麦冬皂苷D调节SphK1/S1P/S1PR1信号通路对心肌缺血再灌注损伤大鼠心肌炎症的影响

目的探讨麦冬皂苷D调节鞘氨醇激酶1(SphK1)/1-磷酸鞘氨醇(S1P)/鞘氨醇1磷酸酯受体1(S1PR)通路对心肌缺血再灌注损伤(MIRI)大鼠心肌炎症的影响。方法将大鼠随机分为MIRI组、麦冬皂苷D组、SphK1激活剂(K6PC-5)组、麦冬皂苷D+K6PC-5组、假手术组,每组12只。除假手术组外,其它组大鼠均通过结扎冠状动脉左前降支法构建MIRI模型。建模成功后,立即给药处理,每日1次,持续2周。超声成像系统评估大鼠左心室射血分数(LVEF)、左心室分数缩短(LVFS)变化;HE染色检测心肌组织的病理;ELISA法检测心肌组织中肌酸激酶同工酶(CK-MB)、乳酸脱氢酶(LDH)、白细胞介素(IL)-1β、肿瘤坏死因子α(TNF-α)水平;TUNEL染色检测心肌组织的心肌细胞凋亡;免疫组化染色心肌组织中Bim、天冬氨酸特异性半胱氨酸蛋白酶-3(Caspase-3)阳性细胞数占比;Western Blot法检测心肌组织中S1P、SphK1、S1PR1蛋白水平。结果与假手术组比较,MIRI组大鼠心肌结构损伤、纤维排列紊乱、心肌细胞减少、细胞核固缩且有大量炎症细胞浸润;LVFS、LVEF降低(P<0.05);心肌组织中CK-MB、LDH、IL-1β、TNF-α水平,心肌细胞凋亡率,Bim、Caspase-3阳性细胞数占比及S1P、SphK1、S1PR1蛋白水平升高(P<0.05)。与MIRI组比较,麦冬皂苷D组大鼠心肌结构损伤、纤维排列紊乱、心肌细胞减少、细胞核固缩及有大量炎症细胞浸润现象有所缓解;LVFS、LVEF升高(P<0.05);心肌组织中CK-MB、LDH、IL-1β、TNF-α水平,心肌细胞凋亡率,Bim、Caspase-3阳性细胞数占比及S1P、SphK1、S1PR1蛋白水平降低(P<0.05)。K6PC-5逆转了麦冬皂苷D对MIRI大鼠心功能障碍、心肌炎症及心肌细胞凋亡的影响(P<0.05)。结论麦冬皂苷D抑制MIRI大鼠心肌炎症及心肌细胞凋亡的机制可能与抑制SphK1/S1P/S1PR1通路有关。

Herbicide resistance: Development of wheat production systems and current status of resistant weeds in wheat cropping systems

Herbicide resistance in crops has extended the scope of herbicide applications to control weeds. The introduction of herbicide resistant crops resulted in a major shift in the way that herbicides are used in many crops, but not necessarily increased the prevalence of herbicide use, especially in wheat. Wheat is one of the most widely grown crops in the world and currently only two major herbicide-resistant wheat groups have been commercialized to manage weeds in a cost-effective manner. However, sustainable wheat production is threatened by the expanding occurrence of herbicide-resistant weed populations with limited efforts to discover new herbicide molecules. Selective control of certain problematic weeds in wheat was impossible until development and introduction of the technologies, Clearfield and Co AXium Production Systems. However, the current limitations of reliance on specific herbicides and evolution of resistant weeds mandate precautions and considerations when using these systems to prevent the loss of existing herbicide resources and continue sustainable wheat production. The focus of this review is to provide an overview of natural pre-existing herbicide resistance and development of herbicide-resistant technologies in wheat. The mechanisms of resistance to herbicides in wheat as well as the weed populations in wheat cropping systems, and implications for weed management are discussed.

Polymorphisms of the oxidant enzymes glutathione S-transferase and glutathione reductase and their association with resistance of Plasmodium falciparum isolates to antimalarial drugs

Objective:To investigate the association between amplification of the two regulatory genes controlling glutathione(GSH) levels,glutathione reductase(PfGR) and glutathione S-transferase (PfGST) genes and sensitivity of Plasmodium falciparum(P.falciparum) isolates collected from different malaria endemic areas of Thailand to standard antimalarial drugs.Methods:A total of 70 P.falciparum isolates were collected from endemic areas of multi-drug resistance (Tak,Chantaburi and Ranong Provinces) during the year 2008-2009.The in vitro assessment of antimalarial activity of P.falciparum clones(K1- and Dd2 chloroquine resistant and 3D7- chloroquine sensitive) and isolates to chloroquine,quinine,mefloquine and arteusnate was performed based on SYBR Green modified assay.Results:68(97.14%),11(15.71%) and 28(40%) isolates respectively were classified as chloroquine-,quinine- and mefloquine-resistant isolates. With this limited number of P.falciparum isolates included in the analysis,no significant association between amplification of PfGST gene and sensitivity of the parasite to chloroquine, quinine,mefloquine and quinine was found.Based on PCR analysis,Dd2,Kl and 3D7 clones all contained only one copy of the PfGST gene.All isolates(70) also carried only one copy number of PfGST gene.There appears to be an association between amplification of PfGR gene and chloroquine resistance.The 3D7 and Dd2 clones were found to carry only one PfGR gene copy, whereas the K1 clone carried two gene copies.Conclusions:Chloroquine resistance is likely to be a consequence of multi-factors and enzymes in the GSH system may be partly involved. Larger number of parasite isolates are required to increase power of the hypothesis testing in order to confirm the involvement of both genes as well as other genes implicated in glutathione metabolism in conferring chloroquine resistance.

Expression of multidrug-resistance associated proteins in human retinoblastoma treated by primary enucleation

AIM： To reveal the expression of multidrug-resistance associated proteins： glutathione-S-transferase π（GSTπ）, P-glycoprotein（P-gp） and vault protein lung resistance protein（LRP） in retinoblastoma（RB） without any conservative treatment before primary enucleation and to correlate this expression with histopathological tumor features. METHODS： A total of 42 specimens of RB undergone primary enucleation were selected for the research. Sections from the formalin-fixed, paraffin-embedded specimens were stained with HE and immunohistochemistry to detect the expression of GSTπ, P-gp and LRP.RESULTS： GSTπ was expressed in 39/42（92.86%） RBs and in 9/9（100%） well-differentiated RBs. P-gp/GSTπ was found in 30（71.42%） of 42 RBs. Totally 9（21.43%） tumors were well differentiated and 33（78.57%） were poorly differentiated. Totally 15（35.71%） eyes had optic nerve（ON） tumor invasion, 36（85.71%） had choroidal tumor invasion, and 14（33.33%） had simultaneous choroidal and ON invasion. There was no statistically significant relationship between P-gp, GSTπ, LRP positivity and the degree of ocular layer tumor invasion and ON tumor invasion（P〉0.05）. CONCLUSION： RB intrinsically expresses GSTπ, P-gp and LRP. GSTπ expression is positive in 100% welldifferentiation ones, so in which way it is correlated with differentiation. But the other two proteins expressions are not related to tumor differentiation and to the degree of tumor invasion. GSTπ may be a new target of chemotherapy in RB.

Insulin Resistance in Alzheimer＇s Disease and the Role of p53 Protein

Recent evidence reveals significant metabolic changes in AD （Alzheimer＇s disease）, in which brain glucose utilization and energy production are impaired. The complex picture of metabolic disturbances in AD brains could be explained by increase of p53 protein stabilization and activation in neurons exposed to diverse metabolic stress conditions. Activated p53 helps cells to adapt to various types of metabolic stresses. Chronic stress and long lasting p53 increase lead to inhibition of glucose uptake, downregulation of glycolysis, enhancement of lipid catabolism and fatty acid β-oxidation, also promote function of tricarboxylic acid cycle and force an oxidative phosphorylation. These effects are opposite to those of insulin, thus p53 activation leads to insulin resistance of cells. However, prolonged stress conditions unveil deleterious effects of p53-evoked insulin resistance in neurons; enhancement of transcription of pro-oxidant factors, accumulation of toxic rnetabolites （e.g., cerarnide, products of advanced glycation） and ROS （reactive oxygen species）---modified cellular components, together with activation of proapoptotic genes, could finally move a suicide death program of autophagy/apoptosis in neurons. The important role of p53 in driving insulin resistance in AD brains validates attempts to inhibit p53 activity in neurons since it could promise an improvement of the disease therapy.

基于DSP多轴运动控制系统的研究实现

运动控制技术及系统是影响智能装备功能及性能的关键技术之一。本文介绍了研究实现高速高精度DSP多轴运动控制系统的策略及技术。该运动控制系统实现3个运动轴的位置控制、各种较为复杂的控制算法,以及大量传感器信息的快速处理,并具有开放性功能、高速高性能和模块化等特点,适用于各种先进智能装备的系统控制。

Biochemical Characterization of Detoxifying Enzymes in Dimethoate-Resistant Strains of Melon Aphid, Aphis gossypii(Hemiptera: Aphididae)

The melon aphid, Aphis gossypii Glover (Hemiptera: Aphididae), is a highly polyphagous sap sucking pest on wide varieties of crops including cotton and vegetables. It is a notorious vector of many plant viruses that are persistently and non-persistently transmitted. In nature, aphids are regulated by their natural enemies. However, chemical control remains a major management tool even though resistance to insecticides has been documented worldwide. A better understanding of mechanisms by which insecticide resistance occurs and its early detection is desirable to develop effective management strategies. The present investigation was conducted to study the development of resistance to an organophosphate (OP) compound-dimethoate, identify biochemical mechanism(s) involved in resistance and study cross-resistance to imidacloprid in laboratory selected A. gossypii strains in comparison to susceptible strains. Bioassay studies revealed that the LC50 values increased dramatically with dimethoate selection in resistant strains and the resistance ratio (RR) was 270-, 243- and 210-fold greater than that of the susceptible strains by 30th generation. Further, biochemical assays revealed enhanced activities of carboxylesterases (CarE), glutathione S-transferases (GSTs) and cytochrome P450-mediated p-Nitroanisole O-demethylase (PNOD) in resistant strains supporting their role in dimethoate detoxification. This study thus revealed that enhanced activity of detoxifying enzymes viz., CarE, GSTs and PNODs is one of the mechanisms underlying dimethoate resistance in A. gossypii collected from South India. Interestingly, the possibility of negatively correlated cross-resistance to imidacloprid was identified in three OP- resistant strains exhibiting 2.97-, 2.56- and 3.76-fold sensitivity to imidacloprid (a novel neonicotinoid). This indicated that the latter was less affected by the resistance mechanism(s) present.

Biochemical Characterization of Detoxifying Enzymes in Dimethoate-Resistant Strains of Melon Aphid, <i>Aphis gossypii</i>(Hemiptera: Aphididae)

The melon aphid, Aphis gossypii Glover (Hemiptera: Aphididae), is a highly polyphagous sap sucking pest on wide varieties of crops including cotton and vegetables. It is a notorious vector of many plant viruses that are persistently and non-persistently transmitted. In nature, aphids are regulated by their natural enemies. However, chemical control remains a major management tool even though resistance to insecticides has been documented worldwide. A better understanding of mechanisms by which insecticide resistance occurs and its early detection is desirable to develop effective management strategies. The present investigation was conducted to study the development of resistance to an organophosphate (OP) compound-dimethoate, identify biochemical mechanism(s) involved in resistance and study cross-resistance to imidacloprid in laboratory selected A. gossypii strains in comparison to susceptible strains. Bioassay studies revealed that the LC50 values increased dramatically with dimethoate selection in resistant strains and the resistance ratio (RR) was 270-, 243- and 210-fold greater than that of the susceptible strains by 30th generation. Further, biochemical assays revealed enhanced activities of carboxylesterases (CarE), glutathione S-transferases (GSTs) and cytochrome P450-mediated p-Nitroanisole O-demethylase (PNOD) in resistant strains supporting their role in dimethoate detoxification. This study thus revealed that enhanced activity of detoxifying enzymes viz., CarE, GSTs and PNODs is one of the mechanisms underlying dimethoate resistance in A. gossypii collected from South India. Interestingly, the possibility of negatively correlated cross-resistance to imidacloprid was identified in three OP- resistant strains exhibiting 2.97-, 2.56- and 3.76-fold sensitivity to imidacloprid (a novel neonicotinoid). This indicated that the latter was less affected by the resistance mechanism(s) present.

p38 MAPK/NF-κB/cyclin D1信号传导通路在乳房外Paget's病中的意义

目的探讨磷酸化p38细胞丝裂原活化蛋白激酶α(phospho-p38 mitogen-activated protein kinase,p-p38 MAPKα)、磷酸化核因子-κB(phosphor-nuclear factor kappaB,p-NF-κB)及细胞周期蛋白D1(cyclin D1)在乳房外Paget’s病(extramammary Paget’s disease,EMPD)表达的意义及评价它们之间的相关性。方法采用免疫组化ABC法检测了p-p38MAPK,p-NF-κB及Cyclin D1蛋白在来源于30例患者的35张EMPD石蜡包埋切片中的表达(5张来源于有转移的EMPD淋巴结标本)。结果①在35张标本中EMPD石蜡包埋切片中有30例p-p38 MAPK表达阳性,28例p-NF-κB表达阳性,27例cyclin D1表达阳性,并且在其中5张来源于有转移的EMPD淋巴结标本中,5例均p-p38 MAPK和p-NF-κB表达阳性,4例cyclin D1表达阳性;②在EMPD中,p-p38 MAPK,p-NF-κB和cyclin D1阳性表达两两间均有明显的相关性。结论p-p38 MAPK,p-NF-κB和cyclin D1在EMPD中有过度表达,p38 MAPK/NF-κB/cyclin D1信号传导通路可能在EMPD肿瘤形成机制中起重要作用。

肺癌中MDR基因产物LRP、P-gp、GST-π、TopoⅡ的表达及临床意义

目的:探讨多药耐药(MDR)基因产物LRP、P-gp、GST-π、TopoⅡ在肺癌中的表达及临床相关性。方法:应用单克隆抗体、免疫组化技术S-P法,对70例肺癌标本进行上述4种MDR指标检测。结果:在肺癌组织中LRP、P-gp、GST-π、TopoⅡ表达的阳性率分别为75.7%、70.0%、82.9%、84.3%,其与性别、年龄、部位、临床分期无关(P>0.05);在未分化、小细胞型肺癌中LRP、P-gp、GST-π表达的阳性率明显降低(P<0.05),而TopoⅡ表达的阳性率则升高(P<0.05,低分化型肺癌除外)。结论:LRP、P-gp、GST-π、TopoⅡ在未化疗过的肺癌组织中均有不同程度的高表达,且与肺癌的某些生物学行为有关,联合检测有助于化疗药物的选择及预后的判断。

基于DSP控制数字化弧焊电源的设计与实现

DSP控制技术是目前数字化弧焊电源数字控制系统中的核心技术。利用DSP具有的结构与性能特点,采用合理的控制策略和算法,进行数字化弧焊电源的软件设计与编程,来实现熔化极气体保护焊中典型的电源特性控制、送丝系统控制、焊接参数的调节控制等功能。DSP控制系统数据处理能力强、运行速度快,提高了弧焊电源数字控制的精度和实时性。

1,25-二羟维生素D3对子宫内膜癌HEC-1-A细胞增殖与S期激酶相关蛋白及抑癌基因p27表达的影响

目的 观察1,25-二羟维生素D3对人子宫内膜癌HEC-1-A细胞增殖及S期激酶相关蛋白（Skp2）基因、抑癌基因p27表达的影响,探讨其抗癌机制.方法 应用免疫组织化学方法检测人子宫内膜癌HEC-1-A细胞表达维生素D受体（VDR） 选用人子宫内膜癌HEC-1-A细胞进行体外培养,用CCK-8法测定不同浓度1,25-二羟维生素D3作用细胞后不同时间后细胞生长抑制率,流式细胞仪进行细胞周期分析,采用荧光实时定量聚合酶链反应（PCR）及蛋白质印迹法检测Skp2/p27基因表达的变化.结果 人子宫内膜癌HEC-1-A细胞表达VDR,且定位于细胞核内 1×（10-8～10-6）mol/L浓度的1,25-二羟维生素D3作用于HEC-1-A细胞1～5 d范围内各不同浓度处理组细胞生长增殖均受到明显抑制,并且随着作用浓度增加,细胞增殖能力逐渐下降 1,25-二羟维生素D3能增加G0/G1期细胞比例,降低S、G2/M期细胞比例,从而降低细胞增殖指数（P＜0.01） 在mRNA、蛋白质水平上,能降低Skp2表达,而p27mRNA减少,p27蛋白表达明显增加.结论 1,25-二羟维生素D3对人子宫内膜癌HEC-1-A细胞有抑制作用,可能是通过转录水平下调Skp2基因表达,同时由于Skp2的减少增加p27蛋白稳定性,减少其降解,从而产生抑癌作用.

基于P·S·T分析的柳州旅游4C·D营销策略研究

基于柳州旅游的现状 ,研究了其市场定位 (Positioning)、市场细分 (Segm enting)、目标市场的确定 (Target-ing)问题 ,在此分析的基础上确定了不同于传统 4P'S理论的柳州旅游的 4C· D区域营销策略 ,即注重旅游者的需求和欲望 (Consumers'wants and needs)、成本 (Cost)、方便 (Convenience)旅游者的购买、与旅游者有效沟通 (Com munication)、以及实施数据库营销 (Database Marketing)

基于dSPACE的永磁同步电机控制系统研究

传统的永磁同步电机(PMSM)控制系统开发方法,为研究一种合适的控制算法和设计一套可行的硬件控制系统,须对软硬件系统多次开发设计,这种开发方法既耗时又费力、成本也偏高。为此提出了一种基于dSPACE半实物仿真系统的PMSM控制系统快速开发方法。从系统控制原理、控制策略、系统硬件以及dSPACE软件设计等方面给出了较详细的论述,并研制出试验样机。仿真和实验结果表明,系统具有良好的动态和静态性能,同时也验证了dSPACE实时仿真平台在电机控制方面具有快速性和便利性。

基于DSP+ARM模式的自动刹车系统的研制

为进一步提高汽车的安全性能,研制了一种基于DSP(数字信号处理)技术和ARM(嵌入式技术)的自动刹车系统。该系统采用ARM和DSP两个处理器协同工作的模式,其中DSP芯片负责处理行驶车辆及其附近的交通信息,ARM处理器负责建立本车的运动模型,并据此来完成对车辆的实时监控和紧急情况下的自动刹车功能。本文着重介绍了系统的目标、总体方案、硬件组成和软件系统的运行原理。

动态p-坚持CSMA/CD协议的统计改进

p-坚持CSMA/CD协议在计算机终端数据发送上有着广泛的应用。针对计算机终端中p-坚持CSMA/CD协议的信道利用率的问题进行研究,为了能更好的利用信道发送数据,提高信道利用率,采用了统计方法中的贝叶斯决策统计理论,通过全概率公式拆分,对p-坚持CSMA/CD协议中的参数p进行动态自适应拟合的一种CSMA/CD协议方法,并进行改进使之有更好的信道利用率。用MATLAB2010a进行模拟仿真实验,得出改进后的自适应p-坚持CSMA/CD协议比静态的p-坚持CSMA/CD协议对信道有高20%左右的利用率。

(d-p)π共轭作用对簇合物Mo_2S_4(dtp)_2和Mo_3S_4(dtp)_4·Py电子光谱的影响

比较了含有配位不饱和过渡金属原子簇合物Mo_2S_4(dtp)_2,(Ⅰ)和Mo_3S_4(dtp)_4·Py,(Ⅱ)的紫外—可见电子吸收光谱实验数据和半经验的量子化学方法INDO计算得到的电子跃迁能,讨论了(d-p)π型共轭作用对其电子吸收光谱位移的影响。结果表明,过渡金属簇合物中电子吸收光谱位移,与有机共轭体系有着类似的变化规律,即随着共轭π键数目增加,π-π电子跃迁的吸收光谱红移。

1,25(OH)_2D_3对人肾小球系膜细胞增殖及mTOR/p70s6K表达的影响

目的：探讨1,25-二羟基维生素D3[1,25（OH）2D3]对人肾小球系膜细胞增殖的影响及其在肾小球系膜细胞调控中对mTOR/p70s6K信号通路的作用。方法体外培养人肾小球系膜细胞，取传代培养至3～7代细胞分为4组：正常对照组（加含5%胎牛血清DMEM培养基），VD组[加1,25（OH）2D310-8 mol/L]，R组（加雷帕霉素5 mg/L），R＋VD组[加雷帕霉素5 mg/L及1,25（OH）2D310-8 mol/L]，干预48 h。采用细胞增殖与活性检测试剂盒CCK-8检测细胞增殖情况，流式细胞术检测细胞周期时相分布，免疫荧光法检测细胞中mTOR、p70s6K的表达情况。结果正常对照组、VD组、R组、R＋VD组：（1）吸光度值（A450）依次降低，组间多重比较差异均有统计学意义（均P＜0.05）；抑制率（IR）依次升高。（2）G1期细胞比例依次增加，S期、G2/M期依次减少，增殖指数（PI）依次降低，除R组与VD组比较差异无统计学意义外，其余组间多重比较差异均有统计学意义。（3）系膜细胞中mTOR、p70s6K蛋白表达强度均依次降低，除R组与VD组比较差异无统计学意义外，其余组间多重比较差异均有统计学意义。结论1,25（OH）2D3可显著抑制人系膜细胞增殖，且其可能通过抑制mTOR/p70s6K信号通路调控肾小球系膜细胞增殖。

短段Barrett’s食管的不同组织类型、内镜形态、异型程度与Cyclin D1、P53表达的相关性研究

目的研究细胞周期蛋白D1(Cyclin D1)、P53蛋白在短段Barrett’s食管(short segment Barrett’s esophagus,SSBE)不同组织类型、不同内镜形态、不同异型程度分组中的表达,预测不同类型SSBE上皮癌变的风险性,准确筛选高危人群,为指导制定内镜随访计划提供依据。方法选取经电子胃镜、病理检查确诊为SSBE的患者51例,另取32例正常食管黏膜组织作为对照。再根据SSBE不同内镜下形态分为全周型16例、舌型13例、岛型22例,根据不同病理组织类型分为胃底型20例、贲门型21例、特殊肠化型10例,根据BE组织异型增生的程度分为无异型增生组37例、轻度异型增生组14例、重度异型增生组0例。采用免疫组化法检测不同亚组细胞Cyclin D1和P53蛋白的表达,并进行统计学分析。结果 Cyclin D1、P53在SSBE组及正常食管黏膜组中的表达均较低,差异无统计学意义(P>0.05)。Cyclin D1、P53在SSBE不同内镜下形态分型、不同组织学分型各亚组中的表达差异均无统计学意义(P>0.05)。Cyclin D1、P53在合并异型增生组中均表达升高,Cyclin D1在无异型增生、轻度异型增生组中的表达阳性率分别为21.6%、64.3%,组间差异有统计学意义(P=0.007);P53在无异型增生、轻度异型增生组中的表达阳性率分别为27.0%、71.4%,组间差异有统计学意义(P=0.006)。结论 SSBE总体癌变风险低。SSBE的癌变风险与内镜形态分型及组织学分型的不同无直接相关性。对合并异型增生者,Cyclin D1和P53的表达明显升高,提示SSBE伴异型增生者癌变风险明显增加。

D_1S_(80),P_(33.6)位点扩增片段长度多态性在法医学中的应用

用ＰＣＲ技术、小型垂直板聚丙烯酰胺凝胶电泳及银染显色法，分析血痕、精斑、混合斑中的Ｄ１Ｓ８０，Ｐ３３．６ＶＮＴＲ位点的扩增片段长度多态性（ＡｍｐＦＬＰ），获得了满意的结果将该方法运用于案件的鉴定。