Nature Biomedical Engineering最新文献_第7页

Long-term engraftment of human stem and progenitor cells for large-scale production of functional immune cells in engineered pigs 长期植入人干细胞和祖细胞，在工程猪体内大规模生产功能性免疫细胞

IF 28.1 1区医学

Nature Biomedical Engineering Pub Date : 2025-05-20 DOI: 10.1038/s41551-025-01397-6

Zheng Hu, Jun Zou, Zhengzhu Wang, Kai Xu, Tang Hai, Sheng Zhang, Peipei An, Cong Fu, Shuai Dong, Yanan Lv, Jilong Ren, Zhiqiang Han, Chongyang Li, Jing Wang, Qingwei Wang, Renren Sun, Long Su, Hanjing Zuo, Qinghao Ding, Huimin Tian, Xinlan An, Yanhui Zhai, Dawei Yu, Chang Shu, Jin He, Liguang Sun, Tianmeng Sun, Xiangpeng Dai, Ziyi Li, Wei Li, Qi Zhou, Yong-Guang Yang

{"title":"Long-term engraftment of human stem and progenitor cells for large-scale production of functional immune cells in engineered pigs","authors":"Zheng Hu, Jun Zou, Zhengzhu Wang, Kai Xu, Tang Hai, Sheng Zhang, Peipei An, Cong Fu, Shuai Dong, Yanan Lv, Jilong Ren, Zhiqiang Han, Chongyang Li, Jing Wang, Qingwei Wang, Renren Sun, Long Su, Hanjing Zuo, Qinghao Ding, Huimin Tian, Xinlan An, Yanhui Zhai, Dawei Yu, Chang Shu, Jin He, Liguang Sun, Tianmeng Sun, Xiangpeng Dai, Ziyi Li, Wei Li, Qi Zhou, Yong-Guang Yang","doi":"10.1038/s41551-025-01397-6","DOIUrl":"https://doi.org/10.1038/s41551-025-01397-6","url":null,"abstract":"Existing immunodeficient pig models have demonstrated limited success in supporting robust human haematopoietic engraftment and multilineage differentiation. Here we hypothesize that the targeted deletion of integrin-associated protein (Cd47) in severe combined immunodeficient pigs, with deletions in the X-linked interleukin-2 receptor gamma chain and recombination activating gene 1, would enable long-term haematopoietic engraftment following transplantation with human haematopoietic stem/progenitor cells. In Cd47-deficient pigs, we observed high levels of human haematopoietic chimerism in the blood and spleen, with functional T and B lymphocytes, natural killer and myeloid cells, as well as robust thymopoiesis. Our findings suggest that severe combined immunodeficient pigs with Cd47 deletion represent an improved preclinical model for studying human haematopoiesis, disease mechanisms and therapies, and offer potential as a bioreactor for large-scale production of human immune cells.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"38 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144096866","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

siRNA conjugate with high albumin affinity and degradation resistance for delivery and treatment of arthritis in mice and guinea pigs 具有高白蛋白亲和力和降解抗性的siRNA偶联物用于小鼠和豚鼠关节炎的递送和治疗

IF 28.1 1区医学

Nature Biomedical Engineering Pub Date : 2025-05-16 DOI: 10.1038/s41551-025-01376-x

Juan M. Colazo, Megan C. Keech, Veeraj Shah, Ella N. Hoogenboezem, Justin H. Lo, Nora Francini, Nina T. Cassidy, Fang Yu, Alexander G. Sorets, Joshua T. McCune, Carlisle R. DeJulius, Hongsik Cho, Danielle L. Michell, Tristan Maerz, Kacey C. Vickers, Katherine N. Gibson-Corley, Karen A. Hasty, Leslie J. Crofford, Rebecca S. Cook, Craig L. Duvall

{"title":"siRNA conjugate with high albumin affinity and degradation resistance for delivery and treatment of arthritis in mice and guinea pigs","authors":"Juan M. Colazo, Megan C. Keech, Veeraj Shah, Ella N. Hoogenboezem, Justin H. Lo, Nora Francini, Nina T. Cassidy, Fang Yu, Alexander G. Sorets, Joshua T. McCune, Carlisle R. DeJulius, Hongsik Cho, Danielle L. Michell, Tristan Maerz, Kacey C. Vickers, Katherine N. Gibson-Corley, Karen A. Hasty, Leslie J. Crofford, Rebecca S. Cook, Craig L. Duvall","doi":"10.1038/s41551-025-01376-x","DOIUrl":"https://doi.org/10.1038/s41551-025-01376-x","url":null,"abstract":"Osteoarthritis and rheumatoid arthritis are debilitating joint diseases marked by pain, inflammation and cartilage destruction. Current osteoarthritis treatments only relieve symptoms, while rheumatoid arthritis therapies can cause immune suppression and provide variable efficacy. Here we developed an optimized small interfering RNA targeting matrix metalloproteinase 13 for preferential delivery to arthritic joints. Chemical modifications in a stabilizing ‘zipper’ pattern improved RNA resistance to degradation, and two independent linkers with 18 ethylene glycol repeats connecting to tandem C18 lipids enhanced albumin binding and targeted delivery to inflamed joints following intravenous administration. In preclinical models of post-traumatic osteoarthritis and rheumatoid arthritis, a single intravenous injection of the albumin-binding small interfering RNA achieved long-term joint retention, sustained gene silencing and reduced matrix metalloproteinase 13 activity over 30 days, resulting in decreased cartilage erosion and improved clinical outcomes, including reduced joint swelling and pressure sensitivity. This approach demonstrated superior efficacy over corticosteroids and small-molecule MMP inhibitors, highlighting the therapeutic promise of albumin ‘hitchhiking’ for targeted, systemic delivery of gene-silencing therapeutics to treat osteoarthritis and rheumatoid arthritis.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"41 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144066269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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Activating membrane receptors with ultrasound 用超声波激活膜受体

IF 28.1 1区医学

Nature Biomedical Engineering Pub Date : 2025-05-16 DOI: 10.1038/s41551-025-01395-8

Yi-Xian Qin, Elias Georgas

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A compact, wireless system for continuous monitoring of breast milk expressed during breastfeeding 一种紧凑的无线系统，用于持续监测母乳喂养期间分泌的乳汁

IF 28.1 1区医学

Nature Biomedical Engineering Pub Date : 2025-05-14 DOI: 10.1038/s41551-025-01393-w

Jihye Kim, Seyong Oh, Raudel Avila, Hee-Sup Shin, Matthew Banet, Jennifer Wicks, Anthony R. Banks, Yonggang Huang, Jae-Young Yoo, Daniel T. Robinson, Craig F. Garfield, John A. Rogers

{"title":"A compact, wireless system for continuous monitoring of breast milk expressed during breastfeeding","authors":"Jihye Kim, Seyong Oh, Raudel Avila, Hee-Sup Shin, Matthew Banet, Jennifer Wicks, Anthony R. Banks, Yonggang Huang, Jae-Young Yoo, Daniel T. Robinson, Craig F. Garfield, John A. Rogers","doi":"10.1038/s41551-025-01393-w","DOIUrl":"https://doi.org/10.1038/s41551-025-01393-w","url":null,"abstract":"Human milk is the ideal source of nutrition for infants. Most health organizations recommend direct breastfeeding from the first hour of life, extending throughout the first and second year. However, uncertainties regarding the volumes of milk ingested by the infant contribute to suboptimal rates of breastfeeding. Here we introduce a compact and unobtrusive device that gently interfaces to the breast via four electrodes and accurately measures expressed milk volume during breastfeeding through changes in the alternating current impedance. The data pass wirelessly to a smartphone continuously throughout each breastfeeding session for real-time graphical display. Comprehensive experimental and computational results establish the operating principles and guide engineering choices for optimized performance. Evaluations with 12 breastfeeding mothers over periods of as long as 17 weeks in the neonatal intensive care unit and in home settings illustrate the practical utility of this technology in addressing a critically important unmet need in maternal and neonatal care.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"68 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143945869","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

Multiplex imaging of amyloid-β plaques dynamics in living brains with quinoline-malononitrile-based probes 基于喹啉-丙二腈探针的活体大脑淀粉样蛋白-β斑块动力学的多重成像

IF 28.1 1区医学

Nature Biomedical Engineering Pub Date : 2025-05-13 DOI: 10.1038/s41551-025-01392-x

Jianfeng Dai, Weijun Wei, Chenxu Yan, Ding-Kun Ji, Caiqi Liu, Jialiang Huang, Chenyi Liang, Jianjun Liu, Zhiqian Guo, Wei-Hong Zhu

{"title":"Multiplex imaging of amyloid-β plaques dynamics in living brains with quinoline-malononitrile-based probes","authors":"Jianfeng Dai, Weijun Wei, Chenxu Yan, Ding-Kun Ji, Caiqi Liu, Jialiang Huang, Chenyi Liang, Jianjun Liu, Zhiqian Guo, Wei-Hong Zhu","doi":"10.1038/s41551-025-01392-x","DOIUrl":"https://doi.org/10.1038/s41551-025-01392-x","url":null,"abstract":"The dynamic behaviour of amyloid-β (Aβ) plaques in Alzheimer’s disease remains poorly understood, and accumulation and distribution of Aβ plaques must be inferred from in vitro pathological changes in brain tissue. In situ detection of Aβ plaques in live imaging is challenging because of the lack of adequate probes. Here we report the design of unimolecular quinoline-malononitrile-based Aβ probes, termed QMFluor integrative framework, that binds in vivo to Aβ plaques, making them detectable via near-infrared fluorescence imaging, magnetic resonance imaging, positron emission tomography and computed tomography. QMFluor probes are permeable to the blood–brain barrier, and, upon systematic injection, enable real-time magnetic resonance imaging and positron emission tomography–computed tomography imaging of the Aβ biodistribution in the hippocampus and cerebral cortex, and accurately differentiate the brains of living Alzheimer’s disease mouse models from wild-type controls. We further demonstrate the ability of QMFluor probes to reach the brain after intravenous injection in a large animal model. This strategy expands the toolbox of probes for in vivo visualization of amyloids in Alzheimer’s disease pathological analysis, drug screening and clinical applications.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"117 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143940153","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

Focused ultrasound-microbubble treatment arrests the growth and formation of cerebral cavernous malformations 聚焦超声微泡治疗可抑制脑海绵状畸形的生长和形成

IF 28.1 1区医学

Nature Biomedical Engineering Pub Date : 2025-05-13 DOI: 10.1038/s41551-025-01390-z

Delaney G. Fisher, Tanya Cruz, Matthew R. Hoch, Khadijeh A. Sharifi, Ishaan M. Shah, Catherine M. Gorick, Victoria R. Breza, Anna C. Debski, Joshua D. Samuels, Jason P. Sheehan, David Schlesinger, David Moore, James W. Mandell, John R. Lukens, G. Wilson Miller, Petr Tvrdik, Richard J. Price

{"title":"Focused ultrasound-microbubble treatment arrests the growth and formation of cerebral cavernous malformations","authors":"Delaney G. Fisher, Tanya Cruz, Matthew R. Hoch, Khadijeh A. Sharifi, Ishaan M. Shah, Catherine M. Gorick, Victoria R. Breza, Anna C. Debski, Joshua D. Samuels, Jason P. Sheehan, David Schlesinger, David Moore, James W. Mandell, John R. Lukens, G. Wilson Miller, Petr Tvrdik, Richard J. Price","doi":"10.1038/s41551-025-01390-z","DOIUrl":"https://doi.org/10.1038/s41551-025-01390-z","url":null,"abstract":"Cerebral cavernous malformations (CCMs) are vascular lesions within the central nervous system that cause debilitating neurological symptoms. Currently, surgical excision and stereotactic radiosurgery, the primary treatment options, pose risks to some patients. Here we tested whether pulsed, low intensity, focused ultrasound-microbubble (FUS-MB) treatments control CCM growth and formation in a clinically representative Krit1 null murine model. FUS-MB under magnetic resonance imaging (MRI) guidance opened the blood–brain barrier, with gadolinium contrast agent deposition most evident at perilesional boundaries. Longitudinal MRI revealed that, at 1 month after treatment, FUS-MB halted the growth of 94% of treated CCMs. In contrast, untreated CCMs grew ~7-fold in volume. FUS-MB-treated CCMs exhibited a marked reduction in Krit1 null endothelial cells. In mice receiving multiple FUS-MB treatments with fixed peak-negative pressures, de novo CCM formation was reduced by 81%, indicating a prophylactic effect. Our findings support FUS-MB as a minimally invasive treatment modality that can safely arrest murine CCM growth and prevent de novo CCM formation in mice. If proven safe and effective in clinical trials, FUS-MB treatment may enhance therapeutic options for CCM patients.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"31 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143940148","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

Targeting inflammation with chimeric antigen receptor macrophages using a signal switch 利用信号开关靶向嵌合抗原受体巨噬细胞炎症

IF 28.1 1区医学

Nature Biomedical Engineering Pub Date : 2025-05-07 DOI: 10.1038/s41551-025-01387-8

Qi Cao, Yiping Wang, Jianwei Chen, Ruifeng Wang, Titi Chen, Brian Gloss, Scott A. Read, Xuerong Wang, Vincent W. S. Lee, Leighton Clancy, Natasha M. Rogers, Stephen I. Alexander, Guoping Zheng, Di Yu, David C. H. Harris

{"title":"Targeting inflammation with chimeric antigen receptor macrophages using a signal switch","authors":"Qi Cao, Yiping Wang, Jianwei Chen, Ruifeng Wang, Titi Chen, Brian Gloss, Scott A. Read, Xuerong Wang, Vincent W. S. Lee, Leighton Clancy, Natasha M. Rogers, Stephen I. Alexander, Guoping Zheng, Di Yu, David C. H. Harris","doi":"10.1038/s41551-025-01387-8","DOIUrl":"https://doi.org/10.1038/s41551-025-01387-8","url":null,"abstract":"Chimeric antigen receptor (CAR) T-cell immunotherapy has shown great success in clinical cancer, bringing hope to apply CAR strategies to other clinical settings. Here we developed a CAR macrophage (CAR-M) that recognizes the major inflammatory molecule tumour necrosis factor (TNF) and activates an intracellular IL-4 signalling pathway, thereby programming engineered macrophages for an anti-inflammatory function. CAR-M therapy has exhibited efficacy in mouse models of both acute and chronic inflammatory diseases. In kidney ischaemia reperfusion injury (IRI), infused CAR-Ms switched to an anti-inflammatory phenotype in inflamed kidney and attenuated kidney IRI. The anti-inflammatory phenotype of infused CAR-Ms switched off during the recovery phase of kidney IRI, coinciding with the disappearance of TNF. In Adriamycin-induced nephropathy, a model of chronic inflammatory disease, infused CAR-Ms maintained an anti-inflammatory phenotype for several weeks in response to sustained high levels of TNF and improved kidney function and structure. CAR-Ms also effectively reduced tissue injury in another organ, the liver. Human anti-TNF CAR-Ms exhibit anti-inflammatory phenotype and function in response to TNF. The CAR-M design, using signal switching, holds promise for the treatment of a broad range of acute and chronic inflammatory diseases.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"43 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143915707","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

Antimicrobial peptides boosted by ultrasound 超声增强抗菌肽

IF 28.1 1区医学

Nature Biomedical Engineering Pub Date : 2025-05-02 DOI: 10.1038/s41551-025-01388-7

Soraia Fernandes, Francesca Cavalieri

引用次数: 0

Enhanced nanoparticle delivery across vascular basement membranes of tumours using nitric oxide 利用一氧化氮增强肿瘤血管基底膜上纳米颗粒的传递

IF 28.1 1区医学

Nature Biomedical Engineering Pub Date : 2025-05-02 DOI: 10.1038/s41551-025-01385-w

Wei Jiang, Zixuan Guo, Qin Wang, Ziqi Chen, Wang Dong, Qirui Liang, Yinghong Hao, Huimin Pan, Cici Zeng, Hang Liu, Yucai Wang

{"title":"Enhanced nanoparticle delivery across vascular basement membranes of tumours using nitric oxide","authors":"Wei Jiang, Zixuan Guo, Qin Wang, Ziqi Chen, Wang Dong, Qirui Liang, Yinghong Hao, Huimin Pan, Cici Zeng, Hang Liu, Yucai Wang","doi":"10.1038/s41551-025-01385-w","DOIUrl":"https://doi.org/10.1038/s41551-025-01385-w","url":null,"abstract":"The delivery of nanoparticles (NPs) into solid tumours is challenged by the tumour vascular basement membrane (BM), a critical barrier beneath the endothelium with robust mechanical properties resistant to conventional treatments. Here we propose an approach that uses nitric oxide (NO) to induce the opening of endothelial junctions, creating gaps between endothelial cells and enabling the navigation of NPs through these gaps. Subsequently, NO orchestrates a transient degradation of the BM encasing NP pools in a precise, localized action, allowing the enhanced passage of NPs into the tumour interstitial space through explosive eruptions. We have engineered a NO nanogenerator tailored for near-infrared laser-triggered on-demand NO release at tumour sites. Through breaching the BM barrier, this system results in an increase of clinical nanomedicines within the tumour, boosting the tumour suppression efficacy in both mouse and rabbit models. This approach delicately manages BM degradation, avoiding excessive degradation that might facilitate cancer metastasis. Our NO nanogenerator serves as a precise spatial catalytic degradation strategy for breaching the tumour vascular BM barrier, holding promise for NP delivery into non-tumour diseases.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"22 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143898133","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 sonosensitive diphenylalanine-based broad-spectrum antimicrobial peptide 一种基于二苯丙氨酸的声敏广谱抗菌肽

IF 28.1 1区医学

Nature Biomedical Engineering Pub Date : 2025-05-02 DOI: 10.1038/s41551-025-01377-w

Xiaoguang Zhang, Xiaobo Feng, Liang Ma, Jie Lei, Gaocai Li, Weifeng Zhang, Huaizhen Liang, Bide Tong, Di Wu, Cao Yang, Lei Tan

{"title":"A sonosensitive diphenylalanine-based broad-spectrum antimicrobial peptide","authors":"Xiaoguang Zhang, Xiaobo Feng, Liang Ma, Jie Lei, Gaocai Li, Weifeng Zhang, Huaizhen Liang, Bide Tong, Di Wu, Cao Yang, Lei Tan","doi":"10.1038/s41551-025-01377-w","DOIUrl":"https://doi.org/10.1038/s41551-025-01377-w","url":null,"abstract":"The antimicrobial effect of antimicrobial peptides is typically slow; they can be rapidly biodegraded and often have non-selective toxicity and elaborate sequences. Here we report a short peptide that is activated by ultrasound, that shows high broad-spectrum antibacterial efficiency (>99%) against clinically isolated methicillin-resistant bacteria (specifically, Staphylococcus aureus, Escherichia coli, Staphylococcus epidermidis, Enterobacter cancerogenus and Pseudomonas aeruginosa) with 15 min of ultrasound irradiation, and that has negligible toxicity and low self-antibacterial activity. We selected the peptide, FFRKSKEK (a segment from the human host-defence LL-37 peptide), from a library of peptides with piezoelectric diphenylalanine (FF) sequences, low toxicity, hydrophobicity and net positive charge. We show via all-atom molecular dynamics simulations that ultrasound amplifies the membrane-penetrating ability of peptides with FF sequences and that its piezoelectric polarization generates reactive-oxygen species and disturbs bacterial electron-transport chains. In a goat model of hard-to-treat intervertebral infection, the sonosensitive peptide led to better outcomes than vancomycin. Antimicrobial peptides activated by ultrasound may offer a clinically relevant strategy for combating antibiotic-resistant infections.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"44 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143898137","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