rs10505474 and rs7837328 at 8q24 Cumulatively Confer Risk of Prostate Cancer in Northern Han Chinese

Zhang, Lin-Lin,Sun, Liang,Zhu, Xiao-Quan,Xu, Yong,Yang, Kuo,Yang, Fan,Yang, Yi-Ge,Chen, Guo-Qiang,Fu, Ji-Cheng,Zheng, Chen-Guang,Li, Ying,Mu, Xiao-Qiu,Shi, Xiao-Hong,Zhao, Fan,Wang, Fei,Yang, Ze,Wang, Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.7

Aims: Genome-wide association studies (GWAS) have identified several risk variants for prostate cancer (pCa) mainly in Europeans, which need to be further verified in other racial groups. We selected six previously identified variants as candidates and to define the association with PCa in Northern Han Chinese. Methods: 749 subjects from Beijing and Tianjin in Northern China were included. Six variants (rs10505474, rs7837328, rs4242384, rs7813, rs486907 and rs1058205) were genotyped by high resolution melting (HRM) assays. The individual and cumulative contribution for of the risk of PCa and clinical covariates were analyzed. Results: Among the six candidate variants, onlyrs10505474, and rs7837328, both locating at 8q24 region, were associated with PCa in our population.rs10505474 (A) was associated with PCa ($OR_{recessive}=1.56$, p=0.006); and rs7837328 (A) was associated with PCa ($OR_{dominant}=1.38$, p=0.042/$OR_{recessive}=1.99$, p=0.003). Moreover, we observed a cumulative effects between them ($p_{trend}=2.58{\times}10^{-5}$). The joint population attributable risk showed the two variants might account for 71.85% of PCa risk. In addition, we found the homozygotes of rs10505474 (A) and rs7837328 (A) were associated with PCa clinical covariants (age at onset, tumor stage, respectively) ($p_{age}=0.046$, $P_{tumorstage}=0.048$). Conclusion: rs10505474 (A) and rs7387328 (A) at 8q24 are associated with PCa and cumulatively confer risk, suggesting the two variations could determine susceptibility to PCa in the Northern Chinese Han population.

Association of Leptin Receptor Lys109Arg and Gln223Arg Polymorphisms with Increased Risk of Clear Cell Renal Cell Carcinoma

Mu, Hui-Jun,Zou, Jian,Xie, Ping,Xu, Zhuo-Qun,Ruan, Jun,Yang, Shu-Dong,Yin, Ying Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.10

Background: Although roles of genetic polymorphisms of leptin receptor (LEPR) gene in several cancers have been documented, the association between polymorphisms of LEPR and clear cell renal cell carcinoma (CC-RCC) remains unknown. The aim of this study was to explore any relation. Materials and Methods: The study population consisted of 77 patients with CC-RCC and 161 healthy control subjects. Polymorphism analyses of Lys109Arg and Gln223Arg were performed by direct DNA sequencing and PCR-restriction fragment length polymorphism approaches respectively. Results: Comparisons of allelic and genotypic frequencies in Lys109Arg and Gln223Arg showed no significant difference between the cases and controls. However, when evaluating the combined genotype of Lys109Arg and Gln223Arg, risk with GG/GG was increased (OR=1.85, 95%CI=1.04-3.30) and with GA/GG or GG/GA was decreased (OR=0.07, 95%CI=0.01-0.54; OR and 95%CI of the latter could not be calculated for a value of zero). Furthermore, the G-G haplotype frequency of Lys109Arg and Gln223Arg in the cases was higher (OR=1.68; 95%CI=1.02-2.76). In contrast, the A-G and G-A haplotype frequencies in the cases were lower than those in the controls (OR=0.06; 95%CI=0.01 to 0.47; OR and 95%CI of the latter could not be calculated for a value of zero). In addition, the Lys109Arg A allele was in LD with the Gln223Arg A allele (d'=0.9399) in the CC-RCC subjects, but not in the controls. Conclusions: Our data suggest that the GG/GG combined genotype and G-G haplotype of Lys109Arg and Gln223Arg can act as evaluating factors for CC-RCC risk.

A computational integrating kinetic study on the flexible active site of human acetaldehyde dehydrogenase 1

Xu, Y.,Lee, J.,Yang, H.S.,Lu, Z.R.,Mu, H.,Yang, J.M.,Zhang, Q.,Park, Y.D. Elsevier Science B.V., Amsterdam. 2016 PROCESS BIOCHEMISTRY Vol.51 No.6

In order to gain more insight into the relation between the structure of acetaldehyde dehydrogenase 1 (ALDH1) and its catalytic and regional active site properties, the denaturant guanidine hydrochloride (GdnHCl) was employed in this study. The effects of GdnHCl on ALDH1 conformational and functional changes were evaluated by kinetic analysis and by performing computational molecular dynamics (MD) simulations. We found that direct binding of GdnHCl to ALDH1 induced complete inactivation prior to conspicuous changes in its tertiary structure or hydrophobic exposure, indicating that the active site is flexible compared to the overall structure. Kinetic experimental results and computational simulations indicated that there are specific sites on ALDH1 to which guanidine binds, resulting in blocking of catalytic function without a large degree of structural disruption. These sites may lay specifically in a cofactor-binding region, which was suggested by the observation of mixed-type inhibition. Our study provides insight into the flexibility of the ALDH1 active site through the use of GdnHCl denaturant and computational simulations to suggest possible binding mechanisms of inhibitors for the clinical applications.

Gastrin stimulates pancreatic cancer cell directional migration by activating the Gα12/13–RhoA–ROCK signaling pathway

Ganggang Mu,Qianshan Ding,Hongyan Li,Li Zhang,Lingli Zhang,Ke He,Lu Wu,Yunchao Deng,Dongmei Yang,Lianlian Wu,Ming Xu,Jie Zhou,Honggang Yu 생화학분자생물학회 2018 Experimental and molecular medicine Vol.50 No.-

The mechanism by which gastrin promotes pancreatic cancer cell metastasis is unclear. The process of directing polarized cancer cells toward the extracellular matrix is principally required for invasion and distant metastasis; however, whether gastrin can induce this process and its underlying mechanism remain to be elucidated. In this study, we found that gastrin-induced phosphorylation of paxillin at tyrosine 31/118 and RhoA activation as well as promoted the metastasis of PANC-1 cancer cells. Depletion of Gα12 and Gα13 inhibited the phosphorylation of paxillin and downstream activation of GTP-RhoA, blocked the formation and aggregation of focal adhesions and facilitated polarization of actin filaments induced by gastrin. Suppression of RhoA and ROCK also exhibited identical results. Selective inhibition of the CCKBR–Gα12/13–RhoA–ROCK signaling pathway blocked the reoriented localization of the Golgi apparatus at the leading edge of migrated cancer cells. YM022 and Y-27632 significantly suppressed hepatic metastasis of orthotic pancreatic tumors induced by gastrin in vivo. Collectively, we demonstrate that gastrin promotes Golgi reorientation and directional polarization of pancreatic cancer cells by activation of paxillin via the CCKBR–Gα12/13–RhoA–ROCK signal pathway.

Molecular and Biochemical Characterization of a Novel Xylanase from Massilia sp. RBM26 Isolated from the Feces of Rhinopithecus bieti

( Bo Xu ),( Li Ming Dai ),( Jun Jun Li ),( Meng Deng ),( Hua Biao Miao ),( Jun Pei Zhou ),( Yue Lin Mu ),( Qian Wu ),( Xiang Hua Tang ),( Yun Juan Yang ),( Jun Mei Ding ),( Nan Yu Han ),( Zun Xi Huang 한국미생물 · 생명공학회 2016 Journal of microbiology and biotechnology Vol.26 No.1

Xylanases sourced from different bacteria have significantly different enzymatic properties. Therefore, studying xylanases from different bacteria is important to their applications in different fields. A potential xylanase degradation gene in Massilia was recently discovered through genomic sequencing. However, its xylanase activity remains unexplored. This paper is the first to report a xylanase (XynRBM26) belonging to the glycosyl hydrolase family (GH10) from the genus Massilia. The gene encodes a 383-residue polypeptide (XynRBM26) with the highest identity of 62% with the endoxylanase from uncultured bacterium BLR13. The XynRBM26 expressed in Escherichia coli BL21 is a monomer with a molecular mass of 45.0 kDa. According to enzymatic characteristic analysis, pH 5.5 is the most appropriate for XynRBM26, which could maintain more than 90% activity between pH 5.0 and 8.0. Moreover, XynRBM26 is stable at 37°C and could maintain at least 96% activity after being placed at 37°C for 1 h. This paper is the first to report that GH10 xylanase in an animal gastrointestinal tract (GIT) has salt tolerance, which could maintain 86% activity in 5 M NaCl. Under the optimum conditions, Km, Vmax, and kcat of XynRBM26 to beechwood xylan are 9.49 mg/ml, 65.79 μmol/min/mg, and 47.34 /sec, respectively. Considering that XynRBM26 comes from an animal GIT, this xylanase has potential application in feedstuff. Moreover, XynRBM26 is applicable to high-salt food and seafood processing, as well as other high-salt environmental biotechnological fields, because of its high catalytic activity in high-concentration NaCl.

Novel artesunate-metformin conjugate inhibits bladder cancer cell growth associated with Clusterin/SREBP1/FASN signaling pathway

Lin Peiyu,Yang Xiyue,Wang Linghui,Zou Xin,Mu Lingli,Xu Cangcang,Yang Xiaoping 대한약리학회 2024 The Korean Journal of Physiology & Pharmacology Vol.28 No.3

Bladder cancer remains the 10th most common cancer worldwide. In recent years, metformin has been found to have potential anti-bladder cancer activity while high concentration of IC50 at millimolar level is needed, which could not be reached by regular oral administration route. Thus, higher efficient agent is urgently demanded for clinically treating bladder cancer. Here, by conjugating artesunate to metformin, a novel artesunate-metformin dimer triazine derivative AM2 was designed and synthesized. The inhibitory effect of AM2 on bladder cancer cell line T24 and the mechanism underlying was determined. Anti-tumor activity of AM2 was assessed by MTT, cloning formation and wound healing assays. Decreasing effect of AM2 on lipogenesis was determined by oil red O staining. The protein expressions of Clusterin, SREBP1 and FASN in T24 cells were evaluated by Western blotting. The results show that AM2 significantly inhibited cell proliferation and migration at micromolar level, much higher than parental metformin. AM2 reduced lipogenesis and down-regulated the expressions of Clusterin, SREBP1 and FASN. These results suggest that AM2 inhibits the growth of bladder cancer cells T24 by inhibiting cellular lipogenesis associated with the Clusterin/SREBP1/FASN signaling pathway.

Transcriptome sequencing and analysis of sweet osmanthus (Osmanthus fragrans Lour.)

Hong Na Mu,Liang Gui Wang,Huo Gen Li,Xiu Lian Yang,Tao Ze Sun,Chen Xu 한국유전학회 2014 Genes & Genomics Vol.36 No.6

Osmanthus fragrans is a woody, evergreenspecies of shrubs and small trees that is extensively plantedin sub-tropical and temperate climates as an ornamentalplant in gardens and for its health benefits. The flower colorranges from ivory to orange to pink among different varietiesand even color difference during the whole blossom inthe sweet osmanthus. Sweet osmanthus is widely cultivatedthroughout China and other countries due to its prominentfragrance, colorful flowers, and medicinal properties. However, the scanty genomic resources in the Olea familyhave greatly hindered further exploration of its geneticmechanism on these economically important traits. In thisstudy, transcriptome sequencing of O. fragrans was performedusing the Illumina HighSeqTM2000 sequencingplatform. Next generation sequencing (NGS) of the transcriptomeof O. fragrans produced 31.7G of clean bases(211,266,818 clean reads) that were assembled into256,774 transcripts and 117,595 unigenes. Of them, 197and 237 candidate genes involved in fragrance and pigmentbiosynthesis respectively were identified based on functionannotation. Meanwhile, 1 unnamed protein and 468 functionalunknown genes were also identified. Furthermore,mRNA sequencing expression profiling of O. fragranswere compared to previous genes’. In summary, thiscomprehensive transcriptome dataset allows the identificationof genes associated with several major metabolicpathways and provides a useful public information platformfor further functional genomic studiesin O. fragransLour.

DFT study of the oxidation of Hg0 by O2 on an Mn-doped buckled g-C3N4 catalyst

Liu Shuai,Xu Mengxia,Chen Yipei,Mu Xueliang,Yu Jiahui,Yang Gang,Luo Xiang,Jiang Peng,Wu Tao 한국물리학회 2022 Current Applied Physics Vol.40 No.-

Due to the water-insoluble nature of Hg0, its oxidization to Hg2+, which is water-soluble, is a viable approach for its effective removal at coal-fired plants using existing flue gas desulfurization (FGD) unit. In this study, the adsorption and oxidation of elemental mercury on an Mn-doped g-C3N4 material were investigated. The spinpolarized density functional theory method was adapted to optimize the geometry structures and then to determine the corresponding electronic structures, while the CI-NEB method was adopted to search for the stable intermediates during the reaction(s). The analysis of energy and project density of states shows that the Mn-g- C3N4 exhibits an excellent affinity to Hg atoms. It is found that it is feasible for Hg atoms to oxidize on the Mn-g- C3N4 surface via two possible E-R paths, but with relatively high energy barriers. This research provides insights into a viable way for mercury removal using O2 as the oxidizing agent.

Preparation and deposition mechanism of pyrolytic carbon by CVI using 3D Ni/wood-carbon catalyst

Lulu Han,Xiaohong Shi,Xu Han,Li Yang,Kun Li,Tian Xinfa,Mu Jierui,Wang Guoqing 한국탄소학회 2022 Carbon Letters Vol.32 No.1

To improve the pyrolytic carbon (PyC) deposition rate of Carbon/Carbon (C/C) composites prepared by the traditional chemical vapor infiltration (CVI) method, the 3D Ni/wood-carbon (3D Ni/C) catalyst was introduced into the CVI process. The effects of catalyst on the density of C/C composites were studied, and the deposition rate and morphologies of PyC were investigated after catalytic CVI. The morphologies of catalyst and PyC were characterized by scanning electron microscope and polarized light microscopy. The catalytic deposition mechanism of PyC was studied by density functional theory. The experimental results show that the initial carbon deposition efficiency of the catalytic pyrolysis process was 3–4 times that of the noncatalytic process. The catalyst reduced the energy barrier in the first step of deposition reaction from 382.55 to 171.67 kJ/mol according to simulation results. The pyrolysis reaction energy with Ni catalyst is reduced by 54% than that without the catalyst.

AUV hull lines optimization with uncertainty parameters based on six sigma reliability design

Hou, Yuan hang,Liang, Xiao,Mu, Xu yang The Society of Naval Architects of Korea 2018 International Journal of Naval Architecture and Oc Vol.10 No.4

Autonomous Underwater Vehicle (AUV), which are becoming more and more important in ocean exploitation tasks, needs energy conservation urgently when sailing the complex mission path in long time cruise. As hull lines optimization design becomes the key factor, which closely related with resistance, in AUV preliminary design stage, uncertainty parameters need to be considered seriously. In this research, Myring axial symmetry revolution body with parameterized expression is assumed as AUV hull lines, and its travelling resistance is obtained via modified DATCOM formula. The problems of AUV hull lines design for the minimum travelling resistance with uncertain parameters are studied. Based on reliability-based optimization design technology, Design For Six Sigma (DFSS) for high quality level is conducted, and is proved more reliability for the actual environment disturbance.