目的探讨NAT10在肝癌中的临床意义与潜在作用机制。方法基于癌症基因组图谱(The Cancer Genome Atlas,TCGA)获得的50例正常和374例肿瘤样本,采用R 4.2.1处理所获数据。结果NAT10在肿瘤样本中的表达显著高于正常样本(P<0.001)。与NAT1...目的探讨NAT10在肝癌中的临床意义与潜在作用机制。方法基于癌症基因组图谱(The Cancer Genome Atlas,TCGA)获得的50例正常和374例肿瘤样本,采用R 4.2.1处理所获数据。结果NAT10在肿瘤样本中的表达显著高于正常样本(P<0.001)。与NAT10低表达患者比较,NAT10高表达患者预后较差(P<0.001)。Logistic回归分析结果表明,NAT10高表达与肝癌患者临床预后不良因素相关,NAT10高表达患者更易于进展到晚期。基因集富集分析(gene set enrichment analysis,GSEA)结果显示,NAT10高表达样本中,异生物质代谢、凝血、脂肪酸代谢等相关基因特征均有差异富集。蛋白互作分析结果显示,NAT10可能与IGF2、SST、MUC2、CHGA、AGR2等基因存在相互作用。结论NAT10在肝癌中高表达,且表达水平与肝癌的临床特征及患者生存率存在相关性。NAT10可能是一种潜在的肝癌预后生物学标志物。展开更多
Lead(Pb)plays a significant role in the nuclear industry and is extensively used in radiation shielding,radiation protection,neutron moderation,radiation measurements,and various other critical functions.Consequently,...Lead(Pb)plays a significant role in the nuclear industry and is extensively used in radiation shielding,radiation protection,neutron moderation,radiation measurements,and various other critical functions.Consequently,the measurement and evaluation of Pb nuclear data are highly regarded in nuclear scientific research,emphasizing its crucial role in the field.Using the time-of-flight(ToF)method,the neutron leakage spectra from three^(nat)Pb samples were measured at 60°and 120°based on the neutronics integral experimental facility at the China Institute of Atomic Energy(CIAE).The^(nat)Pb sample sizes were30 cm×30 cm×5 cm,30 cm×30 cm×10 cm,and 30 cm×30 cm×15 cm.Neutron sources were generated by the Cockcroft-Walton accelerator,producing approximately 14.5 MeV and 3.5 MeV neutrons through the T(d,n)^(4)He and D(d,n)^(3)He reactions,respectively.Leakage neutron spectra were also calculated by employing the Monte Carlo code of MCNP-4C,and the nuclear data of Pb isotopes from four libraries:CENDL-3.2,JEFF-3.3,JENDL-5,and ENDF/B-Ⅷ.0 were used individually.By comparing the simulation and experimental results,improvements and deficiencies in the evaluated nuclear data of the Pb isotopes were analyzed.Most of the calculated results were consistent with the experimental results;however,a few areas did not fit well.In the(n,el)energy range,the simulated results from CENDL-3.2 were significantly overestimated;in the(n,inl)D and the(n,inl)C energy regions,the results from CENDL-3.2 and ENDF/B-Ⅷ.0 were significantly overestimated at 120°,and the results from JENDL-5 and JEFF-3.3 are underestimated at 60°in the(n,inl)D energy region.The calculated spectra were analyzed by comparing them with the experimental spectra in terms of the neutron spectrum shape and C/E values.The results indicate that the theoretical simulations,using different data libraries,overestimated or underestimated the measured values in certain energy ranges.Secondary neutron energies and angular distributions in the data files have been presented to explain these discrepancies.展开更多
Existing studies have underscored the pivotal role of N-acetyltransferase 10(NAT10) in various cancers. However, the outcomes of protein-protein interactions between NAT10 and its protein partners in head and neck squ...Existing studies have underscored the pivotal role of N-acetyltransferase 10(NAT10) in various cancers. However, the outcomes of protein-protein interactions between NAT10 and its protein partners in head and neck squamous cell carcinoma(HNSCC) remain unexplored. In this study, we identified a significant upregulation of RNA-binding protein with serine-rich domain 1(RNPS1) in HNSCC, where RNPS1 inhibits the ubiquitination degradation of NAT10 by E3 ubiquitin ligase, zinc finger SWIM domain-containing protein 6(ZSWIM6), through direct protein interaction, thereby promoting high NAT10 expression in HNSCC. This upregulated NAT10 stability mediates the enhancement of specific tRNA ac^(4)C modifications, subsequently boosting the translation process of genes involved in pathways such as IL-6 signaling, IL-8 signaling, and PTEN signaling that play roles in regulating HNSCC malignant progression, ultimately influencing the survival and prognosis of HNSCC patients. Additionally, we pioneered the development of TRMC-seq, leading to the discovery of novel t RNA-ac^(4)C modification sites, thereby providing a potent sequencing tool for tRNAac^(4)C research. Our findings expand the repertoire of tRNA ac^(4)C modifications and identify a role of tRNA ac^(4)C in the regulation of mRNA translation in HNSCC.展开更多
文摘目的探讨NAT10在肝癌中的临床意义与潜在作用机制。方法基于癌症基因组图谱(The Cancer Genome Atlas,TCGA)获得的50例正常和374例肿瘤样本,采用R 4.2.1处理所获数据。结果NAT10在肿瘤样本中的表达显著高于正常样本(P<0.001)。与NAT10低表达患者比较,NAT10高表达患者预后较差(P<0.001)。Logistic回归分析结果表明,NAT10高表达与肝癌患者临床预后不良因素相关,NAT10高表达患者更易于进展到晚期。基因集富集分析(gene set enrichment analysis,GSEA)结果显示,NAT10高表达样本中,异生物质代谢、凝血、脂肪酸代谢等相关基因特征均有差异富集。蛋白互作分析结果显示,NAT10可能与IGF2、SST、MUC2、CHGA、AGR2等基因存在相互作用。结论NAT10在肝癌中高表达,且表达水平与肝癌的临床特征及患者生存率存在相关性。NAT10可能是一种潜在的肝癌预后生物学标志物。
基金supported by the National Natural Science Foundation of China(Nos.11775311 and U2067205)the Stable Support Basic Research Program Grant(BJ010261223282)the Research and Development Project of China National Nuclear Corporation。
文摘Lead(Pb)plays a significant role in the nuclear industry and is extensively used in radiation shielding,radiation protection,neutron moderation,radiation measurements,and various other critical functions.Consequently,the measurement and evaluation of Pb nuclear data are highly regarded in nuclear scientific research,emphasizing its crucial role in the field.Using the time-of-flight(ToF)method,the neutron leakage spectra from three^(nat)Pb samples were measured at 60°and 120°based on the neutronics integral experimental facility at the China Institute of Atomic Energy(CIAE).The^(nat)Pb sample sizes were30 cm×30 cm×5 cm,30 cm×30 cm×10 cm,and 30 cm×30 cm×15 cm.Neutron sources were generated by the Cockcroft-Walton accelerator,producing approximately 14.5 MeV and 3.5 MeV neutrons through the T(d,n)^(4)He and D(d,n)^(3)He reactions,respectively.Leakage neutron spectra were also calculated by employing the Monte Carlo code of MCNP-4C,and the nuclear data of Pb isotopes from four libraries:CENDL-3.2,JEFF-3.3,JENDL-5,and ENDF/B-Ⅷ.0 were used individually.By comparing the simulation and experimental results,improvements and deficiencies in the evaluated nuclear data of the Pb isotopes were analyzed.Most of the calculated results were consistent with the experimental results;however,a few areas did not fit well.In the(n,el)energy range,the simulated results from CENDL-3.2 were significantly overestimated;in the(n,inl)D and the(n,inl)C energy regions,the results from CENDL-3.2 and ENDF/B-Ⅷ.0 were significantly overestimated at 120°,and the results from JENDL-5 and JEFF-3.3 are underestimated at 60°in the(n,inl)D energy region.The calculated spectra were analyzed by comparing them with the experimental spectra in terms of the neutron spectrum shape and C/E values.The results indicate that the theoretical simulations,using different data libraries,overestimated or underestimated the measured values in certain energy ranges.Secondary neutron energies and angular distributions in the data files have been presented to explain these discrepancies.
基金supported by the National Natural Science Foundation of China(82173362 and 81872409)the Guangdong Basic and Applied Basic Research Foundation(2019A1515110110)。
文摘Existing studies have underscored the pivotal role of N-acetyltransferase 10(NAT10) in various cancers. However, the outcomes of protein-protein interactions between NAT10 and its protein partners in head and neck squamous cell carcinoma(HNSCC) remain unexplored. In this study, we identified a significant upregulation of RNA-binding protein with serine-rich domain 1(RNPS1) in HNSCC, where RNPS1 inhibits the ubiquitination degradation of NAT10 by E3 ubiquitin ligase, zinc finger SWIM domain-containing protein 6(ZSWIM6), through direct protein interaction, thereby promoting high NAT10 expression in HNSCC. This upregulated NAT10 stability mediates the enhancement of specific tRNA ac^(4)C modifications, subsequently boosting the translation process of genes involved in pathways such as IL-6 signaling, IL-8 signaling, and PTEN signaling that play roles in regulating HNSCC malignant progression, ultimately influencing the survival and prognosis of HNSCC patients. Additionally, we pioneered the development of TRMC-seq, leading to the discovery of novel t RNA-ac^(4)C modification sites, thereby providing a potent sequencing tool for tRNAac^(4)C research. Our findings expand the repertoire of tRNA ac^(4)C modifications and identify a role of tRNA ac^(4)C in the regulation of mRNA translation in HNSCC.
