腺病毒介导N-乙基顺丁烯二酰亚胺敏感因子小干扰RNA对心肌梗死大鼠心功能的影响

目的探索腺病毒介导的N-乙基顺丁烯二酰亚胺敏感因子小干扰RNA(NSF-siRNA)对急性心肌梗死大鼠模型心功能的影响。方法 36只成年SD大鼠,随机分为实验组、对照组和生理盐水组,每组12只。实验组经结扎左冠状动脉前降支建立急性心肌梗死模型,模型成功后,大鼠心脏左心室壁梗死区周围局部注射NSF-siRNA重组腺病毒载体。2周后,通过无创超声心动图测定心脏LVEF;用BL-420生物功能实验系统测定左心室舒张末压(LVEDP)及左心室压力最大上升速率(+dp/dtmax);随后取心脏,连续切片行TTC染色,沿分界线剪下梗死区,测量心肌梗死区质量占全部心脏组织质量的比例,观察心肌梗死范围。结果 2周时,实验组LVEF较对照组及生理盐水组明显增加[(46.0±7.5)%vs(34.0±9.0)%和(27.5±4.5)%,P<0.05];LVEDP较对照组及生理盐水组显著降低[(18.5±5.9)mm Hg vs(39.5±24.0)mm Hg和(26.6±24.0)mm Hg(1mm Hg=0.133kPa),P<0.05];+dp/dtmax较对照组及生理盐水组明显增加[(9.7±1.2)mm Hg/s×103 vs(4.3±2.2)mm Hg/s×103和(5.2±2.5)mm Hg/s×103,P<0.05];与生理盐水组和对照组比较,实验组心肌梗死范围虽降低,但差异无统计学意义(P>0.05)。结论心肌梗死周围注射NSF-siRNA腺病毒表达载体,能显著改善大鼠急性心肌梗死后2周心功能,但对心肌梗死范围无明显影响。

高梯度绝缘子初步研究及Kapton绝缘性能分析

为发展高梯度绝缘子,介绍了这种新型绝缘子的耐压机理,利用单电子理论对绝缘层厚度进行了初步的定量估计,从材料耐热性能、出气率、介电常数、耐辐射等几个方面对Kapton用于真空高压绝缘的优越性进行了讨论,利用经验公式绘制了Kapton材料的二次电子发射数量随能量的变化关系曲线图,对实际设计微堆层绝缘子具有参考价值。

Effects of N-(3',4',5'-Trimethoxycinnamoyl) ortho-Aminobenzoic Acid on Antigen-induced Contraction of Guinea-pig Ileum and the Degranulation of and Histamine Release from Mast Cells

N-(3′,4′,5′-Trimethoxycinnamoyl)ortho-aminobenzoic acid(TOA),at the concentration of 80μg/ml,significantly inhibited the antigen-induced contraction of ileum isolated from the actively sensitized guinea-pig.At the concentrations of 25 and 50μg/ml, TOA inhibited homocytotropic antibody-mediated degranulation of mast cells in the rat mesentery,and also inhibited anaphylactic histamine release from rat peritoneal mast cells.

Polymethylenebis [acetamides] Analogues.Synthesis and Differentiation-Inducing Activity on HL-60 Cells

报导了一系列多亚甲基双［酰胺］类化合物的合成，由－摩尔多亚甲基二甲酰氯分别和二摩尔２－氨基噻唑啉及５－氨基－１－甲基吡啶酮反应制得。测定了其体外对ＨＬ－６０人早幼粒白血病细胞的分化诱导活性，初步结果表明：Ｎ，Ｎ｀－双吡啶酮基六二甲酰胺和Ｎ，Ｎ｀－双噻唑啉基八亚甲基二甲酰胺分别在０．１ｍｍｏｌ／Ｌ和０．５ｍｍｏｌ／Ｌ浓度时，诱导分化百分率可达６０％。此浓度下细胞存活率分别为２６％及２２％，其有效诱导浓度比ＨＭＢＡ低十倍。

瑞飞特稻田除草试验初报

瑞飞特是瑞士诺华公司开发的一种新型酰类胺稻田除草剂。试验表明瑞飞特比丁草胺具有较好的保护根系的作用 ,具有活性高、扩散性好、杀草普广、安全高效等特点 ,除草效果达86 4% ,比丁草胺高 2 0个百分点 ,最终产量比丁草胺增产 5 1% ,比空白对照增产 9

The Syntheses of β-Carboline-3-carboxamides Derivatives and TheirInteraction with DNA

To study the interactions of these compounds with calf thymus DNA(CT-DNA), seven b-carboline-3-carboxamides were designed and synthesized. The interactions of these compounds with CT-DNA were determined by the viscometric titration assay and Tm (melting temperature) value assay. Binding strengths were evaluated by spectrophotometric titration experiment and microcalorimetric measurement. The interactions of these compounds were tested with CT-DNA. It was showed that all of these compounds were able to change the Tm value of CT-DNA. The results of viscometric titration assay indicated that these compounds interacted with CT-DNA by intercalation. Spectrophotometric titration experiment showed that the binding strengths of these compounds with CT-DNA were different, which was well in agreement with the cell culture results. The binding was driven by entropy according to the results of the microcalorimetric measurement. This series of b-carboline-3-carboxamides is DNA targeting compounds. Their obvious antitumor biological effect is based on the intercalation with DNA base-pairs.

RNA干扰抑制内皮细胞韦伯潘力氏小体的释放

目的探讨利用RNA干扰方法抑制内皮细胞韦伯潘力氏小体(WPB)释放的效果和意义,为防治心血管病和开发小分子RNA药物奠定基础。方法设计腺病毒介导的针对调节WPB释放的关键蛋白N-乙基顺丁烯二酰亚胺敏感因子(NSF)N端功能区的小发卡RNA(shRNA),筛选鉴定收获病毒,使用NSF shRNA转染人主动脉内皮细胞为实验组、阴性对照病毒感染为阴性组、不加任何干扰为空白组,RT-PCR和Western blot法观察对NSFmRNA及蛋白表达的抑制作用,免疫荧光染色观察对WPB释放的影响。结果用携带NSF shRNA的腺病毒感染内皮细胞后,实验组NSF mRNA表达与空白组(P=0.02)及阴性组(P=0.035)比较,差异有统计学意义;实验组NSFmRNA表达随时间延长持续下降,24、48及72 h明显下降,差异有统计学意义(P=0.048)。实验组NSF蛋白表达,与空白组(P=0.031)及阴性组(P=0.004)比较.差异有统计学意义;而空白组与阴性组差异无统计学意义(P=0.249)。免疫荧光染色显示,NSF-shRNA腺病毒感染,明显抑制凝血酶诱导的WPB释放。结论携带NSF-shRNA的腺病毒感染人主动脉内皮细胞,能明显抑制NSF mRNA及蛋白表达,抑制凝血酶诱导的WPB释放,对未来动脉粥样硬化及急性冠状动脉综合征的防治有一定的参考价值。

Research Status of Amide Herbicides and Their Safeners

The widespread use of chemical herbicides especially amide herbicides has promoted the innovation of chemical weeding in farmland, but amide herbicides have brought invisible chemical injuries to crops in addition to weeding. Herbi-cidesafeners should be applied at the same time with herbicides to ensure herbi- cides will not injure crops while controlling weeds. The research and application of safeners is of great significance to resolving or alleviating the negative effects of herbicides on crop growth. The overview, mechanism, applied research progress and existing problems of amide herbicides and their safenars are summarized.

Product selectivity controlled by manganese oxide crystals in catalytic ammoxidation

The performances of heterogeneous catalysts can be effectively tuned by changing the catalyst structures.Here we report a controllable nitrile synthesis from alcohol ammoxidation,where the nitrile hydration side reaction could be efficiently prevented by changing the manganese oxide catalysts.α-Mn_(2)O_(3)based catalysts are highly selective for nitrile synthesis,but MnO_(2)-based catalysts includingα,β,γ,andδphases favour the amide production from tandem ammoxidation and hydration steps.Multiple structural,kinetic,and spectroscopic investigations reveal that water decomposition is hindered onα-Mn2O3,thus to switch off the nitrile hydration.In addition,the selectivity-control feature of manganese oxide catalysts is mainly related to their crystalline nature rather than oxide morphology,although the morphological issue is usually regarded as a crucial factor in many reactions.

Isolation of Multi-Drug Resistant Paenibacillus sp. from Fertile Soil： An Imminent Menace of Spreading Resistance

There are a good number of reports in the literature stating spread of resistance from normal soil flora to nosocomial microorganism through various ways. Similarly during the study of antimicrobial susceptibility pattern in the microflora, a multidrug resistant bacterium has been isolated from soil collected in Maharashtra state （India）. The bacterium exhibited a resistance to various classes of antibiotics namely glycopeptide, beta-lactams, aminoglycosides, macrolides and lincosomides. The bacterial strain showed its resemblance to the genus Paenibacillus. This constitutes the first report of its kind as to the multi-drug resistance trait in the genus Paenibacillus phenotype, especially in close phylogenetic neighbour of Paenibacillus daejeonensis. The resistance pattern displayed by this strain particularly highlights the possible presence of multiple resistant determinants in microflora of the soil rhizosphere. In view of the recent reports about the Paenibacillus spp. in clinical derived strains, such multi-drug resistance factors in this genus adds to menace of transmission of resistance to common soil originating pathogen. The data also supports the fact that the resistances to certain antibiotics need not always be due to exposure to particular antibiotic or similar substance.

Propylene Polymerization Catalysts with Sulfonyl Amines as Internal Electron Donors

Three sulfonyl aliphatic amines [（R2SO2）2NR1, viz.： compound 1, in which RI=Me, and R2=Ph; compound 2, in which R1=n-Bu, and R2=CF3; and compound 3, in which RI=C8H17, and R2=CF3], have been synthesized and employed as internal electron donors （IED） for the preparation of Ziegler-Natta catalysts for the polymerization of propylene. The contents of Ti, H and C in these catalysts have been determined by elemental analysis and UV-vis spectrophotometry. The effect of the structure and dosage of the electron donor, the A1/Ti ratio and the polymerization temperature on the catalyst performance has been studied. Under optimized conditions, the catalyst with a highest activity yielded polypropylene with high isotacticity in the absence of external electron donors.

Synthesis, Characterization and Antiepileptic Activity of Some New N-Substituted Phthalimide Analogs

The present study was designed to investigate the anticonvulsant effect of series phthalimides possessing an N-aromatic amines moiety substituted at position 2 （2-7）. The compounds synthesized using phthalic anhydride and various amines in reflux synthesizer. The chemical structures of the titled compound were confirmed by physical and spectra analysis. All the synthesized compounds were evaluated in vivo for antiepileptic activity by using standard experimental models. Compounds： 2-（3H-1, 2, 4-Triazole-3-y） isoindoline-1, 3-dione （2）, Ethyl-4（1, 3-dioxoisoindoline-2-yl） benzoate 3 and 2-（4-nitrophenyl） isoindoline-1,3dione （7） were found significantly （P 〈 0.01-0.00001） delayed the onset and antagonized picrotoxin-induced seizures.

Computational Calculations of Molecular Properties and Molecular Docking of New and Reference Cephalosporins on Penicillin Binding Proteins and Various β-Lactamases

An approach of using molinspiration calculations and molecular docking on PBPs （penicillin-binding proteins） and certain β-lactamases is employed to predict the molecular properties, bioactivity and resistance of newer and reference cephalosporins. The previously synthesized cephalosporins 1-8 and reference cephalosporins were subjected to extensive evaluations by calculating the molecular properties, drug-likeness scores on the bases of Lipinski＇s rule and bioactivity prediction using the method of molinspiration web-based software. The TPSA （topological polar surface area）, OH-NH interactions, n-violation and the molinspiration Log partition coefficient （miLogP） values were also calculated. The investigated cephalosporins were subjected to molecular docking study on PBPs （lpyy） and on β-lactamases produced by S. aureus, K. pneumonia, E. coil and P. auroginosa using 1-click-docking website. Molecular properties of 1-8 recorded higher ＂FPSA than cephalexin and were lower than the reference cephalosporins and do not fulfill the requirements for Lipinski＇s rule. Bioactivities of 1-8 were predicted to be less and their docking scores on PBPs were comparable to those of the reference cephalosporins, particularly ceftobiprole. The references recorded various docking scores on the above β-lactamases and as expected, cefiobiprole recorded the lowest scores on all β-lactarnases. Cephalosporins 1-8 recorded various docking scores on β-lactamases. Molecular docking studies on PBPs and β-lactamases are considered as very useful, reliable and practical approach for predicting the bioactivity scores and to afford some information about the stability and selectivity of the newly proposed cephalosporins against β-lactamases of certain pathogenic microbes, such as P. auroginosa and MRSA, by recording the relative docking scores in comparison with those of reference cephalosporins.

Synthesis of telbivudine 3'-O-acetyl-5'-O-phenyl-N-alkylphosphramidates and evaluation of their anti-HBV activities

A series of telbivudine 3′-O-acetyl-5′-O-phenyl-N-alkylphosphramidate derivatives have been synthesized and their structures were confirmed by El-MS, ^1H NMR and ^13C NMR. We evaluated their anti-HBV activity in vitro. Two compounds 6d and 6f, turned out to be more active than telbivudine.

Correlation analysis of gene polymorphisms and β-lactam allergy

A total of 64 patients with β-lactam allergy and 30 control subjects were enrolled in a case-control study. This study is aimed to analyze the relationship between β-lactam allergy and 10 single nucleotide polymorphisms（SNPs） in interleukin-10（IL-10）, IL-13, IL-4Rα, high-affinity immunoglobulin E-receptor β chain（FcεRIβ）, interferon γ receptor 2（IFNGR2）, and CYP3A4, and within the Han Chinese population of Northwest China. Genotyping for the SNPs was conducted using the Sequenom Mass ARRAY platform. SPSS 17.0 was employed to analyze the statistical data and SHEsis was used to perform the haplotype reconstruction and analyze linkage disequilibrium of SNPs of IL-10 and IL-13. The results showed that the genotype distribution of CYP3A4 rs2242480/CT differed significantly between case and control groups of males（P=0.022; odds ratio（OR）=0.167, 95% confidence interval（CI）： 0.032–0.867）. Further analysis showed that CCA, CCG, and TAA haplotypes of IL-10 had no significant correlation in patients with β-lactam allergy. The correlation between CCT and CAC haplotypes of IL-13 and β-lactam allergy needs to be further studied. The analysis did not reveal any differences in the distribution of others gene polymorphisms between cases and controls.

Multi-responsive wholly aromatic sulfonated polyamide ultra-sensitive to pH value

We demonstrated here a new family of multi-responsive polymer:wholly aromatic sulfonated polyamide(SPA).SPA exhibited the unusual response to temperature and pH with the tunable low critical solution temperature(LCST).LCST of the obtained SPA decreased sharply with the increasing pH,and the difference of LCST between pH 6.0-6.8 is about 60 ℃.

Theoretical studies on selectivities in the Staudinger reaction of vicinal diimines and ketenes

The selectivities, including peri-, regio-, and diastereoselectivities, in the Staudinger reaction involving vicinal diimines and ketenes were investigated theoretically via the density functional theory （DFT） calculation. The results indicate that vicinal diimines prefer stepwise [2＋2] cycloaddition rather than [2＋4] cycloaddition to generate cis-4-imino-β-lactams. The diimines attack the less sterically hindered exo-side of ketenes to generate zwitterionic intermediates, which directly undergo a conrota- tory ring closure to produce cis-4-imino-β-lactams whatever diimines with less or more bulky N-substituents. For unsymmetric vicinal ketoaldehyde-derived diimines, their ketimines attack the exo-side of ketenes and undergo a conrotatory ring closure to produce cis-4-aldimino-β-lactams due to less steric effect. The current theoretical studies provide very important information for in-depth understanding of the selective formation of mono-cis-β-lactams from vicinal diimines and ketenes.

Stereoselective synthesis of cis- and trans-4-acyl-β-lactams from vicinal diketones and ketoaldehydes

4-Acyl-β-lactams are important synthetic intermediates in both pharmaceutical and organic chemistry. Cis- and trans-4-acyl-β- lactams were synthesized stereoselectively from vicinal diketones via the formation of bulky and less bulky diimines as key intermediates, respectively. The diimines reacted with acyl chloride in the presence of triethylamine to give rise to the corre- sponding 4-imino-β-lactams, which were further hydrolyzed to afford 4-acyl-β-lactams. The cis- and trans selectivity is de- pended on the steric hindrance of the imine N-substituents. A series of cis-4-acyl-β-lactams were synthesized from vicinal ketoaldehydes via the formation of their monoimines and diimines as intermediates. Pyruvic aldehyde produced cis-4-acetyl-β- lactams and cis-4-formyl-β-lactams, respectively, through the reactions of its monoimine and diimine with acyl chlorides. Phenylglyoxal generated cis-4-benzoyl-β-lactams via its monoaldimine.

A novel and versatile method for the enantioselective syntheses of tropane alkaloids

A full account of the novel and flexible approach to hydroxylated 8-azabicyclo[3,2,1]octan-3-ones and 9-azabicyclo[3,3,1] nonan-3-ones is presented. Using keto-lactams as the starting materials, this two-step method consists of silyl enol ether for mation with TBDMSOTf, lactam activation with Tf20/DTBMP, and halide-promoted cyclization. Radical dechlorination of the resulting 1-halotropan-3-ones led to the corresponding hydroxylated tropan-3-ones, which can be hydrogenated to yield 3ct,613-dihydroxytropanes. Starting from optically active keto-lactams, the method has been applied to the enantioselective syntheses of （＋）-（1S,3S,5R,6S）-pervilleine C （6）, （＋）-（1S,3R,5S,6R）-valeroidine （3）, （＋）-（1S,3S,5R,6S）-dibenzoyloxytropane （8） and （＋）-（1S,3S,5R,6S）-merredissine （9）.

Synthesis of NAD analogs to develop bioorthogonal redox system

Three new nicotinamide adenine dinucleotide(NAD) analogs were synthesized,and their characteristics as cofactors for Escherichia coli malic enzyme(ME) and its double mutant ME L310R/Q401C were analyzed.Each pair of the NAD analog and the double mutant showed good orthogonality to the natural pair of NAD and ME in terms of catalyzing oxidative decarboxylation of L-malic acid.Results indicated that molecular interactions between redox enzyme and cofactor could be further explored to generate new bioorthogonal redox systems.