DAPT attenuates ox-LDL-induced human umbilical vein endothelial cell injury

目的:; 探究gamma-分泌酶抑制剂N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine; t-butyl ester (DAPT)在氧化低密度脂蛋白(oxidized low-density lipoprotein,; ox-LDL)损伤人脐静脉内皮细胞(human umbilical vein endothelial; cells,HUVECs)模型中的细胞保护作用及其对Notch信号通路的调控。方法:体外培养HUVECs,用ox-; LDL处理HUVECs构建细胞损伤模型。实验分为对照组、ox-LDL处理组、DAPT处理组和DAPT +; ox-LDL处理组。用倒置相差显微镜观察不同处理方法下细胞的形态变化; CCK-8法检测细胞存活率; Western; blot法检测蛋白Notch1、Notch4和Jagged1的表达情况。结果:体外培养HUVECs,倒置相差显微镜下发现ox-LDL处理组细胞死; 亡和碎片增多,经DAPT预处理后,; ox-LDL作用造成的细胞损伤死亡较少,细胞碎片较少。通过CCK-8法检测发现ox-LDL处理组细胞存活率降低,DAPT处理组细胞存活率升高,D; APT预处理后ox-LDL造成存活率降低的幅度变小。在ox-LDL作用下,Notch1和Jagged1蛋白表达量降低,Notch4表达量升高;; 而DAPT作用下Notch1和Jagged1表达量升高,Notch4表达量降低; ox-LDL与DAPT共同作用时蛋白接近正常水平。结论:; ox-LDL对HUVECs具有损伤作用; DAPT减轻ox-LDL对HUVECs造成的损伤;; DAPT保护HUVECs免受ox-LDL损伤的作用与Notch信号通路有关。AIM: To investigate the effect of N-[N-(3,5 -difluorophenacetyl); -L-alanyl]-S-phenylglycine t-butyl ester (DAPT) on the Notch signaling; pathway in a model of oxidized low-density lipoprotein (ox-LDL) -induced; human umbilical vein endothelial cell (HUVEC) damage. METHODS: HUVECs; were divided into control group,ox-LDL group,DAPT group and ox-LDL +; DAPT group. The morphological changes of the HUVECs with different; treatments were observed under light microscope. The viability of the; HUVECs was measured by CCK-8 assay. The protein expression levels of; Notch1,Notch4 and Jagged1 were determined by Western blot. RESULTS:; ox-LDL induced great damage to the HUVECs,evidenced by increased cell; death and debris in the culture. However,the cell damage was abolished; by adding DAPT into the culture. The viability of the HUVECs was; increased by co-treatment with DAPT and ox-LDL. ox-LDL treatment; significantly decreased the protein expression levels of Notch1 and; Jagged1,and elevated Notch4. However,these changes were totally reversed; by DAPT. None of these proteins showed significant change in the HUVECs; co-treated with DAPT and ox-LDL as compared with control group.; CONCLUSION: ox-LDL is able to induce HUVEC damage in vitro. DAPT; attenuates ox-LDL-induced damage in the HUVECs by regulating the Notch; signaling pathway.厦门大学校长基金本科生项

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