Yanbian University

Synaptic dysfunction driven by glutamate-mediated excitotoxicity is a hallmark of hippocampus-dependent memory impairment in Alzheimer's disease (AD). Although GABAergic signaling is known to regulate excitatory/inhibitory (E/I) balance, the precise molecular mechanisms by which GABA and its receptors modulate glutamatergic synaptic plasticity remains incompletely understood. Here, we investigated the role of GABA and its receptors in the dentate gyrus (DG) of a streptozotocin (STZ) induced rat model with sporadic AD (_SAD)-like features. sAD rats exhibited intact emotional and motor functions but showed marked impairments in novel object recognition, Y-maze, and Morris water maze (MWM) performance. In vivo microdialysis combined with HPLC during MWM training revealed decreased GABA levels and selective upregulation of GABA_B receptor (GABA_BR) expression, but not GABA_AR, expression in the DG. Administration of the GABA_BR antagonist 2-hydroxysaclofen improved hippocampal memory performance, reduced glutamate accumulation, and restored the key excitatory synaptic markers, including vGlut1 and PSD-95. Moreover, co-immunoprecipitation and molecular docking identified a specific interaction between GABA_BR and CaMKII. GABA_BR blockade enhanced CaMKII phosphorylation and activated downstream effectors, including p-CREB and BDNF, indicating re-engagement of plasticity-related signaling. These findings demonstrate that GABA_BR upregulation in the DG impairs glutamatergic synaptic plasticity and memory function in sAD like rats, likely via direct suppression of the CaMKII/CREB/BDNF pathway. Targeting GABA_BR may thus offer a promising strategy to restore E/I balance and cognitive performance in a sAD-like rat model.

The electrocatalytic water splitting of urea-containing wastewater represents a promising sustainable approach for hydrogen generation. Therefore, it is crucial to develop efficient and selective electrocatalysts. In this study, we synthesized Fe₂O₃/NiTe₂ heterostructures with controlled S doping through a two-step hydrothermal method. The resulting electrocatalyst features a hierarchical mesoporous structure, enhancing surface accessibility and increasing pore volume, which contributes to a three-dimensional open framework that facilitates gas transport. The construction of the heterojunction causes the local charge density at the interface between Fe₂O₃ and NiTe₂ to redistribute, significantly lowering the energy barrier of the intermediate adsorption/desorption process. The synergistic combination of S doping and heterojunction engineering enables exceptional bifunctional performance. In a solution of 1 M KOH with 0.33 M urea, the voltage of the urea oxidation reaction (UOR) decreased to 1.35 V vs. RHE at 100 mA cm^-2. When integrated into a two-electrode system for urea-assisted water splitting, the optimized S-Fe₂O₃/NiTe₂//S-Fe₂O₃/NiTe₂ assembly demonstrates outstanding operational efficiency, requiring only 1.64 V to maintain 100 mA cm^-2. Both experimental and computational analyses indicate that the enhanced activity is attributed to S doping adjusting the charge distribution in the heterojunction, forming favorable adsorption sites, lowering the energy barrier of the rate determining step, and consequently enhancing UOR performance. This study introduces the first S-doped Fe₂O₃/NiTe₂ heterostructure and highlights the synergy between S doping and the heterojunction design. This dual-regulation strategy effectively optimizes intermediate adsorption, achieving superior urea oxidation performance and providing new perspectives for electrocatalyst design through interface and doping engineering.

This study investigated the therapeutic potential of exosomes derived from fetal muscle stem cells (FMSC-Exos) in mitigating dexamethasone (DEX)-induced muscle atrophy in a mouse model. Kunming (KM) mice were utilized to visualize muscle atrophy at the single muscle fiber level through an optimized isolation technique. Following the induction of muscle atrophy by dexamethasone, mice were treated with FMSC-Exos via local intramuscular injection into the gastrocnemius muscle. Results demonstrated that exosome administration showed a trend towards improved body weight and significantly increased muscle mass and individual muscle fiber diameter compared to the dexamethasone-only group. Histological analysis confirmed that FMSC-Exos effectively alleviated muscle fiber atrophy and promoted regeneration. RT-PCR and Western blot analyses revealed differential expression of the muscle atrophy markers MuRF1 and MAFbx/Atrogin-1. The mRNA expression levels of these atrophy-related factors were significantly elevated in the DEX-treated group compared to the control. Although expression levels in the exosome treatment group remained higher than control, they were significantly lower than in the DEX group. Protein expression followed a similar trend, indicating that dexamethasone modulates MuRF1 and MAFbx at both transcriptional and translational levels, and that exosome treatment counteracts this effect, promoting a restoration towards normal muscle protein expression homeostasis.