Nature Biomedical Engineering最新文献

Isogenic induced-pluripotent-stem-cell-derived airway- and alveolus-on-chip models reveal specific innate immune responses 等基因诱导多能干细胞衍生的气道和肺泡芯片模型揭示了特异性先天免疫反应

IF 28.1 1区医学

Nature Biomedical Engineering Pub Date : 2025-07-16 DOI: 10.1038/s41551-025-01444-2

Sachin Yadav, Kazuya Fujimoto, Toru Takenaga, Senye Takahashi, Yukiko Muramoto, Ryuta Mikawa, Takeshi Noda, Shimpei Gotoh, Ryuji Yokokawa

{"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":"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.","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}

引用次数: 0

Nanobody-based bispecific antibody engagers targeting CTLA-4 or PD-L1 for cancer immunotherapy 靶向CTLA-4或PD-L1的纳米体双特异性抗体接合物用于癌症免疫治疗

IF 28.1 1区医学

Nature Biomedical Engineering Pub Date : 2025-07-16 DOI: 10.1038/s41551-025-01447-z

Xin Liu, Camille Le Gall, Ryan K. Alexander, Ella Borgman, Thomas Balligand, Hidde L. Ploegh

{"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":"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 (VHHkappa) 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-VHHkappa 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-VHHkappa 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-VHHkappa 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.","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}

引用次数: 0

Ultra-high gradient connectomics and microstructure MRI scanner for imaging of human brain circuits across scales 超高梯度连接组学和微结构MRI扫描仪用于跨尺度人脑回路成像

IF 28.1 1区医学

Nature Biomedical Engineering Pub Date : 2025-07-16 DOI: 10.1038/s41551-025-01457-x

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

{"title":"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/s41551-025-01457-x","DOIUrl":"https://doi.org/10.1038/s41551-025-01457-x","url":null,"abstract":"Defining the connectome, the complete matrix of structural connections between the nervous system nodes, is a challenge for human systems neuroscience due to the range of scales that must be bridged. Here we report the design of the Connectome 2.0 human magnetic resonance imaging (MRI) scanner to perform connectomics at the mesoscopic and microscopic scales with strong gradients for in vivo human imaging. We construct a 3-layer head-only gradient coil optimized to minimize peripheral nerve stimulation while achieving a gradient strength of 500 mT m−1 and a slew rate of 600 T m−1 s−1, corresponding to a 5-fold greater gradient performance than state-of-the-art research gradient systems, including the original Connectome (Connectome 1.0) scanner. We find that gains in sensitivity of up to two times were achieved by integrating a 72-channel in vivo head coil and a 64-channel ex vivo whole-brain radiofrequency coil with built-in field monitoring for data fidelity. We demonstrate mapping of fine white matter pathways and inferences of cellular and axonal size and morphology approaching the single-micron level, with at least a 30% sensitivity improvement compared with Connectome 1.0.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"27 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144639729","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}

引用次数: 0

A thermogalvanic cell dressing for smart wound monitoring and accelerated healing 一种用于智能伤口监测和加速愈合的热电电池敷料

IF 28.1 1区医学

Nature Biomedical Engineering Pub Date : 2025-07-14 DOI: 10.1038/s41551-025-01440-6

Jiwu Xin, Liheng Gao, Wenjie Zhang, Xinyu Song, Yuanmeng Yang, Wenrui Li, Xuhui Zhou, Haozhe Zhang, Zhe Wang, Zhixun Wang, Bing He, Yanting Liu, Tianzhu Zhou, Ting Xiong, Shuai Wang, Shixing Yuan, Wulong Li, Say Chye Joahchim Loo, Lu Wang, Lei Wei

{"title":"A thermogalvanic cell dressing for smart wound monitoring and accelerated healing","authors":"Jiwu Xin, Liheng Gao, Wenjie Zhang, Xinyu Song, Yuanmeng Yang, Wenrui Li, Xuhui Zhou, Haozhe Zhang, Zhe Wang, Zhixun Wang, Bing He, Yanting Liu, Tianzhu Zhou, Ting Xiong, Shuai Wang, Shixing Yuan, Wulong Li, Say Chye Joahchim Loo, Lu Wang, Lei Wei","doi":"10.1038/s41551-025-01440-6","DOIUrl":"https://doi.org/10.1038/s41551-025-01440-6","url":null,"abstract":"Current smart dressings with wound monitoring and electrical stimulation capabilities rely on flexible electronics comprising various sensors and external power sources. Despite increasing efforts to integrate all these components onto flexible, breathable and biocompatible substrates, realizing a zero-power electrical stimulation without compromising the clinical applicability remains challenging. Here we report a solution that harnesses the temperature gradient between the wound and dressing to generate an electric stimulus that provides active wound healing management. This was achieved by a thermogalvanic cell (TGC) dressing composed of Fe2+/Fe3+ cross-linked alginate hydrogel reinforced by nanofibres. The TGC dressing exhibits biocompatibility, antibacterial performance, easy re-shaping and moisture permeability. Moreover, the TGC dressing generates an exogenous electric field, promoting the spontaneous acceleration of wound healing. We additionally integrate a sensing system that can monitor respiration rate. In the large porcine wound model, the wound healing rate of a TGC-bandaged group is improved by about 20.6% on day 14 compared with an untreated group. Our wireless wound monitoring system may facilitate real-time monitoring of common wound models at different wound development stages.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"23 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144622202","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}

引用次数: 0

Bispecific killer cell engager-secreting CAR-T cells redirect natural killer specificity to enhance antitumour responses 双特异性杀伤细胞接合分泌CAR-T细胞重定向自然杀伤特异性以增强抗肿瘤反应

IF 28.1 1区医学

Nature Biomedical Engineering Pub Date : 2025-07-14 DOI: 10.1038/s41551-025-01450-4

Ya Fan, Yanting Duan, Jiangqing Chen, Yajie Wang, Kai Shang, Jie Jiang, Lu Su, Chun Zhou, Michel Sadelain, He Huang, Jie Sun

{"title":"Bispecific killer cell engager-secreting CAR-T cells redirect natural killer specificity to enhance antitumour responses","authors":"Ya Fan, Yanting Duan, Jiangqing Chen, Yajie Wang, Kai Shang, Jie Jiang, Lu Su, Chun Zhou, Michel Sadelain, He Huang, Jie Sun","doi":"10.1038/s41551-025-01450-4","DOIUrl":"https://doi.org/10.1038/s41551-025-01450-4","url":null,"abstract":"T cells and natural killer (NK) cells collaborate to maintain immune homeostasis. Current cancer immunotherapies predominantly rely on the individual application of these cells. Here we use bicistronic vectors to co-express chimeric antigen receptors (CARs) and secreted immune cell engagers (ICEs), leveraging the combined therapeutic potential of both effector cell types. After in vitro validation of immune cell engager secretion and function, various combinatorial approaches are systematically compared in mouse models, identifying a highly effective combination of bispecific killer cell engager (BiKE)-secreting CAR-T cells and NK cells. Beyond a simple combination of conventional CAR-T cells and NK cells, this strategy demonstrates superior efficacy in CD19+ B cell leukaemia and lymphoma and EGFR+ solid tumour models while reducing the dosage dependence on CAR-T cells. Moreover, CAR-T cells and BiKEs targeting distinct antigens exhibit suppression of tumour cells with heterogeneous antigen expression. These findings indicate that combining BiKE-secreting CAR-T cells and NK cells offers a promising strategy to combat tumour antigen heterogeneity and immune evasion.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"11 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144622203","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}

引用次数: 0

A generative model uses healthy and diseased image pairs for pixel-level chest X-ray pathology localization 生成模型使用健康和病变图像对进行像素级胸部x线病理定位

IF 28.1 1区医学

Nature Biomedical Engineering Pub Date : 2025-07-14 DOI: 10.1038/s41551-025-01456-y

Kaiming Dong, Yuxiao Cheng, Kunlun He, Jinli Suo

{"title":"A generative model uses healthy and diseased image pairs for pixel-level chest X-ray pathology localization","authors":"Kaiming Dong, Yuxiao Cheng, Kunlun He, Jinli Suo","doi":"10.1038/s41551-025-01456-y","DOIUrl":"https://doi.org/10.1038/s41551-025-01456-y","url":null,"abstract":"Medical artificial intelligence (AI) offers potential for automatic pathological interpretation, but a practicable AI model demands both pixel-level accuracy and high explainability for diagnosis. The construction of such models relies on substantial training data with fine-grained labelling, which is impractical in real applications. To circumvent this barrier, we propose a prompt-driven constrained generative model to produce anatomically aligned healthy and diseased image pairs and learn a pathology localization model in a supervised manner. This paradigm provides high-fidelity labelled data and addresses the lack of chest X-ray images with labelling at fine scales. Benefitting from the emerging text-driven generative model and the incorporated constraint, our model presents promising localization accuracy of subtle pathologies, high explainability for clinical decisions, and good transferability to many unseen pathological categories such as new prompts and mixed pathologies. These advantageous features establish our model as a promising solution to assist chest X-ray analysis. In addition, the proposed approach is also inspiring for other tasks lacking massive training data and time-consuming manual labelling.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"2 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144622201","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}

引用次数: 0

Label-free protein-structure-sensitive live-cell microscopy for patient-specific assessment of myeloma therapy 无标记蛋白结构敏感活细胞显微镜对骨髓瘤治疗的患者特异性评估

IF 28.1 1区医学

Nature Biomedical Engineering Pub Date : 2025-07-14 DOI: 10.1038/s41551-025-01443-3

Francesca Gasparin, Marlene R. Tietje, Eslam Katab, Aizada Nurdinova, Tao Yuan, Andriy Chmyrov, Nasire Uluç, Dominik Jüstel, Florian Bassermann, Vasilis Ntziachristos, Miguel A. Pleitez

{"title":"Label-free protein-structure-sensitive live-cell microscopy for patient-specific assessment of myeloma therapy","authors":"Francesca Gasparin, Marlene R. Tietje, Eslam Katab, Aizada Nurdinova, Tao Yuan, Andriy Chmyrov, Nasire Uluç, Dominik Jüstel, Florian Bassermann, Vasilis Ntziachristos, Miguel A. Pleitez","doi":"10.1038/s41551-025-01443-3","DOIUrl":"https://doi.org/10.1038/s41551-025-01443-3","url":null,"abstract":"The efficacy of drug therapy in multiple myeloma is conventionally assessed by whole-cell-population methods, serum analysis of light chains and monoclonal antibodies, immunofixation electrophoresis, or by flow cytometry of bone marrow aspirates and biopsies. These methods provide relevant information on the presence of specific immunoglobulins at high sensitivity and specificity but require a large number of cells, involve long and laborious sample preparation steps, and provide only tumour bulk information. Here we develop a single-cell imaging technique requiring a reduced number of primary cells for longitudinal evaluation of patient-specific treatment and assessment of treatment heterogeneity. By exploiting the mechanistic action of proteasome inhibition and in synergy with the label-free protein-structure specificity of mid-infrared optoacoustic microscopy, we present a technology that facilitates longitudinal evaluation of myeloma treatment and a patient’s heterogeneous response. Detecting optical-generated ultrasound waves that intensify with optical absorption, this technology allows observation of proteins in living cells with high sensitivity. Specifically, we use intermolecular β-sheet formation as a biomarker for cell viability during therapy and apply it to assess drug-treatment performance in multiple myeloma patients.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"29 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144622204","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}

引用次数: 0

Emergency delivery of particulate drugs by active ejection using in vivo wireless devices 使用体内无线装置通过主动喷射紧急递送颗粒药物

IF 28.1 1区医学

Nature Biomedical Engineering Pub Date : 2025-07-09 DOI: 10.1038/s41551-025-01436-2

Siddharth R. Krishnan, Laura O’Keeffe, Arnab Rudra, Derin Gumustop, Nima Khatib, Claudia Liu, Jiawei Yang, Athena Wang, Matthew A. Bochenek, Yen-Chun Lu, Suman Bose, Kaelan Reed, Robert Langer, Daniel G. Anderson

{"title":"Emergency delivery of particulate drugs by active ejection using in vivo wireless devices","authors":"Siddharth R. Krishnan, Laura O’Keeffe, Arnab Rudra, Derin Gumustop, Nima Khatib, Claudia Liu, Jiawei Yang, Athena Wang, Matthew A. Bochenek, Yen-Chun Lu, Suman Bose, Kaelan Reed, Robert Langer, Daniel G. Anderson","doi":"10.1038/s41551-025-01436-2","DOIUrl":"https://doi.org/10.1038/s41551-025-01436-2","url":null,"abstract":"Rapidly administered emergency drug therapy represents life-saving treatment for a range of acute conditions including hypoglycaemia, anaphylaxis and cardiac arrest. Devices that automate emergency delivery, such as pumps and automated injectors, are limited by the low stability of liquid formulations. In contrast, dry particulate formulations of these drugs are stable but are incompatible with drug pumps and require reconstitution before administration. Here we develop a miniaturized (<3 cm3), lightweight (<2 g), minimally invasive, fully wireless emergency rescue device for the storage and active burst-release of indefinitely stable particulate forms of peptide and hormone drugs into subcutaneous sites for direct reconstitution in interstitial biofluids and rapid (<5 min) therapeutic effect. Importantly, the device delivers drug across fibrotic tissue, which commonly accumulates following in vivo implantation, thereby accelerating systemic delivery. Fully wireless delivery of dry particulate glucagon in vivo is demonstrated, providing emergency hypoglycaemic rescue in diabetic mice. In addition, triggered delivery of epinephrine is demonstrated in vivo. This work provides a platform for the long-term in vivo closed-loop delivery of emergency rescue drugs.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"33 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144586646","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}

引用次数: 0

Enantiomer-dependent and modification-free DNA matrix as an adjuvant for subunit vaccines against SARS-CoV-2 or pneumococcal infections 依赖对映体和无修饰的DNA基质作为抗SARS-CoV-2或肺炎球菌感染亚单位疫苗的佐剂

IF 28.1 1区医学

Nature Biomedical Engineering Pub Date : 2025-07-08 DOI: 10.1038/s41551-025-01431-7

Cuifeng Li, Yuxin Li, Bini Zhou, Tong Li, Xiaohui Wei, Kun Chen, Wenlong Chen, Ziwei Shi, Xiaobin Dai, Jiachen Zhang, Chen Yang, Zhenglin Ji, Wenbo Sun, Ji Gao, Jing Wu, Binbin Zhao, Xin Min, Yujie Li, Lin Lin, Wei Yang, Min Wang, Zezhong Liu, Yaping Liu, Chenyou Zhu, Bo Yang, Jiang-Fei Xu, Li-Tang Yan, Yi Shi, Lu Lu, Linqi Zhang, Qiang Ding, Jing Xue, Baidong Hou, Hai Qi, Jiangning Liu, Yuhe R. Yang, Dongsheng Liu, Wanli Liu

{"title":"Enantiomer-dependent and modification-free DNA matrix as an adjuvant for subunit vaccines against SARS-CoV-2 or pneumococcal infections","authors":"Cuifeng Li, Yuxin Li, Bini Zhou, Tong Li, Xiaohui Wei, Kun Chen, Wenlong Chen, Ziwei Shi, Xiaobin Dai, Jiachen Zhang, Chen Yang, Zhenglin Ji, Wenbo Sun, Ji Gao, Jing Wu, Binbin Zhao, Xin Min, Yujie Li, Lin Lin, Wei Yang, Min Wang, Zezhong Liu, Yaping Liu, Chenyou Zhu, Bo Yang, Jiang-Fei Xu, Li-Tang Yan, Yi Shi, Lu Lu, Linqi Zhang, Qiang Ding, Jing Xue, Baidong Hou, Hai Qi, Jiangning Liu, Yuhe R. Yang, Dongsheng Liu, Wanli Liu","doi":"10.1038/s41551-025-01431-7","DOIUrl":"https://doi.org/10.1038/s41551-025-01431-7","url":null,"abstract":"The emergence of novel infectious disease has intensified demand for more advanced vaccine development and more potent adjuvants to enhance immunogenicity. Here we introduce a dynamic DNA supramolecular matrix assembled from five unmodified, short DNA single strands, serving as a safe, multifaceted adjuvant platform. This DNA matrix elicits a robust humoral response with minimal adverse effects, generating potent neutralizing antibodies and conferring robust protection against SARS-CoV-2 and Streptococcus pneumoniae infections. Its dynamic colloidal feature prolongs the in vivo retention of both DNA and antigen, facilitating lymphatic-targeted transportation and presentation. This process leads to a robust pro-inflammatory response in both the vaccinated site and draining lymph node, which, in turn, promotes the recruitment and activation of immune cells, leading to a rapid, effective antigen-specific antibody response. The enhanced function of DNA matrix depends on the canonical TLR9–MyD88 signalling axis in dendritic cells. In addition, only right-handed, not left-handed, chirality of the DNA strands forms d-DNA matrix and promotes immune activations. Thus, this DNA matrix functions as an all-in-one adjuvant platform, opening promising avenues for future vaccine design.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"21 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144577974","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}

引用次数: 0

Holographic transcranial ultrasound neuromodulation enhances stimulation efficacy by cooperatively recruiting distributed brain circuits 全息经颅超声神经调节通过协同招募分布式脑回路来提高刺激效果

IF 28.1 1区医学

Nature Biomedical Engineering Pub Date : 2025-07-07 DOI: 10.1038/s41551-025-01449-x

Hector Estrada, Yiming Chen, Théo Lemaire, Neda Davoudi, Ali Özbek, Qendresa Parduzi, Shy Shoham, Daniel Razansky

{"title":"Holographic transcranial ultrasound neuromodulation enhances stimulation efficacy by cooperatively recruiting distributed brain circuits","authors":"Hector Estrada, Yiming Chen, Théo Lemaire, Neda Davoudi, Ali Özbek, Qendresa Parduzi, Shy Shoham, Daniel Razansky","doi":"10.1038/s41551-025-01449-x","DOIUrl":"https://doi.org/10.1038/s41551-025-01449-x","url":null,"abstract":"Precision-targeted ultrasonic neuromodulation offers immense potential for studying brain function and treating neurological diseases. Yet, its application has been limited by challenges in achieving precise spatio-temporal control and monitoring of ultrasound effects on brain circuits. Here we show that transcranial ultrasound elicits direct and highly focal responses, which can be dynamically steered at spatio-temporal scales relevant for neural function. Furthermore, holographic transcranial ultrasound stimulation allows direct control of the stimulated volume and actively modulates local and mid-range network projections, effectively lowering the activation threshold by an order of magnitude. To better understand this previously unexplored excitability regime not fully explained by the conventional pressure–frequency dyad, we developed a dual modelling framework, where both an empirical and a mechanistic model were constructed to capture the intricacies of holographic transcranial ultrasound stimulation. These models achieve qualitative agreement with our experimental results, suggesting that these findings are predominantly driven by putative network interactions. Our results bring insight on the complex interaction mechanisms of ultrasound with neural tissue and highlight its potential for the noninvasive interfacing of distributed brain networks.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"50 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144568360","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}

引用次数: 0