Phoxim and fenvalerate are pesticides that are most widely used as commercial formulae in China. Fenvalerate belongs to the pyrethroid compounds [Benzeneacetic acid, 4-chloro-α-(1-methylethyl)-, cyano (3-phenoxyphenyl) methyl ester. CAS registry number: 51630-58-1], while phoxim is an organic phosphate (3,5- dioxa-6-aza-4-phosphaoct-6-ene-8-nitrile, 4-ethoxy-7- phenyl-, 4-sulfide. CAS registry number: 14816-18-3). The metabolism of fenvalerate has been studied in vivo1), but the metabolism and distribution of its mixture with phoxim have not been reported in literature. A recent epidemiological investigation showed that the incidence of poisoning caused by the two mixed pesticides was three times higher than that by either one alone under similar exposure conditions2). The purpose of this study was to determine the toxicokinetics of these pesticides in order to provide information for furthering the toxicity mechanism.

将大鼠暴露于10 、20 和30WLM（working level months）的氡浓度后，采用H-TdR掺入法和碱性单细胞凝胶电泳技术（SCGE），研究吸入氡及其子体后大鼠外周血淋巴细胞的DNA 损伤效应。结果表明，各暴露剂量组大鼠外周血淋巴细胞转化均显著低于对照组;淋巴细胞在碱性单细胞凝胶电泳条件下DNA 的迁移距离均显著高于对照组，且呈剂量- 效应关系。大鼠吸入氡及其子体可引起淋巴细胞DNA 合成抑制及淋巴细胞转化能力下降。

Aim: To investigate the effect of 7-hydroxystaurosporine (UCN-01), a selective protein kinase C (PKC) inhibitor, on cell growth, migration, and invasion in invasive human glioblastoma U-87MG cells. Methods: PKC activity was determined based on the PKC-catalyzed transfer of the 32P-phosphate group from [g-32P]ATP into a PKC-specific peptide substrate. Cell viability was measured by MTT assay. Cell invasion and migration were evaluated by a Boyden chamber assay and scratch wound assay, respectively. Protein expression was analyzed using Western blot assay. The formation of 3-dimensional cellular aggregates was examined by a cell-cell aggregation assay. Results: UCN-01 treatment resulted in concentration-and time-dependent inhibition of U-87MG cell growth at higher doses (> 100 nmol/L), and reduced cell invasion and migration capability at less cytotoxic doses (<100 nmol/L). UCN-01 significantly repressed PKC activity. Consistent with this result, UCN-01 blocked cell invasion stimulated by phorbel 12-myristate- 13-acetate (PMA) and ethanol (EtOH), 2 PKC activators. Enforced expression of the tumor suppressor genes BRCA1 and PTEN increased the anti-invasion potential of UCN-01. Exposure to UCN-01 caused a dose-dependent increase in cell adhesion molecule E-cadherin. The effect of UCN-01 on the formation of cell-cell aggregation was significantly reduced by the addition of an anti-E-cadherin antibody. Conclusion: UCN-01 inhibits the invasion and migration of human glioma cells. Accordingly, UCN-01 can have potential clinical applications for the treatment of human glioma metastasis.

In this paper, the circadian pattern of Clock and genes mediated by the Clock was investigated in peripheral lymphocytes of rats. Circadian rhythms of Clock are found under the regimes of constant darkness (DD) and 12-h light–12-h dark (LD12:12 h), with the peak phase at CT7 and ZT21, respectively. Ten differential cDNA fragments were identified to be mediated by the Clock, including three known genes (catalase, myelin proteolipid protein, and histone acetylase), four known expressed sequence tags (ESTs), and three novel ESTs. Experiment of the RNA interference revealed that these ESTs were down-regulated by the Clock gene and three of them were identified as clock-controlled genes. Understanding of clock-mediated genes may lead to a new direction in drug design for control of circadian rhythms.

摘要：探讨12h光照、12h黑暗交替（12 h-light：12 h-dark cycle，LD）及持续黑暗（constant darkness，DD）光制下松果体Clock基因和芳烷脘N-乙酰基转移酶基因（arylalkylamineⅣ-acetyltransferase gene，NAT）是否存在昼夜节律性表达及其光反应变化。Sprague-Dawley大鼠在LD和DD光制下分别被饲养4周（n=36）和8周n=36）后，在一昼夜内每隔4h采集一组松果体组织（n=6），提取总RNA，用竞争性定量RT-PCR测定不同昼夜时点样品中Clock及NAT基因的mRNA相对表达量，通过余弦法和Clock Lab软件获取节律参数，并经振幅检验是否存在昼夜节律。结果如下：（1）在DD或LD光制下，松果体Clock和NAT基因mRNA的表达均呈现夜高昼低的节律性振荡（P<0.05）。（2）与DD光制下比较，LD光制下松果体Clock和NAT基因的表达振幅及峰值相的mRNA水平均降低（P<0.05）。（3）在DD或LD光制下，Clock和NAT基因之间显示相似的节律性表达（P>0.05）。结果表明，Clock和NAT基因在松果体中存在同步的内源性昼夜节律表达，光照作用可使其表达下调。