Background/Aims Chronic ethanol exposure impairs liver regeneration due to inhibition of insulin signaling and oxidative injury. PPAR agonists function as insulin sensitizers and anti-inflammatory agents. We investigated whether treatment with a PPARδ agonist could restore hepatic insulin sensitivity, survival signaling, and regenerative responses vis-a-vis chronic ethanol feeding. Methods Adult rats were fed isocaloric liquid diets containing 0% or 37% ethanol, and administered a PPARδ agonist by i.p. injection. We used liver tissue to examine histopathology, gene expression, oxidative stress, insulin signaling, and regenerative responses to 2/3 hepatectomy. Results Chronic ethanol feeding caused insulin resistance, increased oxidative stress, lipid peroxidation, DNA damage, and hepatocellular injury in liver. These effects were associated with reduced insulin receptor binding and affinity, impaired survival signaling through PI3K/Akt/GSK3β, and reduced expression of insulin responsive genes mediating energy metabolism and tissue remodeling. PPARδ agonist treatment reduced ethanol-mediated hepatic injury, oxidative stress, lipid peroxidation, and insulin resistance, increased signaling through PI3K/Akt/GSK3β, and enhanced the regenerative response to partial hepatectomy. Conclusions PPARδ agonist administration may attenuate the severity of chronic ethanol-induced liver injury and ethanol’s adverse effects on the hepatic repair by restoring insulin responsiveness, even in the context of continued high-level ethanol consumption.

Figure 1a). [2] The metastable 1T MoS2 was reported to have A-b-C layers with edge-sharing [MoS6] octahedron (see Figure 1b), which was derived from electron diffraction [3] and powder X-ray pattern. [4] But the crystal structure of 1T MoS2 has never been collected in the Inorganic Crystal Structure Database (ICSD) due to the lack of a strict structural refinement.Although the single-layer 1T MoS2 has been prepared by using various synthetic methods, [5] the obtained nanosheets always coexist with 2H, 1T, and 1T' phases. The maximal content of 1T/1T' domains have been reported to be up to 80% which was evaluated by XPS measurements.[5b] The 1T/1T' MoS2 phases were observed to start the transformation to thermodynamically more stable 2H phase at around 100 C and be completely converted into 2H phase at 300 C. [6] It was recently reported that 1T/1T' MoS2 domains can be stabilized by electron doping. [7] 2H MoS2 intrinsically behaves as a semiconductor with a band gap of 1.2-1.9 eV, [8] which is consistent with the closeshell electronic configuration of Mo 4+ 4d 2 (dz 2 , dx 2 -y 2 ) in a trigonal prismatic coordination environment (Figure 1a). [9] Previously reported superconductivity in the MoS2 system is based on electron injection to the Fermi surface of 2H MoS2 [9] shown in Figure 1b, whose two electrons are filled in the t states and may also become itinerant electrons. Anomalous superconductivity has recently been reported in the structure-related 1T' MoTe2 at a very low Tc of about 0.1 K.[12] The density functional calculations predicted the metallicity of 1T MoS2. [13] However, the sample of MoS2 nanosheets coexisting with 1T/1T' and 2H phases was found to have a semiconducting behavior. [14] Moreover, the superconductivity of 1T MoS2 has never been discovered yet.So far, it is very important and urgent to synthesize single crystals of 1T-MoS2 for re-determining single crystal structure and investigating intrinsic physical properties. Here, we reported a modified strategy derived from the literature The preparation of 1T-MoS2 started from the intercalated compound LiMoS2, whose synthesis process was described by our previous results. [15] The oxidation processes of LiMoS2 crystals were divided into two steps, in which the corresponding reactions happen as follow:In the first step, lithium atoms undergo the hydration process, which expands the interlayer distance of MoS2. Figure S1a shows the PXRD pattern of as-obtained Li1-x(H2O)yMoS2, which corresponds to 12.149 Å of the d value along the c direction. Expanded layer spacing reduces the interactions between sulfur atoms and lithium atoms, which promotes the removal of lithium ion in the second redox process. Moreover, the deintercalation of Li ions causes fewer damages on the crystal structure of 1T MoS2 compared with that caused by the deintercalation of K ions.[3], [4] As illustrated in Figure 1b, the 1T-MoS2 crystallizes in the trigonal space group P-3m1. The unit cell consists of one independent Mo site and one independent S site. Each layer...