Monoclonal Antibodies in Immunodiagnosis and Immunotherapy最新文献

{"title":"Computer-Aided Tools and Resources for Fungal Pathogens: An Application of Reverse Vaccinology for Mucormycosis.","authors":"Anasuya Bhargav,&nbsp;Firdaus Fatima,&nbsp;Pratibha Chaurasia,&nbsp;Surabhi Seth,&nbsp;Srinivasan Ramachandran","doi":"10.1089/mab.2021.0039","DOIUrl":"https://doi.org/10.1089/mab.2021.0039","url":null,"abstract":"<p><p>Increasing fungal infections in immunocompromised hosts are a growing concern for global public health. Along with treatments, preventive measures are required. The emergence of reverse vaccinology has opened avenues for using genomic and proteomic data from pathogens in the design of vaccines. In this work, we present a comprehensive collection of various computational tools and databases with potential to aid in vaccine development. The ongoing pandemic has directed attention toward the increasing number of mucormycosis infections in COVID-19 patients. As a case study, we developed a computational pipeline for assisting vaccine development for mucormycosis. We obtained 6 proteins from 29,447 sequences from UniProtKB as potential vaccine candidates against mucormycosis, fulfilling multiple criteria. These criteria included potential characteristics, namely adhesin properties, surface or extracellular localization, antigenicity, no similarity to any human proteins, nonallergenicity, stability <i>in vitro</i>, and expression in fungal cells. These six proteins were predicted to have B cell and T cell epitopes, proinflammatory inducing peptides, and orthologs in several mucormycosis-causing species. These data could aid in vaccine development against mucormycosis for at-risk individuals.</p>","PeriodicalId":53514,"journal":{"name":"Monoclonal Antibodies in Immunodiagnosis and Immunotherapy","volume":" ","pages":"243-254"},"PeriodicalIF":0.0,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40679168","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Harnessing Antibody Polyspecificity for Cancer Immunotherapy.","authors":"Anastas Pashov,&nbsp;Ramachandran Murali,&nbsp;Issam Makhoul,&nbsp;Behjatolah Karbassi,&nbsp;Thomas Kieber-Emmons","doi":"10.1089/mab.2022.0025","DOIUrl":"https://doi.org/10.1089/mab.2022.0025","url":null,"abstract":"<p><p>Targeting the diverse glycan repertoire expressed on tumor cells is considered a viable therapeutic strategy to deal with tumor cell heterogeneity. Inherently polyspecific, natural, glycan-reactive antibodies are purported to be protective in thwarting infections and in cancer immunotherapy. Tumor-associated carbohydrate antigens (TACAs) are related to pathogen glycans, to which nascent or natural antibodies exist and IgM responses are elicited. To capture the polyspecific nature of anticarbohydrate responses, we have focused on the rational design of carbohydrate mimetic peptides (CMPs) cross-reactive with TACA reactive antibodies. In particular, we have focused on the development of CMPs that display reactivity to GD2 and Lewis Y (LeY) reactive monoclonal antibodies. They would serve as templates for pan-immunogens inducing biosimilar polyreactive antibodies. In the design, we relied on structural analyses of CMP's enhanced binding to the templates using molecular modeling. Glycan reactivity patterns of affinity CMP-purified human antibodies further refined specificity profiles in comparison with the immune response to the CMP in clinical trials. In this study, we further define the molecular characteristics for this mimicry by considering the polyspecificity of LeY and GD2 reactive antibodies binding to the lacto-ceramide core Galβ(1,4)Glcβ(1-1')Cer. Binding to this minimum building block can be capitalized on for cancer therapy and diagnostics and illustrates a new approach in designing cancer vaccines taking advantage of the latent polyspecificity of antibodies and the relevance of natural antibodies in antigen discovery and design.</p>","PeriodicalId":53514,"journal":{"name":"Monoclonal Antibodies in Immunodiagnosis and Immunotherapy","volume":"41 5","pages":"290-300"},"PeriodicalIF":0.0,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10530656","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Designing Next-Generation Vaccines Against Common Pan-Allergens Using <i>In Silico</i> Approaches.","authors":"Gaurab Sircar,&nbsp;Nandini Ghosh,&nbsp;Sudipto Saha","doi":"10.1089/mab.2021.0033","DOIUrl":"https://doi.org/10.1089/mab.2021.0033","url":null,"abstract":"<p><p>Next-generation allergy vaccines refer to allergen-derived attenuated molecules that can boost allergen-blocking IgG response. These IgG antibodies are specifically directed toward the IgE epitope of allergens and interfere in allergen-IgE interaction. Our study is a computational approach to design such vaccines against four widespread pan-allergens families. Pan-allergens display extensive immunological cross-reactivity due to the presence of conserved IgE epitope and T cell epitope. In this study, the vaccine design is based on hapten-carrier concept in which the carrier protein is an immunogenic component providing T cell help. Either PreS protein of hepatitis B or cholera enterotoxin B (CTB) fused with three tetanus toxoid fragments (TTFrC) was used here as the carrier. The hapten components are nonanaphylactic peptides (NAPs) derived from experimentally determined antigenic regions of the allergens. The charged residues of NAPs are selectively modified to obliterate IgE, as well as T cell reaction, and hence, are safe to apply in allergy patients. Various combinations of vaccine constructs (PreS/CTB+TTFrC and NAPs) were designed with intermediate linker motifs. Screening of constructs was performed through a three-step method such as physicochemical parameters, secondary structures, and tertiary structures using various bioinformatic tools. The final construct with best quality and stability was selected for each allergen family. Suitability of these constructs for being expressed in recombinant form was checked at DNA, RNA, and protein level. Presence of putative epitopes inducing tolerogenic interleukin-10 was also predicted for these constructs. The present work led to the design of putative vaccines with immunotherapeutic potential and broad applicability for allergic diseases caused by a wide array of cross-reactive allergens.</p>","PeriodicalId":53514,"journal":{"name":"Monoclonal Antibodies in Immunodiagnosis and Immunotherapy","volume":"41 5","pages":"231-242"},"PeriodicalIF":0.0,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9547223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"National Control Laboratory Assessment of Quality of Rituximab Biosimilars in India.","authors":"Nripendra Nath Mishra,&nbsp;Anu Sharma,&nbsp;Swati Shalini,&nbsp;Sonia Sharma,&nbsp;Paras Jain,&nbsp;Ratnesh K Sharma,&nbsp;Harish Chander,&nbsp;J P Prasad,&nbsp;Anupkumar R Anvikar,&nbsp;Subhash Chand","doi":"10.1089/mab.2021.0066","DOIUrl":"https://doi.org/10.1089/mab.2021.0066","url":null,"abstract":"<p><p>In past few years many rituximab (RTX) biosimilars have been launched in India. Biosimilars are products that are similar in terms of quality, safety, and efficacy to its innovator product and are expected to offer improved affordability. The less clinical examination is a significant source of reduction in the cost of development of a biosimilar. However, this clinical relief is predicated on the assumption that there is analytical similarity between the biosimilar and the innovator product. Therefore, the role of National Control Laboratory become very important to ensure the quality of these drugs by carrying out analytical characterization at the point of drug product release level as when referred by National Regulatory Authority for quality evaluation. To assess the similarity between innovator and biosimilars, different physicochemical and biological quality attributes were assessed. A multitude of state-of-the-art analysis of <i>N</i> = 3 RTX biosimilars marketed in India revealed that the impurity profiles of these biosimilars measured by charge variant analysis (cation exchange chromatography-high performance liquid chromatography [HPLC], capillary zone electrophoresis, and capillary isoelectric focusing), aggregates profiling (size exclusion chromatography-HPLC), fragments analysis (capillary electrophoresis-sodium dodecyl sulfate) were found to be significantly varying as compared with the innovator product. There were significant variations in acidic variants (<i>p</i> = 0.023) and basic variants (<i>p</i> = 0.0005), isoelectric point value (<i>p</i> < 0.0001), aggregates (<i>p</i> = 0.0231), and fragments (<i>p</i> < 0.0001) of biosimilars were found as that of innovator product. However, these differences were not affecting the biological activity in the cell-based potency analysis by complement-dependent cytotoxicity (CDC) assay (<i>p</i> = 0.1026), antibody-dependent cell-mediated cytotoxicity (ADCC) (<i>p</i> = 0.3736), and binding assay by flow cytometer fluorescence-activated cell sorting (<i>p</i> = 0.4005) of these biosimilars as compared with the innovator product.</p>","PeriodicalId":53514,"journal":{"name":"Monoclonal Antibodies in Immunodiagnosis and Immunotherapy","volume":" ","pages":"260-274"},"PeriodicalIF":0.0,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40431681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epitope Mapping of an Anti-Mouse CXCR6 Monoclonal Antibody (Cx₆Mab-1) Using the 2 × Alanine Scanning Method.","authors":"Yu Isoda,&nbsp;Tomohiro Tanaka,&nbsp;Hiroyuki Suzuki,&nbsp;Teizo Asano,&nbsp;Takuro Nakamura,&nbsp;Miyuki Yanaka,&nbsp;Saori Handa,&nbsp;Yu Komatsu,&nbsp;Saori Okuno,&nbsp;Nozomi Takahashi,&nbsp;Yuki Okada,&nbsp;Hiyori Kobayashi,&nbsp;Guanjie Li,&nbsp;Ren Nanamiya,&nbsp;Nohara Goto,&nbsp;Nami Tateyama,&nbsp;Takeo Yoshikawa,&nbsp;Mika K Kaneko,&nbsp;Yukinari Kato","doi":"10.1089/mab.2022.0019","DOIUrl":"https://doi.org/10.1089/mab.2022.0019","url":null,"abstract":"<p><p>The CXC chemokine receptor 6 (CXCR6) is a member of the G protein-coupled receptor family that is highly expressed in helper T type 1 cells, cytotoxic T lymphocytes (CTLs), and natural killer cells. CXCR6 plays critical roles in local expansion of effector-like CTLs in tumor microenvironment to potentiate the antitumor response. Therefore, the development of anti-CXCR6 monoclonal antibodies (mAbs) is essential to evaluate the immune microenvironment of tumors. Using N-terminal peptide immunization, we previously developed an anti-mouse CXCR6 (mCXCR6) mAb, Cx₆Mab-1 (rat IgG1, kappa) , which is useful for flow cytometry and western blotting. In this study, we determined the critical epitope of Cx₆Mab-1 by enzyme-linked immunosorbent assay (ELISA) using the 1 × alanine scanning (1 × Ala-scan) method or the 2 × alanine scanning (2 × Ala-scan) method. Although we first performed ELISA by 1 × Ala-scan using one alanine-substituted peptides of mCXCR6 N-terminal domain (amino acids 1-20), we could not identify the Cx₆Mab-1 epitope. We next performed ELISA by 2 × Ala-scan using two alanine (or glycine) residues-substituted peptides of mCXCR6 N-terminal domain, and found that Cx₆Mab-1 did not recognize S8A-A9G, A9G-L10A, L10A-Y11A, and G13A-H14A of the mCXCR6 N-terminal peptide. The results indicate that the binding epitope of Cx₆Mab-1 includes Ser8, Ala9, Leu10, Tyr11, Gly13, and His14 of mCXCR6. Therefore, we could demonstrate that the 2 × Ala scan method is useful for determining the critical epitope of mAbs.</p>","PeriodicalId":53514,"journal":{"name":"Monoclonal Antibodies in Immunodiagnosis and Immunotherapy","volume":" ","pages":"275-278"},"PeriodicalIF":0.0,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40428117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Generation of Rat Monoclonal Antibody for Mouse Nucleolin by Immunization of Ferroptosis-Induced Hepa 1-6 Cells.","authors":"Chikako Yokoyama, Sho Kobayashi, Yumi Harada, Yuki Nishino, Junichi Fujii, Taro Tachibana","doi":"10.1089/mab.2022.0005","DOIUrl":"10.1089/mab.2022.0005","url":null,"abstract":"<p><p>Nucleolin is a multifunctional phosphoprotein that is ubiquitously distributed in the nucleus, nucleoplasm, cytoplasm, and cell membrane. The principal functions of nucleolin involve DNA and RNA metabolism, gene transcription and translation, ribosome biogenesis, and mRNA stability. Ferroptosis is a type of regulated cell death that is characterized by the iron-dependent accumulation of lipid peroxidation products. In a previous study, we produced monoclonal antibodies (mAbs) against lysates prepared from ferroptosis-induced Hepa 1-6 cells. In this study, we describe one of those rat mAbs, 4B5, which was generated against mouse nucleolin. This mAb was useful in immunofluorescence staining, immunoblotting, and immunoprecipitation experiments, and was confirmed to recognize endogenous nucleolin in mouse cell lines and tissues. We anticipate that mAb 4B5 will be useful for functional analyses of nucleolin.</p>","PeriodicalId":53514,"journal":{"name":"Monoclonal Antibodies in Immunodiagnosis and Immunotherapy","volume":" ","pages":"255-259"},"PeriodicalIF":0.0,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40650940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epitope Mapping of the Anti-Human CC Chemokine Receptor Type-2 Monoclonal Antibody (K036C2).","authors":"Tomohiro Tanaka,&nbsp;Hiroyuki Suzuki,&nbsp;Guanjie Li,&nbsp;Ren Nanamiya,&nbsp;Yu Isoda,&nbsp;Yuki Okada,&nbsp;Hiyori Kobayashi,&nbsp;Takeo Yoshikawa,&nbsp;Mika K Kaneko,&nbsp;Yukinari Kato","doi":"10.1089/mab.2022.0018","DOIUrl":"https://doi.org/10.1089/mab.2022.0018","url":null,"abstract":"<p><p>CC chemokine receptor type-2 (CCR2) belongs to the G protein-coupled receptors superfamily, and is localized on cell surface of tumor cells and some immune cells, including monocytes and macrophages. CCR2 is a receptor for monocyte chemoattractant protein-1/C-C motif chemokine 2, and is involved in the progression of various diseases such as cancers. Therefore, the development of CCR2-targeted monoclonal antibody (mAb) is desired. Its characterization, including epitope of mAb, is very important for antibody applications. In this study, we investigated the critical epitope of K036C2, which is a commercially available anti-human CCR2 (hCCR2) mAb. We conducted enzyme-linked immunosorbent assay (ELISA) using three N-terminal peptides of hCCR2 and demonstrated that K036C2 recognizes 11-29 and 21-39 amino acids of hCCR2. We further performed ELISA using 20 peptides, which include alanine substitution of hCCR2. K036C2 lost the reaction to the alanine-substituted peptides of D25A, Y26A, D27A, G29A, and A30G. These results indicate that the critical binding epitope of K036C2 includes Asp25, Tyr26, Asp27, Gly29, and Ala30 of hCCR2.</p>","PeriodicalId":53514,"journal":{"name":"Monoclonal Antibodies in Immunodiagnosis and Immunotherapy","volume":" ","pages":"285-289"},"PeriodicalIF":0.0,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40439198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Production and Characterization of Monoclonal Antibodies Against the VP7 Protein of Epizootic Hemorrhagic Disease Virus.","authors":"Gisella Armillotta,&nbsp;Tiziana Di Febo,&nbsp;Simonetta Ulisse,&nbsp;Caterina Laguardia,&nbsp;Mariangela Iorio,&nbsp;Ivanka Krasteva,&nbsp;Manuela Tittarelli,&nbsp;Maria Teresa Mercante,&nbsp;Mirella Luciani","doi":"10.1089/mab.2021.0019","DOIUrl":"https://doi.org/10.1089/mab.2021.0019","url":null,"abstract":"<p><p>Monoclonal antibodies (MAbs) against epizootic hemorrhagic disease virus (EHDV) were produced by immunizing BALB/c mice with rec-VP7-EHDV2; 66 clones producing MAbs able to recognize the VP7-EHDV with a strong reaction were obtained and tested in indirect enzyme-linked immunosorbent assay (i-ELISA) against the whole epizootic hemorrhagic disease (EHD) virus serotype 2; potential cross-reactions with related orbiviruses, as Bluetongue virus (BTV) and African horse sickness virus (AHSV), were investigated as well by i-ELISA, Western blot, and immunofluorescence. Fifty-three MAbs were specific for EHDV (VP7 recombinant protein and whole virus) and 13 reacted also with the VP7 of BTV. None of the MAbs reacted with AHSV. MAbs specific for EHDV were further characterized in a competitive ELISA (c-ELISA): 20 among them were found useful to develop a c-ELISA for the detection of antibodies against EHDV in bovine sera. The availability of this extensive set of MAbs provides the opportunity to develop a c-ELISA for the serological diagnosis of EHDV and to tune new methods for the isolation and identification of the virus in biological samples and cell cultures. The experimentation protocol was approved by the Italian Ministry of Health (number 639/2018-PR, Resp. to Prot. BDF16.13#295833199#).</p>","PeriodicalId":53514,"journal":{"name":"Monoclonal Antibodies in Immunodiagnosis and Immunotherapy","volume":" ","pages":"181-187"},"PeriodicalIF":0.0,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40431222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Establishment of Neutralizing Monoclonal Antibodies Against Severe Acute Respiratory Syndrome Coronavirus 2 by the Screening with Exosomes Expressing the Viral Spike Protein.","authors":"Chihiro Okada,&nbsp;Etsuko Ikeda-Ishizaka,&nbsp;Chikako Ono,&nbsp;Yoshiharu Matsuura,&nbsp;Hikaru Sonoda","doi":"10.1089/mab.2021.0043","DOIUrl":"https://doi.org/10.1089/mab.2021.0043","url":null,"abstract":"<p><p>Monoclonal antibodies (mAbs) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes COVID-19, are the important tools both for the diagnosis and therapeutics of this infectious disease. The high-performance antibody against spike protein of SARS-CoV-2 is expected to inhibit the binding of viruses to their receptors on the surface of their target cells. In this study, we propose the novel screening method for mAbs against the pathogenic infectious virus using exosome. By this method, the exosome that artificially expresses SARS-CoV-2 spike protein was purified and used as a virus-like vesicle, which could bind to the viral receptor, angiotensin-converting enzyme 2 (ACE2). As a result, seven mAbs that could bind to the spike protein were obtained and six of these clones could strongly inhibit the binding to ACE2 of both the protein corresponding to the receptor binding domain (RBD) and the exosome expressing the spike protein. Interestingly, some of these antibodies seemed to share their epitopes in RBD, suggesting that highly antigenic sites exist in the spike protein. In view of the neutralizing activities on infection, five clones of these antibodies could inhibit the internalization of vesicular stomatitis virus-based pseudo viruses expressing various types of spike proteins derived from SARS-CoV-2 variants. In addition, these antibodies inhibited the infection of SARS-CoV-2 to cultured mammalian cells. These antibodies are expected to be utilized for both diagnosis and therapeutics of COVID-19.</p>","PeriodicalId":53514,"journal":{"name":"Monoclonal Antibodies in Immunodiagnosis and Immunotherapy","volume":" ","pages":"173-180"},"PeriodicalIF":0.0,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40431227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Living with Endemic COVID-19.","authors":"Thomas Kieber-Emmons,&nbsp;Anastas Pashov","doi":"10.1089/mab.2022.29009.editorial","DOIUrl":"https://doi.org/10.1089/mab.2022.29009.editorial","url":null,"abstract":"","PeriodicalId":53514,"journal":{"name":"Monoclonal Antibodies in Immunodiagnosis and Immunotherapy","volume":" ","pages":"171-172"},"PeriodicalIF":0.0,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40431225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}