Signal Transduction and Targeted Therapy最新文献_第3页

Neutrophil diversity and function in health and disease

IF 39.3 1区医学

Signal Transduction and Targeted Therapy Pub Date : 2024-12-06 DOI: 10.1038/s41392-024-02049-y

Fengyuan Zhang, Yidan Xia, Jiayang Su, Fushi Quan, Hengzong Zhou, Qirong Li, Qiang Feng, Chao Lin, Dongxu Wang, Ziping Jiang

{"title":"Neutrophil diversity and function in health and disease","authors":"Fengyuan Zhang, Yidan Xia, Jiayang Su, Fushi Quan, Hengzong Zhou, Qirong Li, Qiang Feng, Chao Lin, Dongxu Wang, Ziping Jiang","doi":"10.1038/s41392-024-02049-y","DOIUrl":"https://doi.org/10.1038/s41392-024-02049-y","url":null,"abstract":"Neutrophils, the most abundant type of granulocyte, are widely recognized as one of the pivotal contributors to the acute inflammatory response. Initially, neutrophils were considered the mobile infantry of the innate immune system, tasked with the immediate response to invading pathogens. However, recent studies have demonstrated that neutrophils are versatile cells, capable of regulating various biological processes and impacting both human health and disease. Cytokines and other active mediators regulate the functional activity of neutrophils by activating multiple receptors on these cells, thereby initiating downstream signal transduction pathways. Dysfunctions in neutrophils and disruptions in neutrophil homeostasis have been implicated in the pathogenesis of numerous diseases, including cancer and inflammatory disorders, often due to aberrant intracellular signaling. This review provides a comprehensive synthesis of neutrophil biological functions, integrating recent advancements in this field. Moreover, it examines the biological roles of receptors on neutrophils and downstream signaling pathways involved in the regulation of neutrophil activity. The pathophysiology of neutrophils in numerous human diseases and emerging therapeutic approaches targeting them are also elaborated. This review also addresses the current limitations within the field of neutrophil research, highlighting critical gaps in knowledge that warrant further investigation. In summary, this review seeks to establish a comprehensive and multidimensional model of neutrophil regulation, providing new perspectives for potential clinical applications and further research.","PeriodicalId":21766,"journal":{"name":"Signal Transduction and Targeted Therapy","volume":"79 1","pages":""},"PeriodicalIF":39.3,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142782828","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

New insights into protein–protein interaction modulators in drug discovery and therapeutic advance

IF 39.3 1区医学

Signal Transduction and Targeted Therapy Pub Date : 2024-12-06 DOI: 10.1038/s41392-024-02036-3

Hossam Nada, Yongseok Choi, Sungdo Kim, Kwon Su Jeong, Nicholas A. Meanwell, Kyeong Lee

{"title":"New insights into protein–protein interaction modulators in drug discovery and therapeutic advance","authors":"Hossam Nada, Yongseok Choi, Sungdo Kim, Kwon Su Jeong, Nicholas A. Meanwell, Kyeong Lee","doi":"10.1038/s41392-024-02036-3","DOIUrl":"https://doi.org/10.1038/s41392-024-02036-3","url":null,"abstract":"Protein-protein interactions (PPIs) are fundamental to cellular signaling and transduction which marks them as attractive therapeutic drug development targets. What were once considered to be undruggable targets have become increasingly feasible due to the progress that has been made over the last two decades and the rapid technological advances. This work explores the influence of technological innovations on PPI research and development. Additionally, the diverse strategies for discovering, modulating, and characterizing PPIs and their corresponding modulators are examined with the aim of presenting a streamlined pipeline for advancing PPI-targeted therapeutics. By showcasing carefully selected case studies in PPI modulator discovery and development, we aim to illustrate the efficacy of various strategies for identifying, optimizing, and overcoming challenges associated with PPI modulator design. The valuable lessons and insights gained from the identification, optimization, and approval of PPI modulators are discussed with the aim of demonstrating that PPI modulators have transitioned beyond early-stage drug discovery and now represent a prime opportunity with significant potential. The selected examples of PPI modulators encompass those developed for cancer, inflammation and immunomodulation, as well as antiviral applications. This perspective aims to establish a foundation for the effective targeting and modulation of PPIs using PPI modulators and pave the way for future drug development.","PeriodicalId":21766,"journal":{"name":"Signal Transduction and Targeted Therapy","volume":"27 1","pages":""},"PeriodicalIF":39.3,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142782829","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

CXCR1+ neutrophil infiltration orchestrates response to third-generation EGFR-TKI in EGFR mutant non-small-cell lung cancer

IF 39.3 1区医学

Signal Transduction and Targeted Therapy Pub Date : 2024-12-06 DOI: 10.1038/s41392-024-02045-2

Haowei Wang, Anwen Xiong, Xiaoxia Chen, Junhong Guo, Zhuoran Tang, Chunyan Wu, Shengxiang Ren, Caicun Zhou, Jian Chen, Likun Hou, Tao Jiang

{"title":"CXCR1+ neutrophil infiltration orchestrates response to third-generation EGFR-TKI in EGFR mutant non-small-cell lung cancer","authors":"Haowei Wang, Anwen Xiong, Xiaoxia Chen, Junhong Guo, Zhuoran Tang, Chunyan Wu, Shengxiang Ren, Caicun Zhou, Jian Chen, Likun Hou, Tao Jiang","doi":"10.1038/s41392-024-02045-2","DOIUrl":"https://doi.org/10.1038/s41392-024-02045-2","url":null,"abstract":"Although third-generation Epidermal growth factor receptor—tyrosine kinase inhibitors (EGFR-TKI) is standard of care for patients with EGFR-mutant Non-small cell lung cancer (NSCLC), little is known about the predictors of response or resistance. Here, we integrated single-cell RNA (scRNA) sequencing, bulk RNA sequencing, multiplexed immunofluorescence and flow cytometry data from pretreatment and post-resistant tumor samples of EGFR-mutant NSCLC patients received third-generation EGFR-TKIs. We show that resistant samples had a markedly enriched CXCR1+ neutrophils infiltration (P < 0.01) than pretreatment samples, which were distinguished from other subtypes of neutrophils and displayed immunosupressive characteristics. Spatial analysis showed that increased CXCR1+ neutrophils predominantly infiltrated into the tumor core in resistant samples and the average distance of neutrophils to tumor cells markedly reduced from 33 to 19 μm. Deep analysis of scRNA and bulk RNA sequencing data revealed the increased interactions between CXCR1+ neutrophils and tumor cells and activated TNF-α/NF-κB signaling pathway in tumor cells of resistant samples. In vitro and in vivo experiments validated that CXCR1+ neutrophils resulted in resistance to third-generation EGFR-TKI via activating TNF-α/NF-κB signaling pathway in tumor cells. Importantly, patients with low pretreatment CXCR1+ neutrophil infiltration abundance had a dramatically longer progression-free survival (11.8 vs. 7.5 months; P = 0.019) and overall survival (33.0 vs. 23.5 months; P = 0.029) than those with high infiltration abundance. Collectively, these findings suggest that CXCR1+ neutrophils infiltration was associated with the efficacy of third-generation EGFR-TKI in patients with EGFR-mutant NSCLC.","PeriodicalId":21766,"journal":{"name":"Signal Transduction and Targeted Therapy","volume":"25 1","pages":""},"PeriodicalIF":39.3,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142782824","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

Integration of novel biomarkers in prospective trials: biological insights from CHOICE-01

IF 39.3 1区医学

Signal Transduction and Targeted Therapy Pub Date : 2024-12-05 DOI: 10.1038/s41392-024-02078-7

Edward Christopher Dee, Puneeth Iyengar

引用次数: 0

Inside help for brain tumors: macrophage-mediated myelin recycling promotes cell state-specific glioblastoma progression

IF 39.3 1区医学

Signal Transduction and Targeted Therapy Pub Date : 2024-12-04 DOI: 10.1038/s41392-024-02055-0

Antonio C. Pagano Zottola, Thomas Daubon, Varun Venkataramani

引用次数: 0

Efficacy and safety of minocycline in retinitis pigmentosa: a prospective, open-label, single-arm trial

IF 39.3 1区医学

Signal Transduction and Targeted Therapy Pub Date : 2024-12-04 DOI: 10.1038/s41392-024-02037-2

Yuxi Chen, Yuan Pan, Yanyan Xie, Yuxun Shi, Yao Lu, Yiwen Xia, Wenru Su, Xiaoqing Chen, Zuoyi Li, Minzhen Wang, Siyu Miao, Yating Yang, Chenjin Jin, Guangwei Luo, Shixian Long, Hui Xiao, Chuangxin Huang, Jian Zhang, Dan Liang

{"title":"Efficacy and safety of minocycline in retinitis pigmentosa: a prospective, open-label, single-arm trial","authors":"Yuxi Chen, Yuan Pan, Yanyan Xie, Yuxun Shi, Yao Lu, Yiwen Xia, Wenru Su, Xiaoqing Chen, Zuoyi Li, Minzhen Wang, Siyu Miao, Yating Yang, Chenjin Jin, Guangwei Luo, Shixian Long, Hui Xiao, Chuangxin Huang, Jian Zhang, Dan Liang","doi":"10.1038/s41392-024-02037-2","DOIUrl":"https://doi.org/10.1038/s41392-024-02037-2","url":null,"abstract":"Retinitis pigmentosa (RP) is characterized by progressive photoreceptor cells death accelerated by the proliferation and activation of microglia pathologically. No consensus exists on the treatment. Minocycline is recognized as a microglia inhibitor with great anti-inflammatory and neuro-protective functions. However, efficacy of minocycline in RP patients is lacking. We conducted a prospective, open-label, and single-arm trial, in which daily oral minocycline of 100 mg was administered for 12 months in RP patients with light-adapted 30 Hz flicker electroretinography (ERG) amplitude >0 µV in at least one eye (NCT04068207). The primary outcome was the proportion of participants with improvement in the ERG amplitude at month 12. The secondary outcomes included improvements of the following items: other ERGs amplitudes, visual field, best-corrected visual acuity, contrast sensitivity, color vision, and NEI-VFQ-25. 35 of 288 patients met inclusive criteria were enrolled (median [IQR] age, 36 [31–45] years; 17 female [48.6%]). 32 participants completed all examinations, while 3 participants completed the 12-month online visit via conducting NEI-VFQ-25. The primary outcome showed improvement was 34.3% (12 of 35 [95% CI 19.1–52.2]). Similarly, all secondary outcomes showed improvements. Adverse events were reported in 22 participants (62.9%) and were all resolved without extra medication during the study period. No severe adverse events were recorded. Our findings identified daily oral minocycline of 100 mg for 12 months was beneficial in improving the visual function of RP patients with good safety. This study indicates minocycline may be a promising therapy for RP, but a randomized controlled trial is still needed of further exploration.","PeriodicalId":21766,"journal":{"name":"Signal Transduction and Targeted Therapy","volume":"9 1","pages":""},"PeriodicalIF":39.3,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142763432","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

Chromatin accessibility: biological functions, molecular mechanisms and therapeutic application

IF 39.3 1区医学

Signal Transduction and Targeted Therapy Pub Date : 2024-12-04 DOI: 10.1038/s41392-024-02030-9

Yang Chen, Rui Liang, Yong Li, Lingli Jiang, Di Ma, Qing Luo, Guanbin Song

{"title":"Chromatin accessibility: biological functions, molecular mechanisms and therapeutic application","authors":"Yang Chen, Rui Liang, Yong Li, Lingli Jiang, Di Ma, Qing Luo, Guanbin Song","doi":"10.1038/s41392-024-02030-9","DOIUrl":"https://doi.org/10.1038/s41392-024-02030-9","url":null,"abstract":"The dynamic regulation of chromatin accessibility is one of the prominent characteristics of eukaryotic genome. The inaccessible regions are mainly located in heterochromatin, which is multilevel compressed and access restricted. The remaining accessible loci are generally located in the euchromatin, which have less nucleosome occupancy and higher regulatory activity. The opening of chromatin is the most important prerequisite for DNA transcription, replication, and damage repair, which is regulated by genetic, epigenetic, environmental, and other factors, playing a vital role in multiple biological progresses. Currently, based on the susceptibility difference of occupied or free DNA to enzymatic cleavage, solubility, methylation, and transposition, there are many methods to detect chromatin accessibility both in bulk and single-cell level. Through combining with high-throughput sequencing, the genome-wide chromatin accessibility landscape of many tissues and cells types also have been constructed. The chromatin accessibility feature is distinct in different tissues and biological states. Research on the regulation network of chromatin accessibility is crucial for uncovering the secret of various biological processes. In this review, we comprehensively introduced the major functions and mechanisms of chromatin accessibility variation in different physiological and pathological processes, meanwhile, the targeted therapies based on chromatin dynamics regulation are also summarized.","PeriodicalId":21766,"journal":{"name":"Signal Transduction and Targeted Therapy","volume":"261 1","pages":""},"PeriodicalIF":39.3,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142763427","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

Liquid biopsy in cancer current: status, challenges and future prospects

IF 39.3 1区医学

Signal Transduction and Targeted Therapy Pub Date : 2024-12-02 DOI: 10.1038/s41392-024-02021-w

Liwei Ma, Huiling Guo, Yunxiang Zhao, Zhibo Liu, Chenran Wang, Jiahao Bu, Ting Sun, Jianwei Wei

{"title":"Liquid biopsy in cancer current: status, challenges and future prospects","authors":"Liwei Ma, Huiling Guo, Yunxiang Zhao, Zhibo Liu, Chenran Wang, Jiahao Bu, Ting Sun, Jianwei Wei","doi":"10.1038/s41392-024-02021-w","DOIUrl":"https://doi.org/10.1038/s41392-024-02021-w","url":null,"abstract":"Cancer has a high mortality rate across the globe, and tissue biopsy remains the gold standard for tumor diagnosis due to its high level of laboratory standardization, good consistency of results, relatively stable samples, and high accuracy of results. However, there are still many limitations and drawbacks in the application of tissue biopsy in tumor. The emergence of liquid biopsy provides new ideas for early diagnosis and prognosis of tumor. Compared with tissue biopsy, liquid biopsy has many advantages in the diagnosis and treatment of various types of cancer, including non-invasive, quickly and so on. Currently, the application of liquid biopsy in tumor detection has received widely attention. It is now undergoing rapid progress, and it holds significant potential for future applications. Around now, liquid biopsies encompass several components such as circulating tumor cells, circulating tumor DNA, exosomes, microRNA, circulating RNA, tumor platelets, and tumor endothelial cells. In addition, advances in the identification of liquid biopsy indicators have significantly enhanced the possibility of utilizing liquid biopsies in clinical settings. In this review, we will discuss the application, advantages and challenges of liquid biopsy in some common tumors from the perspective of diverse systems of tumors, and look forward to its future development prospects in the field of cancer diagnosis and treatment.","PeriodicalId":21766,"journal":{"name":"Signal Transduction and Targeted Therapy","volume":"203 1","pages":""},"PeriodicalIF":39.3,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142758199","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

Phosphorylation determines the glucose metabolism reprogramming and tumor-promoting activity of sine oculis homeobox 1

IF 39.3 1区医学

Signal Transduction and Targeted Therapy Pub Date : 2024-12-02 DOI: 10.1038/s41392-024-02034-5

Yanni Lin, Ling Li, Bin Yuan, Fei Luo, Xiujuan Zhang, Yuanjun Yang, Shaliu Luo, Jing Lin, Tianxing Ye, Youzhi Zhang, Shan Gao, Qinong Ye

{"title":"Phosphorylation determines the glucose metabolism reprogramming and tumor-promoting activity of sine oculis homeobox 1","authors":"Yanni Lin, Ling Li, Bin Yuan, Fei Luo, Xiujuan Zhang, Yuanjun Yang, Shaliu Luo, Jing Lin, Tianxing Ye, Youzhi Zhang, Shan Gao, Qinong Ye","doi":"10.1038/s41392-024-02034-5","DOIUrl":"https://doi.org/10.1038/s41392-024-02034-5","url":null,"abstract":"Aerobic glycolysis is a hallmark of cancer and is regulated by growth factors, protein kinases and transcription factors. However, it remains poorly understood how these components interact to regulate aerobic glycolysis coordinately. Here, we show that sine oculis homeobox 1 (SIX1) phosphorylation integrates growth factors (e.g. TGFβ, EGF) to control aerobic glycolysis and determines its tumor-promoting activity. SIX1 is phosphorylated at serine 225 (S225) by growth factors-activated protein kinases ERK1/2 and its phosphorylation is responsible for glycolysis stimulated by some growth factors. SIX1 is dephosphorylated by the atypical protein phosphatase eyes absent 4 (EYA4). Phosphorylation blocks non-canonical ubiquitination and degradation of SIX1 through the E3 ubiquitin ligase FZR1. Unexpectedly, the non-canonical phosphorylation mimic SIX1 (S225K), but not the canonical phosphorylation mimic SIX1 (S225D/E), phenocopies the effects of SIX1 phosphorylation on glycolysis and cancer cell growth and metastasis in vitro and in mice. Compared to normal liver tissues, SIX1 phosphorylation at S225 (pS225) is upregulated in human liver cancer tissues. ERK1/2 expression is positively correlated with pS225 and EYA4 expression is negatively associated with pS225 in liver cancer specimens. Moreover, low expression of pS225 had longer disease-free survival and overall survival in patients with liver cancer. Thus, we identify a common mechanism underlying growth factors-mediated glycolysis, and provide a previously unidentified mode for non-classical phosphorylation mimics of a protein. Targeting growth factors/SIX1 signaling pathway may be beneficial to cancer treatment.","PeriodicalId":21766,"journal":{"name":"Signal Transduction and Targeted Therapy","volume":"11 1","pages":""},"PeriodicalIF":39.3,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142758201","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

BRAF inhibitors enhance erythropoiesis and treat anemia through paradoxical activation of MAPK signaling

IF 39.3 1区医学

Signal Transduction and Targeted Therapy Pub Date : 2024-12-02 DOI: 10.1038/s41392-024-02033-6

Shunkang Wu, Yuelin Deng, Haobo Sun, Xuewen Liu, Shuo Zhou, Hanxi Zhao, Huan Li, Fusheng Guo, Qiuyu Yue, Fan Wu, Xinying Zhao, Na Li, Shicong Zhu, Qi Hu, Si Xie, Jie Zheng, Meng Lv, Yuan Kong, Xiao-Jun Huang, Xiaoguang Lei, Xiangmin Tong, Xiaofei Gao, Hsiang-Ying Lee

{"title":"BRAF inhibitors enhance erythropoiesis and treat anemia through paradoxical activation of MAPK signaling","authors":"Shunkang Wu, Yuelin Deng, Haobo Sun, Xuewen Liu, Shuo Zhou, Hanxi Zhao, Huan Li, Fusheng Guo, Qiuyu Yue, Fan Wu, Xinying Zhao, Na Li, Shicong Zhu, Qi Hu, Si Xie, Jie Zheng, Meng Lv, Yuan Kong, Xiao-Jun Huang, Xiaoguang Lei, Xiangmin Tong, Xiaofei Gao, Hsiang-Ying Lee","doi":"10.1038/s41392-024-02033-6","DOIUrl":"https://doi.org/10.1038/s41392-024-02033-6","url":null,"abstract":"Erythropoiesis is a crucial process in hematopoiesis, yet it remains highly susceptible to disruption by various diseases, which significantly contribute to the global challenges of anemia and blood shortages. Current treatments like erythropoietin (EPO) or glucocorticoids often fall short, especially for hereditary anemias such as Diamond-Blackfan anemia (DBA). To uncover new erythropoiesis-stimulating agents, we devised a screening system using primary human hematopoietic stem and progenitor cells (HSPCs). We discovered that BRAF inhibitors (BRAFi), commonly used to treat BRAFV600E melanoma, can unexpectedly and effectively promote progenitor cell proliferation by temporarily delaying erythroid differentiation. Notably, these inhibitors exhibited pronounced efficacy even under cytokine-restricted conditions and in patient samples of DBA. Mechanistically, although these BRAFi inhibit the MAPK cascade in BRAFV600E mutant cells, they paradoxically act as amplifiers in wild-type BRAF cells, potently enhancing the cascade. Furthermore, we found that while the oncogenic BRAFV600E mutation disrupts hematopoiesis and erythropoiesis through AP-1 hyperactivation, BRAFi minimally impact HSPC self-renewal and differentiation. In vivo studies have shown that BRAFi can enhance human hematopoiesis and erythropoiesis in severe immunodeficient mouse models and alleviate anemia in the Rpl11 haploinsufficiency DBA model, as well as other relevant anemia models. This discovery underscores the role of the MAPK pathway in hematopoiesis and positions BRAFi as a promising therapeutic option for improving hematopoietic reconstitution and treating anemias, including DBA.","PeriodicalId":21766,"journal":{"name":"Signal Transduction and Targeted Therapy","volume":"21 1","pages":""},"PeriodicalIF":39.3,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142758257","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