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.     

Thermoplastic and low dielectric constants polyimides based on BPADA-BAPP

ABSTRACT

The thermoplastic and low dielectric constants polyimides were introduced. The polyimides were prepared by pyromellitic dianhydride (PMDA) or 4,4?-(4,4?-Isopropylidenediphenoxy)diphthalic anhydride (BPADA) as anhydride monomer and 4,4?-oxydianiline (ODA) or 2,2-bis(4-(4-aminephenoxy)phenyl)propane (BAPP) as amine monomer. The polyimides were well characterized by FT-IR, thermogravimetric analysis, dynamic thermomechanical analysis, dielectric measurement, and tensile test. The dielectric constants were 2.32–2.95 compared with 3.10 of ODA-PMDA polyimide, while partly polyimides were thermoplastic. The results indicated anhydride monomers, containing lateral methyl groups, made polyimides become thermoplastic. The results of molecular simulations via Materials Studio also proved this conclusion.     

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.     

Synergistic flame retardant effects of activated carbon and molybdenum oxide in poly(vinyl chloride)

The synergistic effects of activated carbon (AC) and molybdenum oxide (MoO₃) in improving the flame retardancy of poly(vinyl chloride) (PVC) were investigated. The effects of AC, MoO₃ and their mixture with a mass ratio of 1:1 on the flame retardancy and smoke suppression properties of PVC were studied using the limiting oxygen index and cone calorimeter tests. It was found that the flame retardancy of the relatively cheaper AC was slightly weaker than that of MoO₃. In addition, the incorporation of AC and MoO₃ greatly reduced the total heat release and improved smoke suppressant property of PVC composites. When the total content of AC and MoO₃ was 10 phr, PVC/AC/MoO₃ had the lowest peak heat release rate and peak smoke production rate values of 173.80 kW m^?2 and 0.1472 m² s^?1, which represented reductions of 47.3 and 59.9%, respectively, compared with those of PVC. Furthermore, thermogravimetric analysis and gel content tests were used to analyze the flame retardant mechanism of AC and MoO₃, with results showing that AC could promote early crosslinking in PVC. Char residue left after heating at 500 °C was analyzed using scanning electron microscopy and Raman spectroscopy, and the results showed that MoO₃ produced the most compact char, with the smallest and most organized carbonaceous microstructures. © 2017 Society of Chemical Industry     

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.     

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。     

Using electroencephalogram to continuously discriminate feelings of personal thermal comfort between uncomfortably hot and comfortable environments

Thermal comfort is an important factor for the design of buildings. Although it has been well recognized that many physiological parameters are linked to the state of thermal comfort or discomfort of humans, how to use physiological signal to judge the state of thermal comfort has not been well studied. In this paper, the feasibility of continuously determining feelings of personal thermal comfort was discussed by using electroencephalogram (EEG) signals in private space. In the study, 22 subjects were exposed to thermally comfortable and uncomfortably hot environments, and their EEG signals were recorded. Spectral power features of the EEG signals were extracted, and an ensemble learning method using linear discriminant analysis or support vector machine as a sub-classifier was used to build the discriminant model. The results show that an average discriminate accuracy of 87.9% can be obtained within a detection window of 60 seconds. This study indicates that it is feasible to distinguish whether a person feels comfortable or too hot in their private space by multi-channel EEG signals without interruption and suggests possibility for further applications in neuroergonomics.     

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.