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| 1 | Downregulation of ceramide synthase 1 promotes oral cancer through endoplasmic reticulum stress显示文摘C18 ceramide plays an important role in the occurrence and development of oral squamous cell carcinoma.However,the function of ceramide synthase 1,a key enzyme in C18 ceramide synthesis,in oral squamous cell carcinoma is still unclear.The aim of our study was to investigate the relationship between ceramide synthase 1 and oral cancer.In this study,we found that the expression of ceramide synthase 1 was downregulated in oral cancer tissues and cell lines.In a mouse oral squamous cell carcinoma model induced by 4-nitroquinolin-1-oxide,ceramide synthase 1 knockout was associated with the severity of oral malignant transformation.Immunohistochemical studies showed significant upregulation of PCNA,MMP2,MMP9,and BCL2 expression and downregulation of BAX expression in the pathological hyperplastic area.In addition,ceramide synthase 1 knockdown promoted cell proliferation,migration,and invasion in vitro.Overexpression of CERS1 obtained the opposite effect.Ceramide synthase 1 knockdown caused endoplasmic reticulum stress and induced the VEGFA upregulation.Activating transcription factor 4 is responsible for ceramide synthase 1 knockdown caused VEGFA transcriptional upregulation.In addition,mild endoplasmic reticulum stress caused by ceramide synthase 1 knockdown could induce cisplatin resistance.Taken together,our study suggests that ceramide synthase 1 is downregulated in oral cancer and promotes the aggressiveness of oral squamous cell carcinoma and chemotherapeutic drug resistance. | Wen Chen Chenzhou Wu Yafei Chen Yuhao Guo Ling Qiu Zhe Liu Haibin Sun Siyu Chen Zijian An Zhuoyuan Zhang Yi Li Longjiang Li | 2021 | International Journal of Oral Science2021，13，1： | 3 |
| 2 | Visualization Experiment and Numerical Analysis of Cavitation Flow Characteristics in Diesel Fuel Injector Control Valve with Different Structure Design显示文摘Increasing the injection pressure has been proven an effective method to enhance performance and reduce pollutant of diesel engine.With the increase of the injection pressure,the cavitation damage problem inside common rail fuel injector is more significant,which has direct influences on reliability of diesel engine.While the most studies so far have focused on cavitation occurred in injector nozzle and its atomization characteristics,few researchers studied the cavitation phenomenon in fuel injector control valve.But due to the complexity of flow field and difficulty of experiment,the cavitation in control valve could not be fully described by existing theories.In this paper,the two-dimensional visualization experiment and numerical simulation of control valve was implemented to acquire the image of cavitation intuitively and validate the simulation method and model.Then a new structure design of control valve named convergent model was presented for comparison.The origin model and convergent model with different valve lifts were simulated in three dimensions.The results showed that the sheet cavitation occurred at the surface of seal cone and steel ball then turned to cloud cavitation in downstream area.The intensity of cavitation increased with the increase of valve lift.Convergent model could efficiently reduce the cavitation intensity near the seal area.This research could provide references for engineering optimization design of control valve. | MA Haoyuan ZHANG Tong AN Qingsong TAO Yuhao XU Yue | 2021 | Journal of Thermal Science2021，30，1： | 3 |
| 3 | Observation of the Hydrogen-Dislocation Interactions in a High-Manganese Steel after Hydrogen Adsorption and Desorption显示文摘Hydrogen embrittlement(HE)poses a significant challenge for the development of high-strength metallic materials.However,explanations for the observed HE phenomena are still under debate.To shed light on this issue,here we investigated the hydrogen-defect interaction by comparing the dislocation structure evolution after hydrogen adsorption and desorption in a Fe-28Mn-0.3C(wt%)twinning-induced plasticity steel with an austenitic structure using in situ electron channeling contrast imaging.The results indicate that hydrogen can strongly affect dislocation activities.In detail,hydrogen can promote the formation of stacking faults with a long dissociation distance.Besides,dislocation movements are frequently observed during hydrogen desorption.The required resolved shear stress is considered to be the residual stresses rendered by hydrogen segregation.Furthermore,the microstructural heterogeneity could lead to the discrepancy of dislocation activities even within the same materials. | Dayong An Yuhao Zhou Yao Xiao Xinxi Liu Xifeng Li Jun Chen | 2023 | Acta Metallurgica Sinica(English Letters)2023，36，7： | 0 |
| 4 | Targeting UBE2C for degradation by bioPROTACs based on bacterial E3 ligase显示文摘UBE2C(Ubiquitin conjugating enzyme E2 C), a key regulator of cell cycle progression, is a promising target for discovery of antitumor agents. However, it is challenging to develop inhibitors of UBE2C owing to its lack of “druggable” pockets. Bio PROTACs(biological proteolysis targeting chimeras) are a kind of protein-based degraders by fusing an adaptor to a subunit of E3 ligase for ubiquitination and subsequent proteasome-dependent degradation of target protein. We report herein the design and biological evaluation of a UBE2C-targeting bio PROTAC based on the NEL(novel E3 ligase) domain of bacterial E3 ligase Ipa H9.8 and the UBE2C-binding WHB(winged-helix B) domain of APC_(2)(anaphase promoting complex subunit 2). The in vitro ubiquitination test and Mass Spectrometry analysis showed that the bio PROTAC could transfer ubiquitin to surface exposed lysines on UBE2C and catalyzed the formation of polyubiquitin chains. In addition, the transient co-expression experiment showed that the bio PROTAC could promote proteasomal degradation of heterologous UBE2C and rescue its downstream substrates in mammalian cells. | Jinpeng Wang Min Zhang Susheng Liu Zhipeng He Rui Wang Minchan Liang Yuhao An Chenran Jiang Chunli Song Zigong Ning Feng Yin Hao Huang Zigang Li Yuxin Ye | 2023 | Chinese Chemical Letters2023，34，4： | 0 |
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