微流控芯片-质谱联用技术在细胞代谢与药物代谢中的研究进展

细胞代谢与药物代谢是新药筛选和研发的关键环节,在推动人类大健康发展进程中具有重要意义。通常情况下,细胞代谢和药物筛选以传统细胞培养测定研究为主,多为静态培养条件,无法很好地模拟体内细胞动态微环境。微流控芯片-质谱联用是近年发展起来的一种新型高通量分析技术。微流控芯片模块可高度模拟细胞体内动态微环境,与质谱联用可实时在线检测样品物质,具有高效、快速、简便、样品和试剂消耗低等特点,广泛应用于细胞代谢和药物代谢分析,有利于加速药物筛选研发进程。该文重点综述了微流控芯片-质谱联用技术及其在细胞代谢和药物代谢方面的应用概况,并对目前存在的局限性进行了讨论和展望,以期为微流控芯片-质谱联用技术在新药研发与细胞分析领域的发展提供参考。     

INHERITANCE OF DIVISIBILITY FORMS A LARGE SUBALGEBRA

Let A be an infinite dimensional stably finite unital simple separable C^*-algebra.Let B■A be a stably(centrally)large subalgebra in A such that B is m-almost divisible(m-almost divisible,weakly(m,n)-divisible).Then A is 2(m+1)-almost divisible(weakly m-almost divisible,secondly weakly(m,n)-divisible).     

Cytosolic escape of mitochondrial DNA triggers cGAS-STING-NLRP3 axis-dependent nucleus pulposus cell pyroptosis

Low back pain (LBP) is a major musculoskeletal disorder and the socioeconomic problem with a high prevalence that mainly involves intervertebral disc (IVD) degeneration, characterized by progressive nucleus pulposus (NP) cell death and the development of an inflammatory microenvironment in NP tissue. Excessively accumulated cytosolic DNA acts as a damage-associated molecular pattern (DAMP) that is monitored by the cGAS-STING axis to trigger the immune response in many degenerative diseases. NLRP3 inflammasome-dependent pyroptosis is a type of inflammatory programmed death that promotes a chronic inflammatory response and tissue degeneration. However, the relationship between the cGAS-STING axis and NLRP3 inflammasome-induced pyroptosis in the pathogenesis of IVD degeneration remains unclear. Here, we used magnetic resonance imaging (MRI) and histopathology to demonstrate that cGAS, STING, and NLRP3 are associated with the degree of IVD degeneration. Oxidative stress induced cGAS-STING axis activation and NLRP3 inflammasome-mediated pyroptosis in a STING-dependent manner in human NP cells. Interestingly, the canonical morphological and functional characteristics of mitochondrial permeability transition pore (mPTP) opening with the cytosolic escape of mitochondrial DNA (mtDNA) were observed in human NP cells under oxidative stress. Furthermore, the administration of a specific pharmacological inhibitor of mPTP and self-mtDNA cytosolic leakage effectively reduced NLRP3 inflammasome-mediated pyroptotic NP cell death and microenvironmental inflammation in vitro and degenerative progression in a rat disc needle puncture model. Collectively, these data highlight the critical roles of the cGAS-STING-NLRP3 axis and pyroptosis in the progression of IVD degeneration and provide promising therapeutic approaches for discogenic LBP.Subject terms: Cell death, Diseases     

Rapid Screening of Lipase Inhibitors from Ophiopogonis Radix Using High-Performance Thin Layer Chromatography by Two Step Gradient Elution Combined with Bioautographic Method

In this study, a high-performance thin layer chromatography (HPTLC) method by two step gradient elution with two mobile phases was developed for the simultaneous analysis of seven constituents in Ophiopogonis Radix. The chromatography was performed on silica gel 60 F₂₅₄ plate with dichloromethane-methanol-ethyl acetate-water (70:25:12:3, v/v/v/v) and dichloromethane-methanol (300:1, v/v) as the mobile phase for two step gradient elution. Then, the HPTLC profiles were observed after derivatization with 10% sulfuric acid in ethanol solution. The obtained HPTLC images were further analyzed by chemometric approaches and the samples could be clustered based on regions and/or growth years, which were two important factors affecting the constituents in Ophiopogonis Radix. Furthermore, five compounds including ophiopogonin D, ophiopojaponin C, ophiopogonin D’, ophiopogonin C’ and methylophiopogonanone B were screened as potential lipase inhibitors from Ophiopogonis Radix by the HPTLC-bioautographic method. The binding modes and interactions between the five compounds and lipase were further explored by molecular docking analysis. The developed HPTLC method could be used for quality control of Ophiopogonis Radix and screening of the potential lipase inhibitors.     

大学化学实验电势-pH曲线测定探讨

大学化学实验电势-pH曲线测定中采用的电极反应S 2H 2e-=H2S(g)的电极电势表达式有误,导致所绘制的电势-pH曲线与教科书要求不符;没有给出电极反应FeY- e-= FeY2-的标准电极电势φθ,易使学生误将电极反应Fe3 e-=Fe2 的φθ=0.771V作为电极反应FeY- e-= FeY2-的φθ;仅从两个电极反应电极电势的差值来确定脱硫氧化-还原反应的最佳pH范围不够全面,应结合溶液中络合物的稳定性、液相催化湿法脱硫原理、脱硫溶液pH对H2S吸收反应的影响、对再生反应的影响和脱硫过程的经济性等多方面考虑,使学生有全面综合的认识.     

基于应变片的自由活塞斯特林制冷机位移测试研究

压缩活塞与排出器的位移大小及相位差对自由活塞斯特林制冷机的制冷性能具有极其重要的影响。文中通过对目前各种位移测试方法优缺点分析,结合自由活塞式斯特林制冷机自身特点,提出了采用应变片响应涡旋柔性弹簧形变来测量活塞和排出器位移的新方法。通过分析、设计和标定,建立了一套基于应变片的自由活塞斯特林制冷机位移测量系统。实验测试结果表明,该位移测量系统是可靠的,具有体积小、投资省等优点,且不需要特别的安装空间。     

Cobalt Element Effect of Ternary Mesoporous Cerium Lanthanum Solid Solution for the Catalytic Conversion of Methanol and CO2 into Dimethyl Carbonate

A citric acid ligand assisted self-assembly method is used for the synthesis of ternary mesoporous cerium lanthanum solid solution doped with metal elements (Co, Zr, Mg). Their textural property was characterized by X-ray diffraction, transmission electron microscopy, N₂ adsorption-desorption, X-ray photoelectron spectroscopy and TPD techniques, and so on. The results of catalytic testing for synthesis of dimethyl carbonate (DMC) from CH₃OH and CO₂ indicated that the DMC yield reached 316 mmol/g on Ce-La-Co solid solution when the reaction temperature was 413 K and the reaction pressure was 8.0 MPa. It was found that Co had synergistic effect with La and Ce, doping of Co on the mesoporous Ce-La solid solution was helpful to increase the surface area of the catalyst, promote CO₂ adsorption and activation, and improve the redox performance of solid solution catalyst. The conversion of Co²⁺ to Co³⁺ resulted in the continuous redox cycle between Ce⁴⁺ and Ce³⁺, and the oxygen vacancy content of the catalyst was increased. Studies have shown that the catalytic performance of Ce-La-Co solid solution is positively correlated with oxygen vacancy content. On this basis, the reaction mechanism of DMC synthesis from CO₂ and CH₃OH on the catalyst was speculated.     

"一锅煮"合成异黄酮

以芳基酚和苯乙酸为原料,用三氟化硼乙醚作溶剂和催化剂,在C1试剂DMF/PC l5体系中,“一锅煮”合成7-羟基异黄酮及其类似物,产率在90%以上。其结构经1H NMR,IR和MS确证。     

窄分子量分布聚四氢呋喃的合成

以发烟硫酸-高氯酸为催化剂,通过四氢呋喃的阳离子开环聚合合成了窄分子量分布的聚四氢呋喃(PTHF)。研究了发烟硫酸和高氯酸用量、反应时间、反应温度等对PTHF分子量(Mn)及其分布(Mw/Mn)的影响。结果表明,减少发烟硫酸或增加高氯酸用量可使Mn上升;反应时间超过3 h后,反应时间对Mn及Mw/Mn的影响不大;于2℃反应Mn有最大值(11 760);反应时间5 h,在N2中聚合的Mw/Mn较小;低转化率(Mw/Mn小于1.2)时,通N2对Mn(4 000~5 500)及Mw/Mn(1.12~1.19)的影响不大。     

燃烧管内悬浮铝粉燃烧爆炸过程的研究

 铝粉的燃烧与加速机理一直是相关部门研究的热点。为了深入研究其在受限空间内的燃烧与传播特性,基于双流体模型、湍流k-ε模型以及铝粉燃烧等模型,选用SIMPLE格式,对大型卧式燃烧管内铝粉颗粒与空气的两相悬浮流湍流燃烧加速转爆炸现象进行了数值研究,得到了铝粉火焰在管内的燃烧传播过程中管内各相关参数的详细变化情况,并与相关的实验结果吻合。