A new metabolite of nodakenetin by rat liver microsomes and its quantification by RP‐HPLC method

The biotransformation of nodakenetin (NANI) by rat liver microsomes in vitro was investigated. Two major polar metabolites were produced by liver microsomes from phenobarbital‐pretreated rats and detected by reversed‐phase high‐performance liquid chromatography (RP‐HPLC) analysis. The chemical structures of two metabolites were firmly identified as 3′(R)‐hydroxy‐nodakenetin‐3′‐ol and 3′(S)‐hydroxy‐nodakenetin‐3′‐ol, respectively, on the basis of their ¹H‐NMR, MS and optical rotation analysis. The latter was a new compound. A sensitive, selective and simple RP‐HPLC method has been developed for the simultaneous determination of NANI and its two major metabolites in rat liver microsomes. Chromatographic conditions comprise a C₁₈ column, a mobile phase with MeOH‐H₂O (40 : 60, v/v), a total run time of 40 min, and ultraviolet absorbance detection at 330 nm. In the rat heat‐inactivated liver microsomal supernatant, the lower limits of detection and quantification of metabolite I, metabolite II and NANI were 5.0, 2.0, 10.0 ng/mL and 20.0, 5.0, 50.0 ng/mL, respectively, and their calibration curves were linear over the concentration range 50–400, 20–120 and 150–24000 ng/mL, respectively. The results provided a firm basis for further evaluating the pharmacokinetics and clinical efficacy of NANI. Copyright © 2009 John Wiley & Sons, Ltd.     

Strengthening of the C−F Bond in Fumaryl Fluoride with Superacids

The reaction of fumaryl fluoride with the superacidic solutions XF/MF₅ (X=H, D; M=As, Sb) results in the formation of the monoprotonated and diprotonated species, dependent on the stoichiometric ratio of the Lewis acid to fumaryl fluoride. The salts [C₄H₃F₂O₂]⁺[MF₆]⁻ (M=As, Sb) and [C₄H₂X₂F₂O₂]²⁺([MF₆]⁻)₂ (X=H, D; M=As, Sb) are the first examples with a protonated acyl fluoride moiety. They were characterized by low-temperature vibrational spectroscopy. Low-temperature NMR spectroscopy and single-crystal X-ray structure analyses were carried out for [C₄H₃F₂O₂]⁺[SbF₆]⁻ as well as for [C₄H₄F₂O₂]²⁺([MF₆]⁻)₂ (M=As, Sb). The experimental results are discussed together with quantum chemical calculations of the cations [C₄H₄F₂O₂ ⋅ 2 HF]²⁺ and [C₄H₃F₂O₂ ⋅ HF]⁺ at the B3LYP/aug-cc-pVTZ level of theory. In addition, electrostatic potential (ESP) maps combined with natural population analysis (NPA) charges were calculated in order to investigate the electron distribution and the charge-related properties of the diprotonated species. The C−F bond lengths in the protonated dication are considerably reduced on account of the +R effect.     

IL-18与IL-18R分子对接计算发展模拟蛋白质互作研究方法

研究蛋白质互作的化学生物学方法主要有荧光共振能量转移(Fluorescence resonance energy transfer, FRET)、酵母双杂交(Yeast two-hybrid technology, YTH)、免疫共沉淀(Co-immunoprecipitation, Co-IP)等。在此基础上,为了发展一种新的研究生物大分子互作,特别是膜蛋白相互作用的定量计算方法,依据前期研究发现,应用ELISA方法与QAH-NEU-1定量芯片技术检测NLRP2:ShRNAs慢病毒(Lentivirus)感染人脑微血管内皮细胞(Human brain microvascular endothelial cells, HBMEC), 敲除(Knocking down)NLRP2基因后的IL-18的分泌量与对照组比较, 显著提高(IL-18: 998 pg/mL),表明它在炎症免疫中起关键调控作用。本文采用高性能的Discovery Studio 2021(DS2018R2)大分子计算模拟软件,在RCSB PDB数据库中调用蛋白质文件建立其立体结构,应用ZDOCK程序算法探究IL-18亚基(AB亚基或B亚基)与IL-18R互作的空间结构与构象变化,计算找到了相互作用界面的氨基酸的一级序列与二级结构,以及它们之间的相互作用力,并用拉氏图评估对接构象,研究发现B亚基在IL-18与IL-18R的结合中起主要作用。该计算方法与实验方法比较,可快速找到蛋白-蛋白相互作用的构象空间,优化膜蛋白互作的精度;能从原子与量子水平探究细胞因子与膜蛋白受体的互作;更深入解析分子机理,数据精确定量。研究结果表明本文应用ZDOCK算法建立了通过计算模拟膜蛋白生物大分子互作的新领域,为细胞因子与化学因子的多肽类药物开发提供新的思路; 为细菌病毒感染/肿瘤疾病的防治提供科学理论依据; 在分子识别,神经元网络深度学习,生物信息处理领域具有广泛的应用。     

Bézoutians and injectivity of polynomial maps

We prove that an endomorphism f of affine space is injective on rational points if its Bézoutian is constant. Similarly, f is injective at a given rational point if its reduced Bézoutian is constant. We also show that if the Jacobian determinant of f is invertible, then f is injective at a given rational point if and only if its reduced Bézoutian is constant.     

The Webster scalar curvature flow on CR sphere. Part I

This is the first of two papers, in which we prove some properties of the Webster scalar curvature flow. More precisely, we establish the long-time existence, L^p$L^p$ convergence and the blow-up analysis for the solution of the flow. As a by-product, we prove the convergence of the CR Yamabe flow on the CR sphere. The results in this paper will be used to prove a result of prescribing Webster scalar curvature on the CR sphere, which is the main result of the second paper.     

Elliptic Yang–Mills flow theory

We lay the foundations of a Morse homology on the space of connections on a principal G‐bundle over a compact manifold Y, based on a newly defined gauge‐invariant functional on . While the critical points of correspond to Yang–Mills connections on P, its L²‐gradient gives rise to a novel system of elliptic equations. This contrasts previous approaches to a study of the Yang–Mills functional via a parabolic gradient flow. We carry out the analytical details of our programme in the case of a compact two‐dimensional base manifold Y. We furthermore discuss its relation to the well‐developed parabolic Morse homology over closed surfaces. Finally, an application of our elliptic theory is given to three‐dimensional product manifolds .     

Lifting problems and transgression for non-abelian gerbes

We discuss lifting and reduction problems for bundles and gerbes in the context of a Lie 2-group. We obtain a geometrical formulation (and a new proof) for the exactness of Breen’s long exact sequence in non-abelian cohomology. We use our geometrical formulation in order to define a transgression map in non-abelian cohomology. This transgression map relates the degree one non-abelian cohomology of a smooth manifold (represented by non-abelian gerbes) with the degree zero non-abelian cohomology of the free loop space (represented by principal bundles). We prove several properties for this transgression map. For instance, it reduces–in case of a Lie 2-group with a single object–to the ordinary transgression in ordinary cohomology. We describe applications of our results to string manifolds: first, we obtain a new comparison theorem for different notions of string structures. Second, our transgression map establishes a direct relation between string structures and spin structures on the loop space.     

Algebraic topology and the quantization of fluctuating currents

We give a new approach to the study of statistical mechanical systems: algebraic topology is used to investigate the statistical distributions of stochastic currents generated in graphs. In the adiabatic and low temperature limits we will demonstrate that quantization of current generation occurs.