RESUMEN
A short peptide termed NEMO-binding domain (NBD) peptide has an inhibitory effect on nuclear factor kappa-B (NF-κB). Despite its efficacy in inhibiting inflammatory responses, the precise neuroprotective mechanisms of NBD peptide in spinal cord injury (SCI) remain unclear. This study aims to determine whether the pyroptosis-related aspects involved in the neuroprotective effects of NBD peptide post-SCI.Using RNA sequencing, the molecular mechanisms of NBD peptide in SCI are explored. The evaluation of functional recovery is performed using the Basso mouse scale, Nissl staining, footprint analysis, Masson's trichrome staining, and HE staining. Western blotting, enzyme-linked immunosorbent assays, and immunofluorescence assays are used to examine pyroptosis, autophagy, lysosomal membrane permeabilization (LMP), acid sphingomyelinase (ASMase), and the NF-κB/p38-MAPK related signaling pathway.NBD peptide mitigated glial scar formation, reduced motor neuron death, and enhanced functional recovery in SCI mice. Additionally, NBD peptide inhibits pyroptosis, ameliorate LMP-induced autophagy flux disorder in neuron post-SCI. Mechanistically, NBD peptide alleviates LMP and subsequently enhances autophagy by inhibiting ASMase through the NF-κB/p38-MAPK/Elk-1/Egr-1 signaling cascade, thereby mitigating neuronal death. NBD peptide contributes to functional restoration by suppressing ASMase-mediated LMP and autophagy depression, and inhibiting pyroptosis in neuron following SCI, which may have potential clinical application value.
RESUMEN
High-performance amorphous silica-aluminas (ASAs) were prepared prior to the formation of the 10-membered ring (10-MR) ZSM-5 zeolite by regulating the hydrothermal processing time. Their structures, morphologies, acidity properties, and Si-Al coordination were well studied. Particularly, a facile FTIR method of in-situ adsorbing bulky 2,6-dimethlypyridine followed by pyridine adsorption was innovatively utilized to quantify the Brønsted acid sites in micropores. All the ASAs samples were transformed into catalysts by loading with 0.5 wt % Pt. The structure-activity relationship, especially from the strength, density, and location of Brønsted acid sites, was investigated by Fischer-Tropsch synthesis (FTS) wax hydrocracking. The evaluation results showed that the medium strong Brønsted acid sites located on the external surface played a crucial role in the activity. Contrary to the general belief that larger pores favor the production of heavy cracking fractions, the ASAs with a 10-MR microporous structure proved to be more effective for diesel production than those with a 12-membered ring (12-MR). Strong Brønsted acid sites in micropores were less conducive to diesel production mainly due to stronger adsorption at these sites and steric hindrance from the microporous system. Furthermore, the Pt/AS-20 catalyst with few intramicropore Brønsted acid sites exhibited high diesel selectivity (83.3%) at 50.5% conversion under industrially relevant reaction conditions, which provides a significant opportunity to develop FTS wax hydrocracking catalysts more rationally.
RESUMEN
Lysosomes play a crucial role in various intracellular pathways as their final destination. Various stressors, whether mild or severe, can induce lysosomal membrane permeabilization (LMP), resulting in the release of lysosomal enzymes into the cytoplasm. LMP not only plays a pivotal role in various cellular events but also significantly contributes to programmed cell death (PCD). Previous research has demonstrated the participation of LMP in central nervous system (CNS) injuries, including traumatic brain injury (TBI), spinal cord injury (SCI), subarachnoid hemorrhage (SAH), and hypoxic-ischemic encephalopathy (HIE). However, the mechanisms underlying LMP in CNS injuries are poorly understood. The occurrence of LMP leads to the activation of inflammatory pathways, increased levels of oxidative stress, and PCD. Herein, we present a comprehensive overview of the latest findings regarding LMP and highlight its functions in cellular events and PCDs (lysosome-dependent cell death, apoptosis, pyroptosis, ferroptosis, and autophagy). In addition, we consolidate the most recent insights into LMP in CNS injury by summarizing and exploring the latest advances. We also review potential therapeutic strategies that aim to preserve LMP or inhibit the release of enzymes from lysosomes to alleviate the consequences of LMP in CNS injury. A better understanding of the role that LMP plays in CNS injury may facilitate the development of strategic treatment options for CNS injury.
