NMR联用HILIC-UPLC-MS/MS测定TNBS诱导的结肠炎大鼠尿液和血浆代谢物变化

目的基于非靶标和靶标代谢组学技术，探讨三硝基苯磺酸（TNBS）诱导的结肠炎模型大鼠尿液以及血浆中内源性代谢物的变化。方法16只雄性SD大鼠随机分成对照组和模型组，每组8只，对模型组大鼠给予TNBS灌肠以建立实验性大鼠结肠炎模型。利用核磁共振氢谱（1H NMR）检测两组大鼠尿液代谢物，同时联用HILIC模式超高效液相色谱串联三重四级杆质谱（HILIC-UPLC-MS/MS）测定以上大鼠尿液以及血浆中氨基酸水平，并通过多元变量统计方法对代谢组学数据进行分析。结果同对照组相比，1H NMR结果表明模型组大鼠尿液代谢轮廓发生明显改变，其中丙酮酸、甲酸、甲胺与柠檬酸水平升高，氧化三甲胺和丙二酸水平降低（均P < 0.05）；HILIC-UPLC-MS/MS结果显示模型组大鼠尿液中苯丙氨酸、组氨酸水平显著上升，血浆中赖氨酸、精氨酸、苯丙氨酸、亮氨酸、甘氨酸、色氨酸、脯氨酸、组氨酸和酪氨酸水平显著升高，但谷氨酰胺、缬氨酸、丙氨酸和异亮氨酸水平明显降低（均P < 0.05）。结论经TNBS诱导的结肠炎模型大鼠，其能量代谢、胺类代谢以及氨基酸代谢通路受到影响；采用的1H NMR与HILIC-UPLC-MS/MS联用的多元代谢组学方法，揭示了结肠炎大鼠尿液及血浆代谢物的变化，为炎症性肠病的机制研究与相关生物标志物的探索提供了新的思路

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