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ABSTRACTTrimetazidine (TMZ) has been used extensively to treat coronary artery disease and to reduce fibrosis. Liver fibrosis is a reversible process. However, the impacts of TMZ on liver fibrosis triggered by CCl4and on hepatic stellate cells in liver fibrosis remain to be elaborated. In the current study, the liver fibrosis models were constructed by using CCl4-induced mice and TGF-β-induced hepatic stellate cells. The involvement of TMZ in liver fibrosis was subsequently investigated. In the CCl4-induced hepatic fibrosis mouse model, it was shown that the expression levels of alanine aminotransferase and aspartate aminotransferase were reduced after TMZ treatment; the expression levels of the extracellular matrix proteins colla1 and α-SMA were down-regulated; furthermore, the expression levels of TGFβ/Smad signaling proteins were inhibited. In TGF-β-induced hepatic stellate cells, compared to the TGF-β-induced group, cell proliferation and migration were inhibited after TMZ treatment; meanwhile, extracellular matrix protein and TGFβ/Smad signaling protein expression levels followed the same trend as in the hepatic fibrosis model. In conclusion, TMZ could block the TGFβ/Smad signaling in liver fibrosis model, with inhibiting liver fibrosis and hepatic stellate cell proliferation. This may broaden the application sphere of TMZ in liver fibrosis therapy.

Lithium–sulfur (Li–S) batteries have been known to be a promising substitute because of their much higher theoretical energy density than that of traditional Li-ion batteries. However, the low utilization of sulfur caused by the poor conductivity of sulfur and shuttle of lithium polysulfides (LiPSs) severely restrict the commercial application of Li–S batteries, especially in flexible wearable devices. Herein, a hierarchical nitrogen-doped carbon nanotube (NCNT)@Co–Co3O4nanowire array (NWA)-integrated electrode was developed based on the rational design of density functional theory calculations, which shows simultaneous confinement adsorption and catalysis conversion of LiPSs. In situRaman spectra further proved that the NCNT@Co–Co3O4NWAs exhibit sufficient adsorption capacity and high catalytic conversion of LiPSs. As a result, the NCNT@Co–Co3O4@S electrode exhibited the desirable specific capacity and excellent cyclic stability at both low and high sulfur loadings. Moreover, pouch cells with the NCNT@Co–Co3O4@S cathode show higher capacity under flat or bending states and longer cycle stability than that of the reported results. This work provides a new approach for the development of high-performance Li–S batteries toward future wearable electronics.

Altered abundance or activity of the dual-function transient receptor potential melastatin-like 7 (TRPM7) protein is implicated in neurodegenerative disorders, including Alzheimer’s disease (AD). Toxic aggregation of amyloid-β (Aβ) in neurons is implicated in AD pathology. Here, we found that the kinase activity of TRPM7 is important to stimulate the degradation of Aβ. TRPM7 expression was decreased in hippocampal tissue samples from patients with AD and two mouse models of AD (APP/PS1and 5XFAD). In cultures of hippocampal neurons from mice, overexpression of full-length TRPM7 or of its functional kinase domain M7CK prevented synapse loss induced by exogenous Aβ. In contrast, this neuroprotection was not afforded by overexpression of either the functional ion channel portion alone or a TRPM7 mutant lacking kinase activity. M7CK overexpression in the hippocampus of young and old 5XFADmice prevented and reversed, respectively, memory deficits, synapse loss, and Aβ plaque accumulation. In both neurons and mice, M7CK interacted with and activated the metalloprotease MMP14 to promote Aβ degradation. Thus, TRPM7 loss in patients with AD may contribute to the associated Aβ pathology.

Flexible zinc (Zn) metal batteries (ZMBs) has attracted particularly attention due to much high volumetric capacity of Zn anodes (5845 mAh cm−3) and abundant Zn resources in the earth. However, the unfavorable mechanical flexibility and poor cycling stability caused by the rigid and uncontrolled dendrites of Zn anodes hinder their development. Herein, a dendrite-free Zn metal anode is acheived by an ultrathin NH4V4O10film modified carbon cloth, which can be served as Zn nucleation sites to effectively reduce the overpotential for Zn uniform deposition. As a result, the half-cell with carbon cloth@NH4V4O10-16 (CC@NVO-16) electrode exhibited a stable cycling performance of over 280 cycles at 1 mA cm−2with a high Coulombic efficiency of 99.21% and much lower overpotential. Excitingly, the flexible solid-state ZMB with the CC@NVO-16@Zn exhibits a superior stability and a high energy density of 374.6 Wh kg−1/980.0 W kg−1, which is superior to the most recent report so far. This work also provides an efficient strategy in constructing long-life and safe flexible ZMBs systems.