EBioMedicine最新文献

{"title":"Spatial membrane lipid remodelling encodes epithelial lineage and state in human colon cancer.","authors":"Ramon M Rodriguez, Karim Pérez-Romero, Albert Maimó-Barceló, Teresa Ximelis, Cristina Huergo-Baños, Marcos A Martínez, Juan José Segura-Sampedro, Rafael Morales-Soriano, Cristina Pineño-Flores, Álvaro García-Granero, Sebastián Jerí, Ana M Aransay, José A Fernández, Gwendolyn Barceló-Coblijn","doi":"10.1016/j.ebiom.2026.106473","DOIUrl":"10.1016/j.ebiom.2026.106473","url":null,"abstract":"<p><strong>Background: </strong>Cancer progression is driven by spatially organised intratumoural heterogeneity, yet the molecular basis of this organisation remains incompletely understood. While spatial transcriptomics has advanced rapidly, the spatial architecture and functional relevance of tumour lipid metabolism remain poorly characterised. We aimed to resolve whether membrane phospholipid remodelling is spatially organised across epithelial cell states in human colon cancer.</p><p><strong>Methods: </strong>We developed an integrative spatial multi-omic strategy linking mass spectrometry imaging to transcriptome-defined cellular states on consecutive tissue sections from primary and intraperitoneal metastatic human colon cancer specimens. Epithelial lipid phenotypes were characterised, validated in an independent cohort, and linked to transcriptional programmes.</p><p><strong>Findings: </strong>We identified four spatially organised epithelial lipid phenotypes defined by membrane phospholipid composition. These phenotypes aligned with transcriptional programmes reflecting epithelial lineage and differentiation state, and were organised along a differentiation axis marked by coordinated remodelling of arachidonic acid-, oleic acid-, and linoleic acid-containing phospholipids. Secretory-associated states, enriched in metastatic lesions, showed increased DHA-containing phospholipids and activation of peroxisomal pathways. Lipid phenotype assignments were reproducible across an independent cohort.</p><p><strong>Interpretation: </strong>Membrane phospholipid composition encodes biologically meaningful epithelial cell states within human tumours, establishing lipid remodelling as a structured and spatially organised dimension of tumour heterogeneity.</p><p><strong>Funding: </strong>This study was supported by the ISCIII (PI19/00002, PI24/00313), the Health Research Institute of the Balearic Islands (IMP22/04), the Government of the Balearic Islands (AP_2021_001), the Basque Government (IT1491-22), the European Regional Development Fund, and the Scientific Foundation, Spanish Association Against Cancer (INVES222995RODR).</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"132 ","pages":"106473"},"PeriodicalIF":11.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13581992/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148929019","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":"Cancer genomic data systems in precision oncology: from integration to clinical implementation.","authors":"David Torrents, Oliver Hofmann, Karen Ann Cranston, Raffaella Casolino, Andrew V Biankin, Andrés F Cardona, Robert L Grossman, Amber Johns, Mark Lawler, Kjong-Van Lehmann, Raquel Manzano Garcia, Nicola Mulder, Travis Osterman, Timothy Rebbeck, Solomon Rotimi, Zbyslaw Sondka, Shawn Sweeney, Samuel Volchenboum, Alex Wagner, Jianmin Wu, Takayuki Yoshino, Mélanie Courtot, Lincoln Stein","doi":"10.1016/j.ebiom.2026.106480","DOIUrl":"10.1016/j.ebiom.2026.106480","url":null,"abstract":"<p><p>Cancer genomic data sharing is a core pillar of precision oncology, underpinning reproducibility, scalability, and equity. The ability to discover, access, integrate, interpret, and reuse cancer 'omics data is a key determinant of precision oncology's value and benefit at scale. This work has been conducted as part of The Lancet Oncology Commission on Cancer Genomics and Precision Oncology to examine the practical data architecture required to support cancer genomics in research, clinical care, and health-system learning. We conclude that without robust data stewardship, including effective data sharing and global integration, the potential of cancer genomics will remain fragmented across projects, platforms, and jurisdictions. This disaggregation limits reproducibility, equity, patient benefit, and societal value. Healthcare systems must prioritise implementing fully efficient data ecosystems as a central challenge for precision oncology.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":" ","pages":"106480"},"PeriodicalIF":11.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13688039/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149059180","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":"Integration of biological avatars and digital twins for \"ex vivo clinical trials\".","authors":"Charles L Howe","doi":"10.1016/j.ebiom.2026.106467","DOIUrl":"10.1016/j.ebiom.2026.106467","url":null,"abstract":"<p><p>Drug development is slow, costly, and prone to late-stage failure, in part because animal models poorly predict human responses. Two human-relevant technologies are maturing in parallel: biological avatars, defined as patient- or stem-cell-derived models such as organoids and organ-on-a-chip systems, and digital twins, defined as computational models that integrate a patient's molecular and clinical data to forecast treatment responses. We propose the ex vivo clinical trial concept, in which an avatar and a digital twin are coupled in an iterative loop so that laboratory measurements refine the computational prediction and the prediction guides the next experiment, allowing candidate therapies to be tested and prioritised before a patient is exposed. We review the platforms, their predictive performance in cancer, cystic fibrosis, and liver toxicity, the conditions under which they fail, and the qualification, turnaround, and standardisation requirements that must be met before such trials can inform drug development or clinical care.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"132 ","pages":"106467"},"PeriodicalIF":11.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13570278/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148873175","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":"Metabolomic profiling of ultra-processed food consumption and cardiovascular risk in Spanish preschool children: a cross-sectional study.","authors":"Josué A Pérez-Acosta, Jesús F García-Gavilán, Hernando J Margara-Escudero, Concepción M Aguilera, Rosaura Leis, Irina Gheorghita, María L Miguel-Berges, Santiago Navas-Carretero, José V Sorlí, Iolanda Lázaro, Belén Pastor-Villaescusa, Rocío Vázquez-Cobela, Lucía Iglesias-Vázquez, Pilar De Miguel-Etayo, Natalia Vazquez-Bolea, José Manuel Jurado-Castro, Rosaura Picáns-Leis, Joaquín Escribano, Luis A Moreno, MJosé de la Torre-Aguilar, Mercedes Gil-Campos, Jordi Salas-Salvadó, Nancy Babio","doi":"10.1016/j.ebiom.2026.106488","DOIUrl":"10.1016/j.ebiom.2026.106488","url":null,"abstract":"<p><strong>Background: </strong>Ultra-processed food (UPF) consumption has increased substantially among children worldwide and has been associated with early cardiovascular alterations. We aimed to identify plasma metabolomic profiles associated with UPF consumption in children aged 3-6 years and to assess their association with cardiovascular risk factors.</p><p><strong>Methods: </strong>This cross-sectional analysis used baseline data from the Childhood Obesity Risk Assessment Longitudinal Study (CORALS), with children recruited between March 2019 and June 2022 through primary schools and health-care centres in seven Spanish cities. 1148 children were included (mean age 5.0 years [SD 1.1]; 50.6% girls) after exclusions due to medical conditions and incomplete or implausible dietary or metabolomic data. Energy-adjusted UPF intake (g/d) was assessed using a validated food frequency questionnaire and categorised with NOVA classification. 249 metabolites were quantified by NMR-based metabolomics, and lipid-related and amino acid-related profiles/scores were derived. A composite cardiovascular risk score (CVRs) was constructed by summing sex-specific, age-adjusted z-scores for fat-mass index, HDL-and LDL-cholesterol, triglycerides, mean arterial pressure, and Homoeostatic Model Assessment for Insulin Resistance.</p><p><strong>Findings: </strong>19 metabolites were associated with UPF consumption after false discovery rate correction (FDR). A lipid-related score was positively associated with CVRs (β = 0.511; 95% CI: 0.413-0.610; FDR <0.001) and the amino acid-related score was associated with a lower CVRs (β = -0.494; 95% CI: -0.667 to -0.321; FDR <0.001). Discrimination of cardiovascular risk beyond covariates alone was higher after inclusion of metabolomic scores, particularly when both scores were considered jointly (ΔAUC 0.092, 95% CI: 0.013-0.172; p = 0.020).</p><p><strong>Interpretation: </strong>In Spanish pre-schoolers UPF-related metabolomic profiles were associated with different cardiovascular risk factors. These diet-related metabolomic scores capture biological correlates relevant to early cardiovascular health and align with early-life metabolic pattering, supporting future longitudinal studies and prevention strategies.</p><p><strong>Funding: </strong>CIBEROBN; Instituto de Salud Carlos III (ISCIII-FIS; EU ERDF/ESF); ISCIII PFIS.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"132 ","pages":"106488"},"PeriodicalIF":11.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13634276/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149030139","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":"Proteomic signatures during pregnancy: an exploratory cohort study of long-term health indicators.","authors":"Lucy A Bartho, Susan P Walker, Teresa MacDonald, Danica Idzes, Ping Cannon, Tuong-Vi Nguyen, Gordon Smith, D Stephen Charnock-Jones, Stephen Tong, Tu'uhevaha J Kaitu'u-Lino","doi":"10.1016/j.ebiom.2026.106491","DOIUrl":"10.1016/j.ebiom.2026.106491","url":null,"abstract":"<p><strong>Background: </strong>Pregnancies complicated by fetal growth restriction (FGR) and preeclampsia are associated with increased long-term chronic disease risk. A blood test could possibly identify those at risk, opening the door to early interventions soon after delivery. Prior work in non-pregnant people have identified protein signatures associated with 18 different health parameters, called SomaSignal Tests.</p><p><strong>Methods: </strong>This study applied SomaSignal tests to plasma samples collected in pregnancy from two independent cohorts to assess the 18 health parameters in those who later developed FGR and preeclampsia. SomaScan Assay measured ∼7000 modified aptamers in plasma from two independent cohorts. Plasma samples (Melbourne, Australia) were collected at 36 weeks' gestation from women who later delivered an FGR infant (<3rd birthweight centile, n = 118), preeclampsia at term (n = 92) or did not develop either condition (n = 177). The second cohort (Cambridge, UK) were plasma samples collected at 36 weeks' gestation from women who later delivered an FGR infant (n = 80), and those who did not (n = 172).</p><p><strong>Findings: </strong>In the Australian cohort, women who later delivered growth-restricted infants had composite protein signatures associated with reduced cardiac function (p = 0.001), increased cardiovascular events (p = 7.6 × 10^-6), mid-life dementia (p = 1.5 × 10^-9), and higher visceral fat (p = 4.06 × 10^-6), compared to pregnancies without complications. Findings were largely consistent in both Australian and UK sample sets. Those who developed preeclampsia had protein signatures signifying cardiovascular (p = 5.54 × 10^-6), hepatic (p = 0.001), and renal (p = 0.0007) disease risks, compared to pregnancies without complications.</p><p><strong>Interpretation: </strong>Since signatures were more pronounced in pregnancies that were later diagnosed with FGR and preeclampsia, underlying physiological changes may have been present before diagnosis. These changes result in protein signatures concordant with those associated with poor long-term health outcomes in non-pregnant populations. These associations require validation in large, longitudinal cohorts investigating pregnancy, with long-term maternal follow-up.</p><p><strong>Funding: </strong>Stillbirth CRE, Mercy Hospital Foundation and National Health and Medical Research Council, Royal Australian and New Zealand College of Obstetricians and Gynaecologists, Taylor Hammond Scholarship, National Health and Medical Research Council Fellowships and Australian Research Council Future Fellowships.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"132 ","pages":"106491"},"PeriodicalIF":11.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13638798/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149059191","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":"Age-related molecular IgE sensitization to indoor and outdoor respiratory allergens: a two-step cross-sectional study in Algeria and Türkiye.","authors":"Lydia Lamara Mahammed, Susanne Vrtala, Oluwatoyin Akinfenwa, Maria-Roxana Buzan, Kuan-Wei Chen, Alp Kazancioglu, Raffaela Campana, Monica-Daniela Cotarcă, Mirela Curin, Yulia Dorofeeva, Nishelle Dsouza, Alexandra Dubovets, Margarete Focke-Tejkl, Pia Gattinger, Heinrich Grausgruber, Huey-Jy Huang, Alexander Karaulov, Evgenii Kozlov, Andrea Krisai, Lun Li, Birgit Linhart, Carmen Panaitescu, Eszter Sarzsinszky, Daria Trifonova, Mikhail Tulaev, Milena Weber, Brahim Belaid, Recep Sancak, Mehmet Halil Celiksoy, Lynda Sekfali, Nafissa Benhalla, Merzak Gharnaout, Bulent Enis Sekerel, Rudolf Valenta, Reda Djidjik","doi":"10.1016/j.ebiom.2026.106484","DOIUrl":"10.1016/j.ebiom.2026.106484","url":null,"abstract":"<p><strong>Background: </strong>Immunoglobulin E-mediated allergy is the most important hypersensitivity disease affecting more than 30% of the population worldwide. The analysis of molecular IgE sensitization profiles in defined populations and age groups is important for the development of allergen-specific preventive and therapeutic interventions. The present study was performed to examine if there are differences regarding molecular IgE reactivity profiles in children and adults from two regions with similar climate and exposome.</p><p><strong>Methods: </strong>This two-step cross-sectional study assessed molecular IgE reactivity profiles using an experimental allergen microarray comprising 105 allergen molecules. In the first step, an exploratory cross-sectional study, serum samples from 539 allergic patients (259 children, 280 adults) who were born and grew up in the Algiers region were analyzed. The second step was a prospective cross-sectional study performed in 272 Turkish allergic patients (133 children, 139 adults) from Istanbul and Samsun regions with a climate and allergen exposome similar to Algiers, with the goal of investigating the reproducibility of possible differences in molecular IgE sensitization profiles between children and adults.</p><p><strong>Findings: </strong>In both the exploratory Algiers study and the prospective Turkish study, significantly more children than adults with respiratory allergy were sensitized to major respiratory house dust mite allergens (Algiers: Der p 1, Der p 2: p < 0.001 and Der p 23: p = 0.001; Türkiye: Der p 1: p = 0.018 and Der p 2: p = 0.019) whereas significantly more adults than children were sensitized to regionally common respiratory outdoor allergens (Algiers: Ole e 1: p = 0.037; Phl p 1: p = 0.046; Türkiye: Ole e 1: p = 0.016; Amb a 1: p = 0.002; Amb a 8: p < 0.001). Asthma was significantly more common in children than in adult patients with respiratory allergy (Algiers: p < 0.001; Türkiye: p = 0.034).</p><p><strong>Interpretation: </strong>Our study demonstrates different molecular IgE sensitization profiles in two age groups (children and adults) on two different continents with a similar climate and allergen exposome which may be due to exogenous factors such as climate change, different lifestyles, pollution and changes in vegetation. Both major house dust mite sensitization and asthma were more common in children, suggesting sensitization profile may contribute to asthma risk.</p><p><strong>Funding: </strong>Danube Allergy Research Cluster, Country of Lower Austria, Medical University of Vienna and Russian Science Foundation.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":" ","pages":"106484"},"PeriodicalIF":11.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13688041/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149037053","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":"Multi-omic profiling and pathways related to changes in liver histology after Roux-en-Y gastric bypass: a longitudinal study.","authors":"Yasaman Ghorbani, Katherine J P Schwenger, Heather Maughan, Anastasia Teterina, Wendy Lou, Elena M Comelli, Sandra E Fischer, Timothy D Jackson, Allan Okrainec, Johane P Allard","doi":"10.1016/j.ebiom.2026.106498","DOIUrl":"10.1016/j.ebiom.2026.106498","url":null,"abstract":"<p><strong>Background: </strong>Roux-en-Y gastric bypass (RYGB) improves metabolic dysfunction-associated steatotic liver disease (MASLD). However, the impact of RYGB on hepatic transcriptome, faecal microbiome and serum/faecal metabolome remain understudied. Our objective was to investigate the change in these omics and their relationships with changes in liver histology.</p><p><strong>Methods: </strong>In this prospective cohort study, patients undergoing RYGB were recruited between 2013 and 2020 and followed for 12 months. Anthropometrics, biochemistry, hepatic transcriptome, faecal microbiome (shotgun metagenomics) and serum/faecal metabolomes were measured. Liver histology and NAFLD Score (NAS) were assessed.</p><p><strong>Findings: </strong>Thirty-eight patients completed the study. Anthropometrics, biochemical and histological parameters improved post-RYGB (p < 0.05). Hepatic transcriptome analysis revealed a co-expression module enriched in fatty acid metabolism which correlated with changes in NAS post-RYGB (ρ = 0.38, p = 0.019). The core enrichment genes in this pathway were involved in mitochondrial and peroxisomal β-oxidation (ACADVL, ACOX1, and EHHADH) and the tricarboxylic acid (TCA) cycle (SUCLG2, SDHC, and SERINC1). There was an increase in TCA cycle gene expression associated with the resolution of ballooning, while upregulation of β-oxidation genes correlated with less reduction in NAS, ballooning, and inflammation. Metabolomic changes related to the identified co-expression module and pathways reveal a significant increase in faecal acylcarnitines, likely due to malabsorption from RYGB, with a significant reduction in circulating acylcarnitines which correlated positively with SUCLG2 expression and resolution of ballooning. Additionally, the increase in faecal acylcarnitines positively correlated with the bacterial species utilising acylcarnitines. In network analysis, ballooning of hepatocytes was associated with faecal/serum acylcarnitines and TCA metabolites while SUCLG2 was the hub gene associated with these changes.</p><p><strong>Interpretation: </strong>These findings provide insight on how post-RYGB changes in the transcriptome, metabolome, and microbiome could be associated with improvement in liver histology and may inform the development of future strategies for MASLD management.</p><p><strong>Funding: </strong>Canadian Institutes of Health Research and American College of Gastroenterology.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"132 ","pages":"106498"},"PeriodicalIF":11.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13653980/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149080043","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 tablet-based attentional cognitive bias modification intervention for positive emotion processing in major depressive disorder: a single-blind randomised controlled two-centre trial.","authors":"Zoe Katharina Kratochwil, Jessica Kesik, Duygu Keskin-Gökcelli, Katrin Sakreida, Norbert Scherbaum, Bernhard Wolfram Müller, Thomas Frodl","doi":"10.1016/j.ebiom.2026.106453","DOIUrl":"10.1016/j.ebiom.2026.106453","url":null,"abstract":"<p><strong>Background: </strong>Patients with Major Depressive Disorder (MDD) exhibit biased information processing. This study investigates the clinical and neural efficacy of a cognitive bias modification (CBM) training in patients and healthy control (HCS), fostering processing of positive emotion stimuli.</p><p><strong>Methods: </strong>In a single-blind randomised controlled trial (DRKS00029756), MDD outpatients and HCS, aged 18-60 years, were randomised to positivity training (PT) or control training (CT). Randomisation was carried out by study assistants, blinding researchers. Participants underwent 10 tablet-based dot-probe sessions over 14 days. PT implicitly redirected attention toward positive stimuli to improve depressive symptoms. Primary outcome was pre and post-training EEG-derived Early Posterior Negativity (EPN), investigating neural sensitivity towards positive stimuli. Secondary clinical outcomes included changes in depression symptoms.</p><p><strong>Findings: </strong>From February 2023 to October 2024, 240 participants were included (119 MDD; 121 HCS). 62 MDD and 61 HCS underwent PT; 57 MDD and 60 HCS received CT. In MDD, EPN to positive high arousal stimuli revealed an interaction between time (pre/post) and training (PT/CT), F(1,97) = 5.017, p < 0.028, η² = 0.049. The between-treatment difference was 1.65 μV, 95% CI [0.19, 3.11]. EPN amplitudes shifted towards negativity in PT and positivity in CT. Depression symptom decreased from pre to post and from pre to follow-up. With respect to adverse events, one patient in the control training was regularly admitted to hospital.</p><p><strong>Interpretation: </strong>CBM positivity training was associated with neural changes in MDD, supporting its potential to target pre-attentive positive emotion processing. Further EEG follow-up and higher stimulus contrasts in the training conditions may clarify clinical relevance.</p><p><strong>Funding: </strong>Funded by DFG (ID: 507720021).</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"132 ","pages":"106453"},"PeriodicalIF":11.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13570274/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148873061","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":"Sebum-associated type 17 inflammation in atopic dermatitis: a single-cell and in vivo study of body-site immune heterogeneity.","authors":"Zhuoqiong Qiu, Ronghui Zhu, Yanan Li, Huibin Yin, Chaoying Gu, Shangshang Wang, Yu Wang, Tianze Yu, Xiaoyu Pan, Yuemeng Wu, Xu Yao, Wei Li","doi":"10.1016/j.ebiom.2026.106496","DOIUrl":"10.1016/j.ebiom.2026.106496","url":null,"abstract":"<p><strong>Background: </strong>Inflammatory skin diseases exhibit striking anatomical predilections, yet the mechanisms shaping site-specific immune programs remain poorly understood. Although atopic dermatitis (AD) is classically considered a type 2-driven disease, lesions arising in sebum-rich skin such as the face often show suboptimal responses to type 2-targeting biologics, suggesting the presence of distinct site-specific immune programs shaped by the local tissue environment.</p><p><strong>Methods: </strong>We performed single-cell RNA sequencing (scRNA-seq) on matched facial and popliteal lesions from adult male patients with AD (n = 3 facial lesions, n = 3 popliteal lesions) to characterize site-specific immune landscapes. MC903-induced AD mouse models were used to investigate the effects of topical sebum on cutaneous inflammation, with mechanistic studies focusing on macrophage lipid metabolism and inflammatory signaling assessed by flow cytometry, quantitative PCR, and pharmacological inhibition approaches.</p><p><strong>Findings: </strong>scRNA-seq analysis revealed enhanced type 17-associated immune signatures in facial AD lesions relative to matched popliteal lesions, despite preservation of type 2 inflammatory features. In mouse models, topical sebum selectively amplified Th17 responses through FABP5-dependent induction of macrophage IL-1β production. Sebum also reduced the therapeutic response to Th2 blockade, accompanied by further enhancement of type 17 inflammation. Pharmacological inhibition of FABP5 attenuated sebum-induced immune deviation and reduced disease severity.</p><p><strong>Interpretation: </strong>These findings suggest that a sebum-associated macrophage metabolic axis contributes to type 17-skewed inflammation in sebaceous skin regions, providing a mechanistic framework for understanding anatomical immune heterogeneity and highlighting potential targets for modulating site-specific inflammation.</p><p><strong>Funding: </strong>The National Natural Science Foundation of China; Natural Science Foundation of Zhejiang Province; China Postdoctoral Science Foundation; Natural Science Foundation of Hubei Province; Bethune Charitable Foundation; Wuhan Municipal Natural Science Foundation; Wuhan Municipal Health Commission; The Shanghai Municipal Commission of Health and Family Planning; The Program of Shanghai Academic/Technology Research Leader.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"132 ","pages":"106496"},"PeriodicalIF":11.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13651824/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149073944","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":"Gut microbiome profiling at multiple sclerosis onset as a potential early prognostic marker of disease course: evidence from an observational cohort study.","authors":"Alessandro Maglione, Rachele Rosso, Dora Tortarolo, Francesco Pantini, Simone Pernice, Sandro Gepiro Contaldo, Roberta Lanzillo, Antonio Luca Spiezia, Cinzia Cordioli, Eleonora Virgilio, Federica Masuzzo, Manuela Matta, Simona Malucchi, Paola Cavalla, Luca Cocolin, Roberta Sirovich, Marco Beccuti, Ilario Ferrocino, Francesca Cordero, Marinella Clerico, Simona Rolla","doi":"10.1016/j.ebiom.2026.106470","DOIUrl":"10.1016/j.ebiom.2026.106470","url":null,"abstract":"<p><strong>Background: </strong>Alterations in gut microbiome composition have been associated with multiple sclerosis (MS), but their impact on disease severity and early progression remains poorly understood. In this study we investigated whether gut microbiome profiling at diagnosis could identify microbial signatures associated with clinical and radiological features of early MS and provide prognostic information.</p><p><strong>Methods: </strong>We analysed the gut microbiome of 53 treatment-naïve patients with MS (pwMS) and 55 healthy donors (HD) using shotgun metagenomic sequencing, combined with clinical features collected over 1 year from diagnosis. To clarify whether gut microbiome composition at MS onset could have prognostic relevance, pwMS were stratified according to lesion burden, lesion localisation, and magnetic resonance imaging (MRI) activity.</p><p><strong>Findings: </strong>Overall beta diversity in Bacteria, Archaea, and Eukarya differed significantly between pwMS and HD (p-value <0.001, <0.02, <0.03, respectively). Within the MS group, glucocorticoid treatment at disease onset was the clinical factor most strongly associated with gut microbiota diversity. Stratification according to lesion burden, lesion localisation, and MRI activity identified two clinically distinct MS subgroups with different baseline clinical characteristics at onset (p-value <0.03) and different risk of early disease progression. The cluster associated with an unfavourable prognosis showed greater progression within 12 months and was enriched for motor symptoms and spinal cord lesions at diagnosis.</p><p><strong>Interpretation: </strong>Our findings suggest that gut microbiome alterations are detectable at the earliest stages of MS and are associated with clinical and radiological features linked to short-term disease evolution. Gut microbial profiling may therefore represent a promising early prognostic biomarker and may help to identify candidate targets for early intervention and therapeutic development in MS, although further validation in larger longitudinal cohorts is needed.</p><p><strong>Funding: </strong>This study was supported by grants from the Italian Multiple Sclerosis Foundation, the Cassa di Risparmio di Torino Foundation, and the Italian Ministry of University and Research.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"132 ","pages":"106470"},"PeriodicalIF":11.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13688122/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148896627","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}