Search Results (542)

Background/Objectives: Low-fishmeal diets are widely adopted to improve sustainability in shrimp aquaculture, yet reduced palatability and metabolic stress frequently suppress feed intake and growth. We evaluated whether a crayfish (Procambarus clarkii) by-product protein hydrolysate (CBPH) could mitigate low-fishmeal-induced performance losses by modulating feeding-related metabolic signaling and gut microbiota features in Pacific white shrimp (Litopenaeus vannamei). Methods: In an 8-week feeding trial, 360 juveniles (initial body weight 0.46 g) were assigned to three diets (four replicates per diet): a commercial control (CON), a low-fishmeal diet (LFM), and LFM supplemented with 2% CBPH (CBPH). Growth, feed utilization, whole-body composition, hemolymph biochemical indices (TP, TG, GLU, AST, ALT), intestinal appetite-related gene expression (5-HTR, CART, CCK1R, D2-like, NPY), and intestinal microbiota profiles (full-length 16S rRNA sequencing, V1–V9, PacBio) were assessed. Results: Compared with the LFM group, CBPH supplementation increased feed intake and improved feed conversion, restoring final body weight and growth rates to levels comparable to CON. CBPH also alleviated low-fishmeal-associated metabolic stress, including reduced AST and ALT activities and lower glucose levels. The LFM diet induced upregulation of anorexigenic genes (5-HTR, CART, D2-like) and downregulation of NPY in the shrimp intestine, whereas CBPH supplementation reversed these transcriptional changes. In addition, microbiota richness indices (ACE and Chao1) were elevated by CBPH relative to LFM, accompanied by compositional shifts at the phylum and genus levels. Conclusions: CBPH effectively alleviated low-fishmeal-induced reductions in feeding and growth, accompanied by coordinated changes in feeding-related gene expression, systemic biochemical markers, and gut microbiota composition, supporting its potential as a functional ingredient to stabilize metabolic responses in low-fishmeal shrimp feeds. Full article

Objectives: This study aimed to identify factors influencing the magnitude of the difference between plasma glucose concentration (Glu(P)) and serum glucose concentration (Glu(S)). Methods: A total of 333 healthy Japanese adults aged 22–29 years (212 males and 121 females) were enrolled. Plasma samples were collected using glycolytic inhibitors, whereas serum samples were obtained without glycolytic inhibitors and kept at room temperature. Glu(P) and Glu(S) were measured and compared. Results: The median difference between Glu(P) and Glu(S), defined as Glu(P-S), was 4 mg/dL across all participants, with no gender-related differences. A strong positive correlation was observed between Glu(P) and Glu(S). Glu(P-S) was positively correlated with body mass index, Glu(P), triglyceride–glucose index, white blood cell count, serum sodium, magnesium, and zinc levels. In contrast, Glu(P-S) was negatively correlated with Glu(S), hemoglobin A1c (HbA1c), homeostasis model assessment of beta-cell function, and high-density lipoprotein cholesterol (HDL-C). Multiple regression analysis demonstrated that HDL-C and HbA1c were independent determinants of Glu(P-S) in the overall cohort. Among females, HDL-C, triglyceride, low-density lipoprotein cholesterol, ferritin, and C-reactive protein independently influenced Glu(P-S), whereas no independent determinants were identified in males. Conclusions: Plasma glucose concentrations measured with glycolytic inhibitors were significantly higher than serum glucose concentrations measured without inhibitors at room temperature. The magnitude of Glu(P-S) appears to be associated with markers of insulin resistance, particularly HDL-C levels. Full article

Fruit spoilage caused by fungal pathogens jeopardizes food safety and inflicts significant economic damage. Cyclic lipopeptides (CLPs) have been applied as biofungicides by disrupting the cell membrane and intracellular components; however, the first target for antifungal action is the fungal cell wall. This study elucidates the molecular mechanism by which CLPs compromise cell wall integrity using molecular dynamics simulation and experimental validation. Among Surfactin C, Iturin A, and Fengycin A, Surfactin C exhibited the strongest binding to β-glucan (ΔE = −1970.536 kcal/mol) and the lowest free volume (7.302%), with enhanced effects at higher concentrations. Key interaction sites were identified at C=O of D-Leu3, -N-H of Leu2, and -COOH of Glu1 by Radial distribution function. In vivo assays with Aspergillus niger confirmed a MIC of 40 µg/mL and Surfactin-induced β-glucan exposure. FTIR and XPS analyses revealed structural reorganization and hydrogen bonding, while SEM/TEM showed spore deformation and wall rupture. These findings demonstrate that Surfactin disrupts fungal cell walls via direct complexation with β-glucan, leading to structural collapse and cell death, supporting its potential as a targeted biofungicide. Full article

A composite beam consisting of two layers is experimentally tested as an energy harvesting device. The substrate layer is made of aluminum and the piezoelectric layer is glued at 90% of the length of the alumina layer. The beam is clamped at one end and is free at the other. The cantilever is subjected to periodic kinematic excitation, and the tip acceleration as well as the generated electricity are measured. A 3D finite element model of the beam is created and the coupled mechanical and electrical fields are studied numerically. The results are compared with those obtained experimentally. A parametric study is conducted to investigate the influence of the loading parameters (frequency and amplitude of excitation) and the electric resistance in the circuit on the generated electricity. Conclusions about the optimal conditions with respect to energy harvesting are made. The importance of proper modelling of the contact between the PZT layer and the substrate is demonstrated. Full article

Atrial fibrillation (AF) is the most common cardiac arrhythmia, and both metabolic reprogramming and autophagy have been implicated in its pathogenesis. However, the expression pattern of autophagy-related genes during metabolic reprogramming in AF remains elusive. We aimed to characterize the expression profiles of autophagy- and metabolic reprogramming-related genes in atrial tissue to gain pathophysiological insights into AF. Three datasets obtained from the Gene Expression Omnibus (GSE2240, GSE79768, and GSE14975) that included atrial tissue samples from patients with or without AF were subjected to a bioinformatics analysis, which identified 2812 differentially expressed genes. Eight autophagy- and metabolic reprogramming-related differentially expressed genes (A&MRRDEGs) were identified as key candidates through least absolute shrinkage and selection operator regression combined with the random forest approach. Meanwhile, mice underwent transverse aortic constriction (TAC) for 2 weeks in an AF model, and gene expression in atrial tissue was analyzed. In atrial tissues from TAC mice, only Akt1 and Hspa5 of the eight A&MRRDEGs exhibited expression changes concordant with the human datasets, while Glud1 showed discordant regulation. Collectively, these cross-species findings highlight that the eight A&MRRDEGs, particularly AKT1 and HSPA5, are potentially involved in autophagy and metabolic reprogramming during AF pathogenesis. Full article

Airborne organic dust has rarely been subject to immunotoxicological analysis. A pilot study was undertaken to link exposure metrics (respirable crystalline silica (RCS), bacteria, fungi, endotoxins (END), peptidoglycans (PGN), (1 → 3)-β-D-glucans (GLU)) with in vitro cytotoxicity and cytokine responses based on analysis of airborne organic dust samples collected during a single work shift at six different facilities. The A549 and BEAS-2B cell lines were used to assess cytotoxicity and proinflammatory cytokine release. The general linear model (GLM) and taxonomic linear ordering were used to identify key determinants and rank facilities by the hazard level they pose. The highest cytotoxicity of organic dust was observed at the sewage treatment plant, while the lowest was at the poultry farm. The most hazardous agents present in organic dust included RCS, aerobic bacteria, fungi, PGN, and GLU. They significantly affected cytokine release, particularly of IL-6 and IL-8. The use of a synthetic measure showed that inhalable organic dust from the composting plant presented the highest potential to induce adverse effects on human health, while the lowest one was characterized by the biomass-fired power plant samples. The open-ended statistical method can significantly increase awareness of occupational hazards and promote more responsible protection for exposed workers. Full article

Glutamine is a known regulator of vascular smooth muscle cell (VSMC) function, but the molecular pathways underlying this response remain incompletely understood. This study investigated how glutamine metabolism influences VSMC behavior and identified the responsible enzymes and metabolites. Glutamine deprivation markedly reduced VSMC proliferation, migration, and collagen synthesis, while modestly decreasing viability. Pharmacological inhibition of glutaminase-1 (GLS1) or aminotransferases (AT) similarly suppressed these cellular functions, whereas inhibiting glutamate dehydrogenase 1 (GLUD1) had no effect. Metabolite analysis revealed that glutamine deprivation or AT inhibition, but not GLUD1 inhibition, reduced intracellular α-ketoglutarate (αKG) concentrations, establishing AT as the primary enzyme converting glutamine-derived glutamate to αKG. To identify which metabolite drives VSMC responses, glutamine-starved cells were supplemented with various glutamine-derived molecules. The cell-permeable αKG analog dimethyl-αKG significantly restored VSMC proliferation, migration, collagen synthesis, and survival, while ammonia only enhanced viability, demonstrating αKG’s primary role in mediating glutamine-dependent functions. These findings establish that glutamine metabolism via the GLS1-AT-αKG pathway is a critical driver of VSMC activation and survival. Targeting this glutamine-αKG metabolic axis through GLS1 inhibition, AT blockade, or downstream αKG disruption offers a compelling therapeutic strategy for ameliorating fibroproliferative vascular diseases, including atherosclerosis, post-angioplasty restenosis, and pulmonary hypertension. Full article

Mangosteen (Garcinia mangostana L.) has long been used in traditional Southeast Asian medicine to treat inflammatory-related conditions. In this study, three new compounds, including garcimangone A (1), garcimangone B (2), and the S-form of garcimangone C (3), and 18 known compounds were isolated and investigated for their anti-inflammatory properties and effects on M1- and M2-associated markers. Among the isolated components, γ-mangostin (5), garcinone D (6), morusignin J (15), and fuscaxanthone C (16) showed the most potent NO-inhibitory effects in LPS-stimulated RAW264.7 cells. SAR study revealed that chromeno moiety at C-3,4, oxygen substituents at C-1,3,6,7, and isoprenyl groups at C-2,8 are key structural features that promoted anti-inflammatory activity. Cytokine analysis results indicated that morusignin J (15) and fuscaxanthone C (16) could modulate the production of pro-inflammatory cytokines, such as TNF-α and IL-6, while modulating the anti-inflammatory cytokine IL-10. Western blot results demonstrated that morusignin J (15) modulated the inflammatory response through NF-κB and MAPK signaling and increased the expression of M2-associated markers KLF4 and arginase-1 in LPS-induced RAW264.7 macrophages. Further molecular docking analysis confirmed the high binding affinity of morusignin J (15) with key iNOS residues, such as Gln257, Pro344, Glu371, and Hem901, and the in silico prediction supported its potent oral bioavailability and drug-likeness. These in vitro and in silico findings highlight that pericarps of G. mangostana possess potential as promising natural sources for functional extracts and bioactive constituents for the development of antioxidative and anti-inflammatory candidates, and warrant further in vivo investigation in the future. Full article

Dextrin-based nanosponges (D-NS) are promising candidates for oral drug delivery due to their biocompatibility, mucoadhesive properties, and tunable swelling behavior. In this study, pH-sensitive nanosponges were synthesized using β-cyclodextrin (β-CD), GluciDex^®2 (GLU2), and KLEPTOSE^® Linecaps (LC) as building blocks, crosslinked with pyromellitic dianhydride (PMDA) and citric acid (CA). The nanosponges were mechanically size-reduced via homogenization and ball milling, and characterized by FTIR, TGA, dynamic light scattering (DLS), and zeta potential measurements. Swelling kinetics, cross-linking density (determined using Flory–Rehner theory), rheological behavior, and mucoadhesion were evaluated under simulated gastric and intestinal conditions. The β-CD:PMDA 1:4 NS was selected for drug studies due to its optimal balance of structural stability, swelling capacity (~863% at pH 6.8), and highest apomorphine (APO) loading (8.23%) with 90.58% encapsulation efficiency. All nanosuspensions showed favorable polydispersity index values (0.11–0.30), homogeneous size distribution, and stable zeta potentials, confirming suspension stability. Storage at 4 °C for six months revealed no changes in physicochemical properties or apomorphine (APO) degradation, indicating protection by the nanosponge matrix. D-NS exhibited tunable swelling, pH-responsive behavior, and mucoadhesive properties, with nanoparticle–mucin interactions quantified by the rheological synergism parameter (∆G′ = 53.45, ∆G″ = −36.26 at pH 6.8). In vitro release studies demonstrated slow, sustained release of APO from D-NS in simulated intestinal fluid compared to free drug diffusion, highlighting the potential of D-NS as pH-responsive, mucoadhesive carriers with controlled drug release and defined nanoparticle–mucin interactions. Full article

Ionotropic receptors (IRs) are a divergent subfamily of ionotropic glutamate receptors (iGluRs) that detect olfactory and environmental cues, influencing behaviors such as foraging and adaptation. To explore the evolution of IRs in relation to feeding ecology, we identified IRs and iGluRs from the genomes of four gastropods with distinct diets: Pomacea canaliculata (9 IRs/18 iGluRs), Bellamya purificata (10/22), Cipangopaludina chinensis (11/23), and Babylonia areolata (22/41). IRs were markedly expanded in B. areolata, suggesting lineage-specific diversification. Phylogenetic analysis grouped IRs and iGluRs into three clades, with IRs clustered with GluD, supporting early functional divergence following gene duplication. In all species, IR25b showed tandem duplication and played a central role in protein–protein interaction (PPI) networks. Most IRs were acidic, whereas IR-A and IR-C subgroups were basic, suggesting functional specialization among subfamilies. Structural analysis showed that IRs share conserved domains and motifs across species. Most IRs experienced purifying selection, while P. canaliculata showed relaxed constraints, suggesting weaker functional limitation. Collinearity analysis identified conserved genes, such as BarIR-A.6 and BarIR-D.1, across species. qPCR confirmed tissue-specific expression of IRs in multiple organs. Together, these results reveal the molecular features and evolutionary patterns of IRs in gastropods, highlighting their potential roles in olfaction and dietary adaptation. Full article

Background: The STAT4 gene plays a key role in immune regulation and is associated with susceptibility to autoimmune diseases such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Objectives: The objective of this study is to analyze variants of uncertain significance (VUSs) in STAT4 using bioinformatics tools to predict their functional and structural impact. Methods: A total of 48,295 variants of the STAT4 gene (ENSG00000138378) were retrieved from the Ensembl database. A tiered filtering approach was used to assess VUS pathogenicity, integrating in silico prediction tools such as SIFT, PolyPhen, MutPred2, and Align-GVGD, as well as structural modeling platforms including Chimera, ModRefiner, Missense3D, HOPE, and DynaMut2. Results: Eighty missense VUSs were identified; of these, 13 were prioritized based on concordant signals across multiple computational predictors. These variants showed significant alterations in the physicochemical properties of the protein, including changes in hydrophobicity and disruption of hydrogen bonding. Notably, the rs140675301 (Glu128Val) variant lies within a conserved loop, and in silico analyses suggest that this mutation may alter kinase specificity regarding the phosphorylation of serine 130. Conclusions: The integrative use of the bioinformatic tools employed represents a valuable preliminary step prior to undertaking more complex and resource-intensive functional studies. This complementary strategy strengthens the interpretative framework for VUS, guiding subsequent experimental validation and supporting a structured assessment of variant relevance, particularly in the context of immune-related genes such as STAT4. Full article

Fusarium oxysporum-induced soft rot severely threatens postharvest pitaya quality and storage life, and while vanillin shows promise in the disease management, its mechanisms for controlling pitaya decay remain incompletely understood. In this study, we systematically investigated the molecular mechanism by which vanillin inhibits soft rot in postharvest pitaya, employing physiological and biochemical characterization, bioinformatics analysis, and molecular biology techniques. Compared with control fruit on 10 d, vanillin treatment significantly reduced disease index and lesion area by 27.12% and 67.43%, respectively. Meanwhile, vanillin treatment delayed the degradation of total soluble solids (TSSs) and titratable acidity (TA) and promoted the accumulation of total phenolics and flavonoids. Additionally, vanillin enhanced the activities of defense-related enzymes, such as catalase (CAT), superoxide dismutase (SOD), phenylalanine ammonia-lyase (PAL), β-1,3-glucanase (GLU), chitinase (CHI), peroxidase (POD) and polyphenol oxidase (PPO), and increased antioxidant capacity, as evidenced by increased DPPH radical scavenging capacity and ascorbic acid content. This resulted in reduced oxidative damage, as indicated by decreased levels of malondialdehyde (MDA), H₂O₂ and O₂^•−. Yeast one-hybrid (Y1H), dual-luciferase reporter (DLR) and subcellular localization revealed that HuTGA1, a nuclear-localized transcriptional activator, specifically bound to the as-1 cis-acting element and activated expression of HuNPR1 and HuNPR5-1. Transient overexpression of HuTGA1 reduced reactive oxygen species (ROS) accumulation and upregulated related genes. These findings suggest that vanillin treatment might enhance pitaya resistance by activating the HuTGA1-HuNPR signaling module, providing insights into the molecular mechanisms underlying vanillin-induced resistance. Full article

Currently, there is no report on prediction models of standardized ileal amino acid digestibilities (SIAADs) in soybean meals (SBMs) for medium-growing yellow-feathered chickens. This study firstly analyzed the chemical compositions of 10 SBMs, then determined their SIAADs in chickens, and finally established and verified prediction models for SBM SIAADs based on their chemical compositions and amino acid (AA) profiles. A total of 276 55 d-old Tianluma roosters were selected and randomly divided by body weight into 11 treatment groups. On d 63, chickens were fed either a nitrogen-free diet (NFD) or one of 10 SBM diets for 5 d. On d 67, ileal chyme samples were collected to determine SIAADs. Data from nine SBM samples and stepwise regressions were employed to build prediction models, while one SBM sample was randomly selected to validate model accuracy. Different SBM sources affected (p ≤ 0.007) SIAADs in medium-growing yellow-feathered chickens. The standardized ileal digestibility (SID) of glutamic acid (Glu) was the highest (93.9%), whereas that of cysteine (Cys) was the lowest (81.7%). Fifteen prediction models (R² = 0.567–0.993, p < 0.03) for the SIDs of methionine (Met), isoleucine (Ile), leucine (Leu), phenylalanine (Phe), lysine (Lys), histidine (His), arginine (Arg), aspartic acid (Asp), serine (Ser), Glu, glycine (Gly), alanine (Ala), Cys, tyrosine (Tyr), and proline (Pro) in SBMs for medium-growing yellow-feathered chickens were effectively established based on chemical compositions and AA profiles. Among them, the prediction model for the SID of Cys showed the best fit (R² = 0.993, p = 0.002), while the model for the SID of Ala had the lowest fit (R² = 0.567, p = 0.019). Except for His and Pro, which exhibited poor predictive accuracy, all other models showed good accuracy. These prediction models thus provide a valuable reference for rapidly estimating the SIDs of key AAs in SBMs for medium-growing yellow-feathered chickens. Full article

Astrocytes are increasingly recognized as active participants of synaptic communication, yet their role in the basal ganglia circuitry remains poorly defined. Emerging evidence indicates that astrocytes in this region express a diverse array of neurotransmitter receptors thought to regulate intracellular calcium signaling, gliotransmitter release, synaptic plasticity, and neuroimmune responses. However, the literature is limited by methodological variability and a pronounced focus on the striatum, with comparatively little data on other basal ganglia nuclei. This review aims to organize the current literature on astrocytic receptor systems within the basal ganglia, including dopaminergic (D1–D5), glutamatergic (AMPA, NMDA, mGluRs), GABAergic (GABA-A, GABA-B), purinergic (P1, P2), and adrenergic (α, β) receptors. By organizing receptor-specific findings across basal ganglia structures, this review provides a foundation for future investigations into astrocytic function in this complex neural network. Full article

Glutamate delta 1 receptor (GluD1) has various functional roles in the brain, such as high-frequency hearing, synapse formation and maintenance, and regulation of cognition disorders and neurodevelopmental disease. However, the underlying molecular mechanism, especially at the genetic level, remains to be elucidated. In this study, we use transcriptomics analysis to define the genetic impact of GluD1 across the brain regions in GluD1 knockout mice. Our results show that GluD1 deletion induced pronounced differences in gene expression both across the four brain regions (cortex, cerebellum, hippocampus, and striatum) and the distinct hippocampal subregions. Despite differences in transcriptional profiles, the differentially expressed genes (DEGs) across all four brain regions show significant enrichment in synaptic signaling pathways, highlighting the critical role of GluD1 in synaptic function. The GluD1 interaction network and its downstream target genes are closely linked to the pathogenesis of intellectual disability (ID) and autism spectrum disorders (ASDs). In conclusion, our work reveals that GluD1 deletion leads to brain-region-specific transcriptional changes and establishes a genetic link between the interaction network with GluD1 and the risk genes for ID and ASD. Full article