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.     

Covalent triazine framework with efficient photocatalytic activity in aqueous and solid media

Covalent triazine frameworks (CTFs) have been recently employed for visible light-driven photocatalysis due to their unique optical and electronic properties. However, the usually highly hydrophobic nature of CTFs, which originates from their overall aromatic backbone, leads to limitations of CTFs for applications in aqueous media. In this study, we aim to extend the range of the application media of CTFs and design hybrid material of a CTF and mesoporous silica (SBA-15) for efficient photocatalysis in aqueous medium. A thiophene-containing CTF was directly synthesized in mesopores of SBA-15. Due to the high surface area and the added hydrophilic properties by silica, the hybrid material demonstrated excellent adsorption of organic molecules in water. This leads not only to high photocatalytic performance of the hybrid material for the degradation of organic dyes in water, but also for efficient photocatalysis in solvent-free and solid state. Furthermore, the reusability, stability and easy recovery of the hybrid material offers promising metal-free heterogeneous photocatalyst for broader applications in different reaction media.     

Ferroelastic domain structure and phase transition in single-crystalline [PbZn1/3Nb2/3O3]1-x[PbTiO3]x observed via in situ x-ray microbeam

(1-x)Pb(Zn_1/3Nb_2/3)O₃-xPbTiO₃ ((1-x)PZN-xPT in short) is one of the most important piezoelectric materials. In this work, we extensively investigated (1-x)PZN-xPT (x = 0.07–0.11) ferroelectric single crystals using in-situ synchrotron μXRD, complemented by TEM and PFM, to correlate microstructures with phase transitions. The results reveal that (i) at 25 °C, the equilibrium state of (1-x)PZN-xPT is a metastable orthorhombic phase for x = 0.07 and 0.08, while it shows coexistence of orthorhombic and tetragonal phases for x = 0.09 and x = 0.11, with all ferroelectric phases accompanied by ferroelastic domains; (ii) upon heating, the phase transformation in x = 0.07 is Orthorhombic → Monoclinic → Tetragonal → Cubic. The coexistence of ferroelectric tetragonal and paraelectric cubic phases was in-situ observed in x = 0.08 above Curie temperature (T_C), and (iii) phase transition can be explained by the evolution of the ferroelectric and ferroelastic domains. These results disclose that (1-x)PZN-xPT are in an unstable regime, which is possible factor for its anomalous dielectric response and high piezoelectric coefficient.     

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 study on the permeability and self-healing capacity of geosynthetic clay liners in heavy metal solutions

Geosynthetic clay liners (GCLs), which have a very low permeability to water and a considerably high self-healing capacity, are widely used in liner systems of landfills. In this study, a series of experimental tests were carried out under complex conditions on typical commercial GCLs from China. In particular, the effects of pH values and lead ions (Pb²⁺) were tested in addition to other factors. The swelling properties of natural bentonite encapsulated between geotextile components in the GCLs were tested first. The swelling capacity was reduced rapidly at pH values < 3 and concentrations of Pb²⁺ >40 mM. Permeability tests on GCLs with different concentrations of lead ions were then performed by using the self-developed multi-link flexible wall permeameter, and data showed that increases in lead ion concentrations greatly improved the permeability. Finally, self-healing capacity tests were conducted on needle-punched GCLs under different levels of damage. Results showed that the GCLs have a good self-healing capacity with small diameter damage holes (2 mm, close to three times the original aperture), but with a damage aperture larger than 15% of the sample area, the self-healing capacity could not prevent leakage; hence, in certain situations it will be necessary to repair the damage to meet the anti-seepage requirement.     

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。     

Microstructure and damage evolution of SiCf/PyC/SiC and SiCf/BN/SiC mini-composites: A synchrotron X-ray computed microtomography study

SiC_f/PyC/SiC and SiC_f/BN/SiC mini-composites comprising single tow SiC fibre-reinforced SiC with chemical vapor deposited PyC or BN interface layers are fabricated. The microstructure evolutions of the mini-composite samples as the oxidation temperature increases (oxidation at 1000, 1200, 1400, and 1600?°C in air for 2?h) are observed by scanning electron microscopy, energy dispersive spectrometry, and X-ray diffraction characterization methods. The damage evolution for each component of the as-fabricated SiC_f/SiC composites (SiC fibre, PyC/BN interface, SiC matrix, and mesophase) is mapped as a three-dimensional (3D) image and quantified with X-ray computed tomography. The mechanical performance of the composites is investigated via tensile tests.The results reveal that tensile failure occurs after the delamination and fibre pull-out in the SiC_f/PyC/SiC composites due to the volatilization of the PyC interface at high temperatures in the air environment. Meanwhile, the gaps between the fibres and matrix lead to rapid oxidation and crack propagation from the SiC matrix to SiC fibre, resulting in the failure of the SiC_f/PyC/SiC composites as the oxidation temperature increases to 1600?°C. On the other hand, the oxidation products of B₂O₃ molten compounds (reacted from the BN interface) fill up the fracture, cracks, and voids in the SiC matrix, providing excellent strength retention at elevated oxidation temperatures. Moreover, under the protection of B₂O₃, the SiC_f/BN/SiC mini-composites show a nearly intact microstructure of the SiC fibre, a low void growth rate from the matrix to fibre, and inhibition of new void formation and the SiO₂ grain growth from room to high temperatures. This work provides guidance for predicting the service life of SiC_f/PyC/SiC and SiC_f/BN/SiC composite materials, and is fundamental for establishing multiscale damage models on a local scale.