Cancer stem cells (CSCs) and epithelial–mesenchymal transition (EMT)‐type cells are considered as underlying causes of chemoresistance, tumour recurrence and metastasis in pancreatic cancer. We aimed to describe the mechanisms – particularly glycolysis – involved in the regulation of the CSC and EMT phenotypes. We used a gemcitabine‐resistant (GR) Patu8988 cell line, which exhibited clear CSC and EMT phenotypes and showed reliance on glycolysis. Inhibition of glycolysis using 2‐deoxy‐D‐glucose (2‐DG) significantly enhanced the cytotoxicity of gemcitabine and inhibited the CSC and EMT phenotypes in GR cells both in vitro and in vivo. Intriguingly, the use of the reactive oxygen species (ROS) scavenger N‐acetylcysteine (NAC) restored the CSC and EMT phenotypes. H2O2 produced changes similar to those of 2‐DG, indicating that ROS were involved in the acquired cancer stemness and EMT phenotypes of GR cells. Moreover, doublecortin‐like kinase 1 (DCLK1), a pancreatic CSC marker, was highly expressed and regulated the stemness and EMT phenotypes in GR cell. Both 2‐DG and H2O2 treatment suppressed DCLK1 expression, which was also rescued by NAC. Together, these findings revealed that glycolysis promotes the expression of DCLK1 and maintains the CSC and EMT phenotypes via maintenance of low ROS levels in chemoresistant GR cells. The glycolysis‐ROS‐DCLK1 pathway may be potential targets for reversing the malignant behaviour of pancreatic cancer.
Energy harvesting is gaining more and more attentions due to its characteristics of ultra-long operation time without maintenance. However, frequent unpredictable power failures from energy harvesters bring performance and reliability challenges to traditional processors. Nonvolatile processors are promising to solve such a problem due to their advantage of zero leakage and efficient backup and restore operations. To optimize the nonvolatile processor design, this paper proposes new metrics of nonvolatile processors to consider energy harvesting factors for the first time. Furthermore, we explore the nonvolatile processor design from circuit to system level. A prototype of energy harvesting nonvolatile processor is set up and experimental results show that the proposed performance metric meets the measured results by less than 6.27% average errors. Finally, the energy consumption of nonvolatile processor is analyzed under different benchmarks.
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