Clinical and experimental immunology最新文献

{"title":"Thymic stromal lymphopoietin as a therapeutic target in patients with chronic rhinosinusitis and nasal polyps.","authors":"Anju T Peters, Joseph K Han, Enrico Heffler, Freyja McClenahan, Scott Caveney, Tham T Le, Ayman Megally, Joseph D Spahn, Andrew Foster, Joseph D Sherrill","doi":"10.1093/cei/uxaf041","DOIUrl":"10.1093/cei/uxaf041","url":null,"abstract":"<p><p>Chronic rhinosinusitis with nasal polyps (CRSwNP) is an inflammatory disorder of the sinonasal mucosa, predominantly characterized by epithelial dysfunction and chronic heterogeneous mucosal inflammation. CRSwNP and asthma are common comorbidities with overlapping pathophysiology, epithelial impairment, and activation of downstream type 2 inflammation. Thymic stromal lymphopoietin (TSLP) is an epithelial cytokine that sits at the top of the immunological cascade and initiates and amplifies type 2-dependent and -independent inflammatory responses. Although the role of TSLP in asthma has been well described, the role of TSLP in CRSwNP has yet to be comprehensively outlined. This review examines the evidence for TSLP as a key factor in CRSwNP pathogenesis. We explore what is known about TSLP expression patterns within the sinonasal mucosa, finding that TSLP expression is increased in patients with CRSwNP compared with healthy patients, and in eosinophilic- versus non-eosinophilic CRSwNP. We discuss the impact of environmental triggers and genetic factors on TSLP expression and activity, as well as other upstream regulators of TSLP signaling. We then consider the known mechanisms and effects of TSLP signaling on the recruitment and activation of various immune and structural cell types in CRSwNP. Finally, we consider the available evidence on the therapeutic potential of targeting TSLP signaling for the treatment of CRSwNP and discuss ongoing trials of promising therapeutic candidates.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12449146/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145014026","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expression of Concern: Porins and lipopolysaccharide (LPS) from Salmonella typhimurium induce leucocyte transmigration through human endothelial cells in vitro.","authors":"","doi":"10.1093/cei/uxaf021","DOIUrl":"https://doi.org/10.1093/cei/uxaf021","url":null,"abstract":"","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":"219 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12060006/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143978953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intrinsic functional defects in B cells of patients with NFKB2 mutations.","authors":"Qing Min, Yaxuan Li, Xuzhe Wu, Meiping Yu, Wenjing Ying, Qinhua Zhou, Jia Hou, Bijun Sun, Xiaoying Hui, Lulu Dong, Xin Meng, Hai Zhang, Ziying Hu, Xiaoqian Feng, Jinqiao Sun, Wenjie Wang, Xiaochuan Wang, Ji-Yang Wang","doi":"10.1093/cei/uxae090","DOIUrl":"10.1093/cei/uxae090","url":null,"abstract":"<p><p>Mutations in the human nuclear factor-κB2 gene (NFKB2) are associated with common variable immunodeficiency (CVID) or combined immunodeficiency diseases (CID), characterized by B-cell lymphopenia, hypogammaglobulinemia, and T-cell dysfunction. This study investigated whether B cells with NFKB2 mutations exhibit intrinsic impairments in activation, class-switch recombination, and differentiation. We analyzed five patients from four unrelated families with CVID, each carrying a heterozygous NFKB2 mutation: P1 (C.2595_2614del, p.A867Gfs*12), P2 (C.2597G > A, p.S866N), P3 (C.2540dupT, p.R848Efs*38), and P4 and P5 (C.2570_2571insCAGCACA, p.A860Qfs*28). The patients with frameshift mutations (P1, P3, P4, and P5) exhibited truncated proteins detectable in their peripheral blood mononuclear cells, while P2 had a missense mutation. All identified mutations disrupted the processing of p100 into the active p52 form, resulting in NF-κB2 loss of function and IκBδ gain of function. Clinically, P1, P2, and P3 exhibited B-cell lymphopenia, and all five patients presented with hypogammaglobulinemia. Notably, P2 exhibited a markedly low B-cell count, associated with increased proportions of memory B and IgD-CD27- double-negative B cells. In vitro experiments with naïve B cells from P1 and P4 demonstrated decreased survival, impaired activation, and reduced differentiation into CD27+IgD- cells and plasmablasts, while class-switch recombination was unaffected. These findings reveal novel B-cell intrinsic functional defects in patients with NFKB2 mutations.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11773609/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Essential role of interferon-regulatory factor 4 in regulating diabetogenic CD4+ T and innate immune cells in autoimmune diabetes in NOD mice.","authors":"Tetsuro Niri, Shin-Ichi Inoue, Satoru Akazawa, Shinpei Nishikido, Masaki Miwa, Masakazu Kobayashi, Katsuyuki Yui, Minoru Okita, Atsushi Kawakami, Norio Abiru","doi":"10.1093/cei/uxae093","DOIUrl":"10.1093/cei/uxae093","url":null,"abstract":"<p><p>Haploinsufficiency of the transcription factor interferon-regulatory factor 4 (IRF4) prevents the onset of spontaneous diabetes in NOD mice. However, the immunological mechanisms of the IRF4-mediated disease regulation remain unclear. This study aims to investigate the role of IRF4 in the pathogenesis of autoimmune diabetes by conducting adoptive transfer experiments using donor IRF4 gene-deficient CD4+ T cells from BDC2.5-transgenic (Tg) NOD mice and recipient Rag1-knockout NOD mice, respectively. Through this approach, we analyzed both clinical and immunological phenotypes of the recipient mice. Additionally, IRF4-deficient BDC2.5 CD4+ T cells were stimulated to assess their immunological and metabolic phenotypes in vitro. The findings revealed that diabetes was completely prevented in the recipients with Irf4-/- T cells and was approximately 50% lower in those with Irf4+/- T cells than in wild type (WT) controls, whereas Irf4-/- recipients with WT T cells only showed a delayed onset of diabetes. Islet-infiltrating T cells isolated from recipients with Irf4+/- T cells exhibited significantly lower proliferation and IFN-γ/IL-17 double-positive cell fraction rates compared with those in WT controls. Irf4-/- BDC2.5 CD4+ T cells stimulated in vitro showed a reduced number of cell divisions, decreased antigen-specific T-cell markers, and impairment of glycolytic capacity compared with those observed in WT controls. We concluded that IRF4 predominantly regulates the diabetogenic potential in a dose-dependent manner by mediating the proliferation and differentiation of islet-infiltrating T cells while playing an adjunctive role in the innate immune responses toward diabetes progression in NOD mice.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11773818/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expression of sPD-L1 levels in an ex vivo liver perfusion model.","authors":"Christian Irsara, Annemarie Weissenbacher, Felix Julius Krendl, Markus Anliker, Julia Hofmann, Theresa Hautz, Stefan Schneeberger, Andrea Griesmacher, Lorin Loacker","doi":"10.1093/cei/uxae094","DOIUrl":"10.1093/cei/uxae094","url":null,"abstract":"<p><p>The programmed cell death protein 1 (PD-1) acts as a central inhibitory immune checkpoint receptor. The soluble form of its primary ligand, sPD-L1, was found to be elevated in the serum of patients with cancer, infectious diseases, and chronic inflammation. So far, the hepatic origin of sPD-L1 has received relatively little attention and is therefore the subject of this study in the context of normothermic machine perfusion (NMP) of liver grafts. sPD-L1 concentrations as well as several well-established clinically relevant laboratory parameters were determined in the perfusate of 16 donor liver grafts undergoing NMP up to 30 hours. sPD-L1 levels continuously increased during NMP and significantly correlated with markers of hepatic synthesis (cholinesterase), acute-phase proteins (von Willebrand factor, procalcitonin, antithrombin, interleukin-6, fibrinogen), and liver decay markers (gamma-glutamyltransferase, alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase). Perfusate leukocytes were in the lower reference range and decreased after 12 hours. Mean sPD-L1 levels in the perfusate correlated with donor levels of gamma-glutamyltransferase, alanine aminotransferase, creatinine, and blood urea nitrogen. Our study reveals a significant increase in the concentration of sPD-L1 following ischemia-reperfusion injury in a hepatic ex vivo model. sPD-L1 concentrations during NMP correlate with established acute-phase proteins and liver cell decay markers, suggesting that hepatic sPD-L1 synthesis or shedding increases during the acute phase and cell decay. Furthermore, sPD-L1 correlates with established liver function and synthesis parameters as well as with donor laboratory values and might therefore be a potential biomarker for the hepatic function of liver grafts.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11773811/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"T cells immune imbalance presents in patients with multiple intracranial aneurysms.","authors":"Chuming Tao, Chenglong Liu, Peicong Ge, Liujia Chan, Yuheng Pang, Junsheng Li, Qiheng He, Wei Liu, Siqi Mou, Zhiyao Zheng, Bojian Zhang, Zhikang Zhao, Wei Sun, Qian Zhang, Rong Wang, Yan Zhang, Wenjing Wang, Dong Zhang, Jizong Zhao","doi":"10.1093/cei/uxae058","DOIUrl":"10.1093/cei/uxae058","url":null,"abstract":"<p><p>Growing evidence suggests that systemic immune and inflammatory responses may play a critical role in the formation and development of aneurysms. Exploring the differences between single intracranial aneurysm (SIA) and multiple IAs (MIAs) could provide insights for targeted therapies. However, there is a lack of comprehensive and detailed characterization of changes in circulating immune cells in MIAs. Peripheral blood mononuclear cell (PBMC) samples from patients with SIA (n = 16) or MIAs (n = 6) were analyzed using high-dimensional mass cytometry to evaluate the frequency and phenotype of immune cell subtypes. A total of 25 cell clusters were identified, revealing that the immune signature of MIAs included cluster changes. Compared to patients with SIA, patients with MIAs exhibited immune dysfunction and regulatory imbalance in T-cell clusters. They also had reduced numbers of CD8+ T cells and their subgroups CD8+ Te and CD8+ Tem cells, as well as reduced numbers of the CD4+ T-cell subgroup CD27-CD4+ Tem cells. Furthermore, compared to SIA, MIAs were associated with enhanced T-cell immune activation, with elevated expression levels of CD3, CD25, CD27, CCR7, GP130, and interleukin 10. This study provides insights into the circulating immune cell profiles in patients with MIAs, highlighting the similarities and differences between patients with SIA and those with MIAs. Furthermore, the study suggests that circulating immune dysfunction may contribute to the development of MIAs.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11771201/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141589763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi-dimensional analysis of B cells reveals the expansion of memory and regulatory B-cell clusters in humans living in rural tropical areas.","authors":"Mathilde A M Chayé, Oscar R J van Hengel, Astrid L Voskamp, Arifa Ozir-Fazalalikhan, Marion H König, Koen A Stam, Mikhael D Manurung, Yoanne D Mouwenda, Yvonne A Aryeetey, Agnes Kurniawan, Yvonne C M Kruize, Erliyani Sartono, Anne-Marie Buisman, Maria Yazdanbakhsh, Tamar Tak, Hermelijn H Smits","doi":"10.1093/cei/uxae074","DOIUrl":"10.1093/cei/uxae074","url":null,"abstract":"<p><p>B-cells play a critical role in the formation of immune responses against pathogens by acting as antigen-presenting cells, by modulating immune responses, and by generating immune memory and antibody responses. Here, we studied B-cell subset distributions between regions with higher and lower microbial exposure, i.e. by comparing peripheral blood B-cells from people living in Indonesia or Ghana to those from healthy Dutch residents using a 36-marker mass cytometry panel. By applying an unbiased multidimensional approach, we observed differences in the balance between the naïve and memory compartments, with higher CD11c+ and double negative (DN-IgDnegCD27neg) memory (M)B-cells in individuals from rural tropical areas, and conversely lower naïve B-cells compared to residents from an area with less pathogen exposure. Furthermore, characterization of total B-cell populations, CD11c+, DN, and Breg cells showed the emergence of specific memory clusters in individuals living in rural tropical areas. Some of these differences were more pronounced in children compared to adults and suggest that a higher microbial exposure accelerates memory B-cell formation, which \"normalizes\" with age.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11771192/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141916227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of neutrophils in allergic disease.","authors":"James Trayer, Johana Isaza-Correa, Lynne Kelly, Maeve Kelleher, Jonathan Hourihane, Aideen Byrne, Eleanor Molloy","doi":"10.1093/cei/uxae126","DOIUrl":"10.1093/cei/uxae126","url":null,"abstract":"<p><p>Neutrophils are short-lived cells of the innate immune system and represent 50-70% of the circulating leucocytes. Their primary role is antimicrobial defence which they accomplish through rapid migration to sites of inflammation followed by phagocytosis, degranulation, and the release of neutrophil extracellular traps (NETosis). While previously considered terminally differentiated cells, they have been shown to have great adaptability and to play a role in conditions ranging from cancer to autoimmunity. This review focuses on their role in allergic disease. In particular: their role as potential amplifiers of type 1 hypersensitivity reactions leading to anaphylaxis; their involvement in alternative pathways of food and drug allergy; their role in allergic rhinitis and asthma and neutrophil dysfunction in atopic dermatitis. The use of potential biomarkers and therapeutic targets is also discussed with a view to guiding future research.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11747999/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142892592","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discovery and experimentally mice model validation of CFI, a natural killer T cell-related gene, as a key biomarker in osteoarthritis.","authors":"Xueliang Han, Shujing Tan, Bencai Du, Jian Liu, Lianjun Qu","doi":"10.1093/cei/uxaf054","DOIUrl":"10.1093/cei/uxaf054","url":null,"abstract":"<p><p>We attempted to perform a comprehensive bioinformatics analysis on osteoarthritis (OA) based on the NKT-related genes and explore the clinically related critical genes. Differentially expressed genes (DEGs) and NKT-related genes from WGCNA were obtained using the dataset GSE114007, followed by intersection analysis to obtain NKT-related DEGs. Lasso regression, support vector machine, and random forest were performed to screen feature genes, followed by verification with receiver operator curves and a nomogram model. Protein-protein interaction network, gene set enrichment analysis was performed based on the four marker genes. Finally, the immune infiltration of 64 types of immune cells was analyzed between OA samples and normal samples. The significance of biomarkers was validated in clinical samples and OA mice models. A total of four NKT-related biomarker genes (CCNJ, CFI, PREX2, and SMIM13) were identified. These genes were all upregulated in OA samples. CFI exerted promising diagnostic value for OA with an AUC of 0.994 in GSE114007 training dataset and 0.98 in the validation dataset. A significantly negative correlation between CFI and NKT cells and a significantly positive correlation between CFI and conventional dendritic cells (cDC) were found. All the biomarkers were determined to be upregulated in OA patients by clinical samples. CFI knockdown significantly reduced DC infiltration and inflammation in the knee joints of OA mice models. CFI has potential value in the pathogenesis of OA and can be used as a candidate biomarker for OA diagnosis and treatment.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12449135/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145014001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Senolytic treatment to rescue hallmarks of senescence in lymph node fibroblasts from patients with rheumatoid arthritis: Implications for premature aging and potential therapeutic intervention in early rheumatoid arthritis.","authors":"T A de Jong, J F Semmelink, J W Bolt, C Grasso, R A Hoebe, P M Krawczyk, L G M van Baarsen","doi":"10.1093/cei/uxaf029","DOIUrl":"10.1093/cei/uxaf029","url":null,"abstract":"<p><p>Cellular senescence, a state of proliferation arrest, is implicated in the pathogenesis of age-related diseases such as rheumatoid arthritis (RA). The pathogenesis of RA, characterized by immune dysregulation and systemic autoimmunity preceding clinical onset of disease, may involve early accumulation of senescent lymph node (LN) fibroblasts driving immune tolerance breakdown. This study aims to explore the hallmarks of senescence in LN fibroblasts during the earliest phases of RA and evaluate the effects of dasatinib. Human LN fibroblasts were isolated from inguinal LN needle biopsies from autoantibody-positive individuals at risk of developing RA (RA-risk individuals), RA patients, and seronegative healthy volunteers. Senescence hallmarks and the effects of dasatinib treatment were assessed using quantitative gene expression analysis, flow cytometry, microscopy, and live-cell imaging. Cell size, granularity, and autofluorescence were significantly greater in RA LN fibroblasts compared with controls. Altered gene expression of senescence-associated genes was observed in RA LN fibroblasts. Elevated senescence-associated β-galactosidase activity, more lipofuscin-positive granules, and DNA damage were observed in RA-risk and RA LN fibroblasts. Notably, RA(-risk) LN fibroblasts presented impaired DNA damage repair capacity. Dasatinib treatment significantly improved the size and ability of the LN fibroblast pool to repair DNA damage. We observed multiple senescence hallmarks in RA LN fibroblasts and, to a lesser extent, in RA-risk LN fibroblasts, which could be partially restored by senescent cell removal via dasatinib treatment. These findings suggest a role for senescent LN fibroblasts in RA pathogenesis and highlight the potential of dasatinib as a potential therapeutic intervention to mitigate senescence-associated defects in RA.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12188290/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143983773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}