JCI insight最新文献

{"title":"ASCL1 regulates and cooperates with FOXA2 to drive terminal neuroendocrine phenotype in prostate cancer.","authors":"Shaghayegh Nouruzi, Takeshi Namekawa, Nakisa Tabrizian, Maxim Kobelev, Olena Sivak, Joshua M Scurll, Cassandra Jingjing Cui, Dwaipayan Ganguli, Amina Zoubeidi","doi":"10.1172/jci.insight.196861","DOIUrl":"10.1172/jci.insight.196861","url":null,"abstract":"","PeriodicalId":14722,"journal":{"name":"JCI insight","volume":"10 15","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12333938/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144804101","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":"NAT10-mediated ac4C modification of Lipin1 mRNA contributes to the pathogenesis of PWMI.","authors":"Xinyu Li, Meng Zhang, Yanan Liu, Chunjie Guo, Yiwei Liu, Lei Han, Zhaowei Feng, Xiue Wei, Ruiqin Yao","doi":"10.1172/jci.insight.193712","DOIUrl":"10.1172/jci.insight.193712","url":null,"abstract":"<p><p>Preterm white matter injury (PWMI) is a leading cause of cerebral palsy and chronic neurological disabilities in premature infants. It is characterized by defects in oligodendrocyte precursor cell (OPC) differentiation and dysmyelination. Currently, there are no effective therapeutic strategies available in clinical practice. Lipid homeostasis plays a crucial role in myelin development, yet the function of Lipin1 - a key phosphatidic acid phosphatase involved in phospholipid synthesis - remains unclear. In this study, we identified a significant downregulation of Lipin1 in OPCs from PWMI mice, which impaired OPC differentiation and myelin formation. Conversely, Lipin1 overexpression in these mice promoted OPC maturation and enhanced myelin development. We found evidence that N-acetyltransferase 10 (NAT10) acts as a regulator of Lipin1 expression through RNA pull-down and mass spectrometry. NAT10-mediated N4-acetylcytidine (ac4C) modification enhanced Lipin1 mRNA stability and translation, and NAT10 knockdown in OPCs impaired myelination, highlighting its crucial role in Lipin1-mediated myelination. Our study revealed that the downregulation of Lipin1 impaired OPC differentiation and myelination in PWMI, with NAT10-mediated ac4C modification playing a critical role in regulating Lipin1 expression. These findings highlight Lipin1 and NAT10 as promising therapeutic targets for treating myelination defects in PWMI, warranting further investigation into their potential in preterm birth-related neurological disorders.</p>","PeriodicalId":14722,"journal":{"name":"JCI insight","volume":"10 15","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12333955/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144804103","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":"STAC3 binding to CaV1.1 II-III loop is nonessential but critically supports skeletal muscle excitation-contraction coupling.","authors":"Wietske E Tuinte, Enikő Török, Petronel Tuluc, Fabiana Fattori, Adele D'Amico, Marta Campiglio","doi":"10.1172/jci.insight.191053","DOIUrl":"10.1172/jci.insight.191053","url":null,"abstract":"<p><p>Skeletal muscle excitation-contraction (EC) coupling depends on the direct coupling between CaV1.1 on the sarcolemma and ryanodine receptor (RyR1) on the sarcoplasmic reticulum. A key regulator of this process is STAC3, a protein essential for both the functional expression of CaV1.1 and its conformational coupling with RyR1. Mutations in Stac3 cause STAC3 disorder, a congenital myopathy characterized by muscle weakness. STAC3 interacts with CaV1.1 in 2 key regions: the II-III loop and the proximal C-terminus. While the II-III loop has been previously found to be essential for skeletal muscle EC coupling, here we demonstrated that the interaction between STAC3 and the proximal C-terminus is necessary and sufficient for CaV1.1 functional expression and minimal EC coupling. In contrast, the interaction with the II-III loop is not essential for EC coupling, though it plays a facilitating role in enhancing the process. Supporting this finding, we identified a patient with STAC3 disorder carrying a mutation that deletes the domain of STAC3 involved in the II-III loop interaction. Collectively, our results established that STAC3 binding to CaV1.1 C-terminus is essential for its functional expression, whereas STAC3 interaction with the II-III loop serves to enhance the conformational coupling with RyR1.</p>","PeriodicalId":14722,"journal":{"name":"JCI insight","volume":"10 15","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12333939/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144804104","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":"Tubulin tyrosine ligase variant perturbs microtubule tyrosination, causing hypertrophy in patient-specific and CRISPR gene-edited iPSC-cardiomyocytes.","authors":"Pratul Kumar Jain, Susobhan Mahanty, Harshil Chittora, Veronique Henriot, Carsten Janke, Minhajuddin Sirajuddin, Perundurai S Dhandapany","doi":"10.1172/jci.insight.187942","DOIUrl":"10.1172/jci.insight.187942","url":null,"abstract":"<p><p>Hypertrophic cardiomyopathy (HCM) is a hereditary heart condition characterized by either preserved or reduced ejection fraction without any underlying secondary causes. The primary cause of HCM is sarcomeric gene mutations, which account for only 40%-50% of the total cases. Here, we identified a pathogenic missense variant in tubulin tyrosine ligase (TTL p.G219S) in a patient with HCM. We used clinical, genetics, computational, and protein biochemistry approaches, as well as patient-specific and CRISPR gene-edited induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs), to demonstrate that the TTL pathogenic variant results in a reduced enzymatic activity and the accumulation of detyrosinated tubulin leading to the disruption of redox signaling, ultimately leading to HCM. Our findings highlight - for the first time to our knowledge - the crucial roles of the TTL variant in cardiac remodeling resulting in disease.</p>","PeriodicalId":14722,"journal":{"name":"JCI insight","volume":"10 15","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12333943/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144804105","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":"A prometabolite strategy inhibits cardiometabolic disease in an ApoE-/- murine model of atherosclerosis.","authors":"Taryn N Beckman, Lisa R Volpatti, Salvador Norton de Matos, Anna J Slezak, Joseph W Reda, Ada Weinstock, Leah Ziolkowski, Alex Turk, Erica Budina, Shijie Cao, Gustavo Borjas, Jung Woo Kwon, Orlando deLeon, Kirsten C Refvik, Abigail L Lauterbach, Suzana Gomes, Eugene B Chang, Jeffrey A Hubbell","doi":"10.1172/jci.insight.191090","DOIUrl":"10.1172/jci.insight.191090","url":null,"abstract":"<p><p>Butyrate, a microbiome-derived short-chain fatty acid with pleiotropic effects on inflammation and metabolism, has been shown to significantly reduce atherosclerotic lesions, rectify routine metabolic parameters such as low-density lipoprotein cholesterol (LDL-C), and reduce systemic inflammation in murine models of atherosclerosis. However, its foul odor, rapid metabolism in the gut and thus low systemic bioavailability limit its therapeutic effectiveness. Our laboratory has engineered an ester-linked L-serine conjugate to butyrate (SerBut) to mask its taste and odor and to coopt amino acid transporters in the gut to increase its systemic bioavailability, as determined by tissue measurements of free butyrate, produced by hydrolysis of SerBut. In an apolipoprotein E-knockout (ApoE)-/- mouse model of atherosclerosis, SerBut reduced systemic LDL-C, proinflammatory cytokines, and circulating neutrophils. SerBut enhanced inhibition of plaque progression and reduced monocyte accumulation in the aorta compared with sodium butyrate. SerBut suppressed liver injury biomarkers alanine transaminase and aspartate aminotransferase and suppressed steatosis in the liver. SerBut overcomes several barriers to the translation of butyrate and shows superior promise in slowing atherosclerosis and liver injury compared with equidosed sodium butyrate.</p>","PeriodicalId":14722,"journal":{"name":"JCI insight","volume":"10 15","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12333940/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144804100","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":"BCG immunization mitigates SARS-CoV-2 replication in macaques via monocyte efferocytosis and neutrophil recruitment in lungs.","authors":"Mohammad Arif Rahman, Katherine C Goldfarbmuren, Sarkis Sarkis, Massimiliano Bissa, Anna Gutowska, Luca Schifanella, Ramona Moles, Melvin N Doster, Hanne Andersen, Yogita Jethmalani, Leonid Serebryannyy, Timothy Cardozo, Mark G Lewis, Genoveffa Franchini","doi":"10.1172/jci.insight.194633","DOIUrl":"10.1172/jci.insight.194633","url":null,"abstract":"<p><p>Exposure to Bacillus Calmette-Guérin (BCG) or Canarypox ALVAC/Alum vaccine elicits pro- or antiinflammatory innate responses, respectively. We tested whether prior exposure of macaques to these immunogens protected against SARS-CoV-2 replication in lungs and found more efficient replication control after the pro-inflammatory immunity elicited by BCG. The decreased virus level in lungs was linked to early infiltrates of classical monocytes producing IL-8 with systemic neutrophils, Th2 cells, and Ki67+CD95+CD4+ T cells producing CCR7. At the time of SARS-CoV-2 exposure, BCG-treated animals had higher frequencies of lung infiltrating neutrophils and higher CD14+ cells expressing efferocytosis marker MERTK, responses correlating with decreased SARS-CoV-2 replication in lung. At the same time point, plasma IL-18, TNF-α, TNFSF-10, and VEGFA levels were also higher in the BCG group and correlated with decreased virus replication. Finally, after SARS-CoV-2 exposure, decreased virus replication correlated with neutrophils producing IL-10 and CCR7 preferentially recruited to the lungs of BCG-vaccinated animals. These data point to the importance of the spatiotemporal distribution of functional monocytes and neutrophils in controlling SARS-CoV-2 levels and suggest a central role of monocyte efferocytosis in curbing replication.</p>","PeriodicalId":14722,"journal":{"name":"JCI insight","volume":"10 15","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12333941/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144804102","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":"Transgenic augmentation of erythroferrone in mice ameliorates anemia in adenine-induced chronic kidney disease.","authors":"Brian Czaya, Joseph D Olivera, Moya Zhang, Amber Lundin, Christian D Castro, Grace Jung, Mark R Hanudel, Elizabeta Nemeth, Tomas Ganz","doi":"10.1172/jci.insight.190018","DOIUrl":"10.1172/jci.insight.190018","url":null,"abstract":"<p><p>Anemia is a common and disabling complication of chronic kidney disease (CKD). Current therapies can be burdensome, and full correction of anemia is limited by their cardiovascular side effects. New approaches that may offer additional therapeutic options are needed. We explored the antianemic effects of erythroferrone, an erythroid hormone that induces iron mobilization by suppressing the master iron-regulatory hormone hepcidin. In a preclinical murine model of adenine-induced CKD, transgenic augmentation of erythroferrone mobilized iron, increased hemoglobin concentrations by approximately 2 g/dL, and modestly improved renal function without affecting systemic or renal inflammation, fibrosis, or markers of mineral metabolism. This study supports the concept that therapeutic augmentation of erythroferrone is a promising approach for alleviating CKD-associated anemia.</p>","PeriodicalId":14722,"journal":{"name":"JCI insight","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12487854/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144799144","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":"A ratiometric catalog of protein isoform shifts in the cardiac fetal gene program.","authors":"Yu Han, Shaonil Binti, Sara A Wennersten, Boomathi Pandi, Dominic Cm Ng, Edward Lau, Maggie Py Lam","doi":"10.1172/jci.insight.184309","DOIUrl":"10.1172/jci.insight.184309","url":null,"abstract":"<p><p>Pathological cardiac remodeling is associated with the reactivation of fetal genes, yet the extent of the heart's fetal gene program and its impact on proteome compositions remain incompletely understood. Here, using a proteome-wide protein ratio quantification strategy with mass spectrometry, we identified pervasive isoform usage shifts in fetal and postnatal mouse hearts, involving 145 pairs of highly homologous paralogs and alternative splicing-derived isoform proteins. Proteome-wide ratio comparisons readily rediscovered hallmark fetal gene signatures in muscle contraction and glucose metabolism pathways, while revealing what we believe to be previously undescribed isoform usage in mitochondrial and gene-expression-regulating proteins, including PPA1/PPA2, ANT1/ANT2, and PCBP1/PCBP2 switches. Paralogs with differential fetal usage tend to be evolutionarily recent, consistent with functional diversification. Alternative splicing adds another rich source of fetal isoform usage differences, involving PKM M1/M2, GLS1 KGA/GAC, PDLIM5 long/short, and other spliceoforms. When comparing absolute protein proportions, we observed a partial reversion toward fetal gene usage in pathological hearts. In summary, we present a ratiometric catalog of paralogs and spliceoform pairs in the cardiac fetal gene program. More generally, the results demonstrate the potential of applying the proteome-wide ratio test concept to discover new regulatory modalities beyond differential gene expression.</p>","PeriodicalId":14722,"journal":{"name":"JCI insight","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12487847/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144799141","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":"Longitudinal single-cell analysis of glucagon-like peptide-2 treatment in patients with short bowel syndrome.","authors":"Yumi Kudo, Kentaro Miyamoto, Shohei Suzuki, Akihiko Chida, Anna Tojo, Mai Hasegawa, Arina Shigehara, Ikuko Koya, Yoshinari Ando, Masayasu Sato, Aya Kondo, Tomoko Kumagai, Harunori Deguchi, Yoshiki Sugiyama, Yoko Ito, Koji Shirosaki, Satoko Yamagishi, Yutaro Maeda, Hiroki Kanamori, Motohiro Kano, Mototoshi Kato, Hanako Tsujikawa, Yusuke Yoshimatsu, Kaoru Takabayashi, Koji Okabayashi, Takanori Kanai, Naoki Hosoe, Motohiko Kato, Jonathan Moody, Chung-Chau Hon, Tatsuo Kuroda, Yohei Yamada, Akihiro Fujino, Tomohisa Sujino","doi":"10.1172/jci.insight.194497","DOIUrl":"10.1172/jci.insight.194497","url":null,"abstract":"<p><p>BACKGROUNDGlucagon-like peptide-2 (GLP-2) analogs are used clinically to enhance nutrient absorption in patients with short bowel syndrome (SBS); however, the precise mechanism remains unclear. To address this, the study aimed to clarify the dynamics of intestinal epithelial cells and immune cells in patients with SBS treated with GLP-2 analogs.METHODSFive male patients diagnosed with SBS, all of whom received treatment with the GLP-2 analog teduglutide, were included in the study. We conducted longitudinal single-cell RNA sequencing (scRNA-Seq) analysis of intestinal tissue from patients with SBS over a year, integrating microbiome composition analysis.RESULTSAfter treatment, the α-diversity of the gut microbiome increased, indicating a more varied microbial environment. ScRNA-Seq analysis revealed a reduction of T helper 2 cells and an increase in regulatory T cells, suggesting a shift toward an immunoregulatory intestinal environment. Additionally, nutrient-absorbing enterocyte-Top2 and middle clusters expanded, enhancing the absorption capacity, whereas major histocompatibility complex class I/II-expressing enterocyte-Top1 cells declined, potentially modulating immune responses.CONCLUSIONThe study findings indicate that GLP-2 analogs reshape intestinal immunity and microbiota, fostering a less inflammatory environment while promoting nutrient uptake efficiency. These insights offer a deeper understanding of the role of GLP-2 analogs in gut adaptation and provide a foundation for refining clinical strategies for SBS treatment.FUNDINGThis work was supported by Sakaguchi Memorial Foundation, Grants-in-Aid from the Japanese Society for the Promotion of Science (JSPS) (21K18272, 23H03665, 23H02899, 23K27590, 25K22627, 23K08037), JST FOREST(21457195), and the Takeda Japan Medical Office Funded Research Grant 2022.</p>","PeriodicalId":14722,"journal":{"name":"JCI insight","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12487850/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144799143","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":"BLIMP-1 and CEACAM1 cooperatively regulate human Treg homeostasis and function to control xenogeneic GVHD.","authors":"Ying Ding, Aixin Yu, Milos Vujanac, Sabrina N Copsel, Alejandro Moro, Luis Nivelo, Molly Dalzell, Nicolas Tchitchek, Michelle Rosenzwajg, Alejandro V Villarino, Robert B Levy, David Klatzmann, Thomas R Malek","doi":"10.1172/jci.insight.183676","DOIUrl":"10.1172/jci.insight.183676","url":null,"abstract":"<p><p>Regulatory T cells (Tregs) are essential for peripheral tolerance and depend on TCR and IL-2 receptor (IL-2R) signaling for their homeostasis and function. In mice, IL-2-dependent B-lymphocyte-induced maturation protein 1 (BLIMP-1) contributes to Treg homeostasis. BLIMP-1 is a major transcriptional hub in human Tregs, but its mechanisms of action remain undefined. Here, using CRISPR/Cas9 ablation, we show that BLIMP-1 limits human Treg proliferation but supports IL-10, cytotoxic T lymphocyte-associated protein 4, several immune checkpoints including carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1), and Treg functional activity. BLIMP-1 restrains Treg expansion to IL-2 by downregulating CD25 and IL-2R signaling, and by enhancing CEACAM1 expression, which in turn inhibits responsiveness to CD3/CD28 signaling and activation of mTOR. Prolonged IL-2R signaling optimizes BLIMP-1 expression, supporting chromosomal opening of CEACAM1 to increased CEACAM1 expression through STAT5- and BLIMP-1-driven enhancers. Correspondingly, CEACAM1 is highly induced on Tregs from patients with autoimmune disease undergoing low-dose IL-2 therapy, and these Tregs showed reduced proliferation. A humanized mouse model of xenogeneic graft-versus-host disease demonstrates that BLIMP-1 normally promotes, while CEACAM1 restrains, Treg suppressive activity. Collectively, our findings reveal that BLIMP-1 and CEACAM1 function in an IL-2-dependent feedback loop to restrain Treg proliferation and affect suppressive function. CEACAM1 also acts as a highly selective biomarker of IL-2R signaling in human T cells.</p>","PeriodicalId":14722,"journal":{"name":"JCI insight","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12487853/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144799142","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}