Synthesis,pharmacology and molecular docking on multifunctional tacrine-ferulic acid hybrids as cholinesterase inhibitors against Alzheimer’s disease

The cholinergic hypothesis has long been a “polar star” in drug discovery for Alzheimer’s disease (AD), resulting in many small molecules and biological drug candidates. Most of the drugs marketed for AD are cholinergic. Herein, we report our efforts in the discovery of cholinesterases inhibitors (ChEIs) as multi-target-directed ligands. A series of tacrine-ferulic acid hybrids have been designed and synthesised. All these compounds showed potent acetyl-(AChE) and butyryl cholinesterase(BuChE) inhibition. Among them, the optimal compound 10g, was the most potent inhibitor against AChE (electrophorus electricus (eeAChE) half maximal inhibitory concentration (IC₅₀)?=?37.02?nM), it was also a strong inhibitor against BuChE (equine serum (eqBuChE) IC₅₀?=?101.40?nM). Besides, it inhibited amyloid β-protein self-aggregation by 65.49% at 25?μM. In subsequent in vivo scopolamine-induced AD models, compound 10g obviously ameliorated the cognition impairment and showed preliminary safety in hepatotoxicity evaluation. These data suggest compound 10g as a promising multifunctional agent in the drug discovery process against AD.     

Current situation and future usage of anticancer drug databases

Cancer is a deadly disease with increasing incidence and mortality rates and affects the life quality of millions of people per year. The past 15 years have witnessed the rapid development of targeted therapy for cancer treatment, with numerous anticancer drugs, drug targets and related gene mutations been identified. The demand for better anticancer drugs and the advances in database technologies have propelled the development of databases related to anticancer drugs. These databases provide systematic collections of integrative information either directly on anticancer drugs or on a specific type of anticancer drugs with their own emphases on different aspects, such as drug–target interactions, the relationship between mutations in drug targets and drug resistance/sensitivity, drug–drug interactions, natural products with anticancer activity, anticancer peptides, synthetic lethality pairs and histone deacetylase inhibitors. We focus on a holistic view of the current situation and future usage of databases related to anticancer drugs and further discuss their strengths and weaknesses, in the hope of facilitating the discovery of new anticancer drugs with better clinical outcomes.     

基于大脑皮层信息传输的脑电信息图示方法

提出一种基于大脑皮层信息传输的脑电地形图示方法—脑电信息图（Ｂｒａｉｎ ＩｎｆｏｒｍａｔｉｏｎＭａｐｐｉｎｇ － ＢＩＭ） 。其原理是从不同导联电极上采集脑电信号经相空间重建构成头皮电位信息传输矩阵, 将各导联信息传输时间序列的信息传输量和复杂度数据绘制成头皮拓扑分布图, 以直观地反映脑电信息传输分布模式在不同时相中的变化进程。该方法不仅是从新的角度观察大脑功能变化, 而且可克服传统的脑电频谱分段地形图不能表达长程脑电模式变化的不足。对局限性癫痫病患者的试用表明,脑电信息图能较好地反映癫痫发作前后的信息传输动向和复杂度（Ｋｃ 、Ｃ１ 、Ｃ２） 的变化趋势。结果提示,脑电信息图（ＢＩＭ） 有可能成为一种新的观察大脑功能活动的图示诊断方法,值得进一步深入研究。     

辽西褐土施肥及养分循环再利用中长期试验Ⅲ.磷和氮在堆腐过程中的循环率及有机肥料中养分利用率

9年的试验结果表明 ,农产品中N、P经堆腐后损失率平均为 30 % .在丰产条件下 ,6 0 %的收获产品直接堆腐回田 ,可循环回田的养分量为N 5 5～ 70kg·hm-2 、P 9～ 11kg·hm-2 ,相当于这一系统中每年化肥N用量的 37%～ 4 7%和P肥用量的 36 %～ 4 4 % .有机肥料中N和P的表观利用率随施肥年限延长而有增长趋势 ,表明有残效叠加效应存在 .有机肥料中N和P的当季表观利用率 8年平均分别为 2 3%～5 0 %和 37%～ 6 5 % .通过此项研究可以证明 ,农业生态系统养分的循环再利用是保持土壤肥力 ,提高养分利用效率 ,减少化学肥料消费的重要措施 .     

青藏东缘若尔盖高寒草甸中小型土壤动物群落特征及季节变化

中小型土壤动物是生态系统的重要组成部分。为了查明高寒草甸生态系统的中小型土壤动物群落特征及其变化动态,2008至2009年间,利用定位观测方法对青藏东缘若尔盖高寒草甸的中小型土壤动物进行了5次调查。结果为:(1)捕获中小型土壤动物9318只,隶属于3门7纲88类;平均密度为39941.67 个/m²;大类群中,线虫纲(Nematoda)的个体数占总个体数的91.50%,蛛形纲(Arachnida)(主要为蜱螨目)、弹尾纲(Collembola)、寡毛纲(Oligochaeta)和昆虫纲(Insecta)分别占3.73%、2.55%、1.12%和1.07%;(2)土壤动物的群落密度、类群数、密度-类群指数、Shannon指数、Simpson指数和Pielou指数均有显著的季节差异(P<0.01或P<0.05),表明高寒草甸生态系统的中小型土壤动物群落多样性对季节变化具有高度敏感性;(3)线虫纲、蛛形纲、弹尾纲、寡毛纲和昆虫纲的密度变化趋势基本一致,并均有显著的季节差异(P<0.05);(4)各季节间的Sorensen群落相似性系数低于Morisita-Horn相似性系数,表明季节变化对群落物种组成的影响相对较强,对优势类群个体密度的影响相对较弱;(5)中小型土壤动物群落的类群数和密度,以及弹尾纲、寡毛纲和昆虫纲的密度均与温度有显著的负相关(P<0.01或P<0.05),线虫和蛛形纲的密度与温度和降水均有不显著的负相关(P>0.05)。研究结果表明若尔盖高寒草甸的中小型土壤动物群落组成和多样性具有明显的季节特征,而温度是影响其季节变化的最主要气候因素;另外,从温度、降水及其年间变化对中小型土壤动物的影响可知全球气候变暖在短期内将会对高寒草甸土壤动物群落产生不利的影响。     

生物制造高附加值乳糖衍生物的研究进展

乳糖来自于乳清,是奶酪行业的低附加值副产物.由于亚洲人普遍存在乳糖不耐受性,因此乳糖缺乏有效的经济增值途径.随着我国乳制品行业的不断发展,利用乳糖制备高附加值产品具有重要的经济价值和产业升级意义.本文就近年来发展的利用生物技术转化乳糖为稀少糖或益生寡糖的方法进行了综述,以期对该领域研究提供借鉴.     

Increased Expression of Angiogenic Factors in Cultured Human Brain Arteriovenous Malformation Endothelial Cells

To compare the mRNA level of angiogenic factor vascular endothelial growth factor (VEGF), matrix metalloproteinases (MMP)-2, and MMP-9 in cultured human brain arteriovenous malformation (AVM) endothelial cells (ECs) and normal brain endothelial cells (BECs). Tissue explants both from deformed vessels of AVM and normal microvessel were put into culture for endothelial cells. After the monolayer adherent ECs reached confluence, they were tested with endothelial specific marker CD34 and von Willebrand factor (vWF) by immunochemical assay. mRNA levels of VEGF-A, MMP-2, and MMP-9 in AVM endothelial cells (AVMECs) and BECs were measured by PCR. Immunostaining confirmed that more than 95 % of the cultured cells were CD34 (Fig. 1b) and/or vWF positive. Expression levels of VEGF-A and MMP-2 mRNAs were significantly higher in AVMECs than in BECs. The MMP-9 level was also increased in AVMECs, but the difference was not statistically significant. Vascular tissue explants adherent method is a better approach for isolation and culture of AVMECs. Cultured AVMECs expressed higher angiogenic factors (VEGF, MMP-2) than the controlled BECs, implicating angiogenesis plays an important role in the pathogenesis of AVM.     

川西北草原土壤及冷暖季牧草微量元素含量比较

改善土壤的理化环境及提高牧草的营养水平必须了解草地土壤及牧草微量元素的分布与含量。试验从川西北草地的亚高山丘原草甸、亚高山平坝草甸和沼泽平坝草甸采集土样和冷暖季草样。土样采集深度范围是0～10cm,10～20cm,20～30cm。应用火焰原子吸收光谱法测定了草样中铜、铁、锰、锌和钴的含量和土样中这些元素的有效态含量,应用氟离子选择电极法测定了土样中的氟离子浓度和草样中的氟含量。土壤pH高低顺序为草甸土>冲积土>泥炭草甸土,pH随土壤深度变深而下降;土壤和牧草的钴含量都处于缺乏状态,分别为0.64mg/kg和0.26mg/kg。牧草铁和锰含量都高于正常水平,铁为414.51～565.06mg/kg,锰为138.68～247.09mg/kg.     

采砂活动影响下鄱阳湖水陆交错带形态及景观格局变化

自长江干流限制无序采砂后,大量采砂船涌入鄱阳湖区作业导致水陆交错带形态与景观均发生明显的改变,人类活动深刻影响着鄱阳湖水陆交错带的稳定性。基于Landsat TM/OLI遥感影像数据,定量测算采砂活动对鄱阳湖水陆交错带形态和景观格局产生的影响,结果表明：(1)草滩与滩涂之间转化最为频繁,水域面积缩小,水陆交错带范围扩大;(2)东岸线和西岸线呈侵蚀状态,湖心岸线快速收缩;(3)鄱阳湖水陆交错带形状逐渐变得简单,而入江通道形状复杂化程度提高,其几何形态不规则化;(4)景观类型层次上,滩涂的破碎度最大,形状最为复杂,农田的破碎度和形状复杂程度最小,集聚性最强,草滩的连通性最好,沙地的景观指数幅度变化最大;(5)鄱阳湖水陆交错带破碎化程度逐渐降低,景观形状越来越复杂,景观多样性减少,整体连通性和集聚性增强;(6)采砂规模与鄱阳湖水陆交错带的形态指数呈负相关,与景观形状指数和入江通道的形态指数呈正相关,其均通过显著检验。