Targeting NADPH Oxidase and Phospholipases A2 in Alzheimer’s Disease

Alzheimer’s disease (AD) is marked by an increase in the production of extracellular beta amyloid plaques and intracellular neurofibrillary tangles associated with a decline in brain function. Increases in oxidative stress are regarded as an early sign of AD pathophysiology, although the source of reactive oxygen species (ROS) and the mechanism(s) whereby beta amyloid peptides (Aβ) impact oxidative stress have not been adequately investigated. Recent studies provide strong evidence for the involvement of NADPH oxidase and its downstream oxidative signaling pathways in the toxic effects elicited by Aβ. ROS produced by NADPH oxidase activate multiple signaling pathways leading to neuronal excitotoxicity and glial cell-mediated inflammation. This review describes recent studies demonstrating the neurotoxic effects of Aβ in conjunction with ROS produced by NADPH oxidase and the downstream pathways leading to activation of cytosolic phospholipase A₂ (PLA₂) and secretory PLA₂. In addition, this review also describes recent studies using botanical antioxidants to protect against oxidative damage associated with AD. Investigating the metabolic and signaling pathways involving Aβ NADPH oxidase and PLA₂ can help understand the mechanisms underlying the neurodegenerative effects of oxidative stress in AD. This information should provide new therapeutic approaches for prevention of this debilitating disease.     

CLUE-S模型在南京市土地利用变化研究中的应用

土地利用/覆盖变化模型是研究区域景观动态并解释其驱动机制的重要技术手段.应用CLUE-S模型,在Landsat TM影像等相关数据支持下,对南京地区1998-2006年土地利用的时空动态变化进行了研究.结果表明:各土地利用类型变化受地形因素影响最大,人均GDP与城镇用地和农业用地的分布呈显著相关,城乡主干道对土地利用变化的贡献显著大于省级及以上道路;海拔较高区域林地的发生比率较高,而地形低平区域农田、城建用地的发生比率较高.经检验,在300 m空间分辨率水平,对南京地区2003年、2006年土地利用状况模拟的精度分别达到了85.7%和84.1%;而通过将研究区分成若干子区,分别修正模型参数并重新模拟,准确率提高到89.7%和88.3%,分区赋值法有效地提高了模拟精度.研究表明,CLUE-S模型对城市发展的空间结构也有较强的预测能力,对指导城市规划、分析景观动态的驱动机制有重要参考价值.     

黄土高原半湿润区刺槐树干液流对人工截留降雨输入及环境因子的响应

随着全球气候变化加剧, 局部地区温度上升和降水量改变将对区域植被的分布与生长产生重要影响。在黄土高原半湿润及半干旱地区植被恢复中, 刺槐(Robinia pseudoacacia)是大面积种植的人工林树种。为探究该树种蒸腾耗水特征对降水量改变及水分条件差异的响应, 于2015年4月起, 在地处黄土高原半湿润区的陕西省永寿县槐平林场, 于35年生刺槐人工林样地中布设了人工截留降雨试验, 减少了47.5%的降雨输入。处理当年生长季内, 截留降雨处理区0-100 cm土层的平均土壤含水量相对于对照区(23.76%)有明显降低(22.59%)。采用Granier热扩散探针对截留降雨处理区和对照区的样树树干液流动态进行连续监测, 并同步监测主要气象环境因子(太阳辐射、空气温度和湿度)和林地土壤含水量, 分析了截留降雨处理区与对照区树干液流通量密度动态特征及其对环境因子的响应。结果表明: 截留降雨输入处理降低了刺槐树干液流通量密度, 截留降雨处理期间典型天气的平均液流通量密度(1.64 mL·m ^-2·s ^-1)不仅低于同组样树在处理前一年同期的水平(2.42 mL·m ^-2·s ^-1), 而且远低于试验期间对照区样树的平均水平(3.38 mL·m ^-2·s ^-1); 同时, 截留降雨处理还降低了刺槐液流通量密度对气象因子变化的敏感性, 截留降雨处理区样树液流通量密度响应空气水汽压亏缺的拟合方程参数值与对照区样树差异显著。分析可知, 降水量水平不仅影响土壤水分状况, 而且影响刺槐对气象环境因子响应的敏感性, 降水量减少导致的土壤含水量整体降低会使得该区域刺槐蒸腾耗水量下降, 显示其对环境因子的适应性, 但最终会导致生产力的大幅度降低。     

0.21nm分辨率BO-(L-精氨酸)牛胰岛素晶体结构研究

应用差值Fourier技术,立体化学最小二乘技术和XPLOR程序并辅以电子密度图的人工拟合,以三方二锌猪胰岛素模型为起点,解析了0.21nm分辨率BO-(L-精氨酸)牛胰岛素的晶体结构,最终R因子为18.2%,与标准键长与键角的均方根偏差分别为0.0022nm和 4.3°.从电子密度图与模型的拟合来看,独立区两个分子中B链N端加长的L-精氨酸清晰可见.相对于三方二锌猪胰岛素分子,B链N端晶体学微环境发生了变化.     

人胃癌BGC-823细胞中去甲斑蝥素抑癌作用机理的蛋白质组学研究

去甲斑蝥素是我国自行研制的抗肿瘤药物,在临床上主要用于消化道肿瘤的治疗．实验表明,去甲斑蝥素可引起人胃癌BGC-823细胞发生 M期阻滞及细胞凋亡．进一步利用双向电泳和质谱技术,筛选出了去甲斑蝥素抑癌作用相关蛋白．研究显示,线粒体热休克蛋白CH60、线粒体ATP合酶d亚单位、内质网葡萄糖调节蛋白GRP78、线粒体Hsp70的辅助因子GRPE1、SH3L3以及染色质组装因子1小亚基RBBP4参与了去甲斑蝥素的抑癌作用．研究提示,去甲斑蝥素可能通过促进线粒体热休克蛋白及p53的表达进而激活caspase-3依赖的凋亡通路,并且去甲斑蝥素在引发内质网协迫之后,可通过抑制胞外信号调节激酶(extracellular signal regulated kinase, ERK)的活性促进肿瘤细胞的凋亡．进一步分析了去甲斑蝥素与线粒体ATP合酶抑制剂寡霉素A的联合用药对人胃癌细胞生长的影响,结果表明,联合用药的抑瘤效果比单独用药的抑瘤效果显著,提示去甲斑蝥素可能通过抑制线粒体ATP合酶功能抑制BGC-823生长．上述结果为优化去甲斑蝥素的联合用药方案提供了新线索．     

Engineering imaging probes and molecular machines for nanomedicine

Nanomedicine is an emerging field that integrates nanotechnology, biomolecular engineering, life sciences and medicine; it is expected to produce major breakthroughs in medical diagnostics and therapeutics. Due to the size-compatibility of nano-scale structures and devices with proteins and nucleic acids, the design, synthesis and application of nanoprobes, nanocarriers and nanomachines provide unprecedented opportunities for achieving a better control of biological processes, and drastic improvements in disease detection, therapy, and prevention. Recent advances in nanomedicine include the development of functional nanoparticle based molecular imaging probes, nano-structured materials as drug/gene carriers for in vivo delivery, and engineered molecular machines for treating single-gene disorders. This review focuses on the development of molecular imaging probes and engineered nucleases for nanomedicine, including quantum dot bioconjugates, quantum dot-fluorescent protein FRET probes, molecular beacons, magnetic and gold nanoparticle based imaging contrast agents, and the design and validation of zinc finger nucleases (ZFNs) and TAL effector nucleases (TALENs) for gene targeting. The challenges in translating nanomedicine approaches to clinical applications are discussed.     

外来入侵种--紫茎泽兰花芽分化和胚胎学研究

应用石蜡切片法对紫茎泽兰(Eupatorium adenophorum)从花芽分化到胚胎形成的全过程进行系统观察,结果表明:紫茎泽兰从刚孕花序至头状花序的直径(d)大小为1.6～1.8 mm时为花芽分化期;d在1.8～2.0和3.8～4.0 mm范围内为大小孢子及雌雄配子体发育期,其中d在2.3～3.5 mm之间时为减数分裂的主要过程;药壁分化过程为双子叶型,胞质分裂为同时型,绒毡层发育属腺质绒毡层,成熟花粉粒为3-细胞型;胚囊发育属蓼形,胚珠倒生,单珠被,薄珠心;胚胎发育过程中有双胚现象.     

Human umbilical cord-derived MSC culture: the replacement of animal sera with human cord blood plasma

Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) hold great potential for their therapeutic use in various clinical diseases. Many publications have reported on human blood-derived alternatives to animal serum for culturing mesenchymal stem cells, such as human serum, allogenic umbilical cord blood serum, and human platelet derivatives. However, it is not clear whether human umbilical cord blood plasma (UCBP), as the surplusage of umbilical cord blood mesenchymal stem cell extraction, could be used. In this study, in order to make the best of umbilical cord blood, the human UCBP was dialyzed to replace fetal bovine serum (FBS) in the culture medium. hUC-MSCs were cultured in the new medium. Cell growth rate, specific biomarkers, and differentiation properties were detected to characterize the cell proliferation and MSC-specific properties. The hUC-MSCs cultured in such derived medium were verified with proliferation rate, cluster differentiation markers, cell cycle, as well as differentiation capabilities. Such dialyzed human UCBP is fully comparable with, if not superior to, FBS in deriving and culturing hUC-MSCs.