Journal of Clinical Investigation最新文献

{"title":"Angiopoietin-like protein 2 mediates vasculopathy driven fibrogenesis in a mouse model of systemic sclerosis.","authors":"Dyuti Saha, Ravi Kiran Annadorai, Sujaya Thannimangalath, Neha P Shroff, Sunny Kataria, Binita Dam, Abhik Dutta, Akshay Hegde, Ankita Hiwale, Venkatesh Ravula, Shagnik Saha, Lekshmi Minikumari Rahulan, Neha Nigam, Neha Singh, Vikas Agarwal, Praveen K Vemula, Colin Jamora","doi":"10.1172/JCI177123","DOIUrl":"10.1172/JCI177123","url":null,"abstract":"<p><p>Vasculopathy is a common hallmark of various fibrotic disorders including systemic sclerosis (SSc), yet its underlying etiology and contribution to fibrogenesis remain ill-defined. In SSc the vasculopathy typically precedes the onset of fibrosis and we observed that this phenomenon is recapitulated in the Snail transgenic mouse model of SSc. The vascular anomalies manifest as deformed vessels, endothelial cell dysfunction and vascular leakage. Our investigation into the underlying mechanism of this phenotype revealed that angiopoietin-like protein 2 (ANGPTL2), secreted by the Snail transgenic keratinocytes, is a principal driver of fibrotic vasculopathy. In endothelial cells, ANGPTL2 upregulates pro-fibrotic genes, downregulates various junctional proteins, and prompts the acquisition of mesenchymal characteristics. Inhibiting endothelial cell junctional instability and consequently vascular leakage with a synthetic analog of the microbial metabolite Urolithin A (UAS03) effectively mitigated the vasculopathy and inhibited fibrogenesis. Thus, ANGPTL2 emerges as a promising early biomarker of the disease and inhibiting the vasculopathy inducing effects of this protein with agents such as UAS03 presents an appealing therapeutic avenue to reduce disease severity. These insights hold the potential to revolutionize the approach to the treatment of fibrotic diseases by targeting the vascular defects.</p>","PeriodicalId":15469,"journal":{"name":"Journal of Clinical Investigation","volume":" ","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144336570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Blood immunophenotyping identifies distinct kidney histopathology and outcomes in patients with lupus nephritis.","authors":"Alice Horisberger, Alec Griffith, Joshua Keegan, Arnon Arazi, John Pulford, Ekaterina Murzin, Kaitlyn Howard, Brandon Hancock, Andrea Fava, Takanori Sasaki, Tusharkanti Ghosh, Jun Inamo, Rebecca Beuschel, Ye Cao, Katie Preisinger, Maria Gutierrez-Arcelus, Thomas M Eisenhaure, Joel Guthridge, Paul J Hoover, Maria Dall'Era, David Wofsy, Diane L Kamen, Kenneth C Kalunian, Richard Furie, Michael Belmont, Peter Izmirly, Robert Clancy, David Hildeman, E Steve Woodle, William Apruzzese, Maureen A McMahon, Jennifer Grossman, Jennifer L Barnas, Fernanda Payan-Schober, Mariko Ishimori, Michael Weisman, Matthias Kretzler, Celine C Berthier, Jeffrey B Hodgin, Dawit S Demeke, Chaim Putterman, Michael B Brenner, Jennifer H Anolik, Soumya Raychaudhuri, Nir Hacohen, Judith A James, Anne Davidson, Michelle A Petri, Jill P Buyon, Betty Diamond, Fan Zhang, James A Lederer, Deepak A Rao","doi":"10.1172/JCI181034","DOIUrl":"10.1172/JCI181034","url":null,"abstract":"<p><p>Lupus nephritis (LN) is a frequent manifestation of systemic lupus erythematosus, and fewer than half of patients achieve complete renal response with standard immunosuppressants. Identifying non-invasive, blood-based immune alterations associated with renal injury could aid therapeutic decisions. Here, we used mass cytometry immunophenotyping of peripheral blood mononuclear cells in 145 patients with biopsy-proven LN and 40 healthy controls to evaluate the heterogeneity of immune activation and identify correlates of renal parameters. Unbiased analysis identified three immunologically distinct groups of patients that were associated with different patterns of histopathology, renal cell infiltrates, urine proteomic profiles, and treatment response at one year. Patients with enriched circulating granzyme B+ T cells showed more active disease and increased numbers of activated CD8 T cells in the kidney, yet they had the highest likelihood of treatment response. A second group characterized by a high type I interferon signature had a lower likelihood of response to therapy, while a third group appeared immunologically inactive but with chronic renal injuries. The major immunologic axes of variation could be distilled down to five simple cytometric parameters that recapitulate several clinical associations, highlighting the potential for blood immunoprofiling to translate to clinically useful non-invasive metrics to assess immune-mediated disease in LN.</p>","PeriodicalId":15469,"journal":{"name":"Journal of Clinical Investigation","volume":" ","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144333164","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modulation of the Acod1/itaconate pathway differentially affects atherosclerosis severity across genetic models and sexes.","authors":"Lara Haase, Anouar Belkacemi, Laura Neises, Nicole Kiweler, Christine Wesely, Rosanna Huchzermeier, Maja Bozic, Arefeh Khakdan, Marta Sánchez, Arnaud Mary, Nadja Sachs, Hanna Winter, Enrico Glaab, Michael T Heneka, Emiel Pc van der Vorst, Michel Mittelbronn, Johannes Meiser, Jochen G Schneider","doi":"10.1172/JCI182472","DOIUrl":"https://doi.org/10.1172/JCI182472","url":null,"abstract":"","PeriodicalId":15469,"journal":{"name":"Journal of Clinical Investigation","volume":" ","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144284490","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MuSK cysteine-rich domain antibodies are pathogenic in a mouse model of autoimmune myasthenia gravis.","authors":"Marius Halliez, Steve Cottin, Axel You, Céline Buon, Antony Grondin, Léa S Lippens, Megane Lemaitre, Jérome Ezan, Charlotte Isch, Yann Rufin, Mireille Montcouquiol, Nathalie Sans, Bertrand Fontaine, Julien Messéant, Rozen Le Panse, Laure Strochlic","doi":"10.1172/JCI173308","DOIUrl":"https://doi.org/10.1172/JCI173308","url":null,"abstract":"<p><p>The neuromuscular junction (NMJ), synapse between the motor neuron terminal and a skeletal muscle fiber is crucial, throughout life, in maintaining the reliable neurotransmission required for functional motricity. Disruption of this system leads to neuromuscular disorders, such as auto-immune myasthenia gravis (MG), the most common form of NMJ diseases. MG is caused by autoantibodies directed mostly against the acetylcholine receptor (AChR) or the muscle-specific kinase MuSK. Several studies report immunoreactivity to the Frizzled-like cysteine-rich Wnt-binding domain of MuSK (CRD) in patients, although the pathogenicity of the antibodies involved remains unknown. We showed here that the immunoreactivity to MuSK CRD induced by the passive transfer of anti-MuSKCRD antibodies in mice led to typical MG symptoms, characterized by a loss of body weight and a locomotor deficit. The functional and morphological integrity of the NMJ was compromised with a progressive decay of neurotransmission and disruption of the structure of pre- and post-synaptic compartments. We found that anti-MuSKCRD antibodies completely abolished Agrin-mediated AChR clustering by decreasing the Lrp4-MuSK interaction. These results provide the first demonstration of the role of the MuSK CRD in MG pathogenesis and improve our understanding of the underlying pathophysiological mechanisms.</p>","PeriodicalId":15469,"journal":{"name":"Journal of Clinical Investigation","volume":" ","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144284491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Wilms' tumor 1 impairs apoptotic clearance of fibroblasts in distal fibrotic lung lesions.","authors":"Harshavardhana H Ediga, Chanukya P Vemulapalli, Vishwaraj Sontake, Pradeep K Patel, Hikaru Miyazaki, Dimitry Popov, Martin B Jensen, Anil G Jegga, Steven K Huang, Christoph Englert, Andreas Schedl, Nishant Gupta, Francis X McCormack, Satish K Madala","doi":"10.1172/JCI188819","DOIUrl":"10.1172/JCI188819","url":null,"abstract":"<p><p>Idiopathic pulmonary fibrosis (IPF) is a fatal fibrotic lung disease characterized by impaired fibroblast clearance and excessive extracellular matrix (ECM) protein production. Wilms' Tumor 1 (WT1), a transcription factor, is selectively upregulated in IPF fibroblasts. However, the mechanisms by which WT1 contributes to fibroblast accumulation and ECM production remain unknown. Here, we investigated the heterogeneity of WT1-expressing mesenchymal cells using single-nucleus RNA sequencing of distal lung tissues from IPF patients and control donors. WT1 was selectively upregulated in a subset of IPF fibroblasts that co-expressed several pro-survival and ECM genes. The results of both loss-of-function and gain-of-function studies are consistent with a role for WT1 as a positive regulator of pro-survival genes to impair apoptotic clearance and promote ECM production. Fibroblast-specific overexpression of WT1 augmented fibroproliferation, myofibroblast accumulation, and ECM production during bleomycin-induced pulmonary fibrosis in young and aged mice. Together, these findings suggest that targeting WT1 is a promising strategy for attenuating fibroblast expansion and ECM production during fibrogenesis.</p>","PeriodicalId":15469,"journal":{"name":"Journal of Clinical Investigation","volume":" ","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144266385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Kidney-specific WNK1 amplifies kidney tubule responsiveness to potassium via WNK body condensates.","authors":"Cary R Boyd-Shiwarski, Rebecca T Beacham, Jared A Lashway, Katherine E Querry, Shawn E Griffiths, Daniel J Shiwarski, Sophia A Knoell, Nga H Nguyen, Lubika J Nkashama, Melissa N Valladares, Anagha Bandaru, Allison L Marciszyn, Jonathan Franks, Mara Sullivan, Simon C Watkins, Aylin R Rodan, Chou-Long Huang, Sean D Stocker, Ossama B Kashlan, Arohan R Subramanya","doi":"10.1172/JCI188792","DOIUrl":"https://doi.org/10.1172/JCI188792","url":null,"abstract":"<p><p>To maintain potassium homeostasis, the kidney's distal convoluted tubule (DCT) evolved to convert small changes in blood [K+] into robust effects on salt reabsorption. This process requires NaCl cotransporter (NCC) activation by the With-No-Lysine (WNK) kinases. During hypokalemia, the Kidney-Specific WNK1 isoform (KS-WNK1) scaffolds the DCT-expressed WNK signaling pathway within biomolecular condensates of unknown function termed WNK bodies. Here, we show that KS-WNK1 amplifies kidney tubule reactivity to blood [K+], in part via WNK bodies. Genetically modified mice with targeted condensate disruption trap the WNK pathway, causing renal salt wasting that is more pronounced in females. In humans, WNK bodies accumulate as plasma potassium falls below 4.0 mmol/L, suggesting that the human DCT experiences the stress of potassium deficiency even when [K+] is in the low-normal range. These data identify WNK bodies as kinase signal amplifiers that mediate tubular [K+] responsiveness, nephron sexual dimorphism, and blood pressure salt-sensitivity. Our results illustrate how biomolecular condensate specialization can optimize a mammalian physiologic stress response that impacts human health.</p>","PeriodicalId":15469,"journal":{"name":"Journal of Clinical Investigation","volume":" ","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144266372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Patterns of intra- and inter-tumor phenotypic heterogeneity in lethal prostate cancer.","authors":"Martine P Roudier, Roman Gulati, Erolcan Sayar, Radhika A Patel, Micah Tratt, Helen M Richards, Paloma Cejas, Miguel Munoz Gomez, Xintao Qiu, Yingtian Xie, Brian Hanratty, Samir Zaidi, Jimmy L Zhao, Mohamed Adil, Chitvan Mittal, Yibai Zhao, Ruth Dumpit, Ilsa Coleman, Jin-Yih Low, Thomas Persse, Patricia C Galipeau, John K Lee, Maria Tretiakova, Meagan Chambers, Funda Vakar-Lopez, Lawrence D True, Marie Perrone, Hung-Ming Lam, Lori A Kollath, Chien-Kuang C Ding, Stephanie Harmon, Heather H Cheng, Evan Y Yu, Robert B Montgomery, Jessica E Hawley, Daniel W Lin, Eva Corey, Michael T Schweizer, Manu Setty, Gavin Ha, Charles L Sawyers, Colm Morrissey, Henry W Long, Peter S Nelson, Michael C Haffner","doi":"10.1172/JCI186599","DOIUrl":"10.1172/JCI186599","url":null,"abstract":"<p><p>Metastatic prostate cancer (mPC) is a clinically and molecularly heterogeneous disease. While there is increasing recognition of diverse tumor phenotypes across patients, less is known about the molecular and phenotypic heterogeneity present within an individual. In this study, we aimed to define the patterns, extent, and consequences of inter- and intra-tumoral heterogeneity in lethal prostate cancer. By combining and integrating in situ tissue-based and sequencing approaches, we analyzed over 630 tumor samples from 52 mPC patients. Our efforts revealed phenotypic heterogeneity at the patient, metastasis, and cellular levels. We observed that intra-patient, inter-tumoral molecular subtype heterogeneity was common in mPC and showed associations with genomic and clinical features. Additionally, cellular proliferation rates varied within a given patient across molecular subtypes and anatomic sites. Single-cell sequencing studies revealed features of morphologically and molecularly divergent tumor cell populations within a single metastatic site. These data provide a deeper insight into the complex patterns of tumoral heterogeneity in mPC with implications for clinical management and the future development of diagnostic and therapeutic approaches.</p>","PeriodicalId":15469,"journal":{"name":"Journal of Clinical Investigation","volume":" ","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144266373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TNFα impairs platelet function by inhibiting autophagy and disrupting metabolism via Syntaxin-17 downregulation.","authors":"Guadalupe Rojas-Sanchez, Jorge Calzada-Martinez, Brandon McMahon, Aaron C Petrey, Gabriela Dveksler, Gerardo P Espino-Solis, Orlando Esparza, Giovanny Hernandez, Dennis Le, Eric P Wartchow, Ken Jones, Lucas H Ting, Catherine Jankowski, Marguerite R Kelher, Marilyn Manco-Johnson, Marie L Feser, Kevin D Deane, Travis Nemkov, Angelo D'Alessandro, Andrew Thorburn, Paola Maycotte, José A López, Pavel Davizon-Castillo","doi":"10.1172/JCI186065","DOIUrl":"10.1172/JCI186065","url":null,"abstract":"<p><p>Platelets play a dual role in hemostasis and inflammation-associated thrombosis and hemorrhage. While the mechanisms linking inflammation to platelet dysfunction remain poorly understood, our previous work demonstrated that TNFα alters mitochondrial mass, platelet activation, and autophagy-related pathways in megakaryocytes. Here, we hypothesized that TNFα impairs platelet function by disrupting autophagy, a process critical for mitochondrial health and cellular metabolism. Using human and murine models of TNFα-driven diseases, including myeloproliferative neoplasms and rheumatoid arthritis, we found that TNFα downregulates STX17, a key mediator of autophagosome-lysosome fusion. This disruption inhibited autophagy, leading to the accumulation of dysfunctional mitochondria and reduced mitochondrial respiration. These metabolic alterations compromised platelet-driven clot contraction, a process linked to thrombotic and hemorrhagic complications. Our findings reveal a mechanism by which TNFα disrupts hemostasis through autophagy inhibition, highlighting TNFα as a critical regulator of platelet metabolism and function. This study provides new insights into inflammation-associated pathologies and suggests autophagy-targeting strategies as potential therapeutic avenues to restore hemostatic balance.</p>","PeriodicalId":15469,"journal":{"name":"Journal of Clinical Investigation","volume":" ","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144266384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Disruption of the KLHL37-N-Myc complex restores N-Myc degradation and arrests neuroblastoma growth in mouse models.","authors":"Senfeng Xiang, Pengfei Chen, Xiaoxian Shi, Hanqi Cai, Zihan Shen, Luyang Liu, Aixiao Xu, Jianhua Zhang, Xingya Zhang, Shaowei Bing, Jinhu Wang, Xuejing Shao, Ji Cao, Bo Yang, Qiaojun He, Meidan Ying","doi":"10.1172/JCI176655","DOIUrl":"10.1172/JCI176655","url":null,"abstract":"<p><p>The N-Myc gene MYCN amplification accounts for the most common genetic aberration in neuroblastoma and strongly predicts the aggressive progression and poor clinical prognosis. However, clinically effective therapies that directly target N-Myc activity are limited. N-Myc is a transcription factor, and its stability is tightly controlled by ubiquitination-dependent proteasomal degradation. Here, we discovered that Kelch-like protein 37 (KLHL37) played a crucial role in enhancing the protein stability of N-Myc in neuroblastoma. KLHL37 directly interacted with N-Myc to disrupt N-Myc-FBXW7 interaction, thereby stabilizing N-Myc and enabling tumor progression. Suppressing KLHL37 effectively induced the degradation of N-Myc and had a profound inhibitory effect on the growth of MYCN-amplified neuroblastoma. Notably, we identified RTA-408 as an inhibitor of KLHL37 to disrupt the KLHL37-N-Myc complex, promoting the degradation of N-Myc and suppressing neuroblastoma in vivo and in vitro. Moreover, we elucidated the therapeutic potential of RTA-408 for neuroblastoma using patient-derived neuroblastoma cell and patient-derived xenograft tumor models. RTA408's antitumor effects may not occur exclusively via KLHL37, and specific KLHL37 inhibitors are expected to be developed in the future. These findings not only uncover the biological function of KLHL37 in regulating N-Myc stability, but also indicate that KLHL37 inhibition is a promising therapeutic regimen for neuroblastoma, especially in patients with MYCN-amplified tumors.</p>","PeriodicalId":15469,"journal":{"name":"Journal of Clinical Investigation","volume":" ","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12259267/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144266369","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":"B cell deficiency induces cytotoxic memory CD8+ T cells during influenza-associated bacterial pneumonia.","authors":"Leigh M Miller, Alexis M Duray, Ellyse M Cipolla, Flavia Rago, Brooke P Dresden, Kristen L Parenteau, Abhigya Gupta, John F Alcorn","doi":"10.1172/JCI188342","DOIUrl":"https://doi.org/10.1172/JCI188342","url":null,"abstract":"<p><p>Influenza-associated bacterial super-infections in the lung lead to increased morbidity and mortality. Nearly all people have pre-existing memory to influenza virus, which can protect against subsequent infection in the lung. This study explored the role B cells play in protection against bacterial (Staphylococcus aureus or Klebsiella pneumoniae) super-infection with previous heterotypic influenza memory. B cell deficiency resulted in an increased inflammatory lung environment and lung tissue injury during super-infection. Loss of B cells increased populations of memory CD8+ T cells in the lung and these CD8+ T cells were transcriptionally and functionally distinct from WT mice. Use of antibody-deficient mouse models showed that this phenotype was specifically due to loss of antibody production from B cells. Passive immunization with influenza-antibody serum in B cell deficient mice rescued the CD8+ T cell phenotype. CD8+ T cell depletion and lethal super-infection challenge experiments showed that the cytotoxic memory CD8+ T cells from B cell deficient mice protect against super-infection bacterial burden and mortality. These findings provide insight into the importance of B cells for regulating immune responses against infection.</p>","PeriodicalId":15469,"journal":{"name":"Journal of Clinical Investigation","volume":" ","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144266368","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}