Cloning and Functional Characterization of Dog OCT1 and OCT2: Another Step in Exploring Species Differences in Organic Cation Transporters

OCT1 and OCT2 are polyspecific membrane transporters that are involved in hepatic and renal drug clearance in humans and mice. In this study, we cloned dog OCT1 and OCT2 and compared their function to the human and mouse orthologs. We used liver and kidney RNA to clone dog OCT1 and OCT2. The cloned and the publicly available RNA-Seq sequences differed from the annotated exon-intron structure of OCT1 in the dog genome CanFam3.1. An additional exon between exons 2 and 3 was identified and confirmed by sequencing in six additional dog breeds. Next, dog OCT1 and OCT2 were stably overexpressed in HEK293 cells and the transport kinetics of five drugs were analyzed. We observed strong differences in the transport kinetics between dog and human orthologs. Dog OCT1 transported fenoterol with 12.9-fold higher capacity but 14.3-fold lower affinity (higher K_M) than human OCT1. Human OCT1 transported ipratropium with 5.2-fold higher capacity but 8.4-fold lower affinity than dog OCT1. Compared to human OCT2, dog OCT2 showed 10-fold lower transport of fenoterol and butylscopolamine. In conclusion, the functional characterization of dog OCT1 and OCT2 reported here may have implications when using dogs as pre-clinical models as well as for drug therapy in dogs.     

Recent Advances in Application of Computer-Aided Drug Design in Anti-Influenza A Virus Drug Discovery

Influenza A is an acute respiratory infectious disease caused by the influenza A virus, which seriously threatens global human health and causes substantial economic losses every year. With the emergence of new viral strains, anti-influenza drugs remain the most effective treatment for influenza A. Research on traditional, innovative small-molecule drugs faces many challenges, while computer-aided drug design (CADD) offers opportunities for the rapid and effective development of innovative drugs. This literature review describes the general process of CADD, the viral proteins that play an essential role in the life cycle of the influenza A virus and can be used as therapeutic targets for anti-influenza drugs, and examples of drug screening of viral target proteins by applying the CADD approach. Finally, the main limitations of current CADD strategies in anti-influenza drug discovery and the field’s future directions are discussed.     

一种基于软阈值方法的改进A1/A2极化干涉分类算法

在分析了极化干涉技术的发展现状和发展趋势的基础上,从极化干涉的特殊性入手,分析了干涉相干系数在极化干涉分类中的作用,并且系统分析了基于相干最优优化后的相干系数进行极化干涉分类过程的原理,总结了现有极化干涉分类算法在阈值选择方面存在的不足,阐述了硬阈值方法和软阈值方法的基本原理和它们之间的区别,最后提出基于软阈值方法的改进A1/A2非监督极化干涉分类算法,解决了极化干涉分类现有的分类空间中的阈值问题。实验表明这种方法能够得到更好的分类结果,做出了改进。     

华蟾素注射液对人肝癌HepG-2细胞增殖及周期的影响

Objective: The aim of our study was to investigate the effect of Cinobufacini injection on the proliferation and cell cycle of human hepatoma HepG-2 cells. Methods: Cell proliferation was assessed by MTT assay, cell cycle distributionwas detected by the flow cytometry (FCM). The expression of Cyclin A, CDK2 mRNA levels were examined by RT-PCR.Quantitative colorimetric assay was used to analyze Cyclin NCDK2 activity in HepG-2 cells. Results: Cinobufacini injection significantly inhibited HepG-2 cells proliferation in dose- and time-dependent ways; FCM analysis showed Cinobufacini injection induced cell cycle arrest at S phase; RT-PCR assay showed Cinobufacini injection down-regulated Cyclin A, CDK2expression at mRNA levels; Quantitative colorimetric assay showed Cinobufacini injection deceased Cyclin A/CDK2 activity in HepG-2 cells. Conclusion: Cinobufacini injection can inhibit human hepatoma HepG-2 cells growth, induce cell apoptosis and induce cell cycle arrest at S phase, the mechanism of which might be partly related to the down-regulation of Cyclin A,CDK2 mRNA expression and inhibition of Cyclin A/CDK2 activity.     

TiO2-coated foams as a medium for solar catalysis

Sunlight irradiating the surface of the Earth represents a maximum input available for a solar catalytic process of 50 W_UV m⁻². We propose using high-porosity, metallic, reticulated foams as the support medium for the photocatalyst in order to improve the apparent quantum yield. The layer of TiO₂ was applied by dip-coating. The measurement of the degradation kinetics was carried out on a model target molecule, 2,4 dichlorophenol, at an initial concentration of 10 mg l⁻¹. The aim was to assess the efficiency of the foams as a photocatalytic media compared to that of a suspension of catalytic powder (Degussa P25) and the flat 2D support (Ahlstrom cellulose media). The apparent quantum yield of the foam scaffold carrying the TiO₂ was high, showing that, as with the powder suspension, foam makes good use of the UV rays to break down molecules. It is noteworthy that the apparent quantum yield of the foam tended towards that observed for suspensions which form the ideal support thanks to their optimal ability to harness the light.     

Preparation and properties of UV-cured acrylated silane intercalated polymer/LDH nanocomposite

A novel UV-cured polymer/layered double hydroxide (LDH) nanocomposite was prepared by modifying the LDH with sodium dodecyl sulfate (SDS) and [3-(methyl-acroloxy)propyl]trimethoxysilane (KH570) followed by UV irradiation after blended into a acrylate system. From the XRD analyses, the SDS-modified LDH-DS presented the basal spacing of 2.67 nm, whereas the further KH570-intercalated LDH-KH showed a slight decrease to 2.41 nm. After UV irradiated the exfoliated microstructure was formed, and observed by TEM and HR-TEM, showing the fine dispersion and random orientation of LDH in the polymer matrix. The storage modulus and glass transition temperature of the nanocomposite containing 5% LDH-KH increased to 47.5 MPa and 67.8 °C, respectively, from 39.7 MPa and 66 °C of the pure polymer from DMTA measurements. The tensile strength and Persoz hardness were enhanced to 10.6 MPa and 111 s, respectively, from 7.7 MPa and 85 s of the pure polymer.     

Synthesis of zirconium tungstate–zirconia core–shell composite particles

In this work, ZrW₂O₈–ZrO₂ core–shell composite particles were synthesized. ZrW₂O₈ that was used in the core is a material with negative coefficient of thermal expansion, and it was synthesized from a high-pH precursor based on use of tungstic acid and zirconium acetate. Shell layer was composed of ZrO₂ nanocrystallites and precipitated from an aqueous solution by urea hydrolysis. While volume of the shell was effectively controlled by the initial zirconium ion concentration in the solutions, the rate of precipitation was a function of the ratio of initial concentrations of urea to zirconium ions. It is hypothesized that isolation of the ZrW₂O₈ within a layer of ZrO₂, will be a key element in solving problems associated with reactivity of ZrW₂O₈ towards other components in sintering of ceramic–ceramic composites with tuned or zero thermal expansion coefficient.