~1H-NMR Spectroscopy-based Metabonomic Research on Urine of Model Rats of Wilson's Disease

目的:以基于核磁共振(nuClEAr MAgnETIC rESOnAnCE,nMr)的代谢组学方法对WIlSOn病(WIlSOn'S dISEASE,Wd)铜负荷模型大鼠及正常对照组大鼠的尿液进行研究,分析模型大鼠尿液中代谢物的变化,继而从小分子层面探讨铜过量对机体的损伤机制,以更加清楚的认识本病。方法:28只雄性WISTAr大鼠,体重(180±20)g,随机被分为模型组(n=14)和健康对照组(n=14)。采用铜负荷法制作WIlSOn病大鼠模型,以nMr技术对大鼠尿液进行检测。采用MESTrE-C 2.3软件及自编软件对谱图进行手动调相、基线校正和谱峰对齐。对样品进行分段积分,将积分数据归一化后构成数据矩阵,并利用PCA方法对数据矩阵进行统计分析。结果:相对于正常对照组,模型组大鼠尿液醋酸盐(ACETATE)含量有显著升高,柠檬酸盐(CITrATE)、苯乙酰甘氨酸(PAg)、琥珀酸盐(SuCCInATE)、甲胺(METHylAMInE)、肌氨酸+肌氨酸酐(CrEATInE/CrEATInInE)、丙酮酸盐(PyruVATE)、二甲基甘氨酸(dMg)、丙氨酸(AlAnInE)含量有所升高,胆碱(CHOlInE)、牛磺酸(TAurInE)含量有所降低。这些发生改变的代谢物可能是潜在的Wd铜负荷小分子代谢标志物,可为进一步研究Wd的铜过量代谢机制提供参考。Objective :Applying 1H nuclear magnetic resonance(1H-NMR)based metabonomics to study the changes of small molecular metabolites in the urine of the model rats of Wilson's disease.To explore the pathogenesis of Wilson's disease in small molecular aspect.Methods :28 male Wistar rats[weight=(180±20) g] were divided into two groups randomly,the model group(n=14)and the control group(n=14),with the models established by copper-loaded method.Urine of the rats was tested with 1H-NMR technology.The spectra was edited with MestRe-C2.3 and self-programmed software and then principal component analysis(PCA)was applied to differentiate the two groups.Results :Acetate concentration was found to be significantly higher in the urine of the model group;citrate,PAG,succinate,methylamine,creatine/creatinine,pyruvate,DMG,and alanine were higher,and choline and taurine were lower in the urine of the model group.The small molecular metabolites mentioned above may contribute to the discrimination of the two groups,and provide references for further researches on the pathogenesis of WD.安徽省高校自然科学基金重点项目(KJ2012Z228); 安徽中医学院自然科学基金项目(2011ZR008B

Metabonomic Research on Curative Mechanism of Gandouling Treating Model Rats of Wilson's Disease

目的:以基于核磁共振(nuClEAr MAgnETIC rESOnAnCE,nMr)的代谢组学方法对肝豆灵干预WIlSOn病(WIlSOn'S dISEASE,Wd)模型大鼠进行研究,分析肝豆灵干预后,Wd模型大鼠尿液中代谢物的变化,从小分子层面探讨肝豆灵对Wd的治疗作用机制。方法:42只雄性WISTAr大鼠,体重(180±20)g,随机被分为健康对照组(n=14)、模型组(n=14)和肝豆灵组(n=14)。采用铜负荷法制作WIlSOn病大鼠模型,以nMr技术对大鼠尿液进行检测,经MESTrE-C 2.3软件及自编软件对谱图进行手动调相、基线校正和谱峰对齐。对样品进行分段积分,将积分数据归一化后构成数据矩阵,并利用PCA方法对数据矩阵进行统计分析。结果:相对于模型组,肝豆灵组大鼠尿液色氨酸(TryPTOPHAn)、马尿酸盐(HIPPurATE)、苯基丙氨酸(PHEnylAlAnInE)、甘氨酸(glyCInE)、苯乙酰甘氨酸(PAg)含量有显著升高;乳酸(lACTATE)、甜菜碱(TMAO/bETAInE)、甲酸盐(fOrMATE)、二甲基甘氨酸(dMg)含量有所升高;柠檬酸盐(CITrATE)、肌氨酸酐(CrEATInInE)、谷氨酰胺(gluTAMInE)含量显著降低;丙酮酸盐(PyruVATE)甲基胍(METHylguAnIdInE)、丙酮(ACETOnE)、牛磺酸(TAurInE)含量有所降低。这些发生改变的代谢物可为进一步研究肝豆灵干预Wd的作用机制提供参考。Objective:Applying 1H nuclear magnetic resonance(1H-NMR)based metabonomics to study the changes of small molecular metabolites in the urine of model rats of WD treated with Gandouling.To explore the curative mechanism of Gandouling on the model rats in small molecular aspect.Methods:42 male Wistar rats[weight=(180±20)g]were divided into three groups randomly,the model group(n=14),the control group(n=14),and the Gandouling group(n=14),with the models established with copper-loaded method.Urine of the rats was tested with 1H-NMR technology.The spectra were edited with MestRe-C2.3 and self-programmed software and then principal component analysis(PCA)was applied to differentiate the three groups.Results:Compared with those of the model group,tryptophan,hippurate,phenylalanine,glycine and PAG concentration were found to be significantly higher;lactate,TMAO/betaine,formate and DMG were higher;citrate,creatinine and glutamine were significantly lower;pyruvate,methylguanidine,acetone and taurine were lower in the urine of the Gandouling group.The small molecular metabolites mentioned above may contribute to the curative mechanism of Gandouling,and provide references for further researches on the treatment mechanism of WD.安徽省高校自然科学基金重点项目(KJ2012Z228); 安徽中医学院自然科学基金项目(2011ZR008B

Prediction of Energy Resolution in the JUNO Experiment

International audienceThis paper presents the energy resolution study in the JUNO experiment, incorporating the latest knowledge acquired during the detector construction phase. The determination of neutrino mass ordering in JUNO requires an exceptional energy resolution better than 3% at 1 MeV. To achieve this ambitious goal, significant efforts have been undertaken in the design and production of the key components of the JUNO detector. Various factors affecting the detection of inverse beta decay signals have an impact on the energy resolution, extending beyond the statistical fluctuations of the detected number of photons, such as the properties of liquid scintillator, performance of photomultiplier tubes, and the energy reconstruction algorithm. To account for these effects, a full JUNO simulation and reconstruction approach is employed. This enables the modeling of all relevant effects and the evaluation of associated inputs to accurately estimate the energy resolution. The study reveals an energy resolution of 2.95% at 1 MeV. Furthermore, the study assesses the contribution of major effects to the overall energy resolution budget. This analysis serves as a reference for interpreting future measurements of energy resolution during JUNO data taking. Moreover, it provides a guideline in comprehending the energy resolution characteristics of liquid scintillator-based detectors

Measurement of integrated luminosity of data collected at 3.773 GeV by BESIII from 2021 to 2024

We present a measurement of the integrated luminosity e+e- of collision data collected by the BESIII detector at the BEPCII collider at a center-of-mass energy of Ecm = 3.773 GeV. The integrated luminosities of the datasets taken from December 2021 to June 2022, from November 2022 to June 2023, and from October 2023 to February 2024 were determined to be 4.995±0.019 fb-1, 8.157±0.031 fb-1, and 4.191±0.016 fb-1, respectively, by analyzing large angle Bhabha scattering events. The uncertainties are dominated by systematic effects, and the statistical uncertainties are negligible. Our results provide essential input for future analyses and precision measurements

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

Determination of the number of ψ(3686) events taken at BESIII

The number of ψ(3686) events collected by the BESIII detector during the 2021 run period is determined to be (2259.3±11.1)×106 by counting inclusive ψ(3686) hadronic events. The uncertainty is systematic and the statistical uncertainty is negligible. Meanwhile, the numbers of ψ(3686) events collected during the 2009 and 2012 run periods are updated to be (107.7±0.6)×106 and (345.4±2.6)×106, respectively. Both numbers are consistent with the previous measurements within one standard deviation. The total number of ψ(3686) events in the three data samples is (2712.4±14.3)×10^