Mammalian Genome最新文献_第6页

EEF1A2 identified as a hub gene associated with the severity of metabolic dysfunction-associated steatotic liver disease. EEF1A2 被确定为与代谢功能障碍相关性脂肪肝严重程度有关的枢纽基因。

IF 2.7 4区生物学

Mammalian Genome Pub Date : 2024-10-16 DOI: 10.1007/s00335-024-10078-9

Jian Zhang, Huiwen Wang, Qianbing Wang, Juan Mo, Lei Fu, Shifang Peng

{"title":"EEF1A2 identified as a hub gene associated with the severity of metabolic dysfunction-associated steatotic liver disease.","authors":"Jian Zhang, Huiwen Wang, Qianbing Wang, Juan Mo, Lei Fu, Shifang Peng","doi":"10.1007/s00335-024-10078-9","DOIUrl":"https://doi.org/10.1007/s00335-024-10078-9","url":null,"abstract":"Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent chronic liver disease that ranges from metabolic dysfunction-associated steatotic liver (MASL) to metabolic dysfunction-associated steatohepatitis (MASH), and may eventually progress to cirrhosis and hepatocellular carcinoma (HCC). The underlying mechanism of MASLD remains incompletely understood. This study aimed to identify key gene implicated in MASLD pathogenesis and validate its correlation with disease severity through an integration of bioinformatics and experimental approaches. Liver transcriptome data from MASLD patients were obtained from the Gene Expression Omnibus (GEO) database. A diet-induced MASLD mouse model was developed, and liver RNA-sequencing was performed. Liver specimens and clinical data from patients were collected for further analysis. A total of 120 differentially expressed genes (DEGs) were shared between datasets GSE89632 and GSE213621, with functional enrichment in inflammatory, metabolic, and cell cycle-related pathways. Protein-protein interaction (PPI) network analysis identified three modules associated with MASLD, with the cell cycle-related module being the most notable. EEF1A2 was identified as a novel hub gene and revealed to be elevated with MASLD progression through dataset analysis. EEF1A2 was confirmed to be highly expressed in the livers of both MASLD mouse models and patients. Moreover, the increased expression of EEF1A2 in MASH was positively correlated with higher serum alanine aminotransferase (ALT), alanine aminotransferase (AST), total cholesterol (TC), and body mass index (BMI). In conclusion, EEF1A2 is a novel hub gene significantly associated with MASLD severity and is a promising biomarker and therapeutic target for MASLD.","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142469174","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

A fascination with tailless mice: a scientific historical review of studies of the T/t complex. 无尾小鼠的魅力：T/t复合体研究的科学历史回顾。

IF 2.7 4区生物学

Mammalian Genome Pub Date : 2024-10-14 DOI: 10.1007/s00335-024-10076-x

Robert P Erickson

引用次数: 0

Identification of novel biomarkers for atherosclerosis using single-cell RNA sequencing and machine learning. 利用单细胞 RNA 测序和机器学习鉴定动脉粥样硬化的新型生物标记物。

IF 2.7 4区生物学

Mammalian Genome Pub Date : 2024-10-14 DOI: 10.1007/s00335-024-10077-w

Xi Yong, Tengyao Kang, Mingzhu Li, Sixuan Li, Xiang Yan, Jiuxin Li, Jie Lin, Bo Lu, Jianghua Zheng, Zhengmin Xu, Qin Yang, Jingdong Li

{"title":"Identification of novel biomarkers for atherosclerosis using single-cell RNA sequencing and machine learning.","authors":"Xi Yong, Tengyao Kang, Mingzhu Li, Sixuan Li, Xiang Yan, Jiuxin Li, Jie Lin, Bo Lu, Jianghua Zheng, Zhengmin Xu, Qin Yang, Jingdong Li","doi":"10.1007/s00335-024-10077-w","DOIUrl":"https://doi.org/10.1007/s00335-024-10077-w","url":null,"abstract":"Atherosclerosis (AS) is a predominant etiological factor in numerous cardiovascular diseases, with its associated complications such as myocardial infarction and stroke serving as major contributors to worldwide mortality rates. Here, we devised dependable AS-related biomarkers through the utilization of single-cell RNA sequencing, weighted co-expression network (WGCNA), and differential expression analysis. Furthermore, we employed various machine learning techniques (LASSO and SVM-RFE) to enhance the identification of AS biomarkers, subsequently validating them using the GEO dataset. Following this, CIBERSORT was employed to investigate the correlation between biomarkers and infiltrating immune cells. Consequently, 256 differentially expressed genes (DEGs) were selected in samples of AS and normal. GO and KEGG analyses indicated that these DEGs may be related to the negative regulation of leukocyte-mediated immunity, leukocyte cell-cell adhesion, and immune system processes. Notably, C1QC and COL1A1 were pinpointed as potential diagnostic markers for AS, a finding that was further validated in the GSE21545 dataset. Moreover, the area under the curve (AUC) values for these markers exceeded 0.8, underscoring their diagnostic utility. Analysis of immune cell infiltration revealed that the expression of C1QC was correlated with M0 macrophages, gamma delta T cells, activated mast cells and memory B cells. Similarly, COL1A1 expression was linked to M0 macrophages, memory B cells, activated mast cells, gamma delta T cells, and CD4 native T cells. Finally, these results were validated using mice and human samples through immunofluorescence, immunohistochemistry, and ELISA analysis. Overall, C1QC and COL1A1 would be potential biomarkers for AS diagnosis, and that would provides novel perspectives on the diagnosis and treatment of AS.","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142469175","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

Mammalian genome research resources available from the National BioResource Project in Japan 日本国家生物资源项目提供的哺乳动物基因组研究资源

IF 2.5 4区生物学

Mammalian Genome Pub Date : 2024-09-11 DOI: 10.1007/s00335-024-10063-2

Saori Mizuno-Iijima, Shoko Kawamoto, Masahide Asano, Tomoji Mashimo, Shigeharu Wakana, Katsuki Nakamura, Ken-ichi Nishijima, Hitoshi Okamoto, Kuniaki Saito, Sawako Yoshina, Yoshihiro Miwa, Yukio Nakamura, Moriya Ohkuma, Atsushi Yoshiki

{"title":"Mammalian genome research resources available from the National BioResource Project in Japan","authors":"Saori Mizuno-Iijima, Shoko Kawamoto, Masahide Asano, Tomoji Mashimo, Shigeharu Wakana, Katsuki Nakamura, Ken-ichi Nishijima, Hitoshi Okamoto, Kuniaki Saito, Sawako Yoshina, Yoshihiro Miwa, Yukio Nakamura, Moriya Ohkuma, Atsushi Yoshiki","doi":"10.1007/s00335-024-10063-2","DOIUrl":"https://doi.org/10.1007/s00335-024-10063-2","url":null,"abstract":"Mammalian genome research has conventionally involved mice and rats as model organisms for humans. Given the recent advances in life science research, to understand complex and higher-order biological phenomena and to elucidate pathologies and develop therapies to promote human health and overcome diseases, it is necessary to utilize not only mice and rats but also other bioresources such as standardized genetic materials and appropriate cell lines in order to gain deeper molecular and cellular insights. The Japanese bioresource infrastructure program called the National BioResource Project (NBRP) systematically collects, preserves, controls the quality, and provides bioresources for use in life science research worldwide. In this review, based on information from a database of papers related to NBRP bioresources, we present the bioresources that have proved useful for mammalian genome research, including mice, rats, other animal resources; DNA-related materials; and human/animal cells and microbes.","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":"90 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142200549","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

Identifying new molecular signatures and potential therapeutics for idiopathic pulmonary fibrosis: a network medicine approach 识别特发性肺纤维化的新分子特征和潜在疗法：一种网络医学方法

IF 2.5 4区生物学

Mammalian Genome Pub Date : 2024-09-10 DOI: 10.1007/s00335-024-10069-w

Mecbure Nur Akca, Ceyda Kasavi

{"title":"Identifying new molecular signatures and potential therapeutics for idiopathic pulmonary fibrosis: a network medicine approach","authors":"Mecbure Nur Akca, Ceyda Kasavi","doi":"10.1007/s00335-024-10069-w","DOIUrl":"https://doi.org/10.1007/s00335-024-10069-w","url":null,"abstract":"Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal lung disease characterized by excessive collagen deposition and fibrosis of the lung parenchyma, leading to respiratory failure. The molecular mechanisms underlying IPF pathogenesis remain incompletely understood, hindering the development of effective therapeutic strategies. We have used a network medicine approach to comprehensively analyze molecular interactions and identify novel molecular signatures and potential therapeutics associated with IPF progression. Our integrative analysis revealed dysregulated molecular networks that are central to IPF pathophysiology. We have highlighted key molecular players and signaling pathways that are implicated in aberrant fibrotic processes. This systems-level understanding enables the identification of new biomarkers and therapeutic targets for IPF, providing potential avenues for precision medicine. Drug repurposing analysis revealed several drug candidates with anti-fibrotic, anti-inflammatory, and anti-cancer activities that could potentially slow fibrotic progression and improve patient outcomes. This study offers new insights into the molecular underpinnings of IPF and highlights network medicine approaches in uncovering complex disease mechanisms. The molecular signatures and therapeutic targets identified hold promise for developing precision therapies tailored to individual patients, ultimately advancing the management of this debilitating lung disease.","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":"59 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142200547","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

Commentary: The International Mouse Phenotyping Consortium: high-throughput in vivo functional annotation of the mammalian genome 评论：国际小鼠表型协会：哺乳动物基因组的高通量活体功能注释

IF 2.5 4区生物学

Mammalian Genome Pub Date : 2024-09-10 DOI: 10.1007/s00335-024-10068-x

K. C. Kent Lloyd

引用次数: 0

The interplay of hydrogen sulfide and microRNAs in cardiovascular diseases: insights and future perspectives. 硫化氢和 microRNAs 在心血管疾病中的相互作用：见解和未来展望。

IF 2.7 4区生物学

Mammalian Genome Pub Date : 2024-09-01 Epub Date: 2024-06-04 DOI: 10.1007/s00335-024-10043-6

Yunjia Song, Shuo Cao, Xutao Sun, Guozhen Chen

{"title":"The interplay of hydrogen sulfide and microRNAs in cardiovascular diseases: insights and future perspectives.","authors":"Yunjia Song, Shuo Cao, Xutao Sun, Guozhen Chen","doi":"10.1007/s00335-024-10043-6","DOIUrl":"10.1007/s00335-024-10043-6","url":null,"abstract":"Hydrogen sulfide (H2S) is recognized as the third gasotransmitter, after nitric oxide (NO) and carbon monoxide (CO). It is known for its cardioprotective properties, including the relaxation of blood vessels, promotion of angiogenesis, regulation of myocardial cell apoptosis, inhibition of vascular smooth muscle cell proliferation, and reduction of inflammation. Additionally, abnormal H2S generation has been linked to the development of cardiovascular diseases (CVD), such as pulmonary hypertension, hypertension, atherosclerosis, vascular calcification, and myocardial injury. MicroRNAs (miRNAs) are non-coding, conserved, and versatile molecules that primarily influence gene expression by repressing translation and have emerged as biomarkers for CVD diagnosis. Studies have demonstrated that H2S can ameliorate cardiac dysfunction by regulating specific miRNAs, and certain miRNAs can also regulate H2S synthesis. The crosstalk between miRNAs and H2S offers a novel perspective for investigating the pathophysiology, prevention, and treatment of CVD. The present analysis outlines the interactions between H2S and miRNAs and their influence on CVD, providing insights into their future potential and advancement.","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":" ","pages":"309-323"},"PeriodicalIF":2.7,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141248187","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

Genomic patterns of selection in morphometric traits across diverse Indian cattle breeds. 印度不同牛种形态特征选择的基因组模式。

IF 2.7 4区生物学

Mammalian Genome Pub Date : 2024-09-01 Epub Date: 2024-07-16 DOI: 10.1007/s00335-024-10047-2

Divya Rajawat, Sonali Sonejita Nayak, Karan Jain, Anurodh Sharma, Subhashree Parida, Sarada Prasanna Sahoo, Bharat Bhushan, D B Patil, Triveni Dutt, Manjit Panigrahi

{"title":"Genomic patterns of selection in morphometric traits across diverse Indian cattle breeds.","authors":"Divya Rajawat, Sonali Sonejita Nayak, Karan Jain, Anurodh Sharma, Subhashree Parida, Sarada Prasanna Sahoo, Bharat Bhushan, D B Patil, Triveni Dutt, Manjit Panigrahi","doi":"10.1007/s00335-024-10047-2","DOIUrl":"10.1007/s00335-024-10047-2","url":null,"abstract":"This study seeks a comprehensive exploration of genome-wide selective processes impacting morphometric traits across diverse cattle breeds, utilizing an array of statistical methods. Morphometric traits, encompassing both qualitative and quantitative variables, play a pivotal role in characterizing and selecting livestock breeds based on their external appearance, size, and physical attributes. While qualitative traits, such as color, horn structure, and coat type, contribute to adaptive features and breed identification, quantitative traits like body weight and conformation measurements bear a closer correlation with production characteristics. This study employs advanced genotyping technologies, including the Illumina BovineSNP50 Bead Chip and next-generation sequencing methods like Reduced Representation sequencing, to identify genomic signatures associated with these traits. We applied four intra-population methods to find evidence of selection, such as Tajima's D, CLR, iHS, and ROH. We found a total of 40 genes under the selection signature, that were associated with morphometric traits in five cattle breeds (Kankrej, Tharparkar, Nelore, Sahiwal, and Gir). Crucial genes such as ADIPDQ, DPP6, INSIG1, SLC35D2 in Kankrej, LPL, ATP6V1B2, CDC14B in Tharparkar, HPSE2, PLAG1 in Nelore, PCSK1, PRKD1 in Sahiwal, and GNAQ, HPCAL1 in Gir were identified in our study. This approach provides valuable insights into the genetic basis of variations in body weight and conformation traits, facilitating informed selection processes and offering a deeper understanding of the evolutionary and domestication processes in diverse cattle breeds.","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":" ","pages":"377-389"},"PeriodicalIF":2.7,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141627048","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

Maternal genetic diversity and phylogenetic analysis of Indian riverine and swamp buffaloes: insights from complete mitochondrial genomes. 印度河流水牛和沼泽水牛的母体遗传多样性和系统发育分析：完整线粒体基因组的启示。

IF 2.7 4区生物学

Mammalian Genome Pub Date : 2024-09-01 Epub Date: 2024-06-18 DOI: 10.1007/s00335-024-10048-1

Sonika Ahlawat, Upasna Sharma, Pooja Chhabra, Reena Arora, Rekha Sharma, Karan Veer Singh, R K Vijh

{"title":"Maternal genetic diversity and phylogenetic analysis of Indian riverine and swamp buffaloes: insights from complete mitochondrial genomes.","authors":"Sonika Ahlawat, Upasna Sharma, Pooja Chhabra, Reena Arora, Rekha Sharma, Karan Veer Singh, R K Vijh","doi":"10.1007/s00335-024-10048-1","DOIUrl":"10.1007/s00335-024-10048-1","url":null,"abstract":"This study explored the genetic diversity and evolutionary history of riverine and swamp buffaloes in India, utilizing complete mitochondrial genome sequences. Through comprehensive sampling across varied agro-climatic zones, including 91 riverine buffaloes from 12 breeds and 6 non-descript populations, along with 16 swamp buffaloes of the Luit breed, this study employed next-generation sequencing techniques to map the mitogenomic landscape of these subspecies. Sequence alignments were performed with the buffalo mitochondrial reference genome to identify mitochondrial DNA (mtDNA) variations and distinct maternal haplogroups among Indian buffaloes. The results uncovered the existence of 212 variable sites in riverine buffaloes, yielding 67 haplotypes with high haplotype diversity (0.991), and in swamp buffaloes, 194 variable sites resulting in 12 haplotypes, displaying haplotype diversity of 0.950. Phylogenetic analyses elucidated the genetic relationships between Indian buffaloes and the recognized global haplogroups, categorizing Indian swamp buffaloes predominantly into the SA haplogroup. Intriguingly, the haplogroup SB2b was observed for the first time in swamp buffaloes. Conversely, riverine buffaloes conformed to established sub-haplogroups RB1, RB2, and RB3, underscoring the notion of Northwestern India as a pivotal domestication site for riverine buffaloes. The study supports the hypothesis of independent domestication events for riverine and swamp buffaloes, highlighting the critical role of genetic analysis in unraveling the complex evolutionary pathways of domestic animals. This investigation contributes to the global understanding of buffalo mitogenome diversity, offering insights into this important livestock species' domestication and dispersal patterns.","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":" ","pages":"390-398"},"PeriodicalIF":2.7,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141419784","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

Tachol1 QTL on mouse chromosome 1 is responsible for hypercholesterolemia and diet-induced obesity. 小鼠 1 号染色体上的 Tachol1 QTL 是导致高胆固醇血症和饮食诱发肥胖的原因。

IF 2.7 4区生物学

Mammalian Genome Pub Date : 2024-09-01 Epub Date: 2024-06-05 DOI: 10.1007/s00335-024-10045-4

Jung Han Kim, Marvin A Simpkins, Nicholas T Williams, Emma Cimino, Jadyn Simon, Tanner R Richmond, Jared Youther, Hannah Slutz, James Denvir

{"title":"Tachol1 QTL on mouse chromosome 1 is responsible for hypercholesterolemia and diet-induced obesity.","authors":"Jung Han Kim, Marvin A Simpkins, Nicholas T Williams, Emma Cimino, Jadyn Simon, Tanner R Richmond, Jared Youther, Hannah Slutz, James Denvir","doi":"10.1007/s00335-024-10045-4","DOIUrl":"10.1007/s00335-024-10045-4","url":null,"abstract":"Hypercholesterolemia raises the risk for cardiovascular complications and overall health. Hypercholesterolemia is common, affecting 10% of the general population of the US, and heritable. Most individuals with hypercholesterolemia have a polygenic predisposition to the condition. Previously we identified a quantitative trait locus, Tachol1, linked to hypercholesterolemia on mouse chromosome 1 (Chr1) in a cross between C57BL/6J (B6) and TALLYHO/JngJ (TH) mice, a polygenic model for human obesity, type 2 diabetes and hyperlipidemia. Subsequently, using congenic mice that carry a TH-derived genomic segment of Chr1 on a B6 background, we demonstrated that the distal segment of Chr1, where Tachol1 maps, is necessary to cause hypercholesterolemia, as well as diet-induced obesity. In this study, we generated overlapping subcongenic lines to the distal segment of congenic region and characterized subcongenic mice carrying the smallest TH region of Tachol1, ~ 16.2 Mb in size (B6.TH-Chr1-16.2 Mb). Both male and female B6.TH-Chr1-16.2 Mb mice showed a significantly increased plasma total cholesterol levels compared to B6 on both chow and high fat (HF) diet. B6.TH-Chr1-16.2 Mb mice also had greater fat mass than B6 on HF diet, without increasing food intake. The gene and protein expression levels of absent in melanoma 2 (Aim2) gene were significantly upregulated in B6.TH-Chr1-16.2 Mb mice compared to B6. In summary, we confirmed the effect of Tachol1 on hypercholesterolemia and diet-induced obesity using subcongenic analysis.","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":" ","pages":"324-333"},"PeriodicalIF":2.7,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11339885/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141248185","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