{"title":"Jawbone-like organoids generated from human pluripotent stem cells","authors":"Souta Motoike, Yoshiko Inada, Junya Toguchida, Mikihito Kajiya, Makoto Ikeya","doi":"10.1038/s41551-025-01419-3","DOIUrl":"https://doi.org/10.1038/s41551-025-01419-3","url":null,"abstract":"<p>Engineering jawbone tissues from pluripotent stem cells presents a challenge owing to the lack of protocols for selectively inducing the jawbone progenitor, the first pharyngeal arch (PA1) ectomesenchyme, and for recapitulating three-dimensional osteocyte networks. Here we present a method for generating jawbone-like organoids from human induced pluripotent stem cells through PA1 ectomesenchyme of the mandibular prominence (mdEM). A three-dimensional culture system enables sequential differentiation of induced pluripotent stem cells into neural crest cells and mdEM. The mdEM exhibits proximal–distal patterning from the centre outwards, mirroring mandibular development. The introduction of exogenous pharyngeal epithelial signals induces mandibular prominence-specific regional patterning in the mdEM. When cultured under osteogenic conditions, the mdEM forms jawbone-like organoids comprising osteoblasts and network-forming osteocytes embedded in self-produced mineralized bone matrices. Moreover, these organoids promote bone regeneration when transplanted into jaws containing bone defects and recapitulate phenotypes of osteogenesis imperfecta, a genetic disorder characterized by fragile bones, using patient-derived induced pluripotent stem cells. Our protocols establish a foundation for investigating human jaw embryology and pathophysiology.</p>","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"13 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144533070","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}
An-Yi Chang, Muyang Lin, Lu Yin, Maria Reynoso, Shichao Ding, Ruixiao Liu, Yuma Dugas, Ana Casanova, Geonho Park, Zhengxing Li, Hao Luan, Nelly Askarinam, Fangyu Zhang, Sheng Xu, Joseph Wang
{"title":"Integration of chemical and physical inputs for monitoring metabolites and cardiac signals in diabetes","authors":"An-Yi Chang, Muyang Lin, Lu Yin, Maria Reynoso, Shichao Ding, Ruixiao Liu, Yuma Dugas, Ana Casanova, Geonho Park, Zhengxing Li, Hao Luan, Nelly Askarinam, Fangyu Zhang, Sheng Xu, Joseph Wang","doi":"10.1038/s41551-025-01439-z","DOIUrl":"https://doi.org/10.1038/s41551-025-01439-z","url":null,"abstract":"<p>The development of closed-loop systems towards effective management of diabetes requires the inclusion of additional chemical and physical inputs that affect disease pathophysiology and reflect cardiovascular risks in patients. Comprehensive glycaemic control information should account for more than a single glucose signal. Here, we describe a hybrid flexible wristband sensing platform that integrates a microneedle array for multiplexed biomarker sensing and an ultrasonic array for blood pressure, arterial stiffness and heart-rate monitoring. The integrated system provides a continuous evaluation of the metabolic and cardiovascular status towards improving glycaemic control and alerting patients to cardiovascular risks. The multimodal platform offers continuous glucose, lactate and alcohol monitoring, along with simultaneous ultrasonic measurements of blood pressure, arterial stiffness and heart rate, to support understanding of the interplay between interstitial fluid biomarkers and physiological parameters during common activities. By expanding the continuous monitoring of patients with diabetes to additional biomarkers and key cardiac signals, our integrated multiplexed chemical–physical health-monitoring platform holds promise for addressing the limitations of existing single-modality glucose-monitoring systems towards enhanced management of diabetes and related cardiovascular risks.</p>","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"27 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144533072","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}
Chao Ma, Huishu Wang, Lunan Liu, Ruiqi Chen, Nandana Mukherjee, Jie Tong, Shadab Kazmi, Xiangyi Fang, Matthew T. Witkowski, Iannis Aifantis, Saba Ghassemi, Weiqiang Chen
{"title":"Bioengineered immunocompetent preclinical trial-on-chip tool enables screening of CAR T cell therapy for leukaemia","authors":"Chao Ma, Huishu Wang, Lunan Liu, Ruiqi Chen, Nandana Mukherjee, Jie Tong, Shadab Kazmi, Xiangyi Fang, Matthew T. Witkowski, Iannis Aifantis, Saba Ghassemi, Weiqiang Chen","doi":"10.1038/s41551-025-01428-2","DOIUrl":"https://doi.org/10.1038/s41551-025-01428-2","url":null,"abstract":"<p>Chimeric antigen receptor (CAR) T cell immunotherapy is promising for treatment of blood cancers; however, clinical benefits remain unpredictable, necessitating development of optimal CAR T cell products. Unfortunately, current preclinical evaluation platforms are inadequate owing to their limited physiological relevance to humans. Here we engineer an organotypic immunocompetent chip that recapitulates microarchitectural and pathophysiological characteristics of human leukaemia bone marrow stromal and immune niches for CAR T cell therapy modelling. This leukaemia chip empowers real-time spatiotemporal monitoring of CAR T cell functionality, including T cell extravasation, recognition of leukaemia, immune activation, cytotoxicity and killing. We use our chip to model clinically observed heterogeneous responses such as remission, resistance and relapse under CAR T cell therapy and map factors that drive therapeutic success or failure. Finally, we demarcate functional performance of CAR T cells produced from different healthy donors and patients with cancer, with various CAR designs and protocols, systematically and multidimensionally. Together, our chip introduces an enabling ‘(pre-)clinical-trial-on-chip’ tool for CAR T cell development, which may translate to personalized therapies and improved clinical decision-making.</p>","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"19 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144520438","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}
Bo Ning, Sutapa Chandra, Yongchun Pan, Riti Sharan, Ngan Ha, Sanjay Singh, Alexandra Portillo Varela, Lin Li, Qingli Wu, Alexander Kay, Gugu P. Maphalala, Clement Adu-Gyamfi, Santiago Carrero Longlax, Anna M. Mandalakas, Smriti Mehra, Christopher J. Lyon, Edward A. Graviss, Andrew R. DiNardo, Tony Hu
{"title":"Self-powered rapid antigen-specific T-cell response assay for Mycobacterium tuberculosis infections","authors":"Bo Ning, Sutapa Chandra, Yongchun Pan, Riti Sharan, Ngan Ha, Sanjay Singh, Alexandra Portillo Varela, Lin Li, Qingli Wu, Alexander Kay, Gugu P. Maphalala, Clement Adu-Gyamfi, Santiago Carrero Longlax, Anna M. Mandalakas, Smriti Mehra, Christopher J. Lyon, Edward A. Graviss, Andrew R. DiNardo, Tony Hu","doi":"10.1038/s41551-025-01441-5","DOIUrl":"https://doi.org/10.1038/s41551-025-01441-5","url":null,"abstract":"<p>Interferon-gamma release assays (IGRAs) that evaluate an individual’s T-cell activation response to <i>Mycobacterium tuberculosis</i> (<i>M.tb</i>)-specific peptides serve an important role in diagnosing tuberculosis (TB). However, there are substantial challenges to the use of IGRAs in resource-limited settings. Further, IGRA diagnostic performance can also be compromised in anergic individuals. Here we describe a microfluidic chip-based antigen-specific T-cell response assay (ASTRA) that automates the detection of <i>M.tb</i>-specific T-cell activation responses to facilitate screening for latent <i>M.tb</i> infection and TB. We observe that ASTRA demonstrates high specificity for <i>M.tb</i> infection in independent patient cohorts. Compared with IGRA, ASTRA shows greater diagnostic sensitivity in individuals with HIV-1 co-infections (93.8% versus 67%), comparable diagnostic sensitivity in HIV-negative individuals (92.8%) and faster detection (4 h versus 24–48 h). We also find that a self-powered ASTRA chip that analysed microsample (~25 μl) whole-blood samples produced comparable results. ASTRA holds the potential to facilitate efforts to control the global TB epidemic and serve as a versatile platform for analysing T-cell responses across various infectious diseases and immunotherapeutic interventions.</p>","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"57 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144500406","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":"Extension of replicative lifespan by synthetic engineered telomerase RNA in patient induced pluripotent stem cells","authors":"Neha Nagpal, Suneet Agarwal","doi":"10.1038/s41551-025-01429-1","DOIUrl":"https://doi.org/10.1038/s41551-025-01429-1","url":null,"abstract":"<p>RNA engineering has yielded a new class of medicines but faces limitations depending on RNA size and function. Here we demonstrate the synthesis and enzymatic stabilization of telomerase RNA component (TERC), a therapeutically relevant long non-coding RNA (lncRNA) that extends telomere length and replicative lifespan in human stem cells. Compared with therapeutic mRNAs, engineered TERC RNA (eTERC) depends on avoiding nucleoside base modifications and incorporates a distinct trimethylguanosine 5′ cap during in vitro transcription. We show that the non-canonical polymerase TENT4B can be repurposed to enzymatically stabilize synthetic RNAs of any size by catalysing self-limited 2′-<i>O</i>-methyladenosine tailing, which is critical for optimal eTERC function in cells. A single transient exposure to eTERC forestalls telomere-induced senescence in telomerase-deficient human cell lines and lengthens telomeres in induced pluripotent stem cells from nine patients carrying different mutations in telomere-maintenance genes, as well as primary CD34<sup>+</sup> blood stem/progenitor cells. Our results provide methods and proof of functional reconstitution for a stabilized, synthetic human lncRNA. eTERC may have therapeutic potential to safely extend replicative capacity in human stem cells.</p>","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"16 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144500441","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}
Jaime Ibáñez, Blanka Zicher, Etienne Burdet, Stuart N. Baker, Carsten Mehring, Dario Farina
{"title":"Peripheral neural interfaces for reading high-frequency brain signals","authors":"Jaime Ibáñez, Blanka Zicher, Etienne Burdet, Stuart N. Baker, Carsten Mehring, Dario Farina","doi":"10.1038/s41551-025-01445-1","DOIUrl":"10.1038/s41551-025-01445-1","url":null,"abstract":"Accurate and robust recording and decoding from the central nervous system (CNS) is essential for advances in human–machine interfacing. Technologies for direct measurements of CNS activity are limited by their resolution, sensitivity to interference and invasiveness. Motor neurons (MNs) represent the motor output layer of the CNS, receiving and sampling signals from different regions in the nervous system and generating the neural commands that control muscles. Muscle recordings and deep learning decode the spiking activity of spinal MNs in real time and with high accuracy. The input signals to MNs can be estimated from MN outputs. Here we argue that peripheral neural interfaces using muscle sensors represent a promising, non-invasive approach to estimate some of the neural activity from the CNS that reaches the MNs but does not directly modulate force production. We discuss the evidence supporting this concept and the advances needed to consolidate and test MN-based CNS interfaces in controlled and real-world settings. This Perspective argues that neural activity from the central nervous system that is not directly correlated to force production can be sensed via peripheral neural interfaces.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"9 9","pages":"1391-1402"},"PeriodicalIF":26.8,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144500400","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}
Tanner C. Dixon, Gabrielle Strandquist, Alicia Zeng, Tomasz Frączek, Raphael Bechtold, Daryl Lawrence, Shravanan Ravi, Philip A. Starr, Jack L. Gallant, Jeffrey A. Herron, Simon J. Little
{"title":"Movement-responsive deep brain stimulation for Parkinson’s disease using a remotely optimized neural decoder","authors":"Tanner C. Dixon, Gabrielle Strandquist, Alicia Zeng, Tomasz Frączek, Raphael Bechtold, Daryl Lawrence, Shravanan Ravi, Philip A. Starr, Jack L. Gallant, Jeffrey A. Herron, Simon J. Little","doi":"10.1038/s41551-025-01438-0","DOIUrl":"https://doi.org/10.1038/s41551-025-01438-0","url":null,"abstract":"<p>Deep brain stimulation (DBS) has garnered widespread use as an effective treatment for advanced Parkinson’s disease. Conventional DBS (cDBS) provides electrical stimulation to the basal ganglia at fixed amplitude and frequency, yet patients’ therapeutic needs are often dynamic with residual symptom fluctuations or side effects. Adaptive DBS (aDBS) is an emerging technology that modulates stimulation with respect to real-time clinical, physiological or behavioural states, enabling therapy to dynamically align with patient-specific symptoms. Here we report an aDBS algorithm intended to mitigate movement slowness by delivering targeted stimulation increases during movement using decoded motor signals from the brain. Our approach demonstrated improvements in dominant hand movement speeds and study participant-reported therapeutic efficacy compared with an inverted control, as well as increased typing speed and reduced dyskinesia compared with cDBS. Furthermore, we demonstrate proof of principle of a machine learning pipeline capable of remotely optimizing aDBS parameters in a home setting. This work illustrates the potential of movement-responsive aDBS as a promising therapeutic approach and highlights how machine learning-assisted programming can simplify complex optimization to facilitate translational scalability.</p>","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"46 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144500399","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}
Genta Narazaki, Yuki Miura, Sergey D. Pavlov, Mayuri Vijay Thete, Julien G. Roth, Merve Avar, Sungchul Shin, Ji-il Kim, Zuzana Hudacova, Sarah C. Heilshorn, Sergiu P. Pașca
{"title":"Scalable production of human cortical organoids using a biocompatible polymer","authors":"Genta Narazaki, Yuki Miura, Sergey D. Pavlov, Mayuri Vijay Thete, Julien G. Roth, Merve Avar, Sungchul Shin, Ji-il Kim, Zuzana Hudacova, Sarah C. Heilshorn, Sergiu P. Pașca","doi":"10.1038/s41551-025-01427-3","DOIUrl":"https://doi.org/10.1038/s41551-025-01427-3","url":null,"abstract":"<p>The generation of neural organoids from human pluripotent stem cells holds great promise in modelling disease and screening drugs, but current approaches are difficult to scale due to undesired organoid fusion. Here we develop a scalable cerebral cortical organoid platform by screening biocompatible polymers that prevent the fusion of organoids cultured in suspension. We identify a cost-effective polysaccharide that increases the viscosity of the culture medium, significantly enhancing the yield of cortical organoids while preserving key features such as regional patterning, neuronal morphology and functional activity. We further demonstrate that this platform enables straightforward screening of 298 FDA-approved drugs and teratogens for growth defects using over 2,400 cortical organoids, uncovering agents that disrupt organoid growth and development. We anticipate this approach to provide a robust and scalable system for modelling human cortical development, and facilitate efficient compound screening for neuropsychiatric disorders-associated phenotypes.</p>","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"246 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144500403","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}
Ya-Nan Fan, Long Zhu, Yu-Xin Qing, Si-Yi Ye, Qian-Ni Ye, Xiao-Yi Huang, Dong-Kun Zhao, Tai-Yu Tian, Fang-Chao Li, Guan-Rong Yan, Xian-Zhu Yang, Song Shen, Jun Wang
{"title":"Engineering multi-specific nano-antibodies for cancer immunotherapy","authors":"Ya-Nan Fan, Long Zhu, Yu-Xin Qing, Si-Yi Ye, Qian-Ni Ye, Xiao-Yi Huang, Dong-Kun Zhao, Tai-Yu Tian, Fang-Chao Li, Guan-Rong Yan, Xian-Zhu Yang, Song Shen, Jun Wang","doi":"10.1038/s41551-025-01425-5","DOIUrl":"https://doi.org/10.1038/s41551-025-01425-5","url":null,"abstract":"<p>Immobilizing multiple types of monoclonal antibody (mAb) on nanoparticle surfaces is a promising approach for creating nanomedicines that emulate the functionality of multi-specific antibodies. However, the clinical translation of these multi-specific nano-antibodies (multi-NanoAbs) has been hindered by intricate fabrication procedures, inevitable attenuation in mAb affinity and insufficient carrier biosecurity. Here we develop a versatile nano-adaptor for immobilizing mAbs and construct multi-NanoAbs using a recombinant fusion protein that consists of Fc gamma receptor 1 and serum albumin, along with the biomedical polymer poly(<span>l</span>-lactide). Our findings demonstrate that fusion protein/polymer-based nano-adaptor is facilitated by FcγR1 on its surface to bind mAbs through receptor–ligand interactions rather than complex chemical conjugation and enables convenient and controlled construction of diverse multi-NanoAbs with efficacious therapeutic effects. We achieved large-scale production of humanized fusion protein/polymer-based nano-adaptor and confirmed the antitumour effectiveness of multi-NanoAb in humanized immune system mouse models, highlighting their prospects for clinical translation.</p>","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"21 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144488378","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}
Tony Georgiev, Francesca Migliorini, Andrea Ciamarone, Marco Mueller, Ilaria Biancofiore, Pinuccia Faviana, Francesco Bartoli, Young Seo Park Kim, Lucrezia Principi, Ettore Gilardoni, Gabriele Bassi, Nicholas Favalli, Emanuele Puca, Dario Neri, Sebastian Oehler, Samuele Cazzamalli
{"title":"Discovery of high-affinity ligands for prostatic acid phosphatase via DNA-encoded library screening enables targeted cancer therapy","authors":"Tony Georgiev, Francesca Migliorini, Andrea Ciamarone, Marco Mueller, Ilaria Biancofiore, Pinuccia Faviana, Francesco Bartoli, Young Seo Park Kim, Lucrezia Principi, Ettore Gilardoni, Gabriele Bassi, Nicholas Favalli, Emanuele Puca, Dario Neri, Sebastian Oehler, Samuele Cazzamalli","doi":"10.1038/s41551-025-01432-6","DOIUrl":"https://doi.org/10.1038/s41551-025-01432-6","url":null,"abstract":"<p>Improving the specificity of prostate cancer treatment requires ligands that bind selectively and with ultra-high affinity to tumour-associated targets absent from healthy tissues. Prostatic acid phosphatase has emerged as an alternative target to prostate-specific membrane antigen, as it is expressed in a broader subset of prostate cancers and is not detected in healthy organs such as the salivary glands and kidneys. Here, to discover selective binders to prostatic acid phosphatase, we constructed two DNA-encoded chemical libraries comprising over 6.7 million small molecules based on proline and phenylalanine scaffolds. Screening against the purified human prostatic acid phosphatase yielded OncoACP3, a small organic ligand with picomolar binding affinity. When radiolabelled with lutetium-177, OncoACP3 selectively accumulated in enzyme-expressing tumours with a long residence time (biological half-life greater than 72 h) and a high tumour-to-blood ratio (>148 at 2 h after administration). Lutetium-177-labelled OncoACP3 cured tumours in mice at low, well-tolerated doses. Its conjugation to the cytotoxic agent monomethyl auristatin E facilitated tumour-selective payload deposition, resulting in potent anti-tumour activity. The modular structure of OncoACP3 supports flexible payload delivery for the targeted treatment of metastatic prostate cancer.</p>","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"102 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144488425","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}