Mitochondrial citrate accumulation drives alveolar epithelial cell necroptosis in lipopolysaccharide-induced acute lung injury

Yang Hui-Hui,Jiang Hui-Ling,Tao Jia-Hao,Zhang Chen-Yu,Xiong Jian-Bing,Yang Jin-Tong,Liu Yu-Biao,Zhong Wen-Jing,Guan Xin-Xin,Duan Jia-Xi,Zhang Yan-Feng,Liu Shao-Kun,Jiang Jian-Xin,Zhou Yong,Guan Cha-Xi 생화학분자생물학회 2022 Experimental and molecular medicine Vol.54 No.-

Necroptosis is the major cause of death in alveolar epithelial cells (AECs) during acute lung injury (ALI). Here, we report a previously unrecognized mechanism for necroptosis. We found an accumulation of mitochondrial citrate (citratemt) in lipopolysaccharide (LPS)-treated AECs because of the downregulation of Idh3α and citrate carrier (CIC, also known as Slc25a1). shRNA- or inhibitor–mediated inhibition of Idh3α and Slc25a1 induced citratemt accumulation and necroptosis in vitro. Mice with AEC-specific Idh3α and Slc25a1 deficiency exhibited exacerbated lung injury and AEC necroptosis. Interestingly, the overexpression of Idh3α and Slc25a1 decreased citratemt levels and rescued AECs from necroptosis. Mechanistically, citratemt accumulation induced mitochondrial fission and excessive mitophagy in AECs. Furthermore, citratemt directly interacted with FUN14 domain-containing protein 1 (FUNDC1) and promoted the interaction of FUNDC1 with dynamin-related protein 1 (DRP1), leading to excessive mitophagy-mediated necroptosis and thereby initiating and promoting ALI. Importantly, necroptosis induced by citratemt accumulation was inhibited in FUNDC1-knockout AECs. We show that citratemt accumulation is a novel target for protection against ALI involving necroptosis.

Extrusion of porous silicon nitride using different binders

Jian-Feng Yang,Guang-Peng Jiang,Ji-Qiang Gao 한양대학교 세라믹연구소 2010 Journal of Ceramic Processing Research Vol.11 No.1

Porous silicon nitride ceramics were prepared using an extrusion process. Starch and thermoset phenol-formaldehyde resin were used as binders. The effect of the different binders on the microstructure and mechanical strength of the porous silicon nitride were investigated in detail. It is shown that the microstructure was more uniform when phenol-formaldehyde resin was used as the binder. In contrast, the pore size distribution was bimodal when starch was used. Furthermore, the flexural strength of porous Si3N4 using resin as the binder was higher than that using the starch.

Experimental study on cold-formed lipped channel stub columns reinforced by steel bars or steel strips

Jian-Feng Chen,Ming-Qi Chen,Yong-Kang Shen,Jian-Hua Shao,Xin-Xin Yang 국제구조공학회 2021 Steel and Composite Structures, An International J Vol.40 No.3

In this paper, the axial compressive properties of cold-formed steel lipped channel stub columns strengthened by rebars or steel strips are experimentally studied. The experiment included two sections. A kind of columns with local buckling is reinforced longitudinally by steel strips at the web. The other is the columns with distorted buckling, which is reinforced longitudinally by steel bars at the curling edge. The failure mode, deformation characteristics, ultimate bearing capacity and load displacement curve of the specimen are obtained through the experiment. On the basis of the experiment, the calculation results of theoretical axial bearing capacity of cold-formed steel lipped channel stub columns in Chinese, North American and Australian code are compared and analyzed. Research indicates: First, the cold-formed steel lipped channel stub columns strengthened by steel bars or steel strips can effectively improve the compressive bearing capacity of the specimen. Secondly, when the initial stress ratio of specimen is less than 0.3, the reinforcement effect is ideal. Thirdly, the three standards don’t stipulate the calculation of theoretical bearing capacity of the specimen strengthened after loading, so there is a large deviation between the theoretical calculation value and the test value.

Upper-bound Finite Element Analysis of Stability of Tunnel Face Subjected to Surcharge Loading in Cohesive-frictional Soil

Feng Yang,Jian Zhang,Lianheng Zhao,Junsheng Yang 대한토목학회 2016 KSCE Journal of Civil Engineering Vol.20 No.6

The stability of a plane strain tunnel face in a cohesive-frictional soil (idealized as a homogeneously Mohr-Coulomb material) subjected to ground surface surcharge loading was investigated. Continuous loading is applied to the ground surface, and both smooth and rough interface conditions are modeled. The upper-bound solutions with critical load parameters for a practical range of tunnel depth-to-height values, as well as the soil properties, are obtained by using the Upper-bound Finite Element Method with Rigid Translatory Moving Elements (UBFEM-RTME). For practical use, the results are presented in the form of dimensionless stability charts. Failure mechanisms consisting of two groups of slip lines, which explicitly reflect the relative movement of blocks, are also presented. To verify the solutions, the Upper-bound Finite Element Method with Plastic Deformation Elements (UMFEMPDE) has been developed and the collapsed loads are compared with those from UBFEM-RTME. The solutions obtained with these two upper-bound finite element methods are found to be in good agreement with each other.

Enhanced Visible-Light Driven Photocatalytic Performances Over LaFeO3/NiO Modified Porous g-C3N4 Nanosheets

Ke Xu,Xiaosheng Yang,Dagao Sun,Xin Yang,Yumei Zhou,Wei Li,Qindan Yang,Xianjiong Yang,Rong Li,Jian Feng 성균관대학교(자연과학캠퍼스) 성균나노과학기술원 2020 NANO Vol.15 No.02

LaFeO3/NiO modified g-C3N4 nanosheets (L-N/CNS) were synthesized by a two-step method. HRTEM results showed that an intimate contact between LaFeO3, NiO and N-CNS was successfully established. Ninety percent of phenol was degraded within 120 min, and the hydrogen evolution rate of 171.2 μmol h -1 g -1 was obtained over the L-N/CNS heterojunctions under the visible-light irradiation. It was higher than that of g-C3N4 nanosheets, NiO modified g-C3N4 and LaFeO3/g-C3N4. The ·O2 - radicals acted the crucial role in the photocatalytic degradation reaction. EIS, PL and time-resolved fluorescence spectra demonstrated that L-N/CNS possessed the highest charge separation efficiency. The intimate contact between LaFeO3, NiO and g-C3N4 nanosheets promoted the separation and transfer of photo-induced electron–hole pairs and consequently prolonged the exciton lifetime, and implied more photo-induced electrons could be probably involved in the photocatalytic reactions on the surface of photocatalysts. Thus, the visible-light driven photocatalytic performances of L-N/CNS were effective. This work provided a feasible method to design and construct heterostructures for the exploitation of solar energy.

CK2 phosphorylates AP-2α and increases its transcriptional activity

( Kai Qun Ren ),( Shuang Lin Xiang ),( Fang Li He ),( Wen Feng Zhang ),( Xiao Feng Ding ),( Yan Yang Wu ),( Li Ping Yang ),( Jian Lin Zhou ),( Xiang Gao ),( Jian Zhang ) 생화학분자생물학회(구 한국생화학분자생물학회) 2011 BMB Reports Vol.44 No.7

Transcription factor AP-2α involves in the process of mammalian embryonic development and tumorigenesis. Many studies have shown that AP-2α functions in association with other interacting proteins. In a two-hybrid screening, the regulatory subunit β of protein casein kinase 2 (CK2β) was identified as an interacting protein of AP-2α; we confirmed this interaction using in-vitro GST pull-down and in-vivo co-immunoprecipitation assays; in an endogenous co-immunoprecipitation experiment, we further found the catalytic subunit α of protein casein kinase 2 (CK2α) also exists in the complex. Phosphorylation analysis revealed that AP-2α was phosphorylated by CK2 kinase majorly at the site of Ser429, and such phosphorylation could be blocked by CK2 specific inhibitor 4,5,6,7-tetrabromobenzotriazole (TBB) in a dose-dependent manner. Luciferase assays demonstrated that both CK2α and CK2β enhanced the transcription activity of AP-2α; moreover, CK2β increased the stability of AP-2α. Our data suggest a novel cellular function of CK-2 as a transcriptional co-activator of AP-2α.

Increased Serotonin Signaling Contributes to the Warburg Effect in Pancreatic Tumor Cells Under Metabolic Stress and Promotes Growth of Pancreatic Tumors in Mice

Jiang, Shu-Heng,Li, Jun,Dong, Fang-Yuan,Yang, Jian-Yu,Liu, De-Jun,Yang, Xiao-Mei,Wang, Ya-Hui,Yang, Min-Wei,Fu, Xue-Liang,Zhang, Xiao-Xin,Li, Qing,Pang, Xiu-Feng,Huo, Yan-Miao,Li, Jiao,Zhang, Jun-Feng Elsevier 2017 Gastroenterology Vol.153 No.1

<P><B>Background & Aims</B></P> <P>Desmoplasia and poor vascularity cause severe metabolic stress in pancreatic ductal adenocarcinomas (PDACs). Serotonin (5-HT) is a neuromodulator with neurotransmitter and neuroendocrine functions that contributes to tumorigenesis. We investigated the role of 5-HT signaling in the growth of pancreatic tumors.</P> <P><B>Methods</B></P> <P>We measured the levels of proteins that regulate 5-HT synthesis, packaging, and degradation in pancreata from Kras<SUP>G12D/+</SUP>/Trp53<SUP>R172H/+</SUP>/Pdx1-Cre (KPC) mice, which develop pancreatic tumors, as well as in PDAC cell lines and a tissue microarray containing 81 human PDAC samples. We also analyzed expression levels of proteins involved in 5-HT synthesis and degradation by immunohistochemical analysis of a tissue microarray containing 311 PDAC specimens, and associated expression levels with patient survival times. 5-HT level in 14 matched PDAC tumor and non-tumor tissues were analyzed by ELISA. PDAC cell lines were incubated with 5-HT and cell survival and apoptosis were measured. We analyzed expression of the 5-HT receptor HTR2B in PDAC cells and effects of receptor agonists and antagonists, as well as HTR2B knockdown with small hairpin RNAs. We determined the effects of 5-HT stimulation on gene expression profiles of BxPC-3 cells. Regulation of glycolysis by 5-HT signaling via HTR2B was assessed by immunofluorescence and immunoprecipitation analyses, as well as by determination of the extracellular acid ratio, glucose consumption, and lactate production. Primary PDACs, with or without exposure to SB204741 (a selective antagonist of HTR2B), were grown as xenograft tumors in mice, and SB204741 was administered to tumor-bearing KPC mice; tumor growth and metabolism were measured by imaging analyses.</P> <P><B>Results</B></P> <P>In immunohistochemical analysis of a tissue microarray of PDAC specimens, increased levels of TPH1 and decreased level of MAOA, which regulate 5-HT synthesis and degradation, correlated with stage and size of PDACs and shorter patient survival time. We found levels of 5-HT to be increased in human PDAC tissues compared with non-tumor pancreatic tissues, and PDAC cell lines compared with non-transformed pancreatic cells. Incubation of PDAC cell lines with 5-HT increased proliferation and prevented apoptosis. Agonists of HTR2B, but not other 5-HT receptors, promoted proliferation and prevented apoptosis of PDAC cells. Knockdown of HTR2B in PDAC cells, or incubation of cells with HTR2B inhibitors, reduced their growth as xenograft tumors in mice. We observed a correlation between 5-HT and glycolytic flux in PDAC cells; levels of metabolic enzymes involved in glycolysis, the phosphate pentose pathway, and hexosamine biosynthesis pathway increased significantly in PDAC cells following 5-HT stimulation. 5-HT stimulation led to formation of the HTR2B–LYN–p85 complex, which increased PI3K–Akt–mTOR signaling and the Warburg effect by increasing protein levels of MYC and HIF1A. Administration of SB204741 to KPC mice slowed growth and metabolism of established pancreatic tumors and prolonged survival of the mice.</P> <P><B>Conclusions</B></P> <P>Human PDACs have increased levels of 5-HT, and PDAC cells increase expression of its receptor, HTR2B. These increases allow for tumor glycolysis under metabolic stress and promote growth of pancreatic tumors and PDAC xenograft tumors in mice.</P>

Microstructure analysis of pressure resistance seal welding joint of zirconium alloy tube-plug structure

Feng Gang,Lin Jian,Yang Shuai,Zhang Boxuan,Wang Jiangang,Yang Jia,Xu Zhongfeng,Lei Yongping 한국원자력학회 2023 Nuclear Engineering and Technology Vol.55 No.11

Pressure resistance welding is usually used to seal the connection between the cladding tube and the end plug made of zirconium alloy. The seal welded joint has a direct effect on the service performance of the fuel rod cladding structure. In this paper, the pressure resistance welded joints of zirconium alloy tube-plug structure were obtained by thermal-mechanical simulation experiments. The microstructure and microhardness of the joints were both analyzed. The effect of processing parameters on the microstructure was studied in detail. The results showed that there was no β-Zr phase observed in the joint, and no obvious element segregation. There were different types of Widmanst¨atten structure in the thermo-mechanically affected zone (TMAZ) and heat affected zone (HAZ) of the cladding tube and the end plug joint because of the low cooling rate. Some part of the grains in the joint grew up due to overheating. Its size was about 2.8 times that of the base metal grains. Due to the high dislocation density and texture evolution, the microhardnesses of TMAZ and HAZ were both significantly higher than that of the base metal, and the microhardness of the TMAZ was the highest. With the increasing of welding temperature, the proportion of recrystallization in TMAZ decreased, which was caused by the increasing of strain rate and dislocation annihilation

Estrogen weakens muscle endurance via estrogen receptor-p38 MAPK-mediated orosomucoid (ORM) suppression

Yang Sun,Zhen Qin,Jing-jing Wan,Peng-yuan Wang,Yi-Li Yang,Jian-Guang Yu,Bo-Han Hu,Ding-Feng Su,Zhu-Min Luo,Xia Liu 생화학분자생물학회 2018 Experimental and molecular medicine Vol.50 No.-

Gender differences in fatigue manifest as females being more prone to feel exhaustion and having lower muscle endurance. However, the mechanisms of these effects remain unclear. We investigated whether orosomucoid, an endogenous anti-fatigue protein that enhances muscle endurance, is involved in this regulation. Female rats exhibited lower muscle endurance, and this gender difference disappeared in orosomucoid-1-deficient mice. Female rats also exhibited weaker orosomucoid induction in serum, liver and muscle in response to fatigue compared with male rats. Ovariectomy elevated orosomucoid levels and increased swimming time, and estrogen replenishment reversed these effects. Exogenous estrogen treatment in male and female mice produced opposite effects. Estrogen decreased orosomucoid expression and its promoter activity in C2C12 muscle and Chang liver cells in vitro, and estrogen receptor or p38 mitogen-activated protein kinase blockade abolished this effect. Therefore, estrogen negatively regulates orosomucoid expression that is responsible for the weaker muscle endurance in females.

First-principle study on catalytic activity of functionalized Ti3C2 MXene as cathode catalyst for Li–O2 batteries

Yang Yingying,Chen Jian,Gao Qiqian,Feng Yu,Xing Fei,Yao Man 한국물리학회 2022 Current Applied Physics Vol.34 No.-

Two-dimensional layered Ti3C2, one representative MXene, is notable as promising cathode catalyst for rechargeable lithium-oxygen (Li–O2) batteries. Using first-principles calculations, we construct cathode electrochemical interface catalytic model to simulate the structural evolution during discharging and charging processes, and the calculated ORR, OER and TOT overpotentials are used to quantitatively assess the catalytic activity of Ti3C2 MXene with and without O, F and OH functional groups. Interestingly, we find that the catalytic activity follows such a trend: Ti3C2O2>Ti3C2F2>Ti3C2(OH)2>Ti3C2, which suggests that O-terminated Ti3C2 MXene has great advantages and potentiality for catalyzing ORR and OER in Li–O2 batteries. This is caused by Ti3C2O2 surface shows stronger oxidation capability toward O22 compared to Ti3C2F2, Ti3C2(OH)2 and Ti3C2. The present study may provide a guideline to accelerate ORR and OER reactions of Ti3C2 MXene as cathode catalyst in Li–O2 batteries, with O-terminated group being taken into consideration.