RESUMEN
Neuropathic pain (NPP) remains a clinically challenging condition, driven by the activation of spinal astrocytes and the complex release of inflammatory mediators. This study aimed to examine the roles of Rab8a and SNARE complex proteins in activated astrocytes to uncover the underlying mechanisms of NPP. The research was conducted using a rat model with chronic constriction injury (CCI) of the sciatic nerve and primary astrocytes treated with lipopolysaccharide. Enhanced expression of Rab8a was noted specifically in spinal dorsal horn astrocytes through immunofluorescence. Electron microscopy observations showed increased vesicular transport and exocytic activity in activated astrocytes, which was corroborated by elevated levels of inflammatory cytokines such as interleukin (IL)-1ß and tumor necrosis factor (TNF)-α detected through quantitative PCR. Western blot analyses confirmed significant upregulation of Rab8a, VAMP2, and Syntaxin16 in these cells. Furthermore, the application of botulinum neurotoxin type A (BONT/A) reduced the levels of vesicle transport-associated proteins, inhibiting vesicular transport in activated astrocytes. These findings suggest that the Rab8a/SNARE pathway in astrocytes enhances vesicle transport and anchoring, increasing the secretion of bioactive molecules that may play a crucial role in the pathophysiology of NPP. Inhibiting this pathway with BONT/A offers a novel therapeutic target for managing NPP, highlighting its potential utility in clinical interventions.
RESUMEN
Transition metal phosphides/phosphates (TMPs) are considered appealing electrode materials in energy-related fields, especially in supercapacitors. However, the dilemma of inadequate electrode kinetics and dimensional unreliability evoked by a huge volume variation during cycling significantly plagues their progress. To mitigate this issue, in this work, a 3D cross-network in situ assembled via self-derived N-doped carbon hybrid Ni-Co-P/POx 2D sheets is fabricated. Particularly, high-Fermi-level N-doped carbon well confines Ni-Co-P/POx nanoparticles at the molecular level, and N-doping leads to redistribution of spin/electron density in the carbon skeleton, effectively regulating the electron environment of nearby Ni-Co-based moieties, resulting in a relatively lower surface work function, as known via experimental and Kelvin probe force microscopy (KPFM) results, which favors electron flee from the electrode surface and facilitates electron transport toward a rapid supercapacitor response. Moreover, the well-defined 3D cross-network architectures featured with in-plane pores and interconnected with each other can provide more ion/electron transfer pathways and 2D sheets with excellent surface chemistry available for sustainable ion/electron mobility, synergistically affording the favorable electrode kinetics. Accordingly, the resultant Ni-Co-P/POx@NC electrode shows admirable specific capacitance, excellent rate survivability, and long-term cyclability. The as-assembled asymmetric device exhibits remarkable energy and power outputs (48.5 Wh kg-1 and 7500 W kg-1), superior to many reported devices. Furthermore, our devices possess the prominent ability to power a commercial electronic thermometer for 1560 s at least, showcasing superb application prospects.
