A Dual Inhibitor of DYRK1A and GSK3β for β-Cell Proliferation: Aminopyrazine Derivative GNF4877

Loss of β-cell mass and function can lead to insufficient insulin levels and ultimately to hyperglycemia and diabetes mellitus. The mainstream treatment approach involves regulation of insulin levels; however, approaches intended to increase β-cell mass are less developed. Promoting β-cell proliferation with low-molecular-weight inhibitors of dual-specificity tyrosine-regulated kinase 1A (DYRK1A) offers the potential to treat diabetes with oral therapies by restoring β-cell mass, insulin content and glycemic control. GNF4877, a potent dual inhibitor of DYRK1A and glycogen synthase kinase 3β (GSK3β) was previously reported to induce primary human β-cell proliferation in vitro and in vivo. Herein, we describe the lead optimization that lead to the identification of GNF4877 from an aminopyrazine hit identified in a phenotypic high-throughput screening campaign measuring β-cell proliferation.     

樟芝多糖通过降低NLRP3 Caspase1炎性小体表达改善帕金森小鼠神经行为学的机制研究

目的:研究樟芝多糖通过降低NLRP3-Caspase1炎性小体表达改善6-OHDA构建的帕金森小鼠模型的行为学机制。方法:利用6-OHDA脑内注射构建帕金森小鼠模型，通过酪氨酸羟化酶（TH）免疫组化染色和行为学判定小鼠模型的构建成功。利用樟芝多糖进行干预，分别在干预前、干预后的第1、3、7天4个时间点进行神经行为学实验，分别采用转棒实验、爬杆实验检测小鼠自主行为能力以及协调能力，4个时间点取小鼠尾静脉外周血采用ELISA法检测外周血中Caspase1和IL-1β的表达，樟芝多糖干预第7天时待进行完行为学实验后小鼠断颈处死，取小鼠脑组织-纹状体，Western blot法检测纹状体中Caspase1、proCaspase1、NLRP3的表达，高效液相色谱检测纹状体中单胺类神经递质的表达，RT-QPCR检测Caspase1、NLRP3、IL-1β、IL-4、IL-6的mRNA表达。NISSl染色检测小鼠脑组织神经细胞凋亡情况。 结果:6-OHDA脑内注射可以造成小鼠帕金森样病变，且TH蛋白表达显著下调，樟芝多糖干预后小鼠的行为学得到显著改善（P<0.05），纹状体中Caspase1、proCaspase1、NLRP3的表达显著下调，与模型小鼠相比具有统计学差异（P<0.05），且相关炎症因子Caspase1、NLRP3、IL-1β、IL-4、IL-6的mRNA表达下调（P<0.05），纹状体中单胺类神经递质表达上升（P<0.05）。结论:樟芝多糖可以通过下调NLRP3-Caspase1炎性小体表达来改善6-OHDA构建的帕金森小鼠模型行为改善，这可能是樟芝多糖治疗帕金森的机制之一。     

Regulation of sensory nerve conduction velocity of human bodies responding to annual temperature variations in natural environments

The extensive research interests in environmental temperature can be linked to human productivity / performance as well as comfort and health; while the mechanisms of physiological indices responding to temperature variations remain incompletely understood. This study adopted a physiological sensory nerve conduction velocity (SCV) as a temperature‐sensitive biomarker to explore the thermoregulatory mechanisms of human responding to annual temperatures. The measurements of subjects’ SCV (over 600 samples) were conducted in a naturally ventilated environment over all four seasons. The results showed a positive correlation between SCV and annual temperatures and a Boltzmann model was adopted to depict the S‐shaped trend of SCV with operative temperatures from 5°C to 40°C. The SCV increased linearly with operative temperatures from 14.28°C to 20.5°C and responded sensitively for 10.19°C‐24.59°C, while tended to be stable beyond that. The subjects’ thermal sensations were linearly related to SCV, elaborating the relation between human physiological regulations and subjective thermal perception variations. The findings reveal the body SCV regulatory characteristics in different operative temperature intervals, thereby giving a deeper insight into human autonomic thermoregulation and benefiting for built environment designs, meantime minimizing the temperature‐invoked risks to human health and well‐being.     

Stick-Breaking Dependent Beta Processes with Variational Inference

Neural Processing Letters - The beta processes (BP) is a powerful nonparametric tool in feature learning, which is often used as the prior of Bernoulli process for choosing features from a feature...     

Study of MW-scale biogas-fed SOFC-WGS-TSA-PEMFC hybrid power technology as distributed energy system: Thermodynamic,exergetic and thermo-economic evaluation

Advanced biogas power generation technology has been attracting attentions, which contributes to the waste disposal and the mitigation of greenhouse gas emissions. This work proposes and models a novel biogas-fed hybrid power generation system consisting of solid oxide fuel cell, water gas shift reaction, thermal swing adsorption and proton exchange membrane fuel cell (SOFC-WGS-TSA-PEMFC). The thermodynamic, exergetic, and thermo-economic analyses of this hybrid system for power generation were conducted to comprehensively evaluate its performance. It was found that the novel biogas-fed hybrid system has a gross energy conversion efficiency of 68.63% and exergy efficiency of 65.36%, indicating high efficiency for this kind of hybrid power technology. The market sensitivity analysis showed that the hybrid system also has a low sensitivity to market price fluctuation. Under the current subsidy level for the distributed biogas power plant, the levelized cost of energy can be lowered to 0.02942 $/kWh for a 1 MW scale system. Accordingly, the payback period and annual return on investment can reach 1.4 year and about 20%, respectively. These results reveal that the proposed hybrid system is promising and economically feasible as a distributed power plant, especially for the small power scale (no more than 2 MW).     

汽车空调的操作和应用分析

2013年国内汽车产销量超过2000万台,汽车正在快速进入中国的千家万户,但大部分车主还缺乏对汽车空调知识的了解,夏天又是空调故障多发期,如果车主了解相关汽车空调知识,在实际应用中会达到事倍功半的效果,因此介绍了一般车型的空调结构、工作原理以及特殊气候下的调节。     

三门峡地区黄土工程特性

三门峡地区广泛分布第四纪黄土及黄土状土,通过分析该地区黄土的颗粒成分、矿物成分、化学成分、微观结构特征,分析了黄土的工程特性,结果表明:该地区Q3黄土的组成与中更新统黄土的矿物组成基本相近,颗粒组成以粉粒为主,黏粒含量大于我国西北地区,粉粒含量小于西北地区;全新统黄土、晚更新统黄土为中等、强湿陷性黄土,湿陷性系数为0.020~0.098,中更新统黄土一般不具有湿陷性。     

A computer aided design method for car form and its application based on shape parameters

In the early design stage, automotive modeling should both meet the requirements of aesthetics and engineering. Therefore, a vehicle CAD (computer aided design) model that can be easily adjusted by feedbacks is necessary. Based on CE-Bézier surface, this paper presents a set of algorithms for parametric segmentation and fairing surface generation in a car model. This model is defined by a simplified automotive template and relevant control points, shape parameters and segmentation parameters, which can be modified to alter the car form efficiently. With this model and the corresponding adjustment method, more than fifty various vehicle models are established in this research according to different parameters. And two methods for calculating similarity index between car models are constructed, which are suitable for brand design trend analysis and modelling design decisionmaking.     

调节性B细胞在自身免疫性溶血性贫血患者外周血中的表达及临床意义

目的: 探讨自身免疫性溶血性贫血（AIHA）患者外周血中调节性B细胞（Bregs）的表达及其在该病发病中的意义。方法:选择16例自身免疫性溶血性贫血患者和14例健康志愿者为研究对象，用流式细胞术分析外周血CD19+IL-10+调节性B细胞及CD19+CD24hiCD27+调节性B细胞的表达；ELISA方法检测培养上清液中IL-10的水平。结果:自身免疫性溶血性贫血患者外周血中CD19+IL-10+调节性B细胞、CD19+CD24hiCD27+调节性B细胞的表达分别为（1.27±0.39）％、（9.85±2.18）％，健康志愿者组分别为（2.92±0.71）％、（26.47±4.31）％，两组比较差异有统计学意义（P<0.05）；自身免疫性溶血性贫血患者细胞培养上清中IL-10的水平低于健康志愿者组（P<0.05）。结论:自身免疫性溶血性贫血患者外周血中CD19+IL-10+调节性B细胞及CD19+CD24hiCD27+调节性B细胞比例降低，提示调节性B细胞可能参与自身免疫性溶血性贫血的发病过程。