:"Saeed",middleName:null,surname:"Assarzadeh",slug:"saeed-assarzadeh",fullName:"Saeed Assarzadeh"}]},{id:"50322",title:"Acoustic Wave Velocity Measurement on Piezoelectric Single Crystals",slug:"acoustic-wave-velocity-measurement-on-piezoelectric-single-crystals",totalDownloads:1821,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Sound velocities were measured in relaxor single-crystal plates and piezoelectric ceramics including lead free using an ultrasonic precision thickness gauge with high-frequency pulse generation. Estimating the difference in the sound velocities and elastic constants in the single crystals and ceramics, it was possible to evaluate effects of domain and grain boundaries on elastic constants. Existence of domain boundaries in single crystal affected the decrease in Young’s modulus, rigidity, Poisson’s ratio, and bulk modulus. While existence of grain boundaries affected the decrease in Young’s modulus and rigidity, Poisson’s ratio and bulk modulus increased. It was thought these phenomena come from domain alignment by DC poling and both the boundaries act as to absorb mechanical stress by defects due to the boundaries. In addition, the origin of piezoelectricity in single crystals is caused by low bulk modulus and Poisson’s ratio, and high Young’s modulus and rigidity in comparison with ceramics. On the contrary, the origin of piezoelectricity in ceramics is caused by high Poisson’s ratio by high bulk modulus, and furthermore, low Young’s modulus and rigidity due to domain alignment.",book:{id:"5215",slug:"piezoelectric-materials",title:"Piezoelectric Materials",fullTitle:"Piezoelectric Materials"},signatures:"Toshio Ogawa",authors:[{id:"33684",title:"Prof.",name:"Toshio",middleName:null,surname:"Ogawa",slug:"toshio-ogawa",fullName:"Toshio Ogawa"}]},{id:"50728",title:"Piezoelectric Materials in RF Applications",slug:"piezoelectric-materials-in-rf-applications",totalDownloads:2148,totalCrossrefCites:1,totalDimensionsCites:3,abstract:"The development of several types of mobile objects requires new devices, such as high‐performance filters, microelectromechanical systems and other components. Piezoelectric materials are crucial to reach the expected performance of mobile objects because they exhibit high quality factors and sharp resonance and some of them are compatible with collective manufacturing technologies. We reviewed the main piezoelectric materials that can be used for radio frequency (RF) applications and herein report data on some devices. The modelling of piezoelectric plates and structures in the context of electronic circuits is presented. Among RF devices, filters are the most critical as the piezoelectric material must operate at RF frequencies. The main filter structures and characterisation methods, in accordance with such operating conditions as high frequencies and high power, are also discussed.",book:{id:"5215",slug:"piezoelectric-materials",title:"Piezoelectric Materials",fullTitle:"Piezoelectric Materials"},signatures:"Philippe Benech and Jean‐Marc Duchamp",authors:[{id:"4490",title:"Dr.",name:"Philippe",middleName:null,surname:"Benech",slug:"philippe-benech",fullName:"Philippe Benech"},{id:"182052",title:"Dr.",name:"Jean-Marc",middleName:null,surname:"Duchamp",slug:"jean-marc-duchamp",fullName:"Jean-Marc Duchamp"}]},{id:"11639",title:"Piezoelectric Thin Film Deposition: Novel Self-Assembled Island Structures and Low Temperature Processes on Silicon",slug:"piezoelectric-thin-film-deposition-novel-self-assembled-island-structures-and-low-temperature-proces",totalDownloads:4049,totalCrossrefCites:1,totalDimensionsCites:1,abstract:null,book:{id:"3218",slug:"piezoelectric-ceramics",title:"Piezoelectric Ceramics",fullTitle:"Piezoelectric Ceramics"},signatures:"Sharath Sriram, Madhu Bhaskaran and Arnan Mitchell",authors:[{id:"12171",title:"Dr.",name:"Sharath",middleName:null,surname:"Sriram",slug:"sharath-sriram",fullName:"Sharath Sriram"},{id:"12172",title:"Dr.",name:"Madhu",middleName:null,surname:"Bhaskaran",slug:"madhu-bhaskaran",fullName:"Madhu Bhaskaran"},{id:"12173",title:"Prof",name:"Arnan",middleName:null,surname:"Mitchell",slug:"arnan-mitchell",fullName:"Arnan Mitchell"}]}],onlineFirstChaptersFilter:{topicId:"921",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:0,limit:8,total:null},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:87,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:98,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:27,numberOfPublishedChapters:287,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:9,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:139,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:129,numberOfOpenTopics:0,numberOfUpcomingTopics:2,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!1},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:107,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:10,numberOfPublishedChapters:103,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:12,numberOfOpenTopics:2,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:0,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!1},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:10,numberOfOpenTopics:4,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}},{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}}]},series:{item:{id:"10",title:"Physiology",doi:"10.5772/intechopen.72796",issn:"2631-8261",scope:"Modern physiology requires a comprehensive understanding of the integration of tissues and organs throughout the mammalian body, including the cooperation between structure and function at the cellular and molecular levels governed by gene and protein expression. While a daunting task, learning is facilitated by identifying common and effective signaling pathways mediated by a variety of factors employed by nature to preserve and sustain homeostatic life. \r\nAs a leading example, the cellular interaction between intracellular concentration of Ca+2 increases, and changes in plasma membrane potential is integral for coordinating blood flow, governing the exocytosis of neurotransmitters, and modulating gene expression and cell effector secretory functions. Furthermore, in this manner, understanding the systemic interaction between the cardiovascular and nervous systems has become more important than ever as human populations' life prolongation, aging and mechanisms of cellular oxidative signaling are utilised for sustaining life. \r\nAltogether, physiological research enables our identification of distinct and precise points of transition from health to the development of multimorbidity throughout the inevitable aging disorders (e.g., diabetes, hypertension, chronic kidney disease, heart failure, peptic ulcer, inflammatory bowel disease, age-related macular degeneration, cancer). With consideration of all organ systems (e.g., brain, heart, lung, gut, skeletal and smooth muscle, liver, pancreas, kidney, eye) and the interactions thereof, this Physiology Series will address the goals of resolving (1) Aging physiology and chronic disease progression (2) Examination of key cellular pathways as they relate to calcium, oxidative stress, and electrical signaling, and (3) how changes in plasma membrane produced by lipid peroxidation products can affect aging physiology, covering new research in the area of cell, human, plant and animal physiology.",coverUrl:"https://cdn.intechopen.com/series/covers/10.jpg",latestPublicationDate:"May 14th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:11,editor:{id:"35854",title:"Prof.",name:"Tomasz",middleName:null,surname:"Brzozowski",slug:"tomasz-brzozowski",fullName:"Tomasz Brzozowski",profilePictureURL:"https://mts.intechopen.com/storage/users/35854/images/system/35854.jpg",biography:"Prof. Dr. Thomas Brzozowski works as a professor of Human Physiology and is currently Chairman at the Department of Physiology and is V-Dean of the Medical Faculty at Jagiellonian University Medical College, Cracow, Poland. His primary area of interest is physiology and pathophysiology of the gastrointestinal (GI) tract, with the major focus on the mechanism of GI mucosal defense, protection, and ulcer healing. He was a postdoctoral NIH fellow at the University of California and the Gastroenterology VA Medical Center, Irvine, Long Beach, CA, USA, and at the Gastroenterology Clinics Erlangen-Nuremberg and Munster in Germany. He has published 290 original articles in some of the most prestigious scientific journals and seven book chapters on the pathophysiology of the GI tract, gastroprotection, ulcer healing, drug therapy of peptic ulcers, hormonal regulation of the gut, and inflammatory bowel disease.",institutionString:null,institution:{name:"Jagiellonian University",institutionURL:null,country:{name:"Poland"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:4,paginationItems:[{id:"10",title:"Animal Physiology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/10.jpg",isOpenForSubmission:!0,annualVolume:11406,editor:{id:"202192",title:"Dr.",name:"Catrin",middleName:null,surname:"Rutland",slug:"catrin-rutland",fullName:"Catrin Rutland",profilePictureURL:"https://mts.intechopen.com/storage/users/202192/images/system/202192.png",biography:"Catrin Rutland is an Associate Professor of Anatomy and Developmental Genetics at the University of Nottingham, UK. She obtained a BSc from the University of Derby, England, a master’s degree from Technische Universität München, Germany, and a Ph.D. from the University of Nottingham. She undertook a post-doctoral research fellowship in the School of Medicine before accepting tenure in Veterinary Medicine and Science. Dr. Rutland also obtained an MMedSci (Medical Education) and a Postgraduate Certificate in Higher Education (PGCHE). She is the author of more than sixty peer-reviewed journal articles, twelve books/book chapters, and more than 100 research abstracts in cardiovascular biology and oncology. She is a board member of the European Association of Veterinary Anatomists, Fellow of the Anatomical Society, and Senior Fellow of the Higher Education Academy. Dr. Rutland has also written popular science books for the public. https://orcid.org/0000-0002-2009-4898. www.nottingham.ac.uk/vet/people/catrin.rutland",institutionString:null,institution:{name:"University of Nottingham",institutionURL:null,country:{name:"United Kingdom"}}},editorTwo:null,editorThree:null},{id:"11",title:"Cell Physiology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/11.jpg",isOpenForSubmission:!0,annualVolume:11407,editor:{id:"133493",title:"Prof.",name:"Angel",middleName:null,surname:"Catala",slug:"angel-catala",fullName:"Angel Catala",profilePictureURL:"https://mts.intechopen.com/storage/users/133493/images/3091_n.jpg",biography:"Prof. Dr. Angel Catalá \r\nShort Biography Angel Catalá was born in Rodeo (San Juan, Argentina). He studied \r\nchemistry at the Universidad Nacional de La Plata, Argentina, where received aPh.D. degree in chemistry (Biological Branch) in 1965. From\r\n1964 to 1974, he worked as Assistant in Biochemistry at the School of MedicineUniversidad Nacional de La Plata, Argentina. From 1974 to 1976, he was a Fellowof the National Institutes of Health (NIH) at the University of Connecticut, Health Center, USA. From 1985 to 2004, he served as a Full Professor oBiochemistry at the Universidad Nacional de La Plata, Argentina. He is Member ofthe National Research Council (CONICET), Argentina, and Argentine Society foBiochemistry and Molecular Biology (SAIB). His laboratory has been interested for manyears in the lipid peroxidation of biological membranes from various tissues and different species. Professor Catalá has directed twelve doctoral theses, publishedover 100 papers in peer reviewed journals, several chapters in books andtwelve edited books. Angel Catalá received awards at the 40th InternationaConference Biochemistry of Lipids 1999: Dijon (France). W inner of the Bimbo PanAmerican Nutrition, Food Science and Technology Award 2006 and 2012, South AmericaHuman Nutrition, Professional Category. 2006 award in pharmacology, Bernardo\r\nHoussay, in recognition of his meritorious works of research. Angel Catalá belongto the Editorial Board of Journal of lipids, International Review of Biophysical ChemistryFrontiers in Membrane Physiology and Biophysics, World Journal oExperimental Medicine and Biochemistry Research International, W orld Journal oBiological Chemistry, Oxidative Medicine and Cellular Longevity, Diabetes and thePancreas, International Journal of Chronic Diseases & Therapy, International Journal oNutrition, Co-Editor of The Open Biology Journal.",institutionString:null,institution:{name:"National University of La Plata",institutionURL:null,country:{name:"Argentina"}}},editorTwo:null,editorThree:null},{id:"12",title:"Human Physiology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/12.jpg",isOpenForSubmission:!0,annualVolume:11408,editor:{id:"195829",title:"Prof.",name:"Kunihiro",middleName:null,surname:"Sakuma",slug:"kunihiro-sakuma",fullName:"Kunihiro Sakuma",profilePictureURL:"https://mts.intechopen.com/storage/users/195829/images/system/195829.jpg",biography:"Professor Kunihiro Sakuma, Ph.D., currently works in the Institute for Liberal Arts at the Tokyo Institute of Technology. He is a physiologist working in the field of skeletal muscle. He was awarded his sports science diploma in 1995 by the University of Tsukuba and began his scientific work at the Department of Physiology, Aichi Human Service Center, focusing on the molecular mechanism of congenital muscular dystrophy and normal muscle regeneration. His interest later turned to the molecular mechanism and attenuating strategy of sarcopenia (age-related muscle atrophy). His opinion is to attenuate sarcopenia by improving autophagic defects using nutrient- and pharmaceutical-based treatments.",institutionString:null,institution:{name:"Tokyo Institute of Technology",institutionURL:null,country:{name:"Japan"}}},editorTwo:null,editorThree:{id:"331519",title:"Dr.",name:"Kotomi",middleName:null,surname:"Sakai",slug:"kotomi-sakai",fullName:"Kotomi Sakai",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000031QtFXQA0/Profile_Picture_1637053227318",biography:"Senior researcher Kotomi Sakai, Ph.D., MPH, works at the Research Organization of Science and Technology in Ritsumeikan University. She is a researcher in the geriatric rehabilitation and public health field. She received Ph.D. from Nihon University and MPH from St.Luke’s International University. Her main research interest is sarcopenia in older adults, especially its association with nutritional status. Additionally, to understand how to maintain and improve physical function in older adults, to conduct studies about the mechanism of sarcopenia and determine when possible interventions are needed.",institutionString:null,institution:{name:"Ritsumeikan University",institutionURL:null,country:{name:"Japan"}}}},{id:"13",title:"Plant Physiology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/13.jpg",isOpenForSubmission:!0,annualVolume:11409,editor:{id:"332229",title:"Prof.",name:"Jen-Tsung",middleName:null,surname:"Chen",slug:"jen-tsung-chen",fullName:"Jen-Tsung Chen",profilePictureURL:"https://mts.intechopen.com/storage/users/332229/images/system/332229.png",biography:"Dr. Jen-Tsung Chen is currently a professor at the National University of Kaohsiung, Taiwan. He teaches cell biology, genomics, proteomics, medicinal plant biotechnology, and plant tissue culture. Dr. Chen\\'s research interests include bioactive compounds, chromatography techniques, in vitro culture, medicinal plants, phytochemicals, and plant biotechnology. He has published more than ninety scientific papers and serves as an editorial board member for Plant Methods, Biomolecules, and International Journal of Molecular Sciences.",institutionString:"National University of Kaohsiung",institution:{name:"National University of Kaohsiung",institutionURL:null,country:{name:"Taiwan"}}},editorTwo:null,editorThree:null}]},overviewPageOFChapters:{paginationCount:17,paginationItems:[{id:"81751",title:"NanoBioSensors: From Electrochemical Sensors Improvement to Theranostic Applications",doi:"10.5772/intechopen.102552",signatures:"Anielle C.A. Silva, Eliete A. Alvin, Lais S. de Jesus, Caio C.L. de França, Marílya P.G. da Silva, Samaysa L. Lins, Diógenes Meneses, Marcela R. Lemes, Rhanoica O. Guerra, Marcos V. da Silva, Carlo J.F. de Oliveira, Virmondes Rodrigues Junior, Renata M. Etchebehere, Fabiane C. de Abreu, Bruno G. Lucca, Sanívia A.L. Pereira, Rodrigo C. Rosa and Noelio O. Dantas",slug:"nanobiosensors-from-electrochemical-sensors-improvement-to-theranostic-applications",totalDownloads:4,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Biosignal Processing",coverURL:"https://cdn.intechopen.com/books/images_new/11153.jpg",subseries:{id:"7",title:"Bioinformatics and Medical Informatics"}}},{id:"81766",title:"Evolution of Organoids in Oncology",doi:"10.5772/intechopen.104251",signatures:"Allen Thayakumar Basanthakumar, Janitha Chandrasekhar Darlybai and Jyothsna Ganesh",slug:"evolution-of-organoids-in-oncology",totalDownloads:6,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Organoids",coverURL:"https://cdn.intechopen.com/books/images_new/11430.jpg",subseries:null}},{id:"81678",title:"Developmental Studies on Practical Enzymatic Phosphate Ion Biosensors and Microbial BOD Biosensors, and New Insights into the Future Perspectives of These Biosensor Fields",doi:"10.5772/intechopen.104377",signatures:"Hideaki Nakamura",slug:"developmental-studies-on-practical-enzymatic-phosphate-ion-biosensors-and-microbial-bod-biosensors-a",totalDownloads:3,totalCrossrefCites:0,totalDimensionsCites:0,authors:[{name:"Hideaki",surname:"Nakamura"}],book:{title:"Biosignal Processing",coverURL:"https://cdn.intechopen.com/books/images_new/11153.jpg",subseries:{id:"7",title:"Bioinformatics and Medical Informatics"}}},{id:"81547",title:"Organoids and Commercialization",doi:"10.5772/intechopen.104706",signatures:"Anubhab Mukherjee, Aprajita Sinha, Maheshree Maibam, Bharti Bisht and Manash K. Paul",slug:"organoids-and-commercialization",totalDownloads:30,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Organoids",coverURL:"https://cdn.intechopen.com/books/images_new/11430.jpg",subseries:null}}]},overviewPagePublishedBooks:{paginationCount:12,paginationItems:[{type:"book",id:"6692",title:"Medical and Biological Image Analysis",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/6692.jpg",slug:"medical-and-biological-image-analysis",publishedDate:"July 4th 2018",editedByType:"Edited by",bookSignature:"Robert Koprowski",hash:"e75f234a0fc1988d9816a94e4c724deb",volumeInSeries:1,fullTitle:"Medical and Biological Image Analysis",editors:[{id:"50150",title:"Prof.",name:"Robert",middleName:null,surname:"Koprowski",slug:"robert-koprowski",fullName:"Robert Koprowski",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYTYNQA4/Profile_Picture_1630478535317",biography:"Robert Koprowski, MD (1997), PhD (2003), Habilitation (2015), is an employee of the University of Silesia, Poland, Institute of Computer Science, Department of Biomedical Computer Systems. For 20 years, he has studied the analysis and processing of biomedical images, emphasizing the full automation of measurement for a large inter-individual variability of patients. Dr. Koprowski has authored more than a hundred research papers with dozens in impact factor (IF) journals and has authored or co-authored six books. Additionally, he is the author of several national and international patents in the field of biomedical devices and imaging. Since 2011, he has been a reviewer of grants and projects (including EU projects) in biomedical engineering.",institutionString:null,institution:{name:"University of Silesia",institutionURL:null,country:{name:"Poland"}}}]},{type:"book",id:"7218",title:"OCT",subtitle:"Applications in Ophthalmology",coverURL:"https://cdn.intechopen.com/books/images_new/7218.jpg",slug:"oct-applications-in-ophthalmology",publishedDate:"September 19th 2018",editedByType:"Edited by",bookSignature:"Michele Lanza",hash:"e3a3430cdfd6999caccac933e4613885",volumeInSeries:2,fullTitle:"OCT - Applications in Ophthalmology",editors:[{id:"240088",title:"Prof.",name:"Michele",middleName:null,surname:"Lanza",slug:"michele-lanza",fullName:"Michele Lanza",profilePictureURL:"https://mts.intechopen.com/storage/users/240088/images/system/240088.png",biography:"Michele Lanza is Associate Professor of Ophthalmology at Università della Campania, Luigi Vanvitelli, Napoli, Italy. His fields of interest are anterior segment disease, keratoconus, glaucoma, corneal dystrophies, and cataracts. His research topics include\nintraocular lens power calculation, eye modification induced by refractive surgery, glaucoma progression, and validation of new diagnostic devices in ophthalmology. \nHe has published more than 100 papers in international and Italian scientific journals, more than 60 in journals with impact factors, and chapters in international and Italian books. He has also edited two international books and authored more than 150 communications or posters for the most important international and Italian ophthalmology conferences.",institutionString:'University of Campania "Luigi Vanvitelli"',institution:{name:'University of Campania "Luigi Vanvitelli"',institutionURL:null,country:{name:"Italy"}}}]},{type:"book",id:"7560",title:"Non-Invasive Diagnostic Methods",subtitle:"Image Processing",coverURL:"https://cdn.intechopen.com/books/images_new/7560.jpg",slug:"non-invasive-diagnostic-methods-image-processing",publishedDate:"December 19th 2018",editedByType:"Edited by",bookSignature:"Mariusz Marzec and Robert Koprowski",hash:"d92fd8cf5a90a47f2b8a310837a5600e",volumeInSeries:3,fullTitle:"Non-Invasive Diagnostic Methods - Image Processing",editors:[{id:"253468",title:"Dr.",name:"Mariusz",middleName:null,surname:"Marzec",slug:"mariusz-marzec",fullName:"Mariusz Marzec",profilePictureURL:"https://mts.intechopen.com/storage/users/253468/images/system/253468.png",biography:"An assistant professor at Department of Biomedical Computer Systems, at Institute of Computer Science, Silesian University in Katowice. 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