Biomaterials最新文献

{"title":"Procoagulant, antibacterial and antioxidant high-strength porous hydrogel adhesives in situ formed via self-gelling hemostatic microsheets for emergency hemostasis and wound repair","authors":"Yingli Shan ,&nbsp;Feng Cao ,&nbsp;Xin Zhao ,&nbsp;Jinlong Luo ,&nbsp;Haoliang Mei ,&nbsp;Limou Zhang ,&nbsp;Ying Huang ,&nbsp;Yutong Yang ,&nbsp;Liangruijie Yan ,&nbsp;Yayong Huang ,&nbsp;Yong Han ,&nbsp;Baolin Guo","doi":"10.1016/j.biomaterials.2024.122936","DOIUrl":"10.1016/j.biomaterials.2024.122936","url":null,"abstract":"<div><div>Procoagulant, antibacterial and analgesic hemostatic hydrogel dressing with high wet tissue adhesion, ultra-high burst pressure, and easy preparation shows huge promising for rapid hemostasis in emergencies, yet it remains a challenge. Herein, we propose hemostatic microsheets based on quaternized chitosan-g-gallic acid (QCS-GA) and oxidized hyaluronic acid (OHA), which merge the benefits of sponges, hydrogels, and powders for rapid hemostasis and efficient wound healing. Specifically, they exhibit a large specific surface area and excellent hydrophilicity, rapidly absorbing blood and self-gelling through electrostatic interaction and Schiff base crosslinking. And this results in dense, porous hydrogel adhesives with superior mechanical properties, adhesion strength, and ultra-high burst pressure. Furthermore, the microsheets are biocompatible, biodegradable, and possess procoagulant, antibacterial, and antioxidant properties. In mouse and rat liver hemorrhage models, the optimized formulation (QCS-GA + OHA4) demonstrated superior hemostatic effects compared to Celox. In particular, QCS-GA + OHA4 microsheets could stop bleeding quickly from rat femoral artery transection and deliver lidocaine to provide analgesia during emergency treatment. Additionally, they promoted wound healing in mouse full-thickness skin defect wound. These easy-to-manufacture hemostatic microsheets are adaptable to irregular wounds, providing a novel solution for rapid hemostasis and wound healing.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"315 ","pages":"Article 122936"},"PeriodicalIF":12.8,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602175","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":"Reverse magnetic resonance tuning nanoplatform with heightened sensitivity for non-invasively multiscale visualizing ferroptosis-based tumor sensitization therapy","authors":"Yi Zhu ,&nbsp;Jiali Deng ,&nbsp;Hongwei Lu ,&nbsp;Zhu Mei ,&nbsp;Ziwei Lu ,&nbsp;Jiajing Guo ,&nbsp;An Chen ,&nbsp;Rong Cao ,&nbsp;Xinyi Ding ,&nbsp;Jingyi Wang ,&nbsp;Helen Forgham ,&nbsp;Ruirui Qiao ,&nbsp;Zhongling Wang","doi":"10.1016/j.biomaterials.2024.122935","DOIUrl":"10.1016/j.biomaterials.2024.122935","url":null,"abstract":"<div><div>Ferroptosis-based therapy has garnered considerable attention for its ability to kill drug-resistant cancer cells. Consequently, it holds great significance to assess the therapeutic outcomes by monitoring ferroptosis-related biomarkers, which enables the provision of real-time pathological insights into disease progression. Nevertheless, conventional imaging technology suffers from limitations including reduced sensitivity and difficulty in achieving real-time precise monitoring. Here, we report a tumor acidic-microenvironment-responsive nanoplatform with “Reverse Magnetic Resonance Tuning (ReMRT)” property and effective combined chemodynamic therapy (CDT) through the loading of chemotherapeutic drugs. This reverse MR mapping change is correlated with iron ion, reactive oxygen species (ROS) generation and drug release, etc., contributing to the precise monitoring of chemo-CDT effectiveness. Furthermore, the ReMRT nanoplatform presents as a highly efficacious combined chemo-CDT agent, and when this nanoplatform is used in conjunction with the “Area Reconstruction” method, it can afford a significant sensitivity (95.1-fold) in multiscale visualization of therapeutic, compared with the conventional MR <em>R</em>₁/<em>R</em>₂ values. The high-sensitive biological quantitative imaging provides a novel strategy for MR-guided multiscale dynamic tumor-related ferroptosis therapy.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"315 ","pages":"Article 122935"},"PeriodicalIF":12.8,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142566707","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":"Corrigendum to 'Enhancing CAR-T cell therapy against solid tumor by drug-free triboelectric immunotherapy' [Biomaterials 314 (2025) 122871].","authors":"Haimei Li, Zichen Wang, Yulin Hu, Guangqin He, Liang Huang, Yi Liu, Zhong Lin Wang, Peng Jiang","doi":"10.1016/j.biomaterials.2024.122927","DOIUrl":"10.1016/j.biomaterials.2024.122927","url":null,"abstract":"","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":" ","pages":"122927"},"PeriodicalIF":12.8,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142556562","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":"Nanoradiosentizers with X ray-actuatable supramolecular aptamer building units for programmable immunostimulatory T cell engagement","authors":"Jinming He ,&nbsp;Xijiao Ren ,&nbsp;Qiqi Zhang ,&nbsp;Shuang Wang ,&nbsp;Zhongjun Li ,&nbsp;Kaiyong Cai ,&nbsp;Menghuan Li ,&nbsp;Yan Hu ,&nbsp;Qian Ran ,&nbsp;Zhong Luo","doi":"10.1016/j.biomaterials.2024.122924","DOIUrl":"10.1016/j.biomaterials.2024.122924","url":null,"abstract":"<div><div>The insufficient activation and impaired effector functions of T cells in the immunosuppressive tumor microenvironment (TME) substantially reduces the immunostimulatory effects of radiotherapy. Herein, a multifunctional nanoradiosensitizer is established by integrating molecularly engineered aptamer precursors into cisplatin-loaded liposomes for enhancing radio-immunotherapy of solid tumors. Exposure to ionizing radiation (IR) following the nanoradiosensitizer treatment would induce pronounced immunogenic death (ICD) of tumor cells through cisplatin-mediated radiosensitization while also trigger the detachment of the aptamer precursors, which further self-assemble into PD-L1/PD-1-bispecific aptamer-based T cell engagers (CA) through the bridging effect of tumor-derived ATP to direct T cell binding onto tumor cells in the post-IR TME in a spatial-temporally programmable manner. The CA-mediated post-IR tumor-T cell engagement could override the immunosuppressive barriers in TME and enhance T cell-mediated recognition and elimination of tumor cells while minimizing systemic toxicities. Overall, this work offers an innovative approach to enhance the radio-immunotherapeutic efficacy in the clinics.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"315 ","pages":"Article 122924"},"PeriodicalIF":12.8,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142566693","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":"Targeted sonodynamic therapy induces tumor cell quasi-immunogenic ferroptosis and macrophage immunostimulatory autophagy in glioblastoma","authors":"Meng-Fei Wang ,&nbsp;Jie Guo ,&nbsp;Shen-Jun Yuan ,&nbsp;Ke Li ,&nbsp;Quan Zhang ,&nbsp;Hui-Mei Lei ,&nbsp;Jia-Lin Wu ,&nbsp;Li Zhao ,&nbsp;Yong-Hong Xu ,&nbsp;Xiao Chen","doi":"10.1016/j.biomaterials.2024.122913","DOIUrl":"10.1016/j.biomaterials.2024.122913","url":null,"abstract":"<div><div>In this study, we demonstrated the mechanism of a glioblastoma (GBM)-targeted sonodynamic therapy (SDT) strategy employing platelets loaded with a sonosensitizer based on functionalized boron nitride nanoparticles carrying chlorin e6 (BNPD-Ce6). In the in vitro study, we first found that the BNPD-Ce6-mediated sonodynamic action (SDA) induced remarkable viability loss, DNA damage, and cell death in the GBM cells (GBCs) but not macrophages. Surprisingly, the SDA-exposed GBCs displayed a ferroptotic phenotype while the SDA-exposed macrophages underwent immuno-stimulatory autophagy and potently potentiated the SDA's toxicity to the GBCs. The ferroptotic GBCs induced by the SDA were found to be quasi-immunogenic, characterized by the emission of some alarmins such as ATP, HSP90, and CRT, but absent HMGB1, a potent endogenous adjuvant. As such, the SDA-stressed GBCs were unable to stimulate the BMDMs. This defect, interestingly, could be rescued by platelets as a donor of HMGB1 which markedly enhanced the BNPD-Ce6's sonotoxicity to the GBCs. In the in vivo study, we first employed BNPD-Ce6-loaded platelets to achieve ultrasound-triggered, targeted delivery of BNPD-Ce6 in grafted intra-cranial GBMs and subsequent sonodynamic tumor damage. An SDT regimen designed based on these results slowed the growth of grafted intra-cranial GBMs and significantly increased the survival of the host animals. Pathological examination of the SDT-treated GBMs revealed tissue necrosis and destruction and validated the in vitro observations. Finally, the depletion of macrophages was found to abrogate the efficacy of the SDT in subcutaneous GBC grafts. In conclusion, the BNPD-Ce6@Plt-mediated SDT is a practicable and efficacious anti-GBM therapy. Its therapeutic mechanism critically involves a synergy of tumor cell ferroptosis, macrophage stimulation, and platelet activation induced by the SDA.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"315 ","pages":"Article 122913"},"PeriodicalIF":12.8,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142538497","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":"Nanoparticle-mediated Klotho gene therapy prevents acute kidney injury to chronic kidney disease transition through regulating PPARα signaling in renal tubular epithelial cells","authors":"Hongyu Li ,&nbsp;Yuying Ouyang ,&nbsp;Haoran Lv ,&nbsp;Hanzhi Liang ,&nbsp;Siweier Luo ,&nbsp;Yating Zhang ,&nbsp;Haiping Mao ,&nbsp;Tianfeng Chen ,&nbsp;Wei Chen ,&nbsp;Yiming Zhou ,&nbsp;Qinghua Liu","doi":"10.1016/j.biomaterials.2024.122926","DOIUrl":"10.1016/j.biomaterials.2024.122926","url":null,"abstract":"<div><div>Klotho is an anti-aging protein produced primarily by tubular epithelial cells (TECs). Down-regulated expression of Klotho in injured TECs plays a key pathogenic role in promoting acute kidney injury (AKI) to chronic kidney disease (CKD) transition, yet therapeutic approaches targeting the restoration of renal Klotho levels remain challenging for clinical application. Here, we synthesize polydopamine-polyethylenimine-<span>l</span>-serine-<em>Klotho</em> plasmid nanoparticles (PPSK NPs), which can safely and selectively deliver the <em>Klotho</em> gene to the injured TECs through binding kidney injury molecule-1 and maintain the expression of Klotho protein. <em>In vitro</em>, PPSK NPs effectively reduce the hypoxia-reoxygenation-induced reactive oxygen species production and fibrotic gene expression. In the unilateral ischemia-reperfusion injury- and folic acid-induced AKI-CKD transition mouse models, a single low-dose injection of PPSK NPs is sufficient to preserve the normal kidney architecture and prevent renal fibrosis. Mechanismly, the protective effect of PPSK NPs relies on upregulating a key molecule peroxisome proliferator-activated receptor alpha (PPARα) via the inhibition of p38 and JNK phosphorylation, which in turn improves tubular fatty acid beta-oxidation and reduces renal lipid accumulation, thereby protecting against kidney fibrosis. In conclusion, our results highlight the translational potential of nanoparticle-based <em>Klotho</em> gene therapy in preventing the AKI-CKD transition.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"315 ","pages":"Article 122926"},"PeriodicalIF":12.8,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142580911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhanced tumor-targeting ability of transferrin-functionalized magnetic nanoparticles by in vivo AMF stimulation","authors":"Tingbin Zhang ,&nbsp;Jia Li ,&nbsp;Junjie Lu ,&nbsp;Jianwei Li ,&nbsp;Huan Zhang ,&nbsp;Yuqing Miao ,&nbsp;Xiaoli Liu ,&nbsp;Yuan He ,&nbsp;Lei Yang ,&nbsp;Haiming Fan","doi":"10.1016/j.biomaterials.2024.122925","DOIUrl":"10.1016/j.biomaterials.2024.122925","url":null,"abstract":"<div><div>The protein corona formed on the surface of ligand-functionalized nanoparticles has been associated with the loss of targeting capability of the nanoparticles <em>in vivo</em>. Here, we developed a remote magnetothermal stimulation approach to regulate the <em>in vivo</em> active-targeting capability of transferrin (Tf)-functionalized magnetic nanoparticles (SPIO-Tf). This technique harnesses the heat dissipation by the magnetic nanoparticles in response to alternating magnetic fields to re-expose buried Tf on the nanoparticle surface, thereby restoring its binding function. SPIO-Tf with different grafting densities were prepared and <em>in vitro</em> experiments reveal that AMF stimulation of SPIO-Tf significantly improved its targeting ability to A549 cells in serum-rich environments. In vivo experiments also exhibit a 2.68-fold greater accumulation of magnetothermal-stimulated SPIO-Tf in solid tumors. Moreover, our approach is applicable to various SPIO-Tf formulations with different PEG molecular weights, and antibodies-conjugated SPIO. Overall, this study establishes a versatile, safe and potent strategy to tackle the negative impact of protein corona on the targeting ability of ligand-decorated magnetic nanoparticles <em>in vivo</em>, with promising implications for enhancing the effectiveness of diagnostic and therapeutic interventions across a range of diseases.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"315 ","pages":"Article 122925"},"PeriodicalIF":12.8,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142566691","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":"Rescue of mitochondrial dysfunction through alteration of extracellular matrix composition in barth syndrome cardiac fibroblasts","authors":"Janny Piñeiro-Llanes ,&nbsp;Silveli Suzuki-Hatano ,&nbsp;Ananya Jain ,&nbsp;Sree Venigalla ,&nbsp;Manasi Kamat ,&nbsp;Kari B. Basso ,&nbsp;William T. Cade ,&nbsp;Chelsey S. Simmons ,&nbsp;Christina A. Pacak","doi":"10.1016/j.biomaterials.2024.122922","DOIUrl":"10.1016/j.biomaterials.2024.122922","url":null,"abstract":"<div><div>Fibroblast-ECM (dys)regulation is associated with a plethora of diseases. The ECM acts as a reservoir of inflammatory factors and cytokines that mediate molecular mechanisms within cardiac cell populations. The role of ECM-mitochondria crosstalk in the development and progression of cardiac disorders remains uncertain. We evaluated the influence of ECM produced by stromal cells from patients with the mitochondrial cardiomyopathy (Barth syndrome, BTHS) and unaffected healthy controls on cardiac fibroblast (CF) metabolic function. To do this, cell-derived matrices CDMs were generated from BTHS and healthy human pluripotent stem cell-derived CFs (hPSC-CF) and used as cell culture substrates. BTHS CDMs negatively impacted the mitochondrial function of healthy hPSC-CFs while healthy CDMs improved mitochondrial function in BTHS hPSC-CFs. Mass spectrometry comparisons identified 5 matrisome proteins differentially expressed in BTHS compared to healthy CDM. Our results highlight a key role for the ECM in disease through its impact on mitochondrial function.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"315 ","pages":"Article 122922"},"PeriodicalIF":12.8,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"VEGF-loaded ROS-responsive nanodots improve the structure and function of sciatic nerve lesions in type II diabetic peripheral neuropathy","authors":"Xiaolan Ou ,&nbsp;Ze Wang ,&nbsp;Daojiang Yu ,&nbsp;Wenlai Guo ,&nbsp;Andrei V. Zvyagin ,&nbsp;Quan Lin ,&nbsp;Wenrui Qu","doi":"10.1016/j.biomaterials.2024.122906","DOIUrl":"10.1016/j.biomaterials.2024.122906","url":null,"abstract":"<div><div>Diabetic peripheral neuropathy (DPN) is a prevalent complication of diabetes mellitus (DM), significantly contributing to the risk of amputation and mortality. Reactive oxygen species (ROS) can induce both neurological and structural harm through direct impact and pyroptosis, underscoring the critical role of ROS regulation in mitigating DPN. In this research endeavor, we propose harnessing the inherent antioxidant properties of sulfhydryl groups by grafting them onto gold nanodots through an amidation reaction, resulting in the creation of ROS-responsive AuNDs. Additionally, we aim to synthesize AuNDs-VEGF, wherein VEGF is attached to AuNDs via electrostatic interactions, as a therapeutic strategy for addressing DPN in rat models. The results of in vivo experiments showed that AuNDs and AuNDs-VEGF nanoparticles could increase the nerve conduction velocity, shorten the latency of nerve conduction in the sciatic nerve, promote the regeneration of nerve trophectodermal vessels, improve the structure and function of the sciatic nerve, reduce the apoptosis of neural cells, and alleviate the atrophy of the gastrocnemius muscle. Thus, VEGF-loaded ROS-responsive nanodots present a promising avenue for ameliorating diabetic peripheral neuropathy. This innovative approach not only extends the application possibilities of nanodots but also introduces a novel avenue for the treatment of diabetic neuropathy.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"315 ","pages":"Article 122906"},"PeriodicalIF":12.8,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142563476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioactive mesoporous silica materials-assisted cancer immunotherapy","authors":"Jiali Liu ,&nbsp;Jiying Liu ,&nbsp;Yaxin Wang ,&nbsp;Fangman Chen ,&nbsp;Yan He ,&nbsp;Xiaochun Xie ,&nbsp;Yiling Zhong ,&nbsp;Chao Yang","doi":"10.1016/j.biomaterials.2024.122919","DOIUrl":"10.1016/j.biomaterials.2024.122919","url":null,"abstract":"<div><div>Immunotherapy is initially envisioned as a powerful approach to train immune cells within the tumor microenvironment (TME) and lymphoid tissues to elicit strong anti-tumor responses. However, clinical cancer immunotherapy still faces challenges, such as limited immunogenicity and insufficient immune response. Leveraging the advantages of mesoporous silica (MS) materials in controllable drug and immunomodulator release, recent efforts have focused on engineering MS with intrinsic immunoregulatory functions to promote robust, systemic, and safe anti-tumor responses. This review discusses advances in bioactive MS materials that address the challenges of immunotherapy. Beyond their role in on-demand delivery and drug release in response to the TME, we highlight the intrinsic functions of bioactive MS in orchestrating localized immune responses by inducing immunogenic cell death in tumor cells, modulating immune cell activity, and facilitating tumor-immune cell interactions. Additionally, we emphasize the advantages of bioactive MS in recruiting and activating immune cells within lymphoid tissues to initiate anti-tumor vaccination. The review also covers the challenges of MS-assisted immunotherapy, potential solutions, and future outlooks. With a deeper understanding of material-bio interactions, the rational design of MS with sophisticated bioactivities and controllable responsiveness holds great promise for enhancing the outcomes of personalized immunotherapy.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"315 ","pages":"Article 122919"},"PeriodicalIF":12.8,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142553821","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}