The Role of NQO1 Polymorphisms in the Susceptibility and Chemotherapy Response of Chinese NSCLC Patients

To investigate whether the NAD(P)H:quinone oxidoreductase 1 (NQO1) gene polymorphisms determine the Platinum-based chemotherapy in advanced non-small cell lung cancer (NSCLC) in a Chinese cohort. A total of 391 patients with inoperable advanced stage of NSCLC, namely, stage III (A + B) and IV NSCLC, and 663 age-and sex-matched healthy were enrolled. The effects of chemotherapy were evaluated. NQO1 C609T polymorphism was determined. The NSCLC patients had a significantly higher prevalence of TT than control subjects (33.76 vs. 21.67 %, P < 0.001). For allele comparison, NSCLC subjects had lower T allele frequency than controls as well (55.63 vs. 44.42 %, P < 0.001). multivariate regression analyses showed the TT carriage had a significantly increased risk for development of NSCLC after adjustments with age, sex, smoke, and cancer family history (OR 1.681, 95 % CI 1.242–2.274, P = 0.001). The TT genotype distribution was significantly higher in non-responders than in responders (31.85 vs. 21.96 %, P = 0.003). Logistic regression analysis showed TT genotype carriers had less chance to gain chemotherapy response compared to CC genotype carriers (OR 0.399, P = 0.003) after adjustment with sex, age, tumor histology, disease stage, and chemotherapy regimens. The NQO1 C609T polymorphism is an important molecular marker for advanced NSCLC, since it is associated with the NSCLC risk as well as the response status of platinum-based chemotherapy.     

A Novel Strategy To Develop a Robust Infectious Hepatitis C Virus Cell Culture System Directly from a Clinical Isolate

Hepatitis C virus (HCV) infection is a leading cause of chronic liver diseases. Progress in the HCV field was greatly enhanced by constructing infectious cDNA clone of JFH-1. Since then, JFH-1-based intra- and intergenotypic recombinants have been developed, and this permitted the study of vaccines and antiviral inhibitors for all genotypes. Recently, highly efficient HCV culture systems have been established by using consensus sequence-based clones. We developed a novel strategy to construct infectious HCV cDNA clone by combining functional screening of sequences directly from a genotype 2a clinical isolate (PR63) and cell culture adaptation. Using JFH-1 cDNA as the starting backbone, we sequentially replaced the JFH-1 fragments with a sequence from the pools of PR63 sequences. Through engineering adaptive mutations that improve HCV infectivity, we finally established a full-length cell culture-derived infectious clone of PR63, named PR63cc, that could efficiently produce virus particles in Huh7-derived cells, with peak titers of 1.6 × 10⁵ focus-forming units/ml. The PR63cc could be neutralized by an anti-E2 antibody and inhibited by antiviral agents but appeared more resistant to an NS5A inhibitor than JFH-1. In summary, we developed a new approach to construct an infectious HCV cDNA clone that can produce viruses efficiently in cell culture. This approach could be applied to other viral isolates, with potential implications for individualized treatments of HCV patients.     

CHD1L prevents lipopolysaccharide-induced hepatocellular carcinomar cell death by activating hnRNP A2/B1-nmMYLK axis

Chromodomain helicase/ATPase DNA-binding protein 1-like gene (CHD1L) has been characterized to be a driver gene in hepatocellular carcinoma (HCC). However, the intrinsic connections between CHD1L and intestinal dysbacteriosis-related inflammation reaction in HCC progression remain incompletely understood. In this study, a specific correlation between CHD1L and nonmuscle isoform of myosin light chain kinase (nmMLCK/nmMYLK), a newly identified molecule associated NF-κB signaling transduction, was disclosed in HCC. CHD1L promotes nmMYLK expression and prevents lipopolysaccharide (LPS) induced tumor cell death. In vitro experiment demonstrated that overexpressed nmMYLK is essential for CHD1L to maintain HCC cell alive, while knocking down nmMYLK significantly attenuate the oncogenic roles of CHD1L. Mechanism analysis revealed that nmMYLK can prevent Caspase-8 from combining with MyD88, an important linker of TLRs signaling pathway, while, knocking down nmMYLK facilitate the MyD88 combines with Caspase-8 and lead to the proteolytic cascade of Caspase as well as the consequent cell apoptosis. Mechanism analysis showed that CHD1L promotes the nmMYLK expression potentially through upregulating the heterogeneous nuclear ribonucleoproteins A2/B1 (hnRNP A2/B1) expression, which can bind to myosin light chain kinase (MYLK) pre-mRNA and lead to the regnant translation of nmMYLK. In summary, this work characterizes a previously unknown role of CHD1L in preventing LPS-induced tumor cell death through activating hnRNP A2/B1-nmMYLK axis. Further inhibition of CHD1L and its downstream signaling could be a novel promising strategy in HCC treatment.Subject terms: Cancer microenvironment, Apoptosis, Liver cancer     

16S～23S rDNA间隔区序列在分枝杆菌分类鉴定中的应用研究

采用聚合酶链反应（ＰＣＲ）技术对分枝杆菌１６Ｓ￣２３Ｓ ｒＤＮＡ间隔区序列进行扩增,其产物经聚丙烯酰胺凝胶电泳（ＰＡＧＥ）,并通过计算机聚类分析,在基因水平上评价其对分枝杆菌分类与鉴定的意义。退火温度４５℃时,ＰＣＲ扩增的敏感性为５００ｆｇ／μＬ,而５０℃时的敏感性为５ｐｇ／μＬ。已通过对２２种分枝杆菌和９种非分枝杆菌的特异性实验,结果表明：扩增条带多集中在３００￣６００ｂｐ之间,多数受试快速生长     

城市道路绿化带"微峡谷效应"及其对非机动车道污染物浓度的影响

研究不同绿化带结构对非机动车道污染物浓度的影响,将为城市道路绿化带格局提供依据。利用遮荫网模拟10、20、30 m隔离的道路绿化带,并模拟了3种不同结构的绿化带,分别对各类道路微气候条件(风)及SO₂、NO_x、NH₃、总悬浮颗粒物(TSP)和可吸入颗粒物(PM10)等5种主要污染物浓度进行了观测。结果表明:风速小于2 m/s时,10 m和20 m间隔的道路绿化带会产生"微峡谷效应",使绿化带间隔内风速增加。10 m间隔的绿化带较其它两种绿化带对各种污染物的净化百分率更明显,且污染物净化百分率与风速大多正相关显著。12.5 m的模拟绿化带与10 m的间隔交替的绿化带可以更有效地降低非机动车道的污染物浓度,污染物净化百分率与风速也大多正相关显著。不同结构道路绿化带会影响道路微气候条件,从而影响非机动车道污染物浓度。城市道路绿带存在合理的绿带结构,可以通过设计更合理的城市道路绿带模式有效改善城市非机动车道空气质量。     

祁连山北坡退化林地植被群落的自然恢复过程及土壤特征变化

采用长期定位观测的方法,研究了祁连山北坡退化林地人工抚育下2001-2008年间植被群落的自然恢复过程和土壤特征变化。结果表明:人为干扰消除后,退化林地群落环境逐渐优化,群落的科、属、种均明显增加,物种成员更替频繁;灌木和乔木物种出现后,群落垂直高度增大,群落结构出现成层现象;群落总体多样性指数呈不断增大的趋势,在空间结构上,Patrick丰富度指数、Shannon-Wiener多样性指数和Simpson优势度指数表现出:草本层>灌木层>乔木层的规律,而Pielou均匀度指数变化相反;土壤含水量、土壤有机碳和全氮含量随植被恢复均不断增加。在实施封育禁牧措施后,退化林地实现了由草本群落-灌木群落-乔木群落方向的快速演替,当恢复到早期的先锋乔灌混交阶段时,群落的物种组成、结构和多样性趋于复杂化,土壤性状也得到一定改善,显示出相对较好的适应性和恢复效果。     

基于景观生态学的城市人居环境代谢研究范式与研究框架建构

人居环境建设已经成为中国城市发展和当代生态学研究的新兴命题,基于物质代谢研究成果,系统剖析城市人居环境问题,提升城市化过程的生态文明水准成为推动新型城市化发展的重要路径选择。通过对人居环境视角和社会代谢视角的城市研究进行简要回顾,认为两种视角的有机整合可以弥补各自的理论和方法论缺陷,进而凝练出新的城市生态学研究思路。利用景观生态学理论和概念体系,建构了多层次、多维度的城市人居环境代谢研究范式和基本研究框架。这一范式可以从多尺度和多维度反映城市人居环境代谢的过程特征,厘清城市人为活动和各种资源环境问题的关联关系,整合多学科的知识和技术手段,解析城市人居环境的时空动态演化过程及其驱动机制,为城市人居环境研究学科的发展创造有利条件。通过建构基于景观生态学的城市人居环境物质能量代谢研究框架,还可以有效推进城市人居环境物质能量代谢中的格局-过程-尺度耦合问题,数据采集、储存与分析问题和效应调控与过程管理问题的研究,对于完善城市代谢研究方法,促进城市人居环境建设具有重要的参考和借鉴意义。     

昼间气象条件对城市道路绿化带空气净化效果的影响——以太原市为例

道路绿化带可以净化空气,改善道路环境,道路中的小气候条件会改变道路污染物扩散方式和速度,进而会影响到绿化带对污染物净化效果。气象条件对道路绿地对大气污染物净化效果影响的研究将有助于了解道路绿地的净化途径,为改善城市道路环境提供依据。对太原市18个道路绿地气象因子和5种主要污染物浓度进行了观测。结果表明:夏季,太原市城市道路内各气象要素之间存在一定的相关性,气温和地温正相关显著,空气相对湿度与地温及气温呈显著和极显著负相关。大部分情况下,有绿地非机动车道污染物平均浓度低于无绿地非机动车道对照点平均浓度,即道路绿地起到了对道路污染物的净化作用。道路绿地对污染物的净化百分率与气象因子存在显著的回归关系,并可以建立达到统计显著水平的回归方程,但不同污染物受不同的主导气象因子影响。气象条件会影响道路绿地对道路污染物的净化效果,今后的城市建设和道路绿地规划中应更多地考虑气象条件对绿地净化效果的影响。     

黄土丘陵区退耕地土壤可溶性氮组分季节变化与水热关系

为探究黄土丘陵区退耕地植被恢复土壤有效氮素养分累积的季节动态变化特征及水热驱动效应,以邻近坡耕地为对照,分析了植被恢复15 a的刺槐、柠条、荒草地土壤可溶性氮组分密度、分布比例在4—10月份内的动态变化状况及其与土壤温度和含水量间的关系。结果表明,整个采样期间,0—30 cm土层土壤硝态氮、可溶性有机氮和可溶性全氮动态变化显著,且各可溶性氮组分中仅硝态氮随土层变化差异显著。其中土壤硝态氮变化幅度整体为0.13—1.71 g/m~2,占可溶性全氮的5.1%—52.1%,其最大值出现在4月份,最小值出现在10月份;可溶性有机氮整体变化幅度为0.29—2.92 g/m~2,占可溶性全氮的30.9%—85.3%,在4月份和8月份分别达最小值和最大值;铵态氮动态变化不显著,4—10月份整体变化幅度为0.17—0.74 g/m~2,占6.4%—21.4%,其最小值出现在10月份,最大值出现在4月份;可溶性全氮整体变化幅度为1.25—3.52 g/m~2。可溶性氮组分中,各组分所占比例为可溶性有机氮硝态氮铵态氮,并且可溶性有机氮与硝态氮所占比例动态变化趋势相反。刺槐、柠条林和荒草地0—30 cm土壤硝态氮平均约为耕地的3.42倍、2.54倍和1.26倍,铵态氮平均为耕地的1.71倍、1.37倍和1.30倍,可溶性有机氮约为1.64倍、1.31倍和1.23倍。可溶性氮组分受土壤含水量的影响大于土壤温度,硝态氮对土壤含水量的变化最为敏感,而可溶性全氮则对土壤温度变化最为敏感。综上所述,人工林植被恢复有利于提高土壤可溶性氮组分,增加氮的有效性,同时除铵态氮外,土壤可溶性氮组分随季节变化显著。     

黄芪对镉致大鼠睾丸支持细胞超微结构及波形蛋白、E-钙粘蛋白表达改变的保护作用

目的 探讨黄芪对镉致大鼠睾丸支持细胞损伤的保护作用.方法 21只成年雄性SD大鼠随机分成镉组(0.1％氯化镉腹腔内注射,1mg/Kg体重/天,5天/周,处理后1、2、3、4周取材)、镉加黄芪组(注射氯化镉的同时注射黄芪,10g/Kg体重/天,5天/周,处理后2、4周取材)和对照组(腹腔内注射等量生理盐水).睾丸取材作光镜、免疫组织化学染色和图像分析及超微结构观察.结果 光镜H.E染色对照组支持细胞核不规则,染色浅,核仁明显,镉处理后胞浆内有空泡形成,镉加黄芪组支持细胞未见明显改变.对照组波形蛋白阳性产物在支持细胞靠近基室腔的胞浆中表达,E-钙粘蛋白阳性产物则主要定位于生精上皮近腔室的支持细胞和部分生精细胞胞浆中.镉处理后支持细胞胞浆中波形蛋白和E-钙粘蛋白阳性产物表达的平均光密度值均明显降低(P＜0.05),镉加黄芪组阳性产物表达虽较对照组减弱但明显高于相应镉组(P＜0.05).镉处理组支持细胞胞质特化区和紧密连接破坏,镉加黄芪组支持细胞超微病变较相应镉组为轻.结论 镉降低大鼠睾丸支持细胞波形蛋白和E-钙粘蛋白的表达并造成支持细胞的超微结构损伤,黄芪具有较好的保护效果.