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The energy density of redox flow batteries (RFBs) is generally affected by the standard electrode potential and the solubility of the redox active species. These crucial factors are closely related to the solvent in which the active materials are dissolved. Aqueous RFBs have been widely studied due to their excellent reaction kinetics and high solubility of the redox couple in aqueous media. However, the low voltage of conventional aqueous RFBs has hindered them from being candidates for practical applications. Recently, high‐voltage aqueous RFBs are implemented based on the low negative potential of the Zn/[Zn(OH)4]2− reaction in an alkaline solution. Here, we review recent progress in the design of high energy density RFBs in both aqueous and non‐aqueous electrolytes, notably focusing on the Zn/MnO2 hybrid RFBs in detail. Furthermore, strategies for inhibiting zinc dendritic growth and stabilizing manganese redox couple in the RFBs system are discussed. [ABSTRACT FROM AUTHOR]

Therapeutics targeting the phosphatidylinositol 3‐kinase/mammalian target of rapamycin (PI3K/mTOR) pathway initially produce potent antitumor effects, but resistance frequently occurs. Using a phosphoproteome analysis, we found that colorectal cancer (CRC) cells exhibit resistance against PI3K/mTOR inhibition through feedback activation of multiple receptor tyrosine kinases, and their downstream focal adhesion kinase, Src and extracellular signal‐regulated kinases signaling. Unexpectedly, PI3K/mTOR blockade causes senescence, mediated by the activation of the stress kinase p38. The senescent cancer cells induce the secretion of various cytokines and this senescence‐associated secretome increases migration and invasion capabilities of CRC cells. We found that cotargeting PI3K/mTOR and bromodomain and extra‐terminal domain can suppress activation of many oncogenic kinases involved in resistance to the PI3K/mTOR inhibition, induce cell death in vitro and tumor regression in vivo, and further prolong the survival of xenograft models. Our findings provide a rationale for a novel therapeutic strategy to overcome resistance to the PI3K/mTOR inhibitors in CRC. What's new? Cancer therapeutics targeting the PI3K/mTOR pathway initially produce potent anti‐tumor effects, but resistance frequently occurs. Here, the authors carried out a phosphoproteome analysis to investigate the resistance mechanism against PI3K/mTOR inhibition in colorectal cancer from a systems perspective. They found that multiple oncogenic kinases are activated to contribute to the survival of colorectal cancer cells under PI3K/mTOR blockade, and that these cells undergo pro‐tumorigenic senescence. Cotargeting PI3K/mTOR and BET exerts potent anti‐cancer activity by suppressing the activation of several resistance‐mediating kinases. The findings provide a rationale for a novel therapeutic strategy to overcome resistance to PI3K/mTOR inhibitors in colorectal cancer. [ABSTRACT FROM AUTHOR]

Cetuximab (CTX), a monoclonal antibody against epidermal growth factor receptor, is being widely used for colorectal cancer (CRC) with wild‐type (WT) KRAS. However, its responsiveness is still very limited and WT KRAS is not enough to indicate such responsiveness. Here, by analyzing the gene expression data of CRC patients treated with CTX monotherapy, we have identified DUSP4, ETV5, GNB5, NT5E, and PHLDA1 as potential targets to overcome CTX resistance. We found that knockdown of any of these five genes can increase CTX sensitivity in KRAS WT cells. Interestingly, we further found that GNB5 knockdown can increase CTX sensitivity even for KRAS mutant cells. We unraveled that GNB5 overexpression contributes to CTX resistance by modulating the Akt signaling pathway from experiments and mathematical simulation. Overall, these results indicate that GNB5 might be a promising target for combination therapy with CTX irrespective of KRAS mutation. From gene expression data analysis and mathematical modeling combined with cell experiments, we found that DUSP4, ETV5, GNB5, NT5E, and PHLDA1 expressions are correlated with cetuximab (CTX) resistance. In particular, we discovered that inhibition of GNB5 can overcome CTX resistance irrespective of KRAS mutation. We further revealed that GNB5 can regulate CTX resistance by dominantly modulating Akt signaling. [ABSTRACT FROM AUTHOR]