代谢型谷氨酸受体4亚型(mGluR4)高通量药物筛选模型的建立

为发现代谢型谷氨酸受体4亚型(mGluR4)的调节剂,通过荧光检测胞内钙浓度的方法,建立一个基于细胞功能性检测的高通量筛选(HTS)系统。将人mGluR4基因转染稳定表达Gα15蛋白的人胚肾细胞(HEK-293),用Zeocin筛选获得稳定表达mGluR4的细胞株,并通过钙流检测试验证实该细胞系的生物学功能。优化了实验系统中荧光染料的孵育时间,溶剂二甲基亚砜(DMSO)耐受性,以及溶剂氢氧化钠(NaOH)耐受性,建立了可靠稳定的筛选系统。钙流检测试验数据表明,mGluR4细胞系对其激动剂的活性程度排序是:L-(+)-2-Amino-4-phosphonobutyricacid(L-AP4)>L-Serine-O-phosphate(L-SOP)>L-Glutamicacid(L-Glu);拮抗剂是:(RS)-α-Methylserine-O-phosphate(MSOP)>(RS)-α-Methyl-4-phosphonophenylglycine(MPPG)。在96和384细胞微孔培养板中,得到该筛选系统Z’因子分别是0.80和0.65。结果表明,该稳定细胞系拥有一个稳定的检测系统,适合于mGluR4激动剂...     

Identification of conjugated estrogen metabolites in dog plasma following administration of estriol-2,4,6,7-3H.

Following the constant infusion of 2,4,6,7-3H-estriol in male dogs for a period of 90 minutes, the radioactive metabolites present in arterial plasma were separated by solvent partition, DEAE-Sephadex, Celite partition and thin layer chromatography. The identities of the individual estrogens and estrogen conjugates were confirmed by specific activity determinations after chromatography in several different solvent systems, enzyme hydrolysis and chromatography of the unconjugated steroids and their derivatives.     

Effects of testosterone on the behavior of male cynomolgus monkeys (Macaca fascicularis)

To determine the threshold doses of testosterone propionate (TP) that cause clear-cut behavioral changes in the sexual behavior of castrated male cynomolgus monkeys, observations were made on three males during successive 5-week treatment periods while they received daily subcutaneous doses of 100 μg TP increasing in octaves to 25.6 mg TP. Males were tested with each of the same two ovariectomized, estrogen-treated females (6 pairs, 330 1-hr behavior tests). To mimic the diurnal plasma testosterone rhythm, TP injections were given at 1600 hr and blood samples were obtained at 0800 hr (141 samples). Male ejaculatory activity increased at the threshold dose of 200 μg TP per day giving plasma testosterone levels of 830 ng/100 ml, which is in the physiological range of 600–1600 ng/100 ml for intact males. This threshold dose was eight times higher than in rhesus monkeys on a dose per kilogram body weight basis. There was a further marked increase in ejaculatory performance at higher doses (6.4 to 25.6 mg) giving supraphysiological plasma levels of 4000–9000 ng/100 ml. There were individual differences in the behavioral changes occurring with TP treatment, and the female partner modulated the effects. These findings were generally similar to those obtained with male rhesus monkeys, but certain species differences were noted.     

The role of divalent cations in interactions between lymphokines and macrophages

The divalent cation requirements of lymphokine-mediated alterations in macrophage function (activation and inhibition of migration) were examined. Normal rabbit alveolar macrophages exposed to incubation supernatants of antigen-stimulated sensitized lymphocytes (lymphokine) were activated, manifested by increased adherence and enhanced bactericidal activity, as compared with control cells. This lymphokine-mediated activation was dependent upon the presence of extracellular Mg²⁺ (but not Ca²⁺). Our data from both current and previous studies suggest that Mg²⁺ influx is necessary for initiation or support of the macrophage activation process. The divalent cation requirements for lymphokine (MIF)-induced inhibition of macrophage migration differed from that of the activation phenomenon. Specifically, both Ca²⁺ and Mg²⁺ were required for expression of MIF activity. Adsorption experiments indicate that these cations are needed for binding of MIF to the macrophage surface.     

In Situ Generated Fireproof Gel Polymer Electrolyte with Li6.4Ga0.2La3Zr2O12 As Initiator and Ion‐Conductive Filler

Poly(vinylidene fluoride‐co‐hexafluoropropylene) (PVDF‐HFP) based gel polymer electrolyte is regarded as a promising candidate to settle the safety issues of liquid electrolytes. However, the currently reported gel polymer electrolytes are still not safe enough owing to high amount of flammable liquid solvents contained in them. Herein, a fireproof PVDF‐HFP based gel polymer electrolyte is designed and synthesized through an in situ crosslinking method, with Li_6.4Ga_0.2La₃Zr₂O₁₂ as initiator and ion‐conductive filler. The obtained gel polymer electrolyte demonstrates superior fire resisting properties. The optimized gel polymer electrolyte exhibits an ionic conductivity as high as 1.84 × 10^?3 S cm^?1 at 20 °C with an electrochemical window up to 4.75 V at room temperature. Moreover, the obtained gel polymer electrolyte shows excellent compatibility with lithium anodes. Therefore, the lithium anode is well protected. Lithium batteries assembled with the gel polymer electrolyte possess superb safety properties in cutting and burning tests. Furthermore, the batteries also show a discharge retention rate as high as 94.08% (in comparison with the initial discharge capacity) after cycling at 0.5 C for 360 cycles with an average columbic efficiency higher than 98%. The purpose of this report is to show the great potential of applying fire‐retardant gel polymer electrolyte to achieve high safety lithium batteries.