Oncogene最新文献

{"title":"PrPC controls epithelial-to-mesenchymal transition in EGFR-mutated NSCLC: implications for TKI resistance and patient follow-up","authors":"Claire Lailler, Audrey Didelot, Simon Garinet, Hugo Berthou, Marine Sroussi, Aurélien de Reyniès, Shoukat Dedhar, Séverine Martin-Lannerée, Elizabeth Fabre, Françoise Le Pimpec-Barthes, Alexandre Perrier, Virginie Poindessous, Audrey Mansuet-Lupo, Fatima Djouadi, Jean-Marie Launay, Pierre Laurent-Puig, Hélène Blons, Sophie Mouillet-Richard","doi":"10.1038/s41388-024-03130-0","DOIUrl":"10.1038/s41388-024-03130-0","url":null,"abstract":"Patients with EGFR-mutated non-small cell lung cancer (NSCLC) benefit from treatment with tyrosine kinase inhibitors (TKI) targeting EGFR. Despite improvements in patient care, especially with the 3rd generation TKI osimertinib, disease relapse is observed in all patients. Among the various processes involved in TKI resistance, epithelial-to-mesenchymal transition (EMT) is far from being fully characterized. We hypothesized that the cellular prion protein PrPC could be involved in EMT and EGFR-TKI resistance in NSCLC. Using 5 independent lung adenocarcinoma datasets, including our own cohort, we document that the expression of the PRNP gene encoding PrPC is associated with EMT. By manipulating the levels of PrPC in different EGFR-mutated NSCLC cell lines, we firmly establish that the expression of PrPC is mandatory for cells to maintain or acquire a mesenchymal phenotype. Mechanistically, we show that PrPC operates through an ILK-RBPJ cascade, which also controls the expression of EGFR. Our data further demonstrate that PrPC levels are elevated in EGFR-mutated versus wild-type tumours or upon EGFR activation in vitro. In addition, we provide evidence that PRNP levels increase with TKI resistance and that reducing PRNP expression sensitizes cells to osimertinib. Finally, we found that plasma PrPC levels are increased in EGFR-mutated NSCLC patients from 2 independent cohorts and that their longitudinal evolution mirrors that of disease. Altogether, these findings define PrPC as a candidate driver of EMT-dependent resistance to EGFR-TKI in NSCLC. They further suggest that monitoring plasma PrPC levels may represent a valuable non-invasive strategy for patient follow-up and warrant considering PrPC-targeted therapies for EGFR-mutated NSCLC patients with TKI failure.","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":null,"pages":null},"PeriodicalIF":6.9,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41388-024-03130-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141988422","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":"scRNA‐seq reveals the landscape of immune repertoire of PBMNCs in iMCD","authors":"Xuejiao Yin, Yi Liu, Zuopo Lv, Shengnan Ding, Liya Ma, Min Yang, Meiqiu Yao, Li Zhu, Shuqi Zhao, Yu Chen, Jiaying Ge, Hongyan Tong, Haitao Meng, Liangshun You","doi":"10.1038/s41388-024-03128-8","DOIUrl":"10.1038/s41388-024-03128-8","url":null,"abstract":"The etiology of idiopathic multicentric Castleman disease (iMCD) is poorly understood, and the identification of targetable disease mediators remains an unmet clinical need. Thus, we firstly employed single-cell RNA sequencing (scRNA-seq) to elucidate the landscape of the immune repertoire of peripheral blood mononuclear cells (PBMNCs) in iMCD and to identify additional driver cytokines/cells/pathways to address IL-6 blockade-refractory cases. We revealed that the inflammatory cytokine storm observed in iMCD was a significant phenomenon pervasive across all immune cells. B-plasma cell subsets was the main source of IL-6. The IL-6 signaling pathway was significantly activated across a spectrum of immune cells. Systemic upregulation of CXCL13 is mainly driven by peripheral helper T (Tph) and regulatory T (Treg) cells. Notably, a significant positive interaction was observed between CXCL13-expressing T cells and IL‐6 signaling-activated B cells. This study provides an immune perspective on PBMNCs in iMCD at the single-cell level, unveiling pathways or targets characterized by atypical inflammatory expression that could potentially serve as promising candidates for therapeutic intervention in iMCD.","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":null,"pages":null},"PeriodicalIF":6.9,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41388-024-03128-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141988423","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":"Hypoxia-induced LAMB2-enriched extracellular vesicles promote peritoneal metastasis in gastric cancer via the ROCK1-CAV1-Rab11 axis","authors":"Dongyang Li, Yue Jin, Xin He, Jian Deng, Wenqing Lu, Zichang Yang, Xueying Zheng, Kezuo Hou, Shiying Tang, Bowen Bao, Jie Ren, Xiaojie Zhang, Jin Wang, Hongfei Yan, Xiujuan Qu, Yunpeng Liu, Xiaofang Che","doi":"10.1038/s41388-024-03124-y","DOIUrl":"10.1038/s41388-024-03124-y","url":null,"abstract":"Peritoneal metastasis is one of the most common risk factors contributing to the poor prognosis of gastric cancer. We previously reported that extracellular vesicles from gastric cancer cells could facilitate peritoneal metastasis. However, their impact on gastric cancer-induced peritoneal metastasis under hypoxic conditions remains unclear. This study aims to elucidate how hypoxia-resistant gastric cancer cell-derived extracellular vesicles affect the peritoneal metastasis of normoxic gastric cancer cells. Proteomic analysis revealed elevated levels of Caveolin1 and Laminin β2 in hypoxia-resistant gastric cancer cells and their corresponding extracellular vesicles. Importantly, Caveolin1 was found to play a central role in mediating Laminin β2 sorting into extracellular vesicles derived from hypoxia-resistant gastric cancer cells, and subsequently, extracellular vesicle-associated Laminin β2 promoted peritoneal metastasis in normoxic gastric cancer cells by activating the AKT pathway. Further investigation confirmed that Caveolin1 activation by Rho-related Coiled-coil kinase 1-mediated phosphorylation of Y14 residue is a key factor facilitating Laminin β2 sorting into extracellular vesicles. Moreover, Y14 phosphorylated- Caveolin1 enhanced Laminin β2 sorting by activating Rab11. Finally, our study demonstrated that a combined assessment of plasma extracellular vesicle-associated Caveolin1 and extracellular vesicle-associated Laminin β2 could provide an accurate predictive tool for peritoneal metastasis occurrence in gastric cancer.","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":null,"pages":null},"PeriodicalIF":6.9,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141976287","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":"Spatial proteomic profiling elucidates immune determinants of neoadjuvant chemo-immunotherapy in esophageal squamous cell carcinoma","authors":"Chao Wu, Guoqing Zhang, Lin Wang, Jinlong Hu, Zhongjian Ju, Haitao Tao, Qing Li, Jian Li, Wei Zhang, Jianpeng Sheng, Xiaobin Hou, Yi Hu","doi":"10.1038/s41388-024-03123-z","DOIUrl":"10.1038/s41388-024-03123-z","url":null,"abstract":"Esophageal squamous cell carcinoma (ESCC) presents significant clinical and therapeutic challenges due to its aggressive nature and generally poor prognosis. We initiated a Phase II clinical trial (ChiCTR1900027160) to assess the efficacy of a pioneering neoadjuvant chemo-immunotherapy regimen comprising programmed death-1 (PD-1) blockade (Toripalimab), nanoparticle albumin-bound paclitaxel (nab-paclitaxel), and the oral fluoropyrimidine derivative S-1, in patients with locally advanced ESCC. This study uniquely integrates clinical outcomes with advanced spatial proteomic profiling using Imaging Mass Cytometry (IMC) to elucidate the dynamics within the tumor microenvironment (TME), focusing on the mechanistic interplay of resistance and response. Sixty patients participated, receiving the combination therapy prior to surgical resection. Our findings demonstrated a major pathological response (MPR) in 62% of patients and a pathological complete response (pCR) in 29%. The IMC analysis provided a detailed regional assessment, revealing that the spatial arrangement of immune cells, particularly CD8+ T cells and B cells within tertiary lymphoid structures (TLS), and S100A9+ inflammatory macrophages in fibrotic regions are predictive of therapeutic outcomes. Employing machine learning approaches, such as support vector machine (SVM) and random forest (RF) analysis, we identified critical spatial features linked to drug resistance and developed predictive models for drug response, achieving an area under the curve (AUC) of 97%. These insights underscore the vital role of integrating spatial proteomics into clinical trials to dissect TME dynamics thoroughly, paving the way for personalized and precise cancer treatment strategies in ESCC. This holistic approach not only enhances our understanding of the mechanistic basis behind drug resistance but also sets a robust foundation for optimizing therapeutic interventions in ESCC.","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":null,"pages":null},"PeriodicalIF":6.9,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41388-024-03123-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141913594","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":"CRISPR-based dissection of microRNA-23a ~ 27a ~ 24-2 cluster functionality in hepatocellular carcinoma","authors":"Mengying Cui, Zhichao Liu, Shuaibin Wang, Sejong Bae, Hua Guo, Jiangbing Zhou, Runhua Liu, Lizhong Wang","doi":"10.1038/s41388-024-03115-z","DOIUrl":"10.1038/s41388-024-03115-z","url":null,"abstract":"The miR-23a ~ 27a ~ 24-2 cluster, commonly upregulated in diverse cancers, including hepatocellular carcinoma (HCC), raises questions about the specific functions of its three mature miRNAs and their integrated function. Utilizing CRISPR knockout (KO), CRISPR interference (CRISPRi), and CRISPR activation (CRISPRa) technologies, we established controlled endogenous miR-23a ~ 27 ~ a24-2 cell models to unravel their roles and signaling pathways in HCC. Both miR-23a KO and miR-27a KO displayed reduced cell growth in vitro and in vivo, revealing an integrated oncogenic function. Functional analysis indicated cell cycle arrest, particularly at the G2/M phase, through the downregulation of CDK1/cyclin B activation. High-throughput RNA-seq, combined with miRNA target prediction, unveiled the miR-23a/miR-27a-regulated gene network, validated through diverse technologies. While miR-23a and miR-27a exhibited opposing roles in cell migration and mesenchymal-epithelial transition, an integrated CRISPRi/a analysis suggested an oncogenic role of the miR-23a ~ 27a ~ 24-2 cluster in cell migration. This involvement potentially encompasses two signaling axes: miR-23a-BMPR2 and miR-27a-TMEM170B in HCC cells. In conclusion, our CRISPRi/a study provides a valuable tool for comprehending the integrated roles and underlying mechanisms of endogenous miRNA clusters, paving the way for promising directions in miRNA-targeted therapy interventions.","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":null,"pages":null},"PeriodicalIF":6.9,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41388-024-03115-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141902519","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":"A noncanonical E3 ubiquitin ligase RNF41-mediated MYO1C stability promotes prostate cancer metastasis by inducing actin remodeling","authors":"Situ Xiong, Sheng Li, Zhongqi Li, Yanping Song, Lin Yang, Hailang Yang, Jing Xiong, Wang Pan, Ju Guo, Bin Fu, Songhui Xu","doi":"10.1038/s41388-024-03120-2","DOIUrl":"10.1038/s41388-024-03120-2","url":null,"abstract":"Prostate cancer bone metastasis is a predominant cause of death for prostate cancer (PCa) patients. However, the underlying mechanisms are poorly understood. Here, we report that high levels of RNF41 are associated with metastatic human prostate cancer. RNF41 silencing inhibits prostate cancer cell growth, cell migration and invasion in vitro and in vivo. Mechanistically, we identify that RNF41 induces K27- and K63-linked noncanonical polyubiquitination of MYO1C to enhance its stability and induce actin remodeling, which promotes PCa bone metastasis. RNF41 was significantly upregulated in metastatic prostate cancer tissues and positively associated with MYO1C expression. Furthermore, we show in intraarterial injected-bone metastasis xenograft model that targeting MYO1C stability by inhibition of RNF41 markedly suppressed PCa bone metastasis. Collectively, our findings identify RNF41 is an important regulator of prostate cancer cell growth and metastasis and targeting RNF41/MYO1C could be a valuable strategy to ameliorate prostate cancer progression and metastasis.","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":null,"pages":null},"PeriodicalIF":6.9,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141902517","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":"EZH2 PROTACs target EZH2- and FOXM1-associated oncogenic nodes, suppressing breast cancer cell growth","authors":"Joshua Corbin, Xufen Yu, Jian Jin, Ling Cai, Gang Greg Wang","doi":"10.1038/s41388-024-03119-9","DOIUrl":"10.1038/s41388-024-03119-9","url":null,"abstract":"Breast cancer (BC) remains the second leading cause of cancer-related mortalities in women. Resistance to hormone therapies such as tamoxifen, an estrogen receptor (ER) inhibitor, is a major hurdle in the treatment of BC. Enhancer of zeste homolog 2 (EZH2), the methyltransferase component of the Polycomb repressive complex 2 (PRC2), has been implicated in tamoxifen resistance. Evidence suggests that EZH2 often functions noncanonically, in a methyltransferase-independent manner, as a transcription coactivator through interacting with oncogenic transcription factors. Unlike methyltransferase inhibitors, proteolysis targeting chimeras (PROTAC) can suppress both activating and repressive functions of EZH2. Here, we find that EZH2 PROTACs, MS177 and MS8815, effectively inhibited the growth of BC cells, including those with acquired tamoxifen resistance, to a much greater degree when compared to methyltransferase inhibitors. Mechanistically, EZH2 associates with forkhead box M1 (FOXM1) and binds to the promoters of FOXM1 target genes. EZH2 PROTACs induce degradation of both EZH2 and FOXM1, leading to reduced expression of target genes involved in cell cycle progression and tamoxifen resistance. Together, this study supports that EZH2-targeted PROTACs represent a promising avenue of research for the future treatment of BC, including in the setting of tamoxifen resistance.","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":null,"pages":null},"PeriodicalIF":6.9,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41388-024-03119-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141902520","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":"CCL2 mediated IKZF1 expression promotes M2 polarization of glioma-associated macrophages through CD84-SHP2 pathway","authors":"Yifu Song, Yaochuan Zhang, Zixun Wang, Yibin Lin, Xu Cao, Xiaodi Han, Guangyu Li, Ana Hou, Sheng Han","doi":"10.1038/s41388-024-03118-w","DOIUrl":"10.1038/s41388-024-03118-w","url":null,"abstract":"The proneural-mesenchymal (PN-MES) transformation of glioma stem cells (GSCs) can significantly increase proliferation, invasion, chemotherapy tolerance, and recurrence. M2-like polarization of tumor-associated macrophages (TAMs) has a strong immunosuppressive effect, promoting tumor malignancy and angiogenesis. There is limited understanding on the interactions between GSCs and TAMs as well as their associated molecular mechanisms. In the present study, bioinformatics analysis, GSC and TAM co-culture, determination of TAM polarization phenotypes, and other in vitro experiments confirmed that CCL2 secreted by MES-GSCs promotes TAM-M2 polarization via the IKZF1-CD84-SHP2 pathway and PN-MES transformation of GSCs via the IKZF1-LRG1 pathway in TAMs. IKZF1 inhibitors could significantly reduce tumor volumes in animal glioma models and improve survival, as well as suppress TAM-M2 polarization and the GSC malignant phenotype. The results of this study indicate the important interaction between TAMs and GSCs in the glioma microenvironment as well as its role in tumor progression. The findings also suggest a novel target for follow-up clinical transformation research on the regulation of TAM function and GSCs malignant phenotype.","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":null,"pages":null},"PeriodicalIF":6.9,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41388-024-03118-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141902518","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":"RHNO1: at the crossroads of DNA replication stress, DNA repair, and cancer","authors":"Niphat Jirapongwattana, Samuel F. Bunting, Donald R. Ronning, Gargi Ghosal, Adam R. Karpf","doi":"10.1038/s41388-024-03117-x","DOIUrl":"10.1038/s41388-024-03117-x","url":null,"abstract":"The DNA replication stress (DRS) response is a crucial homeostatic mechanism for maintaining genome integrity in the face of intrinsic and extrinsic barriers to DNA replication. Importantly, DRS is often significantly increased in tumor cells, making tumors dependent on the cellular DRS response for growth and survival. Rad9-Hus1-Rad1 Interacting Nuclear Orphan 1 (RHNO1), a protein involved in the DRS response, has recently emerged as a potential therapeutic target in cancer. RHNO1 interacts with the 9-1-1 checkpoint clamp and TopBP1 to activate the ATR/Chk1 signaling pathway, the crucial mediator of the DRS response. Moreover, RHNO1 was also recently identified as a key facilitator of theta-mediated end joining (TMEJ), a DNA repair mechanism implicated in cancer progression and chemoresistance. In this literature review, we provide an overview of our current understanding of RHNO1, including its structure, function in the DRS response, and role in DNA repair, and discuss its potential as a cancer therapeutic target. Therapeutic targeting of RHNO1 holds promise for tumors with elevated DRS as well as tumors with DNA repair deficiencies, including homologous recombination DNA repair deficient (HRD) tumors. Further investigation into RHNO1 function in cancer, and development of approaches to target RHNO1, are expected to yield novel strategies for cancer treatment.","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":null,"pages":null},"PeriodicalIF":6.9,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41388-024-03117-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141897939","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":"CircVPS8 promotes the malignant phenotype and inhibits ferroptosis of glioma stem cells by acting as a scaffold for MKRN1, SOX15 and HNF4A","authors":"Jinpeng Hu, Xinqiao Li, Kai Xu, Junhua Chen, Shengliang Zong, Haiying Zhang, Hao Li, Guoqing Zhang, Zhengting Guo, Xiang Zhao, Yang Jiang, Zhitao Jing","doi":"10.1038/s41388-024-03116-y","DOIUrl":"10.1038/s41388-024-03116-y","url":null,"abstract":"Exciting breakthroughs have been achieved in the field of glioblastoma with therapeutic interventions targeting specific ferroptosis targets. Nonetheless, the precise mechanisms through which circRNAs regulate the ferroptosis pathway have yet to be fully elucidated. Here we have identified a novel circRNA, circVPS8, which is highly expressed in glioblastoma. Our findings demonstrated that circVPS8 enhances glioma stem cells’ viability, proliferation, sphere-forming ability, and stemness. Additionally, it inhibits ferroptosis in GSCs. In vivo, experiments further supported the promotion of glioblastoma growth by circVPS8. Mechanistically, circVPS8 acts as a scaffold, binding to both MKRN1 and SOX15, thus facilitating the ubiquitination of MKRN1 and subsequent degradation of SOX15. Due to competitive binding, the ubiquitination ability of MKRN1 towards HNF4A is reduced, leading to elevated HNF4A expression. Increased HNF4A expression, along with decreased SOX15 expression, synergistically inhibits ferroptosis in glioblastoma. Overall, our study highlights circVPS8 as a promising therapeutic target and provides valuable insights for clinically targeted therapy of glioblastoma.","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":null,"pages":null},"PeriodicalIF":6.9,"publicationDate":"2024-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141889823","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}