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      • A Study On Critical Thinning In Thin-walled Tube Bending Of Al-Alloy 5052O Via Coupled Ductile Fracture Criteria

        Heng Li,He Yang,Mei Zhan 한국소성가공학회 2010 기타자료 Vol.2010 No.6

        Thin-walled tube bending(TWTB) method of Al-alloy tube has attracted wide applications in aerospace, aviation and automobile,etc. While, under in-plane double tensile stress states at the extrados of bending tube, the overthinning induced ductile fracture is one dominant defect in Al-alloy tube bending. The main objective of this study is to predict the critical wall-thinning of Al-alloy tube bending by coupling two ductile fracture criteria(DFCs) into FE simulation. The DFCs include Continuum Damage Mechanics(CDM)-based model and GTN porous model. Through the uniaxial tensile test of the curved specimen, the basic material properties of the Al-alloy 5052O tube is obtained; via the inverse problem solution, the damage parameters of both the two fracture criteria are interatively determined. Thus the application study of the above DFCs in the TWTB is performed, and the more reasonable one is selected to obtain the critical thinning of Al-alloy tube in bending. The virtual damage initiation and evolution (when and where the ductile fracture occurs) in TWTB are investigated, and the fracture mechanisms of the voided Al-alloy tube in tube bending are consequently discussed.

      • SCIESCOPUSKCI등재
      • The mTOR Signalling Pathway in Cancer and the Potential mTOR Inhibitory Activities of Natural Phytochemicals

        Tan, Heng Kean,Moad, Ahmed Ismail Hassan,Tan, Mei Lan Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.16

        The mammalian target of rapamycin (mTOR) kinase plays an important role in regulating cell growth and cell cycle progression in response to cellular signals. It is a key regulator of cell proliferation and many upstream activators and downstream effectors of mTOR are known to be deregulated in various types of cancers. Since the mTOR signalling pathway is commonly activated in human cancers, many researchers are actively developing inhibitors that target key components in the pathway and some of these drugs are already on the market. Numerous preclinical investigations have also suggested that some herbs and natural phytochemicals, such as curcumin, resveratrol, timosaponin III, gallic acid, diosgenin, pomegranate, epigallocatechin gallate (EGCC), genistein and 3,3'-diindolylmethane inhibit the mTOR pathway either directly or indirectly. Some of these natural compounds are also in the clinical trial stage. In this review, the potential anti-cancer and chemopreventive activities and the current status of clinical trials of these phytochemicals are discussed.

      • 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>

      • KCI등재

        An Efficient Parallel Infilling Strategy and Its Application in Sheet Metal Forming

        Yan-Min Xie,Yuan-Heng Guo,Fei Zhang,Yue-Peng Yue,Mei-Qiang Feng,Jiang-Bo Zhao 한국정밀공학회 2020 International Journal of Precision Engineering and Vol.21 No.8

        Infilling strategies play an important role in kriging based optimization, especially when computationally expensive simulations are involved. In order to improve the efficiency of constructing a high-precision kriging model, an improved expected improvement criterion (IEI) and a parallel infilling strategy are proposed based on the maximum expected improvement (EI) criterion. In the proposed parallel infilling strategy, new sample points are generated by employing IEI criterion coupled with EI criterion. During the improved sampling process, redundant and pseudo sample are deleted in order to avoid failure of constructing a kriging model. An improved weighted particle swarm optimization (WPSO) algorithm is proposed to improve optimization efficiency. The proposed parallel infilling strategy is applied to nonlinear function optimization and variable blank holder force (VBHF) optimization in a double-c stamped part. Based on the LHD and software DYNAFORM, kriging models between the VBHF and forming quality are constructed. Compared with the initial kriging models, the meat relative error of kriging models with the proposed parallel infilling strategy for the wrinkling and average thinning rate are reduced by 95% and 55%, respectively. The optimal VBHF is obtained by the WPSO. The results show that, cracking has been completely eliminated and wrinkling has been decreased, greatly improving the forming quality of the double-c stamped part.

      • KCI등재

        Tissue distribution and functional characterization of odorant binding proteins in Chilo suppressalis (Lepidoptera: Pyralidae)

        Sajjad Ali Khuhro,Hui Liao,Guan-Heng Zhu,Shuang-Mei Li,Zhan-Feng Ye,Shuang-Lin Dong 한국응용곤충학회 2017 Journal of Asia-Pacific Entomology Vol.20 No.4

        Odorant binding proteins (OBPs) play important roles in the insect olfaction and other diverse physiological processes. Forty OBP genes have been molecularly identified from Chilo suppressalis (Walker), a notorious rice pest in Asian countries, but little is known about the olfactory function for most of these genes. In the present study, we first determined the tissue expression profiles of 34 OBPs (excluding two general odorant bonding proteins (GOBPs) and four pheromone binding protein (PBPs)) by quantitative real-time PCR (qPCR), and found that 9 genes (OBP1, 3, 4, 11, 15, 17, 19, 20 and 24) were specifically or predominantly expressed in antennae of both sexes, suggesting their roles in olfaction, while three genes (OBP29, 30 and 32) were almost not expressed in antennae. Focusing on olfactory roles, the ligand specificities of six antenna specifically or predominantly expressed genes were further investigated for 35 plant volatiles, using the fluorescence competitive binding assays. The results revealed that six OBPs displayed different ligand preference, suggesting a differentiation of OBPs in ligand binding spectrum. Of six tested OBPs, OBP3, 11, 17, 19 and 31 showed moderate (Ki =10.21–19.85 μM) or high (Ki < 10.00 μM) binding affinity for 11 and one plant volatiles, respectively. In particular, a plant volatile β-ionone had high or moderate binding to all five OBPs. Our study suggests that these five OBP genes play important roles in the perception of different host plant volatiles, providing insight into the olfactory mechanism in C. suppressalis.

      • KCI등재

        Two New Coumarin Glucosides from the Roots of Angelica apaensis and Their Anti-Platelet Aggregation Activity

        Wei-Lie Xiao,Sheng-Hong Li,Yun-Heng Shen,Xue-Mei Niu,Han-Dong Sun 대한약학회 2007 Archives of Pharmacal Research Vol.30 No.7

        Two new coumarin glucosides, 11-O-β-D-glucopyranosyl thamnosmonin (1) and 12-O-β-D-glucopyranosyl gosferol (2), were isolated from the roots of Angelica apaensis. Their structures were elucidated spectroscopically. Both compounds showed weak inhibitory effects on rabbit platelet aggregation induced by PAF, AA and APD.

      • SCIESCOPUSKCI등재

        Two New Coumarin Glucosides from the Roots of Angelica apaensis and Their Anti-Platelet Aggregation Activity

        Xiao, Wei-Lie,Shen, Yun-Heng,Niu, Xue-Mei,Sun, Han-Dong,Li, Sheng-Hong 대한약학회 2007 Archives of Pharmacal Research Vol.30 No.7

        Two new coumarin glucosides, $11-O-{\beta}-D-glucopyranosyl$ thamnosmonin (1) and $12-O-{\beta}-D-glucopyranosyl$ gosferol (2), were isolated from the roots of Angelica apaensis. Their structures were elucidated spectroscopically. Both compounds showed weak inhibitory effects on rabbit platelet aggregation induced by PAF, AA and APD.

      • SPON2 Promotes M1-like Macrophage Recruitment and Inhibits Hepatocellular Carcinoma Metastasis by Distinct Integrin–Rho GTPase–Hippo Pathways

        Zhang, Yan-Li,Li, Qing,Yang, Xiao-Mei,Fang, Fang,Li, Jun,Wang, Ya-Hui,Yang, Qin,Zhu, Lei,Nie, Hui-Zhen,Zhang, Xue-Li,Feng, Ming-Xuan,Jiang, Shu-Heng,Tian, Guang-Ang,Hu, Li-Peng,Lee, Ho-Young,Lee, Su-J American Association for Cancer Research 2018 Cancer research Vol.78 No.9

        <P>Matricellular protein SPON2 acts as an HCC suppressor and utilizes distinct signaling events to perform dual functions in HCC microenvironment.</P><P>Tumor-associated macrophages (TAM) represent key regulators of the complex interplay between cancer and the immune microenvironment. Matricellular protein SPON2 is essential for recruiting lymphocytes and initiating immune responses. Recent studies have shown that SPON2 has complicated roles in cell migration and tumor progression. Here we report that, in the tumor microenvironment of hepatocellular carcinoma (HCC), SPON2 not only promotes infiltration of M1-like macrophages but also inhibits tumor metastasis. SPON2-α4β1 integrin signaling activated RhoA and Rac1, increased F-actin reorganization, and promoted M1-like macrophage recruitment. F-Actin accumulation also activated the Hippo pathway by suppressing LATS1 phosphorylation, promoting YAP nuclear translocation, and initiating downstream gene expression. However, SPON2-α5β1 integrin signaling inactivated RhoA and prevented F-actin assembly, thereby inhibiting HCC cell migration; the Hippo pathway was not noticeably involved in SPON2-mediated HCC cell migration. In HCC patients, SPON2 levels correlated positively with prognosis. Overall, our findings provide evidence that SPON2 is a critical factor in mediating the immune response against tumor cell growth and migration in HCC.</P><P><B>Significance:</B> Matricellular protein SPON2 acts as an HCC suppressor and utilizes distinct signaling events to perform dual functions in HCC microenvironment.</P><P><B>Graphical Abstract:</B> http://cancerres.aacrjournals.org/content/canres/78/9/2305/F1.large.jpg. <I>Cancer Res; 78(9); 2305–17. ©2018 AACR</I>.</P><P><B>Graphical Abstract</B></P><P> [Figure]</P>

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