Nature Biomedical Engineering最新文献

{"title":"Microfluidics combined with electron microscopy for rapid and high-throughput mapping of antibody–viral glycoprotein complexes","authors":"Leigh M. Sewall, Rebeca de Paiva Froes Rocha, Grace Gibson, Michelle Louie, Zhenfei Xie, Sandhya Bangaru, Andy S. Tran, Gabriel Ozorowski, Subhasis Mohanty, Nathan Beutler, Thomas F. Rogers, Dennis R. Burton, Albert C. Shaw, Facundo D. Batista, Blanca Chocarro Ruiz, Alba Torrents de la Peña, Andrew B. Ward","doi":"10.1038/s41551-025-01411-x","DOIUrl":"https://doi.org/10.1038/s41551-025-01411-x","url":null,"abstract":"<p>Understanding the mechanistic interplay between antibodies and invading pathogens is essential for vaccine development. Current methods are labour and time intensive and limited by sample preparation bottlenecks. Here we present microfluidic electron microscopy-based polyclonal epitope mapping (mEM), which combines microfluidics with single-particle electron microscopy for the structural characterization of immune complexes using small volumes of sera (&lt;4 µl). First, we used mEM to map polyclonal antibodies present in sera from infected and vaccinated individuals against five viral glycoproteins using negative-stain electron microscopy. The mEM detected a greater number of epitopes compared with conventional polyclonal epitope structural mapping methods. Second, we used mEM and cryo-electron microscopy to characterize two coronavirus spikes and one HA glycoprotein with and without polyclonal antibodies. Finally, we mapped individual antibody responses over time in mice vaccinated with human immunodeficiency virus envelope N332-GT5. mEM enables the rapid, high-throughput mapping of antibodies targeting a broad range of glycoproteins, facilitating a better understanding of infection and guiding structure-based vaccine design.</p>","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"30 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144201583","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":"Mechanical forces drive degenerative spine disease through ROCK signalling","authors":"","doi":"10.1038/s41551-025-01398-5","DOIUrl":"https://doi.org/10.1038/s41551-025-01398-5","url":null,"abstract":"Repetitive mechanical forces on the spine cause spinal ligament hypertrophy through an unknown molecular mechanism. We observed in ligaments obtained from patients undergoing surgical spine decompression that force-driven Rho-associated kinase (ROCK) signalling causes accumulation of myofibroblasts from fibroblasts and show that ROCK signalling inhibitors block this force-dependent molecular mechanism contributing to spinal ligament fibrosis.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"81 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144201582","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":"NAD+ biosynthesis and mitochondrial repair in acute kidney injury via ultrasound-responsive thylakoid-integrating liposomes","authors":"Yao Lei, Yuzhu Wu, Wan-Ru Zhuang, Helin Zhao, Weidong Nie, Guanghao Wu, Dai-Wen Pang, Hai-Yan Xie","doi":"10.1038/s41551-025-01402-y","DOIUrl":"https://doi.org/10.1038/s41551-025-01402-y","url":null,"abstract":"<p>Acute kidney injury (AKI) impairs the energy metabolism and antioxidant capacity of renal proximal tubular cells. Here we show that ultrasound-responsive liposomes integrating thylakoid fragments and encapsulating <span>l</span>-ascorbic acid can restore the energy supply and antioxidant capacity of the tubular cells as well as renal function in animal models of AKI. After intravenous injection, the liposomes preferentially accumulated in the injured kidneys and were internalized by proximal tubular cells. Quinolinate phosphoribosyltransferase expressed in thylakoid catalysed the biosynthesis of nicotinamide adenine dinucleotide (NAD⁺), prompting the recovery of damaged mitochondria. Local ultrasound stimulation activated electron transfer from ascorbic acid, which led to the cytoplasmic formation of NADH and to the restoration of adenosine triphosphate through the malate-aspartate shuttle. Concurrently, the enhanced pentose phosphate pathway facilitated NADPH biosynthesis and reduced the levels of reactive oxygen species. In mice and piglets with AKI, low doses of the liposomes prevented kidney damage.</p>","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"168 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144201584","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 brain–computer interface working definition","authors":"Marc W. Slutzky, Mariska J. Vansteensel, Christian Herff, Robert A. Gaunt","doi":"10.1038/s41551-025-01414-8","DOIUrl":"https://doi.org/10.1038/s41551-025-01414-8","url":null,"abstract":"&lt;p&gt;We read with interest the Comment that suggests a taxonomy for brain–computer interfaces (BCIs) based on application&lt;sup&gt;1&lt;/sup&gt;, and we agree that a nomenclature of different types of BCI may be useful for discussing this broad and expanding field comprised of stakeholders with different backgrounds and expertise, including groups new to BCI, such as media, investors and students. Nevertheless, we feel compelled to respond regarding the working definition of BCIs proposed in the article. The definition endorsed by the authors was that a BCI includes “any technology that records brain activity and processes it on an electronic device, or any technology that stimulates brain activity based on computations performed on an electronic device”. Although this may be accurate on a strictly semantic basis — that is, recording and stimulating technically meet the definition of an interface as both involve interactions between two systems — it diverges both from the historical definition of BCIs&lt;sup&gt;2&lt;/sup&gt; and from the results obtained in a consensus survey recently performed by the BCI Society. The survey was sent to a broad range of stakeholders in the field, including scientists, engineers, physicians, therapists, regulators and industry members. Based on the results of this survey and continued discussion, 57% of 137 respondents, all recent or current members of the BCI Society, agreed upon a working definition, reflecting the potential need to revisit this important topic in the future. This working definition was carefully created by an ad hoc committee of the BCI Society, as follows: “A brain-computer interface is a system that measures brain activity and converts it in (nearly) real-time into functionally useful outputs to replace, restore, enhance, supplement, and/or improve the natural outputs of the brain, thereby changing the ongoing interactions between the brain and its external or internal environments. It may additionally modify brain activity using targeted delivery of stimuli to create functionally useful inputs to the brain”.&lt;/p&gt;&lt;p&gt;We believe that this definition captures more clearly the essential features of a BCI and helps to distinguish it from other technologies that interface with or record from the brain, such as clinical electroencephalography and magnetoencephalography used for diagnostic purposes, functional magnetic resonance imaging or nuclear medicine scans, that are all consistent with the recently proposed definition&lt;sup&gt;1&lt;/sup&gt;. These technologies all record brain activity and perform computations on electronic devices, yet no one would consider them BCIs. Other devices such as open-loop deep brain stimulators could also be included under the proposed BCI definition&lt;sup&gt;1&lt;/sup&gt;, as they stimulate the brain based on computations performed on an electronic device. Yet, the responses to the BCI Society survey indicate an overall preference for a definition that includes measuring and responding to brain activity, not sim","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"37 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144193034","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":"Efficient and multiplexed somatic genome editing with Cas12a mice","authors":"Jess D. Hebert, Haiqing Xu, Yuning J. Tang, Paloma A. Ruiz, Colin R. Detrick, Jing Wang, Nicholas W. Hughes, Oscar Donosa, Vicky P. Siah, Laura Andrejka, Saswati Karmakar, Irenosen Aboiralor, Rui Tang, Rocio Sotillo, Julien Sage, Le Cong, Dmitri A. Petrov, Monte M. Winslow","doi":"10.1038/s41551-025-01407-7","DOIUrl":"https://doi.org/10.1038/s41551-025-01407-7","url":null,"abstract":"<p>Somatic genome editing in mouse models has increased our understanding of the in vivo effects of genetic alterations. However, existing models have a limited ability to create multiple targeted edits, hindering our understanding of complex genetic interactions. Here we generate transgenic mice with Cre-regulated and constitutive expression of enhanced <i>Acidaminococcus</i> sp. Cas12a (enAsCas12a), which robustly generates compound genotypes, including diverse cancers driven by inactivation of trios of tumour suppressor genes or an oncogenic translocation. We integrate these modular CRISPR RNA (crRNA) arrays with clonal barcoding to quantify the size and number of tumours with each array, as well as the impact of varying the guide number and position within a four-guide array. Finally, we generate tumours with inactivation of all combinations of nine tumour suppressor genes and find that the fitness of triple-knockout genotypes is largely explainable by one- and two-gene effects. These Cas12a alleles will enable further rapid creation of disease models and high-throughput investigation of coincident genomic alterations in vivo.</p>","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"14 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144176579","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":"Ultrasensitive and long-lasting bioluminescence immunoassay for point-of-care viral antigen detection","authors":"Sungwan Kim, Giwon Cho, Jaebaek Lee, Khushi Doshi, Supriya Gharpure, Jisan Kim, Juyong Gwak, Joseph M. Hardie, Manoj K. Kanakasabapathy, Hemanth Kandula, Prudhvi Thirumalaraju, Younseong Song, Hui Chen, Daniel R. Kuritzkes, Jonathan Z. Li, Athe M. Tsibris, Hadi Shafiee","doi":"10.1038/s41551-025-01405-9","DOIUrl":"https://doi.org/10.1038/s41551-025-01405-9","url":null,"abstract":"<p>Bioluminescence holds notable promise as a modality in diagnostics due to its high signal-to-noise ratio and absence of incident radiation. However, challenges arise from rapid signal decay and reduced enzyme activity when linked to targeting molecules, limiting its reliability in point-of-care diagnostic applications. Here we introduce the luminescence cascade-based sensor (LUCAS) assay, an enzyme cascade system capable of detecting analytes with ultrahigh sensitivity and prolonged bioluminescence. Utilizing a sequential enzymatic reaction, our assay achieves a greater than 500-fold increase in bioluminescence signal and maintains an 8-fold improvement in signal persistence compared to conventional bioluminescence assays. Implemented on a portable, fully automated device designed for point-of-care settings, our system facilitates rapid (&lt;23 min) sample-to-answer analysis of viruses without an external power supply. Its accuracy surpasses 94% in the qualitative classification of 177 viral-infected patient samples and 130 viral-spiked serum samples, various pathogens including the respiratory virus SARS-CoV-2, and blood-borne pathogens such as HIV, HBV and HCV as clinical models. The decentralized, rapid, sensitive, specific and cost-effective nature of LUCAS positions it as a viable diagnostic tool for low-resource environments.</p>","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"3 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144176596","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":"ROCK-dependent mechanotransduction of macroscale forces drives fibrosis in degenerative spinal disease","authors":"Muhamed Hadzipasic, Margaret S. Sten, Elie Massaad, Ali Kiapour, Ian D. Connolly, Eric Esposito, Ryan Burns, George Nageeb, Muneeb A. Sharif, Joseph Bradley, Leland Richardson, Sami Shaikh, Bryan D. Choi, Gunnlaugur P. Nielsen, Jean-Valery C. Coumans, Lawrence F. Borges, John H. Shin, Alan J. Grodzinsky, Hadi T. Nia, Ganesh M. Shankar","doi":"10.1038/s41551-025-01396-7","DOIUrl":"https://doi.org/10.1038/s41551-025-01396-7","url":null,"abstract":"<p>Chronic repetitive forces on the spinal column promote the development of degenerative spinal disease. Yet the mechanisms linking such macroscale mechanical forces to tissue hypertrophy remain unknown. Here we show that fibrotic regions in human ligamentum flavum naturally exposed to high stress display elevated Rho-associated kinase (ROCK) signalling and an increased density of myofibroblasts expressing smooth muscle actin α. The myofibroblasts were localized in regions of elevated stiffness and microstress, such accumulation was ROCK dependent, and ROCK inhibition partially reduced the stress-driven transcriptional responses. Our findings support the further investigation of ROCK inhibitors for the treatment of degenerative spinal disease.</p>","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"36 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144165309","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":"Rapid clearance of achiral small-molecule drugs using de novo-designed proteins and their cyclic and mirror-image variants","authors":"Guilin Chen, Kai Zhao, Mengjiao Li, Yuefei Zhang, Tian Li, Jing Yuan, Lei Lu, Jesús Valdiviezo, Dan Liu, Nicholas F. Polizzi, William F. DeGrado, Bobo Dang","doi":"10.1038/s41551-025-01404-w","DOIUrl":"https://doi.org/10.1038/s41551-025-01404-w","url":null,"abstract":"<p>Small-molecule-binding proteins can neutralize toxins and cytotoxic drugs, but their development is hindered by unpredictable in vivo behaviour and the poor immunogenicity of small molecules, which limits antibody-based approaches. Here we present a strategy to engineer de novo-designed proteins for the effective clearance of Food and Drug Administration-approved drugs in healthy mice. As a proof of concept, we designed proteins that bind to the anticoagulant apixaban. Since apixaban lacks chirality, we used mirror-image synthesis and cyclization to enhance the designed protein’s in vivo stability. Both protein variants demonstrated effective activity, facilitating the rapid clearance of apixaban within 30 min. To assess the broader applicability of this approach, we extended our analysis to a de novo-designed protein targeting the anticancer drug rucaparib, further confirming its potential for small-molecule clearance. Our study shows that de novo-designed small-molecule-binding proteins can be used as antidotes in vivo, and that computational tools can be integrated with medicinal chemistry strategies for precise pharmacological interventions.</p>","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"58 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144165308","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 wireless device for continuous measurement of brain parenchymal resistance tracks glymphatic function in humans","authors":"Paul Dagum, Laurent Giovangrandi, Swati Rane Levendovszky, Jake J. Winebaum, Tarandeep Singh, Yeilim Cho, Robert M. Kaplan, Michael S. Jaffee, Miranda M. Lim, Carla Vandeweerd, Jeffrey J. Iliff","doi":"10.1038/s41551-025-01394-9","DOIUrl":"https://doi.org/10.1038/s41551-025-01394-9","url":null,"abstract":"<p>Glymphatic function in animal models supports the clearance of brain proteins whose mis-aggregation is implicated in neurodegenerative conditions including Alzheimer’s and Parkinson’s disease. The measurement of glymphatic function in the human brain has been elusive due to invasive, bespoke and poorly time-resolved existing technologies. Here we describe a non-invasive multimodal device for the continuous measurement of sleep-active changes in parenchymal resistance in humans using repeated electrical impedance spectroscopy measurements in two separate clinical validation studies. Device measurements successfully paralleled sleep-associated changes in extracellular volume that regulate glymphatic function and predicted glymphatic solute exchange measured by contrast-enhanced MRI. We replicate preclinical findings showing that glymphatic function is increased with increasing sleep electroencephalogram (EEG) delta power and is decreased with increasing sleep EEG beta power and heart rate. The present investigational device permits the continuous and time-resolved assessment of parenchymal resistance in naturalistic settings necessary to determine the contribution of glymphatic impairment to risk and progression of Alzheimer’s disease and to enable target-engagement studies that modulate glymphatic function in humans.</p>","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"7 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144145591","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":"The cerebellum shapes motions by encoding motor frequencies with precision and cross-individual uniformity","authors":"Chia-Wei Liu, Yi-Mei Wang, Shun-Ying Chen, Liang-Yin Lu, Ting-Yu Liang, Ke-Chu Fang, Peng Chen, I-Chen Lee, Wen-Chuan Liu, Ami Kumar, Sheng-Han Kuo, Jye-Chang Lee, Chung-Chuan Lo, Shun-Chi Wu, Ming-Kai Pan","doi":"10.1038/s41551-025-01409-5","DOIUrl":"https://doi.org/10.1038/s41551-025-01409-5","url":null,"abstract":"<p>Understanding brain behaviour encoding or designing neuroprosthetics requires identifying precise, consistent neural algorithms across individuals. However, cerebral microstructures and activities are individually variable, posing challenges for identifying precise codes. Here, despite cerebral variability, we report that the cerebellum shapes motor kinematics by encoding dynamic motor frequencies with remarkable numerical precision and cross-individual uniformity. Using in vivo electrophysiology and optogenetics in mice, we confirm that deep cerebellar neurons encode frequencies using populational tuning of neuronal firing probabilities, creating cerebellar oscillations and motions with matched frequencies. The mechanism is consistently presented in self-generated rhythmic and non-rhythmic motions triggered by a vibrational platform or skilled tongue movements of licking in all tested mice with cross-individual uniformity. The precision and uniformity allowed us to engineer complex motor kinematics with designed frequencies. We further validate the frequency-coding function of the human cerebellum using cerebellar electroencephalography recordings and alternating current stimulation during voluntary tapping tasks. Our findings reveal a cerebellar algorithm for motor kinematics with precision and uniformity, the mathematical foundation for a brain–computer interface for motor control.</p>","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"14 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144145592","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}