Mechanism Of Activation Research Articles

Persulfide Transfer to SufE Activates the Half-Sites Reactivity of the E. coli Cysteine Desulfurase SufS.

The Escherichia coli cysteine desulfurase SufS (EcSufS) is a dimeric, PLP-dependent enzyme responsible for sulfur mobilization in the SUF Fe-S cluster bioassembly pathway. The enzyme uses cysteine as a sulfur source and generates alanine and a covalent persulfide located on an active site of cysteine. Optimal in vitro activity of EcSufS requires the presence of the transpersulfurase protein, EcSufE, and a strong reductant. Here, presteady-state and single-turnover kinetics are used to investigate the mechanism of EcSufS activation by EcSufE. In the absence of EcSufE, EcSufS exhibits a presteady-state burst of product production with an amplitude of ∼0.4 active site equivalents, consistent with a half-sites reactivity. KinTek Explorer was used to isolate the first turnover of alanine formation and fit the data with a simplified kinetic mechanism with steps for alanine formation (k3) and a net rate constant for the downstream steps (k5). Using this treatment, microscopic rate constants of 2.3 ± 0.5 s-1 and 0.10 ± 0.01 s-1 were determined for k3 and k5, respectively. The inclusion of EcSufE in the reaction results in a similar rate constant for k3 but induces a 10-fold enhancement of k5 to 1.1 ± 0.2 s-1, such that both steps are partially rate-determining. The most likely downstream step where EcSufE could exert influence on EcSufS activity is the removal of the persulfide intermediate. Importantly, this step appears to serve as a limiting feature in the half-sites activity such that activating persulfide transfer allows for rapid shifting between active sites. Single-turnover assays show that the presence of EcSufE slightly slowed the rates of alanine-forming steps, suggesting it does not activate steps in the desulfurase half reaction.

Activation and reaction mechanism of nano‐aluminized explosives under shock wave

Activation and reaction mechanism of nano‐aluminized explosives under shock wave

MYC phase separation selectively modulates the transcriptome.

Dysregulation and enhanced expression of MYC transcription factors (TFs) including MYC and MYCN contribute to the majority of human cancers. For example, MYCN is amplified up to several hundredfold in high-risk neuroblastoma. The resulting overexpression of N-myc aberrantly activates genes that are not activated at low N-myc levels and drives cell proliferation. Whether increasing N-myc levels simply mediates binding to lower-affinity binding sites in the genome or fundamentally changes the activation process remains unclear. One such activation mechanism that could become important above threshold levels of N-myc is the formation of aberrant transcriptional condensates through phase separation. Phase separation has recently been linked to transcriptional regulation, but the extent to which it contributes to gene activation remains an open question. Here we characterized the phase behavior of N-myc and showed that it can form dynamic condensates that have transcriptional hallmarks. We tested the role of phase separation in N-myc-regulated transcription by using a chemogenetic tool that allowed us to compare non-phase-separated and phase-separated conditions at equivalent N-myc levels, both of which showed a strong impact on gene expression compared to no N-myc expression. Interestingly, we discovered that only a small percentage (<3%) of N-myc-regulated genes is further modulated by phase separation but that these events include the activation of key oncogenes and the repression of tumor suppressors. Indeed, phase separation increases cell proliferation, corroborating the biological effects of the transcriptional changes. However, our results also show that >97% of N-myc-regulated genes are not affected by N-myc phase separation, demonstrating that soluble complexes of TFs with the transcriptional machinery are sufficient to activate transcription.

PIEZO1 as a new target for hyperglycemic stress-induced neuropathic injury: The potential therapeutic role of bezafibrate

Hyperglycemic stress can directly lead to neuronal damage. The mechanosensitive ion channel PIEZO1 can be activated in response to hyperglycemia, but its role in hyperglycemic neurotoxicity is unclear. The role of PIEZO1 in hyperglycemic neurotoxicity was explored by constructing a hyperglycemic mouse model and a high-glucose HT22 cell model. The results showed that PIEZO1 was significantly upregulated in response to high glucose stress. In vitro experiments have shown that high glucose stress induces changes in neuronal cell morphology and membrane tension, a key mechanism for PIEZO1 activation. In addition, high glucose stress upregulates serum/glucocorticoid-regulated kinase-1 (SGK1) and activates PIEZO1 through the Ca2+ pool and store-operated calcium entry (SOCE). PIEZO1-mediated Ca2+ influx further enhances SGK1 and SOCE, inducing intracellular Ca2+ peaks in neurons. PIEZO1 mediated intracellular Ca2+ elevation leads to calcium/calmodulin-dependent protein kinase 2α (CaMK2α) overactivation, which promotes oxidative stress and apoptosis signalling through p-CaMK2α/ERK/CREB and ox-CaMK2α/MAPK p38/NFκB p65 pathways, subsequently inducing synaptic damage and cognitive impairment in mice. The intron miR-107 of pantothenic kinase 1 (PANK1) is highly expressed in the brain and has been found to target PIEZO1 and SGK1. The PANK1 receptor is activated by peroxisome proliferator-activated receptor α (PPARα), an activator known to upregulate miR-107 levels in the brain. The clinically used lipid-lowering drug bezafibrate, a known PPARα activator, may upregulate miR-107 through the PPARɑ/PANK1 pathway, thereby inhibiting PIEZO1 and improving hyperglycemia-induced neuronal cell damage. This study provides a new idea for the pathogenesis and drug treatment of hyperglycemic neurotoxicity and diabetes-related cognitive dysfunction.

UCP1-dependent brown adipose activation accelerates cardiac metabolic remodeling and reduces initial hypertrophic and fibrotic responses to pathological stress.

Brown adipose tissue (BAT) is correlated to cardiovascular health in rodents and humans, but the physiological role of BAT in the initial cardiac remodeling at the onset of stress is unknown. Activation of BAT via 48 h cold (16°C) in mice following transverse aortic constriction (TAC) reduced cardiac gene expression for LCFA uptake and oxidation in male mice and accelerated the onset of cardiac metabolic remodeling, with an early isoform shift of carnitine palmitoyltransferase 1 (CPT1) toward increased CPT1a, reduced entry of long chain fatty acid (LCFA) into oxidative metabolism (0.59 ± 0.02 vs. 0.72 ± 0.02 in RT TAC hearts, p < .05) and increased carbohydrate oxidation with altered glucose transporter content. BAT activation with TAC reduced early hypertrophic expression of β-MHC by 61% versus RT-TAC and reduced pro-fibrotic TGF-β1 and COL3α1 expression. While cardiac natriuretic peptide expression was yet to increase at only 3 days TAC, Nppa and Nppb expression were elevated in Cold TAC versus RT TAC hearts 2.7- and 2.4-fold, respectively. Eliminating BAT thermogenic activation with UCP1 KO mice eliminated differences between Cold TAC and RT TAC hearts, confirming effects of BAT activation rather than autonomous cardiac responses to cold. Female responses to BAT activation were blunted, with limited UCP1 changes with cold, partly due to already activated BAT in females at RT compared to thermoneutrality. These data reveal a previously unknown physiological mechanism of UCP1-dependent BAT activation in attenuating early cardiac hypertrophic and profibrotic signaling and accelerating remodeled metabolic activity in the heart at the onset of cardiac stress.

CCDC6-RET fusion protein regulates Ras/MAPK signaling through the fusion- GRB2-SHC1 signal niche

Rearranged during transfection (RET) rearrangement oncoprotein-mediated Ras/MAPK signaling cascade is constitutively activated in cancers. Here, we demonstrate a unique signal niche. The niche is a ternary complex based on the chimeric RET liquid-liquid phase separation. The complex comprises the rearranged kinase (RET fusion); the adaptor (GRB2), and the effector (SHC1). Together, they orchestrate the Ras/MAPK signal cascade, which is dependent on tyrosine kinase. CCDC6-RET fusion undergoes LLPS requiring its kinase domain and its fusion partner. The CCDC6-RET fusion LLPS promotes the autophosphorylation of RET fusion, with enhanced kinase activity, which is necessary for the formation of the signaling niche. Within the signal niche, the interactions among the constituent components are reinforced, and the signal transduction efficiency is amplified. The specific RET fusion-related signal niche elucidates the mechanism of the constitutive activation of the Ras/MAPK signaling pathway. Beyond just focusing on RET fusion itself, exploration of the ternary complex potentially unveils a promising avenue for devising therapeutic strategies aimed at treating RET fusion-driven diseases.

TLR4/Rac1/NLRP3 Pathway Mediates Amyloid-β-Induced Neuroinflammation in Alzheimer's Disease.

Neuroinflammation plays a crucial part in the initial onset and progression of Alzheimer's disease (AD). NLRP3 inflammasome was demonstrated to get involved in amyloid-β (Aβ)-induced neuroinflammation. However, the mechanism of Aβ-triggered activation of NLRP3 inflammasome remains poorly understood. Based on our previous data, the study aimed to identify the downstream signals that bridge the activation of TLR4 and NLRP3 inflammasome associated with Aβ. BV-2 cells were transfected with TLR4siRNA or pretreated with a CLI-095 or NSC23766, followed by Aβ1-42 treatment. APP/PS1 mice were injected intraperitoneally with CLI-095 or NSC23766. NLRP3 inflammasome and microglia activation was detected with immunostaining and western blot. G-LISA and Rac1 pull-down activation test were performed to investigate the activation of Rac1. Real-time PCR and ELISA were used to detect the inflammatory cytokines. Aβ plaques were assessed by western blotting and immunofluorescence staining. Morris water maze test was conducted to determine the spatial memory in mice. Rac1 and NLRP3 inflammasome were activated by Aβ in both in vitro and in vivo experiments. Inhibition of TLR4 reduced the activity of Rac1 and NLRP3 inflammasome induced by Aβ1-42. Furthermore, inhibition of Rac1 blocked NLRP3 inflammasome activation mediated by TLR4. Blocking the pathway by CLI095 or NSC23766 suppressed Aβ1-42-triggered activation of microglia, reduced the expression of pro-inflammatory mediators and ameliorated the cognition deficits in APP/PS1 mice. Our study demonstrated that TLR4/Rac1/NLRP3 pathway mediated Aβ-induced neuroinflammation, which unveiled a novel pathway and key contributors underlying the pathogenic mechanism of Aβ.

Comparative Study on the Mechanism of Macrophage Activation Induced by Polysaccharides from Fresh and Dried Longan.

Longan (Dimcarpus longan Lour.) is a kind of traditional fruit used as a medicine and a food. Fresh longan is primarily consumed as a fruit, whereas dried longan is commonly employed for medicinal purposes. The differences in the immunomodulatory activities and mechanisms of polysaccharides between dried and fresh longan remain unclear. The present study comparatively analyzed the mechanisms of macrophage activation induced by polysaccharides from dried (LPG) and fresh longan (LPX). The results revealed that LPG and LPX differentially promoted macrophage phagocytosis and the secretion of NO, TNF-α, and IL-6. RNA-seq analysis revealed that LPG and LPX differentially affected gene expression in macrophages. The LPG treatment identified Tnf and chemokine-related genes as core genes, while myd88 and interferon-related genes were the core genes affected by LPX. A comprehensive analysis of the differentially expressed genes showed that LPG initiated macrophage activation primarily through the TLR2/4-mediated TRAM/TRAF6 and CLR-mediated Src/Raf1 NF-κB signaling pathways. LPX initiated macrophage activation predominantly via the CLR-mediated Bcl10/MALT1 and NLR-mediated Rip2/TAK1 MAPK and NF-κB signaling pathways. Interestingly, the non-classical NF-κB signaling pathway was activated by polysaccharides in both dried and fresh longan to elicit a slow, mild immune response. LPG tends to promote immune cell migration to engage in the immune response, while LPX facilitates antigen presentation to promote T cell activation. These findings contribute insights into the mechanisms underlying the differences in bioactivity between dried and fresh longan and their potential applications in immune-enhancing strategies and functional-food development.

Toward Designing Reactive Metal Clusters for Dinitrogen Activation: A Guideline Based on N2 Initial Adsorption.

Gas-phase metal clusters are ideal models to explore transition-metal-mediated N2 activation mechanism. However, the effective design and search of reactive clusters in N2 activation are currently hindered by the lack of clear guidelines. Inspired by the Sabatier principle, we discovered in this work that N2 initial adsorption energy (ΔEads) is an important parameter to control the N2 activation reactivity of metal clusters in the gas phase. This mechanistic insight obtained from high-level calculations rationalizes the N2 activation reactivity of many previously reported metal clusters when combined with the known factor determining the N≡N cleavage process. Furthermore, based on this guideline of ΔEads, we successfully designed several new reactive clusters for cleaving N≡N triple bond under mild conditions, including FeV2S2-, TaV2C2-, and TaV2C3-, the high N2 activation reactivity of which has been fully corroborated in our gas phase experiments employing mass spectrometry with collision-induced dissociation. The importance of ΔEads revealed in this work not only reshapes our understanding of N2 activation reactions in the gas phase but also could have implication for other N2 activation processes in the condensed phase. The more general establishment of this new perspective on N2 activation reactivity warrants future experimental and computational studies.

Macrophages: Balancing Inflammation and Homeostasis in Health and Disease

Abstract: Inflammation is crucial for maintaining tissue homeostasis and responding to insults, yet dysregulated inflammation can lead to various diseases. Macrophages, central to the immune system, play key roles in initiating, regulating, and resolving inflammation. This review provides an overview of macrophage functions, including activation mechanisms, recruitment to inflamed tissues, interactions with other immune cells and mediators, and their roles in phagocytosis, clearance of apoptotic cells and debris, and secretion of anti-inflammatory cytokines. Additionally, it discusses macrophage-induced regulatory T-cell formation, the impact of pro-inflammatory and anti-inflammatory cytokines on macrophage behavior, and the influence of microbial products and pathogen-associated molecular patterns (PAMPs) on macrophage function. The review also identifies targeting macrophages as a promising strategy for managing inflammatory diseases while acknowledging challenges such as macrophage heterogeneity, limitations of in vitro models, and incomplete understanding of regulatory mechanisms. Finally, it suggests areas for further research, including identifying specific macrophage subsets, understanding macrophage plasticity, exploring resolution signaling pathways, and investigating the role of metabolism and microenvironmental cues in macrophage function, aiming to pave the way for more effective macrophage-targeted therapies in inflammatory diseases.

C-type lectin-like receptor-2 in platelets mediates ferric chloride–induced platelet activation and attenuates ferroptosis of endothelial cells

BackgroundAn iron overload status induces ferroptosis, an iron-dependent nonapoptotic cell death, in various pathological conditions. We previously reported that hemin (heme), protoporphyrin-IX with ferric iron, activates platelets via C-type lectin-like receptor-2 (CLEC-2) and glycoprotein VI/FcRγ, but protoporphyrin-IX alone blocks CLEC-2-dependent platelet activation. Therefore, we hypothesized that free iron has the ability to activate platelets. ObjectivesThis study aimed to elucidate platelet activation mechanisms of iron (ferric chloride), including the identification of signaling pathways and receptors, and to examine whether platelets regulate ferroptosis. MethodsPlatelet aggregometry, platelet activation marker expression, and protein phosphorylation were examined in ferric chloride–stimulated human and murine platelets. Inhibitors of platelet activation signaling pathways and receptor-deleted platelets were utilized to identify the responsible signaling pathway and receptor. The effect of platelets on ferroptosis of endothelial cells was investigated in vitro. ResultsFerric chloride induced platelet activation dependent on Src family kinase pathways in humans and mice. Ferric chloride–induced platelet aggregation was almost lost in CLEC-2–depleted murine platelets and wild-type platelets preincubated with recombinant CLEC-2 proteins. Furthermore, coculture of wild-type platelets, but not CLEC-2–deficient platelets, attenuated ferroptosis of endothelial cells in vitro. ConclusionFerric chloride activates platelets via CLEC-2 and Src family kinase pathways, and platelets have a protective role in the ferroptosis of endothelial cells dependent on CLEC-2.

Peanut-shell-derived biochar mediated peracetic acid activation for the elimination of acetaminophen via an electron-transfer regime

Biochar-based heterogeneous activation of disinfectant peracetic acid (PAA) is an attractive and promising route for micropollutant elimination in water, yet the underlying activation mechanism is still scarce. In this study, PAA was first catalyzed by peanut shell-derived biochar (PSBC) to degrade acetaminophen (ACP). The enhancement of ACP removal was triggered by PAA activation, while the coexisted H2O2 was unexpected to be an adverse factor owing to its occupation of active sites. Higher dosages of PSBC (0–0.30 g/L) and PAA (0–4.0 mM) favored the destruction of ACP, and the activation energy (41.8 kJ/mol) of PSBC/PAA system is lower than that of the thermal or microwave activated PAA system. The experimental results demonstrate that the metastable complex PSBC-PAA* dominated ACP elimination through an electron transfer mechanism. The surface –OH group was validated to be the key active site for PAA activation. Surprisingly, the actual water matrices present a negligible effect and the promotion of HCO3− ion on ACP removal was even observed. Based on the identified intermediates, the transformation of ACP was further proposed with the formation of polymeric products via oxidative coupling reactions. The findings not only shed light on the mechanism of PAA activated by the biochar-based catalyst but also contribute to a novel perspective on future PAA studies in contamination remediation.

Efficient Hydrogen Generation from Ammonia Borane Hydrolysis on a Tandem Ruthenium–Platinum–Titanium Catalyst

Hydrolysis of ammonia borane (NH3BH3, AB) involves multiple undefined steps and complex adsorption and activation, so single or dual sites are not enough for the rapidity of the multiple processes. Designing multi‐site catalysts is necessary to enhance the catalytic performance of AB hydrolysis reactions but revealing the matching reaction mechanisms of AB hydrolysis is a great challenge. In this work, we propose to construct RuPt‐Ti multi‐site catalysts with the metal‐support synergy effect to clarify the multi‐site tandem activation mechanism of AB hydrolysis. Experimental and theoretical studies reveal that the multi‐site tandem mode can respectively promote the activation of NH3BH3 and H2O molecules on the Ru and Pt sites as well as facilitate the fast transfer of *H and the desorption of H2 on Ti sites at the same time. RuPt‐Ti multi‐site catalysts exhibit the highest turnover frequency (TOF) of 1293 min‐1 for AB hydrolysis reaction, outperforming the single‐site Ru, dual‐site RuPt and Ru‐Ti catalysts. This study proposes a multi‐site tandem concept for accelerating the dehydrogenation of hydrogen storage material, aiming to contribute to the development of cleaner, low‐carbon, and high‐performance hydrogen production systems.

Efficient Hydrogen Generation from Ammonia Borane Hydrolysis on a Tandem Ruthenium-Platinum-Titanium Catalyst.

Hydrolysis of ammonia borane (NH3BH3, AB) involves multiple undefined steps and complex adsorption and activation, so single or dual sites are not enough for the rapidity of the multiple processes. Designing multi-site catalysts is necessary to enhance the catalytic performance of AB hydrolysis reactions but revealing the matching reaction mechanisms of AB hydrolysis is a great challenge. In this work, we propose to construct RuPt-Ti multi-site catalysts with the metal-support synergy effect to clarify the multi-site tandem activation mechanism of AB hydrolysis. Experimental and theoretical studies reveal that the multi-site tandem mode can respectively promote the activation of NH3BH3 and H2O molecules on the Ru and Pt sites as well as facilitate the fast transfer of *H and the desorption of H2 on Ti sites at the same time. RuPt-Ti multi-site catalysts exhibit the highest turnover frequency (TOF) of 1293 min-1 for AB hydrolysis reaction, outperforming the single-site Ru, dual-site RuPt and Ru-Ti catalysts. This study proposes a multi-site tandem concept for accelerating the dehydrogenation of hydrogen storage material, aiming to contribute to the development of cleaner, low-carbon, and high-performance hydrogen production systems.

Cu single atoms mediated multiple active site reconfiguration to trigger Dual-pathway nonradical peroxymonosulfate activation process

Developing atomically dispersed metal sites is vital to enhance the activation of peroxymonosulfate (PMS). However, for catalyst systems where single atoms and nanoclusters coexist, how to identify the independent and synergistic effects of atomic sites and investigate the possible coexistence of multiple activation mechanisms still remains a great challenge. Herein, CuSA/CoOx-CeO2 catalysts with Cu single atoms and CoOx nanoclusters were fabricated for PMS activation. The introduction of Cu single atoms led to the reconstruction and diversification of catalytic active sites of CoOx-CeO2. The synergy between CoOx nanoclusters and neighboring Cu single atoms in CuSA/CoOx-CeO2 catalyst led to the 1O2 pathway of PMS activation, while the isolated Cu atom induced the Cu(III) oxidation pathway. The introducing of adjacent Cu single atoms caused the redistribution of the site charges in CoOx nanoclusters, which enhanced the charge transfer and promoted the adsorption and activation behavior of PMS molecules. During the evolution of 1O2, the synergistic effect of Cu single atoms and CoOx nanoclusters increased the stability of the reaction intermediate state (*OO*SO3), reducing the total Gibbs free energy change (ΔG) required for 1O2 formation. Compared with the cooperative site, the isolated Cu-O4 sites exhibited stronger charge transfer capacity to PMS molecules and were more conducive to the activation of the local substrate electronic structure, facilitating the formation and stabilization of Cu(III)–OH metastable intermediates. Overall, this study demonstrated the importance about the construction of multi-site induced multipath coexisting PMS activation system and the accurate identification of active sites.

Research progress of acupuncture regulating ERK signaling pathway in the treatment of depression.

Acupuncture treatment for depression has definite therapeutic efficacy, and its mechanism has been extensively studied. The extracellular regulatory protein kinase(ERK) signaling pathway is involved in the development and progression of depression. This article reviewed and summarized the research progress on the regulation of the ERK signaling pathway by acupuncture in the treatment of depression in recent years, focusing on the physiological activation and regulatory mechanism of the ERK signaling pathway, its association with the occurrence of depression, and the mechanisms through which acupuncture activates the ERK signaling pathway to treat depression (including enhancing neuronal synaptic plasticity, promoting the release of neurotrophic factors, and inhibiting neuronal apoptosis). Future research could explore the relationship between the ERK pathway and other pathways, investigate other brain regions besides the prefrontal cortex and hippocampus, examine differences in regulatory mechanisms between male and female patients, assess the effects of different acupuncture techniques on the ERK pathway, and increase efforts to explore mechanism of synaptic plasticity regulation, so as to provide reference for the clinical application and mechanism sludy of acupuncture in depression treatment.

Phosphorylation of phospholamban promotes SERCA2a activation by dwarf open reading frame (DWORF)

In cardiac myocytes, the type 2a sarco/endoplasmic reticulum Ca-ATPase (SERCA2a) plays a key role in intracellular Ca regulation. Due to its critical role in heart function, SERCA2a activity is tightly regulated by different mechanisms, including micropeptides. While phospholamban (PLB) is a well-known SERCA2a inhibitor, dwarf open reading frame (DWORF) is a recently identified SERCA2a activator. Since PLB phosphorylation is the most recognized mechanism of SERCA2a activation during adrenergic stress, we studied whether PLB phosphorylation also affects SERCA2a regulation by DWORF. By using confocal Ca imaging in a HEK293 expressing cell system, we analyzed the effect of the co-expression of PLB and DWORF using a bicistronic construct on SERCA2a-mediated Ca uptake. Under these conditions of matched expression of PLB and DWORF, we found that SERCA2a inhibition by non-phosphorylated PLB prevails over DWORF activating effect. However, when PLB is phosphorylated at PKA and CaMKII sites, not only PLB's inhibitory effect was relieved, but SERCA2a was effectively activated by DWORF. Förster resonance energy transfer (FRET) analysis between SERCA2a and DWORF showed that DWORF has a higher relative affinity for SERCA2a when PLB is phosphorylated. Thus, SERCA2a regulation by DWORF responds to the PLB phosphorylation status, suggesting that DWORF might contribute to SERCA2a activation during conditions of adrenergic stress.

F.5 A neurotransmitter-dependent mechanism of ependymal cell activation: Insights into a novel therapeutic target for spinal cord injury

Background: The drivers that activate endogenous ependymal-derived neural stem/progenitor cells (epNSPCs) remain unknown. Understanding the mechanisms that govern the biology of these cells is critical in developing a therapeutic strategy to harness their regenerative potential after injury. Methods: FoxJ1-CreER-tdTomato reporter mice were used for epNSPC lineage tracing. A conditional genetic knock-out mouse line of glutamate-subtype AMPA receptor (AMPAR) subunits in epNSPCs was generated. Electrophysiological properties were assessed using single cell patch clamp and slice culture recordings. For in vivo studies, mice underwent cervical SCI. To examine the effect of positive modulation of AMPARs, mice received the ampakine CX546 or vehicle and underwent electrophysiological testing, behavioural assessment and spinal cord extraction. Results: Glutamate excitotoxicity, a hallmark in the pathogenesis of acute SCI, drives epNSPCs activation via AMPARs. Genetic knock-out of AMPARs in epNSPCs inhibits their activation following SCI. Positive pharmacological modulation of AMPARs after SCI enhances the migration and differentiation of epNSPCs, increases neuronal sparing and improves long-term locomotor/forelimb function. SCI decreases the excitability of corticospinal tract projections, which is improved with positive AMPAR modulation. Conclusions: Glutamatergic signaling via AMPARs is an important mediator of epNSPC activation after injury. Pharmacological targeting of this mechanism can be used to enhance endogenous regeneration and improve recovery post-SCI.

Mechanistic insights into C(sp2)-H activation in 1-Phenyl-4-vinyl-1H-1,2,3-triazole derivatives: a theoretical study with palladium acetate catalyst.

The activation of C-H bonds is a fundamental process in synthetic organic chemistry, which enables their replacement by highly reactive functional groups. Coordination compounds serve as effective catalysts for this purpose, as they facilitate chemical transformations by interacting with C-H bonds. A comprehensive understanding of the mechanism of activation of this type of bond lays the foundation for the development of efficient protocols for cross-coupling reactions. We explored the activation of C(sp2)-H bonds in 1-Phenyl-4-vinyl-1H-1,2,3-triazole derivatives with CH3, OCH3, and NO2 substituents in the para position of the phenyl ring, using palladium acetate as catalyst. The studied reaction is the first step for subsequent conjugation of the triazoles with naphthoquinones in a Heck-type reaction to create a C-C bond. The basic nitrogen atoms of the 1,2,3-triazole coordinate preferentially with the cationic palladium center to form an activated species. A concerted proton transfer from the terminal vinyl carbon to one of the acetate ligands with low activation energy is the main step for the C(sp2)-H activation. This study offers significant mechanistic insights for enhancing the effectiveness of C(sp2)-H activation protocols in organic synthesis. All calculations were performed using the Gaussian 09 software package and density functional theory (DFT). The structures of all reaction path components were fully optimized using the CAM-B3LYP functional with the Def2-SVP basis set. The optimized geometries were analyzed by computing the second-order Hessian matrix to confirm that the corresponding minimum or transition state was located. To account for solvent effects, the Polarizable Continuum Model of the Integral Equation Formalism (IEFPCM) with water as the solvent was used.

Fe-Phenanthroline derived FeNx coordinated chitosan effectively activates peroxymonosulfate to degrade tetracycline through both radical and non-radical pathways

Fe-Nx sites can activate peroxymonosulfate (PMS) in advanced oxidation processes (AOPs) to produce various reactive oxygen species, and have great potential for removing tetracycline (TC), but their formation and catalytic mechanism are rarely studied. Herein, the Fe/N-C catalyst was prepared by crosslinking chitosan (CS) using a coordination complex of Fe2+ and phenanthroline as the precursor for FeNx. The results of crystal structure, lattice constant, chemical state of N element and structural analysis have demonstrated the successful construction of FeNx sites. The degradation experiments confirmed that the removal efficiency of tetracycline reached up to 90.7 % within 15 min, with a degradation rate of up to 0.184 min−1. Moreover, the material has exhibited excellent performance in complex water environments and within a broad pH range (pH = 2.30 ∼ 9.88). Mechanism analysis proves that the active substances in the system are 1O2, •O2−, SO4•−, •OH and FeIV = O, of which 1O2 played the principal role. The FeNx structure is the primary active site, where the redox cycle between Fe2+ and Fe3+, electron transport between pyridinic N, electron-deficient C and PMS produces active components. In addition, based on the various intermediate products detected, two possible TC degradation pathways are reasonably speculated. In this study, the highly active FeNx sites were successfully constructed, and elucidated their activation mechanism towards PMS, which proved the broad prospect of Fe/N-C materials in pollutant degradation.