7-Aminoalkoxy-Quinazolines from Epigenetic Focused Libraries Are Potent and Selective Inhibitors of DNA Methyltransferase 1

Inhibitors of epigenetic writers such as DNA methyltransferases (DNMTs) are attractive compounds for epigenetic drug and probe discovery. To advance epigenetic probes and drug discovery, chemical companies are developing focused libraries for epigenetic targets. Based on a knowledge-based approach, herein we report the identification of two quinazoline-based derivatives identified in focused libraries with sub-micromolar inhibition of DNMT1 (30 and 81 nM), more potent than S-adenosylhomocysteine. Also, both compounds had a low micromolar affinity of DNMT3A and did not inhibit DNMT3B. The enzymatic inhibitory activity of DNMT1 and DNMT3A was rationalized with molecular modeling. The quinazolines reported in this work are known to have low cell toxicity and be potent inhibitors of the epigenetic target G9a. Therefore, the quinazoline-based compounds presented are attractive not only as novel potent inhibitors of DNMTs but also as dual and selective epigenetic agents targeting two families of epigenetic writers.     

Cupressus sempervirens Essential Oil: Exploring the Antibacterial Multitarget Mechanisms,Chemcomputational Toxicity Prediction,and Safety Assessment in Zebrafish Embryos

Nowadays, increasing interest has recently been given to the exploration of new food preservatives to avoid foodborne outbreaks or food spoilage. Likewise, new compounds that substitute the commonly used synthetic food preservatives are required to restrain the rising problem of microbial resistance. Accordingly, the present study was conducted to examine the chemical composition and the mechanism(s) of action of the Cupressus sempervirens essential oil (CSEO) against Salmonella enterica Typhimuriumand Staphyloccocus aureus. The gas chromatography analysis revealed α-pinene (38.47%) and δ-3-carene (25.14%) are the major components of the CSEO. By using computational methods, such as quantitative structure–activity relationship (QSAR), we revealed that many CSEO components had no toxic effects. Moreover, findings indicated that α-pinene, δ-3-carene and borneol, a minor compound of CSEO, could inhibit the AcrB-TolC and MepR efflux pump activity of S. enterica Typhimurium and S. aureus, respectively. In addition, our molecular docking predictions indicated the high affinity of these three compounds with active sites of bacterial DNA and RNA polymerases, pointing to plausible impairments of the pathogenic bacteria cell replication processes. As well, the safety profile was developed through the zebrafish model. The in vivo toxicological evaluation of (CSEO) exhibited a concentration-dependent manner, with a lethal concentration (LC₅₀) equal to 6.6 µg/mL.     

基于冠层尺度的枣树色素含量的高光谱估算模型

植物冠层色素含量与氮素含量具有高度的相关性,是农业遥感中的关键研究因素。本研究的主要目的是：(1)对比偏最小二乘回归和支持向量机两种建模方法对枣树冠层色素的预测精度;(2)构建基于高光谱数据的枣树冠层色素含量定量反演模型,为枣树冠层色素含量的快速、无损、廉价、环保的测定提供一定的理论依据和技术支持。相关性分析结果表明,枣树冠层色素与高光谱数据之间具有较好的相关性,但叶绿素、叶绿素a要优于叶绿素b和类胡萝卜素。独立样本对模型的预测性能检验结果表明,偏最小二乘回归和支持向量机均能有效的估算枣树色素含量,但不同色素的偏最小二乘回归模型和支持向量机模型的预测精度存在一定的差异,叶绿素和类胡萝卜素的支持向量机模型的预测精度要高于偏最小二乘回归模型,而叶绿素a和叶绿素b则相反。比较不同色素的最佳反演模型的预测精度表明,叶绿素、叶绿素a和类胡萝卜素的预测精度要优于叶绿素b,前三者的决定系数大于0.8,残余预测误差高于2.0,平均相对误差低于13%,而叶绿素b的对应值分别为0.60%,20.79%和1.79%。     

基于尺度质心统计的纹理分析

结合目前纹理分析的三类算法,提出了尺度质心统计的分析算法。该算法以具有多分辨率特性的小波包为基础,结合结构法的纹理元分析方式,采用区域质心完成局部特征提取,最后使用投影法进行整体的特征提取。实验证明,尺度质心统计取得了令人满意的纹理分析效果。     

多基色LED的照明通信光源显色性研究

可见光无线通信(visible light communication,VLC)是将LED照明技术和光通信技术相结合的一种新兴技术。针对目前LED照明通信光源显色性差、光效低且色温不可调等问题,依据多基色LED白光通信原理进行了相关研究,以Yoshi等提出的高斯分布形式作为基色LED的光谱模型,利用国际照明委员会(CIE)推荐的一般显色指数(R_a)和美国国家标准与技术研究所(National Institute of Standards and Technology,NIST)推荐的一般色质指数(Q_a)评价光源的显色性。采用遗传算法,在2 700~6 500 K色温范围内优化出单个色温以及色温可调光源满足显色性最优的光谱组合,并基于R_a和Q_a大于80的原则优化出色温可调光源光视效能(luminous efficacy of radiation,LER)最优化的光谱组合。最后根据实验结果分析了光源的显色性、光视效能和色温可调性三者之间的关系。结果表明：三基色色温可调白光LED满足显色性最优的峰值波长组合为613 nm/541 nm/464 nm,此时R_a和Q_a的最小值分别为81.2和81,可以满足一般条件下的照明通信需求;四基色色温可调白光LED满足显色性最优的峰值波长组合为620 nm/562 nm/505 nm/449 nm,此时R_a和Q_a的最小值分别为96.7和92.2。在特殊照明场所或要求较高的通信速率时,应采用四基色白光LED作为照明通信光源。仿真得到了三基色和四基色白光LED的最佳光谱组合,为宽通道可见光通信光源的设计提供了参考依据。     

用于近场集成光学头微透镜器件的灰度掩模技术

讨论了制作适用于近场集成光学头中的凸形、凹形微透镜和折衍射复合微透镜的灰度掩模技术。定性地给出了与几种典型的凸形、凹形微透镜和折衍射复合微透镜对应的灰度掩模版的设计实例 ,以及将它应用于光刻操作的情况 ,为采用灰度掩模技术制作适用于近场集成光学头中的微透镜器件奠定了基础。灰度掩模技术在微透镜器件的制作方面具有重要的应用前景 ,有助于简化制备工艺 ,降低制作成本 ,优化微透镜阵列的结构参数。     

Effects of Two Natural Bisbenzylisoquinolines,Curine and Guattegaumerine,Extracted from Isolona hexaloba on Rhodamine Efflux by Abcb1b from Rat Glycocholic-Acid-Resistant Hepatocarcinoma Cells

To develop new therapeutic molecules, it is essential to understand the biological effects and targets of clinically relevant compounds. In this article, we describe the extraction and characterization of two alkaloids from the roots of Isolona hexaloba—curine and guattegaumerine. The effect of these alkaloids on the multidrug efflux pump ABCB1 (MDR1/P-Glycoprotein) and their antiproliferative properties were studied. Compared to verapamil, a widely used inhibitor of P-gp, curine and guattegaumerine were found to be weak inhibitors of MDR1/P-Glycoprotein. The highest inhibition of efflux produced by verapamil disappeared in the presence of curine or guattegaumerine as competitors, and the most pronounced effect was achieved with curine. Altogether, this work has provided new insights into the biological effects of these alkaloids on the rat Mdr1b P-gp efflux mechanism and would be beneficial in the design of potent P-gp inhibitors.     

求解中国农业困局：国际视野中的农业规模经营与农业竞争力

近年来中国粮食生产出现的“高产量、高库存、高进口”现象,是由于农均耕地面积过小引起的规模经营不足。这背后,是户籍制度造成的城市化滞后以及针对外来人口的公共服务不平等。同时,政府大力补贴农业和农村,提高了农民向城市转移的机会成本,导致土地流转率不足,进一步阻碍规模经营。通过国际比较,我们认为规模化农场有利于提高农业竞争力,而小农经济现代化的成本较高。研究还发现,在世界范围内,农业劳动力转移适应农业产出比重下降的国家拥有更大的农均在（可）耕地,它对农均粮食净出口存在显著正效应。反事实分析说明,若中国2011年的农业就业比重能和产出比重相适应（即消除城乡间劳动力流动障碍）,则下一年粮食净输入将下降约89%。     

Coconut coir dust extract: a novel eco-friendly corrosion inhibitor for Al in HCl solutions

Abstract

Corrosion inhibition of aluminium in 1 M HCl by coconut coir dust extract (CCDE) was studied using weight loss and hydrogen evolution techniques at 30 and 60°C. It was found that the studied extract exhibits a very good performance as inhibitor for aluminium corrosion in 1 M HCl. Results show that the inhibition efficiency increases with increasing temperature and concentration of the extract. Inhibitive effect was afforded by adsorption of the extracts' components which was found to accord with Langmuir adsorption isotherm. Inhibition mechanism is deduced from the temperature dependence of the inhibition efficiency and was further corroborated by the values of activation parameters obtained from the experimental data.