过氧化物还原酶3参与肾透明细胞癌发生与发展的分子机制

【目的】探讨肾透明细胞癌组织中硫氧还蛋白依赖的过氧化物还原酶3（PRDX3）的表达与肾透明细胞癌发生发展的关系。【方法】本研究首先在16例肾透明细胞癌组织及癌旁组织中验证了PRDX3的表达。根据表达量构建了786-O的PRDX3过表达细胞系及敲低表达细胞系，考察了PRDX3过表达和敲低表达后，肿瘤细胞的生长情况。通过pull-down试验联合LC-MS/MS技术寻找PRDX3的相互作用蛋白。初步探究了PRDX3与过氧化物酶1（PRDX1）的相互作用关系及PRDX3参与肾透明细胞癌发生发展的机制。【结果】16例肾透明细胞癌组织样本的western blot检测结果表明，有14例样本PRDX3下调表达，下调均值1.78倍左右。成功筛选到PRDX3过表达的786-O单克隆细胞系和对照细胞系［786O-PRDX（3+）和786O-PRDX（3-）］和PRDX3敲低表达的786-O单克隆细胞系和无意义序列对照细胞系（786O-PRDX3KN和786O-PRDX3NCi）。qPCR和western blot结果表明，相比786O-PRDX（3-）组，786O-PRDX（3+）组在mRNA水平过表达约2.1倍，在蛋白水平过表达约1.8倍；相比786O-PRDX3NCi组，786O-PRDX3KN组在mRNA水平低表达约0.48倍，在蛋白水平低表达约0.51倍。CCK-8试验表明，相比786O-PRDX（3-），786O-PRDX（3+）细胞生长速率明显降低。但敲低PRDX3的表达后，敲低组和其对照组细胞的生长速率却无显著性差异。Pull-down试验发现PRDX3可能与PRDX1存在相互作用。结合质谱分析及数据库检索，发现PRDX3通过二硫键与PRDX1结合并发挥作用，分别通过plink软件鉴定到二者可信的结合位点，初步探讨了PRDX3参与肾透明细胞癌发生发展的可能机制。【结论】PRDX3在肾透明细胞癌组织中下调表达，可能参与了肿瘤的发生发展。提高PRDX3的表达水平，能显著降低肿瘤细胞的生长速率。基于PRDX3蛋白，可能开发针对肾透明细胞癌的靶向药物

JUNO Sensitivity on Proton Decay p→νˉK+p\to \bar\nu K^+ Searches

The Jiangmen Underground Neutrino Observatory (JUNO) is a large liquid scintillator detector designed to explore many topics in fundamental physics. In this paper, the potential on searching for proton decay in $p\to \bar\nu K^+$ mode with JUNO is investigated.The kaon and its decay particles feature a clear three-fold coincidence signature that results in a high efficiency for identification. Moreover, the excellent energy resolution of JUNO permits to suppress the sizable background caused by other delayed signals. Based on these advantages, the detection efficiency for the proton decay via $p\to \bar\nu K^+$ is 36.9% with a background level of 0.2 events after 10 years of data taking. The estimated sensitivity based on 200 kton-years exposure is $9.6 \times 10^{33}$ years, competitive with the current best limits on the proton lifetime in this channel

JUNO sensitivity on proton decay p → ν K + searches*

The Jiangmen Underground Neutrino Observatory (JUNO) is a large liquid scintillator detector designed to explore many topics in fundamental physics. In this study, the potential of searching for proton decay in the $p\to \bar{\nu} K^+$ mode with JUNO is investigated. The kaon and its decay particles feature a clear three-fold coincidence signature that results in a high efficiency for identification. Moreover, the excellent energy resolution of JUNO permits suppression of the sizable background caused by other delayed signals. Based on these advantages, the detection efficiency for the proton decay via $p\to \bar{\nu} K^+$ is 36.9% ± 4.9% with a background level of $0.2\pm 0.05({\rm syst})\pm$$0.2({\rm stat})$ events after 10 years of data collection. The estimated sensitivity based on 200 kton-years of exposure is $9.6 \times 10^{33}$ years, which is competitive with the current best limits on the proton lifetime in this channel and complements the use of different detection technologies