JCI insight最新文献

{"title":"Glucagon-like peptide-1 receptor agonism improves lung cancer outcomes and tumor growth control.","authors":"Akhil Goud Pachimatla, Bailey Fitzgerald, Joyce Ogidigo, Meera Bhatia, Randall J Smith, Kalyan Ratnakaram, Sukumar Kalvapudi, Yeshwanth Vedire, Deschana Washington, Robert Vethanayagam Rr, Hua-Hsin Hsiao, Spencer Rosario, Viraj R Sanghvi, Joseph Barbi, Sai Yendamuri","doi":"10.1172/jci.insight.195484","DOIUrl":"10.1172/jci.insight.195484","url":null,"abstract":"<p><strong>Background: </strong>Emerging evidence indicates a reduced incidence of multiple cancers in users of glucagon-like peptide-1 receptor agonists (GLP-1RAs), drugs widely used for glycemic control and weight reduction that modulate several key regulators of metabolism. We sought to examine their association with non-small cell lung cancer (NSCLC) outcomes in overweight and obese patients and gain mechanistic insights from mouse models.</p><p><strong>Methods: </strong>Two clinical cohorts of overweight and obese patients with NSCLC - one undergoing surgical resection (n = 1,177, 71 GLP-1RA users) and another receiving immune checkpoint inhibitors (n = 300, 10 GLP-1RA users), were propensity score matched for relevant covariates and analyzed for clinical outcomes.</p><p><strong>Results: </strong>GLP-1RA use was associated with increased recurrence-free survival in overweight and obese patients (HR: 0.41, 95% CI: 0.16-1.04, P = 0.026) after lobectomy. GLP-1RA treatment reduced tumor burden in obese but not normal-weight mice and altered the frequency and phenotypes of leukocyte populations and gene expression patterns in obese tumors, crucial to cancer progression and antitumor immunity. Concurrent GLP-1RA and immunotherapy was also associated with improved overall (HR: 0.41, 95% CI: 0.16-1.01, P = 0.027) and progression-free survival (HR: 0.31, 95% CI: 0.10-0.94, P = 0.019) for patients with advanced NSCLC.</p><p><strong>Conclusions: </strong>In our cohort, GLP-1RAs enhanced lung cancer-specific clinical outcomes and augment immunotherapy efficacy. Preclinical evidence suggested this effect to be obesity restricted and mediated by immune modulation of the tumor microenvironment.</p><p><strong>Funding: </strong>George Duke, Department of Defense (W81XWH-21-1-0377), NIH/NIGMS (GM147497), American Cancer Society (RSG-22-071-01-TBE), NIH (1R01 CA255515-01A1), NIH/NCI (P30CA013696 and P30CA016056).</p>","PeriodicalId":14722,"journal":{"name":"JCI insight","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12513478/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144954743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NaCl and urea modulate CD8+ T cell survival, renal accumulation, and response to BK virus.","authors":"Peyman Falahat, Adrian Goldspink, Lucia Oehler, Jessica Schmitz, Julia Miranda, Islem Gammoudi, Jan Hinrich Bräsen, Niklas Klümper, Olena Babyak, Christian Kurts, Herrmann Haller, Marieta Toma, Sibylle von Vietinghoff","doi":"10.1172/jci.insight.194570","DOIUrl":"10.1172/jci.insight.194570","url":null,"abstract":"<p><p>BK virus nephropathy is a severe, graft-threatening complication of kidney transplantation that requires an effective T cell response. It typically emerges in the kidney medulla. Elevated osmolyte concentrations that dynamically respond to loop diuretic therapy characterize this environment. Here, BK viremia development in kidney graft recipients negatively correlated with loop diuretic therapy. The association remained significant in multivariable and propensity score-matched analyses. Kidney function was better preserved and CD8+ T cell abundance higher in loop diuretic-exposed allografts. CD8+ T cell densities in healthy human and murine kidney medulla were lower than in cortex and increased upon loop diuretic therapy in mice. As a potential underlying mechanism, kidney medullary NaCl and urea concentrations decreased primary human CD8+ T cell numbers in vitro by induction of cell death and limitation of proliferation, respectively. Both osmolytes downregulated interferon-related gene expression. NaCl induced p53-dependent apoptosis and upregulated Na+-transporter SLC38A2, which promoted caspase-3 activation. Both decreased T cell response and cytokine secretion in response to viral peptide and allogeneic tubular epithelial cell killing, components of anti-BK virus response in the kidney allograft. Our results propose osmolyte-mediated mitigation of CD8+ T cell function as a what we believe to be novel mechanism that impairs immune response to BK virus, the therapeutic potential of which is testable.</p>","PeriodicalId":14722,"journal":{"name":"JCI insight","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12513482/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144954692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigenetic programming of estrogen receptor in adipocytes by high-fat diet regulates obesity-induced inflammation.","authors":"Rui Wu, Fenfen Li, Shirong Wang, Jia Jing, Xin Cui, Yifei Huang, Xucheng Zhang, Jose A Carrillo, Zufeng Ding, Jiuzhou Song, Liqing Yu, Huidong Shi, Bingzhong Xue, Hang Shi","doi":"10.1172/jci.insight.173423","DOIUrl":"10.1172/jci.insight.173423","url":null,"abstract":"<p><p>Adipose inflammation plays a key role in obesity-induced metabolic abnormalities. Epigenetic regulation, including DNA methylation, is a molecular link between environmental factors and complex diseases. Here we found that high-fat diet (HFD) feeding induced a dynamic change of DNA methylome in mouse white adipose tissue (WAT) analyzed by reduced representative bisulfite sequencing. Interestingly, DNA methylation at the promoter of estrogen receptor α (Esr1) was significantly increased by HFD, concomitant with a downregulation of Esr1 expression. HFD feeding in mice increased the expression of DNA methyltransferase 1 (Dnmt1) and Dnmt3a and binding of DNMT1 and DNMT3a to Esr1 promoter in WAT. Mice with adipocyte-specific Dnmt1 deficiency displayed increased Esr1 expression, decreased adipose inflammation, and improved insulin sensitivity upon HFD challenge; mice with adipocyte-specific Dnmt3a deficiency showed a mild metabolic phenotype. Using a modified CRISPR/RNA-guided system to specifically target DNA methylation at the Esr1 promoter in WAT, we found that reducing DNA methylation at Esr1 promoter increased Esr1 expression, decreased adipose inflammation, and improved insulin sensitivity in HFD-challenged mice. Our study demonstrated that DNA methylation at Esr1 promoter played an important role in regulating adipose inflammation, which may contribute to obesity-induced insulin resistance.</p>","PeriodicalId":14722,"journal":{"name":"JCI insight","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12513496/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144954719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-cell spatial transcriptomics unravels the cellular landscape of abdominal aortic aneurysm.","authors":"Guizhen Zhao, Chun-Seok Cho, Hongyu Liu, Yongha Hwang, Yichen Si, Myungjin Kim, Yongjie Deng, Yang Zhao, Chao Xue, Yanhong Guo, Lin Chang, Dogukan Mizrak, Bo Yang, Hyun Min Kang, Jifeng Zhang, Jun Hee Lee, Y Eugene Chen","doi":"10.1172/jci.insight.190534","DOIUrl":"10.1172/jci.insight.190534","url":null,"abstract":"<p><p>Abdominal aortic aneurysm (AAA) is a life-threatening vascular disease with no effective pharmacological interventions. While single-cell transcriptomics has advanced our understanding of AAA, it lacks spatial context. Here, we employed Seq-Scope, an ultra-high-resolution spatial transcriptomic technology, to decipher the spatial landscape of angiotensin II-induced AAA in Apoe-/- mice. Our analysis revealed the heterogeneity of macrophages, fibroblasts, and smooth muscle cells (SMCs), with specific responses in different layers of the AAA tissue. SMCs in the inner layers showed associations with Mgp-expressing fibroblasts and GPNMB-expressing macrophages, whereas the outer layers had different dominant cell types. Notably, GPNMB-expressing macrophages were concentrated near SMCs in regions of severe elastic lamina damage. Immunofluorescent staining confirmed their colocalization, and scRNA-seq reanalysis independently validated the presence of GPNMB-high macrophages in AAA tissues, highlighting their involvement in inflammation and tissue remodeling. Moreover, we discovered that macrophage-derived soluble GPNMB induces SMC phenotypic switching, reducing contractile markers while increasing cytokines and metalloproteinases. This effect was partly mediated by CD44 signaling. These findings suggest that GPNMB-high macrophages contribute to AAA development by driving SMC dysfunction. This study highlights the importance of high-resolution spatial transcriptomics in complementing single-cell transcriptomics, offering valuable insights into molecular and cellular responses in the AAA microenvironment.</p>","PeriodicalId":14722,"journal":{"name":"JCI insight","volume":"10 16","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12406718/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144954710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting pyruvate metabolism generates distinct CD8+ T cell responses to gammaherpesvirus and B lymphoma.","authors":"Taewook Kang, Young-Kwang Usherwood, Julie A Reisz, Sukrut C Kamerkar, Rachel Culp-Hill, Owen M Wilkins, Andreia F Verissimo, Fred W Kolling, Anton M Hung, Shawn C Musial, Pamela C Rosato, Angelo D'Alessandro, Henry N Higgs, Edward J Usherwood","doi":"10.1172/jci.insight.187680","DOIUrl":"10.1172/jci.insight.187680","url":null,"abstract":"<p><p>T cells rely on different metabolic pathways to differentiate into effector or memory cells, and metabolic intervention is a promising strategy to optimize T cell function for immunotherapy. Pyruvate dehydrogenase (PDH) is a nexus between glycolytic and mitochondrial metabolism, regulating pyruvate conversion to either lactate or acetyl-CoA. Here, we retrovirally transduced pyruvate dehydrogenase kinase 1 (PDK1) or pyruvate dehydrogenase phosphatase 1 (PDP1), which control PDH activity, into CD8+ T cells to test effects on T cell function. Although PDK1 and PDP1 were expected to influence PDH in opposing directions, by several criteria they induced similar changes relative to control T cells. Seahorse metabolic flux assays showed both groups exhibited increased glycolysis and oxidative phosphorylation. Both groups had improved primary and memory recall responses following infection with murine gammaherpesvirus-68. However, metabolomics using labeled fuels indicated differential usage of key fuels by metabolic pathways. Importantly, CD8+ T cell populations after B cell lymphoma challenge were smaller in both groups, resulting in poorer protection, which was rescued by glutamine and acetate supplementation. Overall, this study indicates that PDK1 and PDP1 both enhance metabolic capacity, but the context of the antigenic challenge significantly influences the consequences for T cell function.</p>","PeriodicalId":14722,"journal":{"name":"JCI insight","volume":"10 16","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12406717/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144954741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deletion of SH2D5 alleviates epileptic seizures and NMDAR expression via autophagic degradation of STAT1.","authors":"Haokun Guo, Hui Zhang, Chenlu Zhang, Yuanyuan Shen, Liumi Jiang, Min Yang, Yuansong Zhang, Ningning Zhang, Ruirui Zhang, Ran Yu, Yong Yang, Xin Tian","doi":"10.1172/jci.insight.191347","DOIUrl":"10.1172/jci.insight.191347","url":null,"abstract":"<p><p>Epilepsy is a common neurological disorder resulting from an imbalance between neuronal excitation and inhibition. Synapses play a pivotal role in the pathogenesis of epilepsy. Src-homology 2 (SH2) domain-containing protein 5 (SH2D5) is highly expressed in the brain and is implicated in the regulation of synaptic function. However, its role and mechanism in epilepsy remain unclear. In this study, we found that SH2D5 was predominantly localized to pyramidal neurons in the mouse hippocampus and was upregulated in the hippocampus of epileptic brains. KO of Sh2d5 in the hippocampus alleviated both the susceptibility to and severity of epileptic activity. Mechanistically, SH2D5 regulated N-methyl-D-aspartate receptor-mediated (NMDAR-mediated) excitatory synaptic transmission by altering the protein expression levels of NMDAR subunits. We further demonstrated that SH2D5 modulated the transcription of NMDARs by promoting the autophagic degradation of STAT1. These findings suggest that targeting the SH2D5/STAT1/NMDAR pathway may offer a potential therapeutic strategy for epilepsy.</p>","PeriodicalId":14722,"journal":{"name":"JCI insight","volume":"10 16","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12406720/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144954723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The spleen tyrosine kinase inhibitor entospletinib resolves inflammation to promote repair following acute kidney injury.","authors":"Esteban E Elias, Arthur Lau, Sisay Getie Belay, Afshin Derakhshani, Graciela Andonegui, Craig N Jenne, Antoine Dufour, Nathan A Bracey, Justin Chun, Daniel A Muruve","doi":"10.1172/jci.insight.189601","DOIUrl":"10.1172/jci.insight.189601","url":null,"abstract":"<p><p>Nonresolving inflammation and maladaptive renal repair contribute to the pathogenesis of acute kidney injury (AKI) transition to chronic kidney disease (CKD). Few therapies have been identified that can modulate these injurious pathways following AKI. Spleen tyrosine kinase (SYK) is an immune regulator expressed in the kidney and a potential therapeutic target for AKI. The effect of the selective SYK inhibitor entospletinib was studied in AKI-to-CKD transition. Entospletinib was administered to mice undergoing unilateral renal ischemia-reperfusion injury (IRI), with kidneys analyzed over 14 days. Single-cell RNA sequencing, digital spatial profiling, intravital microscopy, and flow cytometry were employed to study renal phenotypes. Entospletinib administered before and after IRI protected ischemic kidneys and significantly attenuated the transition to CKD. Entospletinib targeted leukocyte-expressed SYK and prevented neutrophil/monocyte recruitment to the kidney. Entospletinib reduced nonresolving tubulointerstitial inflammation after AKI by blocking activation of mannose receptor-1- and C-type lectin domain family 7 member A-expressing proinflammatory macrophages. The resolution of renal inflammation mediated by entospletinib was associated with a reciprocal increase in resident macrophages, reparative gene expression, preserved tubular integrity, and reduced renal fibrosis. The SYK inhibitor entospletinib resolves renal inflammation and promotes repair following AKI.</p>","PeriodicalId":14722,"journal":{"name":"JCI insight","volume":"10 16","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12406726/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144954729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chronic-plus-binge alcohol intake induces production of proinflammatory mtDNA-enriched extracellular vesicles and steatohepatitis via ASK1/p38MAPKα-dependent mechanisms.","authors":"Jing Ma, Haixia Cao, Robim M Rodrigues, Mingjiang Xu, Tianyi Ren, Yong He, Seonghwan Hwang, Dechun Feng, Ruixue Ren, Peixin Yang, Suthat Liangpunsakul, Jian Sun, Bin Gao","doi":"10.1172/jci.insight.197929","DOIUrl":"10.1172/jci.insight.197929","url":null,"abstract":"","PeriodicalId":14722,"journal":{"name":"JCI insight","volume":"10 16","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12406712/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144954731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"B3GALT6 mutations lead to compromised connective tissue biomechanics in Ehlers-Danlos syndrome.","authors":"Roméo Milan Diana, Benjamin Jolivet, Jean-Baptiste Vincourt, Sébastien Hergalant, Grégory Francius, Yasaman Karami, Hamed Khakzad, Rebekka Wild, Marie Bourgeais, Anne Robert, Alison Wurtz, Guillermo Barreto, Nick Ramalanjaona, Déborah Helle, Rachel Onifarasoaniaina, Sophie Front, Chrystel Lopin-Bon, Delfien Syx, Fransiska Malfait, Sylvie Fournel-Gigleux, Sandrine Gulberti, Catherine Bui","doi":"10.1172/jci.insight.179474","DOIUrl":"10.1172/jci.insight.179474","url":null,"abstract":"<p><p>Ehlers-Danlos syndromes (EDS) comprise a genetically and clinically heterogenous group of rare diseases that cause severe, often fatal, damage to connective tissue. The molecular basis of EDS implicates defects in extracellular matrix components, including various fibrillar collagens and glycosaminoglycans (GAGs). However, the precise pathogenic mechanisms behind EDS remain elusive. Here, we have implemented a multi-tiered approach to demonstrate the functional impact of B3GALT6 mutations on biochemical and developmental processes, ultimately leading to the spondylodysplastic subtype of EDS (spEDS), characterized by severe musculoskeletal symptoms. We show that the loss of function of β1,3-galactosyltransferase 6 (β3GalT6) is partially compensated by β1,3-glucuronosyltransferase 3 (GlcAT-I), the next enzyme in the GAG biosynthetic pathway. In addition, results from transcriptomics, collagen analysis, and biophysical experiments revealed that impaired collagen maturation, including defective glycosylation of collagen XII, contributes to altered tissue structure and biomechanics, the hallmarks of spEDS. Our findings unravel a new pathogenic mechanism of spEDS and bring us one step closer to therapeutic strategies, including cell and tissue engineering.</p>","PeriodicalId":14722,"journal":{"name":"JCI insight","volume":"10 16","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12406734/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144954768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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 complement in long COVID pathogenesis.","authors":"Rafael Bayarri-Olmos, William Bain, Akiko Iwasaki","doi":"10.1172/jci.insight.194314","DOIUrl":"10.1172/jci.insight.194314","url":null,"abstract":"<p><p>Long COVID is a debilitating condition that can develop after a SARS-CoV-2 infection and is characterized by a wide range of chronic symptoms, including weakness, neurocognitive impairment, malaise, fatigue, and many others, that affect multiple organ systems. At least 10% of individuals with a previous infection may develop long COVID, which affects their ability to perform daily functions and work. Despite its severity and widespread impact, this multisystemic condition remains poorly understood. Recent studies suggest that dysregulation of the complement system, a key component of the innate immune response, may contribute to the pathogenesis of long COVID, particularly in connection with coagulation, inflammation, and vascular injury. In this Review, we examine the evidence linking complement system dysregulation to long COVID and explore its potential role in driving disease pathology.</p>","PeriodicalId":14722,"journal":{"name":"JCI insight","volume":"10 16","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12406719/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144954695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}