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| 1 | Insulin-like growth factor 1-induced enolase 2 deacetylation by HDAC3 promotes metastasis of pancreatic cancer显示文摘Enolase 2(ENO2)is a key glycolytic enzyme in the metabolic process of glycolysis,but its potential function in pancreatic ductal adenocarcinoma(PDAC)is unclear.In this study,we observed a significant overexpression of ENO2 in PDAC tissues,and its expression was correlated with metastasis and poor prognosis in PDAC patients.K394 was identified as a major acetylation site in ENO2 that regulates its enzymatic activity,cell metabolism and PDAC progression.Knockdown of ENO2 suppressed tumor growth and liver metastasis in PDAC.Re-expression of wild-type(WT)ENO2,but not the K394 acetylation mimetic mutant,could reverse the decreased tumor malignancy.We further characterized histone deacetylase 3(HDAC3)and P300/CBP-associated factor(PCAF)as the potential deacetylase and acetyltransferase for ENO2,respectively.HDAC3-mediated deacetylation was shown to lead to ENO2 activation and enhancement of glycolysis.Importantly,insulin-like growth factor-1(IGF-1)was found to decrease K394 acetylation and stimulate ENO2 activity in a dose-and time-dependent manner.The PI3K/AKT/mTOR pathway facilitated the phosphorylation of HDAC3 on S424,which promoted K394 deacetylation and activation of ENO2.Linsitinib,an oral small-molecule inhibitor of IGF-1R,could inhibit IGF-1-induced ENO2 deacetylation by HDAC3 and the PI3K/AKT/mTOR pathway.Furthermore,linsitinib showed a different effect on the growth and metastasis of PDAC depending on the overexpression of WT versus K394-mutant ENO2.Our results reveal a novel mechanism by which acetylation negatively regulates ENO2 activity in the metastasis of PDAC by modulating glycolysis.Blockade of IGF-1-induced ENO2 deacetylation represents a promising strategy to prevent the development of PDAC. | Yan Zheng Chao Wu Jimeng Yang Yue Zhao Huliang Jia Min Xue Da Xu Feng Yang Deliang Fu Chaoqun Wang Beiyuan Hu Ze Zhang Tianen Li Shican Yan Xuan Wang Peter J.Nelson Christiane Bruns Lunxiu Qin Qiongzhu Dong | 2020 | Signal Transduction and Targeted Therapy2020，5，1： | 3 |
| 2 | Longitudinal connection effect on initial support steel frames in tunnels--Take the traffic tunnels as examples显示文摘Most tunnel projects are designed with cross-sectional loads,and the inhomogeneity of the longitudinal forces is ignored.In theory,such a support structure can resist large loads,but in practice,large deformation,concrete cracking,steel frame distortion,and other phenomena often occur in tunnels under poor surrounding rock conditions.Hence,the longitudinal stability of the tunnel must be considered.In this study,the mechanism of longitudinal connecting ribs(LCRs)of tunnels was investigated through element tests,theoretical analyses,and numerical simulations,and the effect of the LCRs was evaluated experimentally.The applicability of the constitutive relations and boundary conditions of the numerical model was verified.The instability mode of the steel frame reflecting the longitudinal stress gradient of the tunnel was analyzed,and the longitudinal surrounding rock pressure and the verified numerical model were applied to analyze the LCR using the load structure method.The results indicate the following:(1)LCRs can effectively improve the ultimate bearing capacity and stability of a structure and reduce the area and degree of damage;(2)Two types of instability modes occur in tunnel steel frames,and the main factor is bending failure caused by the axial force;(3)The distance sensitivity of the LCR in the tunnel is higher than the stiffness sensitivity.For large deformations of tunnels,double rows of rebars with a spacing of less than 1.5 m should be used as longitudinal connections. | Kaimeng Ma Jichun Zhang Junru Zhang Zhiyong Wang Jimeng Feng | 2022 | Underground Space2022，7，4： | 0 |
| 3 | REDUCTION OF NON-POINT SOURCE POLLUTION IN THE YONG'AN RIVER BY CONSTRUCTED WETLAND BASED ON 9 YEARS OF MONITORING显示文摘The agricultural and livestock activities surrounding the rivers flowing into the lakes have caused non-point source pollution, leading to excessive amounts of nutrient salts in downstream rivers. Introducing river water into constructed wetlands along river course has proven to be an effective solution for decreasing nitrogen(N) and phosphorus(P) loads. This paper reports 9 years of monitoring the Yong’an River and its surrounding constructed wetlands in the upper reaches of Erhai Lake, located in Yunnan Province, China. This study analyzed the main types of pollutants in the river, and evaluated the removal efficiency of pollutants by the constructed wetlands. The findings indicate that total nitrogen(TN) and nitrate nitrogen(NO_(3)^(–)-N) are the primary pollutants in the Yong’an River, which exhibit variation throughout the year corresponding to the alternating wet and dry seasons. Although constructed wetlands are effective in removing NO_(3)^(-)-N and P, their efficacy in removing ammonium nitrogen(NH_(4)^(+)-N)and organic pollutants is limited. This limitation can be attributed to the lack of timely disposal of aquatic plant residues. This research contributes to the understanding of the potential issues that may arise during the extended use of constructed wetlands and provides solutions to address them. | Huaji LIU Jian SHEN Jimeng FENG Xinze WANG | 2023 | Frontiers of Agricultural Science and Engineering2023，10，4： | 0 |
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