Novel matrine derivative MD-1 attenuates hepatic fibrosis by inhibiting EGFR activation of hepatic stellate cells

Matrine (MT), the effective component of Sophora flavescens Ait, has been shown to have anti-inflammation, immune-suppressive, anti-tumor, and anti-hepatic fibrosis activities. However, the pharmacological effects of MT still need to be strengthened due to its relatively low efficacy and short half-life. In the present study, we report a more effective thio derivative of MT, MD-1, and its inhibitory effects on the activation of hepatic stellate cells (HSCs) in both cell culture and animal models. Cytological experiments showed that MD-1 can inhibit the proliferation of HSC-T6 cells with a half-maximal inhibitory concentration (IC50) of 62 μmol/L. In addition, MD-1 more strongly inhibits the migration of HSC-T6 cells compared to MT and can more effectively induce G0/G1 arrest and apoptosis. Investigating the biological mechanisms underlying anti-hepatic fibrosis in the presence of MD-1, we found that MD-1 can bind the epidermal growth factor receptor (EGFR) on the surface of HSC-T6 cells, which can further inhibit the phosphorylation of EGFR and its downstream protein kinase B (Akt), resulting in decreased expression of cyclin D1 and eventual inhibition of the activation of HSC-T6 cells. Furthermore, in rats with dimethylnitrosamine (DMN)-induced hepatic fibrosis, MD-1 slowed the development and progression of hepatic fibrosis, protecting hepatic parenchymal cells and improving hepatic functions. Therefore, MD-1 is a potential drug for anti-hepatic fibrosis.     

大豆倒伏性相关QTL的整合及Overview分析

倒伏性是影响大豆产量的重要因素,发掘与大豆倒伏相关的基因对于培育抗倒伏优良高产大豆品种具有重要意义。目前利用不同群体所构建的遗传图谱已经定位了大量与大豆倒伏性相关的QTLs。本研究在对已报道的QTLs进行物理整合的基础上,选择元分析方法将这些倒伏性相关的QTLs进一步整合,鉴定出位于C2(6号染色体)、F(13号染色体)、L(19号染色体)这3个连锁群上重复次数较多的QTL区间6个。选用基于统计学原理的Overview方法进行优化,获得了这些QTL在各个连锁群上的有效遗传位置,这些QTL的置信区间长度最小可缩至0.2 cM。通过在这些区间内进一步筛选,获得一个稳定性较好的标记Satt277。本研究可为大豆抗倒伏基因发掘及分子标记辅助选择育种提供理论依据。     

Narrowband Light Total Antireflection and Absorption in Metal Film–Array Structures by Plasmonic Near-Field Coupling

We study the cooperative effects between plasmon gap modes and optical cavity modes of a novel triple-layer structure consisting of double continuous gold films separated by a gold nanosphere array. Narrowband near-perfect antireflection of optical field is achieved for the first time due to the strong near-field light–matter interaction within the deep sub-wavelength gaps between adjacent nanospheres combined with the spatial field confinement effects of the optical cavity built by the double gold films. The coexistence cooperation of near-field dipole plasmon resonances and spatial optical field confinement presents more efficient light modification than that of the individual subsystem and may open a new approach to manage light flow. By varying the period of nanosphere array, the diameter of nanospheres, and the distance between the array and the film, optical behaviors of the proposed structure can be tuned in a wide range. High environmental sensitivity and large figure of merit factor are obtained using this structure as the detecting substrate. Furthermore, ultra-compact structure and high conduction suggest the proposed structure being a good candidate for potential applications in highly integrated optoelectronic devices, such as plasmonic filters and sensors.     

Localization of a beta-crystallin gene, Hu beta A3/A1 (gene symbol: CRYB1), to the long arm of human chromosome 17

We have assigned a human beta-crystallin gene, Hu beta A3/A1 (gene symbol: CRYB1), to chromosome 17 using a panel of 19 human-hamster somatic cell hybrids and blot-hybridization analysis of cell hybrid DNA. Positive probe-hybridization signal was detected in a hybrid that had lost the short arm of human chromosome 17 but retained the long arm, translocated to a hamster chromosome. In addition, in situ hybridization analysis of metaphase chromosome spreads of this cell line suggested that the most probable location for CRYB1 is on the long arm of chromosome 17, in the region q21.     

脱落酸诱导气孔关闭的信号转导研究

气孔保卫细胞是单个细胞水平研究ABA信号转导机制的一个模式系统。脱落酸(ABA)通过对保卫细胞生理生化状态、胞质Ca^2 浓度及其离子通道调节诱导气孔关闭过程。这个过程涉及的因素有：ROS、IP3、cADPR、蛋白质的可逆磷酸化等。     

蛋白酪氨酸磷酸酶SHP-2在乳腺癌细胞移动及粘附中的作用

探讨蛋白酪氨酸磷酸酶SHP 2在乳腺癌细胞MCF 7的移动及粘附中的作用 .利用基因重组技术分别将野生型SHP 2与突变型SHP 2与绿色荧光蛋白GFP的基因片段构成重组质粒 (SHP 2 GFP、SHP 2C >S GFP) .脂质体转染法分别转入MCF 7中 ,表达成功后筛选并建立SHP 2 GFP和SHP 2C >S GFP细胞株 .荧光显微镜观察细胞移动情况 ,免疫印迹法检测粘附分子E 钙粘蛋白和金属蛋白酶MMP 1及MMP 9的表达 .实验后建立SHP 2 GFP及SHP 2C >S GFP细胞株 ,同时观察到SHP 2C >S GFP细胞的形态发生明显改变 :从梭形状态变成圆形状态 .荧光显微镜发现 ,MCF 7细胞和SHP 2 GFP、SHP 2C >S GFP转染的细胞在 3h、6h、9h的移动情况分别是MCF 7为 10 %、2 3%、5 4% ,SHP 2 GFP为 15 %、4 9%、98% ,SHP 2C >S GFP为 4 %、11%、30 % .免疫印迹结果表明 ,SHP 2C >S GFP细胞的E 钙粘蛋白表达比SHP 2 GFP细胞明显升高 (P <0 0 5 ) .MMP 1及MMP 9的表达量在SHP 2 GFP细胞中有所增强 (P <0 0 5 ) .实验表明 ,SHP 2可能通过调节粘附分子和基质金属磷酸酶而在细胞移动、粘附中发挥重要作用     

Voltage-dependent gating of the cystic fibrosis transmembrane conductance regulator Cl- channel

When excised inside-out membrane patches are bathed in symmetrical Cl--rich solutions, the current-voltage (I-V) relationship of macroscopic cystic fibrosis transmembrane conductance regulator (CFTR) Cl- currents inwardly rectifies at large positive voltages. To investigate the mechanism of inward rectification, we studied CFTR Cl- channels in excised inside-out membrane patches from cells expressing wild-type human and murine CFTR using voltage-ramp and -step protocols. Using a voltage-ramp protocol, the magnitude of human CFTR Cl- current at +100 mV was 74 +/- 2% (n = 10) of that at -100 mV. This rectification of macroscopic CFTR Cl- current was reproduced in full by ensemble currents generated by averaging single-channel currents elicited by an identical voltage-ramp protocol. However, using a voltage-step protocol the single-channel current amplitude (i) of human CFTR at +100 mV was 88 +/- 2% (n = 10) of that at -100 mV. Based on these data, we hypothesized that voltage might alter the gating behavior of human CFTR. Using linear three-state kinetic schemes, we demonstrated that voltage has marked effects on channel gating. Membrane depolarization decreased both the duration of bursts and the interburst interval, but increased the duration of gaps within bursts. However, because the voltage dependencies of the different rate constants were in opposite directions, voltage was without large effect on the open probability (Po) of human CFTR. In contrast, the Po of murine CFTR was decreased markedly at positive voltages, suggesting that the rectification of murine CFTR is stronger than that of human CFTR. We conclude that inward rectification of CFTR is caused by a reduction in i and changes in gating kinetics. We suggest that inward rectification is an intrinsic property of the CFTR Cl- channel and not the result of pore block.     

Studies on Insecticidal Activities and Action Mechanism of Novel Benzoylphenylurea Candidate NK-17

Insecticidal activity of NK-17 was evaluated both in laboratory and in field. It was found that the toxicity of NK-17 against S. exigua was 1.93 times and 2.69 times those of hexaflumuron and chlorfluazuron respectively, and the toxicity of NK-17 against P. xylostella was 1.36 times and 1.90 times those of hexaflumuron and chlorfluazuron respectively, and the toxicity of NK-17 against M. separate was 18.24 times those of hexaflumuron in laboratory, and 5% NK-17 EC at 60 g a.i ha⁻¹ can control S. exigua and P. xylostella with the best control efficiency of about 89% and over 88% respectively in Changsha and Tianjin in field. The insecticidal mechanism of NK-17 was explored for the first time by utilizing the fluorescence polarization method. NK-17 could bind to sulfonylurea receptor (SUR) of B. germanica with stronger affinity comparing to diflubenzuron and glibenclamide, which suggested that NK-17 may also act on the site of SUR to inhibit the chitin synthesis in insect body and the result can well explain that NK-17 exhibited stronger toxicity against B. germanica than diflubenzuron and glibenclamide in vivo.