Clinical and translational discovery最新文献

{"title":"The metabolic-immune hub: Dual roles of indoleamine 2,3-dioxygenase in the acute kidney injury-to-chronic kidney disease transition and therapeutic perspectives","authors":"Ziyi Qiu,&nbsp;Binbin Pan","doi":"10.1002/ctd2.70191","DOIUrl":"https://doi.org/10.1002/ctd2.70191","url":null,"abstract":"<p>The transition from acute kidney injury (AKI) to chronic kidney disease (CKD) represents a critical determinant of long-term prognosis, yet the underlying immunometabolic mechanisms remain incompletely defined. Indoleamine 2,3-dioxygenase (IDO), the rate-limiting enzyme of the kynurenine pathway (KP) of tryptophan (Trp) metabolism, has emerged as a pivotal metabolic-immune checkpoint linking cellular metabolism to the immune microenvironment. This review systematically delineates the dual, time-dependent roles of IDO across the AKI-to-CKD continuum. During early AKI, IDO induction confers protection through expansion of regulatory T cells, M2 macrophage polarisation and IDO2-mediated suppression of ferroptosis via glutathione peroxidase 4 stabilisation. However, sustained IDO activation drives a pathogenic phenotype: persistent Trp depletion activates general control non-derepressible 2 kinase and the DNA damage response, toxic metabolites, including quinolinic acid (QA), promote tubular dysfunction and fibrosis, nicotinamide adenine dinucleotide (NAD⁺) supply contracts, and sustained aryl hydrocarbon receptor (AhR) signalling reshapes the immune microenvironment towards fibrosis. Concurrently, IDO impairs peritubular capillary stability, and hypoxia-inducible factor (HIF)–AhR crosstalk via their shared aryl hydrocarbon receptor nuclear translocator (ARNT/HIF-1β) dimerisation partner amplifies pro-fibrotic transcription. We synthesise the mechanisms driving this functional reversal, evaluate the kynurenine-to-tryptophan ratio as a candidate biomarker for AKI-to-CKD risk stratification benchmarked against conventional renal biomarkers, and propose a precision-timed intervention toolkit, including selective IDO1 inhibitors, AhR modulators, NAD⁺ precursors, QA scavengers, and senolytic combinations—informed by clinical trial experience from oncology. Gene knockout studies that establish causal roles of IDO and downstream targets are systematically reviewed. The framework reframes IDO as a stage-specific metabolic-immune switch whose targeted modulation offers a tractable route to prevent renal fibrosis after AKI.</p>","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"6 4","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70191","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148753056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"APOE expression is associated with molecular class, context-dependent survival and myeloid immune features in lower-grade glioma","authors":"Jiajun Xu,&nbsp;Lin Yang,&nbsp;Yanlong Ma,&nbsp;Yanhui Peng,&nbsp;Juncheng Wang,&nbsp;Wenping Liu","doi":"10.1002/ctd2.70190","DOIUrl":"https://doi.org/10.1002/ctd2.70190","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The <i>APOE</i> gene encodes ApoE, a lipid-transport protein implicated in neuroinflammatory processes. Whether <i>APOE</i> expression independently predicts outcome in lower-grade glioma (LGG), after accounting for IDH mutation and 1p/19q codeletion, remains unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We analysed The Cancer Genome Atlas (TCGA) pan-cancer and LGG transcriptomic and clinical data. In LGG, <i>APOE</i> was modelled continuously in Cox regression adjusted for age, histological grade and IDH/1p/19q molecular class; molecular-class-stratified and interaction analyses were performed. Results were evaluated in the Chinese Glioma Genome Atlas (CGGA)_693 and CGGA_325 cohorts. Immune deconvolution, myeloid/lipid programme scores and author-annotated GSE197543 single-cell data were used to define the immune and cellular context of <i>APOE</i>.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Higher <i>APOE</i> expression was associated with favourable survival in univariable TCGA-LGG analyses, but not after adjustment for molecular class (overall survival hazard ratio per 1-SD increase, 1.021; 95% confidence interval, 0.830–1.256; <i>p</i> = 0.846). The <i>APOE</i>–survival association differed across molecular classes (global interaction <i>p</i> = 1.92 × 10⁻⁴), including an adverse association in IDH-wild-type tumours. External results were heterogeneous: the unadjusted association in CGGA_693 attenuated after adjustment and was not consistently reproduced in CGGA_325. <i>APOE</i> correlated positively with tumour-associated macrophage/macrophage transcriptional programmes in TCGA and both CGGA cohorts. Single-cell data localised <i>APOE</i> expression primarily to microglial and macrophage populations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The apparent favourable association between <i>APOE</i> and LGG survival is molecular-context dependent and not consistently independent across cohorts. <i>APOE</i> may primarily mark a myeloid immune–metabolic context rather than an independently protective prognostic determinant.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"6 4","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70190","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148753058","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Selected monosaccharides in cancer: Metabolic routing, post-translational modification, immunity and therapeutic potential","authors":"Qin Ouyang,&nbsp;Ke Gao,&nbsp;Haojie Lu,&nbsp;Shu Zhang","doi":"10.1002/ctd2.70186","DOIUrl":"https://doi.org/10.1002/ctd2.70186","url":null,"abstract":"<p>Metabolic reprogramming and glycosylation remodelling are hallmarks of cancer, and selected monosaccharides are increasingly recognized as key regulators of both processes. Beyond serving as fuels, glucose, galactose, mannose and fructose shape glycosylation, lipid synthesis, antitumour immunity and tumour–host communication. Here, we discuss how these monosaccharides are rerouted across tumour, immune and stromal compartments to generate context-dependent tumour-promoting or antitumour effects. We further evaluate pharmacological opportunities, including metabolic intervention, glycosylation-directed therapy and rational combination strategies, while highlighting major translational barriers such as tumour heterogeneity, biomarker selection and systemic toxicity. This framework positions monosaccharide metabolism as a potential entry point for precision oncology.</p>","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"6 4","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70186","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148752529","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and validation of individualized prognostic nomograms based on the tumour-stroma percentage in patients with proximal and distal gastric cancer: A population-based study","authors":"Yueling Wang,&nbsp;Yan Yang,&nbsp;Liao Zhang,&nbsp;Yitian Xu,&nbsp;Renchao Zhang,&nbsp;Yuan Fang,&nbsp;Chao Han,&nbsp;Chen Huang","doi":"10.1002/ctd2.70184","DOIUrl":"https://doi.org/10.1002/ctd2.70184","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Gastric cancers (GCs) arising in the proximal and distal stomach are increasingly recognized as biologically and clinically heterogeneous subtypes of GC. However, individualized prognostic tools specifically designed for these two tumour locations remain insufficient.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The clinical records, pathological findings, laboratory indicators, and follow-up data from 813 patients with GC were retrospectively analysed. Survival-related variables were examined separately in the proximal GC (PGC) and distal GC (DGC) cohorts using Cox proportional hazards modelling. Factors that remained relevant in the final models were integrated into two tumour location-based nomograms for overall survival (OS) estimation. The models were examined using receiver operating characteristic (ROC) curves, Harrell's concordance index (<i>C</i>-index), calibration plots and decision curve to assess discrimination, agreement and clinical usefulness.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In patients with PGC, the final model retained tumour-stroma percentage (TSP) (hazard ratio [HR] = 2.485, 95% confidence interval [CI] 1.258–4.908, <i>p</i> = .009), vascular invasion (HR = 1.911, 95% CI 1.018–3.587, <i>p</i> = .044) and pathological TNM stage (pTNM) (HR = 1.943, 95% CI 1.093–3.453, <i>p</i> = .024) regard as survival-related predictors. For DGC, nerve invasion (HR = 2.174, 95% CI 1.227–3.851, <i>p</i> = .005) and pTNM stage (HR = 2.070, 95% CI 1.373–4.177, <i>p</i> = .004) were retained in the final model. The location-specific nomograms demonstrated favourable discriminatory ability for predicting 5-year OS, with AUC values of 0.924 for PGC and 0.861 for DGC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>TSP was associated with survival outcomes in GC and showed particular prognostic relevance in PGC. Developing separate prognostic nomograms for PGC and DGC may provide a practical approach for improving individualized clinical management.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"6 4","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70184","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148752530","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mesenchymal stem cell-derived exosomes for cardiac repair: Challenges, standardization gaps and a realistic path to clinical translation","authors":"Sakhavat Abolhasani,&nbsp;Yasin Ahmadi,&nbsp;Amin Jalizih","doi":"10.1002/ctd2.70185","DOIUrl":"https://doi.org/10.1002/ctd2.70185","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Cardiovascular diseases remain the leading cause of mortality worldwide, accounting for approximately one-third of global deaths annually. Despite advances in pharmacological and interventional therapies, the adult mammalian heart exhibits minimal intrinsic regenerative capacity. Mesenchymal stem cell-derived small extracellular vesicles (MSC-sEVs), commonly referred to as exosomes, have emerged as a promising cell-free therapeutic approach for cardiac repair by delivering bioactive molecules that reduce apoptosis, fibrosis and inflammation while promoting angiogenesis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This review critically assesses current production, purification and engineering methods for MSC-sEVs, highlighting translational challenges and proposing actionable solutions for clinical development.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Key findings</h3>\u0000 \u0000 <p>Preclinical efficacy shows wide variations due to inconsistent isolation methods, dosing protocols and animal models. A standardized potency assay correlating with cardiac functional outcomes is lacking. While completed phase I trials confirm safety, no controlled phase II/III efficacy trials for cardiac indications have been reported. Engineered sEVs demonstrate improved targeting in rodents, but human translation remains unproven. Major barriers include the absence of validated potency assays, GMP-compatible standardization, and large-animal efficacy data.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>MSC-sEVs represent a promising investigational platform requiring substantial methodological advancement before clinical translation. Significant hurdles, particularly the absence of validated potency assays, manufacturing standardization, and controlled efficacy trials, must be overcome before regulatory authorization can realistically be contemplated. The timeline for regulatory approval remains uncertain and depends on successful completion of these prerequisites.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"6 4","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70185","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148616729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of plant-derived biomimetic nanoparticles as a novel targeted drug delivery platform","authors":"Jihad Hasan,&nbsp;Asnaf Nihan Shuvo,&nbsp;Md. Rezaul Karim Sheikh,&nbsp;A. Nayeem Faruqui","doi":"10.1002/ctd2.70183","DOIUrl":"https://doi.org/10.1002/ctd2.70183","url":null,"abstract":"<p>Plant-derived biomimetic nanoparticles (PD-BNPs) have emerged as a very promising and sustainable alternative to traditional nanocarriers for targeted drug delivery. Synthetic nanoparticles provide great tunability but suffer from issues such as cytotoxicity, fast immunological elimination, and sustainability problems, while those of animal origin are restricted by limitations such as difficulties associated with scale-up and safety. On the other hand, plant-based biomimetic nanoparticles (PD-BNPs), especially plant-derived exosome-like nanoparticles, show great biocompatibility, low immunogenicity, and inherent therapeutic properties due to their phytochemicals, lipids, proteins, and RNA. They can provide antioxidant, anti-inflammatory, and immunomodulating activity. With developments in ultracentrifugation techniques, size exclusion chromatography, nanoemulsion technology and green synthesis methods, it has become possible to enhance the purification, stability, and scaling up of PD-BNPs. Natural tissue targeting capabilities and responsive properties make these nanoparticles ideal candidates for drug delivery. Despite some of the limitations, such as variations in sources and non-standardized production, these nanoparticles have immense applications in precision drug delivery and nanomedicine.</p>","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"6 4","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70183","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148616065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vector-based comparison as a novel framework for assessing multi-endpoint clinical trials: Applications to actual data","authors":"Maria Kokkali,&nbsp;Vangelis D. Karalis","doi":"10.1002/ctd2.70180","DOIUrl":"https://doi.org/10.1002/ctd2.70180","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>For clinical trials, the vector-based comparison (VBC) technique presented provides an alternative approach to solve a traditional problem caused by multiple endpoints. VBC uses vector algebra to form an endpoint vector and decompose it into different parts, thus reducing heterogeneity, increasing precision, and establishing a structure for the evaluation of clinical trial outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this study, VBC was applied to 5 clinical trials with 695 patients. The primary clinical endpoint (E1) was defined as the reference endpoint, and the remaining endpoints were expressed relative to the primary endpoint. A paired <i>t</i>-test of the confidence interval widths, per decomposed endpoint, was conducted to test the effect of the VBC. Furthermore, machine learning and principal component analysis were applied to analyze whether the decomposed endpoints maintained the properties of the initial measures.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The vector angle between E1 and the decomposed endpoints remained smaller than 45° in a typical study, which, before decomposing, was found to be correlated. Use of VBC brought down confidence interval widths by approximately 50%, implying less variability. Principal component analysis confirmed preservation of endpoint-specific properties, while Type I error simulations showed that VBC did not elevate false-positive rates under null conditions. Endpoint-specific type I error rates have been close to the nominal value of 0.05.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>VBC can decompose clinical endpoints into nonredundant components while preserving endpoint-specific information and reducing variability without inflating Type I error. VBC serves as a reproducible and practical preprocessing method for clinical trials with many endpoints.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"6 4","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70180","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148615837","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A molecular landscape and prognosis signature based on histone tyrosine sulfation in pan-cancer analysis","authors":"Meijuan Cai,&nbsp;Yuhao Liao,&nbsp;Jun Lin,&nbsp;Xumeng Chen,&nbsp;Jiale Wang,&nbsp;Zhijuan Li,&nbsp;Zhengjun Yang,&nbsp;DianKui Cai","doi":"10.1002/ctd2.70178","DOIUrl":"https://doi.org/10.1002/ctd2.70178","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Tyrosine sulfation, a widespread post-translational modification in mammals mainly associated with secretory and transmembrane proteins, has recently been found to occur on histones. However, the molecular landscape and prognostic signature of pan-cancer based on histone tyrosine sulfation (<i>HYsulf</i>) remain poorly understood.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We investigated the expression diversity, molecular regulation landscape, DNA methylation and mutation patterns of 51 <i>HYsulf</i>-related genes across 33 cancer types from the Cancer Genome Atlas (TCGA). Additionally, we classified pan-cancer samples into high- and low-score subgroups (Hscore and Lscore) by establishing the <i>HYsulf</i> score.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Result</h3>\u0000 \u0000 <p>Enrichment analysis revealed high enrichment of immune-related pathways, cancer-associated hallmarks and pathways, hypoxia, metabolism and cell fate-related pathways in the Hscore subgroup. Infiltration analysis indicated correlations between immune infiltration and <i>HYsulf</i> score, with negative associations observed primarily with activated and resting NK cells, while positive correlations were prominent with Tregs, macrophages M1 and M0. <i>HYsulf</i> score showed significant correlations with immuno-inhibitors, immuno-stimulators, MHC, chemokines and their receptors, as well as emerging biomarkers of immune therapeutic response such as TMB, MSI and neoantigens. Furthermore, evaluations of seven metabolic features suggested a strong link between <i>HYsulf</i> and metabolic reprogramming in pan-cancer. Additionally, drug response evaluation using the CellMiner database uncovered candidate compounds associated with <i>HYsulf</i>‑related genes. Importantly, the <i>HYsulf</i> score demonstrated prognostic stratification capacity in predicting overall survival or progression‑free time in 10 tumour types. Finally, the nomogram based on the <i>HYsulf</i> score was established for prognostic prediction of PCPG and UVM.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>We developed a <i>HYsulf</i>-associated transcriptomic signature based on <i>HYsulf</i> that holds promise for predicting prognosis and drug response.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"6 4","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70178","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148615838","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The FAP+ CAF subset in bladder cancer: A key driver of cancer cell stemness and a promising target for FAPI therapy","authors":"Meiqian Li,&nbsp;Shikun Wang,&nbsp;Hua Xiao,&nbsp;Rong Hu,&nbsp;Yueyun Xie","doi":"10.1002/ctd2.70179","DOIUrl":"https://doi.org/10.1002/ctd2.70179","url":null,"abstract":"&lt;p&gt;Bladder cancer (BCa) is one of the most common malignancies of the urinary system, and its high metastatic rate and recurrence pose major clinical challenges.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; Recent studies indicate that cancer-associated fibroblasts (CAFs) in the stromal compartment can construct a ‘stemness niche’ by secreting specific factors that activate downstream signalling pathways, thereby inducing BCa cells to acquire or maintain cancer stem cell (CSC) properties and mediating metastasis and drug resistance. Therefore, identifying markers of specific CAF subsets that drive stemness niche formation is of significant scientific value for developing novel targeted therapeutic strategies.&lt;/p&gt;&lt;p&gt;CAFs in BCa are highly heterogeneous and are spatially and functionally classified into classical subsets such as myofibroblast-like CAFs (myCAFs) and inflammatory-like CAFs (iCAFs). Among these, fibroblast activation protein-positive (FAP&lt;sup&gt;+&lt;/sup&gt;) CAFs predominantly exhibit a myCAF phenotype and have emerged as a core subset mediating poor prognosis.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; FAP is a type II transmembrane serine protease that is barely expressed in healthy adult tissues but is highly expressed in the tumour microenvironment (TME) of more than 90% of epithelial-derived malignancies.&lt;/p&gt;&lt;p&gt;In May of this year, Wu et al. performed a detailed single-cell RNA-sequencing analysis (scRNA-seq) of the BCa TME using a large-scale dataset (633,702 cells retained) and reported that: (1) malignant proliferative stemness metaprogram (MPS-MP) genes were significantly enriched in Muscle-invasive bladder cancer (MIBC), with Activating Transcription Factor 3 (ATF3) serving as a key driver and showing enhanced interactions with stromal and immune cells; (2) fibroblasts exhibited the highest prognostic risk score, and at the subset level, poor-prognosis-associated cells were mainly concentrated in the FAP&lt;sup&gt;+&lt;/sup&gt; CAF subset, which also displayed stronger invasive, hypoxic and angiogenic phenotypes. By sorting FAP&lt;sup&gt;+&lt;/sup&gt; CAFs and conducting three-dimensional spheroid formation assays as well as stemness-related gene (e.g., OCT4, CD44, SOX2) expression analyses, the authors confirmed that the FAP&lt;sup&gt;+&lt;/sup&gt; CAF subset enhances the stemness phenotype in BCa cells.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; However, the precise mechanism by which FAP&lt;sup&gt;+&lt;/sup&gt; CAFs promote BCa cell stemness remains unclear. In our published work, we found that CAFs mediate stemness through secretion of miR-146a-5p and activation of Signal transducer and activator of transcription 3 (STAT3) signalling;&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; whether this CAF population belongs to the FAP&lt;sup&gt;+&lt;/sup&gt; subset warrants further investigation.&lt;/p&gt;&lt;p&gt;FAP serves as a marker of myofibroblasts.&lt;span&gt;&lt;sup&gt;4, 5&lt;/sup&gt;&lt;/span&gt; In combined analyses of T1 stage and all regions of BCa, FAP expression shows a significant positive correlation with BCa progression and may serve as a potential biomarker for predicting progression in ","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"6 4","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70179","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148615310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring precision medicine strategies for paediatric OSA: Construction of a multimodal intelligent system for surgical indication assessment","authors":"Mingjun Zhang,&nbsp;Xiaoben Liang,&nbsp;Min Guo,&nbsp;Yong Wang,&nbsp;Xiaoyan Li,&nbsp;Jing Wang,&nbsp;Hongming Xu","doi":"10.1002/ctd2.70171","DOIUrl":"https://doi.org/10.1002/ctd2.70171","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Purpose</h3>\u0000 \u0000 <p>The prevalence of obstructive sleep apnoea (OSA) is high in children, for whom accurate diagnosis and timely intervention are crucial. Current single-modal clinical evaluations have limitations. This study aimed to build a multimodal intelligent system to assist diagnosis and surgical decision-making in children presenting with clinical symptoms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A single-centre retrospective study at Shanghai Children's Hospital enrolled 220 paediatric OSA patients between March and June 2025. Comprehensive multimodal data, including medical histories, nasopharyngoscopy images, and snoring recordings, were collected. Among them, 192 children were included in the surgical indication‑positive group and 28 in the surgical indication‑negative group according to the guidelines. To predict surgical need, a multimodal fusion model was trained on a split of 120 training and 100 test samples. Class imbalance was addressed using Focal Loss, inverse weighting, and minority augmentation with regularization.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The multimodal fusion model demonstrated excellent performance, achieving a sensitivity of over 97% in identifying the necessity of adenoidal or tonsillar surgery. Compared to single-modal and bi-modal models, the multi-modal fusion model showed substantial advantages in reducing both misdiagnosis and missed diagnosis, exhibiting strong screening capabilities.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The proposed system, integrating multimodal data, provides a sensitive and accurate tool to assist diagnosis and surgical decision-making in this symptomatic population, offering a promising approach for improving clinical outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Trial registration</h3>\u0000 \u0000 <p>ChiCTR, ChiCTR2500098075.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"6 4","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70171","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148467495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}