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.

Bioinformatic and integrated analysis identifies an lncRNA–miRNA–mRNA interaction mechanism in gastric adenocarcinoma

Yong Liao,Wen Cao,Kunpeng Zhang,Yang Zhou,Xin Xu,Xiaoling Zhao,Xu Yang,Jitao Wang,Shouwen Zhao,Shiyu Zhang,Longfei Yang,Dengxiang Liu,Yanpeng Tian,Weizhong Wu 한국유전학회 2021 Genes & Genomics Vol.43 No.6

Background lncRNAs–miRNAs–mRNAs networks play an important role in Gastric adenocarcinoma (GA). Identifcation of these networks provide new insight into the role of these RNAs in gastric cancer. Objectives Biological information databases were screened to characterize and examine the regulatory networks and to further investigate the potential prognostic relationship this regulation has in GA. Methods By mining The Cancer Genome Atlas (TCGA) database, we gathered information on GA-related lncRNAs, miRNAs, and mRNAs. We identifed diferentially expressed (DE) lncRNAs, miRNAs, and mRNAs using R software. The lncRNA–miRNA–mRNA interaction network was constructed and subsequent survival examination was performed. Representative genes were selected out using The Biological Networks Gene Ontology plug-in tool on Cytoscape. Additional analysis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) terms were used to screen representative genes for functional enrichment. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) were used to identify the expression of fve candidate diferential expressed RNAs. Results Information of samples from 375 cases of gastric cancer and 32 healthy cases (normal tissues) were downloaded from the TCGA database. A total of 1632 DE-mRNAs, 1008 DE-lncRNAs and 104 DE-miRNAs were identifed and screened. Among them, 65 DE-lncRNAs, 10 DE-miRNAs, and 10 DE-mRNAs form lncRNAs–miRNAs–mRNAs regulatory network. Additionally, 10 lncRNAs and 2 mRNAs were associated with the prognosis of GA. Multivariable COX analysis revealed that AC018781.1 and VCAN-AS1 were independent risk factors for GA. GO functional enrichment analysis found DE-mRNA was signifcantly enriched TERM (P<0.05). The KEGG signal regulatory network analysis found 11 signifcantly enrichment networks, the most prevailing was for the AGE-RAGE signaling pathway associated with Diabetic complications. Results of RT-qPCR was consistent with the in silico results. Conclusions The results of the present study represent a view of GA from a analysis of lncRNA, miRNA and mRNA. The network of lncRNA–miRNA–mRNA interactions revealed here may potentially further experimental studies and may help biomarker development for GA.

Proteomic Approach Analysis of Mammary Membrane Proteins Expression Profiles in Holstein Cows

Yang, Yong-xin,Cao, Sui-zhong,Zhang, Yong,Zhao, Xing-xu Asian Australasian Association of Animal Productio 2009 Animal Bioscience Vol.22 No.6

To investigate host defense mechanisms for protecting the mammary gland from mastitis infection, the membrane fraction of mammary tissues from Holstein cows was purified by differential velocity centrifugation, and then the sodium dodecyl sulfate-polyacrylamid gel electrophoresis (SDS-PAGE) separated proteins were identified by ion trap mass spectrometer equipped with a Surveyor high performance liquid chromatography (HPLC) system. A total of 183 proteins were identified. Bioinformatics software was applied to analyse physicochemical characteristics of the identified proteins and to predict biochemical function. These data may provide valuable information to investigate the mechanisms of mammary gland milk secretion and infectious disease, and enable a clear identification of proteins and potential protein targets for therapies.

Dosimetric Verification for Primary Focal Hypermetabolism of Nasopharyngeal Carcinoma Patients Treated with Dynamic Intensity-modulated Radiation Therapy

Xin, Yong,Wang, Jia-Yang,Li, Liang,Tang, Tian-You,Liu, Gui-Hong,Wang, Jian-She,Xu, Yu-Mei,Chen, Yong,Zhang, Long-Zhen Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.3

Objective: To make sure the feasibility with $^{18F}FDG$ PET/CT to guided dynamic intensity-modulated radiation therapy (IMRT) for nasopharyngeal carcinoma patients, by dosimetric verification before treatment. Methods: Chose 11 patients in III~IVA nasopharyngeal carcinoma treated with functional image-guided IMRT and absolute and relative dosimetric verification by Varian 23EX LA, ionization chamber, 2DICA of I'mRT Matrixx and IBA detachable phantom. Drawing outline and making treatment plan were by different imaging techniques (CT and $^{18F}FDG$ PET/CT). The dose distributions of the various regional were realized by SMART. Results: The absolute mean errors of interest area were $2.39%{\pm}0.66$ using 0.6cc ice chamber. Results using DTA method, the average relative dose measurements within our protocol (3%, 3 mm) were 87.64% at 300 MU/min in all filed. Conclusions: Dosimetric verification before IMRT is obligatory and necessary. Ionization chamber and 2DICA of I'mRT Matrixx was the effective dosimetric verification tool for primary focal hyper metabolism in functional image-guided dynamic IMRT for nasopharyngeal carcinoma. Our preliminary evidence indicates that functional image-guided dynamic IMRT is feasible.

Wood Vinegar Exerts Hypoglycemic Effect in Normal and Diabetic Rats

Yu Xin Yang,Ji Soon Yong,Jae Yong Choi,Lokahare Jayant,Byung Jo Chae 강원대학교 동물생명과학연구소(구 강원대학교 동물자원공동연구소) 2007 동물자원연구 Vol.18 No.-

Wood vinegar, an extract from Acer Tegmentosum Maximowicz, was evaluated for its hypoglycemic and anti-diabetic properties by using normal and diabetic rats. The extract was dissolved in water and administered daily for six or seven weeks. In experiment 1, thirty normal Sprague- Dawley (SD) male rats were randomly divided into five treatments of 6 rats each. The treatments were T1 (mineral water), T2 (mineral water), T3 (silver solution), T4 (wood vinegar), and T5 (silver solution + wood vinegar) and diabetes was induced by intravenous injection of streptozotocin except T1. In experiment 2, sixteen diabetic Goto-Kakizaki (GK) male rats were randomly divided into four treatments of 4 rats each. The treatments were T1 (mineral water), T2 (silver solution), T3 (wood vinegar), and T4 (silver solution + wood vinegar). Streptozotocin-induced diabetic rats showed less body weight gain, more food intake and less water consumption as compared with normal non-diabetic rats. Oral administration of wood vinegar resulted in more weight gain, lower blood glucose concentration and urine pH among all the diabetic rats. In experiment 2, diabetic GK rats administrated with wood vinegar showed higher weight gain, food intake and less water intake when compared with control. However, supplementation with wood vinegar did not result in any decrease of blood glucose concentrations. It could be concluded that wood vinegar extracted from Acer Tegmentosum Maximowicz exerted hypoglycemic effect in diabetic-induced normal rats, but not in diabetic GK rats.

Bond-Orientational Order in Melting of Colloidal Crystals

Xin Qi,Yong Chen,Yan Jin,Yao-Hui Yang 한국물리학회 2006 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.49 No.4

Using Brownian dynamics simulation, we study the orientational order in the melting transition of a colloidal system with a `soft' Yukawa potential. The bond-orientational order parameter ⓒ6 and the bond-orientational order function gB(r) are calculated in two-dimensional systems. We found that a two-stage transition and a hexatic phase indeed exist in two-dimensional melting, which is consistent with the prediction of the Kosterlitz-Thouless-Halperin-Nelson-Young theory. For comparing with the melting process in three-dimensional systems, we introduce the probability distribution of the single-particle local-order parameter. Based on extensive simulations, the break- down of local order is qualitatively suggested only to occur on the fractional part of the colloidal system for the two-dimensional melting, but in three-dimensional melting, that breakdown takes place on the whole system at the same time.F

Toll-like receptor 4-mediated immunoregulation by the aqueous extract of Mori Fructus

Yang, Xin-Ying,Park, Gil-Soon,Lee, Moo Hyung,Chang, In Ae,Kim, Youn Chul,Kim, Sung Yeon,Lee, Joo Young,Yun, Yong Gab,Park, Hyun John Wiley Sons, Ltd. 2009 Phytotherapy research Vol.23 No.12

<P>The aqueous extract of Mori Fructus (MF) exerts a change of phenotype and a cytoprotective effect in macrophages. The present study was carried out to investigate the immunomodulating activity of MF on the expression of nitric oxide (NO), tumor necrosis factor alpha (TNF-&agr;), co-stimulatory molecules and also interferon-gamma (IFN-&ggr;) in macrophages and splenocytes. Toll-like receptor 4 (TLR4) is a promising molecular target for immune-modulating drugs. It was hypothesized that one possible upstream signaling pathway leading to immunoregulation of MF may be mediated by TLRs. Multiple signaling molecules (NF-&kgr;B, ERK1/2, p38 and JNK) of the TLR4 signaling pathway were also detected. It was found that MF increased NO production and TNF-&agr; secretion in RAW 264.7 and peritoneal macrophages, co-stimulatory molecules expression in peritoneal macrophages and IFN-&ggr; expression in splenocytes. Further studies indicated that MF could significantly induce the phosphorylation of signal molecules of MAPKs and the degradation of I&kgr;B&agr; which finally led to the activation and nuclear translocation of nuclear factor-&kgr;B (NF-&kgr;B) for the target gene expression. All those notions disclosed that the aqueous extract MF is a new TLR4 activator, which induces a Th1 immune response as a consequence of induction of cytokines secretion, especially TNF-&agr; and IFN-&ggr;. Copyright © 2009 John Wiley & Sons, Ltd.</P>

Stability Analysis of Crack Slope Considering Nonlinearity and Water Pressure

Yong-xin Li,Xiao-li Yang 대한토목학회 2016 KSCE JOURNAL OF CIVIL ENGINEERING Vol.20 No.6

The soil slopes tend to induce the appearance of tension cracks at the top of slope under various factors, which poses an adverse impact on slope stability. Based on Power-Law nonlinear failure criterion, kinematical approach is adopted in this paper to investigate the effects of underground water and vertical tension cracks on stability of slopes. Notice that the tension cracks tend to propagate vertically, and thus a novel failure mechanism composed by the tension crack and logarithmic spiral shear slide plane is postulated. Theoretically, the worst position of crack propagation makes the stability factor minimal, and the failure surfaces can be obtained under different conditions through optimization. According to the proposed mechanism and nonlinear Mohr-Coulomb strength criterion, the stability factor and safety coefficient of slopes are derived. Subsequently, sensitivity analysis with respect to specific examples is conducted to analyze the influence of tension cracks, nonlinear strength parameters and pore water pressure on the slope stability. The results indicate that slope stability weakens gradually at the presence of tension cracks, and the changing degree is more evident with the increase of the slope angle. Meanwhile, nonlinear parameters have more significant impact on the safety factor with the decreasing value of the slope angle. However, the bigger the slope angle, the greater the height of tension cracks, and therefore the more obvious influence of pore water pressure on slope stability. When the slope angle approaches to be vertical, the height of tension cracks increases sharply. As a matter of fact, the height of tension cracks is highly related to geometrical conditions, strength parameters and water effect, which build a mutual relationship to determine slope stability.

Long-Term Oncologic Outcomes of Liver Resection for Hepatocellular Carcinoma in Adolescents and Young Adults: A Multicenter Study from A Hepatitis B Virus-Endemic Area

( Yong-kang Diao ),( Jun-wei Liu ),( Wan Yee Lau ),( Xin-ping Fan ),( Ting-hao Chen ),( Ya-hao Zhou ),( Wei-min Gu ),( Hong Wang ),( Jie Li ),( Ying-jian Liang ),( Tian Yang ) 대한간학회 2021 춘·추계 학술대회 (KASL) Vol.2021 No.1

Three-dimensional Seismic Displacement Analysis of Rock Slopes based on Hoek-Brown Failure Criterion

Yong-xin Li,Xiao-li Yang 대한토목학회 2018 KSCE JOURNAL OF CIVIL ENGINEERING Vol.22 No.11

Seismic force is one of the main factors resulting in the slip failure of steep rock slopes. In this paper, the seismic displacement analysis of rock slopes is carried out by virtue of the kinematical theorem of limit analysis and the Newmark method. It is assumed that the slope has a curvilinear cone-shaped failure mechanism and its materials are subjected to the Hoek-Brown failure criterion. The generalized tangential technique is employed to obtain equivalent parameters from the Hoek-Brown criterion. According to the three-dimensional failure mechanism, the internal energy dissipation and external work are respectively calculated, and the effect of horizontal seismic force is included by using the equivalent pseudo-static method. Subsequently, the yield acceleration is calculated for three-dimensional failure mechanism, and the results are shown to be valid when compared with the previous solutions. Parameter analysis is used to represent how the Hoek-Brown criterion parameters impact on the yield acceleration. The failure mechanism is also obtained during the process of limit analysis, and a dimensionless coefficient is adopted to investigate the influence of it on the seismic displacements of slopes. The results of calculations are given for a series of actual seismic waves and compared with the results calculated from empirical formula.