黄瓜苗病拮抗菌的筛选与活性测定

试验筛选出具有生物防治作用的3株细菌B2、B3、B9和1株真菌FT3（水霉菌）。它们对由立枯丝核菌（Rhizoctoniasolani)和瓜果腐霉菌（Pythium aphanidermatum)引起的苗病有较明显的防治效果，其中B9和FT3对由瓜果腐霉菌引起的苗病防治效果高达70％以上。B9和FT3在病菌接种量不高的条件下混合使用可表现出协同防病作用。化学农药福美双对生防细菌B9的防病功能有促进作用，但却抑制木霉菌的生物防治效果。     

咪唑斯汀的合成新工艺

4-氟苄基氯与2-氯-1H-苯并咪唑反应所得2-氯-1-(4-氟苄基)-1H-苯并咪唑,与4-氯哌啶反应后用甲胺氨解,得1-(4-氟苄基)-2-(4-甲胺基)哌啶基-1H-苯并咪唑,最后与2-甲硫基-1H-嘧啶-4-酮缩合,得H1受体拮抗剂咪唑斯汀,总收率为32%。     

Anti-Inflammatory Therapeutic Approaches to Prevent or Delay Post-Traumatic Osteoarthritis (PTOA) of the Knee Joint with a Focus on Sustained Delivery Approaches

Inflammation plays a central role in the pathogenesis of knee PTOA after knee trauma. While a comprehensive therapy capable of preventing or delaying post-traumatic osteoarthritis (PTOA) progression after knee joint injury does not yet clinically exist, current literature suggests that certain aspects of early post-traumatic pathology of the knee joint may be prevented or delayed by anti-inflammatory therapeutic interventions. We discuss multifaceted therapeutic approaches that may be capable of effectively reducing the continuous cycle of inflammation and concomitant processes that lead to cartilage degradation as well as those that can simultaneously promote intrinsic repair processes. Within this context, we focus on early disease prevention, the optimal timeframe of treatment and possible long-lasting sustained delivery local modes of treatments that could prevent knee joint-associated PTOA symptoms. Specifically, we identify anti-inflammatory candidates that are not only anti-inflammatory but also anti-degenerative, anti-apoptotic and pro-regenerative.     

3Z,6Z,9Z-Trienes and unsaturated epoxides as sex attractants for geometrid moths

Sex attractants for three species of geometrid moths were discovered during field screening of 3Z,6Z,9Z-trienes, and the racemic monoepoxydienes derived therefrom. MaleProbole amicaria moths were attracted to lure blends containing 6Z,9Z-cis-3,4-epoxy-nonadecadiene (6Z,9Z-cis-3,4-epoxy-19H) with 3Z,9Z-cis-6,7-epoxy-19H. 3Z,6Z,9Z-19H was positively identified and 6Z,9Z-cis-3,4-epoxy-19H was tentatively identified in extracts of female pheromone glands by coupled gas chromatography-electroantennogram detection (GC-EAD) and gas chromatography-mass spectrometry (GC-MS).Sicya macularia male moths were attracted by blends of 3Z,6Z,9Z-19H and 6Z,9Z-cis-3,4-epoxy-19H. The attractive response was strongly antagonized by small amounts of 3Z,9Z-cis-6,7-epoxy-19H, or by larger amounts of 3Z,6Z-cis-9,10-epoxy-19H.Lomographa semiclarata male moths were attracted by a variety of lures containing 3Z,6Z,9Z-17H as a major component. 3Z,6Z,9Z-17H was tentatively identified in a female pheromone gland extract by GC-EAD.Issued as NRCC No. 30258.     

Investigating detailed interactions between novel PAR1 antagonist F16357 and the receptor using docking and molecular dynamic simulations

Currently, Vorapaxar is the only recently FDA-approved antiplatelet drug targeting Protease-activated receptor 1 (PAR1). However, a novel antagonist, F16357, has been shown to prevent painful bladder syndrome, also known as interstitial cystitis (IC). Unfortunately, there is no high resolution structure of the F16357-receptor complex, hindering its optimization as a therapeutic agent. In this study, we used docking and molecular dynamic (MD) simulations to investigate the detailed interactions between F16357 and PAR1 at a molecular level. The recently solved crystal structure of human PAR1 complexed with Vorapaxar was used in our docking of F16357 into the binding pocket of the receptor. To enhance binding pose selection, F16357 was docked first without constraints and then with a positional constraint to invert its orientation to become similar to that of Vorapaxar. The three systems, with crystal Vorapaxar, F16357 and an inverted F16357, were subjected to 3.0 μs MD simulations. The MM-GBSA binding energy analysis showed that F16357 binds more strongly in a pose obtained from an unrestrained docking than in the inverted pose from a restrained docking; and Vorapaxar binds more strongly than F17357. This ordering is consistent with the experimental pIC₅₀ values. Our structural data showed subtle changes in the binding pose between Vorapaxar and F16357. Transmembrane helices 1, 2, 5, and 7 were most significantly affected; most notably a large kink at F279^5.47 in TM helix 5 of the Vorapaxar complex was completely absent in the F16357 complex. The results of this study facilitate the future development of other therapeutic PAR1 antagonists.     

新型钙拮抗剂Nimodipine的质谱研究

本文报告了新型钙拮抗剂Nimodipine的EIMS谱、HR -EIMS数据和1 3 CNMR(COM .INEPT)谱和数据。根据HREI数据讨论了主要特征碎片离子的可能裂解途径。其中许多碎片离子是由麦氏重排而得。     

[β-Glu2]TRH Is a Functional Antagonist of Thyrotropin-Releasing Hormone (TRH) in the Rodent Brain

Selective antagonists of thyrotropin-releasing hormone (TRH; pGlu-His-Pro-NH₂), in order to enable a better understanding of this peptide’s central functions, have not been identified. Using pGlu-Glu-Pro-NH₂ ([Glu²]TRH) as a lead peptide and with modification at its central residue, our studies focused on some of its analogues synthesized as potential functional antagonists of TRH in the rodent brain. Among the peptides studied, the novel isomeric analogue [β-Glu²]TRH was found to suppress the analeptic and antidepressant-like pharmacological activities of TRH without eliciting intrinsic effects in these paradigms. [β-Glu²]TRH also completely reversed TRH’s stimulation of acetylcholine turnover in the rat hippocampus without a cholinergic activity of its own, which was demonstrated through in vivo microdialysis experiments. Altogether, [β-Glu²]TRH emerged as the first selective functional antagonist of TRH’s prominent cholinergic actions, by which this endogenous peptide elicits a vast array of central effects.     

高铁酸盐对水中H2受体拮抗剂的降解特性

高铁酸盐［Fe(Ⅵ)］兼具氧化、絮凝和消毒等功能,是备受关注的一类多功能水处理剂。本文针对在自然水域中H₂受体拮抗剂类药品（HRAs）经常被检出并难以去除的问题,通过高铁酸钾（K₂FeO₄）对5种临床上常见HRAs［即法莫替丁（FMTD）、雷尼替丁（RNTD）、罗沙替丁（RXTD）、西咪替丁（CMTD）和尼扎替丁（NZTD）］进行氧化降解研究。结果表明,在pH=7条件下,K₂FeO₄更倾向与带有硫醚键结构和羧基结构的HRAs反应。HRAs（除RXTD外）对K₂FeO₄具有较高的反应活性,降解率高达98.4%,并且符合二级反应动力学特性。反应二级速率常数与pH有较高的相关性,其主要是由于K₂FeO₄质子化和HRAs形态受pH的影响。不同浓度的水体基质（Cl^-、HCO₃^-和腐殖酸）对K₂FeO₄氧化降解HRAs有不同程度的抑制作用。实际水体中复杂的水质特征影响K₂FeO₄对HRAs的去除,但除医疗废水外,K₂FeO₄对RNTD的去除率高达80%,医疗废水中的去除率为65%。经K₂FeO₄处理后,HRAs的生态毒性可显著降低。     

缬沙坦及苯那普利对5/6肾切除大鼠肾小球硬化的影响

目的: 观察并比较缬沙坦及苯那普利对5/6肾切除大鼠肾小球硬化的改善作用,探讨其作用机制。方法: 选用SD 雄性大鼠30 只,通过5/6 肾切除法制造慢性肾功能衰竭模型,术后2 周随机分为模型组、缬沙坦组及苯那普利组,并设假手术组作为对照。术后第6 周末各组大鼠进行体重、血压、血清肌酐(Scr)及尿素氮(BUN)的测定,处死大鼠,取出肾组织进行病理组织形态学观察,并采用免疫组织化学方法检测肾组织转化生长因子β₁ (TGF-β₁ )、IV 型胶原、纤维连接蛋白(FN)表达。结果: 同模型组相比,两治疗组收缩压下降(P均<0.01),肾功能改善;肾小球系膜增殖程度、肾小球硬化指数(GSI)降低(P均<0.01);免疫组化染色显示,两治疗组肾小球转化生长因子β₁ (TGF-β₁)、纤维连接蛋白(FN)及IV 型胶原表达均较模型组下降(P均<0.01)。结论: 缬沙坦及苯那普利对慢性肾功能衰竭大鼠具有同等的肾脏保护作用;改善肾小球硬化是通过减少肾小球TGF-β₁ 表达,从而减少FN 及IV 型胶原生成来实现的。