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| 1 | Sorafenib inhibits growth and metastasis of hepatocellular carcinoma by blocking STAT3显示文摘AIM: To investigate the inhibitory role and the underlying mechanisms of sorafenib on signal transducer and activator of transcription 3 (STAT3) activity in hepatocellular carcinoma (HCC).METHODS: Human and rat HCC cell lines were treated with sorafenib. Proliferation and STAT3 dephosphorylation were assessed. Potential molecular mechanisms of STAT3 pathway inhibition by sorafenib were evaluated. In vivo antitumor action and STAT3 inhibition were investigated in an immunocompetent orthotopic rat HCC model.RESULTS: Sorafenib decreased STAT3 phosphorylationat the tyrosine and serine residues (Y705 and S727), but did not affect Janus kinase 2 (JAK2) and phosphatase shatterproof 2 (SHP2), which is associated with growth inhibition in HCC cells. Dephosphorylation of S727 was associated with attenuated extracellular signal-regulated kinase (ERK) phosphorylation, similar to the effects of a mitogen-activated protein kinase (MEK) inhibitor U0126, suggesting that sorafenib induced S727 dephosphorylation by inhibiting MEK/ERK signaling. Meanwhile, sorafenib could also inhibit Akt phosphorylation, and both the phosphatidylinositol-3-kinase (PI3K) inhibitor LY294002 and Akt knockdown resulted in Y705 dephosphorylation, indicating that Y705 dephosphorylation by sorafenib was mediated by inhibiting the PI3K/Akt pathway. Finally, in the rat HCC model, sorafenib signifi cantly inhibited STAT3 activity, reducing tumor growth and metastasis.CONCLUSION: Sorafenib inhibits growth and metastasis of HCC in part by blocking the MEK/ERK/STAT3 and PI3K/Akt/STAT3 signaling pathways, but independent of JAK2 and SHP2 activation. | Fang-Ming Gu, Quan-Lin Li, Qiang Gao, Jia-Hao Jiang, Xiao-Yong Huang, Jin-Feng Pan, Jia Fan, Jian ZhouFang-Ming Gu, Quan-Lin Li, Qiang Gao, Jia-Hao Jiang, Xiao-Yong Huang, Jin-Feng Pan, Jia Fan, Jian Zhou, Liver Cancer Institute, Zhongshan Hospital and Shanghai Medical School, Fudan University, Shanghai 200032, China Author contributions: Gu FM, Li QL and Gao Q contributed equally to this work Gu FM and Li QL performed the experi- ments and interpretation of the data and statistical analysis Zhou J and Gao Q contributed to the conception and design of the study Gu FM, Gao Q, Li QL and Zhou J wrote the manuscript Jiang JH, Huang XY, Pan JF and Fan J made substantial contri- bution to the design and conception of the study and interpreta- tion of data all authors read and approved the f inal manuscript. | 2011 | World Journal of Gastroenterology2011，17，34： | 18 |
| 2 | A long-form α-neurotoxin from cobra venom produces potent opioid-independent analgesia显示文摘Aim:In light of the antinociceptive activity of the short-chain neurotoxin,cobrotoxin,and other acetylcholine antagonists,the antinociceptive activity andmechanisms of cobratoxin(CTX),a long-chain postsynaptic α-neurotoxin,wasinvestigated in rodent pain models.Methods:CTX was administered intraperito-neally(30,45,68 μg/kg),intra-cerebral ventricularly(4.5 μg/kg)or microinjectedinto periaqueductal gray(PAG;4.5 μg/kg).The antinociceptive action was testedusing the hot-plate and acetic acid writhing tests m mice and rats.The involve-ment of the cholinergic system and opioid system in CTX-induced analgesia wasexamined by pretreatment of animals with atropine(0.5 mg/kg,im;or 10 mg/kg,ip)or naloxone(1 and 5 mg/kg,ip).The effect of CTX on motor activity was testedusing the Animex test.Results:CTX exhibited a dose-dependent analgesic ac-tion in mice as determined by both the hot-plate and acetic acid writhing tests.The peak effect of analgesia was seen 3 h after administration.In the mouse aceticacid writhing test,the intra-cerebral ventricular administration of CTX at 4.5 μg/kg(1/12th of a systemic dose)produced marked analgesic effects.Microinjection ofCTX(4.5 μgkg)into the PAG region did not elicit an analgesic action in rats in thehot-plate test.Atropine at 0.5 mg/kg(im)and naloxone at 1 and 5 mg/kg(ip)bothfailed to block the analgesic effects of CTX,but atropine at 10 mg/kg(ip)didantagonize the analgesia mediated by CTX in the mouse acetic acid writhing test.Acetylsalicylic acid(300 mg/kg)did not enhance the analgesic effects of CTX.Atthe highest effective dose of 68 μg/kg the neurotoxin did not change the sponta-neous mobility of mice.Conclusion:CTX has analgesic effects,which are medi-ated in the central nervous system though not through the PAG.The centralcholinergic system but not opioid system appears to be involved in theantinociceptive action of CTX. | Zhi-xin CHEN Hui-ling ZHANG Zhen-lun GU Bo-wen CHEN Rong HAN Paul F REID Laurence N RAYMOND Zheng-hong QIN | 2006 | Acta Pharmacologica Sinica2006，27，4： | 7 |
| 3 | A Power and Area Optimization Approach of Mixed Polarity Reed-Muller Expression for Incompletely Specified Boolean Functions显示文摘力量和芦苇思考(RM ) 电路的区域优化广泛地被担心了。然而,几乎没有退出的力量和区域,优化来临能获得所有 Pareto 原版的最佳的答案问题并且足够有效。而且,他们没认为 dont 是照顾术语,它使电路成为性能不能进一步优化。在这糊,我们建议混合极性 RM 的一条力量和区域优化途径为不完全地指定的布尔功能的表示(MPRM ) 基于非统治的排序基因算法 II (NSGA-II ) 。第一,不完全地指定的布尔功能不完全地被转变成零极性由使用的指定 MPRM (ISMPRM ) 一篇小说 ISMPRM 获得算法。第二,极性和分配 ISMPRM 的照顾术语没作为染色体被编码。最后, Pareto 最佳的答案被使用 NSGA-II 获得,在里面哪个 MPRM 相应于给定的染色体被使用一个染色体获得变换算法。结果上重要力量和区域改进能与存在力量和区域优化相比被做的电路表演 RM 接近的不完全地指定的布尔功能和 MCNC 基准电路。 | Zhen-Xue He Li-Min Xiao Li Ruan Fei Gu Zhi-Sheng Huo Guang-Jun Qin Ming-Fa Zhu F Long-Bing Zhang Rui Liu Xiang Wang | 2017 | Journal of Computer Science & Technology2017，32，2： | 4 |
| 4 | Voltage-induced penetration effect in liquid metals at room temperature显示文摘Room-temperature liquid metal is discovered to be capable of penetrating through macro-and microporous materials by applying a voltage.The liquid metal penetration effects are demonstrated in various porous materials such as tissue paper;thick and fine sponges;fabrics;and meshes.The underlying mechanism is that the high surface tension of liquid metal can be significantly reduced to near-zero due to the voltage-induced oxidation of the liquid metal surface in a solution.It is the extremely low surface tension and gravity that cause the liquid metal to superwet the solid surface^leading to the penetration phenomena.These findings offer new opportunities for novel microfluidic applications and could promote further discovery of more exotic fluid states of liquid metals. | Frank F Yun Zhenwei Yu Yahua He Lei Jiang Zhao Wang Haoshuang Gu Xiaolin Wang | 2020 | National Science Review2020，7，2： | 3 |
| 5 | Prevalence of the metabolic syndrome and overweight among adults in China显示文摘 | Dongfeng Gu Kristi Reynolds Xigui Wu Jing Chen Xiufang Duan Robert F Reynolds Paul K Whelton Jiang He | 2005 | 2005 (9468)2005，，9468： | 3 |
| 6 | Enzymatic hydrolysis of proteins from yellowfin tuna ( Thunnus albacares ) wastes using Alcalase显示文摘 | F Guérard L Dufossé D De La Broise A Binet | 2001 | Journal of Molecular Catalysis B Enzymatic2001，，4： | 3 |
| 7 | Solving surface plasmon resonances and near field in metallic nanostructures:Green’s matrix method and its applications显示文摘With the development of nanotechnology,many new optical phenomena in nanoscale have been demonstrated.Through the coupling of optical waves and collective oscillations of free electrons in metallic nanostructures,surface plasmon polaritons can be excited accompanying a strong near field enhancement that decays in a subwavelength scale,which have potential applications in the surface-enhanced Raman scattering,biosensor,optical communication,solar cells,and nonlinear optical frequency mixing.In the present article,we review the Green's matrix method for solving the surface plasmon resonances and near field in arbitrarily shaped nanostructures and in binary metallic nanostructures.Using this method,we design the plasmonic nanostructures whose resonances are tunable from the visible to near-infrared,study the interplay of plasmon resonances,and propose a new way to control plasmonic resonances in binary metallic nanostructures. | GU Ying LI Jia MARTIN Olivier J F GONG QiHuang | 2010 | Chinese Science Bulletin2010，55，24： | 3 |
| 8 | A comparative study on the electron microscopic enzymo-cytochemistry of Paramecium bursaria from light and dark cultures显示文摘 | Gu F K Chen L Ni B | 2002 | Europ J Protistol2002，38，： | 2 |
| 9 | Prevalence of the metabolic syndrome and overweight among adults in China显示文摘 | Dongfeng Gu Kristi Reynolds Xigui Wu Jing Chen Xiufang Duan Robert F Reynolds Paul K Whelton Jiang He | 2005 | The Lancet . 2005 (9468)2005，，9468： | 2 |
| 10 | Secular change of annual and interannual variability in the tropics during the past century 显示文摘 | Gu D F Phlander S G H | 1995 | J Climate1995，8，4： | 2 |
| 11 | Direct shear test of sandstone-concrete joints显示文摘 | GU X F SEIDEL J P HABERFIELD C M | 2003 | International Journal of Geomechanics2003，3，1： | 1 |
| 12 | Mg-Ca-Zn bulk metallic glasses with high strength and significant ductility显示文摘 | GU X SHIFLET G J GUO F Q POON S J | 2005 | Journal of Materials Research2005，20，8： | 1 |
| 13 | Identification of cryll-type genes from Bacillus thuringiensis strains and characterization of novel cryll-type gene显示文摘 | Song F Zhang J Gu A | 2003 | Appl Environ Microbiol2003，69，9： | 1 |
| 14 | Combustion synthesis and lumines-cence properties ofDy3+-doped MgO nanoerystals显示文摘 | GU F WANG S E L0 M K | 2004 | J Cryst Growth2004，260，34： | 1 |
| 15 | The development of an adaptive threshold for model-based fault detection of a nonlinear electro-hydraulic system显示文摘 | Shi Z Gu F Lennox B | 2005 | Control Engineering Practice2005，，13： | 1 |
| 16 | Improved Nitrogen Transport in Surface Nanocrystallized Low Carbon Steels during Gaseous Nitridation 显示文摘 | Gu J F Bei D H Pan J S | 2002 | Mater Lett2002，55，： | 1 |
| 17 | Partial agonist actions of aripiprazole and the candidate antipsychotics S33592, bifeprunox, N-desmethylclozapine and preclamol at dopamine D(2L) receptors are modified by co-transfection of D3 receptors: potential role of heterodimer formation显示文摘 | Novi F Millan MJ Corsini GU | 2007 | J Neurochem2007，102，4： | 1 |
| 18 | Research progress of double-strained RNA interference( RNAi )in the application of different creatures 显示文摘 | Han P Wang X M Gu X F | 2002 | Nature2002，24，2： | 1 |
| 19 | Lipid distributions in loess-paleosol sequences from Northwest China显示文摘 | Xie S Chen F Wang Z Wang H Gu Y Huang Y | | 0，，08： | 1 |
| 20 | Early diagnosis of sepisis using serum biomarkers 显示文摘 | Chart T Gu F | 2011 | Exper Rev Mol Diagn2011，11，5： | 1 |
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