4-Methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene,a Major Active Metabolite of Bisphenol A,Triggers Pancreatic β-Cell Death via a JNK/AMPKα Activation-Regulated Endoplasmic Reticulum Stress-Mediated Apoptotic Pathway

4-methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene (MBP), a major active metabolite of bisphenol A (BPA), is generated in the mammalian liver. Some studies have suggested that MBP exerts greater toxicity than BPA. However, the mechanism underlying MBP-induced pancreatic β-cell cytotoxicity remains largely unclear. This study demonstrated the cytotoxicity of MBP in pancreatic β-cells and elucidated the cellular mechanism involved in MBP-induced β-cell death. Our results showed that MBP exposure significantly reduced cell viability, caused insulin secretion dysfunction, and induced apoptotic events including increased caspase-3 activity and the expression of active forms of caspase-3/-7/-9 and PARP protein. In addition, MBP triggered endoplasmic reticulum (ER) stress, as indicated by the upregulation of GRP 78, CHOP, and cleaved caspase-12 proteins. Pretreatment with 4-phenylbutyric acid (4-PBA; a pharmacological inhibitor of ER stress) markedly reversed MBP-induced ER stress and apoptosis-related signals. Furthermore, exposure to MBP significantly induced the protein phosphorylation of JNK and AMP-activated protein kinase (AMPK)α. Pretreatment of β-cells with pharmacological inhibitors for JNK (SP600125) and AMPK (compound C), respectively, effectively abrogated the MBP-induced apoptosis-related signals. Both JNK and AMPK inhibitors also suppressed the MBP-induced activation of JNK and AMPKα and of each other. In conclusion, these findings suggest that MBP exposure exerts cytotoxicity on β-cells via the interdependent activation of JNK and AMPKα, which regulates the downstream apoptotic signaling pathway.     

Optimized Biocatalytic Synthesis of 2-Selenopyrimidine Nucleosides by Transglycosylation**

Selenium-modified nucleosides are powerful tools to study the structure and function of nucleic acids and their protein interactions. The widespread application of 2-selenopyrimidine nucleosides is currently limited by low yields in established synthetic routes. Herein, we describe the optimization of the synthesis of 2-Se-uridine and 2-Se-thymidine derivatives by thermostable nucleoside phosphorylases in transglycosylation reactions using natural uridine or thymidine as sugar donors. Reactions were performed at 60 or 80 °C and at pH 9 under hypoxic conditions to improve the solubility and stability of the 2-Se-nucleobases in aqueous media. To optimize the conversion, the reaction equilibria in analytical transglycosylation reactions were studied. The equilibrium constants of phosphorolysis of the 2-Se-pyrimidines were between 5 and 10, and therefore differ by an order of magnitude from the equilibrium constants of any other known case. Hence, the thermodynamic properties of the target nucleosides are inherently unfavorable, and this complicates their synthesis significantly. A tenfold excess of sugar donor was needed to achieve 40−48 % conversion to the target nucleoside. Scale-up of the optimized conditions provided four Se-containing nucleosides in 6–40 % isolated yield, which compares favorably to established chemical routes.     

有机二氟化硼配合物的合成及压致变色性能表征

以阿伏苯宗和三氟化硼为原料,经过一步反应,合成阿伏苯宗二氟化硼(BF2AVB),产物的结构经1HNMR谱确证.基于荧光光谱与X射线粉末衍射测试,对BF2AVB的压致发光性能和机理进行研究.本实验原料易得,反应条件温和,实验操作简单,反应收率高.BF2AVB的压致变色现象明显,通过探讨压致变色机理,加深同学对压致变色材料的了解.同时,该实验可以拓展学科知识,激发学生的专业热情和科研兴趣.     

An index structure supporting rule activation in pervasive applications

World Wide Web - Rule mechanism has been widely used in many areas, such as databases, artificial intelligent and pervasive computing. In a rule mechanism, rule activation decides which rules are...     

破损水文观测孔涌水封堵技术在高河矿的应用

针对高河矿奥灰水文观测孔空水管锈蚀断裂漏水严重的问题,分析了存在的问题,制定了钻孔涌水封堵技术方案及相应的注浆施工工艺,并进行了为期7天的井下试验。封堵注浆压力达到6 MPa,使用注浆水泥50 t,水泥浆液凝固良好,注浆阀门打开后无出水现象。     

长走向平行钒铁矿体协同开采方案研究

七角井矿区的钒、铁双层矿体走向长度超4 km且呈近似平行产出，下盘铁矿开采时损失贫化率高且上盘钒矿资源保护难度大。根据钒铁矿体走向长、近平行产出、厚度负相关、空区隐患大的开采技术条件 特征，采用平面分区、开采时序规划、采矿方法优化、区域稳定性控制等技术来实现钒铁矿协同开采。根据铁矿“中间厚、两端薄”、钒矿“中间薄、两端厚”的形态特征，将长走向的钒铁矿体分为东区、中区及西 区。工程空间上，双层矿体共用一套开拓、采准、运输等开采系统；开采时序上，在提高铁矿生产能力的同时保证了钒矿开采的时间灵活性；采矿方法上，东区及西区铁矿采用阶段矿房嗣后膏体微胶结充填法，中区 铁矿采用阶段矿房法转崩落法；此外，通过中区崩落顶板及上盘围岩，东、西区膏体充填方式保证了矿区开采时及开采后的区域稳定性。研究表明：所提出的协同开采方案使矿山铁矿设计开采储量增加了1 064.7万t ，膏体充填每年消耗干抛层、尾矿等矿山固废86万t以上，矿山安全及经济效益明显。