MURAMYL DIPEPTIDE CAUSES MITOCHONDRIAL DYSFUNCTION AND INTESTINAL INFLAMMATORY CYTOKINE RESPONSES IN RATS.

ABSTRACT: Introduction: Intestinal flora and the translocation of its products, such as muramyl dipeptide (MDP), are common causes of sepsis. MDP is a common activator of the intracellular pattern recognition receptor NOD2, and MDP translocation can cause inflammatory damage to the small intestine and systemic inflammatory responses in rats. Therefore, this study investigated the effects of MDP on the intestinal mucosa and distant organs during sepsis and the role of the NOD2/AMPK/LC3 pathway in MDP-induced mitochondrial dysfunction in the intestinal epithelium. Methods: Fifty male Sprague Dawley rats were randomly divided into five treatment groups: lipopolysaccharide (LPS) only, 1.5 and 15 mg/kg MDP+LPS, and 1.5 and 15 mg/kg MDP+short-peptide enteral nutrition (SPEN)+LPS. The total caloric intake was the same per group. The rats were euthanized 24 h after establishing the model, and peripheral blood and small intestinal mucosal and lung tissues were collected. Results: Compared to the LPS group, both MDP+LPS groups had aggravated inflammatory damage to the intestinal mucosal and lung tissues, increased IL-6 and MDP production, increased NOD2 expression, decreased AMPK and LC3 expression, increased mitochondrial reactive oxygen species production, and decreased mitochondrial membrane potential. Compared to the MDP+LPS groups, the MDP+SPEN+LPS groups had decreased IL-6 and MDP production, increased AMPK and LC3 protein expression, and protected mitochondrial and organ functions. Conclusions: MDP translocation reduced mitochondrial autophagy by regulating the NOD2/AMPK/LC3 pathway, causing mitochondrial dysfunction. SPEN protected against MDP-induced impairment of intestinal epithelial mitochondrial function during sepsis.

Synergistic Optimization Strategy Involving Sandwich-like MnO2@rGO and Laponite-Modified PAM for High-Performance Zinc-Ion Batteries and Zinc Dendrite Suppression.

Optimization of the cathode structure and exploration of a novel electrolyte system are important approaches for achieving high-performance zinc-ion batteries (ZIBs) and zinc dendrite suppression. Herein, a quasi-solid-state ZIB combining a sandwich-like MnO2@rGO cathode, a laponite (Lap)-modified polyacrylamide (PAM) hydrogel electrolyte, and an electrodeposited zinc anode is designed and constructed by a synergistic optimization strategy. The MnO2 composite prepared through the intercalation of rGO shows developed mesopores, providing accessible ion transport channels and exhibiting a high electrical conductivity. Thanks to the high dispersion of Lap nanoplates in the hydrogel and good charge-averaging effect, the Zn//PAM-5%Lap//Zn symmetrical battery exhibits a consistent low-voltage polarization of less than 60 mV within 2000 h without a short-circuit phenomenon or any over-potential rise, indicating a stable zinc peeling/plating process. The optimized quasi-solid-state ZIB delivers a high reversible capacity of 291 mA h g-1 at a current density of 0.2 A g-1 due to the synergistic effect of each component of ZIB. Even at a high rate of 2 A g-1, it still maintains a high reversible capacity of 97 mA h g-1 after 2000 cycles, indicating its excellent electrochemical performance. Furthermore, the assembled flexible battery performs excellently in terms of damage and bending resistance.