目的探讨中心体蛋白78(centrosomal protein 78,CEP78)对内皮细胞生物学行为的影响及其与冠心病(coronary heart disease,CHD)的关系。方法通过Gene Expression Omnibus(GEO)数据库检索CHD相关数据集,利用StataSE 15求CEP78的总标准化...目的探讨中心体蛋白78(centrosomal protein 78,CEP78)对内皮细胞生物学行为的影响及其与冠心病(coronary heart disease,CHD)的关系。方法通过Gene Expression Omnibus(GEO)数据库检索CHD相关数据集,利用StataSE 15求CEP78的总标准化平均差(standardized mean difference,SMD)并绘制总受试者操作特征(summary receiver operating characteristic,SROC)曲线。利用单细胞RNA测序分析CEP78在不同细胞中的表达情况。在人脐静脉内皮细胞株(EA.hy926)中构建过表达CEP78(OE_CEP78)和过表达空载质粒(OE_NC)模型,通过细胞划痕、Transwell、CCK8和细胞凋亡实验验证CEP78和CHD之间的相关性。利用SMD和Spearman相关性分析求CEP78差异共表达基因,通过Metascape数据库对CEP78差异共表达基因进行基因本体(gene ontology,GO)和京都基因和基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)富集分析。结果CEP78在CHD中低表达(总SMD=-0.99,95%CI:-1.79~-0.20,P=0.015),SROC曲线下面积(area under the curve,AUC)为0.77(0.73~0.81),证明CEP78对CHD具有中等诊断能力。单细胞RNA测序分析结果显示,CEP78在正常外周血自然杀伤细胞中高表达。OE_CEP78可以抑制EA.hy926细胞的增殖、迁移和凋亡。KEGG通路富集分析显示CEP78差异正相关基因富集在FOXO信号通路。结论CEP78在CHD中低表达,对CHD具有中等诊断能力,并通过抑制内皮细胞的增殖、迁移和凋亡来抑制CHD的发生发展。展开更多
新型混凝土扩盘桩(New type concrete expanded-plate pile,简称NT-CEP桩)作为变截面桩在工程领域应用渐广,与传统直孔桩相比,它具有承载能力高、沉降小及承力盘设计灵活等优势。运用ANSYS软件对NT-CEP桩群桩的桩身及桩周土体应力进行分...新型混凝土扩盘桩(New type concrete expanded-plate pile,简称NT-CEP桩)作为变截面桩在工程领域应用渐广,与传统直孔桩相比,它具有承载能力高、沉降小及承力盘设计灵活等优势。运用ANSYS软件对NT-CEP桩群桩的桩身及桩周土体应力进行分析,在不考虑上部承台对桩顶约束的情况下,研究NT-CEP桩抗压群桩在达到破坏时,桩身应力和桩周土体应力的变化规律,揭示竖向压力作用下NT-CEP桩群桩的破坏机理,进而确定合理盘端净间距(以下简称桩间距)。研究表明,竖向压力下NT-CEP群桩承载能力随桩间距增大而提高,但不是线性增长,桩间距超4倍盘悬挑径时,承载力提升效率开始降低,故工程设计中的桩间距控制在3~4倍盘悬挑径较为合理。完善NT-CEP桩群桩在竖向荷载作用下的理论体系,为其设计应用和技术推广提供了重要技术支撑。展开更多
Introduction:Acral melanoma(AM)is the predominant subtype of cutaneous melanoma in Asian populations,characterized by more aggressive clinical features and limited neoadjuvant therapy response.Centrosomal protein 55 k...Introduction:Acral melanoma(AM)is the predominant subtype of cutaneous melanoma in Asian populations,characterized by more aggressive clinical features and limited neoadjuvant therapy response.Centrosomal protein 55 kDa(CEP55)has been implicated in the pathogenesis of various malignancies,but its role in AM remains undefined.Methods:CEP55 expression in melanoma tissues and cell lines was analyzed by RT-qPCR,Western blotting,and immunohistochemistry(IHC).Databases(GEPIA,Sangerbox,Kaplan-Meier plotter,and TIMER)were used to analyze the expression of CEP55 and its correlation with clinical data of melanoma patients.Functional assays were conducted in vitro and in vivo.RNA sequencing(RNA-seq)and rescue experiments were used to explore underlying mechanisms.Tissue microarrays were used to verify the relationship between CEP55 and immune checkpoints.Results:CEP55 overexpression is associated with Breslow thickness and TNM stage in melanoma tissues and cell lines.CEP55 knockdown inhibited melanoma cell proliferation,migration,and invasion.And CEP55 activated mitogen-activated protein kinase(MAPK)signaling,leading to BRAF inhibitor resistance.Besides,CEP55 overexpression was associated with more favorable responses to immunotherapy in melanoma patients.Conclusions:CEP55 plays a critical role in AM progression and immunotherapy.Targeting CEP55 may be a promising therapeutic strategy for AM.展开更多
文摘目的探讨中心体蛋白78(centrosomal protein 78,CEP78)对内皮细胞生物学行为的影响及其与冠心病(coronary heart disease,CHD)的关系。方法通过Gene Expression Omnibus(GEO)数据库检索CHD相关数据集,利用StataSE 15求CEP78的总标准化平均差(standardized mean difference,SMD)并绘制总受试者操作特征(summary receiver operating characteristic,SROC)曲线。利用单细胞RNA测序分析CEP78在不同细胞中的表达情况。在人脐静脉内皮细胞株(EA.hy926)中构建过表达CEP78(OE_CEP78)和过表达空载质粒(OE_NC)模型,通过细胞划痕、Transwell、CCK8和细胞凋亡实验验证CEP78和CHD之间的相关性。利用SMD和Spearman相关性分析求CEP78差异共表达基因,通过Metascape数据库对CEP78差异共表达基因进行基因本体(gene ontology,GO)和京都基因和基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)富集分析。结果CEP78在CHD中低表达(总SMD=-0.99,95%CI:-1.79~-0.20,P=0.015),SROC曲线下面积(area under the curve,AUC)为0.77(0.73~0.81),证明CEP78对CHD具有中等诊断能力。单细胞RNA测序分析结果显示,CEP78在正常外周血自然杀伤细胞中高表达。OE_CEP78可以抑制EA.hy926细胞的增殖、迁移和凋亡。KEGG通路富集分析显示CEP78差异正相关基因富集在FOXO信号通路。结论CEP78在CHD中低表达,对CHD具有中等诊断能力,并通过抑制内皮细胞的增殖、迁移和凋亡来抑制CHD的发生发展。
文摘新型混凝土扩盘桩(New type concrete expanded-plate pile,简称NT-CEP桩)作为变截面桩在工程领域应用渐广,与传统直孔桩相比,它具有承载能力高、沉降小及承力盘设计灵活等优势。运用ANSYS软件对NT-CEP桩群桩的桩身及桩周土体应力进行分析,在不考虑上部承台对桩顶约束的情况下,研究NT-CEP桩抗压群桩在达到破坏时,桩身应力和桩周土体应力的变化规律,揭示竖向压力作用下NT-CEP桩群桩的破坏机理,进而确定合理盘端净间距(以下简称桩间距)。研究表明,竖向压力下NT-CEP群桩承载能力随桩间距增大而提高,但不是线性增长,桩间距超4倍盘悬挑径时,承载力提升效率开始降低,故工程设计中的桩间距控制在3~4倍盘悬挑径较为合理。完善NT-CEP桩群桩在竖向荷载作用下的理论体系,为其设计应用和技术推广提供了重要技术支撑。
基金supported by CAMS Innovation Fund for Medical Sciences(CIFMS)(2024-I2M-C&T-B-089)National Key Research and Development Program(2022YFC2504700,2022YFC2504701,2022YFC2504705)National Natural Science Foundation of China(NSFC81872216).
文摘Introduction:Acral melanoma(AM)is the predominant subtype of cutaneous melanoma in Asian populations,characterized by more aggressive clinical features and limited neoadjuvant therapy response.Centrosomal protein 55 kDa(CEP55)has been implicated in the pathogenesis of various malignancies,but its role in AM remains undefined.Methods:CEP55 expression in melanoma tissues and cell lines was analyzed by RT-qPCR,Western blotting,and immunohistochemistry(IHC).Databases(GEPIA,Sangerbox,Kaplan-Meier plotter,and TIMER)were used to analyze the expression of CEP55 and its correlation with clinical data of melanoma patients.Functional assays were conducted in vitro and in vivo.RNA sequencing(RNA-seq)and rescue experiments were used to explore underlying mechanisms.Tissue microarrays were used to verify the relationship between CEP55 and immune checkpoints.Results:CEP55 overexpression is associated with Breslow thickness and TNM stage in melanoma tissues and cell lines.CEP55 knockdown inhibited melanoma cell proliferation,migration,and invasion.And CEP55 activated mitogen-activated protein kinase(MAPK)signaling,leading to BRAF inhibitor resistance.Besides,CEP55 overexpression was associated with more favorable responses to immunotherapy in melanoma patients.Conclusions:CEP55 plays a critical role in AM progression and immunotherapy.Targeting CEP55 may be a promising therapeutic strategy for AM.
