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.     

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.     

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.     

Analysis of Phytochemical Composition of Camellia oleifera Oil and Evaluation of its Anti-Inflammatory Effect in Lipopolysaccharide-Stimulated RAW 264.7 Macrophages

In China, Camellia oleifera oil (COO) is not only a common edible oil but also a traditional remedy widely applied to ameliorate a variety of illnesses associated with inflammation, such as mouth ulcers, thrush, eczema, etc. However, there has been a lack of relevant biological research on the anti-inflammatory capacity of COO, and the specific bioactive lipid phytochemicals contributing to the anti-inflammatory effect need further research. In this study, the RAW 264.7 macrophages model was used to investigate the anti-inflammatory capacity of COO. Our data showed that 33–200 μg/mL COO markedly inhibited the lipopolysaccharide lipopolysaccharide (LPS)-stimulated nitric oxide (NO.) secretion via the suppression of Nos2 and Cox-2 expression. The enzyme immunoassay confirmed that COO also exhibited a strong suppressive effect on the expression of proinflammatory cytokines such as Tnf-α and Il-6. To further explore the correlation between the anti-inflammatory effects and the lipid phytochemicals in COO, 10 samples were collected and screened for their chemical compositions. It was interestingly demonstrated that the polyphenol extracts of COO play a vital role in its anti-inflammatory properties. In addition, an oil-in-water (O/W) emulsion-based system was also developed to deliver the liposoluble COO into the cells, and the feasibility of this system was confirmed. Our research confirms the anti-inflammatory potential of COO and highlights that the main functional ingredient is polyphenol extracts. This may provide a scientific basis for the comprehensive utilization and development of COO and related functional foods.     

A robust control of robot manipulators for physical interaction: stability analysis for the interaction with unknown environments

Intelligent Service Robotics - A robust control designed for multiple degrees-of-freedom (DOF) robot manipulators performing complex tasks requiring frequent physical interaction with unknown...     

基于密闭爆发器试验的发射装药内弹道性能预估

为了预估发射装药的内弹道性能,建立了一种基于密闭爆发器试验检测发射药的静态燃烧性能参数进而预测其装药内弹道性能的方法,采用不同批次的单樟-5/7发射药进行了装药性能预估计算,并基于30 mm火炮对内弹道性能预估精度进行了试验验证。结果表明,采用所建立的基于密闭爆发器试验的发射装药内弹道性能预估方法计算获得的最大膛压为376.0 MPa,与试验测试的膛压平均值388.7 MPa的计算误差为3.27%;计算的炮口初速为1143.5 m/s,与试验测试的炮口初速平均值1156.3 m/s的计算误差为1.11%。所建立的基于密闭爆发器试验的发射装药内弹道性能预估方法具有较高的精度,可对发射药样品不同批次间的内弹道性能进行高效精确的预估,为长期贮存发射药使用寿命的判定及发射药产品的出厂校验提供了一种高效低成本的弹道性能评价方法。     

Large increase of Curie temperature in (110)-oriented La0.7Sr0.3MnO3 films

From the perspectives of scientific researches and practical applications, it is desirable to explore high operating temperature ferromagnetic films. The effect of biaxial strain on magnetic properties of (110)-oriented La_0.7Sr_0.3MnO₃ films was studied. High quality La_0.7Sr_0.3MnO₃ films were grown on (110)-oriented perovskite single crystal substrates using pulsed laser deposition, varying substrate-induced misfit strains from ??2.27–0.75%. A remarkable enhancement of Curie temperature has been achieved for (110)-oriented La_0.7Sr_0.3MnO₃ films clamped with small misfit strains (i.e., grown on LAST (110)). The enhanced Curie temperature of (110)-oriented La_0.7Sr_0.3MnO₃ films could be attributed to the misfit strain between the films and the underlying substrates and may have technological implication for applications at high temperature environments.     

Overseas Cooperation of Chinese Oil Enterprises in 2017

This paper analyzes the status quo and progress of overseas oil and gas business cooperation built by Chinese oil enterprises in 2017. With the slow recovery of the oil and gas industries as a whole, the overseas oil and gas business of Chinese oil enterprises has continued to grow in size, and all-round cooperation progress was made along the Belt and Road. Breakthroughs were made in oil and gas cooperation between China and the United States. In the meantime, new features have emerged in the overseas cooperation of Chinese enterprises, and a pattern of diversified investors has basically taken shape.     

Preparation of biaxially textured Ce1-x(Y0.2Zr0.8)xOδ buffer layers on RABiTS NiW tapes by chemical solution deposition

Highly (100)-oriented Ce_1-x(Y_0.2Zr_0.8)_xO_δ (CYZO) films were prepared on biaxially textured NiW substrates by a chemical solution deposition approach using metal inorganic salts as starting materials. It has been found that both the preferential orientation and surface roughness of CYZO films decrease gradually with increasing of the doping percentage of Y³⁺ and Zr⁴⁺ ions. The epitaxial growth relationship of (220)_CYZO//(200)_NiW and [00?l]_CYZO//[001]_NiW was demonstrated by XRD texture measurement as well as atomic resolution STEM observation. XRD, Raman and XPS spectra results indicate that Y³⁺ and Zr⁴⁺ ions were indeed introduced into CeO₂ lattice to substitute Ce⁴⁺ ions and form cubic fluorite CYZO solid solution. Moreover, CeO₂ buffer layer can be endowed a strong enough capability to prevent element diffusion through co-doping of yttrium and zirconium, provided that an optimal doping ratio of them is adopted. This will provide a new approach to fabricating strong-barrier single buffer layer for coated conductor.