EBioMedicine最新文献

{"title":"Cataract GWAS meta-analysis and multi-omics Mendelian randomisation inform disease mechanisms and candidate target prioritisation.","authors":"Xuanming Hong, Linxuan Zhang, Verena Zuber, Zihao Zhuang, Héléne T Cronjé, Stephen Burgess, Dipender Gill","doi":"10.1016/j.ebiom.2026.106485","DOIUrl":"10.1016/j.ebiom.2026.106485","url":null,"abstract":"<p><strong>Background: </strong>Cataract is a highly prevalent cause of visual impairment and blindness worldwide. Although genome-wide association studies (GWAS) have mapped multiple cataract risk loci, further work is required towards translating these signals and integrating multi-omics evidence for preventing or delaying age-related cataract progression.</p><p><strong>Methods: </strong>A senile cataract GWAS was first conducted in All of Us, followed by ancestry-specific GWAS meta-analyses in European-ancestry (161,812 cases and 1,099,738 controls) and East Asian ancestry (66,679 cases and 521,995 controls). To prioritise candidate targets, we performed Mendelian randomisation (MR) and colocalisation using cis-expression quantitative trait loci (cis-eQTL) instruments from eQTLGen. We then conducted a plasma proteome-wide cis-pQTL MR scan with colocalisation using UKB-PPP and deCODE for European analyses, and cis-pQTL data from the China Kadoorie Biobank for East Asian analyses.</p><p><strong>Findings: </strong>We identified 78 and 4 independent loci for cataract in Europeans and East Asians, respectively, including 8 and 3 putatively unreported loci. By integrating the meta-GWAS with cis-eQTL MR, we prioritised 16 genes, including MTMR3, NT5DC2, and EFNA1, with eQTL-GWAS colocalisation further supporting MTMR3 and NT5DC2. Proteome-wide cis-pQTL MR prioritised 32 proteins for senile cataract in Europeans, and colocalisation refined these to EFNA1 and RALY. In East Asians, MR highlighted APOE and ALDH2 as candidate targets. We also identified colocalised pleiotropic signals shared between cataract and related traits, including myopia, hypertension, and type 2 diabetes, highlighting candidate genes such as TCF7L2, BMP4, CDKAL1, PAX4, and ALDH2.</p><p><strong>Interpretation: </strong>These findings advance cross-ancestry understanding of cataract genetic architecture and prioritise genetically supported candidates.</p><p><strong>Funding: </strong>This work was supported by the Joint Funds for the Innovation of Science and Technology, Fujian Joint Innovation Fund in Science and Technology Project (Grant No. 2025Y9437).</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"132 ","pages":"106485"},"PeriodicalIF":11.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13631533/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149024266","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":"Tumour-associated dsRNA accumulation and innate immune activation: mechanistic basis and therapeutic strategies.","authors":"Shaoping Li, Yanfei Huo, Hangwei Fa, Linyu Han, Huiwen Luan, Pengxiao Han, Yi Liu, Lixin Zheng, Chang Liu, Kaiyue Fan, Nasha Zhang, Ming Yang","doi":"10.1016/j.ebiom.2026.106493","DOIUrl":"10.1016/j.ebiom.2026.106493","url":null,"abstract":"<p><p>Endogenous double-stranded RNA (dsRNA) links disrupted RNA homoeostasis in cancer to innate immunity. Tumour-associated dsRNA arises from complementary repeat transcripts, mitochondrial transcriptional imbalance, defective RNA processing and cellular stress. Its immunogenicity depends on ligand structure, editing, persistence, localisation, sensor access and pathway competence. ADAR1 and RNA-binding or decay factors buffer self-dsRNA, allowing tumour cells to tolerate potentially immunogenic RNA. Disruption of this control engages RIG-I-MAVS, MDA5-MAVS, TLR3-TRIF, PKR-eIF2α, and OAS-RNase L pathways; Z-conformation RNA can activate ZBP1. Outputs include interferon responses, translational arrest, RNA degradation, and regulated cell death, which can promote antigen presentation and immune-cell recruitment or drive chronic interferon adaptation, suppressive inflammation and treatment resistance. This Review examines critical-target and cumulative-burden models, methods for ligand identification, biomarker-guided patient selection and therapeutic strategies based on viral mimicry, ADAR1 targeting, engineered dsRNA agonists, and delivery platforms.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"132 ","pages":"106493"},"PeriodicalIF":11.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13638791/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149059235","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":"Residential early-life air pollution exposure and oculomotor markers of cognitive workload in children: a prospective birth cohort study.","authors":"Kenneth Vanbrabant, Eleni Renaers, Liesa Engelen, Brigitte Reimann, Hanne Croons, Thessa Van Pee, Maartje Vangeneugden, Nick Giesberts, Marcel Ameloot, Tim S Nawrot, Michelle Plusquin","doi":"10.1016/j.ebiom.2026.106469","DOIUrl":"10.1016/j.ebiom.2026.106469","url":null,"abstract":"<p><strong>Background: </strong>Growing evidence indicates that early brain development is particularly vulnerable to environmental influences, with early-life air pollution exposure linked to attention problems, anxiety, and depression. In this study, we examined associations of early-life air pollution exposure with eye-tracking-derived measures of cognitive workload and emotion-related attentional bias in school-aged children, while also assessing whether recent exposure was associated with these outcomes.</p><p><strong>Methods: </strong>This prospective cohort study was conducted within the ongoing ENVIRONAGE birth cohort, which has enrolled over 2400 mother-child pairs. The present study included 196 children aged 9-11 years who had reached the eligible age for follow-up and completed eye-tracking paradigms assessing cognitive workload and subconscious attention bias between September 2021 and November 2023. Residential black carbon (BC), nitrogen dioxide (NO₂), and fine particulate matter (PM_2.5) exposures were estimated using a high-resolution spatiotemporal modelling framework based on fixed-site monitoring data, land-use/land-cover information, and dispersion modelling. Associations between predefined exposure windows and eye-tracking outcomes were first assessed using multiple linear regression models, followed by Bayesian kernel machine regression distributed lag models (BKMR-DLM) to evaluate multi-pollutant and multi-window exposure-response patterns.</p><p><strong>Findings: </strong>Higher recent residential air pollution exposure was most consistently associated with saccadic outcomes. After correction for multiple testing, an interquartile range (IQR) increase in last-month BC and NO₂ exposure was associated with lower saccade velocity (BC: -10.97°/s; 95% CI -18.67, -3.26; NO₂: -10.81°/s; 95% CI -18.13, -3.49), and last-month NO₂ and PM_2.5 exposure were associated with fewer saccades. Early-life exposure windows also showed associations mainly with saccade velocity, including first-trimester BC and PM_2.5, whole-pregnancy PM_2.5, and first-1000-days BC exposure. Associations with pupil diameter, fixation count, urinary BC, and emotion-related attention-bias outcomes did not remain statistically significant after correction for multiple testing.</p><p><strong>Interpretation: </strong>Using objective eye-tracking outcomes within a prospective birth cohort, our findings suggest that residential air pollution exposure is associated with subtle oculomotor differences in school-aged children, particularly patterns consistent with increased cognitive workload. Emotion-related attention-bias findings were exploratory after correction for multiple testing.</p><p><strong>Funding: </strong>Special Research Fund (BOF), Flemish Scientific Research Fund (FWO), Methusalem, and Horizon Europe project MISTRAL.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"132 ","pages":"106469"},"PeriodicalIF":11.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13572176/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148896731","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":"Liver disease reveals KIF12 as a regulator of mitochondria, lysosome and cilia localisation in human cholangiocytes.","authors":"Anubha Seth, Joseph Brancale, Nina Dashti-Gibson, Rodrigo M Florentino, Lanuza A P Faccioli, Zhenghao Liu, Chigoziri Konkwo, Hyunseok Hong, Alejandro Soto-Gutierrez, Silvia Vilarinho","doi":"10.1016/j.ebiom.2026.106474","DOIUrl":"10.1016/j.ebiom.2026.106474","url":null,"abstract":"<p><strong>Background: </strong>Rare bi-allelic mutations in kinesin family member 12 (KIF12) cause high gamma-glutamyl transferase (GGT) cholestatic liver disease, yet the cellular mechanisms driving this phenotype remain unknown.</p><p><strong>Methods: </strong>To investigate the role of KIF12 in biliary pathology, we introduced the homozygous p.Arg219∗ KIF12 mutation, previously identified in affected patients, into induced pluripotent stem cells (iPSCs). These cells were differentiated into 2D human cholangiocyte-like cells (iCCs) and 3D biliary organoids.</p><p><strong>Findings: </strong>Analysis of healthy human liver single cell RNA-sequencing datasets demonstrated that KIF12 is primarily detected in biliary epithelial cells. Pioneering single-molecule fluorescence microscopy in live iCCs, we observed wildtype KIF12 co-localising with microtubules, supporting its predicted function as a microtubule-associated motor protein. The p.Arg219∗ variant was associated with reduced KIF12 transcript abundance and markedly reduced detectable tagged mutant protein in an overexpression system. Mutant iCCs exhibited abnormal perinuclear clustering of mitochondria and lysosomes, mislocalisation of primary cilia, and increased GGT activity, all of which were rescued by re-expression of wildtype KIF12.</p><p><strong>Interpretation: </strong>This study identifies KIF12 as a key regulator of organelle localisation in human cholangiocytes, expanding our understanding of kinesin roles beyond their established functions in neuronal systems. Our findings provide new insights into the pathogenesis of KIF12-related cholestatic liver disease and establish a foundation for developing targeted genetic therapies.</p><p><strong>Funding: </strong>This study was supported by Doris Duke Charitable Foundation, the National Institutes of Health and internal funds from the Center for Transcriptional Medicine at the University of Pittsburgh.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"132 ","pages":"106474"},"PeriodicalIF":11.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13587065/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148944470","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":"Association of gut microbiota and regulatory T cells with vaccine immunogenicity in HIV-exposed uninfected and HIV-unexposed infants: a longitudinal cohort study.","authors":"Michael J Johnson, Daniel N Frank, Adriana Tovar Salazar, Marta C Nunes, Shabir A Madhi, Adriana Weinberg","doi":"10.1016/j.ebiom.2026.106500","DOIUrl":"10.1016/j.ebiom.2026.106500","url":null,"abstract":"<p><strong>Background: </strong>Responses to vaccines reflect the functionality of the immune system. We measured BCG, tetanus and measles vaccine responses in HIV-exposed uninfected (HEU) and HIV-unexposed (HUU) infants to identify factors associated with HEU immunologic defects.</p><p><strong>Methods: </strong>We assessed cell-mediated immunity (CMI) by FluoroSpot, antibodies by ELISA, regulatory and immunologic checkpoint inhibitor-expressing T cells (Tregs/Ticis) by flow cytometry, and gut microbiota by 16S rRNA gene sequencing. CMI and antibody responses were the primary outcome measures. Associations with Tregs/Ticis and gut microbiome parameters were identified using the hurdle model, Spearman correlations and enrichment analyses.</p><p><strong>Findings: </strong>Among 123 HEUs and 117 HUUs, HEUs tended to have lower BCG-CMI than HUUs without reaching statistical significance (p = 0.07) and similar tetanus-CMI, measles-CMI, and measles-antibodies. Multiple Treg and Tici subsets had significant or marginal negative effects on CMI (p = 0.003-0.10). Treg/Tici inclusion in the hurdle model decreased the statistical significance of the negative effect of HEU status on BCG-CMI suggesting that Tregs/Ticis may have contributed to the difference between HEUs and HUUs. Enrichment of the gut microbiota in Actinobacteria and Firmicutes was significantly associated with low vaccine immunogenicity (p = 0.002-0.04), and Bacteroidetes and Proteobacteria with high immunogenicity (p < 0.0001-0.10). The Firmicute Murdochiella sp. had a higher negative effect size on BCG-CMI in HEUs than HUUs (p < 0.0001). High microbiome diversity negatively correlated with CMI responses (p = 0.002-0.03), with higher effect sizes in HEUs than HUUs (p = 0.047).</p><p><strong>Interpretation: </strong>The frequency of Tregs/Ticis and the composition of the gut microbiome are associated with immune responses to vaccines and may contribute to decreased responses in HEUs. The internally consistent association between the enrichment of gut microbiota in specific phyla and the immunogenicity of several vaccines suggests the possibility of designing mitigating interventions that target the gut microbiome.</p><p><strong>Funding: </strong>National Institute of Allergy and Infectious Diseases and Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"132 ","pages":"106500"},"PeriodicalIF":11.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13656862/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149105824","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 GrimAge clock corresponds to brain ageing and social determinants of health in people with HIV.","authors":"Kalen J Petersen, Seungjae Kim, Pete Canfield, June Roman, Sarah A Cooley, Manjula Bhuma, Adam Anderson, Brittany Nelson, Patricia Reid, Elizabeth Westerhaus, Maurizio Caocci, Tricia H Burdo, Aristeidis Sotiras, Beau M Ances","doi":"10.1016/j.ebiom.2026.106492","DOIUrl":"10.1016/j.ebiom.2026.106492","url":null,"abstract":"<p><strong>Background: </strong>DNA methylation (DNAm)-based epigenetic clocks can measure biological ageing. However, newer epigenetic clocks sensitive to morbidity, mortality, and longitudinal change have not been compared to brain health biomarkers in virally suppressed people with HIV (PWH) and without HIV (PWoH).</p><p><strong>Methods: </strong>Participants in this case-control study underwent blood draws, brain MRI, and neuropsychological testing. Four DNAm-based epigenetic clocks were calculated: GrimAge (mortality-predictive), PhenoAge (morbidity-sensitive), DunedinPACE (longitudinal), and DNAm telomere length. Clocks were correlated with MRI features and cognitive domains. Neighbourhood socioeconomics, unemployment, early life stress, education, and medical comorbidities were examined as risk factors for epigenetic ageing.</p><p><strong>Findings: </strong>126 virologically suppressed PWH (age = 53.8 ± 12.2 yr) and 145 PWoH (age = 48.1 ± 16.4) participated. Elevated GrimAge (p < 0.001; +1.8 years), PhenoAge (p = 0.002; +2.4 years), and DunedinPACE (p < 0.001; +5.1% ageing rate) were found for PWH vs. PWoH, controlling for demographic factors. Predicted telomere length was shorter for PWH vs. PWoH (p < 0.001). GrimAge correlated with brain age gap (p = 0.002; +5.9 years of brain age per decade of GrimAge) across all participants. Epigenetic clocks were linked to poorer cognition in specific domains. Area Deprivation Index was positively associated with GrimAge (p = 0.001) in PWH, while education was negatively associated (p = 0.002). Cardiovascular risk was associated with increased GrimAge (p = 0.008) across all participants.</p><p><strong>Interpretation: </strong>Biological age alterations persist in PWH despite viral suppression, as revealed by multiple epigenetic clocks. GrimAge and other clocks are linked with brain morphology and cognitive dysfunction. Results suggest that biological ageing is influenced by modifiable social and comorbid risk factors.</p><p><strong>Funding: </strong>United States National Institutes of Health (National Institute of Mental Health, National Institute on Drug Abuse, National Institute of Nursing Research) and amfAR, The Foundation for AIDS Research.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"132 ","pages":"106492"},"PeriodicalIF":11.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13625693/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149037135","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":"Discovering repurposable drugs for Alzheimer's disease and related dementias: target trial emulation using decentralised real-world data.","authors":"Qiong Wu, Lu Li, Yuqing Lei, Ting Zhou, Huilin Tang, Bingyu Zhang, Yiwen Lu, Maxwell Salvatore, Dazheng Zhang, Jiayi Tong, Tingyin Wang, Siqi Chen, Haoyang Li, Zhenxing Xu, Yu Huang, Yu Hu, Na Hong, Yujia Zhou, Fongci Lin, Kyra S O'Brien, Yong Chen, Ruowang Li, Hua Xu, Fei Wang, Jiang Bian, David A Wolk, Yong Chen","doi":"10.1016/j.ebiom.2026.106466","DOIUrl":"10.1016/j.ebiom.2026.106466","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Alzheimer's disease and related dementias (ADRD) affect nearly 6.9 million Americans, with the number expected to triple by 2050, while disease-modifying therapies remain unavailable. Drug repurposing, which identifies new indications for already approved medications, offers a more efficient and cost-effective pathway to accelerate development of effective therapies for ADRD. The aim of this study is to identify potential drug repurposing signals by systematically screening routinely prescribed drugs for associations with progression from mild cognitive impairment (MCI) to ADRD.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We conducted a multi-site target trial emulation using electronic health record (EHR) data from four decentralised databases: INSIGHT Clinical Research Network, OneFlorida + Clinical Research Consortium, the University of Pennsylvania Health System, and Yale New Haven Health System. We performed an independent validation using EHR data from the TriNetX Research Network and a genetic risk-stratified sensitivity analysis in the Penn Medicine BioBank (PMBB) database. Eligible participants were adults aged 50 years or older at the time of MCI diagnosis, with no prior diagnosis of ADRD and no prior use of the trial drugs. Initiation of each of 181 routinely prescribed drugs was compared with two active control groups defined by initiation of supplements or cardiovascular medications. Risk ratios (RRs) and 95% CIs were estimated using a federated target trial emulation framework (LATTE) with stabilised inverse probability of treatment weighting and Poisson regression.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Findings: &lt;/strong&gt;A total of 122,972 eligible patients were identified from the four decentralised databases, 335,506 patients identified from the TriNetX network for validation and 898 from PMBB database. Federated, multi-site target trial emulation identified 20 drug repurposing hypotheses with statistically significant protective effects, including anti-inflammatory and pain-modulating agents (celecoxib: RR 0.43; 95% CI: 0.23-0.81; dexamethasone RR 0.46; 95% CI: 0.29-0.73; gabapentin: RR 0.55; 95% CI: 0.36-0.83; ketorolac: RR 0.50; 95% CI: 0.31-0.80; methylprednisolone: RR 0.43; 95% CI: 0.24-0.76; prednisone: RR 0.48; 95% CI: 0.28-0.83; pregabalin: RR 0.53; 95% CI: 0.35-0.79), antimicrobial and microbiome-associated agents (cefazolin: RR 0.62; 95% CI: 0.45-0.84; clavulanate: RR 0.56; 95% CI: 0.44-0.71; fluconazole: RR 0.36; 95% CI: 0.23-0.58), neuromodulators and adrenergic agents (epinephrine: RR 0.42; 95% CI: 0.31-0.56; propranolol: RR 0.56; 95% CI: 0.37-0.85; salmeterol: RR 0.49; 95% CI: 0.32-0.74; tizanidine: RR 0.29; 95% CI: 0.14-0.57), vascular, metabolic, and hormonal modulators (empagliflozin: RR 0.29; 95% CI: 0.17-0.50; oestradiol: RR 0.47; 95% CI: 0.28-0.81; ezetimibe: RR 0.69; 95% CI: 0.52-0.91; sodium bicarbonate: RR 0.49; 95% CI: 0.29-0.84; spironolactone: RR 0.43; 95% CI: 0.31-0.60), and histamine-related and gastrointe","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"132 ","pages":"106466"},"PeriodicalIF":11.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13572180/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148891317","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":"Molecular epidemiology and genomic characteristics of clinical Acinetobacter baumannii isolates from patients with hospital-acquired pneumonia in China, 2019-2020: a multicentre retrospective study.","authors":"Jintao He, Qingye Xu, Minfei Peng, Haiyang Liu, Li Fang, Siyuan Yang, Yisha Zhang, Hanqi Zhang, Xiaochen Liu, Xi Li, Xiaoting Hua, Yunsong Yu, Hua Zhou","doi":"10.1016/j.ebiom.2026.106483","DOIUrl":"10.1016/j.ebiom.2026.106483","url":null,"abstract":"<p><strong>Background: </strong>Carbapenem-resistant Acinetobacter baumannii (CRAB) is a leading cause of hospital-acquired pneumonia (HAP) with high mortality. However, large-scale nationwide data of HAP-causing CRAB in China remain limited.</p><p><strong>Methods: </strong>Here, we performed a nationwide multicentre retrospective study to characterise the molecular epidemiology and genomic features of 802 A. baumannii isolates from patients with HAP across 33 tertiary hospitals in China during 2019-2020. Antimicrobial susceptibility testing (AST), whole-genome sequencing (WGS), phylogenetic and comparative genomic analysis were used to investigate molecular epidemiology of HAP-causing CRAB strain. Clinical comparative analyses were carried out on data from 500 patients with HAP stratified by distinct antimicrobial susceptibility and genomic profiles, and a Galleria mellonella infection model was utilised for in vivo virulence assessment.</p><p><strong>Findings: </strong>The overall carbapenem resistance rate of A. baumannii was 82.0% (658/802), with marked regional variations. CRAB exhibited high resistance to conventional agents but remained largely susceptible to polymyxin, tigecycline, cefiderocol and sulbactam-durlobactam. Among enrolled patients, CRAB infection was linked to substantially higher mortality (39.0% vs. 17.5%), and multivariate analysis confirmed ICU admission and advanced age as independent risk factors for patients with CRAB infection. Molecular typing revealed ST_Pas2 (96.2%) as the absolutely predominant type; ST_Oxf208, ST_Oxf195, ST_Oxf540, and ST_Oxf369 were the most prevalent Oxford sequence types with obvious geographic stratification and divergent comorbidity profiles among corresponding patients. A total of 654 CRAB isolates harboured carbapenemase genes, with bla_OXA-23 dominating at 98.8%. Genomic analysis revealed lineage-specific features: ST_Oxf208 carried more virulence genes, while ST_Oxf540 harboured a broader antimicrobial resistance genes (ARGs). The ST_Oxf208 clone mainly belonged to KL2 (62.1%) and KL7 (36.8%) serotypes, with KL2 strains possessing richer ARGs and virulence factors, and in vivo virulence assays further validated that KL2 strains possessed higher pathogenicity than KL7 strains.</p><p><strong>Interpretation: </strong>This study demonstrates the extremely high prevalence and clonal dominance of CRAB in Chinese patients with HAP, providing critical evidence for clinical treatment, antimicrobial stewardship, and targeted infection control.</p><p><strong>Funding: </strong>National Key Research and Development Program of China (2024YFE0106200), National Natural Science Foundation of China (U22A20338, 82502763, W2621007), Zhejiang Provincial Natural Science Foundation of China (LQN25H190006), Zhejiang Provincial Postdoctoral Science Foundation (ZJ2025058).</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"132 ","pages":"106483"},"PeriodicalIF":11.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13597179/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148975906","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":"Corrigendum to \"Loss of vesicular monoamine transporter 2 in striatum of long COVID and relationship to neuropsychiatric symptoms\" [EBioMedicine (2026) Jul 10: 106339].","authors":"Yuhan Karida Liu, Devina Persaud, Erica L Vieira, Joeffre Braga, Pablo Rusjan, Laura Miler, Jennifer S Rabin, Tina McCluskey, Isabelle Boileau, Thomas Chao, Michael Bagby, Lucas Narciso, Lauren Rose Gray, Neil Vasdev, Kimberly Desmond, Stefan Kloiber, Jerry Warsh, Muhammad Ishrat Husain, Kelly Smart, Wei Wang, Jeffrey H Meyer","doi":"10.1016/j.ebiom.2026.106472","DOIUrl":"10.1016/j.ebiom.2026.106472","url":null,"abstract":"","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"132 ","pages":"106472"},"PeriodicalIF":11.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13688036/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148896505","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":"DNA methylation landscape of cerebrospinal fluid cells in multiple sclerosis: an epigenome-wide association study.","authors":"Yanan Han, Galina Yurevna Zheleznyakova, Heng Liang, Chiara Sorini, Majid Pahlevan Kakhki, Nicolas Ruffin, Nils Hallén, Chandana Rao Prakash, Viveca Beckers, Elena Ivanova, Mohsen Khademi, Tomas Olsson, Mikael C I Karlsson, Fredrik Piehl, Gavin Kelsey, Lara Kular, Maria Needhamsen, Maja Jagodic","doi":"10.1016/j.ebiom.2026.106454","DOIUrl":"10.1016/j.ebiom.2026.106454","url":null,"abstract":"<p><strong>Background: </strong>Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system in which DNA methylation may link genetic and environmental risk factors.</p><p><strong>Methods: </strong>We profiled genome-wide DNA methylation in cerebrospinal fluid (CSF) cells from people with MS (pwMS) and matched controls. Differentially methylated positions (DMPs) and regions (DMRs) were integrated with transcriptomic data, T-cell chromatin annotations, and pathway analyses. Protocadherin gamma (PCDHγ) expression was assessed in primary CD4+ T-cell subsets and confirmed by flow cytometry.</p><p><strong>Findings: </strong>We identified 2710 DMPs and 4330 DMRs associating with genes that were enriched in immune signalling, adhesion and migration processes, and were accompanied by corresponding RNA changes. MS-associated methylation changes enriched in the cohesin chromatin-regulation pathway localised to T-cell regulatory regions, and this pathway included multiple protocadherin (PCDH) genes, which displayed consistent methylation and expression changes in CSF cells of pwMS compared to controls. PCDHγ cluster gene expression was detected in CD4⁺ T-cell subsets, and flow cytometry confirmed PCDHγ protein expression in peripheral blood T cells. Moreover, co-expression analysis suggests a role of PCDH genes in aryl hydrocarbon receptor (AHR) signalling. Protein-level validation showed fewer PCDHγ-positive CD4+ T cells in pwMS and activation-induced PCDHγ upregulation after T-cell stimulation.</p><p><strong>Interpretation: </strong>DNA methylation changes in CSF resident cells reflect dysregulated T cell activation and migration in pwMS and suggest involvement of protocadherin molecules in MS pathogenesis.</p><p><strong>Funding: </strong>European Research Council, Swedish Research Council, Swedish Brain Foundation, Swedish MS Foundation, Knut and Alice Wallenberg Foundation, European Union and others.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"131 ","pages":"106454"},"PeriodicalIF":11.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13545696/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148839536","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}