Search Results (1,770)

The market value of fragrant rice is largely defined by the presence and intensity of its aroma, which is primarily attributed to volatile compound 2-acetyl-1-pyrroline (2-AP). The biosynthesis of 2-AP is chiefly governed by recessive alleles of the badh2 gene. Nevertheless, 2-AP accumulation is also profoundly shaped by environmental factors and agronomic management. Field practices—such as balanced nitrogen and potassium fertilization, supplementation with trace elements, and application of plant growth regulators like methyl jasmonate—promote 2-AP synthesis by increasing precursor availability and enhancing the activity of key enzymes. Additionally, tillage systems, alternate wetting and drying irrigation, optimal planting density, and harvest timing significantly affect aroma quality. Abiotic stresses, including moderate drought, salinity, optimal temperatures around 25 °C, and low light during grain filling, can also stimulate 2-AP accumulation, often through shifts in proline metabolism and activation of stress-responsive pathways involving GABA and methylglyoxal. Despite the promise of these strategies, several challenges persist, such as the common trade-off between yield and aroma intensity, complex genotype-by-environment interactions, and incomplete elucidation of the molecular mechanisms involved. Moving forward, integrating multi-omics analyses with smart agriculture technologies will be essential to unravel the regulatory networks underlying aroma formation and to advance the breeding of high-yielding fragrant rice varieties with stable aroma traits under changing climate scenarios. Full article

Background: Neurodevelopmental disorders span a wide spectrum of deficits, often with a known or suspected genetic basis. While some genetic determinants may indicate treatment with selective compounds, more often both the molecular cause of the disorder and the mechanism of action for the therapeutic compound are more ambiguously matched. Due to the polypharmacological nature of most neuroactive compounds, measuring gene expression changes following drug perturbation could be an effective strategy to gain insight into shared therapeutic action downstream of diversity in receptor interaction. High-throughput drug discovery platforms have effectively measured changes in gene expression following drug perturbation in cell cultures, but unfortunately, these platforms often lack specificity for neuroactive compounds, fail to capture the developmental influence of cell–cell interactions, and do not accurately model drug metabolism in an intact system. Methods: In this study, we present a high-throughput, low-cost and cell-type-specific approach for capturing transcriptional changes in neural cell populations following neuroactive compound exposure through the combined use of transgenic zebrafish, cell sorting, and bulk RNA-seq. Results: Our system captures unique transcriptional profiles between neuronal and non-neuronal cell populations and demonstrates specific drug responsiveness within our neuronal cell population. We assessed two known positive allosteric modulators (PAMs) of γ-Aminobutyric acid sub-type A receptors (GABA_AR), ivermectin and propofol, as a case study to explore shared pathway and gene expression changes following drug exposure; these chemically distinct agents share a mechanistic signature that dampens the neuronal hyperexcitability characteristic of a broad spectrum of neurodevelopmental disorders. Two shared downregulated genes reflect a core expression module for modulating GABAergic tone: SRC proto-oncogene, non-receptor tyrosine kinase (SRC), and Glutamate decarboxylase 2 (GAD2). Conclusions: We provide this methodology and analysis as a framework for exploring shared changes in gene expression following neuroactive compound exposure in vivo, leading to a more complete and nuanced understanding of therapeutic effects on neurons that can aid in drug repurposing efforts for neurodevelopmental disorders. Full article

The common bean (Phaseolus vulgaris L.) cultivar Jalo Vermelho carries the Co-12 gene, which confers resistance to both Andean and Mesoamerican races of Colletotrichum lindemuthianum. Despite its importance for breeding programs, the genomic location and candidate genes underlying this resistance remain poorly defined. The Co-12 locus was fine-mapped using a biparental population derived from the cross Jalo Vermelho × Crioulo 159. A total of 172 F₂ plants were used to generate 172 F_2:3 families, which were phenotyped after inoculation with race 1545 of C. lindemuthianum. Segregation analysis confirmed a 1:2:1 Mendelian ratio, consistent with a single dominant resistance gene. Genotyping of resistant and susceptible plants using the BARBean6K_3 Illumina BeadChip (5398 SNP markers) mapped Co-12 to chromosome Pv04, between 1695 bp (ss715649768) and 9,651,954 bp (ss715646644). Subsequent fine mapping with simple sequence repeat (SSR) markers delimited the locus to a 41 kb genomic interval flanked by BARCPVSSR04557 and BARCPVSSR04570. Within this region, three candidate genes were identified, including one encoding a gamma-glutamyl-GABA enzyme and two encoding lipid transfer proteins (LTP2). Lipid transfer proteins are widely recognized components of plant defense; however, their association with anthracnose resistance in the common bean has not been previously reported. The identification of LTP2 genes within the Co-12 interval suggests a previously unrecognized resistance mechanism and expands the current understanding of host defense pathways in Phaseolus vulgaris. The markers identified here provide valuable tools for marker-assisted selection and will facilitate efficient introgression of Co-12 into common bean cultivars. Full article

Epilepsy is a neurological disorder characterized by a long-lasting predisposition to recurrently generate unprovoked seizures. Epilepsy affects over 70 million people worldwide, with approximately one-third suffering from pharmacoresistant seizures. Currently, the clinical antiseizure drugs lack efficacy in preventing epileptogenesis. Adenosine, as an endogenous anticonvulsant, inhibits the development of epilepsy via interaction with the molecular epileptogenic network on several levels: (i) Activation of A1 receptor inhibits glutamate release via presynaptic inhibition, and hyperpolarizes the synaptic potentials in postsynaptic neurons. (ii) The A2A receptor on astrocytes interacts with astroglial glutamate transporter GLT-1, controlling glial glutamate homeostasis. (iii) Activation of the A3 receptor inhibits GABA transporter type 1-mediated GABA uptake. (iv) Adenosine kinase (ADK) is highlighted as a pathological hallmark of epilepsy, with its distinct isoforms driving different mechanisms. The cytoplasmic short isoform (ADK-S) in astrocytes controls extracellular adenosine and receptor-mediated pathways, whereas the nuclear long isoform (ADK-L) in astrocytes and specific neurons regulates epigenetic mechanisms without relying on adenosine receptors. Collectively, this review clarifies the adenosine system’s critical regulatory role in the epileptogenic network, highlights adenosine receptors and ADK isoforms as promising therapeutic targets for epilepsy, and provides a theoretical basis for developing novel disease-modifying therapies for pharmacoresistant epilepsy while laying a foundation for subsequent preclinical and clinical translation. Full article

Background: Chronic insomnia disorder (CID) frequently coexists with diarrhea-predominant irritable bowel syndrome (IBS-D), a comorbidity characterized by gut–brain axis dysfunction and persistent inflammatory activation. However, the molecular mechanisms underlying this overlap remain incompletely understood, and effective multitarget interventions are lacking. Objectives: This study aimed to identify quercetin as a potential bioactive compound for IBS-D-associated insomnia and to investigate whether its protective effects are associated with modulation of the PI3K/AKT/NF-κB signaling pathway. Methods: CID- and IBS-D-related targets were collected from public databases. Candidate compounds were screened using bioinformatics and network pharmacology analyses, followed by molecular docking. Experimental validation was conducted in 36 male C57BL/6J mice assigned to control, CID+IBS-D model, quercetin-treated, and quercetin-plus-Recilisib-treated groups. Sleep-related behavior, EEG/EMG-derived sleep architecture, intestinal function, inflammatory markers, and pathway-related proteins were assessed. Results: Quercetin was identified as a core candidate compound. Network pharmacology revealed 43 shared targets among CID, IBS-D, and quercetin, with significant enrichment in PI3K/AKT-related signaling. In vivo, quercetin improved sleep-associated phenotypes and intestinal dysfunction; reduced visceral hypersensitivity; restored ZO-1 and Occludin expression; suppressed hypothalamic and colonic inflammatory responses; and was accompanied by reduced phosphorylation of PI3K, AKT, IκB, and NF-κB p65 in the hypothalamus. Quercetin also increased hypothalamic 5-HT1A and GABA_A Rα5 expression. These effects were partially reversed by Recilisib, supporting the involvement of PI3K/AKT-associated signaling in quercetin-mediated protection. Conclusions: Quercetin alleviated key sleep-related and IBS-D-like phenotypes in a composite murine model of gut–sleep comorbidity. The protective effects were associated with reduced inflammatory activation and modulation of PI3K/AKT/NF-κB-related signaling. These findings support quercetin as a promising candidate for gut–brain axis-related comorbid disorders, while further studies are needed to define pathway specificity, tissue exposure, and translational applicability. Full article

The 2x2 Demonstrator, a prototype for the Deep Underground Neutrino Experiment (DUNE) liquid argon (LAr) Near Detector, was exposed to the Neutrinos from the Main Injector (NuMI) neutrino beam at Fermi National Accelerator Laboratory (Fermilab). This detector is a prototype of a new modular design for a liquid argon time-projection chamber (LArTPC), comprising a two-by-two array of four modules, each further segmented into two optically isolated LArTPCs. The 2x2 Demonstrator features a number of pioneering technologies, including a low-profile resistive field shell to establish drift fields, native 3D ionization pixelated imaging, and a high-coverage dielectric light readout system. The 2.4-tonne active mass detector is flanked upstream and downstream by supplemental solid-scintillator tracking planes, repurposed from the MINERvA experiment, which track ionizing particles exiting the argon volume. The antineutrino beam data collected by the detector over a 4.5 day period in 2024 include over 30,000 neutrino interactions in the LAr active volume—the first neutrino interactions reported by a DUNE detector prototype. During its physics-quality run, the 2x2 Demonstrator operated at a nominal drift field of 500 V/cm and maintained good LAr purity, with a stable electron lifetime of approximately 1.25 ms. This paper describes the detector and supporting systems, summarizes the installation and commissioning, and presents the initial validation of collected NuMI beam and off-beam self-triggers. In addition, it highlights observed interactions in the detector volume, including candidate muon antineutrino events. Full article

Metamorphosis is a critical bottleneck in the bivalve life cycle, usually associated with high mortality and asynchronous development under hatchery conditions. Synthetic chemical inducers are widely used to overcome these constraints. The neuroactive compounds epinephrine (EPI) and γ-aminobutyric acid (GABA) have been reported to be effective metamorphosis inducers in bivalve species. This study evaluated the inductive efficiency and toxicity of EPI and GABA in two economically important clam species, Venerupis corrugata and Ruditapes decussatus. Competent larvae were exposed to different concentrations (10⁻², 10⁻⁴ and 10⁻⁶ M) for 24, 48 and 72 h. Metamorphic progression and mortality were assessed immediately after exposure and following a six-day post-exposure period. Both compounds induced metamorphosis following concentration–time and species-dependent responses, with narrow efficiency windows and pronounced delayed mortality at higher concentrations and/or longer exposure durations. In V. corrugata, the highest metamorphosis rates were obtained with both compounds at 10⁻⁶ M after 48 h. In contrast, R. decussatus required higher EPI concentrations (10⁻⁴ M for 48 h) for optimal induction, while GABA at 10⁻⁶ M was effective after 24 and 48 h. These findings highlight the need for post-exposure assessments and species-specific optimisation of chemical induction protocols to improve metamorphosis success and spat production in bivalve hatcheries. Full article

The objective of this study was to evaluate the preharvest application of γ-aminobutyric acid (GABA), melatonin (MT), and oxalic acid (OA), at different concentrations and application frequencies, on the physicochemical and microbiological quality of dried figs (cv. Calabacita) at commercial harvest and after 3 and 6 months of refrigerated storage. A further aim was to determine their impact on fungal populations and mycotoxin production. The results showed that untreated dried figs had a higher frequency of Aspergillus welwitschiae, A. tubingensis, and Aspergillus section Flavi, whereas elicitor-treated figs exhibited a lower incidence of toxigenic fungi. A. welwitschiae was the main ochratoxin A (OTA)-associated species detected, although the proportion of OTA-positive figs was lower in elicitor-treated samples than in the control. Aflatoxins (AFs) were detected only sporadically in 2 mM OA treatments, consistent with the limited activity of A. flavus at low storage temperatures. Conversely, Penicillium spp. were widespread but were associated with citrinin (CIT) production only under 2 mM OA treatments. Among the Alternaria toxins, alternariol (AOH) was detected solely in dried figs treated with 1 mM OA. Notably, all investigated mycotoxins were below the limit of detection (<LOD) in dried figs treated with 0.5 mM MT. Moderate elicitor concentrations (e.g., 0.5 mM MT and 50 mM GABA) and multiple preharvest applications generally provided the best balance between fungal suppression and fruit quality, significantly reducing Aspergillus spp. occurrence without promoting the growth of undesirable species. Overall, elicitor treatments decreased the incidence of toxigenic fungi, most likely through direct antifungal effects in senescent dried fruit rather than by inducing host defences. The combined use of preharvest elicitors with appropriate drying and storage conditions is a promising strategy to control fungal contamination and mycotoxin accumulation in dried figs while maintaining quality from preharvest storage. Further research is needed to optimise elicitor concentrations and application timing. Full article

Obesity has become a major disease in dogs and cats. Dietary management is a preventive measure because controlling energy intake (e.g., portion size and diet energy density) helps maintain an ideal BCS and reduces the likelihood of progressive weight gain and associated metabolic abnormalities. This study evaluated a low-fat diet, with or without plant-extract supplementation, and its effects on serum biochemistry, lipid metabolism, gut microbiota, and metabolic profiles in healthy beagles. Thirty beagles were randomly divided into three groups (n = 10 per group): a conventional diet (Group A), a low-fat diet (Group B), and a low-fat diet supplemented with plant extract (Group C). The experiment lasted for a total of 9 weeks, comprising an adaptation period of one week and an experimental period of eight weeks. Results showed that, compared with Group A, the low-fat diet interventions (Groups B and C) significantly reduced serum levels of triglycerides, low-density lipoprotein, and total bile acids (p < 0.05). Furthermore, superoxide dismutase activity was significantly higher in Groups B and C than in Group A (p < 0.05). Compared with both Groups A and B, Group C exhibited significantly lower malondialdehyde levels, reduced proinflammatory cytokines (tumor necrosis factor-α, interleukin-1β, interleukin-6; p < 0.05), and decreased serum diamine oxidase activity and lipopolysaccharide levels (p < 0.05). The gut microbiota analysis revealed that Group C had a significantly increased relative abundance of beneficial bacteria, such as Lactobacillus (p < 0.05). Metabolomic analysis further indicated that beneficial metabolites, including γ-aminobutyric acid and glutamine, were significantly upregulated in Group C (p < 0.05). In conclusion, while a low-fat diet effectively regulated serum lipids in healthy dogs, the supplementation of a blended extract from Atractylodes lancea, Magnolia officinalis, and Citrus reticulata Blanco demonstrated broader efficacy. It further improved lipid metabolism, systemic antioxidant status, and intestinal barrier function, while attenuating inflammation and enriching beneficial gut microbes (Lactobacillus) and metabolites (GABA and glutamine). These findings suggest that while a low-fat diet alone is beneficial, its combination with plant extract provides a novel dietary strategy for promoting lipid metabolism and potentially reducing obesity-related disease risk in dogs. Full article

Mesial temporal lobe epilepsy (TLE) is the most common and severe form of focal epilepsy. This review examines the diverse mechanisms by which the GABAergic system contributes both to seizure generation and to protective processes that limit epileptogenesis and seizure progression in TLE. We focus on findings from established animal models of TLE as well as studies of surgically resected tissue from patients who had undergone therapeutic intervention. Experimental models include sustained electrical stimulation of the perforant path, as well as the kainic acid (KA) and Li-pilocarpine models. Although these paradigms induce status epilepticus (SE) through distinct mechanisms, they ultimately converge on prolonged excitation of hippocampal CA3 pyramidal neurons and interconnected regions of the hippocampus and broader limbic network. In response to epileptic seizures, GABA synthesis is enhanced, as evidenced by the marked upregulation of the GABA-synthesizing enzymes GAD65 and GAD67, along with their ectopic expression in glutamatergic mossy fibers of the hippocampus. Shortly after acute seizures, a transient expression of the embryonic GAD67 splice variant, GAD25, is observed, although its functional significance remains unclear. At the receptor level, animal models of TLE show upregulation of GABA_A receptor subunits α2, α4, β3, and γ2, accompanied by downregulation of α5 and δ subunits, suggesting reduced tonic inhibition. In contrast, hippocampal tissue from patients with TLE exhibits pronounced upregulation of α5 and δ subunits, indicative of enhanced extrasynaptic tonic inhibition. Similarly, whereas GABA_A receptor subunits are mildly downregulated in animal models, they are consistently upregulated across hippocampal subfields in human TLE, pointing toward strengthened GABAergic inhibition. Conversely, genetic variants of GABA_A receptor subunits and autoantibodies targeting these receptors can contribute to the etiology of epilepsy, often with onset in childhood. Moreover, degeneration or functional silencing of specific GABAergic interneuron populations—such as parvalbumin-positive neurons in the subiculum—can induce epilepsy in rodent models and is likewise associated with TLE in humans. Full article

Validated instruments assessing gender stereotype endorsement among adolescents are scarce and often overlook contemporary domains like digital privacy. To address this gap, this study developed and validated the Gender Stereotypes and Roles Adherence Battery for Adolescents (GAB-A) in a sample of 2955 Italian adolescents attending public secondary schools in Rome (56.4% male; mean age 14.3 years). The battery comprises three modules: the Gender Stereotyped Attitude Scale (GSAS), Gender Role Activities Scale (GRAS), and Gendered Traits Inventory (GTI). Psychometric analysis confirmed robust factor structures, notably identifying a distinct “Relational Control” factor within the GSAS that assesses beliefs normalizing partner surveillance. The results revealed a stark pattern of gender differentiation: males endorsed prescriptive attitudes (GSAS, d = 1.07) and roles (GRAS, d = 0.88) substantially more than females, particularly regarding violence myths. Conversely, essentialist trait beliefs (GTI) showed negligible gender differences (d = 0.11). Associations between stereotypes and psychological health were gender-moderated; within-group analyses indicated that endorsement predicted higher distress, hostility, and alexithymia in males, while being unrelated to well-being in females. Finally, gender-stratified normative data and operational cut-offs were established. The GAB-A provides a psychometrically sound tool for identifying elevated endorsement profiles and evaluating violence prevention interventions. Full article

Depression-related mood disturbances are increasingly recognized as nutrition-sensitive conditions associated with chronic stress-induced neuroinflammation and metabolic imbalance. Polygonatum sibiricum, Poria cocos, Lilium brownii, and Radix Glycyrrhizae Preparata are edible medicinal plants commonly used in functional foods. In this study, we evaluated the antidepressant effects of a Polygonatum sibiricum-based functional formula (PSF) in a chronic restraint stress (CRS) mouse model. CRS induced prominent anhedonia and behavioral despair, accompanied by microglial overactivation, activation of the NLRP3 inflammasome, and dysregulated tryptophan metabolism. PSF supplementation significantly alleviated depressive-like behaviors and inhibited NLRP3–caspase-1–GSDMD-mediated pyroptosis, leading to reduced hippocampal IL-1β and IL-18 levels. Importantly, PSF restored tryptophan metabolism toward serotonin production, stabilized monoaminergic and glutamate/GABA neurotransmission, and protected hippocampal neurons. Moreover, PSF partially reversed stress-induced gut microbiota dysbiosis. Collectively, these results demonstrate that PSF acts as a neuroimmune–metabolic modulator that improves mood-related behaviors by regulating inflammatory signaling, tryptophan metabolism, and neurotransmitter homeostasis, supporting its potential development as a functional food intervention for stress-induced depression. Full article

Gamma-aminobutyric acid (GABA) has been implicated in gut–brain interactions and neuronal activation. We hypothesized that GABA could ameliorate memory decline. We investigated whether oral GABA administration ameliorated age-related cognitive decline in aged mice (C57BL/6J, male) and explored the role of circulating exosomes in mediating these effects. Aged mice that drank water containing 0.5% GABA exhibited significantly improved discrimination index scores compared with that of controls, indicating enhanced memory function. Their plasma-derived exosomes induced neurite outgrowth and mitochondrial activation and restored neuronal activity in SH-SY5Y cells. GABA enhanced the exosomal expression of several miRNAs linked to neuronal activation, longevity, and anti-senescence pathways. Plasma-derived exosomes also restored object recognition memory, reduced hippocampal neuroinflammation, and decreased senescent cell markers (p21 and γH2AX) in aged mice. Additionally, mitochondria- and neurite-related genes were upregulated, and pathways associated with oxidative phosphorylation and Alzheimer’s disease were enriched. Collectively, long-term GABA administration was found to improve cognitive function of aged mice through the secretion of functional exosomes. Full article

With the global population predicted to reach 10 billion by 2050, pesticides are essential for agricultural production. However, they can introduce chemical stressors into aquatic ecosystems. Chlorpyrifos (CPF) is a widely used organophosphate insecticide that can enter aquatic environments and poses potential risks to early-life-stage fish. Because the retina is an extension of the central nervous system and vision-guided behaviors are highly sensitive to neural dysfunction, we hypothesized that CPF exposure disrupts neurobehavioral and visual function via oxidative stress and PPARα-related signaling. Zebrafish larvae were exposed to CPF (0.01, 0.1, 1, 10, and 100 μg/L) with a vehicle control (VC). During the photomotor response assay, exposure to 100 μg/L CPF reduced overall swimming activity by 48.90% and dark-period activity by 57.71%, whereas 1 μg/L CPF modestly increased total distance by 6.96% (p = 0.003) and dark-period distance by 5.40% (p = 0.011). Transcriptomic profiling highlighted nervous- and vision-related functional categories, and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment implicated pathways including gonadotropin-releasing hormone (GnRH), mitogen-activated protein kinase (MAPK), and peroxisome proliferator-activated receptor (PPAR) signaling. Targeted neurotransmitter metabolomics showed significant increases in dopamine, γ-aminobutyric acid (GABA), and acetylcholine across treatment groups, indicating broad neurotransmitter dysregulation. Consistent with these findings, neuronal fluorescence in Tg (elavl3: EGFP) larvae decreased by 12.1% and 32.5% in the 1 and 100 μg/L groups, respectively (p < 0.001), and glial fibrillary acidic protein (GFAP) immunofluorescence increased in the eye/brain/olfactory bulb at 1 μg/L (p = 0.037) and 100 μg/L (p = 0.002). Histology further showed retinal injury, with a 14.3% reduction in photoreceptor layer thickness at 100 μg/L (p = 0.034). Mechanistically, coexposure to a PPARα antagonist (GW6471) alleviated CPF-induced behavioral deficits (1.80-fold increase in dark locomotion) and reduced elevated GABA and dopamine levels by 36.8% and 47.3%, respectively. Together, these results indicate that CPF can impair neuro-visual development and that oxidative stress and PPARα-related signaling are closely associated with these effects. Full article

This study developed an optimized processing strategy for γ-aminobutyric acid (GABA) instant white tea (GABA-IT) using GABA-enriched white tea as raw material, systematically characterizing its chemical composition and volatile profile. In contrast to the conventional instant tea production process, this work integrates response surface methodology with spray-drying parameter optimization. This integrated approach enables the simultaneous enhancement of functional components and sensory quality. A response surface design was employed to refine the extraction and spray-drying variables following preliminary single-factor trials, and the optimal parameter combination was subsequently determined (40% ethanol concentration, material-to-liquid ratio of 1:15, extraction time of 3 days, atomization speed of 300 rpm, and inlet temperature of 120 °C); the resulting GABA-IT exhibited significantly improved quality characteristics. Specifically, the GABA content increased by 209% (reaching 4.42 mg/g), and theanine, catechins, and caffeine were enriched by 200–300%. Regarding volatile profiles, processing led to a reduction in esters but an increase in aldehydes and hydrocarbons. Relative odor activity value (rOAV) analysis revealed that epoxy-β-ionone and linalool were the key contributors to the characteristic aroma of GABA-IT. Collectively, this study demonstrates the technical feasibility of producing GABA-rich instant tea with enhanced functional components and improved sensory quality, providing practical guidance for the large-scale industrial production of functional tea beverages. Full article