Search Results (713)

In order to innovatively develop high-activity ACE inhibitory peptides from edible fungi, the conditions for a double-enzymatic hydrolysis preparation of ACE inhibitory peptides from Flammulina velutipes were optimized by response surface methodology. After purification by macroporous resin, gel chromatography, and RP-HPLC, a crude peptide fraction was obtained; its ACE inhibition rate was 85.73 ± 0.95% (IC₅₀ = 0.83 ± 0.09 mg/mL). Based on LC-MS/MS sequencing, the four novel peptides, namely, FAGGP, FDGY, FHPGY, and WADP, were screened by computer analysis and molecular docking technology. The four peptides exhibited a binding energy between −9.4 and −10.3 kcal/mol, and formed hydrogen bonds with Tyr523, Ala354, and Glu384 in the S1 pocket, Tyr520 and His353 in the S2 pocket, and His383 in the HEXXH zinc-coordinating motif of ACE, indicating their good affinity with the ACE active site. The IC₅₀ values of the four ACE inhibitory peptides were 29.17, 91.55, 14.79, and 41.27 μM, respectively, suggesting that these peptides could potentially contribute to the development of new antihypertensive products. Full article

In placental mammals, the co-option of vertebrate orthologous ATP1B4 genes has profoundly altered the properties of the encoded BetaM proteins, which function as bona fide β-subunits of Na,K-ATPases in lower vertebrates. Eutherian BetaM acquired an extended Glu-rich N-terminal domain resulting in the complete loss of its ancestral function and became a skeletal and cardiac muscle-specific component of the inner nuclear membrane. BetaM is expressed at the highest level during perinatal development and is implicated in gene regulation. Here we report the long-term consequences of Atp1b4 ablation on metabolic parameters in adult mice. Male BetaM-deficient (Atp1b4−/Y) mice have remarkably lower body weight and adiposity than their wild-type littermates, despite higher food intake. Indirect calorimetry shows higher energy expenditure (heat production and oxygen consumption) with a greater spontaneous locomotor activity in Atp1b4−/Y males. Their lower respiratory exchange ratio suggests a greater reliance on fat metabolism compared to their wild-type counterparts. Consistently, Atp1b4−/Y KO mice exhibit enhanced β-oxidation in skeletal muscle, along with improved glucose and insulin tolerance. These robust metabolic changes induced by Atp1b4 disruption demonstrate that eutherian BetaM plays an important role in regulating adult mouse metabolism. This demonstrates that bypassing the co-option of Atp1b4 potentially reduces susceptibility to obesity. Thus, Atp1b4 ablation leading to the loss of evolutionarily acquired BetaM functions serves as a model for a potential alternative pathway in mammalian evolution. Full article

The paper deals with the issue of obtaining iron-sulfur-containing binders through their mechanochemical treatment using mutual neutralization and detoxification structure formation, and the curing stage of arbolite concrete composites based on industrial waste under long-term loading were also studied. Due to abrasion and impact, the mutual neutralization and detoxification methods of industrial waste toxic components through their mechanochemical treatment on the structures of ball mill LShM-750, were used to obtain iron-sulfur-containing binders. Pyrite cinders acted as oxidizing agents, and elementary technical sulfur had reduced properties. To determine the rate of creep strain growth, the load on prism samples was applied in the form of specially made spring units at stress levels of 0.15 R_bn, 0.44 R_bn, and 0.74 R_bn, where R_bn is the prism strength of iron-sulfur-containing arbolite concrete in compression. The strength and fracture formations of lightweight iron-sulfur concrete were studied using strain gauge apparatus and depth strain gauges glued on shredded reed fibers using adhesive, installed before concreting. It was revealed that the introduction of a sulfur additive within the range from 10 to 13% increases the compressive strength of iron-sulfur-containing concrete composites prepared with that of mortars at a water/solid ratio equal to 0.385 in wet and dry states. It is found that the deformations occurring under applied load growth proportionally to it, and deviation from this regularity was observed for lightweight iron-sulfur-containing concrete only at high compressive stresses. It was also proved that the destruction of iron-sulfur-containing arbolite occurs sequentially. First, the destruction of the mortar component is observed, and then the organic aggregate in the form of crushed reed fiber is destroyed. It was confirmed that arbolite concrete composite can be used as an effective wall material for civil engineering structure, especially in seismic regions of Kazakhstan. Full article

Deep learning has great potential in the field of functional peptide prediction. This study combines metagenomics and deep learning to efficiently discover potential umami peptides in fermented sausages. A candidate peptide library was generated using metagenomic data from fermented sausages, an integrated deep learning model was constructed for prediction, and SHAP (SHapley Additive exPlanations) interpretability analysis was performed to elucidate the key amino acid features and contributions of the model in predicting umami peptides, screening the top ten peptides with the highest predicted probability. Subsequently, molecular docking was performed to assess the binding stability of these peptides with the umami receptor T1R1/T1R3, selecting the three peptides DDSMAATGL, DGEEDASM, and DEEEVDI with the most stable binding for further study. Docking analysis revealed the important roles of the key receptor residues Glu301, Arg277, Lys328, and His71 in hydrogen bond formation. Molecular dynamics simulations validated the robust integrity of the peptide–receptor associations. Finally, sensory evaluation demonstrated that these three peptides possessed significant umami characteristics, with low umami thresholds (0.11, 0.37, and 0.44 mg/mL, respectively). This study, based on metagenomics and deep learning, provides a high-throughput strategy for the discovery and validation of functional peptides. Full article

Objectives: This study investigated the properties of a neutral exopolysaccharide (EPS-LP1) with an average molecular weight of 55,637 Da, isolated from Lactiplantibacillus plantarum DMDL 9010 (LP9010). Results: The composition of EPS-LP1 includes galactose (Gal), glucose (Glu) and mannose (Man) in a molar ratio of 5.35:86.25:8.40. Notably, EPS-LP1 exhibits a smooth and rod-like surface along with thermal stability. Methylation combined with nuclear magnetic resonance analysis revealed that EPS-LP1 structured as t-Galp(1→, →6)-Glcp(1→, 4)-Glcp(1→ and →4,6)-Galp(1→), with relative molar ratio of 1.016:9.874:4.355:78.693:6.062, respectively. In the concentration range of 50 to 400 mg/mL, we observed the absence of cytotoxic effects from EPS-LP1 on RAW264.7 cells. Furthermore, EPS-LP1 demonstrated protective effects on RAW264.7 cells against oxidative damage by reducing the production of reactive oxygen species (ROS), malondialdehyde (MDA), and lactate dehydrogenase (LDH) release. Conversely, an increase in superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and concentrations of glutathione (GSH) was observed. Immunoreactivity assays indicated that EPS-LP1 can effectively reduce the production of nitric oxide (NO) and inhibit the secretion of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). Additionally, it inhibited the activation of the mitogen-activated protein kinase (MAPK)/nuclear factor-kappa B gene binding (NF-kB) signaling pathway. Conclusions: This research provides a foundation basis for further investigations into the neutral exopolysaccharide derived from LP9010. Full article

This study systematically investigated the effects of dietary tea polyphenols (TPs, major bioactive polyphenols from Camellia sinensis with potent antioxidant and anti-inflammatory properties) on the growth performance and intestinal health of hybrid crucian carp HCC2 under chronic crowding stress. A low-density control group (44.4 fish/m³, basal diet without TPs) and four high-density crowding stress groups (222.2 fish/m³) were established, one fed the basal diet without TPs (CS) and three fed basal diets supplemented with 100 (CSLTP), 200 (CSMTP), or 400 (CSHTP) mg/kg TPs. We analyzed the impacts of TPs on growth performance, serum biochemical parameters, antioxidant capacity, expression of lipid metabolism-related genes, and intestinal microbiota composition. The results demonstrated that chronic crowding stress significantly suppressed the final body weight, weight gain rate, and specific growth rate of HCC2, while increasing serum lactate LDH, TG, and ALB and decreasing GLU, LDL-C, ALT, AST, and ALP levels. Dietary TPs supplementation enhanced antioxidant capacity (T-AOC, SOD, CAT, and GSH) and alleviated lipid metabolic disorders by activating the Nrf2/Keap1 and PPARα signaling pathways, thereby upregulating the expression of liver antioxidant genes (CAT and SOD) and fatty acid oxidation genes (CPT1 and acox1). Furthermore, intestinal microbiota analysis revealed that chronic crowding stress significantly increased the abundance of Proteobacteria and decreased the proportion of Firmicutes compared to the low-density control. Dietary TPs intervention, particularly at higher doses, partially restored the Firmicutes abundance and reduced the enrichment of potential pathogenic bacteria associated with stress. This study is the first to comprehensively elucidate the mechanism by which TPs alleviate crowding stress through enhanced antioxidant capacity, metabolic regulation, and microbiota remodeling, providing robust theoretical support for the application of plant-based additives in aquaculture. 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 effects of a fungal elicitor from Trichothecium roseum on signal pathways of salicylic acid (SA), jasmonic acid (JA), and Ca²⁺ in potato tubers were investigated. The results showed that fungal elicitor treatment effectively inhibited the lesion diameter of Fusarium sulphureum in vivo, which was 17.5% lower than that of the control. In addition, fungal elicitor treatment triggered an increase in O₂⁻ production and H₂O₂ content. The fungal elicitor enhanced the activities and gene expression levels of isochorismate synthase (ICS), phenylalanine ammonia lyase (PAL), allene oxide cyclase (AOC), allene oxide synthase (AOS), lipoxygenase (LOX), and Ca²⁺-ATPase. Furthermore, the fungal elicitor promoted an increase in calmodulin (CaM) content. Protective enzymes (dismutase (SOD), catalase (CAT), polyphenol oxidase (PPO), chitinase (CHI), and β-1,3-glucanase (Glu)) and disease-resistance-related genes (PR1, PR2, and PDF1.2) were induced to be upregulated by elicitor treatment. These results indicated that the fungal elicitor induced disease resistance by accelerating the accumulation of reactive oxygen species (ROS), activating SA, JA, and Ca²⁺ signaling, and upregulating resistance genes. The results of this study revealed the molecular mechanism of fungal elicitor-induced resistance in the potato, which provides a theoretical basis for the mining of new, safe, and efficient elicitor-sourced antifungal agents and is of great importance for the effective control of potato dry rot disease. Full article

Magnaporthe oryzae (M. oryzae) is a phytopathogenic fungus that inflicts damage on vital crops, particularly rice. Its asexual reproduction leads to the generation of numerous conidia, which is a critical factor contributing to the prevalence of rice blast disease. However, the molecules regulating the asexual reproduction of M. oryzae are unknown. In our study, to identify the molecules capable of regulating the asexual reproduction of M. oryzae, compositions of the complete medium (CM) were screened. Results showed that acid-hydrolyzed casein (AHC) could remarkably promote conidial production. One M. oryzae conidiation inducer was isolated from AHC using high-performance liquid chromatography (HPLC) under the guidance of bioassay. Its structure was further elucidated as a decapeptide compound (pyroGlu-EQNQEQPIR) by LC-MS/MS, chemical synthesis, and conidium-inducing assays, named M. oryzae conidiation inducer decapeptide (MCIDP). MCIDP could significantly promote the conidiation of M. oryzae and two other filamentous ascomycetes (Botrytis cinerea and Fusarium graminearum). The Mps1 MAPK cascade signaling pathway is crucial for conidiation, and the effect of MCIDP on this pathway was investigated to elucidate the mechanism underlying conidiation enhancement. qRT-PCR analysis demonstrated that MCIDP could remarkably upregulate the gene expression within the Mps1 MAPK cascade signaling pathway, especially the WSC2, WSC3, PKC1, MKK1, MPS1, and MIG1. Furthermore, the ΔMowsc1, ΔMowsc2, ΔMowsc3, and ΔMomid2 mutant strains were constructed. Bioassay results showed that MCIDP failed to promote conidial formation and hyphal growth in these mutant strains. These findings indicate that MCIDP promotes conidiation of M. oryzae by modulating the Mps1 MAPK signaling pathway. Full article

This study aimed to evaluate the impact of Eucommia ulmoides extract (EE) supplementation on the expression of genes related to glucose metabolism and antioxidant capacity of M. salmoides in response to different starch levels. In order to evaluate the effect of EE on fish metabolism and especially to enhance the metabolism of M. salmoides towards glucose metabolism, especially in high and low starch formulations, we designed six experimental feed groups: PC (high-starch control), NC (low-starch control), and four groups supplemented with EE on the basis of PC, with EE concentrations of 0.05%, 0.10%, 0.15%, and 0.20%, respectively. Each feed was administered to fish with an average weight of 36.98 ± 0.08 g, which were cultured for seven weeks, and the water temperature was 31–33 °C. The results demonstrated that increasing the EE concentration in the feed significantly influenced fish growth without affecting the body composition. Regarding the antioxidant activity, the highest CAT (catalase) enzyme activity in the intestine was recorded in the 0.15% EE group. Additionally, the mRNA expression of the antioxidant gene keap1 (kelch-like ECH-associated protein1) increased with higher EE supplementation, and sod (superoxide dismutase) mRNA expression was significantly elevated in the 0.10% EE group compared to that in the PC group. A plasma biochemical analysis revealed a significant increase in the ALP (alkaline phosphatase) activity in the 0.05% EE group relative to the PC group, while the TG (triglycerides) levels progressively decreased as the EE levels increased. Furthermore, the GLU (glucose) levels were significantly reduced in both the EE-supplemented and NC groups compared to those in the PC group. Among the genes associated with glucose metabolism, both gk (glucokinase) and pepck (phosphoenol pyruvate carboxykinase) exhibited a pattern of initially decreasing, followed by an increase, as the EE levels rose, with the pepck (phosphoenol pyruvate carboxykinase) expression being lowest in the 0.10% EE group. In conclusion, appropriate EE supplementation in the diet may promote growth performance, enhance antioxidant capacity, and support the expression of genes related to glucose metabolism of M.salmoides in response to different starch levels. Full article

Glu-Phe-Asp (GFD) proteinoids represent a class of synthetic polypeptides capable of self-assembling into microspheres, fibres, or combinations thereof, with morphology dramatically influencing their electrical properties. Extended recordings and detailed waveforms demonstrate that microspheres generate rapid, nerve-like spikes, while fibres exhibit consistent and gradual variations in voltage. Mixed networks integrate multiple components to achieve a balanced output. Electrochemical measurements show clear differences. Microspheres have a low capacitance of $1.926\pm 5.735$$\mathsf{\mu }$F. They show high impedance at $6646.282\pm 178.664$ Ohm. Their resistance is low, measuring 15,830.739 ± 652.514 m$\mathsf{\Omega }$. This structure allows for quick ionic transport, leading to spiking behaviour. Fibres show high capacitance ($9.912\pm 0.171$$\mathsf{\mu }$F) and low impedance ($209.400\pm 0.286$ Ohm). They also have high resistance (163,067.613 ± 9253.064 m$\mathsf{\Omega }$). This combination helps with charge storage and slow potential changes. The 50:50 mixture shows middle values for all parameters. This confirms that hybrid electrical properties have emerged. The differences come from basic structural changes. Microspheres trap ions in small, round spaces. This allows for quick release. In contrast, fibers spread ions along their length. This leads to slower wave propagation. In mixed systems, diverse voltage zones emerge, suggesting cooperative dynamics between morphologies. This electrical polymorphism in simple proteinoid systems may explain complexity in biological systems. This study shows that structural polymorphism in GFD proteinoids affects their electrical properties. This finding is significant for biomimetic computing and sheds light on prebiotic information-processing systems. 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

Background: In this study, molecular mechanisms contributing to delafloxacin resistance in Pseudomonas aeruginosa strains were investigated. Delafloxacin is a recently approved fluoroquinolone currently introduced to clinical applications. Methods: A total of 52 P. aeruginosa strains were collected from clinical isolates. Antimicrobial susceptibility testing was performed via broth microdilution, and the minimum inhibitory concentration (MIC) values for ciprofloxacin, levofloxacin, delafloxacin, ceftazidime and imipenem were determined. Five delafloxacin-resistant P. aeruginosa strains were selected for whole-genome sequencing (WGS). Results: MIC50 values were determined, and the following results were obtained: ciprofloxacin 0.25 mg/L, levofloxacin 0.25 mg/L and delafloxacin 1 mg/L. All five selected strains showed both extended-spectrum beta-lactamase and carbapenemase production. WGS analysis of these strains determined the sequence types (STs), namely, ST235 (two strains), ST316 (two strains) and ST395. Several mutations in quinolone-resistance-determining regions (QRDRs) were detected in all five delafloxacin-resistant P. aeruginosa strains as follows: gyrA Thr83Ile and parC Ser87Leu mutations were present in all five strains, while parE Thr223Ala in ST235, Glu459Val in ST316 and Val200Met in ST395 were detected. MexAB-OprM and MexCD-OprJ efflux pumps were uniformly present in all delafloxacin-resistant P. aeruginosa strains. All strains of ST235 and ST316 carried bla_NDM-1 in combination with other beta-lactamases. In our study, the in vitro efficacy of delafloxacin is inferior compared to previous fluoroquinolones based on MIC50 values; however, MIC values of delafloxacin ranged between 0.125 and 128 mg/L in our P. aeruginosa collection, and 21 out of 52 strains showed susceptibility to delafloxacin. Conclusions: Multiple QRDR mutations combined with several efflux pumps confer delafloxacin resistance in P. aeruginosa. Among the different detected multidrug-resistant P. aeruginosa strains in this study, we also report on an NDM-1 producing P. aeruginosa ST316 in Hungary. Full article

Rhodotorula mucilaginosa plays a key role in developing the taste of dry-cured ham, while the mechanism of Rhodotorula mucilaginosa proteases on myofibrillar protein (MP) hydrolysis and the evolution of taste substances has not been studied. The enzymatic characteristics, hydrolysis capacities for MPs, free amino acid contents, metabolite compositions, and taste attributes were investigated during the interactions of MPs and proteases. The proteases of R. mucilaginosa EIODSF019 (RE) and R. mucilaginosa XZY63-3 (RX) showed high hydrolytic activities at the conditions of pH 5.0~7.0 and 30~40 °C. Compared with RX, RE showed a lower Michaelis constant (Km) value and a better affinity for protein substrates. RE showed a higher capability to degrade myosin and actin compared with RX and P. kudriavzevii XS-5 proteases (PK). The microtopography of enzyme-treated MPs in RE presented a smoother surface and lower root mean square roughness than that in RX and PK. The total content of free amino acids significantly increased from 0.34 mg/100 mL of CK to 17.10 mg/100 mL of RE after 4 h of hydrolysis of MPs. Sixty-two metabolites were identified by LC-MS/MS, and γ-glutamyl peptides were the main components of MP hydrolysates. Sensory scores of umami, richness, and aftertaste showed the largest values in RE among these groups. Partial least squares discriminant analysis and correlation network demonstrated that γ-Glu-Lys, γ-Glu-Tyr, γ-Glu-Glu, γ-Glu-His, γ-Glu-Leu, γ-Glu-Cys, γ-Glu-Ala, and γ-Glu-Gln were positively correlated with the improvements of umami, richness, and aftertaste in RE. Full article

Ataxia-telangiectasia is a rare autosomal recessive disorder that is difficult to diagnose due to its unpredictable presentation. It is characterized by cerebellar degeneration, telangiectasias, immunodeficiency, frequent pulmonary infections, and tumors. Immune system abnormalities manifest as disruptions in both cellular and humoral immunity. The most common findings include decreased levels of immunoglobulin classes (IgA, IgM, IgG, and IgG subclasses) and a reduced number of T and B lymphocytes. A four-year-old girl was initially evaluated and treated for skin lesions that presented as crusts spreading across her body. She was monitored by a pulmonologist due to frequent bronchial obstructions. Over time, she developed bilateral scleral telangiectasia, saccadic eye movements, and impaired convergence. Her gait was wide-based and unstable, with truncal ataxia and a positive Romberg sign. Laboratory tests revealed decreased immunoglobulin G levels, subclass IgG4 levels, elevated alpha-fetoprotein, and a reduced number of T and B lymphocytes. Brain magnetic resonance imaging showed cerebellar atrophy. Whole-exome sequencing identified heterozygous variants c.1564-165del, p.(Glu5221lefsTer43), and c.7630-2A>C in the serine/threonine-protein kinase ATM (ataxia-telangiectasia mutated) gene, confirming the diagnosis of ataxia-telangiectasia. Following diagnosis, treatment with intravenous immunoglobulin replacement was initiated along with infection prevention and management. The goal of this case report is to raise awareness of the atypical initial presentation that may lead to a diagnostic delay. We emphasize the importance of considering ataxia-telangiectasia in the differential diagnosis, even when classical neurological signs are not yet evident. Full article