Molecular modeling of 5-HT3 receptor ligands.

Ligands of various chemical classes (e.g., indoles, indazoles, benzamides, carbazoles, and quinolines) have demonstrated high affinity for the 5-HT₃ receptor in radiolabeled ligand-binding studies, and have shown 5-HT₃ receptor antagonistic activity in functional assays which utilize the excitatory effects of 5-HT on enteric neurons and autonomic afferents. Several 5-HT₃ antagonists are currently being evaluated for potential use in the treatment of migraine, schizophrenia, and anxiety, and a few have already demonstrated high efficacy as antiemetics in cancer chemotherapy. The purpose of this presentation is to highlight the significant structure-affinity relationships (SAFIR) and common geometrical features among 5-HT₃ receptor ligands, and to describe the three-dimensional pharmacophore for the 5-HT₃ recognition site derived from computational techniques. The chemical template containing the recognition elements (functional groups) for the 5-HT₃ receptor are: an aromatic or heteroaromatic ring system, a coplanar carbonyl group, and a nitrogen center, interrelated by well-defined distances. Two “binding shapes” or “active shapes” for 5-HT₃ ligands have been identified from detailed conformational analyses.     

基于分子对接技术虚拟筛选菊苣与肠道CNT2结合的化学成分研究

利用分子对接技术虚拟筛选菊苣与肠道浓度型核苷转运蛋白2(CNT2)结合的化学成分,为探讨菊苣干预嘌呤核苷吸收的降尿酸作用机制研究提供理论依据。采用同源建模手段构建人CNT2三维结构模型,采用Vina软件虚拟筛选菊苣小分子化合物作用于CNT2的化学成分。以CNT2抑制剂7,8,3'-三羟基黄酮的打分为阈值,筛选出23个打分高于阳性抑制剂的菊苣化学成分。其中打分靠前的菊苣化合物是菊苣降尿酸作用的重要化合物,其能否通过抑制CNT2活性干预肠道嘌呤核苷的吸收降低体内尿酸水平有待生物学实验进一步探讨。CNT2可能是菊苣降尿酸的效用靶点,为指导实验研究菊苣干预嘌呤核苷吸收降尿酸研究提供向导。     

基于生态位模型预测新疆准噶尔盆地大沙鼠适生区分布及风险评估

目的 探讨采用空间信息技术及生态位理论预测新疆准噶尔盆地大沙鼠的适生区分布,提高鼠疫监测效率.方法 通过现场调查获得准噶尔盆地大沙鼠分布的全球定位系统经纬度信息,通过遥感获得环境变量图层,利用Maxent软件建模,结合地理信息系统获得大沙鼠适生区分布图,对模型评价并划分风险分级图,叠加人口数据标示重点关注地区.结果 模型预测精度较高,曲线下面积值为0.968,灵敏度为91.4％,特异度为63.3％,准确度为73.8％,阳性预测值为59.7％,阴性预测值为92.6％,Kappa系数为0.495.大沙鼠适生区分布在准噶尔盆地及其周边大部分区县,高风险地区总面积约37 304 km2,约占总面积的6.2％,主要分布在昌吉回族自治州、乌鲁木齐市米东区及克拉玛依市,其中米东区、克拉玛依市辖区及乌尔禾区的分布较广;区域内人口约12万,分布于261 km2区域内.重点监测地区包括乌鲁木齐市、五家渠市、克拉玛依市、博乐市、精河县、奎屯市、阜康市、吉木萨尔县及木垒哈萨克自治县.结论 生态位理论和遥感环境数据可预测新疆准噶尔盆地大沙鼠潜在适生区,并显著缩小了重点监测的靶地区.     

FEMLAB对OCT在脑外科手术中应用可行性的仿真分析

光学相干层析技术是一种高分辨率成像方法。它是一种无损伤、非介入、非离子辐射的探测技术，具有较高的空间分辨率。有限元分析（FEA）是用于工程科学的重要工具，FEMLAB（Finite Element Modeling Laboratory）是基于偏微分方程的对科学和工程问题进行建模和仿真计算的交互式系统。本文简要介绍了OCT成像技术的原理及FEMLAB的应用步骤，重点用FEMLAB软件对脑组织内光场的分布情况进行分析，从而利用分析结果论证OCT成像在脑外科手术中应用的可行性。     

基于内在驱动因素模型的医院绩效方案评价

目的：从绩效评价系统的内在驱动力因素入手,探索评价绩效方案的方法,辅助医院建立和完善绩效评价体制。方法以某医院为研究对象,通过因子分析验证文献研究,建立评价模型并做模糊综合评价。结果正规化、目标设置、公平感知是评价绩效方案有效性的三个维度;经过计算和检验,该医院运行的绩效方案评价比较好。结论兼顾良好公平性,合理目标设置,适度正规化的绩效制度,能有效提高医疗效率,促进医疗资源的优化配置;助推医院完成战略式发展,最终实现两个效益。     

Cost-Effectiveness of a Community-Level HIV Risk Reduction Intervention for Women Living in Low-Income Housing Developments

We conducted a cost-effectiveness analysis of a multi-site community-level HIV prevention trial that enrolled women living in 18 low-income housing developments in 5 U.S. cities. A mathematical model of HIV transmission was used to estimate the number of HIV infections averted and quality-adjusted life years (QALYs) saved by the community-level intervention, based on data obtained from community-wide sexual behavior surveys at baseline and 12-month follow-up. Results indicated that the intervention prevented approximately 1 infection per 3500 women reached by the intervention, at a total cost of $174,845. The cost per QALY saved by the intervention was $37,433 and the cost per HIV infection averted was $732,072. The community-level intervention was moderately cost-effective in comparison with other HIV prevention programs for at-risk women. Synergistic approaches to HIV prevention that combine community-level sexual norm change interventions with more intensive risk reduction programs for high-risk women are needed.Editors’ Strategic Implications:The authors present a promising and efficient community-level HIV prevention approach, with effects beyond the limited scope of individual or small group interventions. This paper represents an example of how an analysis of cost-effectiveness can provide policymakers with information needed for difficult decisions about prevention resource allocations.     

Investigation of Adhesion Properties of Tire—Asphalt Pavement Interface Considering Hydrodynamic Lubrication Action of Water Film on Road Surface

To obtain the tire–pavement peak adhesion coefficient under different road states, a field measurement and FE simulation were combined to analyze the tire–pavement adhesion characteristics in this study. According to the identified texture information, the power spectral distribution of the road surface was obtained using the MATLAB Program, and a novel tire hydroplaning FE model coupled with a textured pavement model was established in ABAQUS. Experimental results show that here exists an “anti-skid noncontribution area” for the insulation and lubrication of the water film. Driving at the limit speed of 120 km/h, the critical water film thickness for the three typical asphalt pavements during hydroplaning was as follows: AC pavement, 0.56 mm; SMA pavement, 0.76 mm; OGFC pavement, 1.5 mm. The road state could be divided into four parts dry state, wet sate, lubricated state, and ponding state. Under the dry road state, when the slip rate was around 15%, the adhesion coefficient reached the peak value, i.e., around 11.5% for the wet road state. The peak adhesion coefficient for the different asphalt pavements was in the order OGFC > SMA > AC. This study can provide a theoretical reference for explaining the tire–pavement interactions and improving vehicle brake system performance.     

Sukkari dates seed improves type-2 diabetes mellitus-induced memory impairment by reducing blood glucose levels and enhancing brain cholinergic transmission: In vivo and molecular modeling studies

Cognitive decline is one of the serious complications associated with diabetes mellitus (T2DM) of type-2. In this reported work, the effect of aqueous sukkari dates seed extract (ASSE) was evaluated in T2DM-induced rats. T2DM was induced using intraperitoneal injection of nicotinamide and streptozocin (STZ) administration. The diabetic rats were then treated orally with 200 mg/kg and 400 mg/kg of dates seed extract for 30 days and results were compared with metformin-treated groups. The memory functions were assessed using three maze models. Glucose and insulin levels in the blood and acetylcholine, acetylcholinesterase brain homogenates were estimated. The results showed a significant reduction in transfer latency (TL) (p < 0.001) during the elevated plus maze (EPM) test. The novel object recognition (NOR) test revealed a longer exploration time (p > 0.05) with novel objects and a higher discrimination index (p > 0.05). The Y-maze test also showed a significant increase in the number of entries to the novel arm (p > 0.05) and the total number of entries in the trial (p > 0.01) as well as in test (p > 0.05) sessions. Reduction in blood glucose (p > 0.05) and improvement in blood insulin (p > 0.05) levels were also noted. Improvement in ACh levels (p > 0.001) with 400 mg/kg of ASSE and reduction in AChE (p > 0.001) with both doses of ASSE were also observed in the brain homogenates. The results of ASSE were found comparable with the metformin-treated rats. The estimation of phytochemical constituents displayed a significant presence of phenolic content. Further, molecular modeling studies showed ellagic acid, catechin, and epicatechin as the potential molecule interacting with GSK-3β, α-amylase, and AChE and may be responsible for observed bioactivity. In conclusion, ASSE has the ability to alleviate T2DM-related cognitive impairments.     

Assessment of the Impact of Ionizing Radiation Absorption on the Structural,Mechanical and Biophysical Properties of Textiles Used in Multilayer Space Suit

The article presents research on ergonomics, biophysical comfort and safety of protective clothing. The resistance of the structural, thermal and mechanical properties of five fabrics (CBXS400, GG200T, Twaron CT736, Dyneema HB26 and T1790C), differing in geometry and raw material composition used in space suits, to dangerous ionizing radiation (β and γ) occurring in space was tested. For both types of radiation, four identical one-time doses in the range of 25–100 kGy were used. The effect of the applied absorbed doses of β and γ radiation on the parameters of textiles influencing ergonomics and safety of the cosmonaut’s work was verified by structural tests (micro-computed tomography and optical microcopy), thermal resistance tests (sweating guarded-hotplate) and strength tests (tensile testing machine). Experimental studies of thermal properties are supplemented with heat transport simulations using the finite volume method performed with 3D models of real textiles. The greatest reduction of thermal resistance for Twaron CT736 (−0.0667 m²·°C·W⁻¹ for 100 kGy of β-radiation) and Dyneema HB26 (−0.0347 m²·°C·W⁻¹ for 50 kGy of β-radiation) is observed. Strength tests have shown that all tested textiles are resistant to both types of radiation. Three textiles were selected to create a three-layer assembly with potential application in a cosmonaut’s glove (Extravehicular Activity—EVA).