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.     

Determination of sulfa antibiotic residues in river and particulate matter by field-amplified sample injection-capillary zone electrophoresis

In the present research, field-amplified sample injection–CZE (FASI–CZE) coupled with a diode array detector was established to determine trace level sulfa antibiotic. Sulfathiazole, sulfadiazine, sulfamethazine, sulfadimethoxine, sulfamethoxazole, and sulfisoxazole were selected as analytes for the experiments. The background electrolyte solution consisted of 70.0 mmol/L borax and 60.0 mmol/L boric acid (including 10% methanol, pH 9.1). The plug was 2.5 mmol/L borax, which was injected into the capillary at a pressure of 0.5 psi for 5 s. Then the sample was injected into the capillary at an injection voltage of –10 kV for 20 s. The electrophoretic separation was carried out under a voltage of +19 kV. The capillary temperature was maintained at 20˚C throughout the analysis, and six sulfonamides were completely separated within 35 min. Compared with pressure injection-CZE, the sensitivity of FASI-CZE was increased by 6.25–10.0 times, and the LODs were reduced from 0.2–0.5 to 0.02–0.05 μg/mL. The method was applied to the determination of sulfonamides in river water and particulate matter samples. The recoveries were 78.59–106.59%. The intraday and interday precisions were 2.89–7.35% and 2.77–7.09%, respectively. This provides a simpler and faster method for the analysis of sulfa antibiotic residues in environmental samples.     

A self-penetrating and chemically stable zinc (ii)-organic framework as multi-responsive chemo-sensor to detect pesticide and antibiotics in water

Guided by the self-penetrating features can improve the stability of metal organic frameworks (MOFs), an unprecedented 3D self-penetrated framework, {[Zn (tptc)_0.5(bimb)]·H₂O}_n ( NUC-6 , here NUC corresponding to North University of China), with 3D (4,4)-c {8⁶} net, was designed. Benefit from the high chemical stability and excellent luminescent property, NUC-6 can be act as an efficient multi-response chemo-sensor in detecting dichloronitroaniline pesticide and nitrofuran antibiotics in water with the detection limits are 116 ppb for DCN pesticide, 16 ppb for NFT antibiotic, and 12 ppb for NTZ antibiotic. Besides, the mechanisms of luminescence quenching were revealed from the viewpoint of internal filter effect (IFE) and photo-induced electron transfer (PET), implied by the optical spectroscopy and quantum chemical calculation. This work provides a promising strategy to design stable MOFs by improving the self-penetrating features and to expand their practical applications in the detection of organic pollutants in aqueous medium.     

A Photoactivated Cu–CeO2 Catalyst with Cu-[O]-Ce Active Species Designed through MOF Crystal Engineering

Fully utilizing solar energy for catalysis requires the integration of conversion mechanisms and therefore delicate design of catalyst structures and active species. Herein, a MOF crystal engineering method was developed to controllably synthesize a copper–ceria catalyst with well-dispersed photoactive Cu-[O]-Ce species. Using the preferential oxidation of CO as a model reaction, the catalyst showed remarkably efficient and stable photoactivated catalysis, which found practical application in feed gas treatment for fuel cell gas supply. The coexistence of photochemistry and thermochemistry effects contributes to the high efficiency. Our results demonstrate a catalyst design approach with atomic or molecular precision and a combinatorial photoactivation strategy for solar energy conversion.     

基于校园网的实验管理系统的设计

主要讨论了应用实验室管理系统的必要性,并从用户需求分析、系统总体设计、功能模块的设计等方面对B/S实验室管理系统的开发进行了详细的阐述。     

Sobolev-Hardy不等式与临界双重调和问题

该文讨论一类带有奇异系数的双重调和方程{△^2u-μu/|x|^s=f(x,u),x∈Ω,u=δu/δv=0,x∈δΩ，这里Ω包含R^N是包含0的有界光滑区域，u∈H0^2(Ω），μ∈R是参数，0≤s≤2,△^2=△△表示双重拉普拉斯算子，当f(x,u)=u^p,p=2N/N-4时，上述问题就是一个临界双重调和问题，该文运用Sobolev-Hardy不等式和变分方法，得到它的解的存在性的一些结果。     

A method to collect an infrared spectrum in solution.

Herein we report a new method to collect a qualified infrared spectrum of a solute in solution by two solvent cells with different thickness during background single-beam spectrum scanning. By collecting the background spectrum with two cells (two stages), we successfully achieved accurate solvent compensation between a sample and a reference, namely, the solvent amounts in the sample and background measurements could become congruent. Therefore, the solvent bands were thoroughly suppressed in the infrared spectrum and a qualified spectrum of the solute was obtained.     

THERMAL AND THERMO-ELASTIC-PLASTIC RESPONSE OF CERAMIC-METAL FUNCTIONALLY GRADED MATERIALS—THERMAL SHOCK PROBLEM

The thermal and thermo-elastic-plastic response of newly developed ceramic-metalfunctionally graded materials under a thermal shock load is studied.The materials are heated at the ce-ramic surface with a sudden high-intensity heat flux input,and cooled at the metal surface with aflowing liquid nitrogen.Emphasis is placed on two aspects:(1)the influence of the graded composi-tion of the materials on the temperature and stress response;and(2)the optimum design of the gradedcomposition from a unified viewpoint of the heat insulation property and stress relaxation property.Moreover,a comparison between the thermoelastic stress and the thermo-elastic-plastic stress is alsomade to indicate the plasticity effect.     

Experimental study of a plasma-filled backward wave oscillator

Experimental studies of a plasma-filled X-band backward-wave oscillator (BWO) are presented. Depending on the background gas pressure, microwave frequency upshifts of up to 1 GHz appeared along with an enhancement by a factor of 7 in the total microwave power emission. The bandwidth of the microwave emission increased from ⩽0.5 GHz to 2 GHz when the BWO was working at the RF power enhancement pressure region. The RF power enhancement appeared over a much wider pressure range in a high beam current case (10-100 mT for 3 kA) than in a lower beam case (80-115 mT for 1.6 kA). The plasma-filled BWO has higher power output than the vacuum BWO over a broader region of magnetic guide field strength. Trivelpiece-Gould modes (T-G modes) are observed with frequencies up to the background plasma frequency in a plasma-filled BWO. Mode competition between the T-G modes and the X-band Tm₀₁ mode prevailed when the background plasma density was below 6×10¹¹ cm^-3 . At a critical background plasma density of ≃8×10¹¹ cm^-3 power enhancement appeared in both X-band and the T-G modes. Power enhancement of the S-band in this mode collaboration region reached up to 8 dB. Electric fields measured by the Stark-effect method were as high as 34 kV/cm while the BWO power level was 80 MW. These electric fields lasted throughout the high-power microwave pulse