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Xue-Song Bai,1,* Chi Zhang,2,* Rui Peng,2,* Guo-Qing Jiang,2 Sheng-Jie Jin,2 Qian Wang,2 Ai-Wu Ke,3 Dou-Sheng Bai2 1The First Clinical Medical College, Dalian Medical University, Dalian, Liaoning 116044, People’s Republic of China; 2Department of Hepatobiliary Surgery, Clinical Medical College, Yangzhou University, Yangzhou 225009, Jiangsu, People’s Republic of China; 3Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, People’s Republic of China*These authors contributed equally to this workCorrespondence: Dou-Sheng BaiClinical Medical College, Yangzhou University, 98 West Nantong Road, Yangzhou, Jiangsu 225000, People’s Republic of ChinaTel +86-514-87373385Fax +86-514-87990188Email drbaidousheng@163.comBackground: The ubiquitin-proteasome system participates in the pathogenesis and progression of hepatocellular carcinoma (HCC). As an E3 ubiquitin ligase, RNF128 has been proved vital in carcinogenesis, whereas, little is known about the oncogenic mechanisms of RNF128 in HCC.Materials and Methods: Through tissue microarray from HCC patients, we analyzed RNF128 expression and its relationship with clinical outcomes in HCC. Western blot and quantitativerealtime polymerase chain reaction (qRT-PCR) were performed to examine expression levels of RNF128 in HCC tissues and cell lines. Effects of RNF128 on HCC cellular biological functions and the potential mechanism were evaluated through knockdown and overexpression assays in vitro and in vivo methods.Results: RNF128 expression was found to be remarkably elevated in HCC tissues compared with adjacent normal tissues. Furthermore, the overexpression of RNF128 enhanced hepatoma cells proliferation, colony formation, migration, invasion, and apoptotic resistance both in vitro and in vivo. Mechanistically, RNF128 activated EGFR/MEK/ERK signaling pathway and the EGFR inhibitor, gefitinib partially reversed RNF128-enhanced proliferation, invasion, and migration in hepatoma cells.Conclusion: RNF128 promotes HCC progression by activating EGFR/MEK/ERK signaling pathway, which might function as a novel prognostic molecular signature with the potential to be a candidate therapeutic target for HCC patients.Keywords: hepatocellular carcinoma, RNF128, ubiquitination, EGFR/MEK/ERK signaling pathway, prognosis

Direct numerical simulations (DNS) of low and high Karlovitz number (Ka) flames are analysed to investigate the behaviour of the reactive scalar sub-grid scale (SGS) variance in premixed combustion under a wide range of combustion conditions (regimes). An order of magnitude analysis is performed to assess the importance of various terms in the variance evolution equation and the analysis is validated using the DNS results. This analysis sheds light on the relative behaviour among turbulent transport and production, scalar dissipation and chemical processes involved in the evolution of the SGS variance at different Ka. The common expectation is that the variance equation shifts from a reaction-dissipation balance at low Ka to a production–dissipation balance at high Ka with diminishing reaction contribution. However, in large eddy simulation (LES), a high Ka alone does not make the reaction term negligible, as the relative importance of the reaction term has a concurrent increase with filter size. The filter size can be relatively large compared with the Kolmogorov length scale in practical LES of high Ka flames, and as a consequence a reaction–production–dissipation balance may prevail in the variance equation even in a high Ka configuration, and this possibility is quantified using the DNS analysis in this work. This has implications from modelling perspectives, and therefore two commonly used closures in LES for the SGS scalar dissipation rate are investigated a priori to estimate the importance of the above balance in LES modelling. The results are explained to highlight the interplay among turbulence, chemistry and dissipation processes as a function of Ka.