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        Pharmacokinetics of Carbamazepine Polymorphs and Dihydrate in Rats, Related to Dogs and Humans

        Caihong Xu,Gang Cheng,Meijuan Zou,Yi Liu,Jungang Ren,Ye Tian,Jing Yan,Yiping Wang 대한약학회 2011 Archives of Pharmacal Research Vol.34 No.11

        Species differences in the oral pharmacokinetics and absolute bioavailability (F_abs) of carbamazepine polymorphs (form I and form III) and dihydrate were studied. The pharmacokinetics of each form was investigated in rats following a single oral/intravenous administration of 10 mg/kg and an oral dose of 80 mg/kg, which were compared with the published data obtained from dogs and humans. No significant differences were found in their C_max, T_max, AUC_(0-∞) and F_abs among the forms at the low dose. However, significant differences were observed at the high dose. The F_abs of each form was markedly reduced with increasing of doses in species (e.g. F_abs in rats ranged from > 82% to 38.4% - 56.0%). At a comparable dose, the C_max, and AUC_(0-∞)of rats and humans were about 3-10 times higher than in dogs. The absorption rate of form III in rats exhibited a similar trend to that in humans, and was far higher in dogs. A multi-peak phenomenon in plasma curves was observed in rats and humans, but not in dogs. In conclusion, rats appear to be a better predictor of carbamazepine polymorphs absorbed in humans,and form III may be more suitable as a pharmaceutical crystal.

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        A New Method for Determination of 3D Active Earth Pressure of Unsaturated Backfills

        Long Wang,Meijuan Xu,Jie Li,Wenhua Liu,De’an Sun 대한토목학회 2021 KSCE JOURNAL OF CIVIL ENGINEERING Vol.25 No.12

        Determinations of active earth pressures are commonly performed two-dimensionally (2D) based on completely saturated and/or dry assumptions, though the soil in cases of geotechnical interest is mostly unsaturated and the earth pressures are usually of conspicuous three-dimensional (3D) features. In this paper, a novel finite prismoid element method (FPEM) for calculating the lateral earth pressures acting against the retaining wall is suggested. The main feature of the FPEM is that the whole backfill is discretized into numerous horizontally distributed prismoid elements that might characterized with different soil properties. For unsaturated backfills, the prismoid elements are characterized with various soil cohesions and unit soil weights. Upper bound solutions to active earth pressures under 2D and 3D conditions with and without suction are both calculated and compared with several other analytical ones, indicating the reliability and applicability of the proposed method. The responses of unsaturated backfills to surcharge loads on the crest are numerically studied and discussed. An illustrative example is reexamined to further demonstrate the practical use of the technique.

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        LincR-PPP2R5C Promotes Th2 Cell Differentiation Through PPP2R5C/PP2A by Forming an RNA–DNA Triplex in Allergic Asthma

        Ji Ningfei,Chen Zhongqi,Wang Zhengxia,Sun Wei,Yuan Qi,Zhang Xijie,Jia Xinyu,Wu Jingjing,Jiang Jingxian,Song Meijuan,Xu Tingting,Liu Yanan,Ma Qiyun,Sun Zhixiao,Bao Yanmin,Zhang Mingshun,Huang Mao 대한천식알레르기학회 2024 Allergy, Asthma & Immunology Research Vol.16 No.1

        Purpose: The roles and mechanisms of long noncoding RNAs (lncRNAs) in T helper 2 (Th2) differentiation from allergic asthma are poorly understood. We aimed to explore a novel lncRNA, LincR-protein phosphatase 2 regulatory subunit B' gamma (PPP2R5C), in Th2 differentiation in a mouse model of asthma. Methods: LincR-PPP2R5C from RNA-seq data of CD4+ T cells of asthma-like mice were validated and confirmed by quantitative reverse transcription polymerase chain reaction, northern blotting, nuclear and cytoplasmic separation, and fluorescence in situ hybridization (FISH). Lentiviruses encoding LincR-PPP2R5C or shRNA were used to overexpress or silence LincR-PPP2R5C in CD4+ T cells. The interactions between LincR-PPP2R5C and PPP2R5C were explored with western blotting, chromatin isolation by RNA purification assay, and fluorescence resonance energy transfer. An ovalbumin-induced acute asthma model in knockout (KO) mice (LincR-PPP2R5C KO, CD4 conditional LincR-PPP2R5C KO) was established to explore the roles of LincR-PPP2R5C in Th2 differentiation. Results: LncR-PPP2R5C was significantly higher in CD4+ T cells from asthmatic mice ex vivo and Th2 cells in vitro. The lentivirus encoding LincR-PPP2R5C suppressed Th1 differentiation; in contrast, the short hairpin RNA (shRNA) lentivirus decreased LincR-PPP2R5C and Th2 differentiation. Mechanistically, LincR-PPP2R5C deficiency suppressed the phosphatase activity of the protein phosphatase 2A (PP2A) holocomplex, resulting in a decline in Th2 differentiation. The formation of an RNA-DNA triplex between LincR-PPP2R5C and the PPP2R5C promoter enhanced PPP2R5C expression and activated PP2A. LincR-PPP2R5C KO and CD4 conditional KO decreased Th2 differentiation, airway hyperresponsiveness and inflammatory responses. Conclusions: LincR-PPP2R5C regulated PPP2R5C expression and PP2A activity by forming an RNA-DNA triplex with the PPP2R5C promoter, leading to Th2 polarization in a mouse model of acute asthma. Our data presented the first definitive evidence of lncRNAs in the regulation of Th2 cells in asthma.

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