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| 1 | Molecular mechanism underlying the subtype-selectivity of competitive inhibitor NF110 and its distinct potencies in human and rat P2X3 receptors显示文摘P2X receptors are a family of extracellular ATP-gated trimeric cation channels that is widely distributed in human tissues. Quite some drug candidates targeting P2X receptors have entered into preclinical or main phases of clinical trials, but many of them failed due to low subtype-selectivity or species differences in pharmacological activities between human and experimental animals. Here, we identified the distinct inhibitory efficacies of NF110, a competitive inhibitor, between the rat(rP2X3) and human(hP2X3) P2X3 receptors. We demonstrated that this difference is determined by two amino acids located in the dorsal fin(DF) domain of P2X3 receptors. As revealed by mutagenesis, metadynamics, and covalent modification, NF110-mediated rP2X3 inhibition may be through a filling in the cavity formed by the DF,left flipper(LF) and lower body(LB) to partially, rather than fully, occupy the ATP-binding pocket.Moreover, substitution of residues located in the DF and/or LF domains of the rP2X2 receptor, a NF110-insensitive subtype, with the equivalent amino acids of rP2X3, bestowed the sensitivity of rP2X2 to NF110. The critical roles of the DF and LF domains in channel gating of P2X and low conservativity in residue sequences of those two domains raise the possibility that small molecules differentially interacting with the residues of the DF and LF domains of different P2X receptors may modulate channel's activity in a subtype-selective manner. However, the possible species-specificity of P2X inhibitors/modulators makes it more complex when interpreting the preclinical data into clinical researches.Nevertheless, our data provide new insights into the subtype-selectivity of competitive inhibitors and their distinct potencies in the human and experimental animals, both of which are extremely important in the drug discovery of P2X receptors. | Bin Li Jin Wang Xiaoyang Cheng Yan Liu Yang Yang Xiaona Yang Changrun Guod Youya Niu Peng Cao Xiangyang Lu Michael X.Zhu Yun Tian Ye Yu | 2018 | Science Bulletin2018，63，24： | 1 |
| 2 | The interplay between hepatocyte nuclear factor 4α(HNF4α)and cholesterol sulfotransferase(SULT2B1b)in hepatic energy homeostasis显示文摘The nuclear receptor hepatocyte nuclear factor 4alpha(HNF4α)plays a critical role in the regulation of metabolic homeostasis,including glucose homeostasis.Sulfotransferases(SULTs)catalyze the transfer of a sulfate group from 3-phosphoadenosine 5-phosphosulfate(PAPS)to an acceptor molecule.Sulfonation plays an essential role in regulating the chemical and functional homeostasis of endogenous and exogenous molecules.Among SULTs,the cholesterol sulfotransferase 2B1b(SULT2B1b)preferentially catalyzes the sulfoconjugation of cholesterol and oxysterols to form cholesterol sulfate and oxysterol sulfates.Hepatic gluconeogenesis represents a critical component of energy metabolism.Although there have been reviews on the regulation of glucose homeostasis by HNF4a,the interplay between HNF4a and SULT2B1b in hepatic glucose homeostasis remains scattered.In this review,we intend to provide an overview on how HNF4a functionally cross-talks with SULT2B1b to regulate hepatic glucose homeostasis and whether the HNF4a-SULT2B1b axis represents a novel therapeutic target for the management of metabolic liver disease and metabolic syndrome. | Yuhan Bi Youya Wang Wen Xie | 2019 | Liver Research2019，3，3： | 1 |
| 3 | X-site doping in ABX_(3) triggers phase transition and higher T_(c) of the dielectric switch in perovskite显示文摘Material stability is always the key factor for applied materials especially the working environment that requires higher temperature sensitivity or temperature fluctuation range.In which,the stimulus-response perovskite materials are just sensitive to stability to ensure the accuracy and stability of the signals,in the applied devices of batteries and memory storage devices and so on.However,it is still a tremendous challenge to improve the stability of perovskite materials,and maintain reliability in the devices.Here,a novel ABX_(2)X'_(1)(X-site doping in an ABX_(3))compound[CEMP]-[CdBr_(2)(SCN)](1,CEMP=1-(2-chloro-ethyl)-1-methyl-piperidine)with remarkable high-temperature reversible dielectric switching behavior was proposed.The strategy of[SCN]^(−)doping in perovskite for improving the stability was successfully achieved.Meanwhile,the steric hindrance is increased while the energy barrier is also increased by replacing hydrogen with flexible groups,which leads to a high-temperature reversible phase transition.The new finding provides a new direction to enrich new applications and design ideas of perovskite materials.Especially the X-site strategy of doping or substitution in the ABX_(3),it will promote ingenious and perfect experimental results in material synthesis and performance improvement by chemistry disciplines. | Youya Yu Peizhi Huang Yuzhen Wang Zhixu Zhang Tie Zhang Yi Zhang Dawei Fu | 2021 | Chinese Chemical Letters2021，32，11： | 1 |
| 4 | Mass transfer characteristics of chiral pharmaceuticals on membrane used for polar organic chemical integrative sampler显示文摘Passive sampling technology has good application prospects for monitoring trace pollutants in aquatic environments.Further research on the sampling mechanism of this technology is essential to improve the measurement accuracy and extend the application scope of this approach.In this study,adsorption and permeation experiments were performed to investigate the sorption and mass transfer properties of five chiral pharmaceuticals at the enantiomeric level on polyethersulfone(PES)and polytetrafluoroethylene(PTFE)membranes used in a polar organic chemical integrative sampler.Batch adsorption experiments showed that the PES membrane had an adsorption phenomenon for most selected pollutants and an insignificant sorption behavior was observed for all selected pharmaceuticals on the PTFE membrane except for R(S)-fluoxetine.The diffusion coefficients of selected pharmaceuticals onto the PTFE membrane were approximately one order of magnitude higher than those onto the PES membrane.The permeation experiment indicated that under different hydraulic conditions,the change of the relative pollutant concentration through the PTFE membrane for the composite pollutant system was more obvious than that for the single pollutant system,and mass transfer hysteresis exists for both contaminant systems through PES membranes.Using the first-order equation or 3-component model to estimate the overall mass transfer coefficients,the results showed that the overall mass transfer coefficient values of pollutants in the composite pollutant system onto both membranes were higher than those in the single pollutant system.This parameter was mainly influenced by the synergistic effects of the multi-analyte interaction and diminished water boundary layers during the mass transfer process. | Liyang Wang Ruixia Liu Youya Zhou Peng Yuan Xiaoling Liu Hongjie Gao | 2024 | Journal of Environmental Sciences2024，，2： | 0 |
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