Timon Merk,Richard M Köhler,Toni M Brotons,Samed Rouven Vossberg,Victoria Peterson,Laura Freire Lyra,Jojo Vanhoecke,Meera Chikermane,Thomas S Binns,Ningfei Li,Ashley Walton,Clemens Neudorfer,Alan Bush,Nathan Sisterson,Johannes Busch,Roxanne Lofredi,Jeroen Habets,Julius Huebl,Guanyu Zhu,Zixiao Yin,Baotian Zhao,Angela Merkl,Malek Bajbouj,Patricia Krause,Katharina Faust,Gerd-Helge Schneider,Andreas Horn,Jianguo Zhang,Andrea A Kühn,R Mark Richardson,Wolf-Julian Neumann
{"title":"Invasive neurophysiology and whole brain connectomics for neural decoding in patients with brain implants.","authors":"Timon Merk,Richard M Köhler,Toni M Brotons,Samed Rouven Vossberg,Victoria Peterson,Laura Freire Lyra,Jojo Vanhoecke,Meera Chikermane,Thomas S Binns,Ningfei Li,Ashley Walton,Clemens Neudorfer,Alan Bush,Nathan Sisterson,Johannes Busch,Roxanne Lofredi,Jeroen Habets,Julius Huebl,Guanyu Zhu,Zixiao Yin,Baotian Zhao,Angela Merkl,Malek Bajbouj,Patricia Krause,Katharina Faust,Gerd-Helge Schneider,Andreas Horn,Jianguo Zhang,Andrea A Kühn,R Mark Richardson,Wolf-Julian Neumann","doi":"10.1038/s41551-025-01467-9","DOIUrl":"https://doi.org/10.1038/s41551-025-01467-9","url":null,"abstract":"Brain-computer interface research can inspire closed-loop neuromodulation therapies, promising spatiotemporal precision for the treatment of brain disorders. Decoding dynamic patient states from brain signals with machine learning is required to leverage this precision, but a standardized framework for invasive brain signal decoding from neural implants does not exist. Here we develop a platform that integrates brain signal decoding with magnetic resonance imaging connectomics and demonstrate its use across 123 h of invasively recorded brain data from 73 neurosurgical patients treated with brain implants for movement disorders, depression and epilepsy. We introduce connectomics-informed movement decoders that generalize across cohorts with Parkinson's disease and epilepsy from the United States, Europe and China. We reveal network targets for emotion decoding in left prefrontal and cingulate circuits in deep brain stimulation patients with major depression. Finally, we showcase opportunities to improve seizure detection in responsive neurostimulation for epilepsy. Our study highlights the clinical use of brain signal decoding for deep brain stimulation and provides methods that allow for rapid, high-accuracy decoding for precision medicine approaches that can dynamically adapt neurotherapies in response to the individual needs of patients.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"2 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145133941","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 artificial cilia-based array system for sound frequency decoding and resonance-responsive drug release.","authors":"Xinwei Wei,Hanlin Wang,Yanfang Wang,Wentao Zhang,Changming Chen,Kaihui Li,Licheng Han,Joseph Rufo,Jianchang Xu,Yuejun Yao,Yingqi Huang,Tianyu Zhang,Xiangsheng Liu,Jianqing Gao,Ping Wang,Chao Xu,Tony Jun Huang,Jinqiang Wang,Zhen Gu","doi":"10.1038/s41551-025-01505-6","DOIUrl":"https://doi.org/10.1038/s41551-025-01505-6","url":null,"abstract":"Hair cells in the human ear contain cilia of varying lengths that sense varied acoustic signals. Here, inspired by this, we report an artificial cilia-based sound-decoding device capable of directly recognizing and responding to sound frequencies without relying on electricity and algorithms. We create 3D-printed micrometre-sized (40-200 μm) artificial cilia-based arrays with varying length-to-diameter ratios (30-100) that can sense and decode sound frequency signals (100-6,000 Hz), including piano music and human voices, on the basis of acoustic resonance. The artificial cilia can also vibrate accordingly in water to initiate subsequent tasks such as controlling drug release profiles of two distinct therapeutics (insulin and glucagon) in an acoustic-frequency-responsive manner to treat type 1 diabetic mice. This cochlear cilia-inspired device holds potential for broad applications such as recognizing complicated physiological sounds and performing various tasks in personalized voice interactions.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"53 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145133940","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}
Rachel Ringquist,Eshant Bhatia,Paramita Chatterjee,Drishti Maniar,Zhou Fang,Page Franz,Liana Kramer,Delta Ghoshal,Neha Sonthi,Emma Downey,Joshua Canlas,Abigail Ochal,Savi Agarwal,Valeria Cuéllar,Grace Harrigan,Ahmet F Coskun,Ankur Singh,Krishnendu Roy
{"title":"An immune-competent lung-on-a-chip for modelling the human severe influenza infection response.","authors":"Rachel Ringquist,Eshant Bhatia,Paramita Chatterjee,Drishti Maniar,Zhou Fang,Page Franz,Liana Kramer,Delta Ghoshal,Neha Sonthi,Emma Downey,Joshua Canlas,Abigail Ochal,Savi Agarwal,Valeria Cuéllar,Grace Harrigan,Ahmet F Coskun,Ankur Singh,Krishnendu Roy","doi":"10.1038/s41551-025-01491-9","DOIUrl":"https://doi.org/10.1038/s41551-025-01491-9","url":null,"abstract":"Severe influenza affects 3-5 million people worldwide each year, resulting in more than 300,000 deaths annually. However, standard-of-care antiviral therapeutics have limited effectiveness in these patients. Current preclinical models of severe influenza fail to accurately recapitulate the human immune response to severe viral infection. Here we develop an immune-competent, microvascularized, human lung-on-a-chip device to model the small airways, successfully demonstrating the cytokine storm, immune cell activation, epithelial cell damage, and other cellular- and tissue-level human immune responses to severe H1N1 infection. We find that interleukin-1β and tumour necrosis factor-α play opposing roles in the initiation and regulation of the cytokine storm associated with severe influenza. Furthermore, we discover the critical stromal-immune CXCL12-CXCR4 interaction and its role in immune response to infection. Our results underscore the importance of stromal cells and immune cells in microphysiological models of severe lung disease, describing a scalable model for severe influenza research. We expect the immune-competent human lung-on-a-chip device to enable critical discoveries in respiratory host-pathogen interactions, therapeutic side effects, vaccine potency evaluation, and crosstalk between systemic and mucosal immunity in human lung.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"19 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145127082","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 collaborative large language model for drug analysis.","authors":"Hongjian Zhou,Fenglin Liu,Jinge Wu,Wenjun Zhang,Guowei Huang,Lei Clifton,David Eyre,Haochen Luo,Fengyuan Liu,Kim Branson,Patrick Schwab,Xian Wu,Yefeng Zheng,Anshul Thakur,David A Clifton","doi":"10.1038/s41551-025-01471-z","DOIUrl":"https://doi.org/10.1038/s41551-025-01471-z","url":null,"abstract":"Large language models (LLMs), such as ChatGPT, have substantially helped in understanding human inquiries and generating textual content with human-level fluency. However, directly using LLMs in healthcare applications faces several problems. LLMs are prone to produce hallucinations, or fluent content that appears reasonable and genuine but that is factually incorrect. Ideally, the source of the generated content should be easily traced for clinicians to evaluate. We propose a knowledge-grounded collaborative large language model, DrugGPT, to make accurate, evidence-based and faithful recommendations that can be used for clinical decisions. DrugGPT incorporates diverse clinical-standard knowledge bases and introduces a collaborative mechanism that adaptively analyses inquiries, captures relevant knowledge sources and aligns these inquiries and knowledge sources when dealing with different drugs. We evaluate the proposed DrugGPT on drug recommendation, dosage recommendation, identification of adverse reactions, identification of potential drug-drug interactions and answering general pharmacology questions. DrugGPT outperforms a wide range of existing LLMs and achieves state-of-the-art performance across all metrics with fewer parameters than generic LLMs.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"7 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145127078","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":"Intranasal vaccine combining adenovirus and trimeric subunit protein provides superior immunity against SARS-CoV-2 Omicron variant.","authors":"Weiqi Hong,Ping Cheng,Jingyun Yang,Huashan Shi,Zhenling Wang,Jiong Li,Hong Lei,Dandan Peng,Cai He,Wenyan Ren,Xiangyu Pan,Yuhe Huang,Aqu Alu,Furong Qin,Binhan Wang,Yanan Zhou,Yun Yang,Wenhai Yu,Cong Tang,Qing Huang,Mengli Yang,Bai Li,Jingmei Li,Junbin Wang,Jiayuan Ai,Li Chen,Haiying Que,Zhen Zeng,Jian Liu,Ying Hao,Danyi Ao,Yu Zhang,Xiya Huang,Chunjun Ye,MinYang Fu,Xuemei He,Zhenfei Bi,Xuejiao Han,Min Luo,Hongbo Hu,Wei Cheng,Haohao Dong,Jian Lei,Lu Chen,Xikun Zhou,Wei Wang,Guobo Shen,Jinliang Yang,Xiangrong Song,Yuquan Wei,Shuaiyao Lu,Qiangming Sun,Guangwen Lu,Youchun Wang,Li Yang,Weimin Li,Xiawei Wei","doi":"10.1038/s41551-025-01517-2","DOIUrl":"https://doi.org/10.1038/s41551-025-01517-2","url":null,"abstract":"Mucosal immunity provides efficient protection against upper-airway infections, limiting viral shedding and transmission. However, currently, no nasal spray COVID-19 vaccines are approved by WHO for global use. Here we develop a two-component intranasal vaccine that combines an adenovirus vector expressing the spike protein of the XBB.1.5 variant (Ad5XBB.1.5) with a self-assembled trimeric recombinant protein derived from the receptor binding domain (RBDXBB.1.5-HR). This two-component vaccine elicits superior humoral and cellular immunity against XBB.1.5 variants compared with the individual components. It also provides protective immunity against live XBB.1.16 virus challenges in mice, and prevents XBB.1.5 virus transmission in a hamster model. Notably, the activation of the STING signalling pathway in mucosal dendritic cells is essential for the adjuvant effect of the adenovirus vector. We also incorporate another trimeric protein from the BA.5 variant (RBDBA.5-HR), creating a three-component vaccine (Ad5XBB.1.5 + RBDXBB.1.5-HR + RBDBA.5-HR) that shows enhanced broad-spectrum neutralization. The two-component vaccine demonstrates high tolerability and safety in humans, inducing enhanced mucosal immunity and high levels of neutralizing antibodies in all participants. Our findings underscore this strategy for clinical COVID-19 intranasal vaccine development.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"61 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145117058","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}
Sameed M Siddiqui,Nicole L Welch,Tien G Nguyen,Amaya Razmi,Tianyi Chang,Rebecca Senft,Jon Arizti-Sanz,Marzieh E Mirhashemi,David R Stirling,Cheri M Ackerman,Beth A Cimini,Paul C Blainey,Pardis C Sabeti,Cameron Myhrvold
{"title":"Bead-based approaches for increased sensitivity and multiplexing of CRISPR diagnostics.","authors":"Sameed M Siddiqui,Nicole L Welch,Tien G Nguyen,Amaya Razmi,Tianyi Chang,Rebecca Senft,Jon Arizti-Sanz,Marzieh E Mirhashemi,David R Stirling,Cheri M Ackerman,Beth A Cimini,Paul C Blainey,Pardis C Sabeti,Cameron Myhrvold","doi":"10.1038/s41551-025-01498-2","DOIUrl":"https://doi.org/10.1038/s41551-025-01498-2","url":null,"abstract":"CRISPR-based diagnostics have emerged as a promising tool for fast, accurate and portable pathogen detection. There has been rapid progress in pre-amplification processes and CRISPR-related enzymes used in these approaches, but the development of reporter systems and reaction platforms has lagged behind. In this paper, we develop bead-based techniques to address these gaps. First, we develop a novel bead-based split-luciferase reporter system with up to 20× sensitivity compared with standard fluorescence-based reporter design in CRISPR diagnostics. Second, we develop a highly deployable, bead-based platform capable of detecting nine distinct viral targets in parallelized, droplet-based reactions, with sensitivity reaching as low as 2.5 copies per µl of input RNA. We demonstrate the enhanced performance of both approaches on synthetic and clinical sample sensitivity, speed, multiplexing and deployability.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"11 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145117060","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}
Sharan Janjuha,Tatjana Haenggi,Thomas C Chamberlain,Tanja Rothgangl,Lucas Kissling,Maria Wilhelm,Nicolas Mathis,Desiree Boeck,Kim Marquart,Eleonora Ioannidi,Woohyun J Moon,Hiromi Muramatsu,Máté Vadovics,Norbert Pardi,Sean C Semple,Ying K Tam,Gerald Schwank
{"title":"Spatial profiling of gene editing by in situ sequencing in mice and macaques.","authors":"Sharan Janjuha,Tatjana Haenggi,Thomas C Chamberlain,Tanja Rothgangl,Lucas Kissling,Maria Wilhelm,Nicolas Mathis,Desiree Boeck,Kim Marquart,Eleonora Ioannidi,Woohyun J Moon,Hiromi Muramatsu,Máté Vadovics,Norbert Pardi,Sean C Semple,Ying K Tam,Gerald Schwank","doi":"10.1038/s41551-025-01512-7","DOIUrl":"https://doi.org/10.1038/s41551-025-01512-7","url":null,"abstract":"Base and prime editing technologies precisely install defined nucleotide edits in both dividing and non-dividing cells, offering potential for correcting pathogenic mutations directly in organisms. However, to fully leverage their therapeutic potential, accurately measuring editing rates with high spatial resolution is crucial. Here we use imaging-based in situ sequencing (ISS) to map base and prime editing events within native tissues. We establish and validate this technology in mouse brains treated with intein-split adenine base editors or prime editors delivered via adeno-associated viral vectors. We next apply ISS in the liver of mice and macaques treated with adenine base editors encoded on lipid nanoparticle-encapsulated mRNA and guide RNA (RNA-LNP). Effective editing was observed across all metabolic zones of liver lobules. Moreover, in experiments where repeated doses of RNA-LNP are administered, the initial dose does not affect the editing efficiency and distribution of the subsequent dose. Our results demonstrate how ISS can visualize gene editing events in vivo and suggest that base editor delivery using RNA-LNP could be used to address a wide spectrum of metabolic liver diseases.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"4 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145089749","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 warm introduction","authors":"","doi":"10.1038/s41551-025-01526-1","DOIUrl":"10.1038/s41551-025-01526-1","url":null,"abstract":"We introduce the Nature Biomedical Engineering editorial team, including our new Chief Editor, and consider what is to come as we move into our tenth year of publishing.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"9 9","pages":"1385-1385"},"PeriodicalIF":26.8,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41551-025-01526-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145086514","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}
Luke P. Lee, Hiroyuki Fujita, Hidetoshi Kotera, Thomas B. Jones
{"title":"Masao Washizu (1953–2025)","authors":"Luke P. Lee, Hiroyuki Fujita, Hidetoshi Kotera, Thomas B. Jones","doi":"10.1038/s41551-025-01485-7","DOIUrl":"10.1038/s41551-025-01485-7","url":null,"abstract":"Engineer and scientist who contributed to the manipulation of single DNA molecules using electric fields, single-cell fusion and innovative integrated electronic microfluidics.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"9 9","pages":"1390-1390"},"PeriodicalIF":26.8,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145086478","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}
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