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.     

Smart firefighting construction in China: Status,problems, and reflections

“Smart firefighting” construction as a part of the “smart city” has been a concern of the public security and fire agencies at all levels. In this study, the status, problems, and reflections of “smart firefighting” construction in China are discussed. A recent survey indicates that China has launched its smart firefighting construction and initially created a new perspective on its regional smart firefighting work based on three main aspects: intelligent disaster perception by Internet of Things (IoT) construction, intelligent disaster prevention by big data construction, and intelligent disaster disposal by emergency rescue platform construction. However, the current smart firefighting construction in China still has some prominent problems such as the data interconnectivity and normalized management of various platforms, the extensibility of smart firefighting platforms, and the intelligent level of smart firefighting researches, which need to be solved urgently. Therefore, we argue that smart firefighting construction in China should establish data interconnectivity, industrial normalized management, 2D/3D geographic information interaction and extension, high-integration fire protection theory, and many other aspects in the near future and truly realize firefighting visualization and efficient data applications for 4D time space. This study could provide valuable reference for smart firefighting and smart city construction.     

Fabrication of dense nano-laminated tungsten carbide materials doped with Cr3C2/VC through two-step sintering

This work investigates the critical roles of two-step sintering (TSS) and laminated structure on the sintering behavior and mechanical properties of functionally graded WC-TiC-Al₂O₃ nanostructured composite materials doped with Cr₃C₂/VC. Results show that excellent mechanical properties are achieved for tailored TSS conditions with a hardness of 27.91?±?2.3?GPa and a flexural strength of 1423.3?±?23.5?MPa. The desirable mechanical properties are attributed to the suppressed grain growth without densification deterioration. TSS is more effective in facilitating the favorable dispersion of secondary phase toughening nano-particulates in a WC matrix than conventional sintering (CS). Cr₃C₂/VC dopant plays an important role in maximizing and shifting the temperature range of the kinetic window for WC-Al₂O₃ composites. Al₂O₃ crack deflection, transgranular Al₂O₃, microcracking, WC crack bridging and plate-like WC crack deflection are the major toughening mechanisms. Residual surface compressive stress induced by the graded structure is also an appreciated contribution to the improvement of mechanical properties.     

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.     

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。     

PET熔体长距离输送影响因素探讨

介绍了PET熔体长距离输送工艺流程,重点分析易对PET熔体输送带来不利影响的因素,如熔体压力降、停留时间、管道粗糙度、焊缝品质等,并针对熔体输送的不利因素,提出了相应的解决方案,对熔体直纺设计、实践提供必要的参考。