EBioMedicine最新文献

{"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}

{"title":"Single-cell study of human ovarian response to phthalate exposure reveals glial cell susceptibility and disruption of adhesion and mitochondrial pathways.","authors":"Eleftheria Maria Panagiotou, Loren Méar, Ilmatar Rooda, Alesandro Haxhiu, Elisabeth Moussaud-Lamodière, Karolina Wasilewska, Tianyi Li, Catarina Arnelo, Karin Pettersson, Kiriaki Papaikonomou, Cecilia Lindskog, Pauliina Damdimopoulou","doi":"10.1016/j.ebiom.2026.106487","DOIUrl":"10.1016/j.ebiom.2026.106487","url":null,"abstract":"<p><strong>Background: </strong>Phthalates are known male endocrine disruptors and reproductive toxicants. Despite growing evidence of female effects, mechanistic knowledge in key reproductive organs remains limited, hindering regulations. Here, we conducted an experimental study to map the impact of mono(2-ethylhexyl) phthalate (MEHP), the primary metabolite of di(2-ethylhexyl) phthalate (DEHP), on adult human ovarian tissue at single-cell resolution.</p><p><strong>Methods: </strong>Ovarian tissue explants from seven donors (five gender-affirming surgery, two caesarean-section) were exposed to two MEHP concentrations: an epidemiologically relevant 20.51 nM and a 1000-fold higher 20.51 μM. After six days, single-cell RNA sequencing (one donor) and immunostainings (six donors) were used to characterise gene expression changes across cell types. Primary ovarian cells derived from three gender-affirming surgery patients and stem cell-derived Schwann cells were used for validation.</p><p><strong>Findings: </strong>Explants retained all major ovarian cell types, including rare glial cells and oocytes. MEHP altered transcriptomes across all cell types, disrupting pathways related to actin cytoskeleton, cell adhesion, and oxidative phosphorylation (OXPHOS). Protein analyses confirmed altered EIF5A, MT-ND3, MT-ND4L, and VCL expression, genes linked to mitochondrial translation, OXPHOS, adhesion, and cytoskeleton. MEHP also reduced cell-cell communication, particularly glial-stromal interactions. Mitochondrial stress assay in primary cells indicated increased proton leakage, and Schwann cell responses mirrored the scRNA-seq findings.</p><p><strong>Interpretation: </strong>Ovarian toxicity studies traditionally focus on follicles, but this study reveals the susceptibility of non-follicular cells. Importantly, the sensitivity of ovarian nervous system cells to MEHP offers new mechanistic insights into reported links between phthalates, altered ovarian sensitivity index, and polyendocrine metabolic ovarian syndrome. Our findings highlight the need for a holistic assessment of ovarian toxicity that considers all ovarian cell types, not only follicles.</p><p><strong>Funding: </strong>Swedish Research Council for Sustainable Development and the European Union.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":" ","pages":"106487"},"PeriodicalIF":11.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13688040/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149105817","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":"Brain-gut crosstalk associated with brain ageing in young and mid-life adults: a multicohort cross-sectional study.","authors":"Kanhao Zhao, Gabriel A Vignolle, Jennifer S Labus, Emeran A Mayer, Allison Vaughan, Marika Dy, Priten Vora, Ming W Hung, Keith Vossel, Chris Gill, Daniele Del Rio, Catherine Stanton, R Paul Ross, John F Cryan, Rima Kaddurah-Daouk, Yu Zhang, Arpana Church","doi":"10.1016/j.ebiom.2026.106468","DOIUrl":"10.1016/j.ebiom.2026.106468","url":null,"abstract":"<p><strong>Background: </strong>Brain age deviation is a promising neuroimaging biomarker of brain health, but its relevance in young and mid-life adults and its biological underpinnings remain insufficiently characterised. We aimed to test whether a functional-connectivity-derived brain ageing index (BAI) captures reproducible variability in early brain ageing and whether it is associated with cognitive-affective function and gut-derived biological signatures.</p><p><strong>Methods: </strong>We analysed resting-state fMRI from a discovery cohort (n = 674) with validation in a replication cohort (n = 444) and an independent cohort (n = 344). Whole-brain functional connectivity was computed using a 100-region Schaefer parcellation, and Bayesian ridge regression was used to predict chronological age; BAI was defined as the age-bias-corrected residual (predicted brain age minus chronological age). We tested associations between BAI and cognitive and affective measures across cohorts. In the independent cohort, we applied multi-view sparse partial least squares to integrate stool metagenomic and metabolomic profiles with BAI, and performed KEGG pathway enrichment analyses on features with non-zero weights.</p><p><strong>Findings: </strong>Predicted brain age correlated with chronological age across cohorts (r = 0.50-0.59). Higher BAI was consistently associated with connectivity patterns involving posterior cingulate/praecuneus and medial frontal regions, poorer cognitive performance, particularly working memory and executive function, and greater depressive symptoms. Multi-omics integration identified microbial taxa and stool metabolites, including ceramides, 24-hydroxycholesterol, dicarboxylic acids, and inverse associations with estetrol, linked to BAI. Enrichment analyses suggested involvement of neuroimmune, vascular, synaptic, and mitochondrial pathways.</p><p><strong>Interpretation: </strong>A connectivity-derived BAI captures reproducible variability in early brain ageing and links large-scale brain network organisation to gut-derived biological signatures. These findings suggest that BAI captures individual variability associated with brain health-related phenotypes and support the potential association of peripheral brain-gut biological pathways in early brain ageing.</p><p><strong>Funding: </strong>National Institutes of Health, National Institute on Ageing.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":" ","pages":"106468"},"PeriodicalIF":11.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13628603/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148918566","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":"Cepheid 9-gene host mRNA expression across the spectrum of Mycobacterium tuberculosis infection and disease: insights across the lifespan.","authors":"Marva Seifert, Michael Gracia, Donald G Catanzaro, Faiqa Rashid, Rehan R Syed, Faisal Masood, Naomi Hillery, Alamdar Hussain, Ashley Swing, Rebecca E Colman, Uzma Majeed, Antonino Catanzaro, Sabira Tahseen, Timothy C Rodwell","doi":"10.1016/j.ebiom.2026.106462","DOIUrl":"10.1016/j.ebiom.2026.106462","url":null,"abstract":"<p><strong>Background: </strong>Novel diagnostic solutions using host-response-based gene signatures to differentiate between individuals infected with Mycobacterium tuberculosis presenting with active tuberculosis disease (ATB), individuals infected with the bacterium in the absence of active tuberculosis disease (TBI), and individuals with no evidence of ATB or TBI (no TB) have demonstrated limited utility. However, the impact of age-related immunological changes on diagnostic performance remains unclear.</p><p><strong>Methods: </strong>Using blood samples collected from 119 'adolescent/young adults' aged 10-24 years, 259 'adults' aged 25-55 years, and 79 'older adults' aged 56 years and above we explored differences in expression of eight gene targets using a novel research-use-only Cepheid Xpert TB/LTBI assay. We plotted relative expression for each gene by age stratified by TB status, then constructed two composite classifiers using a subset of gene targets. These composite classifiers were compared using AUCs derived from logistic regression models fitted within each age stratum.</p><p><strong>Findings: </strong>Expression of IL2, IFNG, and MIG appeared to best differentiate individuals who were classified as TBI or ATB from no TB and were used to construct an 'exposure' classifier which yielded an AUC of 0.89 (95% CI 0.83-0.96) among adolescent/young adults, 0.82 (95% CI 0.76-0.87) among adults, and 0.71 (95% CI 0.58-0.84) among older adults. Similarly, expression of SLPI, VEGFA, PLAU, and GBP5 appeared to best differentiate between individuals who were classified as ATB from TBI or no TB. The corresponding composite 'disease' classifier yielded an AUC of 0.88 (95% CI 0.80-0.96) among adolescent/young adults, 0.74 (95% CI 0.66-0.82) among adults, and 0.56 (95% CI 0.40-0.73) among older adults.</p><p><strong>Interpretation: </strong>This study demonstrates the importance of considering age in the development and evaluation of host-response-based diagnostics for ATB and TBI and suggests that host-response-based diagnostics may prove most useful in differentiation of ATB, TBI, and no TB among adolescent/young adults.</p><p><strong>Fundings: </strong>This study was supported by the US Department of Defence (award number W81XWH-18-1-0253) and National Institutes of Health (award number R01AI137681). Salary support was received from the National Institutes of Health (training grant number T32AI007384).</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"132 ","pages":"106462"},"PeriodicalIF":11.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13570273/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148873186","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 multi-ancestry genome-wide association study of dry eye disease and systemic comorbidities.","authors":"Bryan R Gorman, Jaxon J Huang, Peter B Barr, Christopher W Halladay, Cari L Nealon, Chris Chatzinakos, Michael Francis, Chen Jiang, Paul B Greenberg, Wen-Chih Wu, Saiju Pyarajan, Hélène Choquet, Tim B Bigdeli, Sudha K Iyengar, Neal S Peachey, Anat Galor","doi":"10.1016/j.ebiom.2026.106490","DOIUrl":"10.1016/j.ebiom.2026.106490","url":null,"abstract":"<p><strong>Background: </strong>Dry eye disease (DED) affects up to 25% of the adult population, with chronic symptoms of pain and dryness often negatively impacting quality of life. Twin studies indicate a substantial heritability. However, the genetic architecture of DED is largely unknown.</p><p><strong>Methods: </strong>We devised a case-control algorithm using a combination of ICD-9/10 codes and prescription records and validated its performance through manual chart review, identifying 132,637 DED cases and 352,201 controls across four ancestry groups in the Million Veteran Program biobank. We then performed multi-ancestry genome-wide and phenome-wide association scans. A replication analysis was performed in the Genetic Epidemiology Research on Adult Health and Aging biobank (up to 16,025 cases and 54,818 controls). Genetic correlations were assessed using linkage disequilibrium score regression and multivariate relationships were modelled using genomic structural equation modelling (genomicSEM).</p><p><strong>Findings: </strong>We identify ten significant loci in nine susceptibility regions with largely consistent effects across ancestries, including loci linked to synapse maintenance (EFNA5, GRIA1, and SYNGAP1) and autoimmunity (BLK). Phenome-wide scans for genetic pleiotropy indicate substantial genetic correlations of DED with numerous comorbidities, including fibromyalgia (r_G = 0.69, 95% confidence interval, CI: [0.58, 0.81]), post-traumatic stress disorder (r_G = 0.58, 95% CI: [0.42, 0.75]), and Sjögren's disease (r_G = 0.40, 95% CI: [0.23, 0.57]). GenomicSEM identified a latent factor underlying DED and other chronic pain traits which accounted for 51% of the genetic variance of DED.</p><p><strong>Interpretation: </strong>The observed genetic correlations are consistent with shared genetic liability between DED and chronic pain, autoimmune, and psychiatric traits, but do not establish causal direction.</p><p><strong>Funding: </strong>This work was supported by the US Department of Veterans Affairs, the Department of Defense, the National Eye Institute/NIH, and Research to Prevent Blindness. Full funding details are provided in the Acknowledgements.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"132 ","pages":"106490"},"PeriodicalIF":11.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13635402/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149059253","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":"Multidimensional molecular profiling reveals decidual and circulating NK cell dynamics in early and late pregnancy.","authors":"Jennifer R Habel, Thi H O Nguyen, Lilith F Allen, Morgan J Skinner, Lukasz Kedzierski, E Kaitlynn Allen, Shihan Li, Natasha de Alwis, Ruth R Hagen, Karen Doggett, Xiaoxiao Jia, Ilariya Tarasova, Anastasia A Minervina, Mikhail V Pogorelyy, Ashleigh I Holloway, Nikita L Mathew, Philippa M Saunders, Allison Clatch, Maximilien Evrard, Calvin Xu, Hui-Fern Koay, Md Abdullah-Al-Kamran Khan, Laura K Mackay, Alexander D Barrow, Celia Douros, Theo Karapanagiotidis, Suellen Nicholson, Katherine Bond, Deborah A Williamson, Lisa Hui, Martha Lappas, Susan Walker, Sandra E Nicholson, Natalie J Hannan, Andrew G Brooks, Jan Schroeder, Jeremy Chase Crawford, Paul G Thomas, Louise C Rowntree, Katherine Kedzierska","doi":"10.1016/j.ebiom.2026.106495","DOIUrl":"10.1016/j.ebiom.2026.106495","url":null,"abstract":"<p><strong>Background: </strong>Human pregnancy presents a unique physiological state that allows for growth of an antigenically dissimilar foetus. The immune system plays a key role in establishing and maintaining successful pregnancy, yet detailed understanding of immunological responses in pregnancy is lacking.</p><p><strong>Methods: </strong>We defined the immunological landscape in pregnancy by screening >350 markers on NK cells, CD4⁺, CD8⁺ and γδ T cells, B cells and monocytes in third-trimester pregnancy peripheral blood, cord blood and decidua, and by performing single-cell RNA sequencing (scRNAseq), including 130 CITE-seq antibodies, on NK cells from the blood and decidua of third-trimester pregnancies. We validated our findings in additional blood and decidua samples from first- and third-trimester pregnancies. Blood samples from non-pregnant women were used as a control group for comparison.</p><p><strong>Findings: </strong>Our multiomic approaches revealed altered surface proteomes in lymphoid and myeloid immune subsets during third-trimester pregnancy, in comparison to non-pregnant women. In the blood during pregnancy, circulating NK cells displayed increased SOCS1 (FDR < 0.001) and AREG (FDR < 0.001), both involved in tightly regulating immune responses, as well as HLA-D family (FDR < 0.05-0.0001) gene expression, with increased CCR5 (p < 0.01-0.001) and HLA-DR (p < 0.01-0.001), and decreased CD9 (p < 0.001), CD36 (p < 0.05-0.001), and CX3CR1 (p < 0.05) at the protein level, validated in samples from first- and third-trimester pregnancies. Our analysis of decidual NK (dNK) cells demonstrated a decline in the dNK1 subset between first-trimester decidua and third-trimester decidua basalis (p < 0.0001) and parietalis (p < 0.01), and identified an adaptive-like subset with high expression of cytotoxic molecules, which could be distinguished from the previously described dNK1-3 subsets and was enriched in decidua from women with a history of cytomegalovirus infection (p < 0.05). Functionally, we observed enhanced control of IFN-γ secretion in response to proinflammatory IL-12/IL-18 cytokines in pregnancy (p < 0.05-0.01), however induction of SOCS1 protein expression remained similar between pregnant and non-pregnant women.</p><p><strong>Interpretation: </strong>Overall, our study provides key insights into immunity in pregnancy and reveals fundamental differences in the NK cell compartment. Understanding pregnancy-specific immunology fills important knowledge gaps to better inform the rational design of vaccines, immunotherapies and identification of biomarkers for safe pregnancy outcomes.</p><p><strong>Funding: </strong>Australian National Health and Medical Research Council, Australian Medical Research Future Fund, and the National Institute of Allergy and Infectious Diseases.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"132 ","pages":"106495"},"PeriodicalIF":11.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13657211/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149105841","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":"Engineering clinically actionable nanomedicine for cancer immunometabolic ecosystem reprogramming.","authors":"Yuhong Gao, Xiulin Dong, Sijia Hua, Lingyun Li, Xiaofeng Zhang, Jianfeng Yang","doi":"10.1016/j.ebiom.2026.106501","DOIUrl":"10.1016/j.ebiom.2026.106501","url":null,"abstract":"<p><p>Traditional metabolic inhibitors have limited clinical efficacy, with issues such as narrow window periods, and compensatory effects. These barriers indicate that effective metabolic therapy requires spatially restricted, temporally coordinated, cell-context-aware, and clinically stratifiable intervention. This review examines how glucose-lactate, lipid-redox, amino acid-immune checkpoint, and nucleotide-adenosine circuits drive tumour progression, immune suppression, and therapeutic escape. We then define the engineering advantages that distinguish nanomedicine from free metabolic drugs, including spatiotemporal control, smart and responsive release, multi-target co-delivery, and organelle targeting. Representative nanomedicine strategies are discussed according to the immunometabolic circuits they modulate, with emphasis on their ability to overcome metabolic compensation, restore immune cell function, and address tumour heterogeneity. Finally, we evaluate key translational challenges, including chemistry, manufacturing and control (CMC), regulatory obstacles, and biomarker selection. This review proposes clinically actionable design principles of nanomedicine for immunometabolic reprogramming.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"132 ","pages":"106501"},"PeriodicalIF":11.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13673106/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149105829","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":"Converging arboviral outbreaks demand disease-agnostic public health responses.","authors":"eBioMedicine","doi":"10.1016/j.ebiom.2026.106519","DOIUrl":"10.1016/j.ebiom.2026.106519","url":null,"abstract":"","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"132 ","pages":"106519"},"PeriodicalIF":11.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13688038/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149180031","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":"Safety and efficacy of cisplatin and nab-paclitaxel pressurised intraperitoneal aerosol chemotherapy (PIPAC) in patients with peritoneal carcinomatosis: Nab-PIPAC phase 1b study.","authors":"Manuela Undurraga, Noemie Lang, Thibaud Koessler, Antonella Diciolla, Mariagrazia Di Marco, Nicolas Mach, Catherine Raimond, Vassilis Genoud, Valentine Du Bois, Jean-Christophe Tille, Aurelie Bornand, Jonathan S Moore, Marc Weiner, Laure Smekens, José L Sandoval, Julie Terzic, Yann Christinat, Jennifer Veillard, Petros Tsantoulis, Paul Thoueille, Thomas Mercier, Stefan Monig, Patrick Petignat, Christian Toso, Laurent Decosterd, Martin Hübner, Intidhar Labidi-Galy, Frederic Ris","doi":"10.1016/j.ebiom.2026.106477","DOIUrl":"10.1016/j.ebiom.2026.106477","url":null,"abstract":"<p><strong>Background: </strong>Platinum and taxanes are backbone chemotherapy in multiple solid tumours. We aimed to investigate the safety, tolerability, and pharmacokinetics of nab-paclitaxel and cisplatin administered by pressurised intraperitoneal aerosol chemotherapy (PIPAC).</p><p><strong>Methods: </strong>Nab-PIPAC is a phase 1b trial investigating PIPAC administration of cisplatin at 10.5 mg/m² and escalating dose of nab-paclitaxel with a 3 + 3 design (7.5, 15, 25, 37.5, 52.5 and 70 mg/m²). PIPAC was repeated at 4-6 weeks intervals for up to three courses to estimate the maximum tolerated dose (MTD).</p><p><strong>Findings: </strong>We enrolled 22 patients with peritoneal carcinomatosis, of whom 18 received at least one PIPAC: 6 ovarian, 9 gastric and 3 pancreatic cancers. Four patients (ovarian cancer) did not receive PIPAC due to bowel obstruction (n = 1) or no access to peritoneal cavity (n = 3). Median age was 67 years (43-81). In total, 45 PIPAC procedures were administered and 12 of 18 (67%) patients completed three PIPAC cycles. There was no dose limiting toxicity. The most common side effect was abdominal pain. One patient had grade 3 treatment related adverse event: bladder lesion requiring surgical reintervention. Median progression-free survival was 3.5 months and median overall survival was 9.4 months. Five patients with gastrointestinal cancer survived more than one year (3 gastric and 2 pancreatic). Pharmacokinetic analyses showed good linearity between nab-paclitaxel dose and the AUC_0-last (R² = 0.90).</p><p><strong>Interpretation: </strong>The combination of nab-paclitaxel and cisplatin administered by PIPAC was safe and well tolerated in patients with peritoneal carcinomatosis. Further investigation of this combination is warranted.</p><p><strong>Funding: </strong>The study was supported by la bourse jeune chercheur des Hopitaux Universitaires de Geneve (NL), Fondation Fond'action (ILG) and Fondation NOVA (ILG).</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"132 ","pages":"106477"},"PeriodicalIF":11.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13587052/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148944542","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}