Search Results (538)

Experimental and theoretical studies were applied to investigate the adsorption properties of testagen (KEDG) peptide on copper surfaces in sodium chloride solution and, implicitly, its inhibition efficiency (IE) on metal corrosion. The tetrapeptide synthesized from the amino acids lysine (Lys), glutamic acid (Glu), aspartic acid (Asp), and glycine (Gly), named as H-Lys-Glu-Asp-Gly-OH, achieved an inhibition efficiency of around 86% calculated from electrochemical measurements, making KEDG a promising new copper corrosion inhibitor. The experimental data were best fitted to the Freundlich adsorption isotherm. The standard free energy of adsorption ($\mathsf{\Delta }{\mathrm{G}}_{\mathrm{a}\mathrm{d}\mathrm{s}}^{\mathrm{o}}$) reached the value of −30.86 kJ mol⁻¹, which revealed a mixed action mechanism of tetrapeptide, namely, chemical and physical spontaneous adsorption. The copper surface characterization was performed using optical microscopy and SEM/EDS analysis. In the KEDG presence, post-corrosion, SEM images showed a network surface morphology including microdeposits with an acicular appearance, and EDS analysis highlighted an upper surface layer consisting of KEDG, sodium chloride, and copper corrosion compounds. The computational study based on DFT and Monte Carlo simulation confirmed the experimental results and concluded that the spontaneous adsorption equilibrium establishment was the consequence of the contribution of noncovalent (electrostatic, van der Waals) interactions and covalent bonds. Full article

The integration of HS-SPME-GC/MS and UPLC-MS/MS techniques enabled the profiling of volatile organic compounds (VOCs) and amino acids (AAs) in 18 crabapple flower cultivars, facilitating the development of a novel VOC–AA model. Among the 51 identified VOCs, benzyl alcohol, benzaldehyde, and ethyl benzoate were predominant, categorizing cultivars into fruit-almond, fruit-sweet, and mixed types. The amino acids, namely glutamic acid (Glu), asparagine (Asn), aspartic acid (Asp), serine (Ser), and alanine (Ala) constituted 83.6% of the total AAs identified. Notably, specific amino acids showed positive correlations with key VOCs, suggesting a metabolic regulatory mechanism. The Orthogonal Partial Least Squares Discriminant Analysis (OPLS-DA) model, when combined with volatile organic compounds (VOCs) and amino acid profiles, enabled more effective aroma type classification, providing a robust foundation for further studies on aroma mechanisms and targeted breeding. Full article

Background: The N-methyl-d-aspartate receptor (NMDA-R) is a glutamate ionotropic receptor in the brain that is crucial for synaptic plasticity, which underlies learning and memory formation. Dysfunction of NMDA receptors is implicated in various neurological diseases due to their roles in both normal cognition and excitotoxicity. However, their dynamics are challenging to capture accurately due to their high complexity and non-linear behavior. Methods: This article presents the elaboration and calibration of experimentally constrained computational models of GluN1/GluN2A NMDA-R dynamics: (1) a nine-state kinetic model optimized to replicate experimental data and (2) a computationally efficient look-up table model capable of replicating the dynamics of the nine-state kinetic model with a highly reduced footprint. Determination of the kinetic model’s parameter values was performed using the particle swarm optimization algorithm. The optimized kinetic model was then used to generate a rich input–output dataset to train the look-up table synapse model and estimate its coefficients. Results: Optimization produced a kinetic model capable of accurately reproducing experimentally found results such as frequency-dependent potentiation and the temporal response due to synaptic release of glutamate. Furthermore, the look-up table synapse model was able to closely mimic the dynamics of the optimized kinetic model. Conclusions: The results obtained with both models indicate that they constitute accurate alternatives for faithfully reproducing the dynamics of NMDA-Rs. High computational efficiency is also achieved with the use of the look-up table synapse model, making this implementation an ideal option for inclusion in large-scale neuronal models. Full article

Glutamate and dopamine receptors play a crucial role in regulating synaptic plasticity throughout the sleep–wake cycle. These receptors form various heterocomplexes in synaptic areas; however, the role of this protein interactome in sleep–wake cycles remains unclear. Co-immunoprecipitation experiments were conducted to observe the complexation of the NMDA glutamate receptor (NMDAR) subunits GluN2A and GluN2B, metabotropic glutamate receptors mGluR1/5, and dopamine receptors (D1R and D2R) with the scaffold protein Homer in the synaptic membranes of the hippocampus after six hours of sleep deprivation (SD) in rats. Our findings indicate that the level of Homer in the GluN2A/mGluR1/D1R interactome decreased during SD, while the content of Homer remained unchanged in the GluN2B/mGluR1/D2R heterocomplex. Moreover, Homer immunoprecipitated a reduced amount of inositol trisphosphate receptor (IP3R) in the microsomal and synaptic fractions, confirming the dissociation of the ternary supercomplex Homer/mGluR1/IP3R during SD. Additionally, our findings indicate that SD increases the synaptic content of the AMPA receptor (AMPAR) subunit GluA1. Unlike AMPAR, NMDAR subunits in synaptic membranes do not undergo significant changes. Furthermore, the G-to-F actin ratio decreases during SD. Changes in the assembly of actin filaments occur due to the dephosphorylation of cofilin. These results suggest that SD causes the dissociation of the GluN2A/mGluR1/D1R/Homer/IP3R heterocomplex in synaptic and endoplasmic membranes. Full article

The giant freshwater prawn (Macrobrachium rosenbergii, GFP) is a highly valuable crustacean species in global aquaculture. However, a social hierarchy exists among the distinct male morphotypes, specifically blue-clawed males (BC), orange-clawed males (OC), and small males (SMs). In this study, to identify the specific metabolites among BC, OC, and SM, hemolymph samples were collected for the untargeted liquid chromatography–mass spectrometry metabolomics (LC–MS). A total of 172, 546, and 578 significantly different metabolites (SDMs) were identified in OC vs. BC, SM vs. BC, and SM vs. OC, respectively. Notably, creatine and glutamate in BC males likely enhance their aggressive behavior through improved energy metabolism. In the SM group, the up-regulation of prostaglandin E3, testosterone, and arachidonic acid may lead to premature gonadal maturation and enhance immunity. Serotonin, Glu-Pro, and pentanoylcarnitine detected in OC males reflect their physiological need for rapid growth and adaptation to social behaviors. In the SM group, the up-regulation of prostaglandin E3, arachidonic acid, and testosterone may promote premature gonadal maturation and enhance immunodominance. These findings will enhance the understanding of the physiological basis of social hierarchy formation in male GFPs from a metabolomics perspective. Full article

Anxiety disorders, as common neurological diseases in clinical practice, often coexist with depression. Epidemiological surveys indicate that approximately 85% of patients with depression exhibit significant anxiety symptoms. This comorbid state not only exacerbates clinical symptoms but also leads to treatment resistance and prolonged disease duration. This study innovatively developed a compound aromatic plant essential oil (EO) formulation with remarkable anxiolytic and antidepressant effects and systematically elucidated its mechanism of action. The study found that the essential oil formulation, administered via inhalation, could significantly improve behavioral abnormalities in animals subjected to the chronic unpredictable mild stress (CUMS) model, specifically manifesting as (1) the reversal of stress-induced weight gain retardation; (2) a significant increase in sucrose preference; (3) an increase in the total distance of spontaneous activity; and (4) the prolongation of exploration time in the open arms of the elevated plus maze. Neuropathological examinations confirmed that the formulation could effectively protect the structural integrity of hippocampal neurons and alleviate CUMS-induced neural damage. In terms of mechanism of action, the study revealed that the formulation regulates the neurotransmitter system through multiple targets: (1) the upregulation of serotonin (5-HT) and γ-aminobutyric acid (GABA) levels; (2) the downregulation of glutamate (GLU) concentration; and (3) key targets identified via network pharmacological analysis, such as ESR1, STAT3, and PPARG. These findings provide molecular-level evidence for understanding the neuromodulatory effects of aromatic essential oils. Pharmaceutical formulation studies showed that the oil-in-water (O/W) type compound essential oil microemulsion, prepared using microemulsification technology, has a uniform particle size and excellent stability, maintaining stable physicochemical properties at room temperature for an extended period, thus laying a foundation for its clinical application. This study not only validates the practical value of traditional medicine but also provides new ideas for the development of novel anxiolytic and antidepressant drugs, achieving an organic integration of traditional experience and modern technology. Full article

Hans Selye’s stress concept, first introduced in the 1930s, has undergone substantial evolution, extending beyond biology and medicine to influence diverse academic disciplines. Initially, Selye’s General Adaptation Syndrome (GAS) described nonspecific physiological responses to stressors exclusively in mammals, without addressing other biological systems. Consequently, the concept of stress developed independently in biology and medicine, shaped by distinct physiological contexts. This review provides a historical overview of stress research, highlights both parallels and divergences between the stress responses of plants and animals, and integrates insights from traditional Eastern philosophies. We propose an updated GAS framework that incorporates the dynamic balance among reactive oxygen species (ROS), reactive nitrogen species (RNS), and reactive sulfur species (RSS) within the broader context of oxidative stress. We highlight the ionotropic glutamate receptor (iGluR) family and the transient receptor potential (TRP) channel superfamily as minimal molecular architectures for achieving GAS. This perspective expands the classical stress paradigm, providing new insights into redox biology, interspecies stress adaptation, and evolutionary physiology. Full article

As one kind of renewable aromatic polymer, lignin is severely underused due to its chemical recalcitrance. Lignin can endure demethylation modification to improve its activation by releasing more active functional groups. However, the process suffers from expensive, corrosive, and toxic issues by employing halogen-containing reagents, which has become an obstacle to industrial applications. Herein, a series of dicarboxylic acid-based protic ionic liquids (DAPILs) systems composed of ethanolamine and dibasic organic acids (e.g., aspartic acid (Asp), glutamic acid (Glu), succinic acid (SA), and glutaric acid (GA)) with 1~2:1 stoichiometric ratio, have been finely designed for the demethylation of industrial lignin. With [EOA][GA] treatment, the polyphenol content in lignin was favorably increased beyond 1.58 times. The structural tailoring and variation were fully characterized by 2D HSQC and ¹H NMR. The analysis results indicated that, with the increase of phenolic hydroxyl content in lignin, the β-O-4′ bond was broken and the content of structural units (S, G) and the S/G ratio of lignin decreased accordingly. After the treatment, the used IL and tailored lignin can be recovered over 95%. This novel, halogen-free and environmentally friendly lignin-cutting strategy not only opens avenues for high-value utilization of lignin but also expands the field of application of dicarboxylic acid-based protic ionic liquids. Full article

Mild traumatic brain injury (mTBI), a leading cause of disability in young adults, often results from external forces that damage the brain. Cellularly, mTBI induces oxidative stress, characterized by excessive reactive oxygen species (ROS) and diminished antioxidant capacity. This redox imbalance disrupts hippocampal glutamatergic transmission and synaptic plasticity, where NMDA receptors (NMDARs) are crucial. The exocyst, a vesicle tethering complex, is implicated in glutamate receptor trafficking. We previously showed that Exo70, a key exocyst subunit, redistributes within synapses and increases its interaction with the NMDAR subunit GluN2B following mTBI, suggesting a role in GluN2B distribution from synaptic to extrasynaptic sites. This study investigated whether Exo70 could mitigate mTBI pathology by modulating NMDAR trafficking under elevated oxidative stress. Using a modified Maryland mTBI mouse model, we overexpressed Exo70 in CA1 pyramidal neurons via lentiviral transduction. Exo70 overexpression prevented mTBI-induced cognitive impairment, assessed by the Morris water maze. Moreover, these mice exhibited basal and NMDAR-dependent hippocampal synaptic transmission comparable to sham animals, preventing mTBI-induced deterioration. Preserved long-term potentiation, abundant synaptic GluN2B-containing NMDARs, and downstream signaling indicated that Exo70 overexpression prevented mTBI-related alterations. Our findings highlight Exo70’s crucial role in NMDAR trafficking, potentially counteracting oxidative stress effects. The exocyst complex may be a critical component of the machinery regulating NMDAR distribution in health and disease, particularly in pathologies featuring oxidative stress and NMDAR dysfunction, like mTBI. Full article

Opioid use induces neurobiological adaptations throughout mesolimbic brain regions, such as the orbitofrontal cortex (OFC), which mediates decision-making and emotional–cognitive regulation. Previously, we showed that a circular RNA (circRNA) species, rno_circGrin2b_011731 (circGrin2b), is upregulated in the OFC of rats following chronic self-administration (SA) of the opioid heroin. circGrin2b is derived from Grin2b, which encodes the regulatory subunit of the glutamate ionotropic NMDA receptor, GluN2B. However, the upstream regulatory mechanisms of circGrin2b biogenesis and the downstream consequences of circGrin2b dysregulation remain unknown. We hypothesized that opioid-induced elevation of circGrin2b is accompanied by regulation of circRNA biogenesis enzymes, and that circGrin2b may sponge microRNAs (miRNAs), as miRNA sponging is a well-described characteristic of circRNAs. To test these hypotheses, we established an in vitro primary cortical cell culture model to examine alterations in circGrin2b expression following exposure to the opioid morphine. We measured mRNA expression of known circRNA splicing factors and observed significant downregulation of Fused in Sarcoma (Fus), a negative regulator of circRNA biogenesis, following 90 min or 24 h of morphine exposure. Downregulation of Fus at 24 h post-morphine was accompanied by upregulation of circGrin2b and downregulation of miR-26b-3p, a predicted miRNA target of circGrin2b. Luciferase reporter assays confirmed interaction of miR-26b-3p with circGrin2b. Finally, we report a significant negative relationship between circGrin2b and miR-26b-3p expression in the OFC of rats following heroin SA. We conclude that regulation of circGrin2b is an opioid-induced neuroadaptation that may impact downstream signaling of miRNA pathways in the frontal cortex. Full article

L-Glutamate (L-Glu) and its salt derivatives are widely used in the food industry as flavor enhancers. Although the consumption of these compounds is generally considered safe, some studies suggest that chronically consuming L-Glu may be associated with various disorders. In this study, Wistar pregnant rats were treated daily with 1 g/L of L-Glu in their drinking water throughout the gestational period. OPA-1, DRP-1, and mitofusin 2—key proteins involved in mitochondrial fusion and fission—were analyzed by Western blot. The results showed that L-Glu exposure significantly decreased DRP-1 levels, while OPA-1 and mitofusin 2 levels were unaffected. This was accompanied by a notable decrease in mitochondrial complexes III and V. The activities of Mg²⁺-ATPase and Na⁺/K⁺-ATPase were also analyzed in fetal cerebellar plasma membranes. Maternal L-Glu intake significantly increased Mg²⁺-ATPase activity. Regarding Na⁺/K⁺-ATPase, the data showed that L-Glu exposure did not modulate the protein level or its activity. However, a positive interaction with glutamate receptors was observed in both activities, although neither AMPA nor NMDA receptors appeared to be involved. These results suggest that chronic maternal L-Glu intake during gestation modulates Mg²⁺-ATPase activity and protein markers of mitochondrial dynamics in the fetal cerebellum, which could affect neonatal development. Full article

Elucidating the interfacial interaction mechanisms between biomolecules and metal surfaces is crucial for designing functionalized biomedical materials. This study employs first-principles calculations based on density functional theory (DFT) to investigate the adsorption behaviors of arginine (Arg), glutamic acid (Glu), aspartic acid (Asp), and valine (Val) on magnesium (Mg) and Mg alloy surfaces. The adsorption behaviors of four kinds of amino acids on Mg and Mg alloy surfaces were analyzed through optimized adsorption configurations, adsorption energies (E_ads), bond lengths, projected densities of states (PDOSs), and differential charge densities. The calculated results of E_ads followed the order of Arg > Glu > Asp > Val, driven by functional group spatial configurations and electron transfer efficiency. Alloying elements facilitated charge redistribution on the Mg and Mg alloy surfaces, enhancing the interaction between amino acids and the alloy surfaces. Notably, the guanidino group of Arg exhibited exceptional adsorption stability and multi-dentate bonding, increasing electron donation to the Mg(0001) surface, achieving the highest E_ads (−1.67 eV). This work provides insights into the structure–activity relationships between amino acids and Mg and Mg alloy surfaces, offering a foundation for designing biomolecule-derived functional coatings and strategies for improving the biocompatibility of Mg and Mg alloy implants. Full article

Schizophrenia is a complex neuropsychiatric disorder composed of primary cluster-positive symptoms, negative symptoms, disorganization, neurocognitive deficits, and social cognitive impairments. While traditional antipsychotics primarily target dopamine pathways, they provide limited efficacy against cognitive deficits and negative symptoms. Growing evidence implicates glutamatergic dysregulation, particularly N-methyl-D-aspartate receptor (NMDA-R) hypofunction, in the pathophysiology of schizophrenia, making glutamate modulation a promising therapeutic approach. This review explores emerging glutamate-based treatment strategies, including NMDA receptor modulators, metabotropic glutamate receptor (mGluR) agents, glutamate transporter regulators, and kynurenine pathway inhibitors. We summarize preclinical and clinical findings on NMDA co-agonists (D-serine and glycine), glycine transporter inhibitors, D-amino acid oxidase inhibitors, and mGluR-targeted therapies, highlighting their mechanisms, efficacy, and limitations. In addition, we discuss novel interventions aimed at restoring glutamate homeostasis, including neuroinflammatory modulation and synaptic plasticity enhancers. Despite promising results, many glutamate-targeting therapies have yielded inconsistent clinical outcomes, underscoring the need for biomarker-driven patient selection and optimized treatment protocols. We propose that integrating glutamate modulators with existing antipsychotic regimens may enhance therapeutic response while minimizing side effects. Future research should focus on refining glutamate-based interventions, identifying predictive biomarkers, and addressing the heterogeneity in schizophrenia pathology. With continued advancements, glutamate modulation has the potential to transform schizophrenia treatment, particularly for cognitive and negative symptoms that remain largely unaddressed by current therapies. Full article

This study aimed to systematically investigate and compare the biochemical composition of 13 locally abundant shellfish species (Dalian, China) and the taste characteristics of these shellfish and their boiling liquids. The results showed that Chlamys farreri exhibited the highest level of protein (64.58%) and polyunsaturated fatty acids (53.84% of total fatty acids), whereas Scapharca subcrenata showed a better composition and proportion of essential amino acids (EAA/TAA = 39.02%, EAA/NEAA = 63.98%) compared to other species. Glu, Gly, Ala, Arg, 5′-monophosphate (GMP), lactic acid, succinic acid, and malic acid were quantitatively determined as the main taste compounds in shellfish and their boiling liquids. The equivalent umami concentration (EUC) values, reflecting the synergistic effect of umami compounds, showed distinct characteristics, and the maximum umami intensities were found in Meretrix meretrix (586.8 g monosodium glutamate (MSG)/100 g) and the boiling liquid of Clinocardium californiense (358.3 g MSG/100 g), respectively. Based on these experimental results, C. californiense was found to have the highest prehensive quality score as revealed by principal component analysis (PCA). These results are important for promoting studies aimed at nutritional value development and taste compounds improvement of these shellfish species, especially for flavor enhancer development. Meanwhile, different shellfish species can be comprehensively developed and utilized based on their distinct nutritional properties, and this would translate into greater profitability for producers. Full article

Octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX) is a globally recognized energetic material that widely used in industrial, mining, and military fields. Like hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) and other nitramine compounds, HMX has also been reported to exhibit neurotoxicity. However, the molecular mechanisms underlying the toxic effects of HMX remain poorly understood. Therefore, this study aims to investigate the neurotoxicity induced by HMX by adopting PC12 cells. The results show that HMX treatment decreased cell viability and upregulated the intracellular free calcium ions (Ca²⁺) in PC12 cells. Furthermore, HMX caused aggravated oxidative stress in PC12 cells, as evidenced by the upregulations of reactive oxygen species (ROS) and malondialdehyde (MDA). Intracellular biochemical assays demonstrated that HMX induced loss of mitochondrial membrane potential in PC12 cells. Notably, altered expression of brain-derived neurotrophic factor (BDNF) and ionotropic glutamate receptors (iGluRs), as well as an abnormal transcription profile, were also observed in PC12 cells treated by HMX. These findings suggest that HMX exerts toxic effects on PC12 cells, involved in oxidative stress, and disturbances in Ca²⁺ and BDNF, accompanied by aberrant iGluRs. Overall, the present study helps us better understand the health hazards associated with HMX and provides valuable insights for developing the health protection standards related to HMX exposure. Full article