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Dengqi Xue Yani Liu Yilin Zheng Heling Niu Liying Dong Xiangshuo Ouyang Siyu Song Denggao Zhang Qianwei Ge Kewei Wang Liming Shao 《中国化学快报》2022,33(3):1643-1646
Three novel series of α-aminoamides derivatives were designed and synthesized based on ralfinamide,and their Nav1.7 inhibitory activities were evaluated using manual patch clamp electrophysiology. Active compounds inhibited Nav1.7 with half maximal inhibitory concentration(IC50) values ranging from2.9 μmol/L to 21.4 μmol/L. Among them, the most potent compound 19h exhibited about 12-fold potency better than ralfinamide. The investigation of their structure-activity relationship gives a strategy ... 相似文献
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《中国化学快报》2020,31(12):3183-3189
Engineered nanomaterials have attracted significantly attention as one of the most promising antimicrobial agents for against multidrug resistant infections. The toxicological responses of nanomaterials are closely related to their physicochemical properties, and establishment of a structure-activity relationship for nanomaterials at the nano-bio interface is of great significance for deep understanding antibacterial toxicity mechanisms of nanomaterials and designing safer antibacterial nanomaterials. In this study, the antibacterial behaviors of well-defined crystallographic facets of a series of Au nanocrystals, including {100}-facet cubes, {110}-facet rhombic dodecahedra, {111}-facet octahedra, {221}-facet trisoctahedra and {720}-facet concave cubes, was investigated, using the model bacteria Staphylococcus aureus. We find that Au nanocrystals display substantial facet-dependent antibacterial activities. The low-index facets of cubes, octahedra, and rhombic dodecahedra show considerable antibacterial activity, whereas the high-index facets of trisoctahedra and concave cubes remained inert under biological conditions. This result is in stark contrast to the previous paradigm that the high-index facets were considered to have higher bioactivity as compared with low-index facets. The antibacterial mechanism studies have shown that the facet-dependent antibacterial behaviors of Au nanocrystals are mainly caused by differential bacterial membrane damage as well as inhibition of cellular enzymatic activity and energy metabolism. The faceted Au nanocrystals are unique in that they do not induce generation of reactive oxygen species, as validated for most antibiotics and antimicrobial nanostructures. Our findings may provide a deeper understanding of facet-dependent toxicological responses and suggest the complexities of the nanomaterial-cell interactions, shedding some light on the development of high performance Au nanomaterials-based antibacterial therapeutics. 相似文献
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Nonlinear Dynamics - A complex system’s structural–dynamical interplay plays a profound role in determining its collective behavior. Irregular behavior in the form of macroscopic chaos,... 相似文献
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PurposeTo evaluate the diagnostic performance of a multiparametric approach to breast lesions including apparent diffusion coefficient (ADC) from diffusion-weighted images (DWI), maximum slope (MS) from ultrafast dynamic contrast enhanced (UF-DCE) MRI, lesion size, and patient's age.Materials and methodsIn total, 96 lesions (73 malignant, 23 benign) were evaluated. UF-DCE MRI was acquired using a prototype 3D-gradient-echo volumetric interpolated breath-hold examination (VIBE) with compressed sensing. Images were obtained up to 1 min after gadolinium injection. MS was calculated as the percentage relative enhancement/s. An ADC map was automatically generated from DWI at b = 0 and b = 1000 s/mm2. MS and ADC values were measured by two radiologists independently. Interrater agreement was evaluated using intraclass correlation coefficients. Univariate and multivariate logistic regression analyses were performed using MS, ADC, lesion size, and the patient's age. The parameters of the prediction model were generated from the results of the multivariate logistic regression analysis. Area under the curve (AUC) was used to compare diagnostic performance of the prediction model and each parameter.ResultsInterrater agreements on MS and ADC were excellent (ICC 0.99 and 0.88, respectively). MS, ADC, and patient's age remained as significant parameters after univariate and multivariate logistic regression analysis. The prediction model using these significant parameters yielded an AUC of 0.90, significantly higher than that of MS (AUC 0.74, p = 0.01). The AUCs of ADC, MS, patient's age were 0.87, 0.74 and 0.73, respectively.ConclusionsA multiparametric model using ADC from DWI, MS from UF-DCE MRI, and patient's age showed excellent diagnostic performance, with greater contribution of ADC. Combining DWI and UF-DCE MRI might reduce scanning time while preserving diagnostic performance. 相似文献
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Development of an LC‐MS/MS method for determining the pharmacokinetics of clonidine following oral administration of Zhenju antihypertensive compound 下载免费PDF全文
Jing Qin Limin Wang Lihong Wu Jun Chen Teng Shen Yongji Li Limei Han Jianxin Wang 《Biomedical chromatography : BMC》2015,29(7):1068-1075
Zhenju antihypertensive compound (ZJAHC) is a combined Chinese–Western medicine formula including clonidine (CLO), hydrochlorothiazide (HCT), rutin, Chrysanthemum indicum extract and pearl powder. Compared with CLO preparations, ZJAHC shows improved activities and decreased adverse effects. It is believed that the side effects of CLO are caused by its high peak plasma concentration. Hence, study of the influence of ZJAHC on the pharmacokinetic behaviors of clonidine seems essential. In present study, the plasma concentrations of CLO were determined with a liquid chromatography–tandem mass spectrometry (LC‐MS/MS) method. The MS/MS transitions monitored for clonidine and internal standard were 230.2 → 213.1 and 152.2 → 110.2, respectively. The analyte was quantified in a single run within 3 min. The pharmacokinetic study showed that the area under the plasma concentration–time curve of CLO in ZJAHC (60 µg/kg CLO) was similar to that of CLO‐HCT‐high (120 µg/kg CLO) but the peak concentration was much lower than that in CLO‐HCT‐high. ZJAHC could enhance the bioavailability without greatly increasing peak concentration of clonidine. This comprehensive effect of enhancing the bioavailability and avoiding the high peak plasma concentration for CLO might mainly result from the co‐contribution of Western medicine and traditional Chinese medicine (TCM), while the effect of TCM was stronger than that of Western medicine. Copyright © 2014 John Wiley & Sons, Ltd. 相似文献
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