Discovery of novel substituted octahydropyrrolo[3,4-c]pyrroles as dual orexin receptor antagonists for insomnia treatment

A series of octahydropyrrolo[3,4-c]pyrroles were synthesized and evaluated by orexin 1 and 2 receptor (OX_{1 & 2} R) antagonists assays. Compound 14l with potent OXR antagonist activity and suitable pharmacokinetic behavior was chosen to be investigated in an EEG study, which demonstrated effects of sleep promotion comparable to Suvorexant. Furthermore, the di-fluro substituted analogs exhibited reduced hERG inhibition while maintaining moderate potency.     

朊病毒疾病

朊病毒是一种蛋白性质的感染颗粒,它能引起动物的一类大脑功能紊乱疾病:可传染海绵样脑病(TSE)。本文就朊病毒、朊病毒引起的疾病、牛海绵样脑病(BSE)及BSE能否传给人类进行一些讨论。     

两种病毒与细胞结合诱导的原癌基因早期表达

脊髓灰质炎病毒和单纯疱疹病毒Ⅰ型结合人二倍体细胞后１ｈ内,导致了不 同的早期基因形式的原癌基因表达反应,其主要表现为ｃ－ｆｏｓ、ｃｒｃ等的表达增强或抑制。     

β2-adrenergic receptor promotes liver regeneration partially through crosstalk with c-met

The β₂-adrenergic receptor (β₂AR) is a G protein-coupled receptor (GPCR) that mediates the majority of cellular responses to external stimuli. Aberrant expression of β₂AR results in various pathophysiological disorders, including tumorigenesis, but little is known about its role in liver regeneration. This study aims to investigate the impact and the underlying mechanism of β₂AR in liver regeneration. Here, we found that β₂AR was upregulated during liver regeneration induced by 70% PH. Deletion of β₂AR in mice resulted in 62% mortality 2 days post-PH, decreased proliferative marker expression and impaired liver function throughout regeneration. Moreover, AAV8-mediated overexpression of β₂AR in hepatocytes accelerated the regeneration process and increased target gene expression. Mechanistically, β₂AR recruited G-protein-coupled receptor kinase 2 (GRK2) to the membrane and then formed a complex with c-met to transactivate c-met signaling, which triggered downstream extracellular regulated protein kinase (ERK) signaling activation and nuclear translocation. Inhibition of c-met with SU11274 or ERK with U0126 decreased β₂AR overexpression-induced hepatocyte proliferation. Our findings revealed that β₂AR might act as a critical mediator regulating liver regeneration by crosstalk with c-met and activation of ERK signaling.Subject terms: Cell proliferation, Endocytosis     

Studies on the Somaclonal Variation of Regenerated Plants from Protoplasts of Actinidia deliciosa

Protoplasts were isolated from leaf, petiole and stem segment-derived calli induced from one pistillate plant of Actinidia deliciosa line No. 26. Regenerated plantlets were obtained from protoplasts of leaf-derived and stem segment-derived calli, while only calli regenerated from protoplasts of petiole-derived calli. Seventy-six plants from protoplasts of leaf-derived calli and 21 plants from that of stem segment-derived calli survived after transplanting or grafting during 1987–1989. One staminate plant and two pistillate plants bloomed in May, 1991 and fruited soon afterwards. In all of those three plants regenerated from protoplasts of leafderived calli, sex differentiation occurred from somatic cells of Actinidia was verified. Somaclonal variation on leaf shape and plant morphology was obviously appeared. Chromosome number identified from 16 plants varied from 116 to 180.     

The sgp gene modulates stress responses of Streptococcus mutans: utilization of an antisense RNA strategy to investigate essential gene functions

The sgp gene from Streptococcus mutans has been previously isolated, characterized, and demonstrated to encode a G-protein. In order to investigate the function of this gene, a novel antisense RNA strategy was developed. Expression of sgp antisense RNA in Escherichia coli led to transient inhibition of growth. In addition, sgp antisense RNA expression in S. mutans resulted in decreased growth under environmental stress conditions (44°C, acidic pH, and high osmolarity). Therefore, these results suggest that the sgp gene plays a role in modulating the stress responses of S. mutans. This approach could be applicable for investigating the function of essential genes in other organisms for which mutants are not available.     

流域森林资源调查及生物量动态研究——以潭江流域为例

对潭江流域森林组分与生物量调查研究发现:与1990年比较,2002年整个流域的林业用地面积增加了18962.1hm2,增长4.48%。流域生物量以湿地松和马尾松占优势,分别占流域森林生物量的39.12%和21.38%,阔叶树占15.39%,桉树和杉树分别占9.08%和7.97%,其它树种只占7.06%,总体来说,流域平均生物量2002年比1995年提高了6.21t·hm-2,平均每年提高0.89t·hm-2。说明近十二年来,植树造林的生态效益逐步体现出来,但同时也存在生物群落以马尾松、湿地松等先锋物种为主,森林结构单一的问题。通过分析研究,为潭江流域森林结构优化与科学管理提供依据。