Nature Medicine最新文献

{"title":"Immune impacts of fire smoke exposure","authors":"Mary M. Johnson, Abhinav Kaushik, Olivia A. Kline, Eric M. Smith, Xiaoying Zhou, Yagiz Pat, Laura Buergi, Juan Aguilera, Shifaa Alkotob, Elisabeth M. Simonin, Alberto Favaro, Miguel Couto, Oscar Bennett, R. Sharon Chinthrajah, Ella Parsons, Mohamed Shamji, Marshall Burke, Melissa Bondy, Mubeccel Akdis, Cezmi A. Akdis, Kari C. Nadeau","doi":"10.1038/s41591-025-03777-6","DOIUrl":"https://doi.org/10.1038/s41591-025-03777-6","url":null,"abstract":"<p>Exposure to fire smoke has become a global health concern and is associated with increased morbidity and mortality. There is a lack of understanding of the specific immune mechanisms involved in smoke exposure, with preventive and targeted interventions needed. After exposure to fire smoke, which includes PM_2.5, toxic metals and perfluoroalkyl and polyfluoroalkyl substances, epidemiology-based studies have demonstrated increases in respiratory (for example, asthma exacerbation), cardiac (for example, myocardial infarction, arrhythmias), neurological (for example, stroke) and pregnancy-related (for example, low birthweight, premature birth) outcomes. However, mechanistic studies exploring how smoke exposure disrupts cellular homeostasis are lacking. Therefore, we collected blood from smoke-exposed individuals (<i>n</i> = 31) and age-matched and sex-matched non-smoke-exposed controls (<i>n</i> = 29), and investigated these complex interactions using a single-cell exposomic approach based on both methylation and mass cytometry. Overall, our data demonstrated a strong association between smoke exposure and methylation at 133 disease-relevant gene loci, while immunophenotyping showed increased homing and activation biomarkers. We developed an application of mass cytometry to analyze single-cell/metal binding and found, for example, increased levels of mercury in dead cells and cadmium in the live and dead cell populations. Moreover, mercury levels were associated with years of smoke exposure. Several epigenetic sites across multiple chromosomes were associated with individual toxic metal isotopes in single immune cells. Our methods for detecting the effect of smoke exposure at the single-cell level and the study results may help to determine the timing of exposure and identify specific molecular targets that could be modified to prevent and manage exposure to smoke.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"46 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144488407","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":"Microbes convert plastic waste into paracetamol","authors":"","doi":"10.1038/d41591-025-00041-9","DOIUrl":"https://doi.org/10.1038/d41591-025-00041-9","url":null,"abstract":"Merging synthetic organic chemistry and biotechnology, researchers have engineered Escherichia coli that can synthesize small molecules (including paracetamol) from a plastic waste product","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"28 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144500429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A new hormone arrives in the middle of the night","authors":"","doi":"10.1038/s41591-025-03797-2","DOIUrl":"https://doi.org/10.1038/s41591-025-03797-2","url":null,"abstract":"Jeffrey Friedman recalls the heady excitement when his group discovered leptin, a hormone that regulates appetite.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"70 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144488404","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":"Building resilience when neural implants are abandoned","authors":"George Kouvas, Christopher Coenen, Dirk Hommrich, Thomas Stieglitz, Bernice Simone Elger, Fabrice Jotterand","doi":"10.1038/s41591-025-03772-x","DOIUrl":"https://doi.org/10.1038/s41591-025-03772-x","url":null,"abstract":"As neural implants become more integrated with human cognition and identity, the risks posed by their sudden discontinuation are unique and demand urgent attention.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"70 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144479117","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":"Efficacy, public health impact and optimal use of the Takeda dengue vaccine","authors":"Bethan Cracknell Daniels, Neil M. Ferguson, Ilaria Dorigatti","doi":"10.1038/s41591-025-03771-y","DOIUrl":"https://doi.org/10.1038/s41591-025-03771-y","url":null,"abstract":"<p>Dengue is the most common arboviral infection, causing substantial morbidity and mortality globally. The licensing of Qdenga, a second-generation vaccine developed by Takeda Pharmaceuticals, is therefore timely, but the potential public health impact of vaccination across transmission settings needs to be evaluated. To address this, we characterized Qdenga’s efficacy profile using mathematical models calibrated to published clinical trial data and estimated the public health impact of routine vaccine use. We find that efficacy against both virologically confirmed dengue and hospitalization depends on the infecting serotype, serological status and age. We estimate that vaccination of children aged over 6 years in moderate-to-high dengue transmission settings (average seroprevalence in 9-year-olds &gt; 60%) could reduce the burden of hospitalized dengue by 10–22% on average over 10 years. We find some evidence of a risk of vaccine-induced disease enhancement in seronegative vaccine recipients for dengue serotypes 3 and 4, especially for children under 6 years of age. Because of this, the benefits of vaccination in lower transmission settings are more uncertain, and more data on the long-term efficacy of Qdenga against serotypes 3 and 4 are needed.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"17 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144479119","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":"Antigen-presenting mast cells are new players in breast cancer immunotherapy","authors":"Carlos Luri-Rey, Álvaro Teijeira, Ignacio Melero","doi":"10.1038/s41591-025-03740-5","DOIUrl":"https://doi.org/10.1038/s41591-025-03740-5","url":null,"abstract":"A new study identifies a novel subset of mast cells that cross-present tumor antigens in patients triple-negative breast cancer — and a pilot clinical trial shows how these can be exploited in immunotherapy strategies.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"39 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144479118","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":"Mobilizing antigen-presenting mast cells in anti-PD-1-refractory triple-negative breast cancer: a phase 2 trial","authors":"Song-Yang Wu, Xi Jin, Yin Liu, Zi-Yu Wang, Wen-Jia Zuo, Ding Ma, Yi Xiao, Tong Fu, Yu-Ling Xiao, Li Chen, Xi-Yu Liu, Lei Fan, Zhong-Hua Wang, Minhong Shen, Ronghua Liu, Wen-Jun Chai, Zhi-Ming Shao, Yi-Zhou Jiang","doi":"10.1038/s41591-025-03776-7","DOIUrl":"https://doi.org/10.1038/s41591-025-03776-7","url":null,"abstract":"<p>The central challenge in triple-negative breast cancer (TNBC) immunotherapy is to identify novel mechanism-derived strategies for anti-programmed death-1 (PD-1) resistance and efficiently assess their efficacy and safety in humans. Understanding the intricate heterogeneity of the tumor microenvironment and its impact on treatment could guide the initiation of proof-of-concept clinical trials. Here, integrating single-cell transcriptome of 44 treatment-naive patients with TNBC, we unveiled an association between intrapatient mast cell heterogeneity and clinical benefit of PD-1 blockade. Upon independent parallel validation in 484 patients with TNBC, high levels of breast tissue antigen-presenting mast cells (apMCs) were associated with enhanced anti-PD-1 efficacy. Mechanistically, apMCs largely located within tertiary lymphoid structures and were efficient in performing presentation and cross-presentation of antigens and expressed co-stimulatory molecules. Conditional deletion of antigen-presenting machinery in mast cells dampened tumor-reactive T cells. A widely prescribed allergy medication, cromolyn, was identified to mobilize apMC-mediated T cell immunity and sensitize tumors to PD-1 blockade. We subsequently initiated a phase 2 clinical trial in female patients with anti-PD-1-refractory metastatic TNBC. Here we report the results of the cromolyn arm (cromolyn plus anti-PD-1 backbone). The prespecified primary endpoint of this arm was met, with a confirmed objective response rate of 50.0%. Our study defines a crucial role of mast cells in cancer immune control, identifies an apMC-directed approach to overcome anti-PD-1 resistance and highlights a reverse-translational framework that offers conceptual advances in precision immuno-oncology with direct implications for clinical therapy. ClinicalTrials.gov identifier: NCT05076682.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"16 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144479120","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":"An international treaty to regulate misuse of alcohol and cannabis","authors":"Cyprian M. Mostert, Agustin Ibanez, Zul Merali, Florence Jaguga, Chinedu Udeh-Momoh","doi":"10.1038/s41591-025-03764-x","DOIUrl":"https://doi.org/10.1038/s41591-025-03764-x","url":null,"abstract":"As alcohol and cannabis consumption rise around the world, we call for a global treaty to regulate misuse, inspired by the WHO Tobacco Control Framework.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"88 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144371111","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":"Training physician-scientists, a view from inside","authors":"Cynthia Y. Tang, Alex D. Waldman, Lawrence F. Brass","doi":"10.1038/s41591-025-03786-5","DOIUrl":"https://doi.org/10.1038/s41591-025-03786-5","url":null,"abstract":"<p>Physician-scientists are essential for translating research into clinical practice, yet recent US policy changes, combined with a protracted training path, threaten the stability of the current workforce and the ability to train their successors. As physician-scientist trainees (C.Y.T. and A.D.W.) and a director of physician-scientist training (L.F.B.), we have seen the US investment in biomedical research rapidly shift from a shared public value to a source of division. Cuts to research funding risk stalling breakthrough discoveries, and the suspension of pipeline training programs raises barriers to entry^1,2,3,4. In less than 6 weeks, over US$1.8 billion of National Institutes of Health (NIH) grant funding was terminated, and 20% of these grants were for training, fellowship, and career development awards⁵. Without urgent intervention, these abrupt policy shifts will compromise medical advances, drive away talented individuals, and move medical discoveries, new drug identification, and therapeutic advances overseas. Here, we examine barriers across the training continuum, concluding with a call to action.</p><p>Historically, federal funding supported crucial entry points for prospective physician-scientists. Competitive programs such as the NIH Summer Internship Program and the National Science Foundation (NSF) Research Experiences for Undergraduates offered early research exposure and mentorship. Suspending these programs disproportionately affects those who rely on structured pathways to enter physician-scientist training, weakening efforts to cultivate a biomedical workforce with diverse perspectives.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"16 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144371114","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":"AI-based large-scale screening of gastric cancer from noncontrast CT imaging","authors":"Can Hu, Yingda Xia, Zhilin Zheng, Mengxuan Cao, Guoliang Zheng, Shangqi Chen, Jiancheng Sun, Wujie Chen, Qi Zheng, Siwei Pan, Yanqiang Zhang, Jiahui Chen, Pengfei Yu, Jingli Xu, Jianwei Xu, Zhongwei Qiu, Tiancheng Lin, Boxiang Yun, Jiawen Yao, Wenchao Guo, Chen Gao, Xianghui Kong, Keda Chen, Zhengle Wen, Guanxia Zhu, Jinfang Qiao, Yibo Pan, Huan Li, Xijun Gong, Zaisheng Ye, Weiqun Ao, Lei Zhang, Xing Yan, Yahan Tong, Xinxin Yang, Xiaozhong Zheng, Shufeng Fan, Jielu Cao, Cheng Yan, Kangjie Xie, Shengjie Zhang, Yao Wang, Lin Zheng, Yingjie Wu, Zufeng Ge, Xiyuan Tian, Xin Zhang, Yan Wang, Ruolan Zhang, Yizhou Wei, Weiwei Zhu, Jianfeng Zhang, Hanjun Qiu, Miaoguang Su, Lei Shi, Zhiyuan Xu, Ling Zhang, Xiangdong Cheng","doi":"10.1038/s41591-025-03785-6","DOIUrl":"https://doi.org/10.1038/s41591-025-03785-6","url":null,"abstract":"<p>Early detection through screening is critical for reducing gastric cancer (GC) mortality. However, in most high-prevalence regions, large-scale screening remains challenging due to limited resources, low compliance and suboptimal detection rate of upper endoscopic screening. Therefore, there is an urgent need for more efficient screening protocols. Noncontrast computed tomography (CT), routinely performed for clinical purposes, presents a promising avenue for large-scale designed or opportunistic screening. Here we developed the Gastric Cancer Risk Assessment Procedure with Artificial Intelligence (GRAPE), leveraging noncontrast CT and deep learning to identify GC. Our study comprised three phases. First, we developed GRAPE using a cohort from 2 centers in China (3,470 GC and 3,250 non-GC cases) and validated its performance on an internal validation set (1,298 cases, area under curve = 0.970) and an independent external cohort from 16 centers (18,160 cases, area under curve = 0.927). Subgroup analysis showed that the detection rate of GRAPE increased with advancing T stage but was independent of tumor location. Next, we compared the interpretations of GRAPE with those of radiologists and assessed its potential in assisting diagnostic interpretation. Reader studies demonstrated that GRAPE significantly outperformed radiologists, improving sensitivity by 21.8% and specificity by 14.0%, particularly in early-stage GC. Finally, we evaluated GRAPE in real-world opportunistic screening using 78,593 consecutive noncontrast CT scans from a comprehensive cancer center and 2 independent regional hospitals. GRAPE identified persons at high risk with GC detection rates of 24.5% and 17.7% in 2 regional hospitals, with 23.2% and 26.8% of detected cases in T1/T2 stage. Additionally, GRAPE detected GC cases that radiologists had initially missed, enabling earlier diagnosis of GC during follow-up for other diseases. In conclusion, GRAPE demonstrates strong potential for large-scale GC screening, offering a feasible and effective approach for early detection. ClinicalTrials.gov registration: NCT06614179.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"639 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144371113","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}