目的探究脯氨酰4-羟化酶α-3(P4HA3)基因在结直肠癌(CRC)的表达及与不良预后的关系。方法从The Cancer Genome Atlas(TCGA)数据库获取CRC基因数据,包含647例CRC患者肿瘤组织和51例癌旁组织。利用R软件对P4HA3表达及配对数据可视化分析...目的探究脯氨酰4-羟化酶α-3(P4HA3)基因在结直肠癌(CRC)的表达及与不良预后的关系。方法从The Cancer Genome Atlas(TCGA)数据库获取CRC基因数据,包含647例CRC患者肿瘤组织和51例癌旁组织。利用R软件对P4HA3表达及配对数据可视化分析。卡方检验分析P4HA3表达与CRC患者临床特征关系。利用R软件survival包对P4HA3进行生存分析。利用基因表达谱交互分析(GEPIA)数据库验证TCGA数据库CRC中P4HA3的表达。通过基因集富集分析(GSEA)对P4HA3进行京都基因与基因组百科全科(KEGG)通路富集分析。采用免疫组化染色检测30例CRC患者手术切除的肿瘤和癌旁组织蜡块样本中的P4HA3蛋白表达。结果R软件分析显示,与癌旁组织比较,P4HA3在CRC组织高表达(P<0.01)。卡方检验显示,P4HA3表达与CRC患者Stage、T和N分期密切相关(P<0.05)。生存分析显示,与低表达P4HA3患者比较,P4HA3高表达CRC患者的生存时间明显缩短(P<0.05)。通过GEPIA数据库分析验证了P4HA3基因与CRC不良预后相关(P<0.05)。进一步GSEA通路富集分析结果显示,P4HA3基因富集到的信号通路与多种恶性肿瘤的发生发展有关(FDR<0.05)。最后,免疫组化检测验证了P4HA3蛋白在CRC组织中高表达。结论基因P4HA3与CRC的进展及不良预后相关,P4HA3有望成为CRC患者新的治疗靶点。展开更多
A series of novel amino-substituted N-aryl benzamide analogs were synthesized and evaluated for their ability to inhibit hepatitis C virus(HCV)replication in acutely infected Huh7.5 cells.Most of the substituted N-ary...A series of novel amino-substituted N-aryl benzamide analogs were synthesized and evaluated for their ability to inhibit hepatitis C virus(HCV)replication in acutely infected Huh7.5 cells.Most of the substituted N-aryl benzamide compounds showed convincing anti-HCV activities.Compounds 1f,1g and 4c exhibited potent anti-replicative activity at low micromolar levels(IC_(50)=1.0–2.0μM)with selective indices(SI)greater than 40.Mechanistic analysis indicated that the active compounds increased intracellular hA3G protein levels and inhibited HCV replication in a dose-dependent manner.The results demonstrate that this series of substituted Naryl benzamide compounds warrant further investigation as inhibitors of HCV replication.展开更多
The co-continuous(HA+β-TCP)/Zn−3Sn composite was fabricated via vacuum casting-infiltration method.The microstructure,mechanical properties,corrosion behaviors,and hemolysis ratio of the composite were studied by sca...The co-continuous(HA+β-TCP)/Zn−3Sn composite was fabricated via vacuum casting-infiltration method.The microstructure,mechanical properties,corrosion behaviors,and hemolysis ratio of the composite were studied by scanning electron microscope,X-ray diffractometer,mechanical testing,electrochemical test,immersion test,and ultraviolet spectrophotometry.The results indicate that Zn−3Sn alloy infiltrated into porous HA+β-TCP scaffold,which resulted in the formation of a compact(HA+β-TCP)/Zn−3Sn co-continuous composite,without any reaction layer between the Zn−3Sn alloy and the HA+β-TCP scaffold.The compressive strength of the composite was equal to about 3/4 that of Zn−3Sn alloy bulk.The corrosion rate of composite in simulated body fluid solution was slightly higher than that of Zn−3Sn alloy bulk.The main corrosion product on the composite surface was Zn(OH)2.The hemolysis rate of the composite was lower than that of Zn–3Sn alloy bulk and exhibited superior blood compatibility.展开更多
Human APOBEC3G(h A3G) is a cytidine deaminase which inhibits HIV-1 replication. The HIV-1 accessory protein viral infectivity factor(Vif) counteracts with hA3G by targeting it for proteasomal degradation. In this work...Human APOBEC3G(h A3G) is a cytidine deaminase which inhibits HIV-1 replication. The HIV-1 accessory protein viral infectivity factor(Vif) counteracts with hA3G by targeting it for proteasomal degradation. In this work, we constructed and optimized molecular models of the hA3G dimer and the h A3G–Vif complex. The molecular modeling study revealed that the loop7 motif of hA3G appears on the interfaces of both the h A3G–Vif complex and the hA3G dimer. Biochemical analysis provided evidence suggesting that binding of Vif to hA3G results in steric blocking of hA3G dimerization, implying that monomeric hA3G serves as a substrate for Vif-mediated degradation.Furthermore, we presented evidence for the important roles of the loop7 motif, especially the central residues within the region, in hA3G dimerization, h A3G–Vif interaction, Vif-mediated hA3G degradation as well as subcellular localization of hA3G. This work highlights a multiple-task interface formed by loop7 motif, which regulates biological function of hA3G, thus providing the feasibility of the strategy of blocking Vif-mediated A3 G degradation by targeting the putative site around loop7.展开更多
文摘目的探究脯氨酰4-羟化酶α-3(P4HA3)基因在结直肠癌(CRC)的表达及与不良预后的关系。方法从The Cancer Genome Atlas(TCGA)数据库获取CRC基因数据,包含647例CRC患者肿瘤组织和51例癌旁组织。利用R软件对P4HA3表达及配对数据可视化分析。卡方检验分析P4HA3表达与CRC患者临床特征关系。利用R软件survival包对P4HA3进行生存分析。利用基因表达谱交互分析(GEPIA)数据库验证TCGA数据库CRC中P4HA3的表达。通过基因集富集分析(GSEA)对P4HA3进行京都基因与基因组百科全科(KEGG)通路富集分析。采用免疫组化染色检测30例CRC患者手术切除的肿瘤和癌旁组织蜡块样本中的P4HA3蛋白表达。结果R软件分析显示,与癌旁组织比较,P4HA3在CRC组织高表达(P<0.01)。卡方检验显示,P4HA3表达与CRC患者Stage、T和N分期密切相关(P<0.05)。生存分析显示,与低表达P4HA3患者比较,P4HA3高表达CRC患者的生存时间明显缩短(P<0.05)。通过GEPIA数据库分析验证了P4HA3基因与CRC不良预后相关(P<0.05)。进一步GSEA通路富集分析结果显示,P4HA3基因富集到的信号通路与多种恶性肿瘤的发生发展有关(FDR<0.05)。最后,免疫组化检测验证了P4HA3蛋白在CRC组织中高表达。结论基因P4HA3与CRC的进展及不良预后相关,P4HA3有望成为CRC患者新的治疗靶点。
基金supported by the National Natural Science Foundation of China(Grants 30873138,81202414).
文摘A series of novel amino-substituted N-aryl benzamide analogs were synthesized and evaluated for their ability to inhibit hepatitis C virus(HCV)replication in acutely infected Huh7.5 cells.Most of the substituted N-aryl benzamide compounds showed convincing anti-HCV activities.Compounds 1f,1g and 4c exhibited potent anti-replicative activity at low micromolar levels(IC_(50)=1.0–2.0μM)with selective indices(SI)greater than 40.Mechanistic analysis indicated that the active compounds increased intracellular hA3G protein levels and inhibited HCV replication in a dose-dependent manner.The results demonstrate that this series of substituted Naryl benzamide compounds warrant further investigation as inhibitors of HCV replication.
基金the National Natural Science Foundation of China(No.51101039)the Fundamental Research Funds for the Central Universities,China(No.3072020CFT0702).
文摘The co-continuous(HA+β-TCP)/Zn−3Sn composite was fabricated via vacuum casting-infiltration method.The microstructure,mechanical properties,corrosion behaviors,and hemolysis ratio of the composite were studied by scanning electron microscope,X-ray diffractometer,mechanical testing,electrochemical test,immersion test,and ultraviolet spectrophotometry.The results indicate that Zn−3Sn alloy infiltrated into porous HA+β-TCP scaffold,which resulted in the formation of a compact(HA+β-TCP)/Zn−3Sn co-continuous composite,without any reaction layer between the Zn−3Sn alloy and the HA+β-TCP scaffold.The compressive strength of the composite was equal to about 3/4 that of Zn−3Sn alloy bulk.The corrosion rate of composite in simulated body fluid solution was slightly higher than that of Zn−3Sn alloy bulk.The main corrosion product on the composite surface was Zn(OH)2.The hemolysis rate of the composite was lower than that of Zn–3Sn alloy bulk and exhibited superior blood compatibility.
基金supported by 973 program (2012CB911102 CS)National Megaproject for Innovative Drugs (2012ZX09301002-001-015 and 2012ZX09301002-005-002 CS)+1 种基金National Mega-Project for Infectious Disease (2013ZX1000 4601-002 CS)The National Natural Science Foundation of China (81271844 ZJM and 31470272 CS)
文摘Human APOBEC3G(h A3G) is a cytidine deaminase which inhibits HIV-1 replication. The HIV-1 accessory protein viral infectivity factor(Vif) counteracts with hA3G by targeting it for proteasomal degradation. In this work, we constructed and optimized molecular models of the hA3G dimer and the h A3G–Vif complex. The molecular modeling study revealed that the loop7 motif of hA3G appears on the interfaces of both the h A3G–Vif complex and the hA3G dimer. Biochemical analysis provided evidence suggesting that binding of Vif to hA3G results in steric blocking of hA3G dimerization, implying that monomeric hA3G serves as a substrate for Vif-mediated degradation.Furthermore, we presented evidence for the important roles of the loop7 motif, especially the central residues within the region, in hA3G dimerization, h A3G–Vif interaction, Vif-mediated hA3G degradation as well as subcellular localization of hA3G. This work highlights a multiple-task interface formed by loop7 motif, which regulates biological function of hA3G, thus providing the feasibility of the strategy of blocking Vif-mediated A3 G degradation by targeting the putative site around loop7.
