Cell structure and function最新文献_第8页

MGSE Regulates Crosstalk from the Mucin Pathway to the TFE3 Pathway of the Golgi Stress Response. MGSE调控高尔基应激反应中从粘蛋白途径到TFE3途径的串扰。

IF 1.5 4区生物学

Cell structure and function Pub Date : 2019-10-19 DOI: 10.1247/csf.19009

Mohamad Ikhwan Jamaludin,Sadao Wakabayashi,Mai Taniguchi,Kanae Sasaki,Ryota Komori,Hirotada Kawamura,Hayataka Takase,Miyu Sakamoto,Hiderou Yoshida

{"title":"MGSE Regulates Crosstalk from the Mucin Pathway to the TFE3 Pathway of the Golgi Stress Response.","authors":"Mohamad Ikhwan Jamaludin,Sadao Wakabayashi,Mai Taniguchi,Kanae Sasaki,Ryota Komori,Hirotada Kawamura,Hayataka Takase,Miyu Sakamoto,Hiderou Yoshida","doi":"10.1247/csf.19009","DOIUrl":"https://doi.org/10.1247/csf.19009","url":null,"abstract":"The Golgi apparatus is an organelle where membrane or secretory proteins receive post-translational modifications such as glycosylation and sulfation, after which the proteins are selectively transported to their final destinations through vesicular transport. When the synthesis of secretory or membrane proteins is increased and overwhelms the capacity of the Golgi (Golgi stress), eukaryotic cells activate a homeostatic mechanism called the Golgi stress response to augment the capacity of the Golgi. Four response pathways of the Golgi stress response have been identified, namely the TFE3, CREB3, HSP47, and proteoglycan pathways, which regulate the general function of the Golgi, apoptosis, cell survival, and proteoglycan glycosylation, respectively. Here, we identified a novel response pathway that augments the expression of glycosylation enzymes for mucins in response to insufficiency in mucin-type glycosylation in the Golgi (mucin-type Golgi stress), and we found that expression of glycosylation enzymes for mucins such as GALNT5, GALNT8, and GALNT18 was increased upon mucin-type-Golgi stress. We named this pathway the mucin pathway. Unexpectedly, mucin-type Golgi stress induced the expression and activation of TFE3, a key transcription factor regulating the TFE3 pathway, suggesting that the activated mucin pathway sends a crosstalk signal to the TFE3 pathway. We identified an enhancer element regulating transcriptional induction of TFE3 upon mucin-type Golgi stress, and named it the mucin-type Golgi stress response element, of which consensus was ACTTCC(N9)TCCCCA. These results suggested that crosstalk from the mucin pathway to the TFE3 pathway has an important role in the regulation of the mammalian Golgi stress response.Key words: Golgi stress, mucin, TFE3, organelle autoregulation, organelle zone.","PeriodicalId":9927,"journal":{"name":"Cell structure and function","volume":"48 3","pages":"137-151"},"PeriodicalIF":1.5,"publicationDate":"2019-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138524159","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Dispersion of endoplasmic reticulum-associated compartments by 4-phenyl butyric acid in yeast cells. 酵母细胞中4-苯基丁酸对内质网相关室的分散作用。

IF 1.5 4区生物学

Cell structure and function Pub Date : 2019-10-17 DOI: 10.1247/csf.19023

T. Mai, Yuki Ishiwata‐Kimata, Q. Le, Hiroyuki Kido, Y. Kimata

{"title":"Dispersion of endoplasmic reticulum-associated compartments by 4-phenyl butyric acid in yeast cells.","authors":"T. Mai, Yuki Ishiwata‐Kimata, Q. Le, Hiroyuki Kido, Y. Kimata","doi":"10.1247/csf.19023","DOIUrl":"https://doi.org/10.1247/csf.19023","url":null,"abstract":"In yeast Saccharomyces cerevisiae cells, some aberrant multimembrane-spanning proteins are not transported to the cell surface but form and are accumulated in endoplasmic reticulum (ER)-derived subcompartments, known as the ER-associated compartments (ERACs), which are observed as puncta under fluorescence microscopy. Here we show that a mutant of the cell surface protein Pma1, Pma1-2308, was accumulated in the ERACs, as well as the heterologously expressed mammalian cystic fibrosis transmembrane conductance regulator (CFTR), in yeast cells. Pma1-2308 and CFTR were located on the same ERACs. We also note that treatment of cells with 4-phenyl butyric acid (4-PBA) compromised the ERAC formation by Pma1-2308 and CFTR, suggesting that 4-PBA exerts a chaperone-like function in yeast cells. Intriguingly, unlike ER stress induced by the canonical ER stressor tunicamycin, ER stress that was induced by Pma1-2308 was aggravated by 4-PBA. We assume that this observation demonstrates a beneficial aspect of ERACs, and thus propose that the ERACs are formed through aggregation of aberrant transmembrane proteins and work as the accumulation sites of multiple ERAC-forming proteins for their sequestration. Key words: protein aggregation, organelle, unfolded protein response, ER stress, 4-PBA.","PeriodicalId":9927,"journal":{"name":"Cell structure and function","volume":"1 1","pages":""},"PeriodicalIF":1.5,"publicationDate":"2019-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1247/csf.19023","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42456783","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 3

Identification of 15 New Bypassable Essential Genes of Fission Yeast. 裂变酵母15个新的可绕过必需基因的鉴定。

IF 1.5 4区生物学

Cell structure and function Pub Date : 2019-09-27 DOI: 10.1247/csf.19025

Aoi Takeda, Shigeaki Saitoh, Hiroyuki Ohkura, Kenneth E Sawin, Gohta Goshima

{"title":"Identification of 15 New Bypassable Essential Genes of Fission Yeast.","authors":"Aoi Takeda, Shigeaki Saitoh, Hiroyuki Ohkura, Kenneth E Sawin, Gohta Goshima","doi":"10.1247/csf.19025","DOIUrl":"https://doi.org/10.1247/csf.19025","url":null,"abstract":"Every organism has a different set of genes essential for its viability. This indicates that an organism can become tolerant to the loss of an essential gene under certain circumstances during evolution, via the manifestation of 'masked' alternative mechanisms. In our quest to systematically uncover masked mechanisms in eukaryotic cells, we developed an extragenic suppressor screening method using haploid spores deleted of an essential gene in the fission yeast Schizosaccharomyces pombe. We screened for the 'bypass' suppressors of lethality of 92 randomly selected genes that are essential for viability in standard laboratory culture conditions. Remarkably, extragenic mutations bypassed the essentiality of as many as 20 genes (22%), 15 of which have not been previously reported. Half of the bypass-suppressible genes were involved in mitochondria function; we also identified multiple genes regulating RNA processing. 18 suppressible genes were conserved in the budding yeast Saccharomyces cerevisiae, but 13 of them were non-essential in that species. These trends suggest that essentiality bypass is not a rare event and that each organism may be endowed with secondary or backup mechanisms that can substitute for primary mechanisms in various biological processes. Furthermore, the robustness of our simple spore-based methodology paves the way for genome-scale screening.Key words: Schizosaccharomyces pombe, extragenic suppressor screening, bypass of essentiality (BOE), cut7 (kinesin-5), hul5 (E3 ubiquitin ligase).","PeriodicalId":9927,"journal":{"name":"Cell structure and function","volume":"44 2","pages":"113-119"},"PeriodicalIF":1.5,"publicationDate":"2019-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1247/csf.19025","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9295691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Mutations in mxc Tumor-Suppressor Gene Induce Chromosome Instability in Drosophila Male Meiosis. mxc抑癌基因突变诱导果蝇雄性减数分裂染色体不稳定。

IF 1.5 4区生物学

Cell structure and function Pub Date : 2019-09-05 DOI: 10.1247/csf.19022

K. Tanabe, Rie Awane, Tsuyoshi Shoda, Kanta Yamazoe, Y. Inoue

{"title":"Mutations in mxc Tumor-Suppressor Gene Induce Chromosome Instability in Drosophila Male Meiosis.","authors":"K. Tanabe, Rie Awane, Tsuyoshi Shoda, Kanta Yamazoe, Y. Inoue","doi":"10.1247/csf.19022","DOIUrl":"https://doi.org/10.1247/csf.19022","url":null,"abstract":"Drosophila Mxc protein is a component of the histone locus body (HLB), which is required for the expression of canonical histone genes, and severe mxc mutations generate tumors in larval hematopoietic tissues. A common characteristic of cancer cells is chromosomal instability (CIN), but whether mxc mutants exhibit this feature is unknown. Here, examination of post-meiotic spermatids created after male meiosis revealed that a fraction of the spermatids in hypomorphic mxcG46 mutants contained extra micronuclei or abnormally sized nuclei, corresponding to CIN. Moreover, we observed that the so-called lagging chromosomes retained between chromosomal masses separated toward spindle poles at telophase I. Time-lapse recordings show that micronuclei were generated from lagging chromosomes, and the abnormal chromosomes in mxcG46 mutants lacked centromeres. In normal spermatocyte nuclei, the HLB component FLASH colocalized with Mxc, whereas FLASH was dispersed in mxcG46 spermatocyte nuclei. Furthermore, we observed genetic interactions between Mxc and other HLB components in meiotic chromosome segregation, which suggests that inhibition of HLB formation is responsible for aberrant chromosome segregation in mxcG46. Quantitative real-time PCR revealed that canonical histone mRNA levels were decreased in mxcG46. Lastly, similar meiotic phenotypes appeared in the spermatids of histone H4 mutants and in the spermatids in testes depleted for chromosome-construction factors. Considering these genetic data, we propose that abnormal chromosome segregation leading to CIN development results from a loss of chromosome integrity caused by diminished canonical histone levels in mxc mutants. Key words: Chromosome instability, Drosophila, meiosis, tumor-suppressor gene.","PeriodicalId":9927,"journal":{"name":"Cell structure and function","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2019-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1247/csf.19022","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44741624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 8

Implication of a novel function of Sar1 in the nucleus. Sar1在细胞核中的新功能。

IF 1.5 4区生物学

Cell structure and function Pub Date : 2019-08-09 DOI: 10.1247/csf.19019

K. Horikawa, Tomohiro Yorimitsu, C. Kodera, Ken Sato

引用次数: 3

A Peptide Derived from Phosphoinositide 3-kinase Inhibits Endocytosis and Influenza Virus Infection. 磷酸肌肽3-激酶衍生肽抑制内吞作用和流感病毒感染。

IF 1.5 4区生物学

Cell structure and function Pub Date : 2019-04-25 Epub Date: 2019-03-21 DOI: 10.1247/csf.19001

Yoichiro Fujioka, Aya O Satoh, Kosui Horiuchi, Mari Fujioka, Kaori Tsutsumi, Junko Sasaki, Prabha Nepal, Sayaka Kashiwagi, Sarad Paudel, Shinya Nishide, Asuka Nanbo, Takehiko Sasaki, Yusuke Ohba

{"title":"A Peptide Derived from Phosphoinositide 3-kinase Inhibits Endocytosis and Influenza Virus Infection.","authors":"Yoichiro Fujioka, Aya O Satoh, Kosui Horiuchi, Mari Fujioka, Kaori Tsutsumi, Junko Sasaki, Prabha Nepal, Sayaka Kashiwagi, Sarad Paudel, Shinya Nishide, Asuka Nanbo, Takehiko Sasaki, Yusuke Ohba","doi":"10.1247/csf.19001","DOIUrl":"https://doi.org/10.1247/csf.19001","url":null,"abstract":"Endocytosis mediates the internalization and ingestion of a variety of endogenous or exogenous substances, including virus particles, under the control of intracellular signaling pathways. We have previously reported that the complex formed between the small GTPase Ras and phosphoinositide 3-kinase (PI3K) translocates from the plasma membrane to endosomes, signaling from which thereby regulates clathrin-independent endocytosis, endosome maturation, influenza virus internalization, and infection. However, the molecular mechanism by which the Ras-PI3K complex is recruited to endosomes remains unclear. Here, we have identified the amino acid sequence responsible for endosomal localization of the Ras-PI3K complex. PI3K lacking this sequence failed to translocate to endosomes, and expression of the peptide comprising this PI3K-derived sequence inhibited clathrin-independent endocytosis, influenza virus internalization, and infection. Moreover, treatment of cells with this peptide in an arginine-rich, cell-penetrating form successfully suppressed influenza virus infection in vitro and ex vivo, making this peptide a potential therapeutic agent against influenza virus infection.Key words: signal transduction, endocytosis, endosome, imaging, influenza virus.","PeriodicalId":9927,"journal":{"name":"Cell structure and function","volume":"44 1","pages":"61-74"},"PeriodicalIF":1.5,"publicationDate":"2019-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1247/csf.19001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37085971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 6

MiR-187-3p Enhances Propranolol Sensitivity of Hemangioma Stem Cells. MiR-187-3p增强血管瘤干细胞对心得安的敏感性。

IF 1.5 4区生物学

Cell structure and function Pub Date : 2019-03-20 Epub Date: 2019-02-02 DOI: 10.1247/csf.18041

Chao Liu, Zeliang Zhao, Zhidong Ji, Yanyan Jiang, Jiawei Zheng

{"title":"MiR-187-3p Enhances Propranolol Sensitivity of Hemangioma Stem Cells.","authors":"Chao Liu, Zeliang Zhao, Zhidong Ji, Yanyan Jiang, Jiawei Zheng","doi":"10.1247/csf.18041","DOIUrl":"https://doi.org/10.1247/csf.18041","url":null,"abstract":"Infantile hemangioma is the most common soft tissue tumors in childhood. In clinic, propranolol is widely used for infantile hemangioma therapy. However, some of the infantile hemangioma patients display resistance to propranolol treatment. Previous studies show that miR-187-3p is inhibited in hepatocellular carcinoma and lung cancer, while the role of miR-187-3p in infantile hemangioma remains unclear. In the present study, we explore the biological role of miR-187-3p in infantile hemangioma. The mRNA and protein levels of related genes were detected by real-time PCR and Western blotting. CCK8 assay was used to detect cell viability and IC50 values of propranolol. Cell apoptosis was detected by Caspase-3 Activity assay. Luciferase reporter assay and biotin RNA pull down assay were used to detect the interaction between miR-187-3p and the targeted gene. MiR-187-3p was down-regulated in infantile hemangioma tissues and promoted propranolol sensitivity of HemSCs. Mechanically, NIPBL was the direct target of miR-187-3p in HemSCs. NIPBL downregulation inhibited propranolol resistance of HemSCs. Re-introduction of NIPBL reversed miR-187-3p-meidated higher propranolol sensitivity of HemSCs. MiR-187-3p enhanced propranolol sensitivity of hemangioma stem cells via targeting NIPBL. MiR-187-3p may serve as a novel prognostic indicator and potential target for infantile hemangioma therapy.Key words: MiR-187-3p, infantile hemangioma, propranolol, resistance, NIPBL.","PeriodicalId":9927,"journal":{"name":"Cell structure and function","volume":"44 1","pages":"41-50"},"PeriodicalIF":1.5,"publicationDate":"2019-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1247/csf.18041","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36923509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 12

PGSE Is a Novel Enhancer Regulating the Proteoglycan Pathway of the Mammalian Golgi Stress Response. PGSE是调节哺乳动物高尔基应激反应蛋白聚糖途径的新型增强子。

IF 1.5 4区生物学

Cell structure and function Pub Date : 2019-01-11 Epub Date: 2018-11-28 DOI: 10.1247/csf.18031

Kanae Sasaki, Ryota Komori, Mai Taniguchi, Akie Shimaoka, Sachiko Midori, Mayu Yamamoto, Chiho Okuda, Ryuya Tanaka, Miyu Sakamoto, Sadao Wakabayashi, Hiderou Yoshida

{"title":"PGSE Is a Novel Enhancer Regulating the Proteoglycan Pathway of the Mammalian Golgi Stress Response.","authors":"Kanae Sasaki, Ryota Komori, Mai Taniguchi, Akie Shimaoka, Sachiko Midori, Mayu Yamamoto, Chiho Okuda, Ryuya Tanaka, Miyu Sakamoto, Sadao Wakabayashi, Hiderou Yoshida","doi":"10.1247/csf.18031","DOIUrl":"https://doi.org/10.1247/csf.18031","url":null,"abstract":"The Golgi stress response is a homeostatic mechanism that augments the functional capacity of the Golgi apparatus when Golgi function becomes insufficient (Golgi stress). Three response pathways of the Golgi stress response have been identified in mammalian cells, the TFE3, HSP47 and CREB3 pathways, which augment the capacity of specific Golgi functions such as N-glycosylation, anti-apoptotic activity and pro-apoptotic activity, respectively. On the contrary, glycosylation of proteoglycans (PGs) is another important function of the Golgi, although the response pathway upregulating expression of glycosylation enzymes for PGs in response to Golgi stress remains unknown. Here, we found that expression of glycosylation enzymes for PGs was induced upon insufficiency of PG glycosylation capacity in the Golgi (PG-Golgi stress), and that transcriptional induction of genes encoding glycosylation enzymes for PGs was independent of the known Golgi stress response pathways and ER stress response. Promoter analyses of genes encoding these glycosylation enzymes revealed the novel enhancer elements PGSE-A and PGSE-B (the consensus sequences are CCGGGGCGGGGCG and TTTTACAATTGGTC, respectively), which regulate their transcriptional induction upon PG-Golgi stress. From these observations, the response pathway we discovered is a novel Golgi stress response pathway, which we have named the PG pathway.Key words: Golgi stress, proteoglycan, ER stress, organelle zone, organelle autoregulation.","PeriodicalId":9927,"journal":{"name":"Cell structure and function","volume":"44 1","pages":"1-19"},"PeriodicalIF":1.5,"publicationDate":"2019-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1247/csf.18031","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36726626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 13

Organelle Zones. 细胞器区。

IF 1.5 4区生物学

Cell structure and function Pub Date : 2019-01-01 DOI: 10.1247/csf.19010

Kanae Sasaki, Hiderou Yoshida

引用次数: 6

CCL20 Promotes Ovarian Cancer Chemotherapy Resistance by Regulating ABCB1 Expression. CCL20通过调控ABCB1表达促进卵巢癌化疗耐药

IF 1.5 4区生物学

Cell structure and function Pub Date : 2019-01-01 DOI: 10.1247/csf.18029

Shan Su, Xueqin Sun, Qinghua Zhang, Zhe Zhang, Ju Chen

{"title":"CCL20 Promotes Ovarian Cancer Chemotherapy Resistance by Regulating ABCB1 Expression.","authors":"Shan Su, Xueqin Sun, Qinghua Zhang, Zhe Zhang, Ju Chen","doi":"10.1247/csf.18029","DOIUrl":"https://doi.org/10.1247/csf.18029","url":null,"abstract":"Ovarian cancer (OC) is one of prevalent tumors and this study aimed to explore CCL20's effects on doxorubicin resistance of OC and related mechanisms. Doxorubicin-resistant SKOV3 DR cells were established from SKOV3 cells via 6-month continuous exposure to gradient concentrations of doxorubicin. Quantitative PCR and Western blot assay showed that SKOV3 DR cells had higher level of CCL20 than SKOV3 cells, and doxorubicin upregulated CCL20 expression in SKOV3 cells. MTT and cell count assay found that CCL20 overexpression plasmid enhanced doxorubicin resistance of SKOV3 and OVCA433 cells compared to empty vector, as shown by the increase in cell viability. In contrast, CCL20 shRNA enhanced doxorubicin sensitivity of SKOV3 DR cells compared to control. CCL20 overexpression plasmid promoted NF-kB activation and positively regulated ABCB1 expression. Besides, ABCB1 overexpression plasmid enhanced the viability of SKOV3 and OVCA433 cells compared to empty vector under treatment with the same concentration of doxorubicin, whereas ABCB1 shRNA inhibited doxorubicin resistance of SKOV3 DR cells compared to control. In conclusion, CCL20 enhanced doxorubicin resistance of OC cells by regulating ABCB1 expression.Key words: CCL20, ovarian cancer, doxorubicin resistance, tumor-promoting, ABCB1.","PeriodicalId":9927,"journal":{"name":"Cell structure and function","volume":"44 1","pages":"21-28"},"PeriodicalIF":1.5,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1247/csf.18029","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36950841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 13