Two novel out-of-plane ordered quaternary borides M'_(4)VSiB_(2) (M'=Nb and Mo) have been synthesized. The out-of-plane ordered characteristic has been confirmed by the X-ray diffraction, the neutron powder di...Two novel out-of-plane ordered quaternary borides M'_(4)VSiB_(2) (M'=Nb and Mo) have been synthesized. The out-of-plane ordered characteristic has been confirmed by the X-ray diffraction, the neutron powder diffraction and the scanning transmission electron microscopy with high-angle angular dark field images. By adjusting the stoichiometric ratio of Mo and V, the 16l site preferentially occupied by relatively larger atom and 4c site by relatively smaller atom have been confirmed. The further first-principle calculation demonstrates the dynamical and thermodynamical stability of Mo_(4)VSiB_(2) o-T2 phase. This work confirms the transition metal occupation strategy of o-T2 phase and enriches the out-of-plane ordered laminated borides family.展开更多
目的探究Cosmc或T-合酶基因敲除引起的异常O-糖基化修饰对结肠癌外泌体中微小RNA表达模式的影响,以揭示O-糖基化在结肠癌发展中的分子机制,并识别潜在的生物标志物,为结肠癌的早期诊断和治疗提供新策略。方法在人结肠癌细胞株HCT116中应...目的探究Cosmc或T-合酶基因敲除引起的异常O-糖基化修饰对结肠癌外泌体中微小RNA表达模式的影响,以揭示O-糖基化在结肠癌发展中的分子机制,并识别潜在的生物标志物,为结肠癌的早期诊断和治疗提供新策略。方法在人结肠癌细胞株HCT116中应用CRISPR/Cas-9基因编辑技术,分别靶向敲除Cosmc或T-合酶基因,以构建两种异常O-糖基化修饰的稳定转染细胞系。提取分离出肠癌细胞来源的外泌体,利用微小RNA(microRNAs,miRNAs)微阵列芯片,对比分析了其外泌体中miRNAs的表达差异。随后,在两组细胞来源的外泌体中筛选出表达量发生显著变化且变化趋势一致的miRNAs群体,采用传统荧光定量聚合酶链式反应(polymerase chain reaction,PCR)技术对这些miRNAs进行了独立验证。最后,通过癌症基因组图谱计划(The Cancer Genome Atlas Program,TCGA)数据库获取结直肠癌患者信息,利用R语言将表达上调的miRNA进行基因集富集分析(Gene Set Enrichment Analysis,GSEA),探索其显著相关的下游通路及表型。结果无论是Cosmc还是T-合酶基因缺失均会导致结肠癌细胞中O-糖基化修饰发生异常,Tn抗原暴露,进而使得结肠癌细胞来源的外泌体中hsa-miR-125b-1-3p表达量下调(P<0.05),而hsa-miR-218-5p表达量上调(P<0.05),且与肿瘤细胞上皮-间质转化过程密切相关(P<0.05)。结论由Cosmc或T-合酶基因缺失所介导的异常O-糖基化对结肠癌外泌体中相关miRNAs表达产生显著影响,进而可能影响结肠癌上皮-间质转化过程,从而促进肠癌远处转移。由此,基于肠癌外泌体的高稳定性及易检出性的天然优势,通过对其所携带miRNAs的表达量变化进行检测,可监测疾病进展和治疗效果,从而为结肠癌患者提供更为个性化的诊疗策略。展开更多
基金supported by the National Youth Talent Support Program(No.QNBJ-2022-03)the National Natu-ral Science Foundation of China(No.52371180)the Fundamental Research Funds for the Central Universities(Nos.N2209005 and N2309001).
文摘Two novel out-of-plane ordered quaternary borides M'_(4)VSiB_(2) (M'=Nb and Mo) have been synthesized. The out-of-plane ordered characteristic has been confirmed by the X-ray diffraction, the neutron powder diffraction and the scanning transmission electron microscopy with high-angle angular dark field images. By adjusting the stoichiometric ratio of Mo and V, the 16l site preferentially occupied by relatively larger atom and 4c site by relatively smaller atom have been confirmed. The further first-principle calculation demonstrates the dynamical and thermodynamical stability of Mo_(4)VSiB_(2) o-T2 phase. This work confirms the transition metal occupation strategy of o-T2 phase and enriches the out-of-plane ordered laminated borides family.
文摘目的探究Cosmc或T-合酶基因敲除引起的异常O-糖基化修饰对结肠癌外泌体中微小RNA表达模式的影响,以揭示O-糖基化在结肠癌发展中的分子机制,并识别潜在的生物标志物,为结肠癌的早期诊断和治疗提供新策略。方法在人结肠癌细胞株HCT116中应用CRISPR/Cas-9基因编辑技术,分别靶向敲除Cosmc或T-合酶基因,以构建两种异常O-糖基化修饰的稳定转染细胞系。提取分离出肠癌细胞来源的外泌体,利用微小RNA(microRNAs,miRNAs)微阵列芯片,对比分析了其外泌体中miRNAs的表达差异。随后,在两组细胞来源的外泌体中筛选出表达量发生显著变化且变化趋势一致的miRNAs群体,采用传统荧光定量聚合酶链式反应(polymerase chain reaction,PCR)技术对这些miRNAs进行了独立验证。最后,通过癌症基因组图谱计划(The Cancer Genome Atlas Program,TCGA)数据库获取结直肠癌患者信息,利用R语言将表达上调的miRNA进行基因集富集分析(Gene Set Enrichment Analysis,GSEA),探索其显著相关的下游通路及表型。结果无论是Cosmc还是T-合酶基因缺失均会导致结肠癌细胞中O-糖基化修饰发生异常,Tn抗原暴露,进而使得结肠癌细胞来源的外泌体中hsa-miR-125b-1-3p表达量下调(P<0.05),而hsa-miR-218-5p表达量上调(P<0.05),且与肿瘤细胞上皮-间质转化过程密切相关(P<0.05)。结论由Cosmc或T-合酶基因缺失所介导的异常O-糖基化对结肠癌外泌体中相关miRNAs表达产生显著影响,进而可能影响结肠癌上皮-间质转化过程,从而促进肠癌远处转移。由此,基于肠癌外泌体的高稳定性及易检出性的天然优势,通过对其所携带miRNAs的表达量变化进行检测,可监测疾病进展和治疗效果,从而为结肠癌患者提供更为个性化的诊疗策略。
