Clinical and Translational Medicine最新文献

{"title":"Nailfold capillary phenotypes distinguish juvenile myositis subtypes and associate with disease activity","authors":"Nicholas McClellan,&nbsp;Li Chen,&nbsp;Sophia Matossian,&nbsp;Aurora Rynda,&nbsp;Kirsten Grant,&nbsp;Erin Janssen,&nbsp;J. Michelle Kahlenberg,&nbsp;Jessica L. Turnier","doi":"10.1002/ctm2.70789","DOIUrl":"10.1002/ctm2.70789","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Nailfold capillaroscopy is a non-invasive method to visualize altered microcirculation in pediatric rheumatic disease, with potential to aid in diagnostic differentiation and disease monitoring. We used nailfold video capillaroscopy (NVC) and machine learning to identify patterns of capillaroscopic features in juvenile dermatomyositis (JDM) and associations of capillaroscopic features with clinical data.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>NVC features were quantified using automated neural network-based software in 76 individuals, including 18 controls, 33 JDM, 17 childhood-onset systemic lupus erythematosus (cSLE), and 8 overlap myositis (OM) patients. Unsupervised cluster analysis by capillaroscopic features was performed, and clinical features were characterized by cluster. Differences in capillaroscopic features between disease groups were assessed using the Kruskal–Wallis test. For JDM and OM patients, capillaroscopic and clinical feature associations were assessed using Spearman correlation. In 10 treatment-naïve myositis patients (JDM + OM), changes in capillaroscopic features between diagnosis and 3-month follow-up were evaluated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Cluster analysis identified three patient clusters, characterized by the presence of either branched or enlarged capillaries, or absence of these abnormalities. The “branched” cluster was most frequently assigned among JDM and OM and consisted of no controls. The majority of TIF1y+ JDM (4/5) were in the “branched” cluster. In JDM and OM, microhaemorrhage density correlated with disease duration (<i>r</i> = −.45, <i>p</i> = .0033), physician global assessment score (<i>r</i> = .6, <i>p</i> = .0004), lactate dehydrogenase (<i>r</i> = .43, <i>p</i> = .01), von Willebrand factor antigen (<i>r</i> = .51, <i>p</i> = .043), and neopterin (<i>r</i> = .69, <i>p</i> = .01). In 10 myositis patients, microhaemorrhage density decreased while capillary density increased from diagnosis to three months post-treatment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>A branched capillaroscopic pattern was observed more frequently in JDM and OM, particularly TIF1y+ JDM patients within our cohort. Microhaemorrhage density was the most changeable capillaroscopic feature and associated with markers of increased disease activity.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10189,"journal":{"name":"Clinical and Translational Medicine","volume":"16 9","pages":""},"PeriodicalIF":7.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13535121/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148873298","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":"Liquid condensates come of age: Nanoscale domains at the crossroads of stress and disease.","authors":"Nils G Walter, Bisal Halder","doi":"10.1002/ctm2.70833","DOIUrl":"10.1002/ctm2.70833","url":null,"abstract":"","PeriodicalId":10189,"journal":{"name":"Clinical and Translational Medicine","volume":"16 9","pages":"e70833"},"PeriodicalIF":7.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13570188/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148954977","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":"Spatiotemporal immune heterogeneity and precision immunotherapy for ovarian cancer.","authors":"Xinfeng Yang, Yida Wang, Haiyue You, Jingyi Gao, Yangkun Feng, Feng Zhang, Yan Zhang, Bing Zhang, Shaojie Zhao, Yanfang Gu","doi":"10.1002/ctm2.70836","DOIUrl":"10.1002/ctm2.70836","url":null,"abstract":"<p><strong>Background: </strong>The clinical benefit of immunotherapy in ovarian cancer (OC) remains limited. The primary reason is not simply a lack of immune activation, but rather the marked spatiotemporal heterogeneity of the tumour immune microenvironment. Previous reviews have mainly focused on individual immune components, immunosuppressive mechanisms, or therapeutic approaches, with less systematic integration of distinct anatomical niches, treatment-stage evolution, and their implications for precision immunotherapy selection.</p><p><strong>Main body: </strong>In this review, we propose a spatiotemporal immune heterogeneity framework to understand differential immunotherapy responses in OC. We first summarize the distinct immune landscapes across different anatomical niches, highlighting how anatomical niches shape immune suppression, immune exclusion and therapeutic vulnerability. We further discuss temporal remodelling of the tumour immune microenvironment during disease progression, emphasizing that immune states represent dynamic biological processes rather than fixed tumour characteristics. Based on this concept, we review biomarker-guided stratification strategies. Precision therapeutic strategies are further discussed according to distinct immune ecosystems. Finally, we highlight major challenges in clinical translation, including biomarker standardization, multicentre validation and the development of artificial intelligence-assisted decision systems.</p><p><strong>Conclusion: </strong>By linking immune ecosystem evolution, this review provides a framework for transitioning OC immunotherapy towards dynamic and precision-guided clinical management.</p>","PeriodicalId":10189,"journal":{"name":"Clinical and Translational Medicine","volume":"16 9","pages":"e70836"},"PeriodicalIF":7.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13574541/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148966420","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":"Bringing human early embryo development to clinical interpretation: HESTA as an evolving reference.","authors":"Yuejiao Li, Ying Zhang, Haoqi Yan, Yiping Zhu, Minghui Yu, Xun Xu, Ya Gao","doi":"10.1002/ctm2.70821","DOIUrl":"10.1002/ctm2.70821","url":null,"abstract":"","PeriodicalId":10189,"journal":{"name":"Clinical and Translational Medicine","volume":"16 9","pages":"e70821"},"PeriodicalIF":7.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13542561/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148886507","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":"Multiomics analyses revealed the roles of the epithelial-mesenchymal transition and novel early candidate diagnostic biomarkers in neonatal necrotising enterocolitis.","authors":"Xiao-Chen Liu, Guo-Bin Liu, Chen Cheng, Jin Zhu, Fei-Fan Chen, Ying Ji, Yu-Ni Zhang, Xiao-Lin Yan, Qing Wang, Xin-Yu Li, Qing Ai, Yuan Shi, Yu He","doi":"10.1002/ctm2.70793","DOIUrl":"10.1002/ctm2.70793","url":null,"abstract":"<p><strong>Background: </strong>Necrotizing enterocolitis (NEC) is a severe neonatal gastrointestinal disease with incompletely understood pathogenesis and a lack of reliable early biomarkers. We investigated intestinal molecular alterations associated with NEC and explored candidate diagnostic biomarkers.</p><p><strong>Methods: </strong>Bulk proteomics of formalin-fixed paraffin-embedded intestinal tissues was integrated with spatial proteomics of an index NEC case, single-cell RNA sequencing, immunohistochemical validation, serum enzyme-linked immunosorbent assays, and a murine NEC model with pharmacological inhibition of Snail-mediated epithelial-mesenchymal transition (EMT).</p><p><strong>Results: </strong>Multiomics analyses indicated layer-associated epithelial injury, inflammatory activation, and EMT-like fibroblast/myofibroblast remodelling during NEC. Single-cell sequencing of six intestinal samples showed reduced epithelial-cell abundance with increased fibroblast and smooth-muscle-cell proportions in NEC. In the murine model, CYD19 treatment was associated with improved intestinal pathology, survival, inflammatory cytokine profiles, and barrier-related readouts. ANXA2, RPL13, RPL23A, and RPS28 were identified as tissue candidate biomarkers and validated by immunohistochemistry. Serum ANXA2 was higher in NEC than in available non-NEC controls (AUC, 0.944) and showed exploratory discrimination between medical NEC and highly suspected cow's-milk protein allergy; the adjusted AUC was 0.899.</p><p><strong>Conclusions: </strong>NEC is associated with inflammation-linked EMT-like intestinal remodelling and epithelial injury. ANXA2 and selected ribosomal proteins are candidate tissue biomarkers, while serum ANXA2 warrants prospective multicentre validation as a blood-based diagnostic and risk-stratification biomarker.</p><p><strong>Key points: </strong>NEC was associated with epithelial injury, excessive inflammation, and EMT-like fibroblast/myofibroblast remodelling, as revealed by integrated bulk proteomics, spatial proteomics, and single-cell sequencing. Pharmacological inhibition of Snail-mediated EMT in a murine NEC model was associated with improved intestinal injury, inflammatory responses, barrier-related readouts, and survival. ANXA2, RPL13, RPL23A, and RPS28 were identified as candidate tissue biomarkers, while serum ANXA2 showed exploratory potential for NEC diagnosis and risk stratification.</p>","PeriodicalId":10189,"journal":{"name":"Clinical and Translational Medicine","volume":"16 9","pages":"e70793"},"PeriodicalIF":7.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13578613/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148975892","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":"Making deep-tissue monitoring clinically accessible with soft, biodegradable inductor-capacitor implants.","authors":"Yuqun Lan, Shuang Li, Yewang Su","doi":"10.1002/ctm2.70844","DOIUrl":"10.1002/ctm2.70844","url":null,"abstract":"","PeriodicalId":10189,"journal":{"name":"Clinical and Translational Medicine","volume":"16 9","pages":"e70844"},"PeriodicalIF":7.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13588270/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149001309","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 the GPR183/EBI2‒oxysterol axis in tuberculosis: Immunometabolic regulation and prospects for host-directed therapy.","authors":"Junfei Wang, Yingnan Zhou, Xunming Ji, Haiping Zhao, Lingjun Zhan","doi":"10.1002/ctm2.70755","DOIUrl":"10.1002/ctm2.70755","url":null,"abstract":"<p><strong>Background: </strong>Tuberculosis (TB), caused predominantly by Mycobacterium tuberculosis (Mtb), remains a major global health challenge despite the availability of antimicrobial chemotherapy. Drug-resistant TB, latent infection, immunopathology and metabolic comorbidities such as diabetes continue to undermine treatment efficacy, highlighting the urgent need for host-directed therapeutic (HDT) strategies that complement antibacterial regimens. G protein-coupled receptors (GPCRs) are highly tractable drug targets that integrate immune and metabolic signals. Among them, GPR183, also known as Epstein‒Barr virus-induced gene 2 (EBI2), has emerged as an oxysterol-sensing receptor with growing relevance to TB pathogenesis.</p><p><strong>Main body: </strong>GPR183 is activated by oxysterol gradients, particularly 7α,25-dihydroxycholesterol (7α,25-OHC), which is generated via the CH25H‒CYP7B1‒HSD3B7 metabolic axis. This pathway regulates diverse immune functions, including immune-cell positioning, macrophage recruitment, dendritic-cell and lymphocyte localisation, type I interferon restraint and autophagy induction. In the context of TB, reduced GPR183 expression and impaired oxysterol signalling have been linked to disease severity, diabetes-associated susceptibility and defective macrophage antimicrobial responses.</p><p><strong>Conclusion: </strong>Collectively, these observations position the GPR183‒oxysterol axis as a potential immunometabolic checkpoint that coordinates macrophage trafficking with autophagic control of intracellular Mtb while simultaneously curbing excessive type I interferon-driven immunopathology. In this review, we summarise current evidence linking GPR183 biology with TB immunity, discuss available pharmacological modulators and GPCR-targeted drug-development challenges, and propose experimental frameworks to evaluate GPR183 as a candidate HDT target for TB.</p>","PeriodicalId":10189,"journal":{"name":"Clinical and Translational Medicine","volume":"16 9","pages":"e70755"},"PeriodicalIF":7.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13570198/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148954897","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":"Organ-specific endothelial heterogeneity: From developmental blueprints to precision vascular medicine.","authors":"Yu-Xiang Wang, Qi Chen, Yang Liu","doi":"10.1002/ctm2.70820","DOIUrl":"10.1002/ctm2.70820","url":null,"abstract":"","PeriodicalId":10189,"journal":{"name":"Clinical and Translational Medicine","volume":"16 9","pages":"e70820"},"PeriodicalIF":7.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13570199/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148954906","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":"CRISPR-Cas9 and precision editing technologies linking functional genomics to clinical translation in genetic diseases.","authors":"Zijing Wen, Jianming Su","doi":"10.1002/ctm2.70764","DOIUrl":"10.1002/ctm2.70764","url":null,"abstract":"<p><strong>Background: </strong>CRISPR-Cas9 and derivative precision-editing platforms increasingly connect pathogenic variant interpretation with functional genomics and therapeutic development in genetic diseases. This narrative review focuses on a variant-mechanism-driven framework for matching editing strategies to mutation structure, functional consequence, disease-model evidence, delivery feasibility, safety risk, and translational readiness.</p><p><strong>Main body: </strong>The review summarizes how monogenic, polygenic, coding, non-coding, mitochondrial, and complex disease contexts influence the choice of canonical Cas9 editing, base editing, prime editing, Cas variants, CRISPR interference/activation, epigenome editing, and disease-model systems. It further compares ex vivo and in vivo delivery routes, safety assessment strategies, immunogenicity and genotoxicity concerns, and clinical implementation barriers, including CMC/manufacturing scalability, long-term follow-up, affordability, and regulatory oversight. Current evidence supports the clinical maturity of ex vivo hematopoietic editing, whereas most in vivo and precision-repair approaches remain constrained by delivery, durability, product heterogeneity, and safety uncertainties.</p><p><strong>Conclusion: </strong>The central conclusion is that future CRISPR-based interventions should be judged not only by editability, but by whether molecular correction can be translated into durable, safe, manufacturable, and clinically meaningful benefit.</p>","PeriodicalId":10189,"journal":{"name":"Clinical and Translational Medicine","volume":"16 9","pages":"e70764"},"PeriodicalIF":7.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13602823/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149036740","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":"Piezo1 in digestive homeostasis and disease: Barrier function, immune signalling, cellular injury and metabolism.","authors":"Yuan Xia, Chang Liang, Zhuoqing Zhuang, Pingrun Chen, Zhe Xiong, Junzhu Lu, Yan Zhang","doi":"10.1002/ctm2.70832","DOIUrl":"10.1002/ctm2.70832","url":null,"abstract":"<p><strong>Background: </strong>Piezo1 is a mechanosensitive cation channel that converts stretch, compression, and shear stress into calcium-dependent signals. This narrative review evaluates how Piezo1 contributes to digestive physiology and disease and why divergent outcomes arise across experimental contexts.</p><p><strong>Main body: </strong>We searched PubMed/MEDLINE, Embase, Web of Science, and Scopus from database inception to 15 July 2026, prioritising primary studies that used Piezo1-specific genetic or pharmacological interventions. Piezo1-specific evidence supports roles in epithelial junctional adaptation, mucus production, stem-cell renewal, immune activation, injury, fibrosis, and gastrointestinal endocrine signalling. A contextual framework based on cell identity and state, mechanical stimulus, and tissue or disease phase helps explain these divergent effects. Transient physiological activation may support homeostasis and repair, whereas persistent or excessive activation can promote Ca²⁺ overload, inflammasome signalling, mitochondrial dysfunction, and matrix remodelling. The strongest digestive-system evidence for mechanometabolic coupling concerns macrophage glycolysis, enterocyte nutrient handling, and selected endocrine and lipid-regulatory pathways. Evidence for Piezo1-dependent lactate production remains model-specific, and direct digestive evidence for lactylation is absent. One mechanistic mouse study supports hepatic endothelial regulation of bile-acid synthesis, whereas intestinal Piezo1 control of bile-acid homeostasis remains unestablished.</p><p><strong>Conclusion: </strong>Therapeutic translation is limited by non-selective tool compounds, broad tissue expression and the need for targeted delivery and phase-appropriate modulation. Piezo1 is therefore best viewed as a context-dependent mechanotransducer rather than a uniformly pathogenic target.</p>","PeriodicalId":10189,"journal":{"name":"Clinical and Translational Medicine","volume":"16 9","pages":"e70832"},"PeriodicalIF":7.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13574540/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148966222","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}