Cancer-initiating cells (CICs) are responsible for tumor initiation, progression, and therapeutic resistance; moreover, redox homeostasis is important in regulating cancer stemness. Previously, we have identified that cancer cells containing low intracellular reactive oxygen species levels (ROSLow cells) display enhanced features of CICs. However, the specific metabolic signatures of CICs remain unclear and are required for further characterization by systemic screenings. Herein, we first showed CICs mainly relying on glycolysis that was important for the maintenance of stemness properties. Next, we revealed that NRF2, a master regulator of antioxidants, was able to maintain low intracellular ROS levels of CICs, even though in the absence of oxidative stress. We further characterized that NRF2 activation was required for the maintenance of CICs properties. Of ROSLow cells, NRF2 activation not only directly activates the transcription of genes encoding glycolytic enzymes but also inhibited the conversion of pyruvate to acetyl-CoA by directly activating pyruvate dehydrogenase kinase 1 (PDK1) to lead to inhibition of tricarboxylic acid (TCA) cycle; therefore, to promote Warburg effect. A positive regulatory ROS-independent ER stress pathway (GRP78/p-PERK/NRF2 signaling) was identified to mediate the metabolic shift (Warburg effect) and stemness of CICs. Lastly, co-expression of p-PERK and p-NRF2 was significantly associated with the clinical outcome. Our data show that NRF2 acting as a central node in the maintenance of low ROS levels and stemness associated properties of the CICs, which is significantly associated with the clinical outcome, but independent from ROS stress. Future treatments by inhibiting NRF2 activation may exhibit great potential in targeting CICs.
Ironmaking process by Blast Furnace (BF) method contributes about 70% of CO 2 emission and energy consumption in steel works. To aim at the sustainable development and environmental protection, decreasing CO 2 emission and energy consumption is always an indispensable task. Using iron ore-coal composite as the raw material of BF is a promising way to mitigate the above issue.In this study, we conducted an experiment procedure which is to simulate the reduction of an iron orecoal composite travelling from the top zone to the cohesive zone of BF. Reduction behavior, morphology changes and carburization characteristic of the composites with the variables of C/O (Carbon to Oxygen) ratio were investigated.As C/O ratio was increased from 0 to 0.6, the reduction rate of composite was accordingly enhanced. It was found that the composite is swelling severely when C/O ratio was lower than 0.4. The swelling occurred in the temperature range from 800°C to 1 100°C which was just under the stage of reduction from wustite to iron. The composite is shattering obviously starting from 1 160°C when C/O ratio was higher than 0.4. It is because the remained free carbon is surplus in reduced iron, causing shattering and powdering. Hence, C/O = 0.4 was suggested to the composite for being charged into BF.
In this study, Ti3SiC2 was successfully synthesized by the combustion of green samples with a composition formula: (3-x)Ti/Si/(2-x)C/xTiC, where x ranged from 1.0 to 1.8. First, the Ti3SiC2 yield monotonically increased with x, but the maximal yield was less than 50%. The most important factor to increase the Ti3SiC2 yield was found to be the post-combustion heating. The yield dramatically increased to about 90% when a 150-second post-combustion heating time was provided. Furthermore, the yield was proportional to the post-heating time, and linearly increased with the amount of applied post-combustion heating energy. Next, excess Si in the starting reactant powders can further increase the extent of Ti3SiC2. When the mole of Si increased from 1.0 to 1.1, the resulted yield was more than 99%. For the study of reaction mechanism, analyses of sequential layers of quenched samples resulted in the following proposed mechanism. First, TiC, TiSi2, Ti5Si3 were formed from the reactions of Ti, Si and C powders. Next, the eutectic liquids (Ti-Ti5Si3 and Si-TiSi2) covered the TiC particles at the elevated temperature. In the final stage, product Ti3SiC2 was resulted from heating the eutectics and TiC. It is noted that the last two steps required large energy, indicating the post-combustion heating was crucial to produce high-purity Ti3SiC2 product.
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