Cell Cycle最新文献_第6页

OTUD5 promotes AML progression by stabilizing SLC7A11 to suppress ferroptosis. OTUD5通过稳定SLC7A11抑制铁下垂来促进AML进展。

IF 3.9 3区生物学

Cell Cycle Pub Date : 2026-12-01 Epub Date: 2026-06-23 DOI: 10.1080/15384101.2026.2687836

Xiaowan Chen, Bingjie Zhao, Wenjing Yang, Zhenzhen Sun, Meng Hu, Pei Xu, Jia Guo, Tao Jiang

{"title":"OTUD5 promotes AML progression by stabilizing SLC7A11 to suppress ferroptosis.","authors":"Xiaowan Chen, Bingjie Zhao, Wenjing Yang, Zhenzhen Sun, Meng Hu, Pei Xu, Jia Guo, Tao Jiang","doi":"10.1080/15384101.2026.2687836","DOIUrl":"10.1080/15384101.2026.2687836","url":null,"abstract":"Acute myeloid leukemia (AML) is a highly aggressive malignancy with frequent therapeutic resistance, necessitating the identification of novel molecular targets. This study aims to elucidate the role of the deubiquitinase OTUD5 in AML progression by regulating SLC7A11 to suppress ferroptosis. We analyzed OTUD5 expression in AML patient samples and cell lines using RNA sequencing and quantitative PCR. Functional roles were assessed through OTUD5 silencing and overexpression in AML cell lines (THP-1, HL-60), followed by proliferation, colony formation, and ferroptosis assays (ROS, labile Fe2 +, GSH, MDA). Co-immunoprecipitation and ubiquitination assays confirmed OTUD5-SLC7A11 interactions, while in vivo xenograft models validated findings. Molecular docking and transmission electron microscopy further elucidated mechanisms. OTUD5 was significantly upregulated in AML, correlating with ferroptosis suppression. OTUD5 directly interacted with and deubiquitinated SLC7A11, enhancing its stability and promoting AML cell survival. OTUD5 silencing induced ferroptosis, marked by increased labile iron, ROS, and mitochondrial damage, which was reversed by SLC7A11 overexpression or GSH supplementation. In vivo, OTUD5 knockdown reduced tumor growth, an effect mitigated by SLC7A11 overexpression or GSH. The OTUD5-SLC7A11 axis drives AML progression by suppressing ferroptosis, offering a novel therapeutic target to exploit ferroptosis sensitivity and overcome treatment resistance in AML.","PeriodicalId":9686,"journal":{"name":"Cell Cycle","volume":"25 1","pages":"1-15"},"PeriodicalIF":3.9,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13313254/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148301142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A paradox in the evolution of HipHop-HOAP and telomere integrity. HipHop-HOAP和端粒完整性进化中的悖论。

IF 3.4 3区生物学

Cell Cycle Pub Date : 2026-12-01 Epub Date: 2026-01-18 DOI: 10.1080/15384101.2026.2618667

Qi Cao, Yuange Duan

引用次数: 0

Cell cycle-regulated expression of Fam72a from the |Srgap2-Fam72a| master gene leads to Mis18a downregulation. Srgap2-Fam72a|主基因在细胞周期中调控Fam72a的表达，导致Mis18a下调。

IF 3.9 3区生物学

Cell Cycle Pub Date : 2026-12-01 Epub Date: 2025-12-18 DOI: 10.1080/15384101.2025.2602824

Tuan Hoang Anh Nguyen, Pok-Son Kim, Arne Kutzner, Klaus Heese

{"title":"Cell cycle-regulated expression of Fam72a from the |Srgap2-Fam72a| master gene leads to Mis18a downregulation.","authors":"Tuan Hoang Anh Nguyen, Pok-Son Kim, Arne Kutzner, Klaus Heese","doi":"10.1080/15384101.2025.2602824","DOIUrl":"10.1080/15384101.2025.2602824","url":null,"abstract":"The novel |Srgap2-Fam72a| master gene, comprising SLIT-ROBO Rho GTPase-activating protein 2 (Srgap2) and family with sequence similarity 72 member A (Fam72a), has attracted attention for its potential role in regulating brain plasticity and supporting advanced cognitive functions in humans. Moreover, recent studies have identified Fam72a as a new cell cycle-regulated gene. In this study, we investigated the activity of the intergenic region (IGR) between the native Srgap2 and Fam72a gene pair and the signaling pathways of Fam72a upon mitogen epidermal growth factor (Egf) stimulation. We found that, under mitogen Egf stimulation, the IGR functions as a divergent promoter, simultaneously driving the transcription of Srgap2 and Fam72a in opposite directions. Furthermore, Fam72a downregulates MIS18 kinetochore protein A (Mis18a), a tightly cell cycle-regulated gene, and interferes with the RAC-alpha serine/threonine-protein kinase (Akt1) signaling pathway by downregulating phosphorylated Akt1 at Serine 473, thereby favoring the more direct mitogen activated protein kinase 1 (Mapk1) route to promote cellular proliferation. These findings provide insight into the role of Fam72a during the cell cycle and suggest that it may contribute to the proliferation of neural stem cells (NSCs).","PeriodicalId":9686,"journal":{"name":"Cell Cycle","volume":" ","pages":"1-13"},"PeriodicalIF":3.9,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12915885/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145780359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

An updated view on lagging strand DNA replication: implications for the replication stress response. 后链DNA复制的最新观点：对复制应激反应的影响。

IF 3.9 3区生物学

Cell Cycle Pub Date : 2026-12-01 Epub Date: 2026-03-22 DOI: 10.1080/15384101.2026.2646889

Rodrigo Martín-Rufo, Emilio Lecona

{"title":"An updated view on lagging strand DNA replication: implications for the replication stress response.","authors":"Rodrigo Martín-Rufo, Emilio Lecona","doi":"10.1080/15384101.2026.2646889","DOIUrl":"10.1080/15384101.2026.2646889","url":null,"abstract":"The process of DNA replication is inherently asymmetric. While the leading strand is synthesized continuously, the lagging strand is copied in small fragments, the Okazaki fragments, requiring the repeated priming by the DNA polymerase alpha/Primase complex (Pol α/Pri). Current evidence is consistent with a semi-distributive model for priming in the lagging strand, as Pol α/Pri acts associated to the replisome and also as a free complex. In addition, there is a strong link between the dynamics of replication in the lagging strand and the basal activation of the replication stress response (RSR) during an unperturbed S phase. We hypothesize that the RSR monitors the generation of Okazaki fragments to control the synthesis of DNA in what we call the DNA replication control (DRC) mode of the RSR. The DRC enforces a gradual progression of DNA replication by restricting origin firing, what is necessary to establish the replication program in the cell and to prevent the appearance of genomic instability. Thus, the RSR coordinates the replication program in the cell, modulating the progression of DNA replication to prevent the exhaustion of cellular resources that would endanger the stability of the genome.","PeriodicalId":9686,"journal":{"name":"Cell Cycle","volume":"25 1","pages":"1-16"},"PeriodicalIF":3.9,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13007448/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147493814","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Amplification of pro-proliferative genes adjacent to the F3 gene in pancreatic adenocarcinoma is associated with worse outcomes. 胰腺腺癌中F3基因附近的促增殖基因扩增与较差的预后相关。

IF 3.9 3区生物学

Cell Cycle Pub Date : 2026-12-01 Epub Date: 2026-05-21 DOI: 10.1080/15384101.2026.2674084

Sreenidhi Nidamanur, Teresa M Thomas, Sami A Soliman, Michael T Aboujaoude, George Blanck

{"title":"Amplification of pro-proliferative genes adjacent to the F3 gene in pancreatic adenocarcinoma is associated with worse outcomes.","authors":"Sreenidhi Nidamanur, Teresa M Thomas, Sami A Soliman, Michael T Aboujaoude, George Blanck","doi":"10.1080/15384101.2026.2674084","DOIUrl":"10.1080/15384101.2026.2674084","url":null,"abstract":"While the elevated expression of F3 is known to contribute to a hyper-venous thromboembolism (VTE) state in pancreatic adenocarcinoma (PAAD), the basis for elevated F3 expression remains unexplored. This study investigated whether amplification of the genes, ARHGAP29 and SLC44A3, which are adjacent to F3, could explain the amplification of the F3 gene. Thus, precision-guided copy number variation (CNV) analyses were performed using two PAAD data sets: Clinical Proteomic Tumor Analysis Consortium (CPTAC)-PAAD and The Cancer Genome Atlas (TCGA)-PAAD. Kaplan-Meier (KM) analyses demonstrated that patients representing the upper percentiles of CNs for ARHGAP29 and SLC44A3 had significantly worse overall survival (OS) and disease-free survival (DFS) for CPTAC-PAAD. Trends for the same outcomes for OS were observed for TCGA-PAAD. Pearson's correlation tests for ARHGAP29, F3, and SLC44A3 CNs and MSIsensor scores showed statistical significance, indicating that higher amplification was consistent with greater genomic instability. F3 CNs and the F3 CN-based outcome assessments were consistent with the outcomes based on the increased CNs for ARHGAP29 and SLC44A3, for both CPTAC-PAAD and TCGA-PAAD. These findings raise the question of whether a selection for increased CNs of pro-proliferative genes, with a corresponding increase in F3 CNs, contributes to increased VTE and worse outcomes for PAAD?","PeriodicalId":9686,"journal":{"name":"Cell Cycle","volume":"25 1","pages":"1-12"},"PeriodicalIF":3.9,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13196647/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147980677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

KIBRA impairs DNA damage repair and suppresses osteosarcoma progression by inhibiting the Wnt/β-catenin signaling activity. KIBRA通过抑制Wnt/β-catenin信号活性，损害DNA损伤修复并抑制骨肉瘤进展。

IF 3.9 3区生物学

Cell Cycle Pub Date : 2026-12-01 Epub Date: 2026-05-18 DOI: 10.1080/15384101.2026.2674076

Jingyuan Zhou, Zhenglin Leng, Qiang Guo, Limin Liu, Zengshun Wang, Junfeng Ma, Angxiu Suonan

{"title":"KIBRA impairs DNA damage repair and suppresses osteosarcoma progression by inhibiting the Wnt/β-catenin signaling activity.","authors":"Jingyuan Zhou, Zhenglin Leng, Qiang Guo, Limin Liu, Zengshun Wang, Junfeng Ma, Angxiu Suonan","doi":"10.1080/15384101.2026.2674076","DOIUrl":"10.1080/15384101.2026.2674076","url":null,"abstract":"Kidney and brain expressed protein (KIBRA) has been implicated in various cancers, but its mechanisms in osteosarcoma remain poorly understood. KIBRA expression was analyzed in osteosarcoma datasets and cell lines. Functional assays, including Cell Counting Kit-8, 5-ethynyl-2'-deoxyuridine staining, wound healing, Transwell, and flow cytometry, were performed to assess proliferation, migration, invasion, and apoptosis in osteosarcoma cells after KIBRA overexpression. A subcutaneous xenograft model was established to evaluate tumor growth in vivo. DNA damage response was examined via immunofluorescence staining of the phosphorylated form of histone H2AX (γH2AX) foci and Western blot analysis of RAD51 Recombinase (RAD51) and γH2AX. KIBRA was significantly downregulated in osteosarcoma tissues and cell lines. Overexpression of KIBRA suppressed proliferation, migration, invasion, and DNA damage repair, while promoting apoptosis in osteosarcoma cells. In vivo, KIBRA overexpression inhibited tumor growth and impaired DNA damage repair, as evidenced by increased γH2AX foci and decreased RAD51 expression. Mechanistically, KIBRA inhibited the Wnt/β-catenin signaling activity, and activating this pathway by SKL2001 reversed the inhibitory effects of KIBRA on osteosarcoma progression and DNA damage repair. Therefore, KIBRA acts as a tumor suppressor in osteosarcoma by inhibiting the Wnt/β-catenin signaling activity, thereby impairing DNA damage repair and suppressing malignant progression.","PeriodicalId":9686,"journal":{"name":"Cell Cycle","volume":"25 1","pages":"1-20"},"PeriodicalIF":3.9,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13185461/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147962423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Metformin counteracts lipid accumulation and cell proliferation in hepatocellular carcinoma via regulating METTL3-mediated m⁶A methylation. 二甲双胍通过调节mettl3介导的m6A甲基化来对抗肝细胞癌的脂质积累和细胞增殖。

IF 3.9 3区生物学

Cell Cycle Pub Date : 2026-12-01 Epub Date: 2026-05-03 DOI: 10.1080/15384101.2026.2665248

Yannan Qi, Chuanrui Chen, Yuwei Dai, Zhouyuan Wang, Xinyi Liu, Chenxi Guo, Meina Wang, Zhigang Hu, Hongjie Di

{"title":"Metformin counteracts lipid accumulation and cell proliferation in hepatocellular carcinoma via regulating METTL3-mediated m6A methylation.","authors":"Yannan Qi, Chuanrui Chen, Yuwei Dai, Zhouyuan Wang, Xinyi Liu, Chenxi Guo, Meina Wang, Zhigang Hu, Hongjie Di","doi":"10.1080/15384101.2026.2665248","DOIUrl":"10.1080/15384101.2026.2665248","url":null,"abstract":"Metformin, a first-line antidiabetic drug, has demonstrated anticancer potential in various malignancies, yet its precise mechanisms in hepatocellular carcinoma (HCC) remain incompletely defined. Here, we show that metformin inhibits lipid accumulation and proliferation in HCC cells through modulation of N6-methyladenosine (m6A) RNA methylation. Treatment of HepG2 and Huh7 cells with metformin significantly reduced intracellular triglyceride and cholesterol levels, concomitant with decreased lipid droplet accumulation and impaired cell proliferation. Mechanistically, metformin lowered global m6A methylation by downregulating the m6A methyltransferase Methyltransferase-like 3 (METTL3), while upregulating the demethylase Fat mass and obesity-associated protein (FTO). Functional assays revealed that METTL3 overexpression restored lipid accumulation and proliferation in metformin-treated cells, whereas METTL3 knockdown phenocopied the lipid-lowering and anti-proliferative effects of metformin. Further analyses identified the METTL3/ACC1/FASN axis as a critical downstream pathway, with metformin suppressing m6A modification and expression of Fatty acid synthase (FASN) and Acetyl-CoA carboxylase 1 (ACC1) transcripts - effects reversed by METTL3 overexpression. These findings establish METTL3 as a central mediator of metformin's metabolic and antiproliferative activities in HCC, uncovering a previously unappreciated epitranscriptomic mechanism by which metformin impedes tumor progression.","PeriodicalId":9686,"journal":{"name":"Cell Cycle","volume":"25 1","pages":"1-15"},"PeriodicalIF":3.9,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13155026/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147811693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

RBMS1 enhances PDPK1 mRNA stability to promote multiple myeloma malignancy and M2 macrophage polarization. RBMS1增强PDPK1 mRNA稳定性，促进多发性骨髓瘤恶性和M2巨噬细胞极化。

IF 3.9 3区生物学

Cell Cycle Pub Date : 2026-12-01 Epub Date: 2026-06-11 DOI: 10.1080/15384101.2026.2686804

Yan Liu, Yue-Qi Geng, Li Jiang, Ai-Chun Liu

{"title":"RBMS1 enhances PDPK1 mRNA stability to promote multiple myeloma malignancy and M2 macrophage polarization.","authors":"Yan Liu, Yue-Qi Geng, Li Jiang, Ai-Chun Liu","doi":"10.1080/15384101.2026.2686804","DOIUrl":"10.1080/15384101.2026.2686804","url":null,"abstract":"Multiple myeloma (MM) is an incurable malignancy of bone marrow plasma cells. Tumor-associated macrophages (TAMs) are the predominant immune cells in the bone marrow microenvironment of MM and play important roles in MM. The effect of RBMS1 on MM has not yet been reported. This study aimed to investigate the function of RBMS1 in MM. Through the analysis of GSE datasets, we identified RBMS1 as a potential pathogenic factor in MM. We further investigated the effects of RBMS1 on the proliferation of MM cells (RPMI8226, MM1S, and KMS11) and its regulation of TAM polarization. An animal model was established by intravenous injection of MM cells into 6-week-old male NOG mice. Bioinformatics analyses, including RRA, WGCNA, and GO enrichment, screened for potential pathogenic genes in MM. Kaplan - Meier survival identified RBMS1 as a prognostic marker associated with poor outcomes in MM. Functionally, RBMS1 enhanced MM cell proliferation, colony formation, and cell cycle. Moreover, RBMS1 promoted M2 polarization of macrophages, as evidenced by elevated levels of M2 macrophage markers, as well as increased CCL2 secretion. Consistently, in a male NOD/Shi-scid IL-2 Rγnull mouse xenograft model, RBMS1 accelerated tumor growth and enhanced M2 macrophage polarization. Mechanistically, RBMS1 bound to the 3'UTR of PDPK1 mRNA, enhancing its stability and activating the pro-tumorigenic β-catenin signaling pathway, thereby promoting tumor growth. Collectively, this study is the first to report the functional role of RBMS1 in MM and highlights the importance of the RBMS1/PDPK1/β-catenin signaling axis in MM, providing new insights for basic research on MM.","PeriodicalId":9686,"journal":{"name":"Cell Cycle","volume":"25 1","pages":"1-21"},"PeriodicalIF":3.9,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13274164/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148223435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The role of IL-37 in inflammatory bowel disease and colitis-associated colorectal cancer. IL-37在炎症性肠病和结肠炎相关结直肠癌中的作用

IF 3.9 3区生物学

Cell Cycle Pub Date : 2026-12-01 Epub Date: 2026-07-16 DOI: 10.1080/15384101.2026.2704405

Fen-Na Zhang, Xin-Yi Zhang, Ting-Ting Zhao, Rong-Rong Sun, Meng Huang, Na He

{"title":"The role of IL-37 in inflammatory bowel disease and colitis-associated colorectal cancer.","authors":"Fen-Na Zhang, Xin-Yi Zhang, Ting-Ting Zhao, Rong-Rong Sun, Meng Huang, Na He","doi":"10.1080/15384101.2026.2704405","DOIUrl":"10.1080/15384101.2026.2704405","url":null,"abstract":"Inflammatory bowel disease (IBD) is an idiopathic inflammatory disorder of intestine and a high risk for colorectal cancer; however, its precise etiology and pathogenesis remain poorly understood. Interleukin (IL)-37, a member of IL-1 family, exerts anti-inflammatory effects in various inflammatory diseases and cancers, and is generated by several epithelial cells and immune cells. Mechanistically, IL-37 mediates its anti-inflammatory either by translocating into nucleus in complex with small mother against decapentaplegic homolog 3 or binding to extracellular interleukin-18 receptor and IL-1 receptor-related receptor 8 (IL-1R8), which is abundantly expressed in the gastrointestinal tract. Recently, accumulating evidence has demonstrated that IL-37 expression is upregulated and plays protective roles in IBD and colitis-associated cancer (CAC). This review summarizes the recent advances regarding the expression, biological functions, molecular mechanism, and therapeutic potential of IL-37 in IBD and CAC, aiming to provide novel insights into its underlying mechanism and clinical application.","PeriodicalId":9686,"journal":{"name":"Cell Cycle","volume":"25 1","pages":"1-14"},"PeriodicalIF":3.9,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13378727/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148469138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

ETV2 functions as a pioneer factor and regulates endothelial progenitor cell proliferation. ETV2作为先锋因子，调控内皮祖细胞增殖。

IF 3.9 3区生物学

Cell Cycle Pub Date : 2026-12-01 Epub Date: 2026-09-29 DOI: 10.1080/15384101.2026.2736317

Nicole M Recka, Daniel J Garry

引用次数: 0