| 1 | The interaction between polyphyllin I and SQLE protein induces hepatotoxicity through SREBP-2/HMGCR/SQLE/LSS pathway显示文摘Polyphyllin I(PPI)and polyphyllin II(PII)are the main active substances in the Paris polyphylla.However,liver toxicity of these compounds has impeded their clinical application and the potential hepatotoxicity mechanisms remain to be elucidated.In this work,we found that PPI and PII exposure could induce significant hepatotoxicity in human liver cell line L-02 and zebrafish in a dose-dependent manner.The results of the proteomic analysis in L-02 cells and transcriptome in zebrafish indicated that the hepatotoxicity of PPI and PII was associated with the cholesterol biosynthetic pathway disorders,which were alleviated by the cholesterol biosynthesis inhibitor lovastatin.Additionally,3-hydroxy-3-methy-lglutaryl CoA reductase(HMGCR)and squalene epoxidase(SQLE),the two rate-limiting enzymes in the cholesterol synthesis,selected as the potential targets,were confirmed by the molecular docking,the overexpression,and knockdown of HMGCR or SQLE with siRNA.Finally,the pull-down and surface plasmon resonance technology revealed that PPI could directly bind with SQLE but not with HMGCR.Collectively,these data demonstrated that PPI-induced hepatotoxicity resulted from the direct binding with SQLE protein and impaired the sterol-regulatory element binding protein 2/HMGCR/SQLE/lanosterol synthase pathways,thus disturbing the cholesterol biosynthesis pathway.The findings of this research can contribute to a better understanding of the key role of SQLE as a potential target in drug-induced hepatotoxicity and provide a therapeutic strategy for the prevention of drug toxic effects with similar structures in the future. | Zhiqi Li Qiqi Fan Meilin Chen Ying Dong Farong Li Mingshuang Wang Yulin Gu Simin Guo Xianwen Ye Jiarui Wu Shengyun Dai Ruichao Lin Chongjun Zhao | 2023 | Journal of Pharmaceutical Analysis2023，13，1： | 2 |
| 2 | Molten metal-organic complex to synthesize versatile ultrathin nonlayered oxides显示文摘Two-dimensional(2D)materials have attracted a great deal of research interest because of their unique electrical,magnetic,optical,mechanical,and catalytic properties for various applications.To date,however,it is still difficult to fabricate most functional oxides as 2D materials unless they have a layered structure.Herein,we report a one-step universal strategy for preparing versatile non-layered oxide nanosheets by directly annealing the mixture of metal nitrate and dimethyl imidazole(2-MI).The 2-MI plays the key role for 2D oxides since 2-MI owns a very low molten point and sublimation temperature,in which its molten liquid can coordinate with metal ions,forming a metal-organic framework,and easily puffing by its gas molecules.A total of 17 materials were prepared by this strategy,including non-layered metal oxide nanosheets as well as metal/metal oxide loaded nitrogen-doped carbon nanosheets.The as-prepared cobalt particle-loaded nitrogen-doped carbon nanosheets(Co@N/C)exhibit remarkable bifunctional oxygen reduction reaction(ORR)and oxygen evolution reaction(OER)electrocatalytic activity and durability.Besides,the Zn-air battery utilizing a Co@N/C catalyst exhibits high power density of 174.3 mW·cm^(-2).This facile strategy opens up a new way for large-scale synthesis of 2D oxides that holds great potential to push 2D oxides for practical applications. | Kaisi Liu Jiabin Wu Qun Li Hongrun Jin Yongxin Luo Bei Qi Simin Dai Jianquan Zhao Liang Huang Jun Zhou | 2024 | Nano Research2024，17，4： | 0 |
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