Comparison of mechanism for copper-excretion between Gandouling Tablets and penicillamine by metabonomics

目的探讨肝豆灵片(大黄、黄芩、黄连、半枝莲等)和青霉胺对大鼠的代谢物,以比较两者排铜机制异同。方法适应性饲养1周后,大鼠被随机分为对照组、模型组、肝豆灵组、青霉胺组。造模结束后,取各组大鼠血清样品分析其核磁共振谱峰。结果模型组大鼠血清乳酸、糖蛋白、肌酸、肌酐、谷氨酰胺、精氨酸的量升高,葡萄糖、甜菜碱、胆碱、磷酸胆碱、脂质的量降低;青霉胺组大鼠血清葡萄糖、甜菜碱、胆碱、胆碱磷酸、脂质的量升高,糖蛋白、乳酸、肌酸、肌酐、谷氨酰胺的量降低;肝豆灵组大鼠血清3-羟基丁酸、亮氨酸、异亮氨酸、缬氨酸、胆碱、胆碱磷酸、葡萄糖、脂质的量升高,谷氨酰胺、乳酸、肌酸、肌酐、精氨酸的量降低。结论青霉胺与肝豆灵均可明显调节铜负荷大鼠的葡萄糖、乳酸、肌酸、肌酐、胆碱、磷酸胆碱、谷氨酰胺和脂质向正常范围回归的趋势。而肝豆灵片还可调节鸟氨酸循环、支链氨基酸、3-羟基丁酸及氨的代谢。AIM To apply metabonomics to the exploration of differences in mechanism for copper-excretion between Gandouling Tablets( Rheum officinale Baill.,Scutellaria baicalensis Georgi,Coptis chinensis Franch.,Scutellaria barbata D. Don,etc.) and penicillamine. METHODS After adaptive breeding for one week,the tested rats were randomly divided into four groups, including control, model, Gandouling Tablets and penicillamine group. After modeling,the sera of all groups were analyzed by1H-NMR spectroscopy. RESULTS The model group showed increased levels of lactate, glutamine, glycoprotein, creatine, creatinine and arginine,together with decreased levels of glucose,betaine,choline,phosphocholine and lipid. Penicillamine group had increased levels of glucose,betaine,choline,phosphocholine and lipid,together with decreased levels of glutamine,glycoprotein,lactate,creatine and creatinine. While Gandouling Tablets increased 3-hydroxybutyrate,leucine, isoleucine, valine, choline, phosphocholine, glucose and lipid, but decreased glutamine,lactate,creatine,creatinine and arginine. CONCLUSION There is a similarity of mechanism for copper excretion between Gandouling Tablets and penicillamine, mainly in the metabolic regulation of glutamine, lactate,creatine,creatinine, glucose, choline, phosphocholine and lipid returning to normal. Moreover,Gandouling Tablets can regulate the metabolisms of ornithine cycle,3- hydroxybutyric acid and branched chain amino acids.国家自然科学基金青年基金资助(81202691);; 安徽省高校自然科学基金重点项目(KJ2012Z228);; 安徽省高校博士后岗位项目(2013年

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

目的:以基于核磁共振(nMr)的代谢组学方法对WIlSOn病大鼠模型及正常对照组大鼠血清进行研究,分析血清中小分子代谢物的变化,从小分子代谢物层面上探讨WIlSOn病的内在机制,以更加清楚的认识本病。方法:22只雄性WISTAr大鼠,体重(180±20)g,随机被分为模型组(n=11)和健康对照组(n=11),采用铜负荷法制作WIlSOn病大鼠模型,以核磁共振(nMr)技术对大鼠血清进行检测。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,模型组大鼠血清甜菜碱(bETAInE)、氧化三甲胺(TAMO)、低密度脂蛋白(ldl)、极低密度脂蛋白(Vldl)、葡萄糖(gluCOSE)含量有显著降低,胆碱(CHOlInE)、胆碱磷酸(PHOSPHOrylCHOlInE)的含量有所降低,乳酸(lACTATE)、谷氨酰胺(gluTAMInE)、糖蛋白(glyCOPrOTEIn)有显著升高,肌氨酸+肌氨酸酐(CrEATInE+CrEATInInE),精氨酸(ArgInInE)有所升高。这些发生改变的代谢物可以作为Wd的小分子代谢标志物,为进一步研究Wd的内在代谢机制提供参考。Objective:Applying 1H nuclear magnetic resonance(1H-NMR)spectroscopy-based metabonomic approach to investigate the changes of small molecular metabolites in the serum from the rats of the model group of Wilson's disease contrasted with those of the control group.Exploring the pathogenesis of Wilson's disease from small molecular aspect.Methods:22 male Wistar rats[weight=(180±20)g]were divided into two groups randomly,the model group(n=11)and the control group(n=11),with the models established with excessive copper method.The serum 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 two groups.Results:Choline and phosphorylcholine concentrations were found to be lower and TAMO+betaine,LDL,VLDL and glucose were significantly lower in the serum of the model group.While creatinine and arginine concentrations were found to be higher and lactate,glutamine and glycoprotein were significantly higher in the model group.The small molecular metabolites above may contribute to the discrimination,and serve as references for further research on WD pathogenesis.“十一五”国家科技支撑计划分课题重大疑难疾病中医防治研究项目(2006BA104A02

~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

苯胺嘧啶衍生物X-9通过下调整合素β1表达抑制肝细胞癌迁移侵袭

整合素在许多肿瘤细胞中高表达，并且参与肿瘤细胞的侵袭转移。在肝细胞癌中，整合素β1被报导高表达，并促进肿瘤细胞的侵袭。目前，对于整合素的表达调控癌细胞机制以及干预其表达进而抑制肿瘤细胞转移的研究较少。本研究探讨利用小分子化合物抑制整合素表达来抑制肿瘤细胞迁移和侵袭的可能。首先，对临床肝癌细胞患者癌组织和癌旁组织中的整合素β1的表达进行检测，发现其在癌组织中的表达显著高于癌旁组织（P<0.05）。对TCGA肿瘤数据库的生物信息学分析结果同样显示，整合素β1的高表达与肝癌的分期（P=0.019）和预后（P=0.013）相关。通过筛选发现，苯胺嘧啶衍生物X-9可以抑制肝癌细胞中整合素β1的mRNA和蛋白质的表达（P<0.01）。细胞划痕愈合实验和细胞穿孔结果显示，苯胺嘧啶衍生物X-9能够抑制肝癌细胞的迁移和侵袭（P<0.01）。进一步的研究证实，在肝癌细胞中外源表达整合素β1可以逆转X-9对肝癌细胞迁移和侵袭的抑制；而在敲除整合素β1的细胞中，X-9对细胞的迁移和侵袭的抑制被消除。因此，鉴定出苯胺嘧啶衍生物X-9可以通过下调整合素β1表达，进而抑制肝癌细胞的迁移和侵袭。福建省自然科学基金（No.2016J05087,No.2017J01201）;;福建省卫计委医疗创新项目（No.2015-CXB-15

Development of aquantitative ELISA detection method for Varicella Zoster Virus(VZV) antigen

目的:建立水痘-带状疱疹病毒(VzV)抗原的双抗体夹心ElISA定量检测方法,用于质控VzV灭活疫苗研发和生产中抗原含量。方法:以VzV中和单抗5f6C8为包被抗体、8H5d1为酶标抗体,构建定量检测VzV抗原的双抗体夹心ElISA方法,并对本方法的特异性、灵敏度、准确性、线性和稳定性等性能进行分析。结果:建立的双抗体夹心定量检测VzV抗原的ElISA方法,线性范围为0.4μg~13μg/Ml,相关系数为r2=0.994,定量限度为0.4μg/Ml;变异系数CV80%。与VzV以外的相关病毒样本没有交叉反应。结论:构建的VzV抗原ElISA定量检测方法的各项性能符合定量检测需要,可用于VzV灭活疫苗的研发和生产过程的抗原含量检测。Objective:To develop a quantitative enzyme linked immunosorbent assay(Q-ELISA) to determine the concentration of Varicella Zoster Virus(VZV) antigen.This method was used to determine VZV antigen content at each stage of VZV inactived vaccine developing and manufacturing process.Methods: A double antibody sandwich Q-ELISA was developed to determine concentration of VZV antigen,which was based on the the high-affinity neutralizing monoclonal antibodies 5F6C8 as capture antibodies,and 8H5D1 as HRP-labeled antibody.The performance of reagent were evaluated.Results: The Q-ELISA for VZV antigen content was successfully developed.The reagent had good performance.The quantitation scope was 0.4 μg~13 μg/ml,The coefficient correlation was 0.994,the limit of detection was 0.4 μg /ml,the recovery was between 87.5% and 111.6%.The stability was up to 80% after reagent was heated for 6 days at 37℃.The variation coefficient was lower than 15%,and the reagent was no reaction with other sample except VZV antigen.Conclusion: The Q-ELISA for VZV antigen was developed with good specificity,accuracy and stability.The method can be used to determine VZV antigen content during development and production of VZV inactived vaccine

the evolution of security requirements for cryptographic modules:the status quo, dilemma and future trends

联邦信息处理规范FIPS 140系美国国家标准技术研究所(NIST)制定并由美国联邦政府颁布的密码模块安全要求。FIPS 140-1与FIPS 140-2先后于1994年和2001年颁布执行。按照NIST每5年启动1次标准审查的既定方针,FIPS 140-2的审查暨FIPS 140-3的制定工作于2005年1月启动。但是,在先后公布FIPS 140-3草案与修订草案并面向全球征集到2000余条修订意见后,时至今日,FIPS 140-3标准仍未颁布,这一事实引人深思。通过对近20年来FIPS 140系列标准演变的分析,结合密码分析与应用技术的发展,探讨FIPS 140系列标准随着密码模块技术发展产生的结构性与技术性改进以及当前陷于困境的可能原因,展望可能的发展趋势。国家自然科学基金资助项目(61073178)|北京市自然科学基金资助项目(4112064

湖北神农架发现白眉林鸲

首次正式报道了白眉林鸲(Tarsiger indicus)在湖北省的分布以及亚种和繁殖信息,该种为湖北省新纪录

基于测量非金属晶体矿物电荷分布的环境温度变化测定装置和测定方法

本发明公开了一种基于测量非金属晶体矿物电荷分布的环境温度变化测定装置和测定方法。它包括样品腔、热激活单元、光电转换探测单元和分析单元；所述的样品腔用于装载样品；所述的热激活单元用于通过加热热激活样品腔中的样品使其释放热释光；所述的光电转换探测单元用于将样品释放的热释光光信号转换成电信号；所述的分析单元用于读取光电转换探测单元的电信号，分析样品的热释光发光特征，再与经X射线、紫外光或者同位素放射源辐照的、已知受热历史的同种样品的热释光发光特征进行对比，从而估计样品的受热温度变化历史。利用本发明的装置，按照本发明的方法能以非现场方式测量样品受热历史和温度变化历史情况