Some Molecular and Cellular Stress Mechanisms Associated with Neurodegenerative Diseases and Atherosclerosis

Chronic stress is a combination of nonspecific adaptive reactions of the body to the influence of various adverse stress factors which disrupt its homeostasis, and it is also a corresponding state of the organism’s nervous system (or the body in general). We hypothesized that chronic stress may be one of the causes occurence of several molecular and cellular types of stress. We analyzed literary sources and considered most of these types of stress in our review article. We examined genes and mutations of nuclear and mitochondrial genomes and also molecular variants which lead to various types of stress. The end result of chronic stress can be metabolic disturbance in humans and animals, leading to accumulation of reactive oxygen species (ROS), oxidative stress, energy deficiency in cells (due to a decrease in ATP synthesis) and mitochondrial dysfunction. These changes can last for the lifetime and lead to severe pathologies, including neurodegenerative diseases and atherosclerosis. The analysis of literature allowed us to conclude that under the influence of chronic stress, metabolism in the human body can be disrupted, mutations of the mitochondrial and nuclear genome and dysfunction of cells and their compartments can occur. As a result of these processes, oxidative, genotoxic, and cellular stress can occur. Therefore, chronic stress can be one of the causes forthe occurrence and development of neurodegenerative diseases and atherosclerosis. In particular, chronic stress can play a large role in the occurrence and development of oxidative, genotoxic, and cellular types of stress.     

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.     

Farmers' preferences for adopting on-farm concentration of raw milk: Results from a discrete choice experiment in Germany

Milk concentrates are used in the manufacturing of dairy products such as yogurt and cheese or are processed into milk powder. Processes for the nonthermal separation of water and valuable milk ingredients are becoming increasingly widespread at farm level. The technical barriers to using farm-manufactured milk concentrate in dairies are minimal, hence the suspicion that the practice of on-farm raw milk concentration is still fairly uncommon for economic reasons. This study, therefore, set out to investigate farmers' potential willingness to adopt a raw milk concentration plant. The empirical analysis was based on discrete choice experiments with 75 German dairy farmers to identify preferences and the possible adoption of on-farm raw milk concentration. The results showed that, in particular, farmers who deemed the current milk price to be insufficient viewed on-farm concentration using membrane technology as an option for diversifying their milk sales. We found no indication that adoption would be impeded by a lack of trustworthy information on milk processing technologies or capital.     

基于乙酰胆碱酯酶和氧化应激研究海胆酮对阿尔茨海默症的作用机制

海胆酮是一种酮式类胡萝卜素，主要从海胆及藻类等海洋生物中提取。本文研究海胆酮对乙酰胆碱酯酶（acetylcholinesterase，AChE）的抑制作用，应用酶动力学、荧光光谱、圆二色光谱和分子对接技术研究海胆酮对AChE的抑制机理，并用淀粉样β蛋白片段25～35（amyloid beta-peptide 25-35，Aβ25-35）诱导大鼠肾上腺嗜铬细胞瘤细胞（PC12细胞）建立阿尔茨海默症（Alzheimer’s disease，AD）模型，研究海胆酮对AD细胞模型氧化应激损伤的作用。结果表明，海胆酮有很强的AChE抑制活性，其半抑制质量浓度为（16.29±0.97）μg/mL，抑制常数Ki为3.82 μg/mL，表现为竞争性抑制；海胆酮可诱导AChE二级结构改变，更容易与AChE活性中心氨基酸Ser200、His440、Trp84和Tyr121结合，阻碍底物碘代硫代乙酰胆碱（acetylthiocholine iodide，ATCI）与酶结合，从而引起酶活力降低。海胆酮能有效抑制Aβ25-35诱导PC12细胞的AChE活力，降低丙二醛含量，增加超氧化物歧化酶、过氧化氢酶和谷胱甘肽过氧化物酶活力，减轻Aβ25-35诱导的PC12细胞氧化应激损伤。本研究基于AChE和氧化应激阐明了海胆酮对AD的潜在作用机制，为海胆酮在功能食品、生物医药等领域的应用提供了数据支持和理论根据。     

综采工作面巷道内瓦斯分布规律研究

为了研究综采工作面巷道内瓦斯运移规律，摸清瓦斯流动的状态，采用理论分析、数值模拟和现场试验相结合的方法，理论分析得到了工作面风流特性及瓦斯运移规律，数值模拟得到了瓦斯异常释放后工作面瓦斯浓度分布变化情况及工作面正常工作瓦斯浓度分布，然后进行现场试验，试验结果和数值模拟结果相似。研究为工作面瓦斯治理提供了技术支持。     

轻量级电驱水下机械臂设计与运动学分析

设计了一款四功能水下机械臂，并对驱动关节进行了模块化设计和密封测试。为了保证水下机械臂的可靠性，在水下机械臂水下测试前，进行了强度校核和模态分析。为了验证水下机械臂的性能，通过 Ｄ- Ｈ法建立了其运动学模型，在此基础上分别进行了正、逆运动学分析。此外还采用蒙特卡洛法，在正运动学分析的基础上研究了工作空间特点。研究结果将为进一步的运动控制提供有益的帮助。     

黔北桑木场背斜铅锌矿深部找矿实例分析*#br#

黔北桑木场背斜位于上扬子地块黔北隆起区毕节弧形褶皱带与赤水克拉通盆地的交汇部位，属于有利的铅锌成矿区带。区内铅锌矿的赋矿层位主要有震旦系灯影组、寒武系清虚洞组、高台组及石冷水组，矿体多产于背斜核部并受断层或裂隙控制。通过对地层岩性特征、地表矿化特征、控容矿构造特征、化探异常特征、物探异常特征等进行综合研究，选择在成矿有利地段进行了工程验证，为进一步开展桑木场背斜铅锌矿深部找矿工作提供了思路。     

基于粒子群优化算法的五自由度机械臂轨迹规划

为了让机械臂的工作时间达到最优,以自主研发的抛光机器人样机为研究对象,针对手表表壳表耳部分的抛光过程,提出PSO算法对五自由度机械臂轨迹规划进行优化,并通过MATLAB软件进行机械臂的仿真与分析。仿真结果表明,基于PSO算法的轨迹规划使机械臂在工作过程中加加速度不会产生突变,运动轨迹精度高,机械臂工作时间达到最优。