Frontiers in Immunology最新文献

{"title":"Single-cell profiling indicates a high similarity between immune cells in the cerebrospinal fluid and in meningeal ectopic lymphoid tissue in experimental autoimmune encephalomyelitis","authors":"Tanya Georgieva, Jolien Diddens, Verena Friedrich, G. Lepennetier, R. Brand, K. Lehmann-Horn","doi":"10.3389/fimmu.2024.1400641","DOIUrl":"https://doi.org/10.3389/fimmu.2024.1400641","url":null,"abstract":"B cell depleting anti-CD20 monoclonal antibodies (aCD20 mAbs) are highly effective in treatment of multiple sclerosis (MS) but fail to halt the formation of meningeal ectopic lymphoid tissue (mELT) in the murine model experimental autoimmune encephalomyelitis (EAE). While mELT can be examined in EAE, it is not accessible in vivo in MS patients. Our key objectives were to compare the immune cells in cerebrospinal fluid (CSF), which is accessible in patients, with those in mELT, and to study the effects of aCD20 mAbs on CSF and mELT in EAE.Applying single cell RNA sequencing, we compared gene expression profiles in immune cells from (1) CSF with mELT and (2) aCD20 mAbs treated with control treated mice in a spontaneous 2D2xTh EAE model.The immune cell composition in CSF and mELT was very similar. Gene expression profiles and pathway enrichment analysis revealed no striking differences between the two compartments. aCD20 mAbs led not only to a virtually complete depletion of B cells in the CSF but also to a reduction of naïve CD4+ T cells and marked increase of macrophages. No remarkable differences in regulated genes or pathways were observed.Our results suggest that immune cells in the CSF may serve as a surrogate for mELT in EAE. Future studies are required to confirm this in MS patients. The observed increase of macrophages in B cell depleted CSF is a novel finding and requires verification in CSF of aCD20 mAbs treated MS patients. Due to unresolved technical challenges, we were unable to study the effects of aCD20 mAbs on mELT. This should be addressed in future studies.","PeriodicalId":505785,"journal":{"name":"Frontiers in Immunology","volume":"32 11","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141354566","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":"Human antibodies neutralizing the alpha-latrotoxin of the European black widow","authors":"Maximilian Ruschig, Jana Nerlich, Marlies Becker, D. Meier, S. Polten, Karla Cervantes-Luevano, P. Kuhn, Alexei Fedorovish Licea-Navarro, Stefan Hallermann, Stefan Dübel, M. Schubert, Jeffrey Brown, Michael Hust","doi":"10.3389/fimmu.2024.1407398","DOIUrl":"https://doi.org/10.3389/fimmu.2024.1407398","url":null,"abstract":"Poisoning by widow-spider (genus Latrodectus) bites occurs worldwide. The illness, termed latrodectism, can cause severe and persistent pain and can lead to muscle rigidity, respiratory complications, and cardiac problems. It is a global health challenge especially in developing countries. Equine serum-derived polyclonal anti-sera are commercially available as a medication for patients with latrodectism, but the use of sera imposes potential inherent risks related to its animal origin. The treatment may cause allergic reactions in humans (serum sickness), including anaphylactic shock. Furthermore, equine-derived antivenom is observed to have batch-to-batch variability and poor specificity, as it is always an undefined mix of antibodies. Because latrodectism can be extremely painful but is rarely fatal, the use of antivenom is controversial and only a small fraction of patients is treated. In this work, recombinant human antibodies were selected against alpha-latrotoxin of the European black widow (Latrodectus tredecimguttatus) by phage display from a naïve antibody gene library. Alpha-Latrotoxin (α-LTX) binding scFv were recloned and produced as fully human IgG. A novel alamarBlue assay for venom neutralization was developed and used to select neutralizing IgGs. The human antibodies showed in vitro neutralization efficacy both as single antibodies and antibody combinations. This was also confirmed by electrophysiological measurements of neuronal activity in cell culture. The best neutralizing antibodies showed nanomolar affinities. Antibody MRU44–4-A1 showed outstanding neutralization efficacy and affinity to L. tredecimguttatus α-LTX. Interestingly, only two of the neutralizing antibodies showed cross-neutralization of the venom of the Southern black widow (Latrodectus mactans). This was unexpected, because in the current literature the alpha-latrotoxins are described as highly conserved. The here-engineered antibodies are candidates for future development as potential therapeutics and diagnostic tools, as they for the first time would provide unlimited supply of a chemically completely defined drug of constant quality and efficacy, which is also made without the use of animals.","PeriodicalId":505785,"journal":{"name":"Frontiers in Immunology","volume":"110 13","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141352129","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":"Elevated extracellular particle concentration in plasma predicts in-hospital mortality after severe trauma","authors":"Nils Becker, N. Franz, Akiko Eguchi, Alessa Wagner, Ramona Sturm, Helen Rinderknecht, Yoshinao Kobayashi, M. Iwasa, Birte Weber, Ingo Marzi, B. Relja","doi":"10.3389/fimmu.2024.1390380","DOIUrl":"https://doi.org/10.3389/fimmu.2024.1390380","url":null,"abstract":"Extracellular particles (EPs), particularly extracellular vesicles, play a crucial role in regulating various pathological mechanisms, including immune dysregulations post-trauma. Their distinctive expression of cell-specific markers and regulatory cargo such as cytokines or micro-ribonucleic acid suggests their potential as early biomarkers for organ-specific damage and for identifying patients at risk for complications and mortality. Given the critical need for reliable and easily assessable makers to identify at-risk patients and guide therapeutic decisions, we evaluated the early diagnostic value of circulating EPs regarding outcomes in severely injured multiple-trauma patients.Plasma samples were collected from 133 severely injured trauma patients (Injury Severity Score (ISS) ≥16) immediately upon arrival at the emergency department (ED). Patients were categorized into survivors and non-survivors. Injury characteristics and outcomes related to sepsis, pneumonia, or early (<1 day after admission) and late mortality were assessed. Circulating EPs, cytokine profiles, and blood counts of platelets and leukocytes were determined. Receiver operating characteristic analyses were conducted.Despite no significant differences in injury pattern or severity, non-survivors exhibited significantly elevated counts of circulating EPs compared to survivors. The optimal cut-off for EPs <200 nm indicating non-survivors was 17380/µl plasma, with a sensitivity of 77% and a specificity of 61% in predicting in-hospital mortality. Later non-survivors received significantly higher numbers of units of packed red blood cells [8.54 ± 5.45 vs. 1.29 ± 0.36 units], had higher serum lactate [38.00 ± 7.51 vs. 26.98 ± 1.58 mg/dL], significantly lower platelet counts [181.30 ± 18.06 vs. 213.60 ± 5.85 *10³/µL] and lower heart rates [74.50 ± 4.93 vs. 90.18 ± 2.06 beats/minute] upon arrival at the ED compared to survivors.Our results demonstrate the high diagnostic potential of elevated concentrations of circulating EPs <200 nm for identifying patients at risk of mortality after severe trauma. This parameter shows comparable sensitivity to established clinical predictors. Early evaluation of EPs concentration could complement assessment markers in guiding early therapeutic decisions.","PeriodicalId":505785,"journal":{"name":"Frontiers in Immunology","volume":"52 23","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141355194","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":"Single cell transcriptomic analysis of the canine duodenum in chronic inflammatory enteropathy and health","authors":"Alison C. Manchester, Dylan T. Ammons, Michael R. Lappin, Steven Dow","doi":"10.3389/fimmu.2024.1397590","DOIUrl":"https://doi.org/10.3389/fimmu.2024.1397590","url":null,"abstract":"Chronic inflammatory enteropathy (CIE) is a common condition in dogs causing recurrent or persistent gastrointestinal clinical signs. Pathogenesis is thought to involve intestinal mucosal inflammatory infiltrates, but histopathological evaluation of intestinal biopsies from dogs with CIE fails to guide treatment, inform prognosis, or correlate with clinical remission. We employed single-cell RNA sequencing to catalog and compare the diversity of cells present in duodenal mucosal endoscopic biopsies from 3 healthy dogs and 4 dogs with CIE. Through characterization of 35,668 cells, we identified 31 transcriptomically distinct cell populations, including T cells, epithelial cells, and myeloid cells. Both healthy and CIE samples contributed to each cell population. T cells were broadly subdivided into GZMAhigh (putatively annotated as tissue resident) and IL7Rhigh (putatively annotated as non-resident) T cell categories, with evidence of a skewed proportion favoring an increase in the relative proportion of IL7Rhigh T cells in CIE dogs. Among the myeloid cells, neutrophils from CIE samples exhibited inflammatory (SOD2 and IL1A) gene expression signatures. Numerous differentially expressed genes were identified in epithelial cells, with gene set enrichment analysis suggesting enterocytes from CIE dogs may be undergoing stress responses and have altered metabolic properties. Overall, this work reveals the previously unappreciated cellular heterogeneity in canine duodenal mucosa and provides new insights into molecular mechanisms which may contribute to intestinal dysfunction in CIE. The cell type gene signatures developed through this study may also be used to better understand the subtleties of canine intestinal physiology in health and disease.","PeriodicalId":505785,"journal":{"name":"Frontiers in Immunology","volume":"6 7","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141355097","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":"Identification of drug targets for Sjögren’s syndrome: multi-omics Mendelian randomization and colocalization analyses","authors":"Yingjie Bai, Jiayi Wang, Xuefeng Feng, Le Xie, Shengao Qin, Guowu Ma, Fan Zhang","doi":"10.3389/fimmu.2024.1419363","DOIUrl":"https://doi.org/10.3389/fimmu.2024.1419363","url":null,"abstract":"Targeted therapy for Sjögren’s syndrome (SS) has become an important focus for clinicians. Multi-omics-wide Mendelian randomization (MR) analyses have provided new ideas for identifying potential drug targets.We conducted summary-data-based Mendelian randomization (SMR) analysis to evaluate therapeutic targets associated with SS by integrating DNA methylation, gene expression and protein quantitative trait loci (mQTL, eQTL, and pQTL, respectively). Genetic associations with SS were derived from the FinnGen study (discovery) and the GWAS catalog (replication). Colocalization analyses were employed to determine whether two potentially relevant phenotypes share the same genetic factors in a given region. Moreover, to delve deeper into potential regulation among DNA methylation, gene expression, and protein abundance, we conducted MR analysis to explore the causal relationship between candidate gene methylation and expression, as well as between gene expression and protein abundance. Drug prediction and molecular docking were further employed to validate the pharmacological activity of the candidate drug targets.Upon integrating the multi-omics data, we identified three genes associated with SS risk: TNFAIP3, BTN3A1, and PLAU. The methylation of cg22068371 in BTN3A1 was positively associated with protein levels, consistent with the negative effect of cg22068371 methylation on the risk of SS. Additionally, positive correlations were observed between the gene methylation of PLAU (cg04939496) and expression, as well as between expression and protein levels. This consistency elucidates the promotional effects of PLAU on SS risk at the DNA methylation, gene expression, and protein levels. At the protein level, genetically predicted TNFAIP3 (OR 2.47, 95% CI 1.56–3.92) was positively associated with SS risk, while BTN3A1 (OR 2.96E-03, 95% CI 2.63E-04–3.33E-02) was negatively associated with SS risk. Molecular docking showed stable binding for candidate drugs and target proteins.Our study reveals promising therapeutic targets for the treatment of SS, providing valuable insights into targeted therapy for SS. However, further validation through future experiments is warranted.","PeriodicalId":505785,"journal":{"name":"Frontiers in Immunology","volume":"40 10","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141353358","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":"Soluble antigen arrays provide increased efficacy and safety over free peptides for tolerogenic immunotherapy","authors":"Rebuma Firdessa-Fite, Stephanie N. Johnson, Camillo Bechi Genzano, Martin A Leon, Amy Ku, Fernando A. Ocampo Gonzalez, Joshua D. Milner, J. Sestak, Cory Berkland, R. Creusot","doi":"10.3389/fimmu.2024.1258369","DOIUrl":"https://doi.org/10.3389/fimmu.2024.1258369","url":null,"abstract":"Autoantigen-specific immunotherapy using peptides offers a more targeted approach to treat autoimmune diseases, but clinical implementation has been challenging. We previously showed that multivalent delivery of peptides as soluble antigen arrays (SAgAs) efficiently protects against spontaneous autoimmune diabetes in the non-obese diabetic (NOD) mouse model. Here, we compared the efficacy, safety, and mechanisms of action of SAgAs versus free peptides. SAgAs, but not their corresponding free peptides at equivalent doses, efficiently prevented the development of diabetes. SAgAs increased the frequency of regulatory T cells among peptide-specific T cells or induce their anergy/exhaustion or deletion, depending on the type of SAgA used (hydrolysable (hSAgA) and non-hydrolysable ‘click’ SAgA (cSAgA)) and duration of treatment, whereas their corresponding free peptides induced a more effector phenotype following delayed clonal expansion. Over time, the peptides induced an IgE-independent anaphylactic reaction, the incidence of which was significantly delayed when peptides were in SAgA form rather than in free form. Moreover, the N-terminal modification of peptides with aminooxy or alkyne linkers, which was needed for grafting onto hyaluronic acid to make hSAgA or cSAgA variants, respectively, influenced their stimulatory potency and safety, with alkyne-functionalized peptides being more potent and less anaphylactogenic than aminooxy-functionalized peptides. Immunologic anaphylaxis occurred in NOD mice in a dose-dependent manner but not in C57BL/6 or BALB/c mice; however, its incidence did not correlate with the level of anti-peptide antibodies. We provide evidence that SAgAs significantly improve the efficacy of peptides to induce tolerance and prevent autoimmune diabetes while at the same time reducing their anaphylactogenic potential.","PeriodicalId":505785,"journal":{"name":"Frontiers in Immunology","volume":"54 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141353265","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":"Editorial: Advances in the management of tuberculosis meningitis","authors":"S. Subbian, Vishwanath Venketaraman","doi":"10.3389/fimmu.2024.1433345","DOIUrl":"https://doi.org/10.3389/fimmu.2024.1433345","url":null,"abstract":"","PeriodicalId":505785,"journal":{"name":"Frontiers in Immunology","volume":"30 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141353765","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":"Air pollution accelerates the development of obesity and Alzheimer’s disease: the role of leptin and inflammation - a mini-review","authors":"C. Campolim, Bianca Camilo Schimenes, Mariana Matera Veras, Young-Bum Kim, Patricia Oliveira Prada","doi":"10.3389/fimmu.2024.1401800","DOIUrl":"https://doi.org/10.3389/fimmu.2024.1401800","url":null,"abstract":"Air pollution is an urgent concern linked to numerous health problems in low- and middle-income countries, where 92% of air pollution-related deaths occur. Particulate matter 2.5 (PM2.5) is the most harmful component of air pollutants, increasing inflammation and changing gut microbiota, favoring obesity, type 2 diabetes, and Alzheimer’s Disease (AD). PM2.5 contains lipopolysaccharides (LPS), which can activate the Toll-like receptor 4 (TLR4) signaling pathway. This pathway can lead to the release of pro-inflammatory markers, including interleukins, and suppressor of cytokine signaling-3 (SOCS3), which inhibits leptin action, a hormone that keeps the energy homeostasis. Leptin plays a role in preventing amyloid plaque deposition and hyperphosphorylation of tau-protein (p-tau), mechanisms involved in the neurodegeneration in AD. Approximately 50 million people worldwide are affected by dementia, with a significant proportion living in low—and middle-income countries. This number is expected to triple by 2050. This mini-review focuses on the potential impact of PM2.5 exposure on the TLR4 signaling pathway, its contribution to leptin resistance, and dysbiosis that exacerbates the link between obesity and AD.","PeriodicalId":505785,"journal":{"name":"Frontiers in Immunology","volume":"95 24","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141352585","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":"Elucidating the molecular landscape of tendinitis: the role of inflammasome-related genes and immune interactions","authors":"Hongwei Xu, Xiao-lang Lu, Yang Yu, Yifei Zhou, Tengfei Qi, Yi-jing Zheng","doi":"10.3389/fimmu.2024.1393851","DOIUrl":"https://doi.org/10.3389/fimmu.2024.1393851","url":null,"abstract":"Tendinitis, characterized by the inflammation of tendons, poses significant challenges in both diagnosis and treatment due to its multifaceted etiology and complex pathophysiology. This study aimed to dissect the molecular mechanisms underlying tendinitis, with a particular focus on inflammasome-related genes and their interactions with the immune system. Through comprehensive gene expression analysis and bioinformatics approaches, we identified distinct expression profiles of inflammasome genes, such as NLRP6, NLRP1, and MEFV, which showed significant correlations with immune checkpoint molecules, indicating a pivotal role in the inflammatory cascade of tendinitis. Additionally, MYD88 and CD36 were found to be closely associated with HLA family molecules, underscoring their involvement in immune response modulation. Contrary to expectations, chemokines exhibited minimal correlation with inflammasome genes, suggesting an unconventional inflammatory pathway in tendinitis. Transcription factors like SP110 and CREB5 emerged as key regulators of inflammasome genes, providing insight into the transcriptional control mechanisms in tendinitis. Furthermore, potential therapeutic targets were identified through the DGidb database, highlighting drugs that could modulate the activity of inflammasome genes, offering new avenues for targeted tendinitis therapy. Our findings elucidate the complex molecular landscape of tendinitis, emphasizing the significant role of inflammasomes and immune interactions, and pave the way for the development of novel diagnostic and therapeutic strategies.","PeriodicalId":505785,"journal":{"name":"Frontiers in Immunology","volume":"04 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141359029","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":"Immune checkpoint inhibitors in colorectal cancer: limitation and challenges","authors":"Suying Yan, Wanting Wang, Zhiqiang Feng, Jun Xue, Weizheng Liang, Xueliang Wu, Zhiquan Tan, Xipeng Zhang, Shuai Zhang, Xichuan Li, Chunze Zhang","doi":"10.3389/fimmu.2024.1403533","DOIUrl":"https://doi.org/10.3389/fimmu.2024.1403533","url":null,"abstract":"Colorectal cancer exhibits a notable prevalence and propensity for metastasis, but the current therapeutic interventions for metastatic colorectal cancer have yielded suboptimal results. ICIs can decrease tumor development by preventing the tumor’s immune evasion, presenting cancer patients with a new treatment alternative. The increased use of immune checkpoint inhibitors (ICIs) in CRC has brought several issues. In particular, ICIs have demonstrated significant clinical effectiveness in patients with MSI-H CRC, whereas their efficacy is limited in MSS. Acquired resistance can still occur in patients with a positive response to ICIs. This paper describes the efficacy of ICIs currently in the clinical treatment of CRC, discusses the mechanisms by which acquired resistance occurs, primarily related to loss and impaired presentation of tumor antigens, reduced response of IFN-λ and cytokine or metabolic dysregulation, and summarizes the incidence of adverse effects. We posit that the future of ICIs hinges upon the advancement of precise prediction biomarkers and the implementation of combination therapies. This study aims to elucidate the constraints associated with ICIs in CRC and foster targeted problem-solving approaches, thereby enhancing the potential benefits for more patients.","PeriodicalId":505785,"journal":{"name":"Frontiers in Immunology","volume":"76 12","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141357959","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}