Oxazolopyridines and thiazolopyridines as monoamine oxidase B inhibitors for the treatment of Parkinson’s disease

In Parkinson’s disease, the motor impairments are mainly caused by the death of dopaminergic neurons. Among the enzymes which are involved in the biosynthesis and catabolism of dopamine, monoamine oxidase B (MAO-B) has been a therapeutic target of Parkinson’s disease. However, due to the undesirable adverse effects, development of alternative MAO-B inhibitors with greater optimal therapeutic potential towards Parkinson’s disease is urgently required. In this study, we designed and synthesized the oxazolopyridine and thiazolopyridine derivatives, and biologically evaluated their inhibitory activities against MAO-B. Structure–activity relationship study revealed that the piperidino group was the best choice for the R¹ amino substituent to the oxazolopyridine core structure and the activities of the oxazolopyridines with various phenyl rings were between 267.1 and 889.5 nM in IC₅₀ values. Interestingly, by replacement of the core structure from oxazolopyrine to thiazolopyridine, the activities were significantly improved and the compound 1n with the thiazolopyridine core structure showed the most potent activity with the IC₅₀ value of 26.5 nM. Molecular docking study showed that van der Waals interaction in the human MAO-B active site could explain the enhanced inhibitory activities of thiazolopyridine derivatives.     

Novel 1,3,4-oxadiazole thioether derivatives targeting thymidylate synthase as dual anticancer/antimicrobial agents

A series of novel 1,3,4-oxadiazole thioether derivatives (compounds 9–44) were designed and synthesized as potential inhibitors of thymidylate synthase (TS) and as anticancer agents. The in vitro anticancer activities of these compounds were evaluated against three cancer cell lines by the MTT method. Among all the designed compounds, compound 18 bearing a nitro substituent exhibited more potent in vitro anticancer activities with IC₅₀ values of 0.7 ± 0.2, 30.0 ± 1.2, 18.3 ± 1.4 μM, respectively, which was superior to the positive control. In the further study, it was identified as the most potent inhibitor against two kinds of TS protein (for human TS and Escherichia coli TS, IC₅₀ values: 0.62 and 0.47 μM, respectively) in the TS inhibition assay in vitro and the most potent antibacterial agents with MIC (minimum inhibitory concentrations) of 1.56–3.13 μg/mL against the tested four bacterial strains. Molecular docking and 3D-QSAR study supported that compound 18 can be selected as dual antitumor/antibacterial candidate in the future study.     

GIV: A Tool for Genomic Islands Visualization

A Genomic Islands (GI) is a chunk of DNA sequence in a genome whose origin can be traced back to other organisms or viruses. The detection of GIs plays an indispensable role in biomedical research, due to the fact that GIs are highly related to special functionalities such as disease-causing GIs - pathogenicity islands. It is also very important to visualize genomic islands, as well as the supporting features corresponding to the genomic islands in the genome. We have developed a program, Genomic Island Visualization (GIV), which displays the locations of genomic islands in a genome, as well as the corresponding supportive feature information for GIs. GIV was implemented in C++, and was compiled and executed on Linux/Unix operating systems.

Availability

GIV is freely available for non-commercial use at http://www5.esu.edu/cpsc/bioinfo/software/GIV     

城市森林碳汇及其抵消能源碳排放效果——以广州为例

城市森林及其管理相关政策作为减少CO₂排放的有效策略得到了较为广泛的关注。采用材积源生物量方程与净初级生产力方法来定量分析了广州市城市森林碳储量和碳固定量,根据化石能源使用量及其碳排放因子核算了广州城市能源碳排放,最后评估了城市森林碳抵消效果。结果显示广州市城市森林碳储量为654.42×10⁴t,平均碳密度为28.81 t/hm²,而森林碳固定量为658732 t/a,平均固碳率为2.90 t·hm^-2·a^-1。2005-2010年广州市年均能源碳排放则达到2907.41×10⁴t。广州城市森林碳储量约为城市年均能源碳排放的22.51%,其通过碳固定年均能够抵消年均碳排放的2.27%,不过从城市森林综合效益来看其仍是城市低碳发展重要举措之一。分析了林型组成和林龄结构对于广州森林碳储量和碳固定量的影响,并从森林管理角度为城市森林碳汇提升提出建议。这些结果和讨论有助于评估城市森林碳汇在抵消碳排放中所起的效果。     

不同温度对脊尾白虾胚胎发育与幼体变态存活的影响

选用实验室内人工控制交尾的脊尾白虾,研究了不同温度对脊尾白虾胚胎发育及幼体变态、存活的影响。结果表明,在盐度为31的条件下,脊尾白虾胚胎发育的生物学零度为12.18℃,有效积温为3828.27℃.h。在15.3—28.1℃范围内,胚胎发育时间随着温度升高而呈双曲线性缩短,而胚胎发育速度随着温度的升高而呈直线性加快,但当温度超过30℃时,胚胎无法正常完成发育。脊尾白虾幼体变态发育速度随着温度的升高而加快,18、20、22、24、26、28℃各实验组开始出现仔虾的时间依次为17、14、11、9、8和8 d,各组90%以上幼体变态为仔虾的时间依次为21、18、15、14、11和11 d。各实验组在幼体变态过程中存活率都呈明显的阶梯式下降趋势,且28℃组的存活率下降最快,但当存活幼体全部变为仔虾时,各实验组间的存活率并无显著性差异(P>0.05)。18℃组仔虾干质量明显高于其它各组(P<0.05),28℃组仔虾干质量最低,但与20、22、24、26℃组无显著性差异(P>0.05)。因此在脊尾白虾育苗中,幼体孵化温度不应低于12℃,最高不超过28℃为宜;幼体培育温度,建议控制在22—26℃为最佳。     

铜尾矿废弃地土壤动物多样性特征

土壤动物的恢复、群落演替及其多样性对于铜尾矿废弃地的生态重建具有重要意义.为了解铜尾矿废弃地土壤动物群落多样性特征,在铜陵市铜尾矿区设置4个样地23采样点,共捕获土壤动物4622只个体,隶属5门10纲18目29类.结果表明,铜尾矿自然废弃地与其对照组土壤动物多样性差异明显,自然废弃地土壤动物丰富度指数d、大型土壤动物密度、中小型土壤动物密度、多样性指数H'和D·G指数均小于其对照组且存在显著差异.而复垦废弃地中小型土壤动物密度和D·G指数小于其对照组且存在显著差异,多样性指数H'大于其对照组且差异极显著,其他土壤动物群落指标与其对照组均无显著差异.相似系数q表明,外围林地间土壤动物群落相似性最大,其次是复垦废弃地与外围林地间,自然废弃地与其它3个样地间相似性最小.从垂直分层来看,复垦废弃地土壤动物表聚性强于自然废弃地,尾矿废弃地表聚性强于外围林地.灰色关联分析表明,铜尾矿区土壤理化性质与土壤动物群落结构指标关系密切,其中最重要的因素是土壤含水量和总钾含量,重金属全镉含量也不容忽视,植被因素和土壤全铜含量对土壤动物的影响相对较小.由此可见,土壤含水量、土壤基质的优劣、土壤有机质与营养元素的含量等因素限制了铜尾矿废弃地土壤动物的恢复与重建,而这些因素的改善主要归功于尾矿废弃地的土地复垦和作物种植.所以,尾矿废弃地的复垦与利用有利于土壤动物的恢复与重建.     

毛乌素沙地南缘沙丘生物结皮对凝结水形成和蒸发的影响

在水分极度匮乏的荒漠生态系统,凝结水是除降雨之外最重要的水分来源之一,它对荒漠生态系统结构、功能和过程的维持产生重要的影响。为探明半干旱沙区生物结皮表面的凝结水形成和蒸发特征,采用自制的微型蒸渗计(直径7 cm、高5 cm的PVC管)实验观测了不同类型地表(裸沙、浅灰色藻类结皮、黑褐色藻类结皮和苔藓结皮)对凝结水形成和蒸发的影响。结果表明:(1)观测期间共有20次凝结水形成记录,除降雨天气外,几乎每天都能观测到水分凝结现象;(2)不同类型地表凝结水总量依次为(1.998±0.075),(2.326±0.083),(2.790±0.058)和(3.416±0.068) mm,生物结皮表面的凝结水总量显著大于裸沙(P < 0.05);随生物结皮的发育,不同类型生物结皮表面的凝结水总量呈增加的趋势,凝结水总量之间差异显著(P < 0.05);观测期间不同类型地表日平均凝结水量依次为(0.100±0.003),(0.116±0.004),(0.140±0.002)和(0.171± 0.003) mm,不同类型地表日平均凝结水量之间差异极显著(P < 0.01);(3)凝结水形成过程的观测结果显示,凝结水19:00开始形成,23:00-凌晨1:00形成不明显,1:00-7:00继续形成,除浅灰色藻类结皮外,太阳升出后在黑褐色藻类结皮和苔藓结皮表面继续形成少量的凝结水;凝结水7:30开始蒸发,10:30到11:00之间结束蒸发,凝结水在裸沙和浅灰色藻类结皮中的保持时间显著大于黑褐色藻类结皮和苔藓结皮中的保持时间(P < 0.05);(4)凝结水的形成受大气温度、地表温度、空气相对湿度和大气地表温度差等气象因素的影响,但其形成过程不与某一个气象因素呈简单的线性关系。     

水足迹研究进展

水为生命之源,水资源的合理分配与科学管理是区域可持续发展与流域综合管理的核心环节;水足迹作为一种全面核算人类活动对水资源真实占用的综合指标,将人类消费终端与水资源利用密切关联,为维护流域水资源安全、提高区域水资源利用效率提供了重要的科学依据,已成为当前国际水资源管理的前沿研究领域。在明确水足迹及水资源生态足迹相关概念的基础上,对比分析了水足迹与生态足迹、水资源生态足迹模型的异同,明晰了过程、产品及区域等不同研究对象的水足迹核算方法,系统梳理了产品和区域水足迹评价、基于水足迹的区域水资源安全研究、区域水足迹可持续性分析等水足迹主要研究内容的近今进展,并展望了进一步的重点研究方向,即水足迹综合研究、水足迹评价不确定性分析、水足迹与物质流核算的关联研究,以及基于足迹整合的可持续发展多维测度等。     

模拟酸雨对蒙古栎幼苗生长和根系伤流量的影响

选择中国北方落叶阔叶林的主要组成树种蒙古栎(Quercus mongolica Fisch.ex Ledeb.)的1年生幼苗为研究对象,设置4个酸雨酸度(重度、中度、轻度和对照)和3个降雨量(自然雨量和增、减雨量30％),以期阐明酸雨对蒙古栎幼苗形态生长、生物量和根系伤流量的影响,探讨中国北方日趋严重的酸雨是否会影响蒙古栎幼苗的生长,为酸雨区森林恢复植物的选择提供依据.研究结果显示:1)在本实验的酸雨酸度下,酸雨降雨量的增加对蒙古栎幼苗各生理生态指标均有一定的促进作用;2)酸雨酸度对蒙古栎幼苗形态和生物量的影响不显著,但酸度增加降低了幼苗的根系伤流量;3)增雨的重度酸雨处理促进了蒙古栎幼苗形态生长和生物量累积;4)两因素对蒙古栎幼苗的影响没有交互作用.说明蒙古栎对酸雨具有一定的抗性,可考虑选择为酸雨区植被构建的物种.