ENO1 expression and Erk phosphorylation in PDAC and their effects on tumor cell apoptosis in a hypoxic microenvironment

Objective: Hypoxia is an important feature of pancreatic ductal adenocarcinoma(PDAC). Previously, we found that hypoxia promotes ENO1 expression and PDAC invasion. However, the underlying molecular mechanism was remains unclear.Methods: The relationship between ENO1 expression and clinicopathological characteristics was analyzed in 84 patients with PADC. The effects of CoCl2-induced hypoxia and ENO1 downregulation on the apoptosis, invasion, and proliferation of PDAC cells were evaluated in vitro and in vivo. Hypoxia-and ENO1-induced gene expression was analyzed by transcriptomic sequencing.Results: The prognosis of PDAC with high ENO1 expression was poor(P < 0.05). High ENO1 expression was closely associated with histological differentiation and tumor invasion in 84 PDAC cases(P < 0.05). Hypoxia increased ENO1 expression in PDAC and promoted its migration and invasion. Apoptotic cells and the apoptosis marker caspase-3 in the CoCl_(2)-treated ENO1-sh group were significantly elevated(P < 0.05). Transcriptomic sequencing indicated that CoCl_(2)-induced PDAC cells initiated MAPK signaling. Under hypoxic conditions, PDAC cells upregulated ENO1 expression, thereby accelerating ERK phosphorylation and inhibiting apoptosis(P < 0.05). Consistent results were also observed in a PDAC-bearing mouse hindlimb ischemia model.Conclusions: Hypoxia-induced ENO1 expression promotes ERK phosphorylation and inhibits apoptosis, thus leading to PDAC survival and invasion. These results suggest that ENO1 is a potential therapeutic target for PDAC.

Effects of processing parameters and addition of flame-retardant into moulding sand on the microstructure and fluidity of sand-cast magnesium alloy Mg-10Gd-3Y-0.5Zr

In this study, the effects of processing parameters（such as pouring temperature and mould pre-heating temperature） and flame-retardant content on the microstructure and fluidity of sand-cast magnesium（Mg） alloy Mg-10Gd-3Y-0.5Zr（GW103K） were systematically investigated. It was found that the increase of pouring temperature leads to coarsened microstructure and decreased fluidity of sand-cast GW103 K alloy. Increase of mould pre-heating temperature incurs coarsening of as-cast microstructure and increase of fluidity. The addition of flame-retardant into moulding sand has a negligible influence on the microstructure of sand-cast GW103 K alloy. With the increase in flame-retardant content,fluidity of the alloy initially increases and then decreases. The optimized process parameters and flameretardant addition were obtained to be pouring temperature of 750？C, mould temperature of 110？C, and flame-retardant addition of 1%. The fire retardant mechanism of moulding sand was determined.