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| 1 | Involvement of aquaporins in a mouse model of rotavirus diarrhea显示文摘Rotavirus diarrhea is a major worldwide cause of infantile gastroenteritis; however, the mechanism responsible for intestinal fluid loss remains unclear. Water transfer across the intestinal epithelial membrane seems to occur because of aquaporins(AQPs). Accumulating evidence indicates that alterations in AQPs may play an important role in pathogenesis. Here, we focus on changes in AQPs in a mouse model of rotavirus diarrhea. In the present study, 32 of 35 mice developed diarrhea and mild dehydration within 24 hours after infection with rotavirus strain SA11. Intestinal epithelial cells demonstrated cytoplasmic vacuolation, malaligned villi, and atrophy. AQP1 expression was significantly attenuated in the ileum and colon in comparison with controls; likewise, AQP4 and-8 protein expression were significantly decreased in the colon of rotavirus diarrhea-infected mice. In contrast, AQP3 protein expression was significantly increased in the colon of rotavirus-infected mice in comparison with controls. These results indicate that rotavirus diarrhea is associated with the downregulation of AQP1,-4, and-8 expression. Therefore, AQPs play an important role in rotavirus diarrhea. | Meiwan Cao Min Yang Zhiying Ou Dingyou Li Lanlan Geng Peiyu Chen Huan Chen Sitang Gong | 2014 | Virologica Sinica2014,29,4: | 13 |
| 2 | Discovery of a series of dimethoxybenzene FGFR inhibitors with 5H-pyrrolo[2,3-b]pyrazine scaffold: structure–activity relationship, crystal structural characterization and in vivo study显示文摘Genomic alterations are commonly found in the signaling pathways of fibroblast growth factor receptors(FGFRs). Although there is no selective FGFR inhibitors in market, several promising inhibitors have been investigated in clinical trials, and showed encouraging efficacies in patients. By designing a hybrid between the FGFR-selectivity-enhancing motif dimethoxybenzene group and our previously identified novel scaffold, we discovered a new series of potent FGFR inhibitors, with the best one showing sub-nanomolar enzymatic activity. After several round of optimization and with the solved crystal structure, detailed structure–activity relationship was elaborated. Together with in vitro metabolic stability tests and in vivo pharmacokinetic profiling, a representative compound(35) was selected and tested in xenograft mouse model, and the result demonstrated that inhibitor 35 was effective against tumors with FGFR genetic alterations, exhibiting potential for further development. | Peng Wei Bo Liu Ruifeng Wang Yinglei Gao Lanlan Li Yuchi Ma Zhiwei Qian Yuelei Chen Maosheng Cheng Meiyu Geng Jingkang Shen Dongmei Zhao Jing Ai Bing Xiong | 2019 | Acta Pharmaceutica Sinica B2019,9,2: | 2 |
| 3 | Study of the phenomenon of water hammer based on sliding mesh method 显示文摘 | GUO Lanlan GENG Jie SH1 Shuo | 2014 | Applied Mechanics and Materials2014,525,: | 1 |
| 4 | Study of the phenomenon of water hammer based on sliding mesh method 显示文摘 | Guo Lanlan Geng Jie | 2014 | Ap- plied Mechanics and Materials2014,,525: | 1 |
| 5 | Semantic segmentation of pyramidal neuron skeletons using geometric deep learning显示文摘Neurons can be abstractly represented as skeletons due to the filament nature of neurites.With the rapid development of imaging and image analysis techniques,an increasing amount of neuron skeleton data is being produced.In some scienti fic studies,it is necessary to dissect the axons and dendrites,which is typically done manually and is both tedious and time-consuming.To automate this process,we have developed a method that relies solely on neuronal skeletons using Geometric Deep Learning(GDL).We demonstrate the effectiveness of this method using pyramidal neurons in mammalian brains,and the results are promising for its application in neuroscience studies. | Lanlan Li Jing Qi Yi Geng Jingpeng Wu | 2023 | Journal of Innovative Optical Health Sciences2023,16,6: | 1 |
| 6 | Suppression of cell pyroptosis by omeprazole through PDE4-mediated autophagy in gastric epithelial cells显示文摘Helicobacter pylori is a risk factor for the development of peptic ulcers with autophagy dysfunction.Omeprazole was widely known as the first-line regimen for H.pylori-associated gastritis.Objectives:The objective of this work was to assess the role of omeprazole on cell pyroptosis and autophagy.Methods:The clinical samples were collected.Quantitative polymerase chain reaction,western blotting,enzyme linked immunosorbent assay,and immunofluorescence(IF)analysis were conducted to reveal the mechanism of omeprazole on cell pyroptosis and autophagy.Results:The results revealed that omeprazole could decrease cell pyroptosis,which was attributed to the downregulation of cleaved caspase-1 expression,resulting in the inhibition of gasdermin E and interleukin-18/1βmaturation and secretion as well as the resolution of inflammation.Mechanistically,omeprazole treatment led to drastic downregulation of mammalian target of rapamycin(mTOR)activity was observed in BGC823 cells,leading to enhanced autophagy characterized by increased LC3II expression,which further reduced cell pyroptosis.This omeprazole-mediated phenomenon was enhanced after phosphodiesterase-4(PDE4)inhibitor dipyridamole(DIP)treatment.In addition,activation of mTOR by MHY1485 could rescue the suppression of cell pyroptosis induced by omeprazole.Most importantly,IF analysis suggested that phosphorylation of mTOR and PDE4 activity and caspase-1 were enhanced in H.pylori-infected gastric mucosa.Conclusion:These findings indicate that omeprazole suppresses cell pyroptosis through PDE4-mediated autophagy in gastric epithelial cells,and DIP enhanced the omeprazole-mediated inhibition of cell pyroptosis,implying that DIP is an alternative combined therapy strategy in improving the treatment of patients with H.pylori infection. | LIPING YE HUIYAN SUN XINHUA LIANG WENXU PAN LI XIANG WENJUN DU LANLAN GENG WANFU XU SITANG GONG | 2023 | BIOCELL2023,47,12: | 0 |