Integrated 3D-QSAR,molecular docking,and molecular dynamics simulation studies on 1,2,3-triazole based derivatives for designing new acetylcholinesterase inhibitors

Alzheimer’s disease (AD) is a multifactorial and polygenic disease. It is the most prevalent reason for dementia in the aging population. A dataset of twenty-six 1,2,3-triazole-based derivatives previously synthetized and evaluated for acetylcholinesterase inhibitory activity were subjected to the three-dimensional quantitative structure-activity relationship (3D-QSAR) study. Good predictability was achieved for comparative molecular field analysis (CoMFA) (Q² = 0.604, R² = 0.863, r_ext² = 0.701) and comparative molecular similarity indices analysis (CoMSIA) (Q² = 0.606, R² = 0.854, r_ext² = 0.647). The molecular features characteristics provided by the 3D-QSAR contour plots were quite useful for designing and improving the activity of acetylcholinesterase of this class. Based on these findings, a new series of 1,2,3-triazole based derivatives were designed, among which compound A1 with the highest predictive activity was subjected to detailed molecular docking and compared to the most active compound. The selected compounds were further subjected to 20 ns molecular dynamics (MD) simulations to study the comparative conformation dynamics of the protein after ligand binding, revealing promising results for the designed molecule. Therefore, this study could provide worthy guidance for further experimental analysis of highly effective acetylcholinesterase inhibitors.     

Multicontrast multiecho FLASH MRI for targeting the subthalamic nucleus

The subthalamic nucleus (STN) is one of the most common stimulation targets for treating Parkinson's disease using deep brain stimulation (DBS). This procedure requires precise placement of the stimulating electrode. Common practice of DBS implantation utilizes microelectrode recording to locate the sites with the correct electrical response after an initial location estimate based on a universal human brain atlas that is linearly scaled to the patient's anatomy as seen on the preoperative images. However, this often results in prolonged surgical time and possible surgical complications since the small-sized STN is difficult to visualize on conventional magnetic resonance (MR) images and its intersubject variability is not sufficiently considered in the atlas customization. This paper proposes a multicontrast, multiecho MR imaging (MRI) method that directly delineates the STN and other basal ganglia structures through five co-registered image contrasts (T1-weighted navigation image, R2 map, susceptibility-weighted imaging (phase, magnitude and fusion image)) obtained within a clinically acceptable time. The image protocol was optimized through both simulation and in vivo experiments to obtain the best image quality. Taking advantage of the multiple echoes and high readout bandwidths, no interimage registration is required since all images are produced in one acquisition, and image distortion and chemical shift are reduced. This MRI protocol is expected to mitigate some of the shortcomings of the state-of-the-art DBS implantation methods.     

Disease-related proteins determination based on surface-enhanced Raman spectroscopy

Abstract

Surface-enhanced Raman spectroscopy (SERS) is a promising platform for simple, rapid, and economical protein quantitation and analysis and can achieve much lower detection limits for the ultrasensitive detection of proteins and a much wider linear concentration range for quantitative analysis than other methods can. In addition, SERS can provide a large amount of fingerprint information for the individual components of a mixture through SERS effects, which are sensitive and selective for different types of proteins and protein mixtures. In general, the occurrence and development of diseases are accompanied by changes in the content or structure of biomarkers (disease-related proteins). Here, we provide an overview of the SERS technique and its applications to disease-related protein determination. Different diseases, such as Alzheimer’s disease (AD), cardiac muscle tissue injury, and multicancer, are discussed and exhibit potential utility in biomarker detection and diagnosis. SERS opens a new path to the early diagnosis of critical diseases, which will effectively reduce human suffering and mortality.     

Magnetic resonance elastography of the brain in a mouse model of Alzheimer's disease: initial results

The increasing prevalence of Alzheimer's disease (AD) has provided motivation for developing novel methods for assessing the disease and the effects of potential treatments. Magnetic resonance elastography (MRE) is an MRI-based method for quantitatively imaging the shear tissue stiffness in vivo. The objective of this research was to determine whether this new imaging biomarker has potential for characterizing neurodegenerative disease. Methods were developed and tested for applying MRE to evaluate the mouse brain, using a conventional large bore 3.0T MRI system. The technique was then applied to study APP-PS1 mice, a well-characterized model of AD. Five APP-PS1 mice and 8 age-matched wild-type mice were imaged immediately following sacrifice. Brain shear stiffness measurements in APP-PS1 mice averaged 22.5% lower than those for wild-type mice (P = .0031). The results indicate that mouse brain MRE is feasible at 3.0T, and brain shear stiffness has merit for further investigation as a potential new biomarker for Alzheimer's disease.     

龙虾叶状幼体聚缩虫病防治的研究

对防治龙虾叶状幼体聚缩虫病采用多种药物、多种措施进行对比试验，表明投金藻、扁藻、光合细菌和丰年虫幼体，优化培育水体生态环境，改善叶状幼体营养，提高叶状幼体自洁力，加速叶状幼体发育变态，适当调高盐度以恶化聚缩虫诉生存环境，及时清除丰年虫卵壳等污物，能有效地防治龙虾叶状幼体聚缩虫病。     

城市元胞自动机模型的构建及其应用研究进展

 元胞自动机(CA)模型对模拟和预测城市空间变化以及进行城市规划具有重大的现实意义。对中国知识基础设施工程(CNKI)中出现城市CA研究以来的期刊文献的年度分布、期刊分布进行统计分析,概述了城市CA模型的构建思路,回顾和总结了城市CA中土地利用、交通、疾病和灾害方面的相关研究成果。同时,分析了城市CA模型应用研究中的主要特点,并根据其存在问题探讨了城市CA未来的发展趋势。研究结果表明,城市CA在中国的应用研究前景良好,尽管近12年中研究情况存在波动,但整体呈增长态势。     

一类传染病模型无病平衡点的全局稳定性

过去的半个多世纪,传染病模型在数学生态学领域已受广泛重视.研究了一个具时滞和扩散的传染病模型,重点讨论了该模型解的定性性质和稳态解的渐近行为;利用线性化和特征值方法讨论了正稳态解的局部稳定性,通过构造单调迭代序列,给出了正稳态解的全局稳定性. 最后给出了数值模拟和讨论,当接触率充分小时,问题的无病平衡点是全局渐近稳定的.     

网络环境下的医院门诊挂号预约系统改善研究

本文对改善挂号预约系统的模型进行了分析探索。根据病人的自报病情信息及医疗经验信息,通过量化的方法,对挂号预约阶段病人对疾病分类和症状程度划分进行了研究。研究结果有助于改善预约挂号系统。新的方法有助于解决挂号难的问题、有助于医疗服务质量的提高、并且有助于医疗资源的优化利用。     

核受体Rev-erbs的能量稳态调控作用及其运动科学研究展望

 核受体Rev-erbs是能量稳态调控的核心转录调节因子,其表达受饮食、药物、运动等因素的影响;Rev-erbs参与糖脂代谢、胰岛素分泌、血糖稳态调节等多个生物学过程,是肥胖症、糖尿病等慢性代谢性疾病治疗的重要药物靶标,通过调节糖脂代谢通路中的靶分子,调控组织的能量稳态。运动干预刺激肝脏、骨骼肌等组织中Rev-erbs表达,调控糖脂代谢基因,维持细胞能量稳态,可能是慢性病运动干预的重要适应机制。简述了Rev-erbs的结构特点、表达调控因素与作用机制,分析了运动干预对Rev-erbs表达的影响与代谢调控机制,以及Rev-erbs在运动科学领域的国际前沿和发展趋势。     

硒化聚甘露糖醛酸的合成及抗阿尔茨海默症细胞氧化与凋亡

以聚甘露糖醛酸为原料, 采用先磺化、 再硒化的方法合成了硒化聚甘露糖醛酸, 产率为54%, 产物硒含量为437.25 μg/g. 在2.5 μmol/L硒浓度下, 硒化聚甘露糖醛酸促细胞生长能力达到最适范围, 能保护细胞免受过氧化氢损伤, 显著提高阿尔茨海默症(AD)模型细胞N2a-APP695-sw中的超氧化物歧化酶和谷胱甘肽过氧化物酶的活性, 降低细胞内活性氧自由基, 增加线粒体膜电位, 抑制细胞色素C的释放, 在促进Bcl-2表达的同时抑制Bax的表达, 从而具有抑制AD细胞凋亡的功能. 硒化聚甘露糖醛酸也能抑制AD病理相关蛋白BACE1和APP的表达. 结果表明, 硒化聚甘露糖醛酸在抗AD方面具有潜在的应用前景.