The industrialization of lithium–sulfur (Li–S) batteries is simultaneously impeded by the shuttle effect of lithium polysulfides and dendrites growth on lithium anode. To address both issues, a novel sulfiphilic and lithiophilic interlayer of Mo2N quantum dots decorated N‐doped graphene‐nanosheet (Mo2N@NG) are presented on polypropylene separator via a facile scalable method. Benefiting from the strong chemisorption ability, eminent electrocatalysis for LiPSs, and high chemical affinity with lithium‐ion (Li+), Mo2N@NG can efficiently catalyze the rapid transformation of LiPSs and induce uniform deposition of Li+. Theoretical calculation and in situ Raman synergistically elucidate the inhibition of shuttle effect and alleviation of dendrite growth. As a result, the assembled Li–S cell with Mo2N@NG/PP separator exhibits remarkable rate performance (860.2 mA h g–1 at 4 C), good cycling stability (0.039% capacity decay per cycle after 800 cycles at 2 C), a high areal capacity of 3.89 mA h cm–2 of Li–S pouch cell (4.5 mg cm–2 and 6 µL mg–1 at 0.2 C), and steady performance in protecting the lithium anode (at 5 mA cm–2 for 1500 h). This present strategy of quantum dots in a hybrid framework has great potential to be generalized to other transition metal‐based catalysts for advanced Li–S batteries.
Patients suffering from glioblastoma have a dismal prognosis, indicating the need for new therapeutic targets. Here we provide evidence that the DNA damage kinase HIPK2 and its negative regulatory E3-ubiquitin ligase SIAH1 are critical factors controlling temozolomide-induced cell death. We show that HIPK2 downregulation (HIPK2kd) significantly reduces the level of apoptosis. This was not the case in glioblastoma cells expressing the repair protein MGMT, suggesting that the primary DNA lesion responsible for triggering HIPK2-mediated apoptosis is O 6 -methylguanine. Upon temozolomide treatment, p53 becomes phosphorylated whereby HIPK2kd had impact exclusively on ser46, but not ser15. Searching for the transcriptional target of p-p53ser46, we identified the death receptor FAS (CD95, APO-1) being involved. Thus, the expression of FAS was attenuated following HIPK2kd, supporting the conclusion that HIPK2 regulates temozolomide-induced apoptosis via p-p53ser46-driven FAS expression. This was substantiated in chromatin-immunoprecipitation experiments, in which p-p53ser46 binding to the Fas promotor was regulated by HIPK2. Other pro-apoptotic proteins such as PUMA, NOXA, BAX, and PTEN were not affected in HIPK2kd, and also double-strand breaks following temozolomide remained unaffected. We further show that downregulation of the HIPK2 inactivator SIAH1 significantly ameliorates temozolomide-induced apoptosis, suggesting that the ATM/ATR target SIAH1 together with HIPK2 plays a proapoptotic role in glioma cells exhibiting p53wt status. A database analysis revealed that SIAH1, but not SIAH2, is significantly overexpressed in glioblastomas.
Implications:The identification of a novel apoptotic pathway triggered by the temozolomide-induced DNA damage O 6 -methylguanine supports the role of p53 in the decision between survival and death and suggests SIAH1 and HIPK2 as new therapeutic targets.
The objective of this study was to test the hypothesis that p-cymene can attenuate acute lung injury induced by lipopolysaccharide (LPS) in vivo. In the mouse model of LPS-induced acute lung injury, intraperitoneal preconditioning with p-cymene resulted in a significant reduction of pro-inflammatory cytokines (TNF-α, IL-1β and IL-6), lung water gain, inflammatory cell infiltration, lung tissue myeloperoxidase activity. In addition, p-cymene blocked the phosphorylation of IκBα protein and mitogen-activated protein kinases (MAPK) signaling pathway activation. Histopathologic examination of lung tissue indicated that p-cymene treatment markedly decreased focal thickening, congestion, pulmonary edema, and inflammatory cells infiltration. The results showed that p-cymene had a protective effect on LPS-induced ALI in mice.
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