EBioMedicine最新文献

{"title":"Characterisation of a secreted MFSD6-Fc microbody as a decoy receptor for respiratory enterovirus D68.","authors":"Zhaoxue Li, Huili Li, Xize Liu, Junfeng Zhou, Delong Gao, Wanying Yang, Huiming Xia, Chao Dou, Zhenglei Yu, Haoran Guo, Wei Wei","doi":"10.1016/j.ebiom.2025.105915","DOIUrl":"10.1016/j.ebiom.2025.105915","url":null,"abstract":"<p><strong>Background: </strong>Enterovirus D68 (EV-D68) is a prominent non-polio enterovirus known to cause severe respiratory infections and poliomyelitis-like illnesses in children. Recently, we identified MFSD6 as a receptor for EV-D68, providing a potential target for blocking viral entry into cells. This study aimed to develop an MFSD6-based decoy receptor to neutralise EV-D68 and elucidate its mechanism of action.</p><p><strong>Methods: </strong>In this study, we engineered a secreted MFSD6-Fc microbody (secMFSD6 Mb) and evaluated its efficacy using in vitro binding assays (co-immunoprecipitation, RT-qPCR), electron microscopy, and functional studies in EV-D68-infected respiratory cell lines (Calu-3, BEAS-2B, A549), primary human bronchial epithelial cells (HBECs), and a neonatal ICR mouse model (n = 9 per group) infected with EV-D68. Statistical significance was determined by two-way ANOVA and t-test (GraphPad Prism 8.0.2; significance threshold P < 0.05).</p><p><strong>Findings: </strong>secMFSD6 Mb occupies the receptor-binding sites on the viral surface, reducing virus attachment to cells by >90% (n = 3 biological replicates). Electron microscopy showed conversion of intact virions to empty capsids after Mb treatment, and sucrose-gradient analysis demonstrated a 6-fold increase in free viral RNA (F2 fraction) compared with control. In mice challenged with 1 × 10⁷ TCID₅₀ of US/MO/14-18947, secMFSD6 Mb increased 15-day survival from 11% (1/9) to 89% (8/9).</p><p><strong>Interpretation: </strong>This decoy receptor strategy may support the development of effective therapeutic approaches against EV-D68 infection.</p><p><strong>Funding: </strong>HYPNSFC Excellent Young Scientist Fund (32222005), the National Natural Science Foundation of China (82372226, 82172246), the National Major Project for Infectious Disease Control and Prevention (2018ZX10731-101-001-016).</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"120 ","pages":"105915"},"PeriodicalIF":10.8,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12452593/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145029339","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 mediating role of epigenetic ageing in the nonlinear association between body mass index and survival: a prospective cohort analysis of the US Health and Retirement Study.","authors":"Peggy Ler, Juulia Jylhävä, Sara Hägg, Deborah Finkel, Anna K Dahl Aslan, Alexander Ploner, Ida K Karlsson","doi":"10.1016/j.ebiom.2025.105883","DOIUrl":"10.1016/j.ebiom.2025.105883","url":null,"abstract":"<p><strong>Background: </strong>The role of biological ageing in the association between body mass index (BMI) and survival remains unclear. We examined whether epigenetic age acceleration (EAA), a biomarker of biological ageing, mediates the BMI-survival association.</p><p><strong>Methods: </strong>We analysed data from 3840 participants (aged 51-100) in the 2016 US Health and Retirement Study, with survival information through 2020. Mediation analyses were performed using linear regression and Gompertz proportional hazards models with restricted cubic splines, adjusting for age, sex, ethnicity/race, smoking, education, and metabolic health. Average direct effects (ADE) of BMI and average causal mediation effects of EAA (HannumAgeAcc, PhenoAgeAcc, GrimAgeAcc, and DunedinPace) on survival time were estimated with 95% confidence intervals (CI).</p><p><strong>Findings: </strong>Associations between BMI, EAA, and survival were nonlinear: high and low BMIs were associated with higher EAA and reduced survival time. ADEs of high BMI (35 kg/m² versus 27 kg/m²) were not statistically significant (reduced survival time: 1.21-1.58 years) but significant for low BMI (19 kg/m² versus 27 kg/m², reduced survival time: 5.60-6.38 years). For high BMI, mediation was significant through all EAAs, with reduced survival time ranging from 0.28 to 0.71 years, accounting for 15-37% of total effects. For low BMI, mediation was statistically significant through HannumAgeAcc (reduced survival time: 0.44, CI: 0.08-0.86) and GrimAgeAcc (reduced survival time: 0.73, CI: 0.15-1.38), accounting for 7-11% of total effects.</p><p><strong>Interpretation: </strong>EAA partially mediated the high BMI-survival association, supporting the mediating role of accelerated ageing in the obesity-survival relationship. Mediation through EAA in the low BMI-survival association was weaker, indicating that alternative mechanisms, other than accelerated ageing, may dominate.</p><p><strong>Funding: </strong>Forte, Vetenskaprådet, SFOepi, Karolinska Institutet's Research Foundation, Loo and Hans Osterman Foundation, the Foundation for Geriatric Diseases at Karolinska Institutet.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"119 ","pages":"105883"},"PeriodicalIF":10.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12391497/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144872000","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":"Volatile pyrethroid spatial repellents for preventing mosquito bites: a systematic review and meta-analysis.","authors":"Ingrid Chen, Sarah L Miller, Daniel Msellemu, Aidi G Lugenge, Johnson Kyeba Swai, Nicole Achee, Marta Andrés, Christopher S Bibbs, Theeraphap Chareonviriyaphap, J Derek Charlwood, Greg Devine, Noel Elman, Ulrike Fillinger, Carmen Flores-Mendoza, Seth Gibson, Nicodem Govella, Steven Gowelo, Sebastian Horstmann, Hitoshi Kawada, Daniel Kline, Aaron Lloyd, Neil F Lobo, Marta F Maia, Arnold Mmbando, Mara Moreno-Gómez, Amy C Morrison, Winifrida Mponzi, Emmanuel P Mwanga, Margaret Njoroge, Sheila B Ogoma, Fredros O Okumu, Mercy Opiyo, Welbeck A Oumbouke, John Paliga, Arissara Pongsiri, Alongkot Ponlawat, Manop Saeaung, Ferdinand Salazar, Onyango Sangoro, Jennifer C Stevenson, Chutipong Sukkanon, Din Syafruddin, Mgeni Mohamed Tambwe, Julie-Anne A Tangena, Elodie A Vajda, Gonzalo Vazquez-Prokopec, Joseph M Wagman, Chanly Yan, Isabel Elaine Allen, Sarah J Moore","doi":"10.1016/j.ebiom.2025.105891","DOIUrl":"10.1016/j.ebiom.2025.105891","url":null,"abstract":"<p><strong>Background: </strong>Volatile pyrethroid spatial repellents (VPSRs) can prevent mosquito-borne diseases including malaria and dengue fever, but the use of varied evaluation methods has resulted in a lack of clarity regarding their protective efficacy (PE) against contact with mosquitoes. This systematic review and meta-analysis consolidates the entomological evidence base on the PE of VPSRs against Anopheles, Aedes, and Culex mosquitoes and different test methods used.</p><p><strong>Methods: </strong>We identified studies completed between January 2000 and September 2023 by searching through databases, conference abstracts, and personal correspondences. Included studies were semi-field or field studies that measured the PE of VPSRs using human landing catch (HLC) of mosquito landings on human legs and/or mosquito trap density, the number of mosquitoes captured using traps per set time period, compared to control groups. The systematic review summarised study-level data using a generalised linear mixed model with random effects. The meta-analysis pooled individual mosquito-level data and weather data on temperature, humidity, and wind from satellites, analysing PE subgrouped by product format, active ingredient, mosquito capture method used, mosquito species, and indoor vs outdoor setting. Risk of bias was assessed using a SYRCLE tool adapted for mosquito studies. Additional studies published from October 2023 to July 2025 were summarised. PROSPERO registration: CRD42021268852.</p><p><strong>Findings: </strong>58 eligible publications showed that VPSRs provided an average of 56% (95% CI 50, 62%) PE from mosquito bites. Meta-analysis of individual mosquito-level data from 50 (86%) of eligible studies involving 1,703,120 mosquitoes showed that PE was highest when measured using HLC, with similar results seen in semi-field (58%, 95% CI 54, 62%) and field studies (50%, 95% CI 40, 59%). Differences between indoor (54%, 95% CI 18, 68%) and outdoor settings (56%, 95% CI 51, 60%) were unclear. Species-level differences were observed with low PE seen in Anopheles funestus (31%, 95% CI 19, 43%); the potential for cross-resistance to solid-state pyrethroids is unclear. Efficacy was not sensitive to combined weather effects.</p><p><strong>Interpretation: </strong>VPSRs offer protection from contact with mosquitoes, with semi-field studies reflecting field data and species-level differences observed. HLC provided the best quality data. Additional field studies that evaluate outdoor protection in malaria-endemic settings are needed, especially in West African, South American, and Southeast Asian settings.</p><p><strong>Funding: </strong>National Institutes of Health (National Institute of Allergy and Infectious Diseases (K01AI156182)) and \"Accelerate to Eliminate Malaria\" program.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":" ","pages":"105891"},"PeriodicalIF":10.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144946959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to 'Immune correlates analysis of the Imbokodo (HVTN 705/HPX2008) efficacy trial of a mosaic HIV-1 vaccine regimen evaluated in Southern African people assigned female sex at birth: a two-phase case-control study'. EBioMedicine 2024;108: 105320.","authors":"Avi Kenny, Janine van Duijn, One Dintwe, Jack Heptinstall, Randy Burnham, Sheetal Sawant, Lu Zhang, Dieter Mielke, Sharon Khuzwayo, Faatima Laher Omar, Sherry Stanfield-Oakley, Taylor Keyes, Brooke Dunn, Derrick Goodman, Youyi Fong, David Benkeser, Rodger Zou, John Hural, Ollivier Hyrien, Michal Juraska, Alex Luedtke, Lars van der Laan, Elena E Giorgi, Craig Magaret, Lindsay N Carpp, Laura Pattacini, Tom van de Kerkhof, Bette Korber, Wouter Willems, Leigh H Fisher, Hanneke Schuitemaker, Edith Swann, James G Kublin, Maria G Pau, Susan Buchbinder, Frank Tomaka, Steven Nijs, Ludo Lavreys, Huub C Gelderblom, Lawrence Corey, Kathryn Mngadi, Glenda E Gray, Erica Borducchi, Jenny Hendriks, Kelly E Seaton, Susan Zolla-Pazner, Dan H Barouch, Guido Ferrari, Stephen C De Rosa, M Juliana McElrath, Erica Andersen-Nissen, Daniel J Stieh, Georgia D Tomaras, Peter B Gilbert","doi":"10.1016/j.ebiom.2025.105874","DOIUrl":"10.1016/j.ebiom.2025.105874","url":null,"abstract":"","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"119 ","pages":"105874"},"PeriodicalIF":10.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144946914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prophylactic protection from lethal henipavirus disease mediated by Nipah-derived defective interfering particles is influenced by challenge virus strain and viral species.","authors":"Stephen R Welch, Jessica R Spengler, Jessica R Harmon, JoAnn D Coleman-McCray, Sarah C Genzer, Katherine A Davies, Teresa E Sorvillo, Florine E M Scholte, Sergio E Rodriguez, Joel M Montgomery, Stuart T Nichol, Christina F Spiropoulou","doi":"10.1016/j.ebiom.2025.105897","DOIUrl":"10.1016/j.ebiom.2025.105897","url":null,"abstract":"<p><strong>Background: </strong>Henipaviruses, including Nipah and Hendra viruses, are zoonotic pathogens that can cause severe respiratory and neurological diseases with high mortality rates in humans. Due to the severity of the disease, the high pandemic potential of these viruses, and the lack of approved treatments, the development of safe and effective medical countermeasures against henipaviruses is a critical priority.</p><p><strong>Methods: </strong>Here, we evaluate treatment efficacy of defective interfering particles (DIPs)-naturally occurring virus-like particles that lack substantial portions of the viral genome-against henipaviruses in the Syrian hamster model of disease.</p><p><strong>Findings: </strong>Prophylactic DIP treatment markedly reduced clinical signs and lethality in Syrian hamsters. Single or repeated pre-exposure regimens, starting up to 3 days before challenge, provided protection, while post-exposure treatment was ineffective. DIPs derived from NiV strain Malaysia were most effective against NiV Malaysia but also provided strong protection against the closely related NiV Bangladesh with certain regimens. However, these DIPs offered minimal or no protection against lethality from the more distantly related Hendra virus.</p><p><strong>Interpretation: </strong>Our data indicate efficacy of DIPs as a pre-exposure prophylactic for henipavirus infection and support a direct mechanism of viral inhibition.</p><p><strong>Funding: </strong>This work was partially supported by the DARPAINTERfering and Co-Evolving Prevention and Therapy (INTERCEPT) program (DARPA-BAA-16-35), CDC Emerging Infectious Disease Research Core Funds, an appointment to the Research Participation Program at the Centers for Disease Control and Prevention (CDC) administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U.S. Department of Energy and CDC (K.A.D., S.E.R.), and by NIAID1R01AI151006 (T.E.S).</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"119 ","pages":"105897"},"PeriodicalIF":10.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144946900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between wearable sensor signals and expected hormonal changes in pregnancy.","authors":"Giulia Milan, Lauren Ariniello, Katie Baca-Motes, Arij Faksh, Jacqueline K Kueper, Jay A Pandit, Tolúwalàṣẹ Àjàyí, Giorgio Quer","doi":"10.1016/j.ebiom.2025.105888","DOIUrl":"10.1016/j.ebiom.2025.105888","url":null,"abstract":"<p><strong>Background: </strong>The rising maternal health crisis in the United States necessitates innovative approaches to pregnancy monitoring. This observational cohort study aimed to assess whether wearable sensors can effectively track physiological and behavioural changes during pregnancy and examine their associations with pregnancy-related hormonal fluctuations.</p><p><strong>Methods: </strong>This longitudinal cohort study recruited participants via a bilingual mobile research platform. Eligible participants were aged ≥16 years, pregnant or within eight weeks postpartum, residing in the United States, and consented to share data collected by their own wearable device (Apple, Garmin, or Fitbit). Self-reported survey responses and wearable sensor data were collected from 99 participants who experienced a live birth pregnancy, from three months pre-pregnancy to six months postpartum. Key outcomes included changes in resting heart rate (RHR), physical activity, and sleep patterns, analysed in relation to expected hormonal fluctuations during pregnancy.</p><p><strong>Findings: </strong>In live birth pregnancies, RHR initially decreased between weeks 5-9, followed by a steady increase until 8-9 weeks before delivery, then declined until birth, dropping below pre-pregnancy levels postpartum before stabilising at six months. Total sleep time increased in the first trimester but decreased throughout the remainder of pregnancy. A strong correlation was observed between RHR fluctuations and pregnancy-induced hormonal changes (R² = 0.93). Pregnancies ending in adverse outcomes displayed distinct RHR patterns compared to live birth pregnancies.</p><p><strong>Interpretation: </strong>These findings suggest that wearable sensors provide a non-invasive method to monitor pregnancy-related physiological and behavioural changes, which align with hormonal shifts. This study provides population-level insights in live birth pregnancies, and an exploratory analysis of adverse outcomes reflecting the feasibility of recruiting and capturing physiological signals also in these cases. This approach may enable early risk assessment for adverse pregnancy outcomes, including miscarriage and preterm birth.</p><p><strong>Funding: </strong>This work was supported by the National Center for Advancing Translational Sciences (UM1TR004407) and from the Patrick J. McGovern Foundation.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"119 ","pages":"105888"},"PeriodicalIF":10.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12410205/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144946951","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":"Deep learning-based prediction of axillary pathological complete response in patients with breast cancer using longitudinal multiregional ultrasound.","authors":"Yu Liu, Ying Wang, Jiaxin Huang, Shufang Pei, Yuxiang Wang, Yanfen Cui, Lifen Yan, Mengxia Yao, Yumeng Wang, Zejun Zhu, Chunwang Huang, Zaiyi Liu, Changhong Liang, Jiayao Shi, Zhenhui Li, Xiaoqing Pei, Lei Wu","doi":"10.1016/j.ebiom.2025.105896","DOIUrl":"10.1016/j.ebiom.2025.105896","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Noninvasive biomarkers that capture the longitudinal multiregional tumour burden in patients with breast cancer may improve the assessment of residual nodal disease and guide axillary surgery. Additionally, a significant barrier to the clinical translation of the current data-driven deep learning model is the lack of interpretability. This study aims to develop and validate an information shared-private (iShape) model to predict axillary pathological complete response in patients with axillary lymph node (ALN)-positive breast cancer receiving neoadjuvant therapy (NAT) by learning common and specific image representations from longitudinal primary tumour and ALN ultrasound images.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;A total of 1135 patients with biopsy-proven ALN-positive breast cancer who received NAT were included in this multicentre, retrospective study. The iShape was trained on a dataset of 371 patients and validated on three external validation sets (EVS1-3), with 295, 244, and 225 patients, respectively. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC). The false-negative rates (FNRs) of iShape alone and in combination with sentinel lymph node biopsy (SLNB) were also evaluated. Imaging feature visualisation and RNA sequencing analysis were performed to explore the underlying basis of iShape.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Findings: &lt;/strong&gt;The iShape achieved AUCs of 0.950-0.971 for EVS 1-3, which were better than those of the clinical model and the image signatures derived from the primary tumour, longitudinal primary tumour, or ALN (P &lt; 0.05, as per the DeLong test). The performance of iShape remained satisfactory in subgroup analyses stratified by age, menstrual status, T stage, molecular subtype, treatment regimens, and machine type (AUCs of 0.812-1.000). More importantly, the FNR of iShape was 7.7%-8.1% in the EVSs, and the FNR of SLNB decreased from 13.4% to 3.6% with the aid of iShape in patients receiving SLNB and ALN dissection. The decision-making process of iShape was explained by feature visualisation. Additionally, RNA sequencing analysis revealed that a lower deep learning score was associated with immune infiltration and tumour proliferation pathways.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Interpretation: &lt;/strong&gt;The iShape model demonstrated good performance for the precise quantification of ALN status in patients with ALN-positive breast cancer receiving NAT, potentially benefiting individualised decision-making, and avoiding unnecessary axillary lymph node dissection.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Funding: &lt;/strong&gt;This study was supported by (1) Noncommunicable Chronic Diseases-National Science and Technology Major Project (No. 2024ZD0531100); (2) Key-Area Research and Development Program of Guangdong Province (No. 2021B0101420006); (3) National Natural Science Foundation of China (No. 82472051, 82471947, 82271941, 82272088); (4) National Science Foundation for Young Scientists of China (No. 8240","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"119 ","pages":"105896"},"PeriodicalIF":10.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12410175/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144946954","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":"Longitudinal association of shorter leukocyte telomere length with CSF biomarker dynamics across early Alzheimer's disease stages in at-risk individuals.","authors":"Blanca Rodríguez-Fernández, Armand González-Escalante, Patricia Genius, Tavia E Evans, Paula Ortiz-Romero, Carolina Minguillón, Gwendlyn Kollmorgen, Nicholas J Ashton, Henrik Zetterberg, Kaj Blennow, Juan Domingo Gispert, Arcadi Navarro, Marc Suárez-Calvet, Aleix Sala-Vila, Marta Crous-Bou, Natàlia Vilor-Tejedor","doi":"10.1016/j.ebiom.2025.105886","DOIUrl":"10.1016/j.ebiom.2025.105886","url":null,"abstract":"<p><strong>Background: </strong>Short telomere length (TL), a hallmark of biological ageing, has been associated with an increased risk of Alzheimer's disease (AD), but its pathophysiological role remains unclear. This study explored the relationship between blood leukocyte TL (LTL), cerebrospinal fluid (CSF) AD biomarkers changes, and brain structure across early stages of the AD continuum.</p><p><strong>Methods: </strong>We included 346 cognitively unimpaired participants (aged 49-71) from the ALFA cohort, enriched for AD risk (53.2% APOE-ε4 carriers; 34% amyloid-positive). LTL was measured at baseline (visit 0) using quantitative PCR. Associations were assessed between baseline LTL and CSF biomarkers at visit 1 (mean follow-up from baseline = 3.98 years, SD = 1.02), and with changes in CSF biomarkers between visits 1 and 2 (mean interval = 3.45 years, SD = 0.58). Cortical thickness in ageing- and AD-vulnerable brain regions was evaluated by magnetic resonance imaging (MRI) at visit 1. Analyses were stratified by APOE-ε4 status and amyloid-tau (AT) profiles. Mediation models tested whether CSF biomarkers mediated LTL-cortical thickness associations.</p><p><strong>Findings: </strong>Shorter LTL was associated with higher astrocytic reactivity at visit 1 and with increased synaptic dysfunction over time. Among APOE-ε4 carriers and AT-positive individuals, shorter LTL was associated with higher p-tau181 and neurodegeneration markers. Shorter LTL was associated with greater cortical thickness in ageing- and AD-vulnerable regions, partially mediated by astrocytic reactivity biomarkers.</p><p><strong>Interpretation: </strong>These findings suggest that shorter telomeres are associated with early AD-related biological changes, potentially via mechanisms involving astrocytic reactivity and brain structural alterations. LTL may serve as an early marker of vulnerability to neurodegenerative processes in at-risk populations.</p><p><strong>Funding: </strong>AARG-19-618265; PI19/00119; LCF/PR/GN17/10300004; TriBEKa-17-519007; # SLT002/16/00201.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"119 ","pages":"105886"},"PeriodicalIF":10.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12395440/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144946964","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":"Specific features of immune ageing are detected in the earliest stages in rheumatoid arthritis development.","authors":"Karim Raza, Archana Sharma-Oates, Leonid Padyukov, Annette H M van der Helm-van Mil, Arthur G Pratt, Simon W Jones, A Filer, Janet M Lord, Niharika A Duggal","doi":"10.1016/j.ebiom.2025.105900","DOIUrl":"10.1016/j.ebiom.2025.105900","url":null,"abstract":"<p><strong>Background: </strong>Rheumatoid arthritis is an age-related disease displaying features of an aged immune system. This study aims to determine premature presence of immune ageing in the early stages of RA development, including in patients with clinically suspected arthralgia and undifferentiated arthritis.</p><p><strong>Methods: </strong>We recruited 224 participants: 69 healthy controls (mean age 57.12 years, 28% male); 32 with clinically suspected arthralgia (mean age 46.50 years, 11% male); 44 with undifferentiated arthritis (mean age 51.96 years, 21% male); 23 with newly presenting DMARD naive RA and 3 months or less symptom duration (mean age 56.5 years, 30% male) and 56 with DMARD naive RA and greater than 3 months symptom duration (mean age 56.41 years, 41% male). Features of immune ageing were assessed via flow cytometry and a subset of 8 immune cell type frequencies were used to generate an integrated score of immune ageing IMM-AGE and transcriptomic analysis for hallmarks of immune ageing was performed.</p><p><strong>Findings: </strong>Reduced frequencies of naive CD4 T cells and recent thymic emigrants were seen in patients with arthralgia or undifferentiated arthritis. Other features of immune ageing, such as raised frequency of Th17, Tregs and senescent-like T cells, were only seen once RA was established. Overall, the IMM-AGE score and other hallmarks of ageing (inflammation, autophagic defects) were raised in patients during early stages of the disease. Lastly, we have provided evidence of immune ageing features as a predictor of RA development in arthralgia patients.</p><p><strong>Interpretation: </strong>We have shown that some features of immune ageing are present in the very early stages of RA and may therefore contribute to disease development. Future research should determine whether geroprotective drugs such as spermidine (autophagy booster), senolytics (clearance of senescent cells) and metformin (attenuates inflammation and boosts autophagy) reduce progression of the disease in patients at risk of RA.</p><p><strong>Funding: </strong>This study was funded by a grant from FOREUM and the European League Against Rheumatism (EULAR).</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":" ","pages":"105900"},"PeriodicalIF":10.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144999933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Toward gender equity in contraception: male contraceptive passes safety trial.","authors":"eBioMedicine","doi":"10.1016/j.ebiom.2025.105938","DOIUrl":"https://doi.org/10.1016/j.ebiom.2025.105938","url":null,"abstract":"","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"119 ","pages":"105938"},"PeriodicalIF":10.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145052425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}