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.     

microRNA在亨廷顿病中的研究进展

亨廷顿病(Huntington's disease, HD)是神经退行性疾病(neurodegenerative disorders)中一种单基因遗传病,由亨廷顿基因(the huntingtin gene, HTT)第一个外显子中的CAG三核苷酸序列重复扩增引起,尚无法治愈。HTT编码的蛋白产物被称为亨廷顿蛋白(Huntingtin protein, Htt)。突变亨廷顿蛋白(mutated huntingtin protein, mHtt)容易形成聚集体,具有毒性,导致一系列细胞学异常和神经元功能障碍。microRNA(miRNA)在基因转录后水平调控中起重要作用,其表达的改变与HD病理过程有关,成为治疗HD的潜在生物标志物。近年来,对一些特定miRNA在HD中调控机制及靶基因预测方面的研究可为HD提供潜在的治疗方法。本文就miRNA在HD中的相关研究进展进行综述。     

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...     

Super-oleophilicity Co-doping Co2+/F-/TiO2 one-dimensional nanotubes for photocatalytic denitrification of light oil

In this study, a simple hydrothermal synthesis method was adapted for the preparation of Co-doping Co²⁺/F^-/TiO₂ nanotubes photocatalyst, and the micro-nano structure of catalysts prepared by biomimetic technology which makes the catalyst have super-oleophilicity property. Co²⁺/F^-/TiO₂ revealed improved photocatalytic performance for denitrification of light oil compared to single TiO₂ photocatalysts. The enhance of photocatalytic activity can be attributed to narrowing the band gap, increasing the light response wavelength and exposing more highly active crystal surfaces due to synergistic effects of Co²⁺ and F^? in the photocatalyst.     

Visual Detection of Adenosine Triphosphate by Taylor Rising: A Simple Point-of-Care Testing Method Based on Rolling Circle Amplification

Rapid and sensitive point-of-care testing (POCT) is an extremely critical mission in practical applications, especially for rigorous military medicine, home health care, and in the third world. Here, we report a visual POCT method for adenosine triphosphate (ATP) detection based on Taylor rising in the corner of quadratic geometries between two rod surfaces. We discuss the principle of Taylor rising, demonstrating that it is significantly influenced by contact angle, surface tension, and density of the sample, which are controlled by ATP-dependent rolling circle amplification (RCA). In the presence of ATP, RCA reaction effectively suppresses Taylor-rising behavior, due to the increased contact angle, density, and decreased surface tension. Without addition of ATP, untriggered RCA reaction is favorable for Taylor rising, resulting in a significant height. With this proposed method, visual sensitive detection of ATP without the aid of other instruments is realized with only a 5 μL droplet, which has good selectivity and a low detection limit (17 nM). Importantly, this visual method provides a promising POCT tool for user-friendly molecular diagnostics.     

3-三氟甲基-5,6,7,8-四氢-1,2,4-三唑[4,3-α]吡嗪盐酸盐的合成

乙二胺与氯乙酸乙酯经取代、环合反应制得2-哌嗪酮,2-哌嗪酮与Boc酸酐进行氨基保护反应后,再与五硫化二磷进行硫代反应制得4-(N-叔丁氧羰基)-2-哌嗪硫酮,其与三氟乙酰肼经取代、环合、脱叔丁氧羰基成盐,得标题化合物,总收率为45.7%(以氯乙酸乙酯计)。为磷酸西他列汀中间体的工业化生产提供了一条较理想的工艺路线。     

High‐performance thermosets with tailored properties derived from methacrylated eugenol and epoxy‐based vinyl ester

A renewable chemical, eugenol, is methacrylated to produce methacrylated eugenol (ME) employing the Steglich esterification reaction without any solvent. The resulting ME is used as a low‐viscosity co‐monomer to replace styrene in a commercial epoxy‐based vinyl ester resin (VE). The volatility and viscosity of ME and styrene are compared. The effect of ME loading and temperature on the viscosity of the VE–ME resin is investigated. Moreover, the thermomechanical properties, curing extent and thermal stability of the fully cured VE–ME thermosets are systematically examined. The results indicate that ME is a monomer with low volatility and low viscosity, and therefore the incorporation of ME monomer in VE resins allows significant reduction of viscosity. Moreover, the viscosity of the VE–ME resin can be tailored by adjusting the ME loadings and processing temperature to meet commercial liquid molding technology requirements. The glass transition temperatures of VE–ME thermosets range from 139 to 199 °C. In addition, more than 95% of the monomer is incorporated and fixed in the crosslinked network structure of VE–ME thermosets. Overall, the developed ME monomer exhibits promising potential for replacing styrene as an effective low‐viscosity co‐monomer. The VE–ME resins show great advantages for use in polymer matrices for high‐performance fiber‐reinforced composites. This work is of great significance to the vinyl ester industry by providing detailed experimental support. © 2018 Society of Chemical Industry