目的分析甲基转移酶3(METTL3)抑制剂STM2457对人肝癌细胞系HepG2的影响,重点研究其对N6-甲基腺苷(m6A)表达的影响及其抗肿瘤机制。方法将HepG2细胞分为实验组(STM2457处理)和对照组(DMSO处理)。利用纳米孔(Nanopore)测序技术,结合m6Anet...目的分析甲基转移酶3(METTL3)抑制剂STM2457对人肝癌细胞系HepG2的影响,重点研究其对N6-甲基腺苷(m6A)表达的影响及其抗肿瘤机制。方法将HepG2细胞分为实验组(STM2457处理)和对照组(DMSO处理)。利用纳米孔(Nanopore)测序技术,结合m6Anet,NanoCount,xPore和GFOLD方法,分别对m6A修饰水平、转录组表达及差异基因进行分析。通过基因本体(GO)和京都基因与基因组百科(KEGG)对差异基因进行功能富集分析。结果STM2457降低HepG2细胞的m6A修饰位点数量(6446 vs 11549)及修饰水平(0.95±0.03 vs 0.98±0.03),差异具有统计学意义(Z=-19.915,P<0.01)。差异基因分析共筛选出109个上调基因和340个下调基因,其中与肝癌发生发展密切相关的基因PDLIM5、AZGP1和RNASET2,其m6A修饰水平降低,而基因表达水平升高。功能富集分析结果显示,差异基因主要富集在细胞黏附、凋亡、翻译调控及肝细胞癌相关通路。结论STM2457通过抑制METTL3活性,降低HepG2细胞的m6A修饰水平,上调基因PDLIM5,AZGP1和RNASET2的表达,促进HepG2细胞凋亡,为肝癌治疗提供潜在治疗靶点。展开更多
Objective:To elucidate the role and clinical potential of the lncRNA DLX6-AS1/miR-26a/PTEN axis in liver fibrosis.Methods:Systematic studies were conducted using cellular and animal models through causal validation,bi...Objective:To elucidate the role and clinical potential of the lncRNA DLX6-AS1/miR-26a/PTEN axis in liver fibrosis.Methods:Systematic studies were conducted using cellular and animal models through causal validation,bivariate experiments,single-cell sequencing,ROC analysis of clinical samples,and humanized mouse models.Results:LncRNA DLX6-AS1 inhibited PTEN by adsorbing miR-26a,promoting hepatic stellate cell activation in a dose/time-dependent manner;the axis demonstrated excellent diagnostic performance(AUC>0.9),and its inhibitors effectively reversed fibrosis in vivo.Conclusion:This study provides new biomarkers and targeted therapeutic strategies for liver fibrosis.展开更多
To explore the formation mechanism of anisotropy in Ti-6Al-4V alloy fabricated by selective laser melting(SLM),the compressive mechanical properties,microhardness,microstructure,and crystallographic orientation of the...To explore the formation mechanism of anisotropy in Ti-6Al-4V alloy fabricated by selective laser melting(SLM),the compressive mechanical properties,microhardness,microstructure,and crystallographic orientation of the alloy across different planes were investigated.The anisotropy of SLM-fabricated Ti-6Al-4V alloys was analyzed,and the electron backscatter diffraction technique was used to investigate the influence of different grain types and orientations on the stress-strain distribution at various scales.Results reveal that in room-temperature compression tests at a strain rate of 10^(-3) s^(-1),both the compressive yield strength and microhardness vary along the deposition direction,indicating a certain degree of mechanical property anisotropy.The alloy exhibits a columnar microstructure;along the deposition direction,the grains appear equiaxed,and they have internal hexagonal close-packed(hcp)α/α'martensitic structure.α'phase has a preferential orientation approximately along the<0001>direction.Anisotropy arises from the high aspect ratio of columnar grains,along with the weak texture of the microstructure and low symmetry of the hcp crystal structure.展开更多
文摘目的分析甲基转移酶3(METTL3)抑制剂STM2457对人肝癌细胞系HepG2的影响,重点研究其对N6-甲基腺苷(m6A)表达的影响及其抗肿瘤机制。方法将HepG2细胞分为实验组(STM2457处理)和对照组(DMSO处理)。利用纳米孔(Nanopore)测序技术,结合m6Anet,NanoCount,xPore和GFOLD方法,分别对m6A修饰水平、转录组表达及差异基因进行分析。通过基因本体(GO)和京都基因与基因组百科(KEGG)对差异基因进行功能富集分析。结果STM2457降低HepG2细胞的m6A修饰位点数量(6446 vs 11549)及修饰水平(0.95±0.03 vs 0.98±0.03),差异具有统计学意义(Z=-19.915,P<0.01)。差异基因分析共筛选出109个上调基因和340个下调基因,其中与肝癌发生发展密切相关的基因PDLIM5、AZGP1和RNASET2,其m6A修饰水平降低,而基因表达水平升高。功能富集分析结果显示,差异基因主要富集在细胞黏附、凋亡、翻译调控及肝细胞癌相关通路。结论STM2457通过抑制METTL3活性,降低HepG2细胞的m6A修饰水平,上调基因PDLIM5,AZGP1和RNASET2的表达,促进HepG2细胞凋亡,为肝癌治疗提供潜在治疗靶点。
基金Study on the Correlation between the Regulation of the miR-26a/PTEN Axis by lncRNA DLX6-AS1 and Post-Hepatitis Liver Fibrosis(Project No.:YKK22233)。
文摘Objective:To elucidate the role and clinical potential of the lncRNA DLX6-AS1/miR-26a/PTEN axis in liver fibrosis.Methods:Systematic studies were conducted using cellular and animal models through causal validation,bivariate experiments,single-cell sequencing,ROC analysis of clinical samples,and humanized mouse models.Results:LncRNA DLX6-AS1 inhibited PTEN by adsorbing miR-26a,promoting hepatic stellate cell activation in a dose/time-dependent manner;the axis demonstrated excellent diagnostic performance(AUC>0.9),and its inhibitors effectively reversed fibrosis in vivo.Conclusion:This study provides new biomarkers and targeted therapeutic strategies for liver fibrosis.
基金National Natural Science Foundation of China(51504138,51674118,52271177)Hunan Provincial Natural Science Foundation of China(2023JJ50181)Supported by State Key Laboratory of Materials Processing and Die&Mould Technology,Huazhong University of Science and Technology(P2024-022)。
文摘To explore the formation mechanism of anisotropy in Ti-6Al-4V alloy fabricated by selective laser melting(SLM),the compressive mechanical properties,microhardness,microstructure,and crystallographic orientation of the alloy across different planes were investigated.The anisotropy of SLM-fabricated Ti-6Al-4V alloys was analyzed,and the electron backscatter diffraction technique was used to investigate the influence of different grain types and orientations on the stress-strain distribution at various scales.Results reveal that in room-temperature compression tests at a strain rate of 10^(-3) s^(-1),both the compressive yield strength and microhardness vary along the deposition direction,indicating a certain degree of mechanical property anisotropy.The alloy exhibits a columnar microstructure;along the deposition direction,the grains appear equiaxed,and they have internal hexagonal close-packed(hcp)α/α'martensitic structure.α'phase has a preferential orientation approximately along the<0001>direction.Anisotropy arises from the high aspect ratio of columnar grains,along with the weak texture of the microstructure and low symmetry of the hcp crystal structure.
