Nature Biomedical Engineering最新文献

{"title":"Publisher Correction: Ultra-high gradient connectomics and microstructure MRI scanner for imaging of human brain circuits across scales","authors":"Gabriel Ramos-Llordén, Hong-Hsi Lee, Mathias Davids, Peter Dietz, Andreas Krug, John E. Kirsch, Mirsad Mahmutovic, Alina Müller, Yixin Ma, Hansol Lee, Chiara Maffei, Anastasia Yendiki, Berkin Bilgic, Daniel J. Park, Qiyuan Tian, Bryan Clifford, Wei-Ching Lo, Stefan Stocker, Jasmine Fischer, Gudrun Ruyters, Manuela Roesler, Andreas Potthast, Thomas Benner, Elmar Rummert, Rebecca Schuster, Peter J. Basser, Thomas Witzel, Lawrence L. Wald, Bruce R. Rosen, Boris Keil, Susie Y. Huang","doi":"10.1038/s41551-025-01484-8","DOIUrl":"https://doi.org/10.1038/s41551-025-01484-8","url":null,"abstract":"<p>Correction to: <i>Nature Biomedical Engineering</i> https://doi.org/10.1038/s41551-025-01457-x, published online 16 July 2025.</p>","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"45 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144677869","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 live, programmable microbiota therapeutic disables virulence in gut pathogens","authors":"","doi":"10.1038/s41551-025-01452-2","DOIUrl":"https://doi.org/10.1038/s41551-025-01452-2","url":null,"abstract":"Treatment of severe gastrointestinal illness caused by Shiga-toxin-producing enteropathogenic bacteria is a growing challenge owing to increasing antimicrobial resistance. We engineered a conjugative CRISPR-associated transposase to insert a genetic payload that inactivates the Shiga toxin gene of Enterobacteriaceae pathogens in the gut, establishing a foundation for microbial gene therapy.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"37 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144669890","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":"Precise virulence inactivation using a CRISPR-associated transposase for combating Enterobacteriaceae gut pathogens","authors":"Carlotta Ronda, Tyler Perdue, Logan Schwanz, Diego Rivera Gelsinger, Leonie Brockmann, Andrew Kaufman, Yiming Huang, Samuel H. Sternberg, Harris H. Wang","doi":"10.1038/s41551-025-01453-1","DOIUrl":"https://doi.org/10.1038/s41551-025-01453-1","url":null,"abstract":"<p>Targeted gene manipulation in a complex microbial community is an enabling technology for precise microbiome editing. Here we introduce BACTRINS, an in situ microbiome engineering platform designed for efficient and precise genomic insertion of a desired payload and simultaneous knockout of target genes. This system leverages conjugation-mediated delivery of CRISPR-associated transposases to achieve RNA-guided genomic integration, allowing precise insertion of a therapeutic payload while neutralizing pathogen virulence without causing cell death. When applied against an Enterobacteriaceae Shiga toxin-producing pathogen in the gut, this system delivers a CRISPR-associated transposase by bacterial conjugation for site-specific inactivation of the Shiga toxin gene and integration of a nanobody therapeutic payload to disrupt pathogen attachment. A single dose of this therapy results in high-efficiency Shiga gene inactivation and improved survival in a murine infection model of Shiga-producing pathogen. This work establishes a new type of live bacterial therapeutic capable of reducing gut infections by transforming toxigenic pathogens into commensal protectors.</p>","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"6 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144652100","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":"Autonomous devices for drug delivery","authors":"Abdulkadir Sanli,&nbsp;Tinghao Hu,&nbsp;Leyang Li,&nbsp;Firat Güder","doi":"10.1038/s41551-025-01473-x","DOIUrl":"10.1038/s41551-025-01473-x","url":null,"abstract":"Advances in implantable and ingestible devices are transforming delivery of drugs for emergencies and chronic care, a giant step towards personalized, precision medicine.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"9 8","pages":"1182-1183"},"PeriodicalIF":26.8,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144652096","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 pattern-learning algorithm associates copy number variations with brain structure and behavioural variables in an adolescent population cohort","authors":"Jakub Kopal, Guillaume Huguet, Justin Marotta, Shambhavi Aggarwal, Nicole Osayande, Kuldeep Kumar, Zohra Saci, Martineau Jean-Louis, Xiaoqian J. Chai, Tian Ge, B. T. Thomas Yeo, Paul M. Thompson, Carrie E. Bearden, Ole A. Andreassen, Sébastien Jacquemont, Danilo Bzdok","doi":"10.1038/s41551-025-01454-0","DOIUrl":"https://doi.org/10.1038/s41551-025-01454-0","url":null,"abstract":"<p>Our genetic makeup, together with environmental and social influences, shape our brain’s development. Yet, the imaging-genetics field has struggled to integrate all these modalities to investigate the interplay between genetic blueprint, brain architecture, environment, human health and daily living skills. Here we interrogate the Adolescent Brain Cognitive Development (ABCD) cohort to outline the effects of rare high-effect genetic variants on brain architecture and their corresponding implications on cognitive, behavioural, psychosocial and socioeconomic traits. We design a holistic pattern-learning framework that quantitatively dissects the impacts of copy number variations (CNVs) on brain structure and 938 behavioural variables spanning 20 categories in 7,338 adolescents. Our results reveal associations between genetic alterations, higher-order brain networks and specific parameters of the family wellbeing, including increased parental and child stress, anxiety and depression, or neighbourhood dynamics such as decreased safety. We thus find effects extending beyond the impairment of cognitive ability or language capacity which have been previously reported. Our investigation spotlights the interplay between genetic variation and subjective life quality in adolescents and their families.</p>","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"109 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144652099","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":"Sensitization of tumours to immunotherapy by boosting early type-I interferon responses enables epitope spreading","authors":"Sadeem Qdaisat,&nbsp;Brandon Wummer,&nbsp;Brian D. Stover,&nbsp;Dingpeng Zhang,&nbsp;James McGuiness,&nbsp;Frances Weidert,&nbsp;Jonathan Chardon-Robles,&nbsp;Adam Grippin,&nbsp;Anna DeVries,&nbsp;Chong Zhao,&nbsp;Christiano Marconi,&nbsp;Aida Karachi,&nbsp;Chao Xie,&nbsp;Gabriel Jobin,&nbsp;Ruixuan Liu,&nbsp;Stephen Michel,&nbsp;Xiaojie Ma,&nbsp;Rachel S. F. Moor,&nbsp;Christina von Roemeling,&nbsp;Duy T. Nguyen,&nbsp;Leighton Elliott,&nbsp;Nagheme Thomas,&nbsp;Arnav Barpujari,&nbsp;Hilary Geffrard,&nbsp;Yodarlynis Campaneria,&nbsp;Elizabeth Ogando-Rivas,&nbsp;Cathleen Rabideau,&nbsp;Dhruvkumar Soni,&nbsp;Jianping Huang,&nbsp;Sheila Carrera-Justiz,&nbsp;Kristianna Fredenburg,&nbsp;Natalie L. Silver,&nbsp;W. Gregory Sawyer,&nbsp;Maryam Rahman,&nbsp;John A. Ligon,&nbsp;Catherine T. Flores,&nbsp;Ji-Hyun Lee,&nbsp;Duane A. Mitchell,&nbsp;Paul Castillo,&nbsp;Hector R. Mendez-Gomez,&nbsp;Elias J. Sayour","doi":"10.1038/s41551-025-01380-1","DOIUrl":"10.1038/s41551-025-01380-1","url":null,"abstract":"The success of cancer immunotherapies is predicated on the targeting of highly expressed neoepitopes, which preferentially favours malignancies with high mutational burden. Here we show that early responses by type-I interferons mediate the success of immune checkpoint inhibitors as well as epitope spreading in poorly immunogenic tumours and that these interferon responses can be enhanced via systemic administration of lipid particles loaded with RNA coding for tumour-unspecific antigens. In mice, the immune responses of tumours sensitive to checkpoint inhibitors were transferable to resistant tumours and resulted in heightened immunity with antigenic spreading that protected the animals from tumour rechallenge. Our findings show that the resistance of tumours to immunotherapy is dictated by the absence of a damage response, which can be restored by boosting early type-I interferon responses to enable epitope spreading and self-amplifying responses in treatment-refractory tumours. Lipid particles loaded with RNA coding for tumour-unspecific antigens can enhance early responses of type-I interferons, mediating the success of immune checkpoint inhibitors as well as epitope spreading.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"9 9","pages":"1437-1452"},"PeriodicalIF":26.8,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144652098","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":"Mannich reaction-based combinatorial libraries identify antioxidant ionizable lipids for mRNA delivery with reduced immunogenicity","authors":"Ningqiang Gong, Dongyoon Kim, Mohamad-Gabriel Alameh, Rakan El-Mayta, Emily L. Han, Garima Dwivedi, Rohan Palanki, Qiangqiang Shi, Xuexiang Han, Lulu Xue, Junchao Xu, Zilin Meng, Tianyu Luo, Christian G. Figueroa-Espada, Drew Weissman, Jinghong Li, Michael J. Mitchell","doi":"10.1038/s41551-025-01422-8","DOIUrl":"https://doi.org/10.1038/s41551-025-01422-8","url":null,"abstract":"<p>The immunogenicity of lipid nanoparticles (LNPs) used for the delivery of nucleoside-modified messenger RNA limits the levels and durability of expression of the encoded protein. Here, by leveraging the Mannich reaction for ionizable lipid synthesis, and via the in vitro and in vivo screening of six combinatorial libraries of synthesized lipids, we report the identification of an antioxidant ionizable lipid, C-a16, exhibiting reduced immunogenicity. When incorporated into LNPs for mRNA delivery, C-a16 mitigated the generation of intracellular reactive oxygen species, thereby extending the duration of protein expression. In mice, and compared with commercial LNPs, LNPs incorporating C-a16 and co-delivering Cas9 mRNA and guide RNA for the editing of the transthyretin gene led to 2.8-fold higher editing efficiency; LNPs with C-a16 delivering fibroblast growth factor 21 mRNA increased the expression of the protein 3.6-fold; and when delivering mRNA encoding a tumour neoantigen or the spike protein of SARS-CoV-2, LNPs with C-a16 induced stronger antigen-specific immune responses. Our findings support the further testing of C-a16 as a promising ionizable lipid for mRNA delivery in therapeutic applications.</p>","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"24 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144652101","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":"Artificial intelligence advances skull stripping across lifespan","authors":"Ping Wang,&nbsp;Yin-Shan Wang,&nbsp;Xi-Nian Zuo","doi":"10.1038/s41551-025-01458-w","DOIUrl":"10.1038/s41551-025-01458-w","url":null,"abstract":"A skull-stripping artificial intelligence model leveraging personalized prior knowledge from brain atlases generates consistent brain extraction across diverse age groups, scanners and protocols.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"9 8","pages":"1180-1181"},"PeriodicalIF":26.8,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144652097","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":"Isogenic induced-pluripotent-stem-cell-derived airway- and alveolus-on-chip models reveal specific innate immune responses","authors":"Sachin Yadav, Kazuya Fujimoto, Toru Takenaga, Senye Takahashi, Yukiko Muramoto, Ryuta Mikawa, Takeshi Noda, Shimpei Gotoh, Ryuji Yokokawa","doi":"10.1038/s41551-025-01444-2","DOIUrl":"https://doi.org/10.1038/s41551-025-01444-2","url":null,"abstract":"<p>The development of microphysiological systems for preclinical research is often hindered by the limited availability of reliable cell sources, especially when multiple organs or tissues from a single patient are needed for comparative studies of the host innate immune response. In this study, we develop human airway-on-chip and alveolus-on-chip models using lung progenitor cells derived from isogenic induced pluripotent stem cells. Our results using SARS-CoV-2 and influenza reveal distinct initial innate immune responses in the airway- and alveolus-on-chip models. SARS-CoV-2-infected airway chips show a robust early interferon-dependent innate immune response, while alveolus chips show dysregulated and delayed interferon activation alongside a significantly upregulated chemokine pathway. In contrast, influenza infection induces a more pronounced innate immune response and greater cellular damage in both chips compared with SARS-CoV-2. Consequently, airway- and alveolus-on-chip models derived from induced pluripotent stem cells offer a viral pathology platform with screening potential for future therapeutic agents.</p>","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"56 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144639728","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":"Nanobody-based bispecific antibody engagers targeting CTLA-4 or PD-L1 for cancer immunotherapy","authors":"Xin Liu, Camille Le Gall, Ryan K. Alexander, Ella Borgman, Thomas Balligand, Hidde L. Ploegh","doi":"10.1038/s41551-025-01447-z","DOIUrl":"https://doi.org/10.1038/s41551-025-01447-z","url":null,"abstract":"<p>As immune checkpoint blockade induces durable responses in only a subset of patients, more effective immunotherapies are needed. Here we present bispecific antibody engagers, fusion proteins composed of a nanobody that recognizes immunoglobulin kappa light chains (VHH_kappa) and a nanobody that recognizes either CTLA-4 or PD-L1. These fusions show strong antitumour activity in mice through recruitment of polyclonal immunoglobulins independently of specificity or isotype. The anti-CTLA-4 VHH-VHH_kappa conjugate demonstrates superior antitumour activity compared with the conventional monoclonal anti-CTLA-4 antibody and reduces the number of intratumoural regulatory T cells in a mouse model of colorectal carcinoma. The anti-PD-L1 VHH-VHH_kappa conjugate is less effective in the colorectal carcinoma model while still outperforming a conventional antibody of similar specificity. The potency of the anti-PD-L1 VHH-VHH_kappa conjugate was enhanced by installation of the cytotoxic drug maytansine or a STING agonist. The ability of such fusions to engage the Fc-mediated functions of all immunoglobulin isotypes is an appealing strategy to further improve on the efficacy of immune checkpoint blockade, commonly delivered as a monoclonal immunoglobulin of a single defined isotype.</p>","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"10 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144639818","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}