Seco-4-methyl-DCK derivatives as potent chemosensitizers

Twenty-five seco-4-methyl-DCK derivatives were designed, synthesized and evaluated for chemoreversal activity when combined with paclitaxel or vincristine in two drug-resistant cancer cell lines (A2780/T and KB-V) respectively. Most of the new compounds displayed moderate to significant MDR reversal activities in the P-gp overexpressing A2780/T and KB-V cells. Especially, compounds 7o and 7y showed the most potent chemosensitization activities with more than 496 and 735 reversal ratios at a concentration of 10?μM. Unexpectedly the newly synthesized compounds did not show chemosensitization activities observed in a non-P-gp overexpressing cisplatin resistant human ovarian cancer cell line (A2780/CDDP), implying that the MDR reversal effects might be associated with P-gp overexpression. Moreover, these compounds did not exhibit significant antiproliferative activities against nontumorigenic cell lines (HUVEC, HOSEC and T29) compared to the positive control verapamil at the tested concentration, which suggested better safety than verapamil. The pharmacological actions of the compounds will be studied further to explore their merit for development as novel candidates to overcome P-gp mediated MDR cancer.     

江苏省县域森林生态安全评价及空间计量分析

通过考察生态区位因素对森林生态安全的影响,建立评价指标体系,研究其空间相关性的内在效应机制,从而实现森林生态安全的评价与监测。以江苏省80个区县为研究对象,基于2000—2015年面板数据,运用熵权法、专家法及模糊物元法计算森林生态安全指数,然后结合气象类指标及地形类指标计算生态区位系数,再用该系数修正森林ESI,同时结合Arc GIS技术、空间相关性分析、SLM与SEM模型得出如下结论:(1)人口密度、单位面积能源消耗量、退耕还林面积占比等指标权重最大;(2)生态区位系数高值区主要分布在江苏南部少数地区,低值区主要分布在江苏东北部;(3)苏南地区森林生态安全状况整体好于苏北及中东部地区;(4) 2000—2015年,江苏省67.5%的区县森林ESI呈现出较明显下降趋势,反映出江苏省森林生态安全发展状况不容乐观;(5)江苏省县域森林ESI整体空间相关性显著(P≤0.01),但2000—2015年空间聚集程度有所下降,且Low-Low聚类显著性更强;(6)森林ESI在江苏省县域间为扩散效应与回流效应并存。     

地黄SCoT分子标记体系的建立和指纹图谱的构建

该研究采用L_(25)(5~6)正交设计和单因素两种方法,对影响地黄SCoT-PCR反应的5个因素(模板DNA浓度,引物浓度,ddH_2O和Mix的用量以及退火温度)进行了优化。结果表明:优化后的反应体系总体积为25μL,含有8μL ddH_2O,1μL模板DNA(80 ng·μL~(-1)),1μL引物(8μmol·L~(-1))和15μL Mix,退火温度为45℃。运用30份地黄种质材料,对优化的SCoT-PCR正交体系进行多次重复验证,获得了多态性丰富、条带清晰的扩增图谱,证明该反应体系稳定可靠。利用该体系对32条SCoT引物进行两次筛选,得到14个扩增产物清晰、重复性好且多态性条带相对较高的引物。利用SCoT_4等5条引物构建了上述地黄2个种共30份种质的SCoT指纹图谱。利用这5个SCoT引物指纹图谱可将7个地黄常用栽培品种区分开。这表明SCoT分子标记体系适用于地黄主要品种亲缘关系及遗传多样性的研究,所构建的指纹图谱也为地黄常见的7个栽培品种的区分提供参考依据。     

原发性乳腺弥漫性大B细胞淋巴瘤5例并文献复习

目的探讨原发性乳腺弥漫性大B细胞淋巴瘤(primary breast diffuse large B-cell lymphoma,PB-DLBCL)的临床病理学特点、诊断及鉴别诊断、治疗及预后。方法采用HE染色和免疫组织化学SP法分析5例PB-DLBCL患者的临床表现、病理学及免疫表型特征,并复习相关文献。结果 5例均为女性患者,发病年龄48~70岁,中位年龄59.2岁,均为单侧乳腺肿块,其中左乳3例,右乳2例。镜下见乳腺正常结构被破坏,成片的中等偏大的肿瘤细胞弥漫浸润乳腺小叶、导管周围、间质及周围脂肪组织。根据免疫组织化学表型,4例为非生发中心型,1例为生发中心型;Ki67增殖指数为60%~90%;根据 Ann Arbor 分期标准,5例均为II E期。病例随访时间截止至2018年6月,随访期内,有2例复发,分别于7和19个月后死亡;2例健在,分别已存活12和72个月;另外一例失访。结论 PB-DLBCL是一种少见的恶性淋巴瘤,临床表现为单侧乳腺无痛性包块进行性增大,以右侧多见。确诊主要依靠病理活检及免疫表型,免疫表型以非生发中心为主,以化疗联合放疗等综合治疗方案为宜。     

过表达水稻OsAQP增强转基因拟南芥耐盐性

水稻OsAQP是实验室前期从cDNA文库中筛选的功能未知的水通道蛋白质编码基因。本文采用DNA重组技术构建其植物过表达载体,并对拟南芥进行了遗传转化,筛选获得转基因拟南芥。采用50、100、125和150 mmol/L梯度盐胁迫处理,结果显示,转基因拟南芥的发芽率、根长以及鲜重分别比对照至少高17%、40.8%和14.29%,且差异达到显著水平（P<0.05）。在正常条件下,转基因植株叶片中抗坏血酸过氧化物酶(APX)活性显著高于WT;经300 mmol/L NaCl处理,转基因拟南芥叶片中超氧化物歧化酶(SOD)、过氧化物酶(POD)、APX酶活性均升高,与处理前相比分别提高7.37倍、30.87倍和1.77倍,且与WT的酶活性差异达到显著水平（P<0.05）;丙二醛(MDA)含量也在处理后上升,但在转基因植株中的含量低于WT,分别是WT的0.74倍、0.68倍和0.62倍,差异同样达到显著水平（P<0.05）。本研究提示,OsAQP过表达不仅能够促进拟南芥种子萌发和根系生长,而且在盐胁迫下通过提高拟南芥内源抗氧化酶活性、降低膜脂过氧化程度,增强了转基因植株对一定程度盐胁迫的耐受性。     

Clopidogrel reduces lipopolysaccharide‐induced inflammation and neutrophil‐platelet aggregates in an experimental endotoxemic model

Platelet activation contributes to organs failure in inflammation and plays an important role in endotoxemia. Clopidogrel inhibits platelet aggregation and activation. However, the role of clopidogrel in modulating inflammatory progression of endotoxemia remains largely unexplored. Therefore, we investigated the role of clopidogrel on the activation of platelet and leukocytes in lipopolysaccharide (LPS)‐induced inflammation in mice. Animals were treated with clopidogrel or vehicle before LPS induction. The expression of neutrophil‐platelet aggregates and platelet activation and tissue factor was determined. Immunofluorescence was used to analyze platelet‐leukocyte interactions and tissue factor (TF) expression on leukocytes. Clopidogrel pretreatment markedly decreased lung damage, inhibited platelet‐neutrophil aggregates and TF expression. In addition, clopidogrel reduced thrombocytopenia and affected the number of circulating white blood cell in endotoxemia mice. Moreover, clopidogrel also reduced platelet shedding of CD40L and CD62P in endotoxemic mice. Taken together, clopidogrel played an important role through reducing platelet activation and inflammatory process in endotoxemia.     

Moderate grazing promotes the root biomass in Kobresia meadow on the northern Qinghai–Tibet Plateau

Grazing is an important modulator of both plant productivity and biodiversity in grassland community, yet how to determine a suitable grazing intensity in alpine grassland is still controversy. Here, we explore the effects of different grazing intensities on plant biomass and species composition, both at community level and functional group level, and examines the productivity–species richness relationship under four grazing patterns: no grazing (CK), light grazing (LG), moderate grazing, (MG) and heavy grazing (HG), attempt to determine a suitable grazing intensity in alpine grassland. The results were as follows. The total aboveground biomass (AGB) reduced with increasing grazing intensity, and the response of plant functional groups was different. AGB of both sedges and legumes increased from MG to HG, while the AGB of forbs reduced sharply and the grass AGB remained steady. There was a significant positive relationship between productivity and species richness both at community level and functional group level. In contrast, the belowground biomass (BGB) showed a unimodal relationship from CK to HG, peaking in MG (8,297.72 ± 621.29 g/m²). Interestingly, the grassland community tends to allocate more root biomass to the upper soil layer under increasing grazing intensities. Our results suggesting that moderate levels of disturbance may be the optimal grassland management strategy for alpine meadow in terms of root production.