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.     

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.     

A Novel Beam Search to Improve Neural Machine Translation for English-Chinese

Neural Machine Translation (NMT) is an end-to-end learning approach for automated translation, overcoming the weaknesses of conventional phrase-based translation systems. Although NMT based systems have gained their popularity in commercial translation applications, there is still plenty of room for improvement. Being the most popular search algorithm in NMT, beam search is vital to the translation result. However, traditional beam search can produce duplicate or missing translation due to its target sequence selection strategy. Aiming to alleviate this problem, this paper proposed neural machine translation improvements based on a novel beam search evaluation function. And we use reinforcement learning to train a translation evaluation system to select better candidate words for generating translations. In the experiments, we conducted extensive experiments to evaluate our methods. CASIA corpus and the 1,000,000 pairs of bilingual corpora of NiuTrans are used in our experiments. The experiment results prove that the proposed methods can effectively improve the English to Chinese translation quality.     

A dynamic SVR–ARMA model with improved fruit fly algorithm for the nonlinear fiber stretching process

Natural Computing - The fiber stretching process plays the key role in the process of fiber production and its effects is measured by the stretching ratio. The stretching ratio is determined by the...     

渣油胶质和沥青质在分散型催化剂作用下的临氢热反应行为

采用四组分法从辽河减压渣油中分离出胶质、沥青质，分别考察了它们在分散型催化剂作用下的临氢热反应行为。结果表明，胶质、沥青质一方面要裂化生成较轻的产物；另一方面也要发生缩合反应生成较重的反应产物以及甲苯不溶物。渣油在临氢热反应过程中，沥青质是生焦的主要来源，其次才是胶质。比较了热反应生成的沥青质与原生沥青质之间以及热反应生成的胶质与原生胶质之间化学组成的区别，结果表明，反应生成的沥青质和胶质较原生的沥青质和胶质分子结构缩合程度高，并且反应苛刻度越高，缩合程度也越高。