Nature Biomedical Engineering最新文献

{"title":"Biomimetic model to study penile dysfunctions","authors":"Isabelle Martinier, Laetitia de Kort, Petra de Graaf","doi":"10.1038/s41551-025-01434-4","DOIUrl":"https://doi.org/10.1038/s41551-025-01434-4","url":null,"abstract":"A multi-layered penis model can be 3D printed with a complex vessel architecture for the study of penile physiology and for restoring erectile functions in vivo.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"35 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144304456","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 robust and scalable framework for hallucination detection in virtual tissue staining and digital pathology","authors":"Luzhe Huang, Yuzhu Li, Nir Pillar, Tal Keidar Haran, William Dean Wallace, Aydogan Ozcan","doi":"10.1038/s41551-025-01421-9","DOIUrl":"https://doi.org/10.1038/s41551-025-01421-9","url":null,"abstract":"<p>Histopathological staining of human tissue is essential for disease diagnosis. Recent advances in virtual tissue staining technologies using artificial intelligence alleviate some of the costly and tedious steps involved in traditional histochemical staining processes, permitting multiplexed staining and tissue preservation. However, potential hallucinations and artefacts in these virtually stained tissue images pose concerns, especially for the clinical uses of these approaches. Quality assessment of histology images by experts can be subjective. Here we present an autonomous quality and hallucination assessment method, AQuA, for virtual tissue staining and digital pathology. AQuA autonomously achieves 99.8% accuracy when detecting acceptable and unacceptable virtually stained tissue images without access to histochemically stained ground truth and presents an agreement of 98.5% with the manual assessments made by board-certified pathologists, including identifying realistic-looking images that could mislead diagnosticians. We demonstrate the wide adaptability of AQuA across various virtually and histochemically stained human tissue images. This framework enhances the reliability of virtual tissue staining and provides autonomous quality assurance for image generation and transformation tasks in digital pathology and computational imaging.</p>","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"21 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144296149","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":"PET-based tracking of CAR T cells and viral gene transfer using a cell surface reporter that binds to lanthanide complexes","authors":"Volker Morath, Katja Fritschle, Linda Warmuth, Markus Anneser, Sarah Dötsch, Milica Živanić, Luisa Krumwiede, Philipp Bösl, Tarik Bozoglu, Stephanie Robu, Silvana Libertini, Susanne Kossatz, Christian Kupatt, Markus Schwaiger, Katja Steiger, Dirk H. Busch, Arne Skerra, Wolfgang A. Weber","doi":"10.1038/s41551-025-01415-7","DOIUrl":"https://doi.org/10.1038/s41551-025-01415-7","url":null,"abstract":"<p>The clinical translation of cell- and gene-based therapies is limited by the lack of non-invasive, quantitative and specific whole-body imaging tools. Here we present a positron emission tomography reporter system based on a membrane-anchored anticalin protein that binds a fluorine-18-labelled lanthanide complex with picomolar affinity via a bio-orthogonal interaction. The reporter was introduced into therapeutic cells, including CAR T cells and adeno-associated virus-transduced cells. In vitro, reporter expression conferred &gt;800-fold higher radioligand binding versus controls. In mice, the radioligand demonstrated rapid renal clearance, showed no off-target accumulation and enabled high-contrast detection of as few as 1,200 CAR T cells in the bone marrow. Longitudinal positron emission tomography imaging over 4 weeks revealed precise tracking of CAR T cell expansion and migration, with signal intensity correlating linearly with flow cytometry data. The system also enabled the quantitative imaging of in vivo gene transfer using an adeno-associated viral vector. This depth-independent whole-body imaging platform offers a powerful tool for monitoring therapeutic cell dynamics and gene delivery in preclinical and potentially clinical settings.</p>","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"553 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144278507","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":"Macrophage-augmented organoids recapitulate the complex pathophysiology of viral diseases and enable development of multitarget therapeutics","authors":"Kuan Liu, Yining Wang, Jiajing Li, Jiahua Zhou, Ana Maria Gonçalves da Silva, Clara Suñer, Zhe Dai, Rick Schraauwen, Patrick P. C. Boor, Kimberley Ober-Vliegen, Francijna van den Hil, Dewy M. Offermans, Theano Tsikari, Ibrahim Ayada, Maikel P. Peppelenbosch, Martin E. van Royen, Monique M. A. Verstegen, Yijin Wang, Chloe M. Orkin, Harry L. A. Janssen, Valeria V. Orlova, Pengfei Li, Oriol Mitjà, Amaro Nunes Duarte-Neto, Luc J. W. van der Laan, Qiuwei Pan","doi":"10.1038/s41551-025-01417-5","DOIUrl":"https://doi.org/10.1038/s41551-025-01417-5","url":null,"abstract":"<p>The pathophysiology of acute viral diseases is complex. It is characterized by strong inflammatory responses driven by immune cells, leading to tissue damage. Currently available in vitro models mainly recapitulate the viral life cycle but fail to model immune cell-mediated pathogenesis. Here we build macrophage-augmented organoids (MaugOs) by integrating macrophages into primary organoids that are cultured from human liver tissues. We test the infections of two RNA viruses, hepatitis E virus and SARS-CoV-2, and one DNA virus, monkeypox virus, which either primarily or secondarily affect the human liver. In all three models of acute viral diseases, MaugOs recapitulate infection and the resulting inflammatory response, although to different levels. We use this system to dissect the multifunctional role of human bile on hepatitis E virus replication and the inflammatory response through distinct mechanisms of action. We also show that MaugOs recapitulate features of inflammatory cell death triggered by hepatitis E virus infection when integrated with pro-inflammatory macrophages. Furthermore, we demonstrate a proof of concept in MaugOs for development of multitarget therapeutics that simultaneously target the virus, inflammatory response and the resultant inflammatory cell death.</p>","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"6 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144278510","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 pig with functional human immunity","authors":"Christopher K. Tuggle, Crystal L. Loving, Beau R. Webber","doi":"10.1038/s41551-025-01426-4","DOIUrl":"https://doi.org/10.1038/s41551-025-01426-4","url":null,"abstract":"Genetically modified immunodeficient pigs support the development of functional human B and T cells and represent a preclinical model for investigating human haematopoiesis and a bioreactor for large-scale production of human immune cells for diverse therapies.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"43 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144260479","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":"Hitchhiking albumin to STING tumours","authors":"Shuyue Ye, Jinming Gao","doi":"10.1038/s41551-025-01401-z","DOIUrl":"https://doi.org/10.1038/s41551-025-01401-z","url":null,"abstract":"A small-molecule STING agonist is conjugated to a nanobody that binds to serum albumins to increase tumour accumulation and augment antitumour immunity.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"585 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144260478","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":"Potentiating cancer immunotherapies with modular albumin-hitchhiking nanobody–STING agonist conjugates","authors":"Blaise R. Kimmel, Karan Arora, Neil C. Chada, Vijaya Bharti, Alexander J. Kwiatkowski, Jonah E. Finkelstein, Ann Hanna, Emily N. Arner, Taylor L. Sheehy, Lucinda E. Pastora, Jinming Yang, Hayden M. Pagendarm, Payton T. Stone, Ebony Hargrove-Wiley, Brandie C. Taylor, Lauren A. Hubert, Barbara M. Fingleton, Katherine N. Gibson-Corley, Jody C. May, John A. McLean, Jeffrey C. Rathmell, Ann Richmond, W. Kimryn Rathmell, Justin M. Balko, John T. Wilson","doi":"10.1038/s41551-025-01400-0","DOIUrl":"https://doi.org/10.1038/s41551-025-01400-0","url":null,"abstract":"<p>The enhancement of antitumour immunity via agonists of the stimulator of interferon genes (STING) pathway is limited by pharmacological barriers. Here we show that the covalent conjugation of a STING agonist to anti-albumin nanobodies via site-selective bioconjugation chemistries prolongs the circulation of the agonist in the blood and increases its accumulation in tumour tissue, stimulating innate immune programmes that increased the infiltration of activated natural killer cells and T cells, which potently inhibited the growth of mouse tumours. The technology is modular, as demonstrated by the recombinant integration of a second nanobody domain targeting programmed death-ligand 1 (PD-L1), which further increased the accumulation of the agonist in tumours while blocking immunosuppressive PD-1/PD-L1 interactions. The bivalent nanobody–STING agonist conjugate stimulated robust antigen-specific T-cell responses and long-lasting immunological memory and conferred enhanced therapeutic efficacy. It was also effective as a neoadjuvant treatment to adoptive T-cell therapy. As a modular approach, hitchhiking STING agonists on serum albumin may serve as a broadly applicable strategy for augmenting the potency of systemically administered cancer immunotherapies.</p>","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"8 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144260480","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":"Neuroimaging endophenotypes reveal underlying mechanisms and genetic factors contributing to progression and development of four brain disorders","authors":"Junhao Wen, Ioanna Skampardoni, Ye Ella Tian, Zhijian Yang, Yuhan Cui, Guray Erus, Gyujoon Hwang, Erdem Varol, Aleix Boquet-Pujadas, Ganesh B. Chand, Ilya M. Nasrallah, Theodore D. Satterthwaite, Haochang Shou, Li Shen, Arthur W. Toga, Andrew Zalesky, Christos Davatzikos","doi":"10.1038/s41551-025-01412-w","DOIUrl":"https://doi.org/10.1038/s41551-025-01412-w","url":null,"abstract":"<p>Recent work leveraging artificial intelligence has offered promise to dissect disease heterogeneity by identifying complex intermediate brain phenotypes, called dimensional neuroimaging endophenotypes (DNEs). We advance the argument that these DNEs capture the degree of expression of respective neuroanatomical patterns measured, offering a dimensional neuroanatomical representation for studying disease heterogeneity and similarities of neurologic and neuropsychiatric diseases. We investigate the presence of nine DNEs derived from independent yet harmonized studies on Alzheimer’s disease, autism spectrum disorder, late-life depression and schizophrenia in the UK Biobank study. Phenome-wide associations align with genome-wide associations, revealing 31 genomic loci (<i>P</i> &lt; 5 × 10⁻⁸/9) associated with the nine DNEs. The nine DNEs, along with their polygenic risk scores, significantly enhanced the predictive accuracy for 14 systemic disease categories, particularly for conditions related to mental health and the central nervous system, as well as mortality outcomes. These findings underscore the potential of the nine DNEs to capture the expression of disease-related brain phenotypes in individuals of the general population and to relate such measures with genetics, lifestyle factors and chronic diseases.</p>","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"26 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144228581","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 deep learning system for detecting silent brain infarction and predicting stroke risk","authors":"Nan Jiang, Hongwei Ji, Zhouyu Guan, Yuesong Pan, Chenxin Deng, Yuchen Guo, Dan Liu, Tingli Chen, Shiyu Wang, Yilan Wu, Dawei Yang, An Ran Ran, Haslina Hamzah, Miao Li Chee, Changchang Yin, Benjamin Sommer Thinggaard, Frederik N. Pedersen, Qingsheng Peng, Ten Cheer Quek, Jocelyn Hui Lin Goh, Sarkaaj Singh, Anis Syazwani Abd Raof, Jian Wen Samuel Lee-Boey, Yuwei Lu, Shan Huang, Jia Shu, Shujie Yu, Yixiao Jin, Tingyao Li, Yiming Qin, Jing Wang, Xiaolong Yang, Tingting Hu, Zheyuan Wang, Yaoning Zhao, Seungmin Lee, Xiaoer Wei, Haotian Zheng, Yuehua Li, Jie Shen, Yan Zhou, Shiqun Lin, Chan Wu, Rongping Dai, Lei Ruan, Ruth E. Hogg, David Wright, Ya Xing Wang, Yingfeng Zheng, Gavin Siew Wei Tan, Charumathi Sabanayagam, Yuqian Bao, Cuntai Zhang, Ping Zhang, Weiwen Zou, Minyi Guo, Xiaokang Yang, Gareth J. McKay, Jakob Grauslund, Lee-Ling Lim, Zixiao Li, Carol Y. Cheung, Yih Chung Tham, Ching-Yu Cheng, Yongjun Wang, Qionghai Dai, Weiping Jia, Huating Li, Bin Sheng, Tien Yin Wong","doi":"10.1038/s41551-025-01413-9","DOIUrl":"https://doi.org/10.1038/s41551-025-01413-9","url":null,"abstract":"<p>Current brain imaging to detect silent brain infarctions (SBIs) is not feasible for the general population. Here, to overcome this challenge, we developed a retinal image-based deep learning system, DeepRETStroke, to detect SBI and refine stroke risk. We use 895,640 retinal photographs to pretrain the DeepRETStroke system, which encodes a domain-specific foundation model for representing eye–brain connections. Then, we validated the downstream clinical tasks of DeepRETStroke using 213,762 retinal photographs from diverse datasets across China, Singapore, Malaysia, the USA, the UK and Denmark to detect SBI and predict stroke events. DeepRETStroke performed well in internal validation datasets, with areas under the curve of 0.901 for predicting incident stroke and 0.769 for predicting recurrent stroke. External validations demonstrated consistent performances across diverse datasets. Finally, in a prospective study comprising 218 participants with stroke, we assessed the performance of DeepRETStroke compared with clinical traits in guiding strategies for stroke recurrence prevention. Altogether, the retinal image-based deep learning system, DeepRETStroke, is superior to clinical traits in predicting stroke events, especially by incorporating the detection of SBI, without the need for brain imaging.</p>","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"17 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144228479","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":"Mechanically knocking out titin reveals protein tension loss as a trigger of muscle disease","authors":"Roberto Silva-Rojas, Natalia Vicente, Manuel Gavilán-Herrera, Verónica Labrador-Cantarero, Jon Sicilia, Olga Giménez-Sáez, Andra C. Dumitru, Mateo I. Sánchez, Mara Gato-Vilaseca, Diana Velázquez-Carreras, Juan Antonio López, Jesús Vázquez, Elías Herrero-Galán, Miguel A. López-Unzu, Maria Rosaria Pricolo, Jorge Alegre-Cebollada","doi":"10.1038/s41551-025-01403-x","DOIUrl":"https://doi.org/10.1038/s41551-025-01403-x","url":null,"abstract":"<p>Titin, the elastic protein scaffold of muscle sarcomeres, has multifunctional roles in mechanosignalling and is implicated in muscle disease. However, the consequences of disrupting titin’s mechanical function in vivo remain incompletely understood. Here, by leveraging site-directed polypeptide severing as a ‘mechanical knock-out’ method for abolishing force transmission across titin, we show that the loss of titin tension in homozygous mechanically knocked-out muscles reduces force generation and induces severe atrophy and widespread transcriptional dysregulation. Although mechanically knocked-out myofibres persist, they shrink and undergo progressive sarcomere depletion, which correlates with the rapid upregulation of muscle-specific RING finger protein 1 (MuRF1) and with altered levels of other titin-associated atrophy regulators. The affected fibres also exhibit mitochondrial aggregation and myonuclei internalization, preceded by desmin mislocalization. Heterozygous mechanically knocked-out muscles show milder phenotypes that closely resemble titin-related human myopathy. Our findings suggest that slack titin molecules drive muscle disease, potentially through mechanisms shared with other mechanical proteins.</p>","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"4 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144218891","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}