Two multidentate ligands 2,9-di[6＇-（2″-hydroxyl-3″-methoxyphenyl）-n-2＇,5＇-diazahexyl]-1,10-phenanthroline（LA）and 2,9-di（6＇-α-phenol-n-2＇,5＇-diazahexyl）-1,10-phenanthroline（LB）were synthesized and full...Two multidentate ligands 2,9-di[6＇-（2″-hydroxyl-3″-methoxyphenyl）-n-2＇,5＇-diazahexyl]-1,10-phenanthroline（LA）and 2,9-di（6＇-α-phenol-n-2＇,5＇-diazahexyl）-1,10-phenanthroline（LB）were synthesized and fully characterized.Protonation of the ligands and the stability of the complexes of the ligands with divalent metal ions were investigated.The trinuclear metal complexes [Cu（Ⅱ）and Zn（Ⅱ）] of the ligands were studied,as catalysts,for the transphosphorylation of the RNA-model substrate 2-hydroxypropyl-p-nitrophenyl phosphate（HPNP）.The second-order rate constants of HPNP-hydrolysis catalyzed by M3L and M3LH-1 were obtained,which indicated that Zn3LBH-1 was the most efficient catalyst among them.The proposed mechanisms included the activation of the substrate via binding to the metal ions and intramolecular nucleophilic attack by the deprotonated C2-hydroxyl of HPNP.展开更多
RNA甲基化占整个RNA修饰的60%以上,而N_(6)-甲基腺苷(N_(6)-methyladenosine,m^(6)A)修饰是人类最常见的一种RNA修饰。m^(6)A修饰对基因表达的调节至关重要,其失调与多种疾病如肿瘤相关。我们以癌症基因组图谱(The Cancer Genome Atlas,...RNA甲基化占整个RNA修饰的60%以上,而N_(6)-甲基腺苷(N_(6)-methyladenosine,m^(6)A)修饰是人类最常见的一种RNA修饰。m^(6)A修饰对基因表达的调节至关重要,其失调与多种疾病如肿瘤相关。我们以癌症基因组图谱(The Cancer Genome Atlas,TCGA)胃癌数据集中的375例患者为对象,研究了m^(6)A相关长非编码RNA(long noncoding RNAs,lncRNAs)的预后意义:先进行Pearson相关性分析,以筛选m^(6)A相关lncRNAs,然后再进行单变量Cox回归分析,确定胃癌患者的预后。确定23种m^(6)A相关lncRNAs为预后lncRNAs后,运用LASSO-Cox回归方法,在TCGA胃癌数据集中构建m^(6)A相关lncRNAs(包括9种m^(6)A相关预后lncRNAs)预后模型。通过计算相关风险评分,并根据风险评分的中位值将胃癌患者分为低、高风险亚组。生存分析曲线和受试者操作特征曲线显示,此预后模型能对胃癌患者的预后进行可靠的预测。本研究揭示了m^(6)A RNA甲基化调节剂在胃癌发生发展中的重要性,并建立了一种m^(6)A基因表达分类模型,该模型可以令人满意地预测胃癌的预后。展开更多
基金Supported by the National Natural Science Foundation of China(Nos.20371028and20671052).
文摘Two multidentate ligands 2,9-di[6＇-（2″-hydroxyl-3″-methoxyphenyl）-n-2＇,5＇-diazahexyl]-1,10-phenanthroline（LA）and 2,9-di（6＇-α-phenol-n-2＇,5＇-diazahexyl）-1,10-phenanthroline（LB）were synthesized and fully characterized.Protonation of the ligands and the stability of the complexes of the ligands with divalent metal ions were investigated.The trinuclear metal complexes [Cu（Ⅱ）and Zn（Ⅱ）] of the ligands were studied,as catalysts,for the transphosphorylation of the RNA-model substrate 2-hydroxypropyl-p-nitrophenyl phosphate（HPNP）.The second-order rate constants of HPNP-hydrolysis catalyzed by M3L and M3LH-1 were obtained,which indicated that Zn3LBH-1 was the most efficient catalyst among them.The proposed mechanisms included the activation of the substrate via binding to the metal ions and intramolecular nucleophilic attack by the deprotonated C2-hydroxyl of HPNP.
文摘目的筛选并构建宫颈癌中与泛凋亡(PANoptosis)相关的长链非编码RNA(long non-coding RNA,lncRNA)预后模型。方法使用生物学数据库筛选出与泛凋亡相关的基因,结合宫颈癌转录组测序数据,筛选与泛凋亡基因表达相关的lncRNA,采用最小绝对值收缩与选择算子(least absolute shrinkage and selection operator,LASSO)-Cox回归分析,构建预后模型。根据模型对宫颈癌样本按风险评分分为高、低风险组。使用Kaplan-Meier、基因集富集分析(gene set enrichment analysis,GSEA)、ESTIMATE、CIBERSORT、Oncopredict等分析方法对高、低风险组进行差异分析。使用实时荧光逆转录聚合酶链式反应(reverse transcription-polymerase chain reaction,RT-PCR)验证相关lncRNAs在宫颈癌组织和癌旁组织中的表达差异。结果成功构建包含11个lncRNAs的预后模型,分别是ARHGEF7-AS2、ASH1L-AS1、BASP1-AS1、C7orf66、CATIP-AS1、CYP4A22-AS1、DBH-AS1、DCST1-AS1、DGUOK-AS1、DPH6-DT、FLJ31104。高风险组患者总生存期较低风险组显著缩短(P<0.001)。模型在宫颈癌患者1、2、3年生存率预测中表现出良好效能,曲线下面积(area under the curve,AUC)分别为0.765(95%CI:0.705~0.825)、0.808(95%CI:0.728~0.868)和0.802(95%CI:0.732~0.852),且风险评分为独立预后因素。列线图预测宫颈癌患者1年期生存率为95%,2年期生存率为91%,而3年期生存率则下降至82%。低风险组患者免疫评分和ESTIMATE评分均高于高风险组(P<0.05)。低风险组CD+8T细胞、激活记忆CD+4 T细胞、调节性T细胞水平明显低于高风险组(P<0.05),休眠记忆CD+4 T细胞、激活肥大细胞、中性粒细胞水平明显高于高风险组(P<0.05)。Afuresertib、奥沙利铂、伏立诺他在高风险组中的药物耐药性较低风险组更强(P<0.05)。ARHGEF7-AS2和DBH-AS1在癌组织中的表达下调(P均<0.001),BASP1-AS1和CYP4A22-AS1在癌组织中的表达上调(P均<0.001)。结论构建的泛凋亡相关lncRNA预后模型能有效预测宫颈癌患者预后,并为个体化治疗提供潜在参考。
