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>

Fluid Solid Coupling Analysis of Large Underground Oil Storage Caverns in Containment of Groundwater

Yang Shang-Yang,Li Shu-Cai,Xue Yi-Guo,Zhang Qing-Song 보안공학연구지원센터 2016 International Journal of Hybrid Information Techno Vol.9 No.11

Triaxial compression tests had been performed to determine the properties of the rock mass around unlining underground crude oil a storage cavern which was the first one in China. The execution situation of the tunnel project and the seepage law of groundwater were taken into account. The stress and the seepage field around the tunnel in different working states were simulated by applying Comsol around a underground crude oil storage caverns. According to the test results, it was found that the excavation process may arise the local damage. The extension of the loose zone induced by excavation ranged from 0 to 15.6 m, depending on the buried depth of the caverns. According to numerical simulation results, the crown settlement and stress concentration was depended on the buried depth and the water pressure distribution after excavation of the main cavity. This research results can provide the reference for analysis on the stability of the underground cavities under low stress level and on the water sealed underground petroleum storage rock caverns.

Finite Element Analysis on Mechanical Behaviour of Yungui Railway Tunnel in Shallow and Unsymmetrical Strata

Yang Shang-Yang,Li Shu-Cai,Xue Yi-Guo,Zhang Qing-Song 보안공학연구지원센터 2016 International Journal of Hybrid Information Techno Vol.9 No.10

Triaxial compression tests had been performed to determine the properties of the surrounding rock. The displacement and stress of surrounding rock had been analyzed according to Silin 2 at Yungui railway under three kinds of conditions: the initial state, excavation without supporting , and supporting after excavation. Plane strain FEM was established to analyze the stability of the surrounding rock. Contrasted the monitor measuring data, the results showed that the most unfavorable position in the tunnel was found at the ridge side of the arch, and the implementation of support afforded to ensure the stability of surrounding rock, and the design of the early support approach had the ability to meet the safety requirements. The results had certain significance for understanding the mechanical behavior of shallow tunnel in unsymmetrical strata. tunnel, mechanical behaviour, numerical simulation, deformation, stability.

Equivocal Association of RAD51 Polymorphisms with Risk of Esophageal Squamous Cell Carcinoma in a Chinese Population

Zhang, Shu-Xiang,Yang, Shan,Xu, Chang-Qing,Hou, Rui-Ping,Zhang, Chuan-Zhen,Xu, Cui-Ping Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.2

Aim: To study the contribution of genetic variation in RAD51 to risk of esophageal squamous cell carcinoma (ESCC). Methods: Three single nucleotide polymorphisms (SNPs) in RAD51 (rs1801320, rs4144242 and rs4417527) were genotyped in 316 ESCC patients and 316 healthy controls in Anyang area of China using PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism). Demographic variables between cases and controls were statistically compared by T test and Chi-square test. Hardy-Weinberg equilibrium was evaluated by the Chi-square test. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to measure any association with ESCC. Haplotype frequencies were estimated by Phase 2.1. Result: The genotype frequencies of rs1801320, rs4144242 and rs4417527 in patients with ESCC demonstrated no significant differences from those in control group (P>0.05). When the haplotypes of these three SNPs were constructed and their relationships with ESCC risk investigated, however, CGG was observed to increase the risk (P=0.020, OR=2.289). Conclusions: There was no association between the three SNPs of RAD51 and ESCC susceptibility in our Chinese population. However, the CGG haplotype might be a risk factor.

Effects of spin-casting speed on solar cell performances and corresponding films morphology and optical properties using 2D perovskite of PEA2MA2Pb3I10

Yang Zhang,Zeyang Wang,Ting Liu,Bo Yang,Shu Hu,Heng Li,ChuanXiang Sheng 대한금속·재료학회 2022 ELECTRONIC MATERIALS LETTERS Vol.18 No.3

On hot substrates with a temperature of 100 °C, the qualities of two-dimensional perovskite PEA2MA2Pb3I10(PEA = phenethylammonium,MA = methylammonium) films have been explored which are constructed with different spin-casting speeds. These films are performed at the speed of 1000, 2000, 4000, and 6000 revolution per minute (RPM). Below 4000 r, a higherRPM results in higher crystalline quality with more uniform morphology. Correspondingly, 4000 r devices show better performanceon average (4.3% power conversion efficiency) and less hysteresis in the J-V curve than 1000 r (3.6%) and 2000 rdevices (3.4%). However, for devices that were fabricated at 6000 r, inferior performance (2.8% on average) may not bepredicted simply by the morphology characterization or optical measurement results at room temperature; instead, carriertrapping states can occur that result in thermally activated PL below 200 K with an activation energy of 18 meV, which donot occur in the 1000 r, 2000 r, and 4000 r films. Our results suggest that for evaluating 2D perovskite films prior to fabricatingoptimal devices, multiple morphology characterizations and optical measurements, including of low-temperature PL,will be helpful.

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>

Systemic Inflammatory Biomarkers, Especially Fibrinogen to Albumin Ratio, Predict Prognosis in Patients with Pancreatic Cancer

Lin Fang,Fei-Hu Yan,Chao Liu,Jing Chen,Dan Wang,Chun-Hui Zhang,Chang-Jie Lou,Jie Lian,Yang Yao,Bo-Jun Wang,Rui-Yang Li,Shu-Ling Han,Yi-Bing Bai,Jia-Ni Yang,Zhi-Wei Li,Yan-Qiao Zhang 대한암학회 2021 Cancer Research and Treatment Vol.53 No.1

Purpose Systemic inflammatory response is a critical factor that promotes the initiation and metastasis of malignancies including pancreatic cancer (PC). This study was designed to determine and compare the prognostic value of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), and fibrinogen-to-albumin ratio (FAR) in resectable PC and locally advanced or metastatic PC. Materials and Methods Three hundred fifty-three patients with resectable PC and 807 patients with locally advan-ced or metastatic PC were recruited in this study. These patients were classified into a training set (n=758) and a validation set (n=402). Kaplan-Meier survival plots and Cox proportional hazards regression models were used to analyze prognosis. Results Overall survival (OS) was significantly better for patients with resectable PC with low preoperative PLR (p=0.048) and MLR (p=0.027). Low FAR, MLR, NLR (p < 0.001), and PLR (p=0.003) were significantly associated with decreased risk of death for locally advanced or metastatic PC patients. FAR (hazard ratio [HR], 1.522; 95% confidential interval [CI], 1.261 to 1.837; p < 0.001) and MLR (HR, 1.248; 95% CI, 1.017 to 1.532; p=0.034) were independent prognostic factors for locally advanced or metastatic PC. Conclusion The prognostic roles of FAR, MLR, NLR, and PLR in resectable PC and locally advanced or metastatic PC were different. FAR showed the most prognostic power in locally advanced or metastatic PC. Low FAR was positively correlated with OS in locally advanced or metastatic PC, which could be used to predict the prognosis.

Interference Alignment in Multi-user MIMO Systems

Zhang, Yang,Gu, Chaozhi,Shu, Ruo,Zhou, Zheng,Zou, Weixia The Korean Institute of Communications and Informa 2015 ICT Express Vol.1 No.1

Interference alignment (IA) has been studied extensively as an advanced technology to obtain the maximum degree of freedom (DoF) of multi-user wireless communication systems. This letter provides a brief review of recent works on IA. The most effective approach of IA is to deploy optimal linear transceivers by exploiting spatial characteristics of wireless channels. It is evaluated in measured multi-input multi-output (MIMO) interference channels. The implementation of IA depends on the characteristics of channel state information (CSI) feedback to the transmitters, such as imperfect, noisy, localized, delayed nature, and so on. In this work, we present a review of existing techniques for IA in typical multi-user MIMO systems. Moreover, we also consider some future research issues related to implementation. The study covers IA's feasibility conditions, solution algorithms in MIMO interference channel and MIMO multi-cell networks, with emphasis on the CSI feedback technology which remains as the major challenge of IA.

Ethyl Methane Sulfonate Induces Disease Resistance in Begonia × hiemalis Fotsch.

Yang-Er Chen,Ying-Hong Zhang,Shu Yuan,Han-Mei Liu,Xian-Yin Zeng,Huai-Yu Zhang 한국원예학회 2014 Horticulture, Environment, and Biotechnology Vol.55 No.6

To evaluate the disease resistance of Begonia × hiemalis Fotsch. ‘Schwabenland Red’ mutants induced byethyl methane sulphonate (EMS), we investigated the incidence and severity of stem rot caused by Rhizoctoniasolani Kuhn, and their morphological changes. In this study, we obtained three mutants with highly resistant diseaseafter two rounds of screening when the inoculated amount was 3 sheets/plant. The severity scale was 0 and therewere no obvious symptoms of stem rot in highly resistant Begonia × hiemalis. However, most of EMS mutagenizedplants were susceptible to stem rot caused by R. solani under this inoculated amount. In addition, these resistantmutants had different phenotypes as compared with the uninfected control plants. The color of leaves of the R. solani-resistent mutants was different with the control plants and their leaves were bigger than that of the control. The shape and number of their flowers were obviously different, as compared to the control plants.

Long-chain alcohols derived from the microalga Monoraphidium

Yang, Xuewei,Dai, Xin,Zhang, Rui,Shao, Cong,Geng, Shu,Chen, Guangyi,Liu, Xianhua,Wang, Guangyi Techno-Press 2013 Advances in energy research Vol.1 No.2

This study was to investigate the composition and characteristics of long-chained alcohols extracted from the algal strain Monoraphidium 3s35. The production of biomass was optimized using different cultivation methods. Under the aerated growth condition, this strain yielded up to 37.26% extracts of dry weight and $576mgL^{-1}$ biomass. The major compounds of the extracts are mainly long-chained alcohols (89.24%), with carbon chain length ranging from 12 to 20. Interestingly, or the long-chained alcohols, 3-(2-Methoxyethyl)-1-nonanol, 3,7,11,15-Tetramethyl-2-hexadecen-1-ol and oleyl alcohol accounted for 53.68%, 23.45%, and 12.11%, respectively. Because of their amphipathic nature, these long-chained alcohols have been widely used in bioenergy production and cosmetics industry. Furthermore, Monoraphidium 3s35 produced 9.73% of $C_{17}$ and $C_{20}$ alkanes, which can be used as an important supplement for the petrodiesel-like fuel.