Chiglitazar monotherapy with sitagliptin as an active comparator in patients with type 2 diabetes:a randomized,double-blind,phase 3 trial(CMAS)

Chiglitazar(Carfloglitazar)is a novel peroxisome proliferator-activated receptor(PPAR)pan-agonist that has shown promising effects on glycemic control and lipid...     

Tumour micro-environment elicits innate resistance to RAF inhibitors through HGF secretion

Drug resistance presents a challenge to the treatment of cancer patients. Many studies have focused on cell-autonomous mechanisms of drug resistance. By contrast, we proposed that the tumour micro-environment confers innate resistance to therapy. Here we developed a co-culture system to systematically assay the ability of 23 stromal cell types to influence the innate resistance of 45 cancer cell lines to 35 anticancer drugs. We found that stroma-mediated resistance is common, particularly to targeted agents. We characterized further the stroma-mediated resistance of BRAF-mutant melanoma to RAF inhibitors because most patients with this type of cancer show some degree of innate resistance. Proteomic analysis showed that stromal cell secretion of hepatocyte growth factor (HGF) resulted in activation of the HGF receptor MET, reactivation of the mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3-OH kinase (PI(3)K)-AKT signalling pathways, and immediate resistance to RAF inhibition. Immunohistochemistry experiments confirmed stromal cell expression of HGF in patients with BRAF-mutant melanoma and showed a significant correlation between HGF expression by stromal cells and innate resistance to RAF inhibitor treatment. Dual inhibition of RAF and either HGF or MET resulted in reversal of drug resistance, suggesting RAF plus HGF or MET inhibitory combination therapy as a potential therapeutic strategy for BRAF-mutant melanoma. A similar resistance mechanism was uncovered in a subset of BRAF-mutant colorectal and glioblastoma cell lines. More generally, this study indicates that the systematic dissection of interactions between tumours and their micro-environment can uncover important mechanisms underlying drug resistance.     

人骨形态发生蛋白6(hBMP6)在毕赤酵母中的分泌表达

以重组质粒pcDNA6A-BMP6为模板PCR扩增hBMP6成熟肽cDNA编码序列,将该序列克隆到酵母分泌表达表达载体pPIC9K中.重组质粒pPIC9K-hBMP6经SacI酶切线性化,电击转化毕赤酵母GS115,PCR法筛选阳性转化子,利用梯度浓度G418筛选到七株高拷贝整合的阳性转化子。用甲醇进行诱导表达,SDSPAGE及Western-blot检测结果表明hBMP6成熟肽以分子量约为34和18 kD两种不同糖基化修饰的单体形式存在,具有良好的免疫原性.     

基于烦恼率模型的人致人行桥振动舒适度分析

为实现人致人行桥振动舒适度定量计算,首先,在同一坐标系中研究隶属度函数与人行桥加速度响应之间的函数关系,联系桥上行人心理连续体上的感受区间呈非等距特征,提出基于Stevens幂函数定律的改进隶属度函数,将改进隶属度函数与传统计算公式及实验结果进行比较;其次,综合考虑行人主观反应随机性、个体差异性及变异性,建立人致人行桥振动烦恼率模型,为舒适度定量计算提供理论依据;最后,在基于烦恼率模型的分析方法框架之下建立人行桥竖向及侧向振动舒适度分析方法,建议同时考虑竖向及侧向耦合振动舒适度评价方法,并采用一个实桥分析案例对上述分析流程的应用进行说明。研究结果表明:隶属度与加速度响应之间呈指数函数关系,即服从Stevens幂函数定律;当加速度响应小于人体承受极限时,可采用逐级增量法对行人心理物理量进行描述;改进隶属度函数值与传统隶属度值、实验值之间的最大误差均不超过1%;竖向及侧向振动烦恼率曲线的误差不超过0.04,且变异系数的影响不超过3%;综合考虑人体在不同振动环境下的敏感程度,建议容许烦恼率指标取为22%,具体评估工作中不可忽略人行桥振动响应对容许烦恼率指标的影响;烦恼率计算值与实测值之间的误差不超过3%;该类结果可为在役桥梁振动舒适度定量计算提供直接参考。     

股票市场普适性规律的分析与研究

分析了国内外许多学者近年来对不同国家或地区股票市场波动规律的研究,提出了股票市场存在普适性,并论述了普适性在收益的概率分布、波动率的变化规律和收益的多重分形分布中的存在,为进一步研究股票市场波动的动力学规律提供了依据.     

Synthesis and characterization of bifunctional terbium complex-based nanoparticles

Novel bifunctional terbium complex-based nanoparticles were developed using a modified Stber method and a layer-by-layer assembly process. A magnetic core of Fe3O4 nanoparticles was coated with a silica shell to form the first layer. Then a ternary Tb3+ complex (TESPPA-Tb), which acted as a luminescent marker, was covalently bound to the silica surface by stable Si-O-Si bonds. The TESPPA monomer was synthesized by binding pyridine 2,6-dicarboxylic acid to 3-aminopropyltriethoxysilane, which was used as a ligand for coordination with the Tb3+ ions. An outer shell of silica was applied to the nanoparticles to allow for versatility with surface functionalization. The nanoparticles were characterized by X-ray powder diffraction, transmission electron microscopy, Fourier transform infrared spectroscopy, ultravioletvisible spectroscopy, vibration sample magnetometer, and photoluminescence spectroscopy. The bifunctional nanoparticles exhibited favorable superparamagnetic behavior and photoluminescence properties of Tb3+. These nanoparticles have potential applications in biolabeling, bioseparation, immunoassays, and pathogenic diagnosis.     

Electromagnetic modification of faceted-faceted Ni<Subscript>31</Subscript>Si<Subscript>12</Subscript>-Ni<Subscript>2</Subscript>Si eutectic alloy

In an electromagnetic field, the morphology of a binary faceted-faceted (FF) Ni31Si12-Ni2Si eutectic microstructure and the alloy’s mechanical properties were investigated. Hardness experiments demonstrated that the solidified ingots were significantly strengthened, and the hardness was improved to 63.1 and 786.6 on the Rockwell hardness C and Vickers hardness scales, respectively. Tests of friction and wear in stirred FF eutectic alloys showed excellent anti-fatigue and anti-adhesion wear performance. Alloy changed from an anomalous microstructure to a refined quasi-regular structure, and there was an increase in the lamellar microstructure fraction. The formation process of the refined quasi-regular microstructure and the resulting mechanical properties were investigated.     

海南县域经济发展水平的空间差异与扶贫开发

自改革开放以来,海南社会经济获得了很大的发展,但是县域经济发展水平的空间差异仍十分显著.为了更好地了解海南县域经济发展水平的空间差异,选取人均GDP、城镇化水平、人均财政收入、农民人均纯收入、非农产值、文盲率等7项指标,采用量图分析法,将全省18个市县行政区分为先进、中等、落后3种类型.确定今后扶贫的重点市县.让真正需要扶贫支持的市县得到必要的扶贫支持.尽快的脱离贫困.     

Fenton氧化工艺处理石油树脂生产废水研究

试验研究了难生物降解石油树脂生产废水Fenton氧化处理效果,考查了各影响因子最佳工艺条件.结果表明,在pH值为2.5、FeSO4投加量为800 mg·L-1、H2O2投加量为3000 mg·L-1、反应时间为2 h、反应温度为50～55℃的条件下,Fenton氧化工艺COD去除率为73%左右.将Fenton氧化处理水同低浓度含油废水混合后经进一步混凝沉淀处理,处理水COD值可降低至350 mg·L-1左右,达到了污水三级排放标准(COD<500 mg·L-1).     

黑龙江省资源经济发展探讨

黑龙江省资源丰富,地大物博,但在多年资源依赖型发展模式的影响下,经济发展已有衰退之势,出现了资源衰竭、生态环境破坏、产业结构单一、接续产业不足等资源经济多方面的问题.针对这些问题本文提出了要以科学发展观为根本理念,大力发展接续产业,并以循环经济发展模式保证资源的可持续利用,以求资源型城市的顺利转型,保证黑龙江省经济的可持续发展.