JCI insight最新文献

{"title":"Identification of asporin as a HER3 ligand exposes a therapeutic vulnerability in prostate cancer.","authors":"Amanda B Hesterberg, Hong Yuen Wong, Jorgen Jackson, Monika Antunovic, Brenda L Rios, Evan Watkins, Riley E Bergman, Brad A Davidson, Sarah E Ginther, Diana Graves, Elliott F Nahmias, Jared A Googel, Lillian B Martin, Violeta Sanchez, Paula I Gonzalez-Ericsson, Quanhu Sheng, Benjamin P Brown, Jens Meiler, Kerry R Schaffer, Jennifer B Gordetsky, Ben H Park, Paula J Hurley","doi":"10.1172/jci.insight.187151","DOIUrl":"10.1172/jci.insight.187151","url":null,"abstract":"<p><p>Cancer-associated fibroblasts (CAFs) are part of the tumor microenvironment (TME) that enable cancer cells to establish metastases, but the mechanisms of these interactions are not fully known. Herein, we identified a paracrine mechanism in which CAF-secreted asporin (ASPN) activated ErbB signaling and subsequent migration of adjacent prostate cancer cells. Our data support that ASPN bound directly to the ligand binding domain of human epidermal growth factor 3 (HER3) and induced HER2/HER3 heterodimerization and activation of the PI3K, MAPK, and calcium pathways. Genetic and therapeutic inhibition of HER2/HER3 ablated ASPN-induced signaling and migration. Clinically, ASPN was detected in the stroma of HER2/HER3-expressing human metastatic prostate cancer, supporting the clinical relevance of these findings and highlighting a potential therapeutic vulnerability. Antibody-drug conjugate (ADC) therapies designed to target HER2 (trastuzumab-deruxtecan) or HER3 (patritumab-deruxtecan) significantly diminished prostate cancer cell growth in vitro and tumor size in vivo, despite Aspn in the TME. Collectively, these findings indicate ASPN functions as a HER3 ligand to induce cellular migration, and inhibition with anti-HER2 or anti-HER3 ADC therapies highlights potential clinical utility for patients with metastatic castration-resistant prostate cancer that expresses HER2 or HER3.</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/PMC12406728/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144954766","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":"An engineered glioblastoma model yields macrophage-secreted drivers of invasion.","authors":"Erin A Akins, Dana Wilkins, Zaki Abou-Mrad, Kelsey Hopland, Robert C Osorio, Kenny Kh Yu, Manish K Aghi, Sanjay Kumar","doi":"10.1172/jci.insight.181903","DOIUrl":"10.1172/jci.insight.181903","url":null,"abstract":"<p><p>While the accumulation of tumor-associated macrophages (TAMs) in glioblastoma (GBM) has been well documented, targeting TAMs has thus far yielded limited clinical success in slowing GBM progression due, in part, to an incomplete understanding of TAM function. Using an engineered 3D hydrogel-based model of the brain tumor microenvironment (TME), we show that M2-polarized macrophages stimulate transcriptional and phenotypic changes in GBM stem cells (GSCs) closely associated with the highly aggressive and invasive mesenchymal subtype. By combining proteomics with GBM patient single-cell transcriptomics, we identify multiple TAM-secreted proteins with putative proinvasive functions and validate TGF-β induced (TGFBI, also known as BIGH3) as a targetable TAM-secreted tumorigenic factor. Our work highlights the utility of coupling multiomics analyses with engineered TME models to investigate TAM-cancer cell crosstalk and offers insights into TAM function to guide TAM-targeting therapies.</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/PMC12406725/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144954690","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":"Hydroxyapatite microspheres induce durable pleurodesis and are rapidly cleared by pleural osteoclasts.","authors":"Yusuke Tanaka, Yuki Takahashi, Yuma Shindo, Lori B Pitstick, Steven L Teitelbaum, Wei Zou, Xiangning Wang, Jason C Woods, Kathryn A Wikenheiser-Brokamp, Francis X McCormack","doi":"10.1172/jci.insight.192981","DOIUrl":"10.1172/jci.insight.192981","url":null,"abstract":"<p><p>Talc pleurodesis is highly effective for preventing recurrence of pneumothorax and pleural effusion, but it can be complicated by dissemination, acute lung injury, lead exposure, and foreign body-induced chronic inflammation and pain. Our objective is to develop a safe, biodegradable, contaminant-free particle for pleurodesis. We used mouse models of pneumothorax and malignant pleural effusion to compare the efficacy and safety of pleurodesis with talc and hydroxyapatite microspheres (HAM). Intrapleural instillation of microspheres induced pleural adhesions, fibrosis, and symphysis as effectively as talc and resulted in more durable protection from experimental pneumothorax. HAM and talc both induced an osteoclastogenic, inflammatory, and fibrotic response in pleural lavage cells. Intrapleural HAM was resorbed by osteoclast action over 3 months, whereas talc was not cleared. Deletion of the osteoclast effector, CTSK, diminished pleural adhesion formation and fibrosis by HAM, and inhibition of osteoclastogenesis with anti-RANKL antibody delayed HAM clearance. We found no difference in activity level, feeding behavior, or lung compliance between particles, but talc induced more persistent pleural inflammation. We conclude that HAM resulted in an osteoclastogenic and fibrogenic pleural response that induced pleurodesis that was more durable than talc with a superior safety profile due in part to osteoclast-mediated particle clearance.</p>","PeriodicalId":14722,"journal":{"name":"JCI insight","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12513485/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144954704","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":"GABAergic interneurons contribute to the fatal seizure phenotype of CLN2 disease mice.","authors":"Keigo Takahashi, Nicholas R Rensing, Elizabeth M Eultgen, Letitia L Williams, Sophie H Wang, Hemanth R Nelvagal, Steven Q Le, Marie S Roberts, Balraj Doray, Edward B Han, Patricia I Dickson, Michael Wong, Mark S Sands, Jonathan D Cooper","doi":"10.1172/jci.insight.184487","DOIUrl":"10.1172/jci.insight.184487","url":null,"abstract":"<p><p>The cellular etiology of seizures in CLN2 disease, a childhood-onset neurodegenerative lysosomal storage disorder caused by a deficiency of tripeptidyl peptidase 1 (TPP1), remains elusive. Given that Cln2R207X/R207X mice display fatal spontaneous seizures and an early loss of several cortical GABAergic interneuron populations, we hypothesized that these 2 events might be causally related. To study the cell-autonomous effects of interneuron-specific TPP1 deficiency, we first generated transgenic mice expressing loxP-flanked lysosomal membrane-tethered TPP1 (TPP1LAMP1 mice) on the Cln2R207X/R207X genetic background, and then crossed TPP1LAMP1 mice with Vgat-Cre mice. These Vgat-Cre; TPP1LAMP1 mice accumulated storage material in cortical and striatal interneurons. Vgat-Cre; TPP1LAMP1 mice also died more readily after pentylenetetrazole-induced seizures, indicating that interneuron-specific TPP1 deficiency renders these mice more susceptible to seizure-induced mortality. We also selectively activated interneurons using designer receptors exclusively activated by designer drugs (DREADDs) in Vgat-Cre; Cln2R207X/R207X mice. Electroencephalogram monitoring revealed that DREADD-mediated activation of interneurons markedly accelerated the onset of spontaneous seizures and seizure-associated death in Vgat-Cre; Cln2R207X/R207X mice, suggesting that modulating interneuron activity can exacerbate epileptiform abnormalities. Taken together, these results provide mechanistic insights into the underlying etiology of seizures and premature death that characterize CLN2 disease.</p>","PeriodicalId":14722,"journal":{"name":"JCI insight","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12513480/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144954774","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":"Essential role of protein kinase R in the pathogenesis of pulmonary veno-occlusive disease.","authors":"Amit Prabhakar, Rahul Kumar, Meetu Wadhwa, Abhilash Barpanda, Joseph Lyons, Asavari Gowda, Simren Gupta, Ananyaa Arvind, Prajakta Ghatpande, Arun P Wiita, Brian B Graham, Giorgio Lagna, Akiko Hata","doi":"10.1172/jci.insight.193495","DOIUrl":"10.1172/jci.insight.193495","url":null,"abstract":"<p><p>Pulmonary veno-occlusive disease (PVOD) is a rare and severe subtype of pulmonary arterial hypertension, characterized by progressive remodeling of small pulmonary arteries and veins with no therapies. Using a mitomycin C-induced (MMC-induced) rat model, we previously demonstrated that protein kinase R-mediated (PKR-mediated) integrated stress response (ISR) drives endothelial dysfunction and vascular remodeling. To determine whether PKR is the primary mediator of ISR and the pathogenesis, we treated control (Ctrl) and PKR-knockout (KO) mice with the same dose of MMC. Consistent with rat data, Ctrl mice displayed ISR activation, vascular remodeling, and pulmonary hypertension after MMC treatment, while KO mice showed none of these phenotypes. Proteomic analysis revealed that MMC-mediated ISR activation attenuated protein synthesis in Ctrl but not in KO mice. These findings underscore the critical role of PKR-dependent ISR activation and subsequent perturbation of proteostasis as central mechanisms driving PVOD pathogenesis and identify PKR as a promising therapeutic target.</p>","PeriodicalId":14722,"journal":{"name":"JCI insight","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12513476/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144954757","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":"Atrial fibroblast-derived macrophage migration inhibitory factor promotes atrial macrophage accumulation in postoperative atrial fibrillation.","authors":"Joshua A Keefe, Jose Alberto Navarro-Garcia, Shuai Zhao, Mihail G Chelu, Xander Ht Wehrens","doi":"10.1172/jci.insight.190756","DOIUrl":"10.1172/jci.insight.190756","url":null,"abstract":"<p><p><br> New study: Blocking MIF protein prevents irregular heartbeats after surgery by reducing harmful immune cell buildup in the atria.</p>","PeriodicalId":14722,"journal":{"name":"JCI insight","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12487863/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144855279","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":"Differential pathology and susceptibility to MBNL loss across muscles in myotonic dystrophy mouse models.","authors":"Mackenzie L Davenport, Amaya Fong, Gloria Montoya-Vazquez, Maria Fernanda Alves de Moura, Jodi L Bubenik, Maurice S Swanson","doi":"10.1172/jci.insight.195836","DOIUrl":"10.1172/jci.insight.195836","url":null,"abstract":"<p><p>There are 2 subtypes of myotonic dystrophy, DM1 and DM2, each caused by repeat expansion mutations. The leading pathogenic mechanism is RNA-mediated toxicity, whereby (C)CUG expansions sequester the muscleblind-like (MBNL) family of RNA binding proteins. However, key differences exist in muscle involvement patterns and histopathology between DM1 and DM2. The cause of these disparities both in how the muscles are affected within each disease and between the 2 diseases is unknown, and it is unclear if current DM mouse models recapitulate these differences or develop differential muscle susceptibility. Here, we examined the expression of disease-relevant genes across healthy human muscles from a transcriptomic atlas and collected a series of muscles from Mbnl-KO mice to evaluate characteristic histologic and molecular features of DM pathology. Our results indicate that MBNL loss discordantly affects muscles, likely through a splicing-independent mechanism, and results in a fiber atrophy profile more like DM1 than DM2. These findings point to a predominant role for MBNL loss in muscle pattern involvement in DM1, provide further evidence for additional DM2 pathomechanisms, and have important implications for muscle choice when performing analyses in new mouse models and evaluating therapeutic modalities and biomarkers.</p>","PeriodicalId":14722,"journal":{"name":"JCI insight","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12487862/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144855280","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":"Photon and particle radiotherapy induce redundant modular chemotaxis of human lymphocytes.","authors":"Joscha A Kraske, Michael M Allers, Aleksei Smirnov, Bénédicte Lenoir, Azaz Ahmed, Meggy Suarez-Carmona, Mareike Hampel, Damir Krunic, Alexandra Tietz-Dalfuß, Tizian Beikert, Jonathan M Schneeweiss, Stephan Brons, Dorothee Albrecht, Thuy Trinh, Muzi Liu, Nathalia A Giese, Christin Glowa, Jakob Liermann, Ramon Lopez Perez, Dirk Jäger, Jürgen Debus, Niels Halama, Peter E Huber, Thomas Walle","doi":"10.1172/jci.insight.190149","DOIUrl":"10.1172/jci.insight.190149","url":null,"abstract":"<p><p>Radiotherapy triggers chemokine release and leukocyte infiltration in preclinical models through activation of the senescence-associated secretory phenotype (SASP). However, effects of irradiation on senescence and SASP in human tissue and in the context of particle radiotherapy remain unclear. Here, we analyzed chemokine patterns after radiotherapy of human pancreatic tumors and cancer cell lines. We show that irradiated tumor cells coexpressed SASP chemokines in defined modules. These chemokine modules correlated with infiltration of distinct leukocyte subtypes expressing cognate receptors. We developed a patient-derived pancreatic tumor explant system, which verified our identified radiation-induced chemokine modules. Chemokine modules were partially conserved in cancer cells in response to photon and particle irradiation, showing a dose-dependent plateau effect, and induced subsequent migration of NK and T cell populations. Hence, our work reveals redundant interactions of cancer cells and immune cells in human tissue, suggesting that targeting multiple chemokines is required to efficiently perturb leukocyte infiltration after photon or particle radiotherapy.</p>","PeriodicalId":14722,"journal":{"name":"JCI insight","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12487834/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144855281","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":"Urine proteomic signatures of kidney function decline after hospitalization.","authors":"Yumeng Wen, Steven Menez, Heather Thiessen Philbrook, Dennis Moledina, Steven G Coca, Jiashu Xue, James Kaufman, Vernon Chinchillil, Paul L Kimmel, T Alp Ikizler, Chi-Yuan Hsu, Tanika Kelly, Ana Ricardo, Jonathan Himmelfarb, Chirag R Parikh","doi":"10.1172/jci.insight.195577","DOIUrl":"10.1172/jci.insight.195577","url":null,"abstract":"<p><strong>Background: </strong>Urine proteomics may provide mechanistic insights on why patients experience a higher risk of kidney function decline after hospitalization.</p><p><strong>Methods: </strong>In 174 patients with and without acute kidney injury (AKI) from the Assessment, Serial Evaluation, and Subsequent Sequelae in AKI (ASSESS-AKI) cohort, we used Olink to profile 2783 urinary proteins collected at 3 months after hospitalization and determined their association with estimated glomerular filtration rate (eGFR) decline during median [IQR] of 5.1 [4.0 to 6.0] years follow-up. In 4 independent cohorts, including the Kidney Precision Medicine Project (KPMP), we determined whether proteins were differentially expressed with AKI. We used weighted correlation network analysis to determine proteins' cellular enrichment in the kidney transcriptome (single-cell and spatial transcriptomics) in patients with AKI receiving research kidney biopsy.</p><p><strong>Results: </strong>We identified 387 and 10 proteins associated with faster and slower eGFR decline, respectively, most of which were differentially expressed in patients at the time of AKI. Among these proteins, 283 (71%) were expressed by kidney cells in participants with AKI from KPMP. The expression formed 3 clusters enriched in the proximal tubule, degenerative tubule and myeloid cells, and stromal cells, and correlated with histopathological features of AKI, such as tubular injury, interstitial inflammation, and fibrosis, respectively.</p><p><strong>Conclusion: </strong>Urinary proteins reflecting degenerative tubular injury, inflammation, and fibrosis are associated with eGFR decline in recently hospitalized patients.</p><p><strong>Funding: </strong>National Institute of Diabetes and Digestive Kidney Diseases grants U01DK133081, U01DK133091, U01DK133092, U01DK133093, U01DK133095, U01DK133097, U01DK114866, U01DK114908, U01DK133090, U01DK133113, U01DK133766, U01DK133768, U01DK114907, U01DK114920, U01DK114923, U01DK114933, U24DK114886, UH3DK114926, UH3DK114861, UH3DK114915, UH3DK114937, K23DK128358, R01DK128087, and R01DK140717.</p>","PeriodicalId":14722,"journal":{"name":"JCI insight","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12487845/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144835123","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":"Normal Treg homeostasis and suppressive function require both FOXP1 and FOXP4.","authors":"Dachuan Dong, Vishal J Sindhava, Ananthakrishnan Ganesan, Martin S Naradikian, Tom L Stephen, Andrew Frisch, Kristen M Valentine, Elizabeth Buza, Karla R Wiehagen, Michael P Cancro, Edward E Morrisey, Haley Tucker, Katrina K Hoyer, Purvesh Khatri, Jonathan S Maltzman","doi":"10.1172/jci.insight.195981","DOIUrl":"10.1172/jci.insight.195981","url":null,"abstract":"<p><p>FOXP3+ Treg cells are critical for immune tolerance. Genetic deletion of the Forkhead domain-containing proteins of the FOXP-subfamily member FOXP1 from Tregs results in impaired function associated with reduced CD25 expression and IL-2 signaling, but to date the only other FOXP family member expressed in Tregs, FOXP4, has been minimally studied. To investigate the potential functional interactions among FOXP family members in Tregs, we specifically deleted Foxp1, Foxp4, or both in FOXP3+ committed Tregs in mice. Our findings show that mice with combined, but not individual, deficiency in FOXP1 and FOXP4 exhibit lymphoproliferation, inflammation, autoimmunity, and early lethality. The combined absence of FOXP1 and FOXP4 in Tregs results in an activated/effector-like phenotype with compromised suppressive function in peripheral lymphoid organs, an enhanced germinal center response, and proinflammatory cytokine production. We further show that FOXP1 and FOXP4 bind to Il2ra promoter regions to regulate CD25 expression in Tregs. Through pairwise comparison among mouse strains with Treg-specific deletion of Foxp1, Foxp4, or both, our findings indicate a nonredundant but insufficient role of FOXP4 in Treg function.</p>","PeriodicalId":14722,"journal":{"name":"JCI insight","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12487849/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144835122","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}