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The volume entropy of a compact metric measure space is known to be the exponential growth rate of the measure lifted to its universal cover at infinity. For a compact Riemannian n -manifold with a negative lower Ricci curvature bound and a upper diameter bound, it was known that it admits an almost maximal volume entropy if and only if it is diffeomorphic and Gromov-Hausdorff close to a hyperbolic space form. We prove the quantitative rigidity of almost maximal volume entropy for RCD ⁎ -spaces with a negative lower Ricci curvature bound and Riemannian manifolds with a negative L p -integral Ricci curvature lower bound. [ABSTRACT FROM AUTHOR]

Grain boundary enriched CuO nanobundle was reported to significantly increased the glucose diffusion as well as reduce the glucose oxidation barrier, thus displayed a lower onset potential of 94 mV, an extremely high sensitivity of 7474 μA mM−1 cm−2 in glucose detection and a high peak power density of 242 W m−2 in a glucose fuel cell. [Display omitted] • CuO nanobundle with high density and homogenous GBs was obtained by a facile and large-scale method. • A high sensitivity of 7474 μA mM−1 cm−2 in glucose detection and a high peak power density of 242 W m−2 in a glucose fuel cell are achieved. • CuO-NB possesses the faster glucose mass transfer due to the terraces in GBs dislocation surface. • Electrons accumulate on GBs interfaces promote glucose adsorption and decrease free energy of dehydrogenation step. Glucose oxidation reaction (GOR) plays a significant role in glucose fuel cells anode and glucose sensors. Therefore, optimizing the GOR catalyst nanostructure is auxiliary to their efficient operation. In this study, we present a cascade-assembled strategy to prepare CuO nanobundles (CuO-NB) with high-density and homogenous grain boundaries (GBs). The essence of activity in GOR that depended on GBs are thoroughly investigated. The increased glucose diffusion coefficient of CuO-NB means that GBs has a faster glucose mass transfer, which is attributed to the terraces in GBs dislocation surface. Furthermore, the accumulation of electrons on GBs makes the glucose adsorption increased and the free energy of dehydrogenation step decreased, leading to a lower glucose oxidation barrier. Therefore, CuO-NB is appropriate for non-invasive glucose detection and glucose fuel cells. This study sheds new light on the GBs effect in GOR and paves the way for developing high-efficiency electrocatalysts. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus (T2DM) is strongly associated with an increased risk of developing cognitive dysfunction. Numerous studies have indicated that erythropoietin (EPO) has neurotrophic effects. Ferroptosis has been reported to be associated with diabetic cognitive dysfunction. However, the impact of EPO on T2DM-associated cognitive dysfunction and its protective mechanism remain unclear. To evaluate the effects of EPO on diabetes-associated cognitive dysfunction, we constructed a T2DM mouse model and found that EPO not only decreased fasting blood glucose but also ameliorated hippocampal damage in the brain. The Morris water maze test indicated that EPO improved cognitive impairments in diabetic mice. Moreover, a ferroptosis inhibitor improved cognitive dysfunction in mice with T2DM in vivo. Furthermore, a ferroptosis inhibitor, but not other cell death inhibitors, mostly rescued high-glucose damaged PC12 cell viability. EPO had a similar effect as the ferroptosis inhibitor, which increased cell viability in the presence of a ferroptosis inducer. In addition, EPO reduced lipid peroxidation, iron levels, and regulated ferroptosis-related expression of proteins in vivo and in vitro. These findings indicate that EPO ameliorates T2DM-associated cognitive dysfunction, which might be related to decreasing iron overload and inhibiting ferroptosis. • Erythropoietin mitigated cognitive dysfunction in T2DM mice. • Erythropoietin inhibits ferroptosis in high-glucose-treated PC12 cells. • Erythropoietin regulated ferroptosis-related proteins in vivo and in vitro. [ABSTRACT FROM AUTHOR]

[Display omitted] • The kinase inhibitory activity of the selected compound 10a with better neuroprotective effect was 2.7 fold than that of Tideglusib. • Similar to Tideglusib, the selected compound 10a showed GSK-3β selective inhibition among the whole tested kinases. • The selected compound 10a could significantly reduce the levels of APP and p-tau via increasing expression of p-GSK-3β. • The selected compound 10a could improve the learning and memory functions of AD mice induced by d -galactose combined with AlCl 3 , and reduce the damage of hippocampal neurons. • Compared to Tideglusib, the selected compound 10a has less hepatotoxicity. Tideglusib is a non-competitive GSK-3β inhibitor which contain 1,2,4-thiadiazolidine-3,5-dione moiety, and now mainly used for progressive supranuclear palsy due to the lack of some primary cognitive endpoints and secondary endpoints in a phase IIb trail for Alzheimer's disease. Additionally, insufficient evidence exists to support that there are obvious covalent bonds between Tideglusib and GSK-3β. Targeted covalent inhibition strategy could improve the binding efficiency, selectivity and duration of kinase inhibitors. Based on the above premise, two series of targeted compounds with acryloyl warheads were designed and synthesized. The kinase inhibitory activity of the selected compound 10a with better neuroprotective effect improved 2.7 fold than that of Tideglusib. After the preliminary screening of GSK-3β inhibition and neuroprotective activity, the mechanism action of the selected compound 10a was investigated in vitro and in vivo. The results confirmed that 10a with excellent selectivity among the whole tested kinases could significantly reduce the expressions of APP and p-Tau via increasing the level of p-GSK-3β. The pharmacodynamic assay in vivo showed that 10a could markedly improve the learning and memory functions in AD mice induced by AlCl 3 combined with d -galactose. At the same time, the damage of hippocampal neurons in AD mice was obviously reduced. Accordingly, the introduction of acryloyl warheads could increase the GSK-3β inhibitory activity of 1,2,4-thiadiazolidine-3,5-dione derivatives, and the selected compound 10a deserves further research as an effective GSK-3β inhibitor for the potential treatment of AD. [ABSTRACT FROM AUTHOR]