Synthesis and anthelmintic activity of 7-substituted 3,4a-dimethyl-4a,5a,8a,8b-tetrahydro-6H-pyrrolo[3',4':4,5]furo[3,2-b]pyridine-6,8(7H)-diones

The racemic 7-substituted 3,4a-dimethyl-4a,5a,8a,8b-tetrahydro-6H-pyrrolo[3',4':4,5]furo[3,2-b]pyridine-6,8(7H)-diones represent novel tricyclic compounds with strong in vivo efficacy against the parasitic nematode Haemonchus contortus Rudolphi in sheep. Here we report on the synthesis of tricyclic endo-2,3-dihydro[3,2-b]pyridine-type cycloadducts and describe the separation of the racemic 3,4a-dimethyl-7-ethyl-4a,5a,8a,8b-tetrahydro-6H-pyrrolo[3',4':4,5]furo[3,2]pyridine-6,8(7H)-dione into the enantiomers by HPLC. The absolute configuration of the most anthelmintically active (4aS,5aS,8aS,8bR)-enantiomer was determined by single crystal X-ray analysis using its stable (4aS,5aS,8aS,8bR)-enantiomer-CuCl2 (2:1)-complex.     

新型非病毒三元复合DNA载体的研究

基因治疗是未来临床医学最具潜力的治疗方式,目前阻碍临床基因治疗发展的主要因素是缺乏安全和高效的基因载体,因此研究理想的非病毒转基因载体具有重要的意义.构建了由质粒DNA(D)-抗DNA抗体(A)-阳离子脂质体(C)组成的三元复合纳米基因载体(DAC),研究表明,三组分在磷酸缓冲液中可通过分子组装形成复合纳米胶束,DAC在细胞培养中表现出显著高效的基因表达,DAC在血管平滑肌细胞中的基因转染效率比不含抗DNA抗体的二元组合(DC)高4倍,比不含阳离子脂质体的二元组合(DA)约高11倍.激光共聚焦荧光显微观察证明,DAC细胞摄取量和DNA进入细胞核的量均明显高于对照组,而DC二元组合(不含抗DNA抗体)的DNA很少进入细胞核,细胞在DAC存在下生长正常.未发现细胞毒性.研究结果提示,DAC的作用机理主要是三元复合胶束中DNA的装载量比二元载体大得多,抗DNA抗体与阳离子脂质体的协同作用明显有利于DNA被细胞摄取和胞吞,从而提高了基因的转染和表达.     

Association between morningness-eveningness and behavioral/emotional problems among adolescents

Adolescent eveningness is associated with age, parental monitoring, daytime sleepiness, sleep problems, moodiness, and the use of coffee. This study investigated the association between adolescent morningness-eveningness and psychopathology, substance use, and suicidality in 1332 students ages 12 to 13. Each student-participant completed the Chinese version of the Child Morningness/Eveningness Scale (CMES), the Pubertal Development Scale, and a questionnaire about their sleep schedule, trouble sleeping, habitual substance use, and suicidality. Their mothers completed the Child Behavioral Checklist and Chinese Health Questionnaire. The morning (n = 412), intermediate (n = 740), and evening (n = 180) groups were operationally defined by the CMES t scores. The mixed model was used for data analysis. The evening group had shorter weekday sleep time, longer weekend sleep time, more daytime napping, and greater sleep compensation on weekends and was more likely than the other 2 groups to have behavioral/emotional problems, suicidality, and habitual substance use. Internalizing and externalizing problems partially explained the association between eveningness, substance use, and suicidality. The findings suggest that eveningness may be an indicator for adolescents with behavioral/emotional problems and risky behaviors and suggest an investigation for possible intervention.     

消减免疫法制备克伦特罗单克隆抗体

目的：制备克伦特罗（CL）单克隆抗体。方法：重氮化法制备克伦特罗完全抗原,消减免疫法免疫BALB／c小鼠,常规杂交瘤技术制备抗克伦特罗单克隆抗体。结果：消减免疫法使小鼠获得了对BSA的耐受,单抗筛选过程中获得了高达8．2％的阳性率。最后得到了针对CL的特异性抗体。结论：用消减免疫法制备针对小分子污染物的单克隆抗体,可减少在制备单克隆抗体时筛选的工作量,可增加获得预期抗体的机会。     

Associations between chronotypes, psychopathology, and personality among incoming college students

Chronotye is associated with age, sex, personality, and parental monitoring during childhood. The evening type is associated with poor school performance, sleep problems, anxious/depressive symptoms, tobacco smoking, caffeine consumption, alcohol drinking, and suicidality in adolescents. The present study tested the relationships between chronotype and a wide range of psychopathology and personality traits among 2919 incoming undergraduate students. Each participant completed a self-administered questionnaire that included demographics, plus the Morningness-Eveningness (M-E) scale, Brief Symptom Rating Scale (BSRS), Tridimensional Personality Questionnaire, and Maudesley Personality Inventory. The t-score distribution of the M-E scale was used to form the morning (t-score >60, n = 419), evening (t-score <40, n = 371), and intermediate (40 ≤ t-score ≤ 60, n = 2129) groups. Multivariable regression was employed for data analysis. For males, the evening type scored higher on all subscales of the BSRS than the morning type, except phobic anxiety. For females, the evening type had higher scores than the other two types on all subscales, except in obsession/compulsion and phobic anxiety, where the evening type only scored higher than the intermediate type. The evening type of both sexes also scored higher than the morning type in novelty seeking, harm avoidance, and neurotic personality characteristics, but lower than the morning type in extraversion and social desirability. In reward dependence, the evening type scored lowest for males, but there was no difference for females. The findings of the evening type being associated with possible psychopathology and certain types of personality have public health implications, that is, chronotype needs to be taken into account in the development of mental health prevention programs and assessment of and intervention for mental problems in young adults.     

Humic acid induces the generation of nitric oxide in human umbilical vein endothelial cells: stimulation of nitric oxide synthase during cell injury

Humic acid (HA) has been implicated as an etiological factor in the peripheral vasculopathy of blackfoot disease (BFD). In this study, we examined the effects of HA upon the generation of nitric oxide (NO) during the process of lethal cell injury in cultured human umbilical vein endothelial cells (HUVECs). NO production was measured by the formation of nitrite (NO(2)(-)), the stable end-metabolite of NO. Cell death was assessed by measuring the release of intracellular lactate dehydrogenase (LDH). Treatment HUVECs with HA at a concentration of 50, 100, and 200 microg/ml concentration-dependently increased nitrite levels, reaching a peak at 12 h subsequent to HA treatment, with a maximal response of approximately 400 pmole nitrite (from 1 x 10(4) cells). HA-induced nitrite formation was blocked completely by N(G)-nitro-L-arginine methyl ester (L-NAME) and also by N(G)-methyl-L-arginine (L-NMA), both being specific inhibitors of NO synthase. The LDH released from endothelial cells was evoked at from 24 h after the addition of HA (50, 100, 200 microg/ml) in a concentration- and time-dependent manner. The HA-induced LDH release was also reduced by the presence of both L-NAME and L-NMA. The addition of Ca(2+) chelator (BAPTA) inhibited both nitrite formation and LDH release by HA. Moreover, the antioxidants (superoxide dismutase, vitamin C, vitamin E) and protein kinase inhibitor (H7) effectively suppressed HA-induced nitrite formation. These results suggest that HA treatment of endothelial cells stimulates NO production, which can elicit cell injury via the stimulation of Ca(2+)-dependent NO synthase activity by increasing cytosolic Ca(2+) levels. Because the destruction of endothelial cells has been implicated in triggering the onset of BFD, the induction of excessive levels of NO and consequent endothelial-cell injury may be important to the etiology of HA-induced vascular disorders associated with BFD for humans.