Search

Lipid metabolism has been considered as a potential therapeutic target in sevoflurane‐induced neurotoxicity that can potentially affect the learning and memory function in the developmental brain. Recently, triggering receptor expressed on myeloid cells 2 (TREM2) is identified as a crucial step in regulating lipid metabolism and associated with the pathogenesis of neurodegenerative diseases. Herein, it is reported that quercetin modified Cu2‐xSe (abbreviated as CSPQ) nanoparticles can ameliorate sevoflurane‐induced neurotoxicity by tuning the microglial lipid metabolism and promoting microglial M2‐like polarization via TREM2 signaling pathway, in which the apolipoprotein E (ApoE), and adenosine triphosphate‐binding cassette transporters (ABCA1 and ABCG1) levels are upregulated. Furthermore, the protective effects of CSPQ nanoparticles against sevoflurane‐induced neurotoxicity via TREM2 are further demonstrated by the small interfering RNA (siRNA)‐TREM2 transfected BV2 cells, which are obviously not influenced by CSPQ nanoparticles. The cell membrane coated CSPQ (referred as CSPQ@CM) nanoparticles can significantly reduce sevoflurane‐induced learning and memory deficits, improve lipid metabolism dysfunction, and promote the remyelination in the hippocampus of mice. The study shows great potential of targeting microglial lipid metabolism in promoting remyelination of neurons for treatment of neurotoxicity and neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Silicon suboxide (SiOx) has attracted widespread interest as Li‐ion battery (LIB) anodes. However, its undesirable electronic conductivity and apparent volume effect during cycling impede its practical applications. Herein, sustainable rice husks (RHs)‐derived SiO2 are chosen as a feedstock to design SiOx/iron–nitrogen co‐doped carbon (Fe–N–C) materials. Using a facile electrospray‐carbonization strategy, SiOx nanoparticles (NPs) are encapsulated in the nitrogen‐doped carbon (N–C) frameworks decorating atomically dispersed iron sites. Systematic characterizations including high‐angle annular dark‐field scanning transmission electron microscopy (HAADF‐STEM) and X‐ray absorption fine structure (XAFS) verify the existence of Fe single atoms and typical coordination environment. Benefiting from its structural and compositional merits, the SiOx/Fe–N–C anode delivers significantly improved discharge capacity of 799.1 mAh g−1, rate capability, and exceptional durability, compared with pure SiO2 and SiOx/N–C, which has been revealed by the density functional theory (DFT) calculations. Additionally, the electrochemical tests and in situ X‐ray diffraction (XRD) analysis reveal the oxidation of LixSi phase and the storage mechanism. The synthetic strategy is universal for the design and synthesis of metal single atoms/clusters dispersed N–C frameworks encapsulated SiOx NPs. Meanwhile, this work provides impressive insights into developing various LIB anode materials suffering from inferior conductivity and huge volume fluctuations. [ABSTRACT FROM AUTHOR]

Targeting the G2/M checkpoint mediator WEE1 has been explored as a novel treatment strategy in ovarian cancer, but mechanisms underlying its efficacy and resistance remains to be understood. Here, it is demonstrated that the WEE1 inhibitor AZD1775 induces endoplasmic reticulum stress and activates the protein kinase RNA‐like ER kinase (PERK) and inositol‐required enzyme 1α (IRE1α) branches of the unfolded protein response (UPR) in TP53 mutant (mtTP53) ovarian cancer models. This is facilitated through NF‐κB mediated senescence‐associated secretory phenotype. Upon AZD1775 treatment, activated PERK promotes apoptotic signaling via C/EBP‐homologous protein (CHOP), while IRE1α‐induced splicing of XBP1 (XBP1s) maintains cell survival by repressing apoptosis. This leads to an encouraging synergistic antitumor effect of combining AZD1775 and an IRE1α inhibitor MKC8866 in multiple cell lines and preclinical models of ovarian cancers. Taken together, the data reveal an important dual role of the UPR signaling network in mtTP53 ovarian cancer models in response to AZD1775 and suggest that inhibition of the IRE1α‐XBP1s pathway may enhance the efficacy of AZD1775 in the clinics. [ABSTRACT FROM AUTHOR]