EBioMedicine最新文献

{"title":"EARLY-ALS: a multicentre study on prodromal amyotrophic lateral sclerosis.","authors":"Isabell Cordts, Ana Galhoz, Laura Tzeplaeff, Anne Gründel, Florian Kohlmayer, Andreas Schwersenz, Ines Marschalkowski, Bogdan Bjelica, Verena Panitz, Christian Schulze, Martin Svačina, Petra Rau, André C Dorigan, Marcus Deschauer, Simon Witzel, David Brenner, Jochen H Weishaupt, Sarah K Bublitz, Stefan Lorenzl, Andreas Hermann, Tim Hagenacker, Joachim Wolf, Martin Regensburger, Helmar C Lehmann, Maike F Dohrn, Johannes Dorst, René Guenther, André Maier, Thomas Meyer, Daniel Zeller, Christoph Neuwirth, Markus Weber, Jan C Koch, Matthias Boentert, Markus Weiler, Susanne Petri, Ute Weyen, Torsten Grehl, Michael P Menden, Paul Lingor","doi":"10.1016/j.ebiom.2026.106505","DOIUrl":"10.1016/j.ebiom.2026.106505","url":null,"abstract":"<p><strong>Background: </strong>Neurodegenerative diseases often feature a prolonged phase of subtle changes preceding diagnosis. In amyotrophic lateral sclerosis (ALS), defining this prodromal period is critical for identifying early disease features and intervention windows.</p><p><strong>Methods: </strong>In this case-control study, 475 patients with ALS and 285 controls from 20 centres in Germany and Switzerland completed a digital questionnaire on prodromal symptoms and health-related factors. Logistic regression included subgroup analyses by sex and clinical strata.</p><p><strong>Findings: </strong>Patients with ALS reported a higher burden of prodromal complaints (OR 7.50, 95% CI 4.27-13.17; P < 0.001), particularly neuro-motor, sensory, and pain-related symptoms. Before symptom onset, patients consulted neurologists more often (OR 1.26, 1.10-1.44; P < 0.001) and females more often received speech therapy (OR 2.35, 1.05-5.28; P = 0.038). Prodromal herniated discs were more common in males (OR 2.21, 1.04-4.68; P = 0.038) and spinal-onset patients (OR 2.14, 1.25-3.67; P = 0.006). Patients more often had lower secondary education (OR 1.93, 1.24-3.01; P = 0.004), physically demanding occupations (OR 2.21, 1.42-3.43; P < 0.001), and higher consumption habits (P < 0.005). Weight trajectories differed by sex (P = 0.009), with pre-onset weight loss in male patients (P < 0.001).</p><p><strong>Interpretation: </strong>Patients with ALS retrospectively reported subtle motor impairment before recognised symptom onset, alongside altered healthcare use and sex- and subgroup-specific patterns. These findings suggest that sporadic ALS may be preceded by a prodromal period and identify mild motor impairment as a potential marker, pending prospective validation.</p><p><strong>Funding: </strong>DGM e. V.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"133 ","pages":"106505"},"PeriodicalIF":11.2,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149147394","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":"Immune effects of faecal microbiota transplantation in amyotrophic lateral sclerosis: a pilot multicentre, randomised, masked, sham-controlled, proof-of concept trial.","authors":"Elisabetta Zucchi, Elena Niccolai, Flavio De Maio, Riccardo Cuoghi Costantini, Gianluca Quaranta, Alessandra Guarnaccia, Stefano Bibbò, Ilaria Martinelli, Giulia Gianferrari, Cecilia Simonini, Giulia Nannini, Matteo Lulli, Simone Baldi, Gianluca Bartolucci, Roberto Vicini, Margherita Capasso, Giulia Bisogni, Amelia Conte, Paola Brunori, Giovanni Cammarota, Sabrina Paganoni, Roberto D'Amico, Amedeo Amedei, Luca Masucci, Jessica Mandrioli","doi":"10.1016/j.ebiom.2026.106509","DOIUrl":"10.1016/j.ebiom.2026.106509","url":null,"abstract":"<p><strong>Background: </strong>The gut microbiota modulates peripheral immunity, which is altered in amyotrophic lateral sclerosis (ALS). Faecal microbiota transplantation (FMT) may exert immunological effects, but its impact in ALS remains unclear.</p><p><strong>Methods: </strong>FETR-ALS was a multicentre, randomised, masked, sham-controlled proof-of-concept trial conducted at four Italian ALS centres. Adults with ALS of 18 months duration or less and forced vital capacity of at least 70% predicted were randomly assigned (2:1) to receive FMT or a sham procedure (SP). The intervention consisted of two nasojejunal administrations of screened-donor faecal suspension at baseline and month 6, without antibiotic preconditioning. The primary endpoint was change in circulating Tregs among CD4⁺ T cells at 6 months. Secondary endpoints included safety, ALS Functional Rating Scale-Revised slope, respiratory and nutritional measures, survival, and exploratory biomarker profiles. Analyses followed the intention-to-treat principle.</p><p><strong>Clinicaltrials: </strong>gov identifier: NCT03766321.</p><p><strong>Findings: </strong>Between 2020 and 2024, 43 individuals were screened and 42 were enrolled and randomly assigned to FMT (n = 28; mean age 56.1 years [SD 8.2]; 14 [50%] male) or SP (n = 14; 59.6 years [9.1]; eight [57%] male). Overall, 29 participants completed the second procedure and 6-month follow-up, and Treg measurements were available for 28. The primary outcome was not met: at 6 months, 8/18 (44%) participant receiving FMT versus 2/10 (20%) receiving SP achieved a ≥20% increase in circulating Tregs (odds ratio [OR] 3.20, 95% CI 0.59-25.36; p = 0.21). Mean Treg increase was 2.36 percentage points higher with FMT (95% CI 0.19-4.55; p = 0.04). ALSFRS-R declined by -1.07 points/month in the SP group and -0.76 points/month in the FMT group, with a between-group difference in monthly decline of 0.31 points/month favouring FMT (95% CI 0.11-0.51; p = 0.002). Conversely, at month 6, the MRC score was lower in the FMT group than in the SP group (0.75 versus 0.89; mean difference -0.13, 95% CI -0.26 to 0.00; p = 0.042). FMT was associated with 32 adverse events (12.5% severe) versus 14 (28.6% severe) in SP, mostly gastrointestinal or infectious.</p><p><strong>Interpretation: </strong>In this exploratory trial, FMT was not associated with major safety concerns. Although the primary endpoint was not met, FMT was associated with a modest increase in circulating Tregs.</p><p><strong>Funding: </strong>Italian Ministry of Health.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"133 ","pages":"106509"},"PeriodicalIF":11.2,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13676721/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149135393","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":"Deciphering the heterogeneity of prodromal α-synucleinopathy: linking brain biotyping and gut dysbiosis in isolated REM sleep behaviour disorder.","authors":"Shi Tang, Yuhua Yang, Yanlin Wang, Siyi Gong, Ningning Li, Zhixuan He, Jianzhang Ni, Jing Wang, Yaping Liu, Joey Wing Yan Chan, Winnie Chiu Wing Chu, Vincent Chung Tong Mok, Zigui Chen, Bei Huang, Yun Kwok Wing","doi":"10.1016/j.ebiom.2026.106503","DOIUrl":"10.1016/j.ebiom.2026.106503","url":null,"abstract":"<p><strong>Background: </strong>Isolated/idiopathic REM sleep behaviour disorder (iRBD) is a specific prodrome of α-synucleinopathies. We previously identified two distinct clinical-neuroimaging biotypes in iRBD: Biotype 1, marked by widespread cortical-subcortical-cerebellar atrophy with motor and cognitive deficits, and Biotype 2, with preserved brain structure and neurocognition. Converging evidence implicates the gut-brain axis in early α-synucleinopathy, yet its role in these divergent iRBD phenotypes remains unexplored.</p><p><strong>Methods: </strong>We analysed faecal microbiota using shotgun metagenomic sequencing and structural neuroimaging data from 167 participants (42 Biotype 1, 50 Biotype 2, 75 controls). Microbial features and brain structure were compared across groups. Gut-brain associations were assessed using sparse partial least squares regression to link microbiome features with neuroanatomical patterns.</p><p><strong>Findings: </strong>Overall microbial composition did not significantly differ between Biotype 1 and Biotype 2, and both biotypes showed depletion of short-chain fatty acid-producing bacteria. Relative to the shared dysbiotic background, Biotype 1 displayed more pronounced taxon- and pathway-level alterations, including enrichment of Collinsella aerofaciens, Cloacibacillus evryensis, and Mogibacterium sp. BX12, which were associated with Biotype 1-specific brain atrophy. Biotype 2 showed milder dysbiosis with fewer differentially abundant species. These patterns were consistent in sensitivity analyses and fully adjusted models.</p><p><strong>Interpretation: </strong>Beyond a shared depletion of short-chain fatty acid-producing bacteria, iRBD biotypes exhibit differences in taxonomic and functional profiles, with these differences being more pronounced in Biotype 1. These findings support a role for the gut-brain axis in early α-synucleinopathy and its phenotypic heterogeneity.</p><p><strong>Funding: </strong>This study was funded by the Health and Medical Research Fund of the Food and Health Bureau (Ref No.: 05162876 and 10210686) and Research Grants Council (RGC-CRF Ref No.: C4044-21G) of Hong Kong.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"133 ","pages":"106503"},"PeriodicalIF":11.2,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13676696/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149135438","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":"The CLEC7A Y238∗ variant and susceptibility to pneumonia: a prospective population-based cohort study and mechanistic investigation.","authors":"Oskar Thofte, Valdemar Öhnström, Linda Yamba Yamba, Ashfaque Memon, Anton Grundberg, Yu-Ching Su, Hortense Slevogt, Peter F Zipfel, Carsten Scavenius, Bruno Steimbrüch, Karin Leandersson, Anders P Håkansson, Kristina Sundquist, Olle Melander, Anna M Blom, Kristian Riesbeck","doi":"10.1016/j.ebiom.2026.106497","DOIUrl":"10.1016/j.ebiom.2026.106497","url":null,"abstract":"<p><strong>Background: </strong>DECTIN-1, a C-type lectin receptor encoded by CLEC7A, mediates antifungal immunity, but its antibacterial role remains unclear. We investigated, using human genetic and animal studies, whether the common loss-of-function CLEC7A Y238∗ variant (rs16910526) influences susceptibility to bacterial respiratory infection, and sought to identify the bacterial ligand mediating DECTIN-1 recognition.</p><p><strong>Methods: </strong>We analysed Y238∗ and pneumonia risk in the Malmö Diet and Cancer Study, a prospective Swedish cohort, using Cox models with age as timescale (28,126 participants, 5493 events; 26,601 and 5190 fully adjusted) over a mean 17·3 years of follow-up. We challenged wild-type, Clec7a^+/-, and Clec7a^-/- mice with Streptococcus pneumoniae and non-typeable Haemophilus influenzae (NTHi). Affinity proteomics, ELISA, flow cytometry, and NF-κB reporter assays identified and validated the ligand.</p><p><strong>Findings: </strong>Y238∗ carriers had elevated pneumonia risk in adjusted Cox models (HR 1·12, 95% CI 1·04-1·20; p = 0·002; concordant competing-risk sHR 1·12, 1·04-1·20). Clec7a-deficient mice showed gene-dose-dependent impairment of S. pneumoniae clearance, impaired NTHi clearance, and blunted cytokine responses. Affinity pull-down identified elongation factor Tu (EF-Tu) as a DECTIN-1 ligand that bound the carbohydrate-recognition domain and activated NF-κB signalling when clustered; orthologues from four bacterial species also bound.</p><p><strong>Interpretation: </strong>These findings support a role for DECTIN-1 in pulmonary antibacterial defence and suggest that inherited deficiency increases pneumonia susceptibility in humans. EF-Tu is a candidate ligand that provides mechanistic support for the association.</p><p><strong>Funding: </strong>Swedish Research Council, Knut and Alice Wallenberg Foundation, Swedish Heart Lung Foundation, Swedish Government Funds for Clinical Research (ALF), Skåne County Council's Research and Development Foundation.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"133 ","pages":"106497"},"PeriodicalIF":11.2,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149135450","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":"A proteome-based classification of paediatric adrenocortical tumours links functional tumour states to clinical outcome and therapeutic vulnerabilities.","authors":"Rainer Claus, Andreas Metousis, Victoria E Fincke, Marina Kunstreich, Stefan A Wudy, Eva Jüttner, Joern Pons-Kühnemann, Christian Vokuhl, Michael C Frühwald, Christoph Röcken, Lisa Schweizer, Pascal D Johann, Antje Redlich, Matthias Mann, Michaela Kuhlen","doi":"10.1016/j.ebiom.2026.106504","DOIUrl":"10.1016/j.ebiom.2026.106504","url":null,"abstract":"<p><strong>Background: </strong>Paediatric adrenocortical tumours (pACT) are rare endocrine neoplasms characterised by marked biological heterogeneity and variable clinical behaviour. Current risk stratification relies largely on histopathology and clinical staging, which incompletely capture underlying tumour biology. We aimed to define proteome-based subtypes of pACT and evaluate their biological, clinical, and therapeutic relevance.</p><p><strong>Methods: </strong>In this retrospective cohort study, we performed mass spectrometry-based proteomic profiling of 83 pACT and adjacent non-tumour adrenal tissues. Differential abundance analysis, pathway enrichment, consensus clustering, survival analyses, and clinicopathological correlations were performed. A minimal protein classifier was derived using forward feature selection and leave-one-out cross-validation. Cluster-specific therapeutic vulnerabilities were assessed using a curated druggability framework.</p><p><strong>Findings: </strong>Tumours displayed profound proteomic differences compared with adjacent non-tumour adrenal cortex, characterised by activation of cholesterol biosynthesis, steroidogenic, MYC, mTORC1, and cell-cycle programs and suppression of extracellular matrix, adhesion, and immune-related pathways. Unsupervised clustering identified four proteome-defined tumour states that only partially overlapped with histopathological diagnosis. These subtypes differed significantly in endocrine phenotype, vascular invasion, Ki67 index, necrosis, and overall survival (log-rank p = 0.00036). Distinct biological programs included stromal-immune-enriched, mitochondrial steroidogenic, IGF/mTOR-driven anabolic, and highly proliferative chromatin-remodelled states. A five-protein classifier (DAAM2, CIP2A, TSC2, PALS2, and P3H1) reproduced cluster assignments with 92.8% leave-one-out cross-validation accuracy. Cluster-specific analyses identified distinct therapeutic target landscapes, including IGF-axis and epigenetic vulnerabilities.</p><p><strong>Interpretation: </strong>Proteomic profiling defines biologically and clinically distinct pACT subtypes that provide prognostic information beyond histopathology. This framework enables proteome-based stratification, identifies candidate therapeutic vulnerabilities, and can be approximated by a five-protein classifier.</p><p><strong>Funding: </strong>German Childhood Cancer Foundation, Mitteldeutsche Kinderkrebsforschung, European Union's EU4Health Programme, Max Planck Society, Onassis Foundation, and Joachim Herz Stiftung.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"133 ","pages":"106504"},"PeriodicalIF":11.2,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13676720/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149126763","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":"NET-derived DNA is associated with cGAS-STING and type I IFN responses, as supported by monocyte stimulation cultures using plasma from female patients with SLE.","authors":"Xiaolin Cao, Dagmar Duijzer, Tineke Kardol-Hoefnagel, Bettina C Geertsema-Hoeve, Jeanette H W Leusen, Maarten Limper, Marianne Boes","doi":"10.1016/j.ebiom.2026.106507","DOIUrl":"10.1016/j.ebiom.2026.106507","url":null,"abstract":"<p><strong>Background: </strong>Neutrophil extracellular traps (NETs) are implicated in type I interferon (IFN) production in Systemic Lupus Erythematosus (SLE). While NETs are known to activate plasmacytoid dendritic cells (pDCs) via binding to Toll-like receptors, their effects on other immune cells remain underexplored. This study investigated whether NETs in plasma from patients with active SLE trigger cGAS-STING signalling in monocytes and induce the production of type I IFN and other immunomodulatory cytokines.</p><p><strong>Methods: </strong>Monocytes from healthy donors were cultured with diluted plasma from healthy donors or patients with SLE across varying disease activity, or with in vitro-generated NETs. Activation of the cGAS-STING pathway was assessed by flow cytometric analysis of phosphorylated STING (pSTING) and TBK1 (pTBK1). Cytokine production, including type I IFNs, was quantified using bead-based immunoassays. Only female donor samples meeting the study eligibility criteria were available for inclusion in this cohort.</p><p><strong>Findings: </strong>Plasma MPO-DNA levels correlated with IFNβ levels in patients with SLE (P = 0.002). SLE plasma induced STING and TBK1 phosphorylation, and IFNβ expression in healthy monocytes, with responses increasing according to donor disease activity (P < 0.0005). Experiments with healthy monocytes exposed to in vitro-generated NETs recapitulated these findings, evidenced by increased pSTING and pTBK1 expression and enhanced IFNα and IFNβ secretion (P < 0.05), which were inhibited by cGAS-IN-1.</p><p><strong>Interpretation: </strong>Our findings support a role for NET-associated DNA in activating cGAS-STING signalling and promoting type I IFN production by monocytes in SLE. These findings identify NET-mediated cGAS-STING signalling in monocytes as a pathway that warrants further investigation in the context of type I IFN-driven inflammation in SLE.</p><p><strong>Funding: </strong>Not Applicable.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"133 ","pages":"106507"},"PeriodicalIF":11.2,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13675855/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149126789","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":"Impact of Wolbachia-mediated incompatible and sterile insect techniques on dengue incidence: a large-scale cluster randomised controlled trial.","authors":"Chia-Chen Chang, Jue Tao Lim, Chee Seng Chong, Diyar Mailepessov, Borame Dickens, Yichen Zhai, Lu Deng, Caleb Lee, Li Yun Tan, Grace Chain, Muhammad Faizal Zulkifli, Jonathan Wee Kent Liew, Kathryn Vasquez, Man Ling Chau, Youming Ng, Vernon Lee, Shuzhen Sim, Cheong Huat Tan, Lee Ching Ng","doi":"10.1016/j.ebiom.2026.106476","DOIUrl":"10.1016/j.ebiom.2026.106476","url":null,"abstract":"<p><strong>Background: </strong>Wild-type female Aedes aegypti which mate with Wolbachia-infected male Aedes aegypti (Wolbachia-Aedes) produce non-viable eggs due to cytoplasmic incompatibility. Sustained releases of Wolbachia-infected male Aedes aegypti can suppress wild-type mosquito populations, but robust evidence of its efficacy in reducing dengue incidence is needed.</p><p><strong>Methods: </strong>We conducted a large-scale cluster-randomised controlled trial involving releases of male wAlbB-infected Ae. aegypti mosquitoes (wAlbB-SG) for dengue control in Singapore. Mosquitoes were irradiated to sterilise potential residual females. Fifteen clusters were randomised: 8 clusters received deployments of male wAlbB-SG infected Ae. aegypti (intervention clusters, n = 393,236) and 7 clusters received no deployments (control clusters, n = 331,192). All clusters practised baseline vector control measures. We assessed the protective efficacy of Wolbachia-Aedes to reduce dengue incidence using a differences-in-differences framework. The trial was registered with ClinicalTrials.gov (Identifier: NCT05505682) on 2022-08-18.</p><p><strong>Findings: </strong>In the pre-intervention period, dengue incidence per 100,000 was similar across control (18.63) and intervention (18.14) arms. During the intervention period, reported dengue incidence was 11.31 and 36.57 cases per 100,000 residents in intervention and control arms, respectively. Six months after releases began, intervention clusters showed reductions in total dengue incidence, ranging from 27.6% (95% CI: -35.4% to 61.3%) to 83.8% (95% CI: 50.4%-94.7%). This protective effect varied across time, with some attenuation observed during the 2023 inter-epidemic period. We estimated that 2351 cases (95% CI: 1968-2735) were averted over the period of the trial, relative to 1037 dengue cases reported in the intervention arm. Reductions in epidemiologically-linked dengue incidence were greater, ranging from 60.9% (95% CI: 21.3%-80.6%) to 99.8% (95% CI: 99.2%-99.9%).</p><p><strong>Interpretation: </strong>Our results demonstrate the high efficacy of Wolbachia-Aedes in reducing dengue incidence.</p><p><strong>Funding: </strong>Ministry of Finance, Singapore.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"132 ","pages":"106476"},"PeriodicalIF":11.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13586744/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148929322","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":"Serum biomarkers for the diagnosis and management of adolescent polyendocrine metabolic ovarian syndrome: a systematic review and meta-analysis.","authors":"Yue Shi, Chi Chiu Wang, Elisabet Stener-Victorin, Pui Wah Chung, Yao Wang","doi":"10.1016/j.ebiom.2026.106471","DOIUrl":"10.1016/j.ebiom.2026.106471","url":null,"abstract":"<p><strong>Background: </strong>Adolescent polyendocrine metabolic ovarian syndrome (PMOS) poses immediate and lifelong risks to women's health. However, reliable biomarkers for adolescent PMOS remain elusive in current clinical practice.</p><p><strong>Methods: </strong>We systematically searched six databases from inception to April 2026, following PRISMA guidelines (PROSPERO No.: CRD420251033057). Eligible studies included adolescents with PMOS and healthy controls. Primary outcomes were effect sizes of serum reproductive hormones, insulin indices, and adipokines (Hedges' g in random-effects models), with diagnostic performance assessed by AUC, sensitivity, and specificity.</p><p><strong>Findings: </strong>Fifty-one moderate-to-high quality studies comprising 4892 adolescents were included. Large effect sizes were observed for total testosterone (TT, 1.10), free androgen index (FAI, 1.19), ratio of luteinising hormone to follicle-stimulating hormone (LH/FSH, 1.07), anti-Müllerian hormone (AMH, 0.98), and adiponectin (-1.12), all with moderate-to-low certainty. Insulin resistance indices (homoeostatic model assessment of insulin resistance [HOMA-IR], 0.64; quantitative insulin sensitivity check index [QUICKI], -0.47) and leptin (0.40) showed small effect sizes with low certainty. In adolescents with obesity, AMH (1.39) and adiponectin (-1.54) showed pronounced effects. For diagnostic performance, TT (cutoff = 55.96 ng/dL), FAI (cutoff = 6.78), and LH/FSH (cutoff = 1.59) each achieved an AUC of 0.74. AMH effectively identified PMOS in obese group (AUC = 0.85, cutoff = 4.47 ng/mL) and the <17-year-old group (AUC = 0.77, cufoff = 6.05 ng/mL). For metabolic stratification, HOMA-IR performed modestly overall AUC of 0.65 (cutoff = 4.35), while adiponectin (AUC = 0.78, cutoff = 10.92 μg/mL) and leptin (AUC = 0.67, cutoff = 36.17 ng/mL) emerged as BMI-dependent markers in obese and non-obese groups, respectively. Of note, LH/FSH and dehydroepiandrosterone sulphate (DHEAS) showed significant publication bias; thus, these results should be interpreted with caution.</p><p><strong>Interpretation: </strong>TT and FAI are primary diagnostic biomarkers in adolescent PMOS, with LH/FSH providing supportive value. AMH is discriminative in adolescents with obesity in early-mid adolescence. HOMA-IR is a primary biomarker for metabolic monitoring, while adiponectin and leptin are BMI-dependent markers for early metabolic risk stratification.</p><p><strong>Funding: </strong>This study was supported by HMRF, CUHK direct grant, CUHK-Chulalongkorn University Research Fund, 1 + 1 + 1 CUHK-CUHK(SZ)-GDST Joint Collaboration Fund, and PhD International Mobility for Partnerships and Collaboration Award.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"132 ","pages":"106471"},"PeriodicalIF":11.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13634440/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149036959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A functional immune-based platform for donor-recipient matching in faecal microbiota transplantation for inflammatory bowel disease.","authors":"Chiara Amoroso, Francesco Strati, Paola Maragno, Bruna Caridi, Daniele Noviello, Martina Gilodi, Martina Muià, Sara Frazzini, Federica Perillo, Maurizio Vecchi, Flavio Caprioli, Federica Facciotti","doi":"10.1016/j.ebiom.2026.106475","DOIUrl":"10.1016/j.ebiom.2026.106475","url":null,"abstract":"<p><strong>Background: </strong>Faecal microbiota transplantation (FMT) shows variable efficacy in inflammatory bowel disease (IBD), and current donor selection strategies rely primarily on microbiome characteristics, while host immune responses to donor microbiota remain largely unexplored. Here, we investigated whether recipient-specific immune responses to donor microbiota could be leveraged to develop a personalised donor-recipient matching strategy for FMT in IBD.</p><p><strong>Methods: </strong>We developed a proof-of-concept (POC) assay, termed Gut Microbiota-Leukocyte Reaction (GMLR), to assess immune compatibility between donor microbiota and recipients with IBD. Lamina propria mononuclear cells isolated from intestinal biopsies were exposed ex vivo to microbiota from healthy donors, and cytokines relevant to IBD pathophysiology were measured.</p><p><strong>Findings: </strong>Donor microbiota clustered into distinct groups associated with differential immune signatures, including significant IL-22 induction (p = 0.033), whereas IL-17 showed a non-significant trend toward reduction (p = 0.054) that was not consistently observed across immune cell subsets. However, immune responses were highly individualised across recipients, with substantial inter-patient variability. Based on these responses, we developed an algorithm to generate donor-recipient compatibility scores, providing a framework to prioritise potential donor-recipient pairs.</p><p><strong>Interpretation: </strong>Our findings suggest that donor-recipient immune compatibility is highly personalised and may represent a key determinant of FMT efficacy, challenging the \"super-donor\" paradigm. This ex vivo proof-of-concept platform may help prioritise donor-recipient pairs and should be prospectively validated against clinical FMT outcomes.</p><p><strong>Funding: </strong>This work was supported by the Italian Ministry of Health, Associazione Italiana per la Ricerca sul Cancro (AIRC), the European Union-NextGeneration EU (HEAL ITALIA project), and the Italian Ministry of Education and Research (MUR).</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"132 ","pages":"106475"},"PeriodicalIF":11.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13578986/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148905345","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":"ERK-dependent hyperexcitability of BLA neurons projecting to dCA3 underlies social dysfunction in a male mouse model of fragile X syndrome.","authors":"Siyu Wang, Xiaotong Wu, Siyuan Dong, Lu Zheng, Libiao Pan, Li Zhan, Hanyang Xiao, Li Yang, Xiaomeng Wang, Huan Ma, Han Xu, Bingxing Pan, Lang Wang, Hao Wang","doi":"10.1016/j.ebiom.2026.106478","DOIUrl":"10.1016/j.ebiom.2026.106478","url":null,"abstract":"<p><strong>Background: </strong>Social dysfunction is a core symptom of autism spectrum disorder (ASD), including fragile X syndrome (FXS), but its underlying neural circuits and molecular mechanisms remain poorly understood. Previous studies have implicated the amygdala and hippocampus in social behaviour, yet the specific pathways and signalling events linking genetic deficits to behavioural dysfunction have not been fully delineated.</p><p><strong>Methods: </strong>Using activity-dependent c-Fos mapping, fibre photometry, closed-loop optogenetics, pharmacological inhibition, and shRNA-mediated knockdown, we investigated the role of the BLA-dCA3 projection and ERK signalling in male Fmr1 KO mice, complemented by re-analysis of human ASD snRNA-seq data and whole-cell patch-clamp recordings.</p><p><strong>Findings: </strong>We found that BLA-dCA3 projecting neurons are aberrantly hyperactivated in Fmr1 KO mice during interactions with both novel and familiar mice, and that closed-loop activation of this pathway in WT mice during familiar interaction impairs social discrimination, whereas its inhibition in KO mice rescues the deficit. Additionally, ERK signalling is upregulated in the BLA of both patients with ASD and Fmr1 KO mice; knocking down FMR1 in the adult BLA recapitulates both the social deficit and ERK hyperactivation, while pharmacological ERK inhibition rescues social behaviour and normalises neuronal hyperexcitability.</p><p><strong>Interpretation: </strong>These findings pinpoint the BLA-dCA3 circuit and BLA-specific ERK signalling as critical mediators of social discrimination deficits in FXS. Our study establishes a causal link from FMRP loss to circuit dysfunction and ERK pathway dysregulation, and suggests that targeting this pathway may offer a promising strategy for treating social dysfunction in ASD and FXS.</p><p><strong>Funding: </strong>This work was supported by grants from the National Science and Technology Major Project (2025ZD0214701), the National Natural Science Foundation of China (32171014, 31970940, and 32500889), Nanhu Brain-Computer Interface Institute (010904018), and the Zhejiang Provincial Natural Science Foundation of China (LMS25C090004).</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"132 ","pages":"106478"},"PeriodicalIF":11.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13572171/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148896550","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}