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further evaluation of the potential anxiolytic activity of imidazo [1,5-a] diazepin agents selective for α2/3-containing GABA_A receptors

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PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR 2017年 157卷 35-40页

作者： Witkin, J. M. Cerne, R. Wakulchik, M. S, J. Gleason, S. D. Jones, T. M. Li, G. Arnold, L. A. Li, J. -X. Schkeryantz, J. M. Methuku, K. R. Cook, J. M. Poe, M. M. Eli Lilly & Co Lilly Res Labs Indianapolis IN 46285 USA Univ Wisconsin Dept Chem & Biochem Milwaukee WI 53201 USA SUNY Buffalo Jacobs Sch Med & Biomed Sci Dept Pharmacol & Toxicol Buffalo NY USA

Positive allosteric modulators of GABA(A) receptors transduce a host of beneficial effects including anxiolytic actions. We have recently shown that bioavailability and anxiolytic-like activity can be improved by eliminating the ester functionality in imidazo[1,5-a] [1,4] diazepines. In the present series of experiments, we further substantiate the value of heterocyle replacement of the ester for potential treatment of anxiety. None of three esters was active in a Vogel conflict test in rats that detects anxiolytic drugs like diazepam. Compounds 7 and 8, ester bioisosters, were selective for alpha 2 and 3 over alpha 1-containing GABA(A) receptors but also had modest efficacy at GABA(A) alpha 5-containing receptors. Compound 7 was efficacious and potent in this anxiolytic-detecting assay without affecting non-punished responding. The efficacies of the esters and of compound 7 were predicted from their efficacies as anticonvulsants against the GABA(A) antagonist pentylenetetrazole (PTZ). In contrast, the related structural analog, compound 8, did not produce anxiolytic-like effects in rats despite anticonvulsant efficacy. These data thus support the following conclusions: 1) ancillary pharmacological actions of compound 8 might be responsible for its lack of anxiolytic-like efficacy despite its efficacy as an anticonvulsant 2) esters of imidazo[1,5-a] [1,4]diazepines do not demonstrate anxiolytic-like effects in rats due to their low bioavailability and 3) replacement of the ester function with suitable heterocycles markedly improves bioavailability and engenders molecules with the opportunity to have potent and efficacious effects in vivo that correspond to human anxiolytic actions.

关键词： HZ-166 ethyl 8-ethynyl-6-(pyridin-2-yl)-4H-benzo[ f ]imidazo[1,5- a ][1,4]diazepine-3-carboxylate

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In situ surface protection for enhancing stability and performance of conversion-type cathodes

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MRS ENERGY & SUSTAINABILITY 2017年第1期4卷 1-15页

作者： Wu, feixiang Borodin, Oleg Yushin, Gleb Georgia Inst Technol Sch Mat Sci & Engn Atlanta GA 30332 USA Army Res Lab Electrochem Branch Sensors & Electron Devices Directorate Adelphi MD 20783 USA

The use of in situ formed protective layer on conversion cathodes was introduced as a cheap and simple strategy to shield these materials from undesirable interactions with liquid electrolytes. Conversion-type cathodes have been viewed as promising candidates to replace Ni-and Co-based intercalation-type cathodes for next-generation lithium (Li) and Li-ion batteries with higher specific energy, lower cost, and potentially longer cycle life. Typically, in conversion reactions two or three Li ions may be stored per just one atom of chalcogen (e.g., S or Se) or transition metal (e.g., fe or Cu used in halides). Unfortunately, in conversion chemistries the active materials or intermediate charge/discharge products suffer from various unfavorable interactions and dissolution in organic electrolytes. In this mini-review article, we discuss the current interfacial challenges and focus on the protective layers in situ formed on the cathode surface to effectively shield conversion materials from undesirable interactions with liquid electrolytes. We further explore the mechanisms and current progress of forming such protective layers by using various salts, solvents, and additives together with the insight from molecular modeling. finally, we discuss future opportunities and perspectives of in situ surface protection.

关键词： Li S f coating energy storage

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^(18)f-Naf PET/CT对前列腺癌骨转移的诊断价值

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实用临床医药杂志 2016年第5期20卷 82-84页

作者：郑文璐四川医科大学附属第一医院核医学科四川泸州646000

目的探讨18f-Na f PET/CT在前列腺癌骨转移中的诊断价值及影像学特征。方法回顾性分析42例经病理证实为前列腺癌的患者的临床资料,均行18f-Na f PET/CT骨显像。比较18f-Na f PET/CT、18f-Na f PET和单独CT诊断前列腺癌骨转移灶的灵敏性... 详细信息

目的探讨18f-Na f PET/CT在前列腺癌骨转移中的诊断价值及影像学特征。方法回顾性分析42例经病理证实为前列腺癌的患者的临床资料,均行18f-Na f PET/CT骨显像。比较18f-Na f PET/CT、18f-Na f PET和单独CT诊断前列腺癌骨转移灶的灵敏性、准确性。结果18f-Na f PET/CT、18f-Na f PET、单独CT诊断前列腺癌骨转移瘤的灵敏度分别为100%、94.4%、77.8%,准确性分别为95.2%、87.0%、71.4%。18f-Na f PET/CT骨显像的准确性显著高于18f-Na f PET和单独CT(P<0.05)。结论18f-Na f PET/CT对前列腺癌骨转移诊断的灵敏度、特异性、准确性较高。

关键词：前列腺癌骨转移 18f-Na f PET/CT

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Rationalising the supply-and-demand cross, 1838-1890

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EUROPEAN JOURNAL Of THE HISTORY Of ECONOMIC THOUGHT 2020年第2期27卷 194-208页

作者： Aspromourgos, Tony Univ Sydney Sch Econ Sydney NSW 2006 Australia

This study takes its bearings from the proposition that the supply-and-demand apparatus of what came to be called the "Marshallian cross" is an unsatisfactory representation of actual supply and demand forces, which are better characterised in the manner of the classical economists. from that point of departure it then enquires into how that representation nevertheless arose in the period from 1838 to 1890, notwithstanding its lack of robustness as economic theory - via consideration of the economics of five key contributors prior to Marshall. The investigation confirms that there is no plausible basis for a general presumption in favour of the conventional rising supply function - other than the marginal productivity theory of factor pricing, which is itself unsatisfactory.

关键词： A -A Cournot f Jenkin H K E von Mangoldt rising supply-price K H Rau

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Progress on research of tissue culture of Bletilla striata

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Chinese Herbal Medicines 2018年第1期10卷 23-26页

作者： Xue-Min Wei Yang Liu Xiao-Yue Wang Zi-Tong Gao Shu-Ming Yao Jian-Ping Han Institute of Medicinal Plant Development Chinese Academy of Medical Sciences & Peking Union Medical CollegeBeijing 100193China Qingdao Guofeng Pharmaceutical Co. Ltdqingdao 266071China

Rhizoma Bletillae is in high demand as a traditional Chinese medicine, and the natural resources have been severely damaged due to excessive exploitation. Because Bletilla striata seeds are small and have no endosperm, the seed germination rate is low in natural conditions. Traditional division propagation could not meet the demands of large-scale cultivation. Tissue culture can provide many seedlings in a short time and is more effective and convenient than other methods. Most studies on tissue culture of B. striata selected seeds as explants. This review summarized the processes of the aseptic seed germination pathway. It included such stages as seed germination, proliferation of clusters of buds, induction of root- ing and transplanting of seedlings. Influential factors as well as optimum combination and concentration of the plant growth regulators of each stage were also summarized. The further research on tissue culture of B. striata was also prospected.

关键词： Aseptic seed germination Bletilla striata （Thunb.） Reichb f research progress tissue culture

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Procoagulant extracellular vesicles in amniotic fluid

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TRANSLATIONAL RESEARCH 2017年 184卷 12-20页

作者： Hell, Lena Wisgrill, Lukas Ay, Cihan Spitiler, Andreas Schwameis, Michael Jilma, Bernd Pabinger, Ingrid Altevogt, Peter Thaler, Johannes Med Univ Vienna Dept Med 1 Clin Div Haematol & Haemostaseol Waehringer Guertel 18-20 A-1090 Vienna Austria Med Univ Vienna Dept Paediat & Adolescent Med Clin Div Neonatol Paediat Intens Care & Neuropaed Vienna Austria Med Univ Vienna Dept Surg Vienna Austria Med Univ Vienna Dept Clin Pharmacol Vienna Austria German Canc Res Ctr Tumor Immunol Programme Heidelberg Germany

Embolization of amniotic fluid (Af) into the blood circulation leads to disseminated intravascular coagulation (DIC). Procoagulant phosphatidylserine (PS)- and tissue factor (Tf)-exposing extracellular vesicles (EVs) might play an important role in Af embolism-induced DIC. It was the aim of the present study to perform analyses of the procoagulant properties of Af with a panel of functional coagulation assays and flow cytometry. We applied a prothrombinase assay (that quantifies PS exposure on EVs), an EV-associated Tf activity assay, a fibrin generation assay, a thrombin generation assay, a whole blood clotting model, and flow cytometry in Af and control plasma. We found that PS exposure on EVs was 21-fold increased in Af compared with plasma. Also, EV-associated Tf activity was highly increased in Af compared with plasma. Af-derived EVs activated the blood coagulation cascade via PS and Tf in the fibrin and thrombin generation assays. In a whole blood clotting model, Af-derived EVs significantly shortened the clotting time from 734 139 seconds in the presence to 232 139 seconds in the absence of an anti-If antibody. The contact activation pathway via factor XII (fXII) was not affected. Applying flow cytometry, a sub population of PS+ and Tf+ EVs was identified in Af but not in control plasma. In conclusion, we investigated the effect of Af on blood coagulation and found that PS+ and Tf+ EVs determine their procoagulant potential. Taken together, our data further delineate the pathomechanisms underlying Af-induced coagulopathy.

关键词： Af amniotic fluid EVs extracellular vesicles DIC disseminated intravascular coagulation f factor NPP normal pooled plasma PS phosphatidylserine Tf tissue factor

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Benzophenone as a photoprobe of polymer films

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CHEMICAL PHYSICS 2017年 495卷 23-28页

作者： Levin, Peter P. Efremkin, Alexei f. Khudyakov, Igor V. Russian Acad Sci Emanuel Inst Biochem Phys Moscow 11933 Russia Russian Acad Sci Semenov Inst Chem Phys Moscow 119334 Russia Columbia Univ Dept Chem New York NY 10027 USA

The review article is devoted to kinetics of fast reactions following photoexcitation of benzophenone in polymer films. We observed three processes by ns laser flash photolysis in elastomers: (i) decay of a triple state of benzophenone with hydrogen abstraction from polymer matrix, (ii) formation and decay of geminate radical pairs, (iii) cross-termination of the formed radicals in the polymer bulk. Application of external magnetic field (Mf) of B = 0.2 T essentially affects recombination of geminate (G-) and a bimolecular recombination of free radicals, which escaped polymer cage (f-pairs). Theoretical calculation of Mf effects on G-and f-pairs is in agreement with corresponding experimental data. Elongation of elastomer leads to an unexpected observation: recombination in the bulk becomes slower. An explanation of this phenomenon based on elastomer free volume V-f approach was suggested. (c) 2017 Elsevier B.V. All rights reserved.

关键词： B benzophenone 3 B benzophenone in a triplet state BH ketyl free radical of benzophenone E film of poly(ethylene- co -butylene), an elastomer l o initial thickness of a film E prior elongation l the measured thickness of an elongated E film O.D. optical density D BH diffusion coefficient of BH in a polymer film G-pair A pair of free radicals formed as a result of photochemical reaction. Here a reaction is a hydrogen atom abstraction f-pair A pair of free radicals encountered each other as a result of random wandering in the solvent bulk. Here solvent is polymer Mf external magnetic field. In this paper B = 0.2 T MfE magnetic field effect p probability of recombination of f-pairs RP RP, radical pair V f free volume of polymer φ cage effect value, or probability of recombination of G-pairs

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车王搭档 2016 BMW f 800 R

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摩托车 2016年第5期 38-41页

作者：孙慕溪

作为摩友,克里斯·菲佛应该知道吧？这位特技车王,多次摘取了世界特技比赛冠军的桂冠,各种扣人心弦的惊险动作,让人手心捏汗、目瞪口呆!同时,克里斯·菲佛的出镜率也非常高,频频出现在各种重要活动上,单轮行驶、翘尾、原地转固... 详细信息

作为摩友,克里斯·菲佛应该知道吧？这位特技车王,多次摘取了世界特技比赛冠军的桂冠,各种扣人心弦的惊险动作,让人手心捏汗、目瞪口呆!同时,克里斯·菲佛的出镜率也非常高,频频出现在各种重要活动上,单轮行驶、翘尾、原地转固、烧胎……各种精彩的特技表演,让观众们眼界大开、尖叫不已!与他一起翩然起舞、一起腾挪跳跃,为他赢取了无数鲜花和荣誉的亲密伙伴,是宝马的并列双缸,拥有动力暴、操控轻、结构紧凑等优点,优秀的平衡性能让菲佛挥洒自如、车随心动!这就是——2016 BMW f 800 R，

关键词：出镜率眼界大开 BMW f 800 R 单轮翘尾平衡锤悬挂性能悬挂系统点火时间平衡轴

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白细胞介素-33在过敏性哮喘小鼠体内的变化及作用

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中国寄生虫学与寄生虫病杂志 2018年第2期36卷 124-128,134页

作者：柴强宋红玉李朝品皖南医学院医学寄生虫学教研室芜湖241002

目的探讨白细胞介素-33(IL-33)在粉尘螨1类变应原(Der f 1)诱导的过敏性哮喘小鼠中的变化及作用。方法将40只雌性BALB/c小鼠用随机数字表法分为哮喘组、免疫治疗组、抑制剂组和阴性对照组(PBS组),每组10只。哮喘组、免疫治疗组和抑制剂... 详细信息

目的探讨白细胞介素-33(IL-33)在粉尘螨1类变应原(Der f 1)诱导的过敏性哮喘小鼠中的变化及作用。方法将40只雌性BALB/c小鼠用随机数字表法分为哮喘组、免疫治疗组、抑制剂组和阴性对照组(PBS组),每组10只。哮喘组、免疫治疗组和抑制剂组分别在第0、7和14天腹腔注射100μl粉尘螨变应原提取液(含100μg/ml Der f 1),抑制剂组小鼠同时注射抑制剂(可溶性ST2 100μl,用于抑制IL-33),PBS组注射等量PBS。第21天起,各组小鼠雾化吸入粉尘螨变应原提取液(0.5μg/ml),30 min/次,1次/d,连续7 d。免疫治疗组小鼠第25天起于雾化前0.5 h,分别用200μl的Der f 1蛋白溶液(100μg/ml)腹腔注射进行免疫治疗,PBS组用PBS代替粉尘螨变应原。第27天雾化吸入后24 h处死小鼠,收集小鼠支气管肺泡灌洗液(BALf)和眼球血,并对BALf中嗜酸粒细胞进行计数,制作肺组织病理切片。ELISA法检测BALf中IL-5、IL-13和γ干扰素(IfN-γ)的含量及血清中特异性Ig E和Ig G2a水平。结果除PBS组小鼠外,其他组小鼠自第21天开始出现不同程度的哮喘症状。自第25天开始,免疫治疗组小鼠的哮喘症状开始缓解。哮喘组和PBS组小鼠BALf中嗜酸粒细胞总数分别为(4.41±0.36)×10~5/ml和(0.37±0.08)×10~5/ml,两组差异有统计学意义(t=24.50,P<0.01);免疫治疗组和抑制剂组小鼠的嗜酸粒细胞总数分别为(1.43±0.14)×10~5/ml和(2.73±0.33)×10~5/ml,均明显低于哮喘组(f=129.72,P<0.01)。ELISA检测结果显示,哮喘组、免疫治疗组、抑制剂组和PBS组BALf中IfN-γ的水平分别为(83.06±11.38)、(277.97±22.46)、(175.13±13.41)和(224.77±19.97)pg/ml,免疫治疗组和抑制剂组均明显高于哮喘组(t=17.31,t=11.71,P<0.01)。哮喘组、免疫治疗组、抑制剂组和PBS组小鼠BALf中IL-5水平分别为(208.64±11.55)、(106.87±11.39)、(140.71±14.58)和(90.15±9.49)pg/ml,哮喘组的水平明显高于其他各组(f=97.19,P<0.01)。哮喘组和免疫治疗组BALf中IL-13水平分别为(308.37±13.67)pg/ml和(175.66±11.79)pg/ml,两者差异有统计学意义(P<0.01);抑制剂组小鼠的为(221.12±21.08)pg/ml,明显低于哮喘组(t=16.44,P<0.01);PBS组为(97.57±18.38)pg/ml。免疫治疗组与哮喘组相比,小鼠肺部炎性症状均减轻,几乎无炎症细胞。抑制剂组小鼠的支气管周围也有嗜酸粒细胞增多症、上皮细胞脱落和支气管上皮细胞肥大,但较哮喘组要减轻许多。血清Ig E抗体水平的检测结果显示,哮喘组、免疫治疗组、抑制剂组和PBS组分别为(31.97±3.48)、(12.86±2.22)、(18.43±2.30)和(9.68±1.27)IU/ml,免疫治疗组和抑制剂组均低于哮喘组(t=-7.77,P<0.01)。Ig G2a抗体水平的变化和Ig E相反,哮喘组、免疫治疗组和PBS组分别为(26.94±2.96)、(35.06±2.57)和(10.31±1.48)μg/ml,免疫治疗组高于哮喘组(t=6.55,P<0.01)。结论 ELISA检测结果表明IL-33/ST2信号通路在小鼠过敏性哮喘中发挥着重要的作用。

关键词：粉尘螨 Der f 1蛋白过敏性哮喘白细胞介素-33

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Multiple plasmid interference - Pledging allegiance to my enemy's enemy

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PLASMID 2017年 93卷 17-23页

作者： Gama, Joao Alves Zilhao, Rita Dionisio, francisco Univ Lisbon Fac Ciencias cE3c P-1749016 Lisbon Portugal Inst Gulbenkian Ciencias Oeiras Portugal Univ Lisbon Dept Biol Vegetal Fac Ciencias Edificio 2Piso 2 P-1749016 Lisbon Portugal

As shown in the previous article, two distinct conjugative plasmids sometimes interact within bacterial cells, implicating changes of transfer rates. In most cases of interactions within bacteria, the transfer of one of the plasmids decreases. Less frequently, the transfer rate of one of the plasmids increases. Here we analyse what happens if three distinct conjugative plasmids colonize the same bacterial cell. Our aim is to understand how interactions between two plasmids affect the transfer rate of the third plasmid. After showing that plasmids interact in 59 out of 84 possible interactions we show that, with some exceptions, if the transfer rate of a plasmid decreases in the presence of a second plasmid, a decrease is also observed in the presence of a third plasmid. Moreover, if the conjugation rate of a plasmid increases in the presence of another, an increase is also observed if there is a third plasmid in the cell. Both types of interactions are mostly independent of the third plasmid's identity, even if sometimes the third plasmid quantitatively distorts the interaction of the other two plasmids. There is a bias towards negative intensifying interactions, which provide good news concerning the spread conjugative plasmids encoding antibiotic-resistance genes and virulence factors.

关键词： Escherichia coli Conjugative plasmids Transfer rate f R1 R1drd19 R124 R6K RP4 R702 R477-1 R57b R16a R388 RN3

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