Abstract WWC family proteins negatively regulate HEK 293 cell proliferation and organ growth by suppressing the transcriptional activity of Yes‐associated protein ( YAP ), a major effector of the Hippo pathway. The function of the scaffolding protein WWC 1 (also called KIBRA ) has been intensively studied in cells and animal models. However, the expression and clinicopathologic significance of WWC 2 in cancer are poorly characterized. This study aimed to clarify the biological function and mechanism of action of WWC 2 in hepatocellular carcinoma ( HCC ). Retrospective analysis revealed WWC 2 was significantly down‐regulated in 95 clinical HCC tissues compared to the paired adjacent non‐cancerous tissues. Moreover, loss of WWC 2 expression was significantly associated with advanced clinicopathological features, including venous infiltration, larger tumour size and advanced TNM stage. Positive WWC 2 expression was associated with significantly better 5‐year overall survival, and WWC 2 was an independent prognostic factor for overall survival in HCC . Moreover, we confirmed WWC 2 inhibits HCC cell invasive ability in vitro . Elevated YAP expression was also observed in the same cohort of HCC tissues. Pearson's correlation coefficient analysis indicated WWC 2 expression correlated inversely with nuclear YAP protein expression in HCC . Mechanistically, we confirmed overexpression of WWC 2 suppresses the invasive and metastatic potential of HCC cells by activating large tumour suppressor 1 and 2 kinases ( LATS 1/2), which in turn phosphorylates the transcriptional co‐activator YAP . Overall, this study indicates WWC 2 functions as a tumour suppressor by negatively regulating the Hippo signalling pathway and may serve as a prognostic marker in HCC .
This paper addresses bitwidth optimization focusing on leakage power reduction for system-level low-power design. By means of tuning the design parameter, bitwidth tailored to a given application requirements, the datapath width of processors and size of memories are optimized resulting in significant leakage power reduction besides dynamic power reduction. Experimental results for several real embedded applications, show power reduction without performance penalty range from about 21.5% to 66.2% of leakage power, and 14.5% to 59.2% of dynamic power. key words: Bitwidth optimization, leakage power reduction, dynamic power reduction
Abstract The therapeutic hypothermia is an effective tool for TBI‐associated brain impairment, but its side effects limit in clinical routine use. Hypothermia up‐regulates RNA‐binding motif protein 3 (RBM3), which is verified to protect synaptic plasticity. Here, we found that cognitive and LTP deficits, loss of spines, AD‐like tau pathologies are displayed one month after TBI in mice. In contrast, the deficits of LTP and cognitive, loss of spines and tau abnormal phosphorylation at several sites are obviously reversed in TBI mice combined with hypothermia pre‐treatment (HT). But, the neuroprotective role of HT disappears in TBI mouse models under condition of blocking RBM3 expression with RBM3 shRNA. In other hand, overexpressing RBM3 by AAV‐RBM3 plasmid can mimic HT‐like neuroprotection against TBI‐induced chronic brain injuries, such as improving LTP and cognitive, loss of spines and tau hyperphosphorylation in TBI mouse models. Taken together, hypothermia pre‐treatment reverses TBI‐induced chronic AD‐like pathology and behaviour deficits in RBM3 expression dependent manner, RBM3 may be a potential target for neurodegeneration diseases including Alzheimer disease.
OBJECTIVE:To study the expression and significance of Ezrin in adenoid cystic carcinoma of salivary gland. METHODS: The expression of Ezrin was detected by the immunohistochemical method in adenoid cystic carcinoma of salivary gland and normal salivary gland tissues, and the correlations among the expression of Ezrin in adenoid cystic carcinoma of salivary gland and invasion, occurrence, metastasis and prognosis were analyzed. RESULTS: The over expression rates of Ezrin in adenoid cystic carcinoma of salivary gland and normal salivary gland tissues were 44.68% and 9.09%, respectively, P0.05; in the adenoid cystic carcinoma tissue, strong Ezrin immunostaining was detected mainly in the cytoplasma, whereas in the normal salivary gland tissue, Ezrin immunostaining was observed principally in the membrane and varied in intensity from weak to negative. The intensity of Ezrin expression was associated with the presence or absence of nerve invasion, locoregional recurrence and distant metastasis, P0.05. The 5-year cumulative survival rates in positive Ezrin expression group and negative Ezrin expression group were 66.70% and 100.00%, respectively; 10-year cumulative survival rates were 27.83% and 95.00%, respectively, and the positive Ezrin expression group had worse prognosis than the negative one, P0.05. CONCLUSION: The intensity of Ezrin expression is correlated with the genesis and ability of invasion, occurrence and metastasis of adenoid cystic carcinoma of salivary gland, and its positive expression indicates poor prognosis.
The huge market potential of some fast growing markets attract many international organizations’ attention, especially China, as a huge automobile market is one of the most typical examples. Theref ...
Purpose Research on grey systems is becoming more sophisticated, and grey relational and prediction analyses are receiving close review worldwide. Particularly, the application of grey systems in marine economics is gaining importance. The purpose of this paper is to summarize and review literature on grey models, providing new directions in their application in the marine economy. Design/methodology/approach This paper organized seminal studies on grey systems published by Chinese core journal database – CNKI, Web of Science and Elsevier from 1982 to 2018. After searching the aforementioned database for the said duration, the authors used the CiteSpace visualization tools to analyze them. Findings The authors sorted the studies according to their countries/regions, institutions, keywords and categories using the CiteSpace tool; analyzed current research characteristics on grey models; and discussed their possible applications in marine businesses, economy, scientific research and education, marine environment and disasters. Finally, the authors pointed out the development trend of grey models. Originality/value Although researches are combining grey theory with fractals, neural networks, fuzzy theory and other methods, the applications, in terms of scope, have still not met the demand. With the increasingly in-depth research in marine economics and management, international marine economic research has entered a new period of development. Grey theory will certainly attract scholars’ attention, and its role in marine economy and management will gain considerable significance.
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