通过FGF401的构效关系研究发现一种新颖的FGFR4选择性抑制剂

设计并合成了一系列FGF401类似物以研究其FGFR4抑制、抗肿瘤活性及其构效关系.研究发现了N-(5-氰基-4-(2-甲氧基乙基氨基)吡啶-2-基)-7-甲酰基-6-(N-甲基四氢吡喃-4-甲酰胺)甲基-1,2,3,4-四氢-1,8-萘啶-1-甲酰胺(8ac)不仅在酶和细胞学水平上对FGFR4具有强效的的抑制活性,并表现出了出色的选择性.其活性及选择性优于阳性对照FGF401,并且在HCC (hepatocellular carcinoma)动物移植瘤模型中显著抑制肿瘤生长,还引起了肿瘤萎缩.     

Rotational Spectra of 2,3,6-Trifluoropyridine: Effect of Fluorination on Ring Geometry

The ground state rotational spectrum of 2, 3, 6-trifluoropyridine has been investigated in the 2.0\begin{document}$ - $\end{document}20.0 GHz region by pulsed jet Fourier transform microwave spectroscopy. The experimental rotational constants are \begin{document}$ A $\end{document} = 3134.4479(2) MHz, \begin{document}$ B $\end{document} = 1346.79372(7) MHz, and \begin{document}$ C $\end{document} = 941.99495(6) MHz. The transitions are so intense that rotational transitions of all mono-\begin{document}$ ^{13} $\end{document}C and \begin{document}$ ^{15} $\end{document}N isotopologues are measured in natural abundance. The semi-experimental equilibrium rotational constants of the 7 isotopologues were derived by taking account of the anharmonic vibrational corrections, which allowed a semi-experimental determination of the equilibrium structure of 2, 3, 6-trifluoropyridine.     

Method development and validation for the determination of biogenic amines in soy sauce using supercritical fluid chromatography coupled with single quadrupole mass spectrometry

Biogenic amines have been reported in many foods such as fish, meat, and soy sauce. The consumption of foods containing high concentrations of biogenic amines has been associated with health hazards. In this study, a green and efficient method using supercritical fluid chromatography coupled with single quadrupole mass spectrometry was developed for determination of biogenic amines in soy sauce. The chromatographic and mass spectrometry conditions were systematically optimized in terms of selectivity and peak shape. Nine biogenic amines were well separated within 25 min on a Cosmosil 5HP column using 5% (v/v) water and 0.2% (v/v) ammonia solution in methanol as mobile phase additives at a backpressure of 120 bar and temperature of 40°C. The established method was fully validated regarding the linearity, sensitivity, precision, and accuracy. The limits of detection and limits of quantification ranged from 0.03 to 10.50 μg/mL and 0.10 to 23.1 μg/mL, respectively. The relative standard deviations for intra‐ and interday precisions were all lower than 9.36% and the recoveries ranged from 75.82 to 99.63% and 80.10 to 99.89% for two levels of standards spiked in soy sauce, respectively. Finally, the established method was successfully applied to the quantitative analysis of biogenic amines in soy sauce.     

Calibration of DC Potential Drop Method Considering Fatigue Load

Experimental Mechanics - The direct current potential drop (DCPD) method is an important method for monitoring crack initiation and propagation in specimens. During fatigue crack growth monitoring,...     

梯级溃坝洪水洪峰增强机制

我国在多条河流上修建了大量梯级水库, 梯级坝溃决诱发洪水大大超过单坝溃决洪水洪峰, 因此亟需加深对梯级坝溃决洪水洪峰增强机制的认识. 本文建立了梯级坝溃决洪水演进过程的一维浅水动力学模型, 发展了一套能捕捉激波、干湿边界和保平衡结构的数值求解方法, 通过大量算例, 系统研究了梯级坝溃决洪水演进过程的质量转化和能量转化机制. 研究结果表明, 梯级溃决中, 上游溃决诱发的洪水大大增大下游水库的质量和动量, 形成一个带动量的水塔, 同时在尾部残留一个动量较大的射流, 不断补充下游坝体溃决后水塔的质量和动量, 持续维持洪峰高度. 根据该射流-水塔机制, 建立了梯级坝溃决洪水演进过程对应的射流-水塔单坝溃决洪水过程等效模型, 该等效模型基本反映了梯级坝溃决诱发洪水的洪峰过程, 并成功预测了多个坝间距为百公里量级的梯级坝溃决洪水洪峰高程和流量, 可望为流域防洪和梯级坝设计提供理论依据.      

有耗介质层上多导体传输线的电磁耦合时域分析方法

目前,针对空间电磁场作用有耗介质层上传输线的电磁耦合,仍缺乏有效的数值分析方法.因此,本文提出一种高效的时域混合算法,很好地解决了有耗介质层上传输线电磁耦合建模难的问题.首先,对经典传输线方程进行改进,推导了适用于有耗介质层上多导体传输线电磁耦合分析的修正传输线方程.然后,结合时域有限差分方法和相应插值技术,求解修正传输线方程,获得多导线及其端接负载上的电压和电流响应,并实现空间电磁场辐射与多导线瞬态响应的同步计算.最后,通过相应计算实例的数值模拟,与CST软件的仿真结果进行对比,验证了时域混合算法的正确性和高效性.     

Synthesis, characterization and luminescence property of N,N'-di(pyridine N-oxide-2-yl)pyridine-2,6-dicarboxamide and corresponding lanthanide (III) complexes

A new ligand, N,N'-di(pyridine N-oxide-2-yl)pyridine-2,6-dicarboxamide (LH2) and its several lanthanide (III) complexes (La, Eu, Gd, Tb, Y) were synthesized and characterized in detail based on elemental analysis, conductivity measurements, IR, 1H NMR, MS (FAB) and UV spectra and TG-DTA studies. The results indicated that the composition of these binary complexes is [Ln(LH2)(NO3)2.H2O]NO3.nH2O (n=0-1); while the ligand has a good planar structure with strong hydrogen bonds. The fluorescence spectra exhibits that the Tb (III) complex and the Eu (III) complex display characteristic metal-centered fluorescence in solid state while ligand fluorescence is completely quenched. However, the Tb (III) complex displays more effective luminescence than the Eu (III) complex, which is attributed to especial effectivity in transferring energy from the lowest triplet energy level of the ligands (T) onto the excited state (5D4) of Tb (III) than that (5D1) of Eu (III).     

Carnation‐like CuO Hierarchical Nanostructures Assembled by Porous Nanosheets for Nonenzymatic Glucose Sensing

Carnation‐like CuO hierarchical nanostructures assembled by ultrathin porous nanosheets were successfully fabricated via a facile solvothermal route followed with heat treatment. As‐prepared CuO nanostructures exhibited excellent catalytic activity toward glucose oxidation in the absence of any enzymes. Under the optimized conditions, the CuO‐based enzymeless glucose sensor showed high sensitivity of 3.15 mA mM^?1 cm^?2, low limit of detection (98 nM, S/N=3), good reproducibility, excellent selectivity and long‐time stability. The superb nonenzymatic glucose sensing performance of the CuO hierarchical nanostructures was attributed to the highly catalytically active sites at the edges and basal planes of the CuO nanosheets, facile transportation of analytes through the abundant mesopores and macropores, robust and stable hierarchical structure. Moreover, the CuO‐based enzymeless glucose sensor showed high accuracy and reliability in comparison with clinical glucometer for quantitative determination of glucose in human blood serum samples.     

Isolation and identification of nondestructive desulfurization bacterium

A nondestructive desulfurization microorganism has been isolated. The metabolism product analyses show that the strain can be a kind of biocatalyst to oxidize dibenzothiophene (DBT) into 2-hydroxydiphenyl (HBP), therefore the sulfur in DBT is removed selectively. The 16SrRNA information, cell wall analysis, physical, biochemical properties and morphological properties suggest that the isolated strain is Rhodococcus erythropolis. The strain can grow in the basal salts medium (BSM) that DBT concentration is no more than 10 mmol/L, and the optimal DBT concentration for growth is 1 mmol/L, however, the optimal DBT concentration for desulfurization is 0.5 mmol/L. The further research shows that the strain can also desulfur some other or-ganosulfur-containing compounds such as thianaphthene, phenyl sulfide and 4,6-dimethyldiben-zothiophene (4,6-DMDBT).     

层状复合氢氧化物对乙酰苯甲酸的负载与体外释放

共沉淀-微波晶化法合成层状复合氢氧化物(LDH)后, 用不同方式将乙酰苯甲酸(ASP)组装到LDH层间制成载药体LDH-ASP, 通过对合成及药物释放前后的液相分析与固相表征数据研究了LDH对ASP的负载及载药体LDH-ASP在磷酸盐介质的溶释现象. 结果表明: LDH层间通道是负载、贮存及控制药物释放的微观基础; 载体选择、药物配比、反应能量供给方式及搅拌强度是决定并影响LDH-ASP载药效率的基本因素, LDH-ASP结构参数可以反映药物负载情况、并与其释放性能明确相关; LDH对ASP的负载与释放均致晶胞参数改变、结晶度下降; 载药体与前体的晶态属性、热力学行为及表面特性相似, 而释放药物后固相的晶态性征减弱、无定形性增强、通道吸附活性降低, 有利于使命后载体在体内降解消除.