Anti-fibrosis attributes: UHPLC-MS/MS-based pharmacokinetics profiling of a novel autotaxin inhibitor with excellent in vivo efficacy in rat

3,4-Difluorobenzyl(1-ethyl-5-(4-((4-hydroxypiperidin-1-yl)-methyl)thiazol-2-yl)-1H-indol-3-yl)carbamate (NAI59), a small molecule with outstanding therapeutic effectiveness to anti-pulmonary fibrosis, was developed as an autotaxin inhibitor candidate compound. To evaluate the pharmacokinetics and plasma protein binding of NAI59, a UPLC–MS/MS method was developed to quantify NAI59 in plasma and phosphate-buffered saline. The calibration curve linearity ranged from 9.95 to 1990.00 ng/mL in plasma. The accuracy was −6.8 to 5.9%, and the intra- and inter-day precision was within 15%. The matrix effect and recovery, as well as dilution integrity, were within the criteria. The chromatographic and mass spectrometric conditions were also feasible to determine phosphate-buffered saline samples, and it has been proved that this method exhibits good precision and accuracy in the range of 9.95–497.50 ng/mL in phosphate-buffered saline. This study is the first to determine the pharmacokinetics, absolute bioavailability, and plasma protein binding of NAI59 in rats using this established method. Therefore, the pharmacokinetic profiles of NAI59 showed a dose-dependent relationship after oral administration, and the absolute bioavailability in rats was 6.3%. In addition, the results of protein binding showed that the combining capacity of NAI59 with plasma protein attained 90% and increased with the increase in drug concentration.     

Convex functions, subdifferentiability and renormings

This paper through discussing subdifferentiability and convexity of convex functions shows that a Banach space admits an equivalent uniformly [locally uniformly, strictly] convex norm if and only if there exists a continuous uniformly [locally uniformly, strictly] convex function on some nonempty open convex subset of the space and presents some characterizations of super-reflexive Banach spaces. Supported by NSFC     

ON THE PRODUCT OF GATEAUX DIFFERENTIABILITY LOCALLY CONVEX SPACES

A locally convex space is said to be a Gateaux differentiability space (GDS)provided every continuous convex function defined on a nonempty convex open subset D of the space is densely Gateaux differentiable in D.This paper shows that the product of a GDS and a family of separable Frechet spaces is a GDS,and that the product of a GDS and an arbitrary locally convex space endowed with the weak topology is a GDS.     

塞曼石墨炉原子吸收光谱法测定粉尘降尘中痕量锡

以KOH熔样,又以KOH作基体改进剂,研究了测定锡的灰化温度、原子化行为和消除干扰及试样前处理的方法,以KOH熔解的粉尘及降尘样液,特别适用于塞曼石墨炉的测定,背景可完全扣除。方法简便、快速、准确,灵敏度和精度高。相对标准偏差为4.0%,回收牢在96.4～110%范围内。     

扰动周期KdV方程的小波基分析

本文利用样条小波基构造近似惯性流形来研究扰动周期ＫｄＶ方程的长期动力学行为·     

Direct, organocatalytic α-sulfenylation of aldehydes and ketones

A method for direct sulfenylation of aldehydes and ketones, catalyzed by a novel pyrrolidine trifluoromethanesulfonamide organocatalyst, has been developed. This process serves as an efficient and mild approach to the preparation of α-phenylthio-ketones and -aldehydes.     

EXACT CONTROLLABILITY FOR FIRST ORDER QUASILINEAR HYPERBOLIC SYSTEMS WITH ZERO EIGENVALUES＊＊＊

For a class of mixed initial-boundary value problem for general quasilinear hyperbolic sys-tems with zero eigenvalues, the authors establish the local exact controllability with boundary controls acting on one end or on two ends and internai controls acting on a part of equations in the system.     

乙醇增敏光泽精－H_2O_2－Pb（Ⅱ）化学发光体系的研究及应用

本文研究了Ｈ＿２Ｏ＿２氧化光泽精发光反应及乙醇的敏化作用，发现加入乙醇可使铅催化Ｈ＿２Ｏ＿２，氧化光泽精的发光强度有较大幅度的增强；铅量在３×１０￣（－７）～８×１０￣（－５）ｇ／ｍＬ。范围内与发光强度成正比．方法检出限为０．１０μｇ／ｍＬ；对含４μｇ／ｍＬＰｂ（Ⅱ）１１次重复测定，其ＲＳＤ为２．３％．对３２种常见的阴阳离子进行了干扰实验，表明方法具有较好的选择性。本法应用于水样及沉积物标样中痕量铅的测定，结果良好。     

一种主链含非线性光学活性基团聚合物的合成

把非线性光学(NLO)发色基团引入到聚合物主链中,既可以增大聚合物中NLO基团的含量,从而提高聚合物的宏观NLO系数,又能够提高NLO聚合物的极化稳定性。本文报道一种由酚酞环氧树脂(PPh)与对硝基苯胺(NA)得到的NLO聚合物的合成及其极化松弛。 所用酚酞环氧树脂系自制,环氧值0.427。对硝基苯胺北京化工厂产,分析纯。N,N-二甲基甲酰胺为中国医药公司售品,化学纯,用前减压蒸馏精制,乙醇、丙酮均为北京化工厂生产,分析纯。在氮气保护下将等当量的PPh与NA溶于DMF中于150℃反应6～8小时后,倒