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.     

Study on Wettability and Corrosion Behavior of Al2O3 Doped Polyurea Coatings

Protection of Metals and Physical Chemistry of Surfaces - The Al2O3 powder was added as a filler to polyurea and the effect of doping amount on Shore hardness and wetting property were...     

快速灵敏的LC-MS/MS法测定人血浆中阿莫西林并应用于两种制剂的一致性评价

目的: 建立快速灵敏的LC-MS/MS法测定人血浆中阿莫西林浓度，并用于两种阿莫西林胶囊的一致性评价。方法: 采用岛津公司LCMS-8060型LC-MS/MS仪，以MRM模式测定阿莫西林（m/z 366.00/114.00）的浓度，d4-阿莫西林作内标（m/z 370.10/114.05），离子源为ESI源。色谱柱选用Waters ACQUITY BEH C18（2.1×50 mm，1.7 μm），梯度洗脱。血浆样本加入内标，经甲醇沉淀蛋白后取上清液进样检测。结果: 所建方法经验证，其线性、准确度、精密度、最低定量限、提取回收率、特异性、基质效应、稳定性等各项指标均符合CFDA的指导原则及最新核查标准要求，并较文献报道中的方法有处理简单、灵敏度高、色谱峰形好的优点。结论: 所建方法快速、灵敏，适用于人血浆中阿莫西林浓度的检测。用于一致性评价的样本实测，两种制剂生物等效。     

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.     

Precipitating spinel into precursor glass and its assistance in crystallization

The crystallization phenomena of spinel in CaO-MgO-Al₂O₃-SiO₂-Fe₂O₃ glass have received much attention due to the particular role in preparation of glass-ceramic materials, which represent an effective option to manage hazardous waste. In this study, both preliminary spinel and secondary spinel were precipitated in the precursor glass. The formation of these spinel was meticulously assessed by a combination of X-ray diffractometry and scanning electron microscopy. The structure of the microenvironment in the precursor glass was characterized by Raman spectrums. These advanced techniques highlight the potential for one-step crystallization of the glass. The investigation, which focused on one-step crystallization, demonstrated the growth of pyroxene on spinel accompanying a migration of chromium. The results also show the microstructure of the obtained glass-ceramic was very dependent on the heat-treat temperature. This study not only unambiguously reveals the precipitation mechanisms of spinel but also provides more documentation for one-step crystallization in the glass-ceramics field.     

基于三相幅度测量的相控阵天线快速校准方法

提出了一种基于三相幅度测量的相控阵天线快速校准方法。该方法将天线阵列进行分组,利用每种分组在三种配相下的阵面合成场幅度测量值,可解算出各个天线单元的初始幅相值。该方法仅需幅度测量,避免了相位测量误差影响单元幅相值的计算精度,而且所需幅度测量次数仅为(2N+1)次,可显著提高校准时效性。另外,利用分组思想,同时改变多个单元相位,使总辐射场的幅度变化显著,提升校准准确性。仿真结果表明:校准后相位均方根误差为2.2°,幅度均方根误差为0.2 dB。     

Experimental and numerical study on compressive performance of perforated brick masonry after fire exposure

This paper discusses the compressive performance of perforated brick masonry after fire exposure. Compressive strength tests of the mortar, clay perforated brick, and perforated brick masonry specimens were performed in accordance with ISO834 fire tests of different durations. The temperature distribution of the masonry materials and specimens was simulated using the finite element software ABAQUS, with the thermal parameters of masonry materials recommended by European standard Eurocode 6 and related literature. The compressive strength reduction factors of mortar and clay perforated brick exposed to different fire durations were calculated via the layered method suggested by European standard Eurocode 1. In addition, the compressive strength reduction factors after cooldown were obtained from the experimental data of the masonry materials, and by considering further reductions in the compressive strength after cooling from high temperatures. Experimental data of the masonry specimens were compared with the numerical results obtained using the reduction factors proposed in this work. The comparison revealed an overall acceptable approximation. Thus, the method presented in this paper can be used to evaluate the residual capacity of masonry structures after fire.     

胸腺五肽辅助治疗肺癌对免疫功能影响及其疗效的系统评价

为了系统地评价胸腺五肽作为辅助药物治疗各种肺癌的疗效及其对机体免疫功能的影响，利用电子检索收集有关胸腺五肽联合放疗或化疗方案治疗肺癌的临床随机对照试验文献，对符合纳入标准的文献，采用RevMan5.3 软件进行系统评价。最终共纳入文献 9 篇，总样本量 784 例。Meta 分析结果表明，胸腺五肽作为辅助药物治疗各种肺癌提高总有效率的差异无统计学意义[OR ＝ 1.44, 95%CI(0.99, 2.10), P ＝0.06 ＞ 0.05]。在对免疫功能的影响方面，胸腺五肽的使用显著增高外周血中的 CD3+ 细胞水平[OR ＝ 5.88, 95% CI(2.34, 9.42), P ＝0.001]，CD4+ 细胞水平也显著上升[OR ＝8.32, 95%CI(5.22, 11.42), P ＜ 0.00001] , CD4＋ /CD8＋比值也有明显的提高[OR ＝ 0.38, 95% CI(0.18, 0.59), P＝0.0002]，但 CD8+ 细胞水平的差异无统计学意义[OR ＝－3.12, 95% CI ( －9.02, 2.79), P ＞0.05]。总的来说，本研究在一定程度上反映了在辅助治疗肺癌方面，胸腺五肽能显著提高外周血中的 CD3+ 细胞水平、CD4+ 细胞水平、CD4+/CD8+ 比值。而对于治疗的有效率、CD8+ 细胞水平，差异无统计学意义。     

课程群案例嵌入协同教学模式的探索

在课程群的教学中由于每门课程各自独立开展教学,缺乏知识的融合和衔接,导致学生运用综合知识解决问题的能力较弱。在课程群的教学中采用案例嵌入协同教学模式,将完整的工程案例嵌入到课程群各门课程的教学中,协同规划各门课程的教学任务,每门课程再围绕案例展开研究性教学。通过嵌入的工程案例衔接各门课程的知识点,帮助学生建构完整的知识体系,强化工程应用的概念；同时通过研究性教学,培养学生分析问题和解决问题的能力,两部分相结合,提高了学生运用综合知识解决复杂问题的能力。