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.     

Tandem silylation—desilylation reaction in the synthesis of N-methyl carboxamides

Russian Chemical Bulletin - The N-methylation of primary carboxamides is based on two consecutive reactions. The silylation of the corresponding carboxamides with chloro(chloromethyl)dimethylsilane...     

Model and nonlinear dynamic analysis of linear guideway subjected to external periodic excitation in five directions

Nonlinear Dynamics - Investigation of the dynamic characteristics of linear guideway is essential for enhancing structural performance of machine tools. However, few mechanical models are...     

Spatiotemporal Magnetocaloric Microenvironment for Guiding the Fate of Biodegradable Polymer Implants

The degradation behavior of implants is significantly important for bone repair. However, it is still unprocurable to spatiotemporally regulate the degradation of the implants to match bone ingrowth. In this paper, a magneto-controlled biodegradation model is established to explore the degradation behavior of magnetic scaffolds in a magnetothermal microenvironment generated by an alternating magnetic field (AMF). The results demonstrate that the scaffolds can be heated by magnetic nanoparticles (NPs) under AMF, which dramatically accelerated scaffold degradation. Especially, magnetic NPs modified by oleic acid with a better interface compatibility exhibit a greater heating efficiency to further facilitate the degradation. Furthermore, the molecular dynamics simulations reveal that the enhanced motion correlation between magnetic NPs and polymer matrix can accelerate the energy transfer. As a proof-of-concept, the feasibility of magneto-controlled degradation for implants is demonstrated, and an optimizing strategy for better heating efficiency of nanomaterials is provided, which may have great instructive significance for clinical medicine.     

Performance analysis of bit error rate of data link system under pulse LFM interference in time-varying rayleigh channel

Wireless Networks - In such mobile platforms as ships and aircraft, the detection and reconnaissance devices are near to the communication facilities. When working at the same time, they will...     

Operator Interpolation and Systems of Linear Equations and Inequalities in Euclidean Spaces

Ukrainian Mathematical Journal - We establish new criteria of compatibility for a linear system of equations (equivalent to the Kronecker–Capelli theorem) or inequalities (equivalent to the...     

Restricted testing conditions for the multilinear maximal operator

Restricted testing conditions were considered recently. For the maximal operator, Hytönen, Li and Sawyer [8] first obtained parental testing condition. Later, they [9] showed that it suffices to restrict testing to doubling cubes. Chen and Lacey [3] gave a similar restricted testing condition. In our paper, we discuss a version of the latter in the multilinear setting.

     

Enhanced Power Density of Alcohol Biofuel Cell by Polymer-assisted Crosslinks of 3D Graphene on Carbon Paper as the Bioanode

Herein, we successfully construct the 3D biocompatible graphene through crosslinking 2D graphene nanosheet onto carbon fiber paper with poly(diallyldimethylammonium chloride) (PDDA) as anode of the alcohol biofuel cell. Compared with the bioanode without 3D graphene, the current density and output power of PDDA-graphene-ADH bioanode is increased by 23 % and 41 % at a high concentration of ethanol at pH 8.9, suggesting the stabilization role of graphene in enzyme loading. The study provides us a deep analysis on structures and performances of the bioanode incl. electrochemistry, X-ray photoelectron spectra, and atomic force microscopy images, which is significant to develop the new methods to construct 3D porous electrodes in energy conversion device.     

Guaranteed cost positive consensus for multi-agent systems with multiple time-varying delays and MDADT switching

Nonlinear Dynamics - This paper investigates the guaranteed cost positive consensus for linear multi-agent systems (MASs) with multiple time-varying delays and switching topologies. First,...     

A posteriori error analysis of a quadratic finite volume method for nonlinear elliptic problems

In this article, we construct and analyze a residual-based a posteriori error estimator for a quadratic finite volume method (FVM) for solving nonlinear elliptic partial differential equations with homogeneous Dirichlet boundary conditions. We shall prove that the a posteriori error estimator yields the global upper and local lower bounds for the norm error of the FVM. So that the a posteriori error estimator is equivalent to the true error in a certain sense. Numerical experiments are performed to illustrate the theoretical results.