ObjectiveCelastrol was recently identified as a potential novel treatment for obesity. However, the effect of Celastrol on nonalcoholic fatty liver disease (NAFLD) remains elusive. The aim of this study is to evaluate the role of Celastrol in NAFLD.MethodsFunctional studies were performed using wild-type C57BL/6J (WT) mice and liver specific Sirt1-deficient (LKO) mice. The molecular mechanism was explored in primary mouse liver and primary hepatocytes.ResultsWhen WT mice receiving a high-fat diet (HFD) were treated with Celastrol, reductions in body weight, subcutaneous and visceral fat content, and liver lipid droplet formation were observed, along with reduced hepatic intracellular triglyceride and serum triglyceride, free fatty acid, and ALT concentrations. Furthermore, Celastrol decreased hepatic sterol regulatory element binding protein 1c (Srebp-1c) expression, enhanced the phosphorylation of hepatic AMP-activated protein kinase α (AMPKα), and increased the expression of hepatic serine–threonine liver kinase B1 (LKB1). Additionally, Celastrol treatment improved glucose tolerance and insulin sensitivity in WT mice fed the HFD. Celastrol administration also improved the anti-inflammatory and anti-oxidative status by inhibiting nuclear factor kappa B (NFκB) activity and the mRNA levels of proinflammatory cytokines and increasing mitochondrial DNA copy number and anti-oxidative stress genes expression in WT mice liver, in vivo and in vitro. Moreover, Celastrol induced hepatic Sirt1 expression in WT mice, in vivo and in vitro. These Celastrol-mediated protective effects in WT mice fed a HFD were abolished in LKO mice fed a HFD. It was more interesting that Celastrol aggravated HFD-induced liver damage in LKO mice fed a HFD by inhibiting the phosphorylation of AMPKα and boosting the translocation of NFκB into the nucleus, thereby resulting in the increase of Srebp-1c expression and the mRNA levels of liver proinflammatory cytokines.ConclusionsCelastrol ameliorates NAFLD by decreasing lipid synthesis and improving the anti-oxidative and anti-inflammatory status. And Sirt1 has an important role in Celastrol-ameliorating liver metabolic damage caused by HFD.

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the CI incidence among older Chinese people decreased from 1998 to 2014. Lower education level and less frequent health practices mentioned above were important risk factors in CI prevention.

of electrode reaction by suppressing the Mn 4+ /Mn 3+ reduction reaction. [3c] Although a series of effective coating, doping and structural design strategies previously reported have been put into practice and significantly improved the electrochemical performance and structural stability from the macro perspective, plenty of the underlying and fundamental reaction mechanisms have not yet been elucidated clearly. [6][7][8] From a more microscopic dimension, root of the decline in electrochemical performance include escape of oxygen atoms, redox of cations and anions, and phase transformation, in which such microscopic characterizations require cutting-edge technologies. Recently, tremendous efforts have been devoted to investigating complex reaction mechanisms behind the structure with the help of state-of-the-art characterization techniques. [8] In general, the superior electrochemical behavior of Li-rich Mn-based cathode materials is not only derived from the contribution of transition metal cations, but also closely related to the anionic redox activity, especially reflected in the unique first charge process. [9] The initial charge process usually consists of two regions: sloping region and plateau region. The first stage occurs below 4.4 V, and lithium ions are extracted from the lithium layer along with the oxidation of transition metal ions to high valence state. [10,11] While the second stage presents a long plateau that appears above 4.4 V and stands for the activation of Li 2 MnO 3 phase. During the plateau region, lithium ions are continuously extracted and interact with oxygen in the form of Li-O-Li configuration as charge compensation. [12] Whereas, the specific role and mechanism of anionic redox activity in electrochemical reactions are still in dispute. This is because oxygen can participate in both reversible and irreversible redox reactions. What kind of intermediate form does oxygen take part in the reversible process? Where does the irreversible oxygen loss originate from, bulk lattice or electrolyte oxidation? How do these two parts contribute to capacities independently and influence mutually? These issues seriously challenge further development and need to be clarified in detail. In addition, the original structure is prone to transition metal migration and phase transformation due to anionic redox activities. [13,14] It is worth noting that not only the intrinsic structure of Li-rich Mn-based cathode materials is very complicated, but also its evolution mechanism of phase transformation during cycling is even more controversial. Furthermore, the lack of powerful characterization tools

The high-nickel layered oxides are potential candidate cathode materials of next-generation high energy lithium–ion batteries, in which higher nickel/lower cobalt strategy is effective for increasing specific capacity and reducing cost of cathode. Unfortunately, the fast decay of capacity/potential, and serious thermal concern are critical obstacles for the commercialization of high-nickel oxides due to structural instability. Herein, in order to improve the structure and thermal stability of high-nickel layered oxides, we demonstrate a feasible and simple strategy of the surface gradient doping with yttrium, without forming the hard interface between coating layer and bulk. As expected, after introducing yttrium, the surface gradient doping layer is formed tightly based on the oxidation induced segregation, leading to improved structure and thermal stability. Correspondingly, the good capacity retention and potential stability are obtained for the yttrium-doped sample, together with the superior thermal behavior. The excellent electrochemical performance of the yttrium-doped sample is primarily attributed to the strong yttrium–oxygen bonding and stable oxygen framework on the surface layer. Therefore, the surface manipulating strategy with the surface gradient doping is feasible and effective for improving the structure and thermal stability, as well as the capacity/potential stability during cycling for the high-Ni layered oxides.