Search Results (201)

Panax notoginseng, a high-value medicinal crop, suffers substantial yield losses due to Fusarium oxysporum-mediated root rot, for which no molecularly defined control targets are currently available. Histone acetyltransferases (HATs) serve as crucial epigenetic regulators of fungal development and stress responses; however, their functional roles in F. oxysporum remain largely unexplored. In this study, we systematically identified six FoHAT genes via genome-wide analysis and classified them into evolutionarily conserved subfamilies through phylogenetic comparison with orthologs from Saccharomyces cerevisiae, Homo sapiens, and Arabidopsis thaliana. Structural analyses revealed distinct motif compositions and domain architectures among FoHAT members, while promoter cis-element profiling suggested potential subfunctionalization via stress-responsive regulatory mechanisms. Functional investigations demonstrated that major notoginsenosides present in P. notoginseng root exudates—R₁, Rg₁, Rg₂, Re, and Rd—dynamically influenced both spore germination and FoHAT expression profiles. Intriguingly, each notoginsenoside exerted concentration-dependent non-linear effects on spore germination, either inhibiting or promoting the process. Concurrently, notoginsenoside exposure triggered compensatory transcriptional responses, most notably a rebound in Fo-Hat1_N expression from 9% to 112% under Rd treatment. This work establishes an initial epigenetic framework for combating Fusarium root rot in medicinal plants and offers a foundation for developing HAT-targeted small-molecule inhibitors. Full article

Background: Mucopolysaccharidosis type IIIC (MPS IIIC) is a rare lysosomal storage disorder caused by pathogenic variants in the HGSNAT gene. Data from large patient cohorts remain scarce, particularly in Latin America. Methods: We retrospectively analyzed clinical, biochemical, and genetic data from patients diagnosed with MPS IIIC through the MPS Brazil Network. Diagnosis was based on reduced activity of acetyl-CoA:α-glucosaminide N-acetyltransferase (HGSNAT), elevated urinary glycosaminoglycans (uGAGs), and/or molecular genetics tests. Results: A total of 101 patients were confirmed with MPS IIIC, representing one of the largest cohorts worldwide. Females accounted for 60% of cases. The mean age at symptom onset was 5.4 ± 3.9 years, while the mean age at diagnosis was 11.7 ± 6.9 years, reflecting a 6-year diagnostic delay. Most patients initially presented with developmental delay (82%) and facial dysmorphism (80%), whereas behavioral manifestations were less frequently identified (25%), suggesting a milder phenotype than previously reported. Genetic information was available for 28% of patients, showing recurrent alleles (c.372-2A>G, c.252dupT) and several novel mutations, which expand the mutational spectrum of the disease. Genotype–phenotype similarities with Portuguese, Italian, and Chinese cases suggest shared ancestry contributions. Regional differences included earlier diagnoses in the North of Brazil and high consanguinity rates in the Northeast region. Conclusions: This study describes the largest Brazilian cohort of MPS IIIC, documenting novel variants and regional heterogeneity. Findings highlight diagnostic delays, ancestry influences, and the urgent need for disease-modifying therapies. Full article

Melatonin is a conserved indolamine implicated in circadian and developmental timing, but its role in social-insect task allocation is unclear. Here, we show that melatonergic signaling modulates the nurse → forager transition in the honey bee (Apis mellifera). A single hemocoelic dose of melatonin (100 ng) markedly reduced hive retention and advanced the age at first waggle dance by ≈9 days (median 11.8 vs. 20.9 days; common-language effect size = 0.94). Complementary manipulations—pharmacological antagonism with luzindole and RNA interference (RNAi)-mediated knockdown of a candidate melatonin receptor (AmMTR/AmMT2; transcript reduction ≈65–79% at 24–72 h)—produced reciprocal suppression of foraging, indicating pathway dependence. Transcriptional profiling revealed a forager-age peak in the arylalkylamine N-acetyltransferase ortholog AmNAT2 (≈10-fold increase near day 23), while AmNAT1 remained unchanged; melatonin treatment was associated with a trend toward increased Amα-glucosidase expression. Computational analyses classify AmMTR as a class-A GPCR and identify plausible melatonin-compatible pockets; promoter scans reveal high-confidence circadian motif matches upstream of AmMTR. These in silico results are presented as hypothesis-generating. Together, the behavioral, molecular, pharmacological and computational lines of evidence support melatonin as a circadian-informed modulatory signal that helps align neuroendocrine and metabolic states with the timing of extranidal behavior. Confirmation via receptor functional assays and broader colony replication will be important. Full article

The whitefly Bemisia tabaci is a globally invasive pest that threatens crop production through feeding and virus transmission. In this study, we identified genes encoding enzymes in the chitin metabolism pathway of B. tabaci—β-N-acetylglucosaminidase (BtNAG), N-acetylglucosamine kinase (BtNAGK), phosphoacetylglucosamine mutase (BtPAGM), UDP-N-acetylglucosamine pyrophosphorylase (BtUAP), and glucosamine-6-phosphate N-acetyltransferase (BtGNA)—using bioinformatic analysis. Quantitative reverse-transcription PCR (RT-qPCR) analyses revealed distinct stage-specific expression patterns for these genes. We used the nanomaterial star polycation (SPc) to deliver gene-specific double-stranded RNA (dsRNA) targeting these genes to fourth instar B. tabaci nymphs, which resulted in significant mortality and developmental defects upon gene silencing. Notably, the fusion dsRNA targeting three genes—BtNAG1, BtNAGK, and BtUAP—achieved approximately 80% nymph mortality, 70% inhibition of adult emergence, and an earlier onset of gene silencing. These findings provide evidence that nanomaterial-assisted delivery of dsRNA can significantly enhance RNAi effects in hemipteran pests and that dsRNA targeting chitin metabolic genes may be an effective strategy for RNAi-based control of B. tabaci. Full article

Porcine circovirus type 2 (PCV2) represents a principal infectious agent causing considerable economic detriment to swine production. N-acetyltransferase 10 (NAT10), which catalyzes N⁴-acetylcytidine (ac⁴C) deposition, has been implicated in regulating immune responses, RNA stability, and viral replication. However, its role in PCV2 infection remains unclear. In this study, we established a PCV2-infected PK15 cell model and observed a marked downregulation of NAT10 expression following infection. Functional assays demonstrated that NAT10 knockdown significantly suppressed PCV2 replication in PK15 cells. Comparative transcriptomic analysis revealed that NAT10 silencing altered the expression of 81 genes, predominantly involved in immune-related signaling pathways. Notably, integrative omics analysis identified NR1H4 as a potential downstream target of NAT10. Collectively, these findings elucidate the regulatory mechanism of NAT10 in PCV2 replication and provide new insights for identifying NAT10 as a potential biomarker and therapeutic target for PCV2 infection in pigs. Full article

Background/Objectives: Plasma glutamine levels in skeletal muscle change in response to exercise intensity and duration, both in physiological and pathological states. Glutamine contributes to muscle differentiation and regeneration; however, the mechanisms underlying this process remain unclear. This study investigated the role of glutamine glutaminolysis in myogenic differentiation, with a focus on epigenetic regulation of myogenin gene expression. Methods: C2C12 myoblasts were differentiated into myotubes using media containing various concentrations of glutamine, glutamate, or dimethyl 2-oxoglutarate (DM-α-KG), a cell-permeable analog of α-ketoglutarate. Results: Glutamine, glutamate, and DM-α-KG promoted C2C12 myoblast differentiation in a concentration-dependent manner, whereas the glutaminase inhibitor CB-839 suppressed differentiation. 4 mM glutamine increased myogenin mRNA expression by about 5-fold. CB-839 also inhibited glutamine-induced expression of myogenin but did not influence the effects of glutamate or DM-α-KG. Furthermore, glutamine increased histone H3 lysine 27 acetylation (H3K27ac) by about two-fold, whereas CB-839 (200 nM) and A-485 (10 µM), a CBP/p300 histone acetyltransferase inhibitor, reduced H3K27ac levels by about half. These results indicate that glutamine not only serves as a structural amino acid for muscle formation but also enhances myogenin transcription through epigenetic mechanisms. Conclusions: This report demonstrates glutaminolysis-dependent histone H3 acetylation, which induces myogenin transcription in myoblasts. These results, connecting glutamine supplementation during resistance training, may make it an effective strategy to accelerate muscle regeneration. Full article

Milk sources directly influence digestion, absorption, and overall nutrient utilization during early infant nutrition. Goat milk features a nutritional composition and digestive properties that are more similar to human breast milk. This study aimed to investigate the effects of different milk sources on the immunity, amino acid and fatty acid metabolism, and intestinal microbiota in neonatal piglets. Sixteen 7-day-old suckling piglets were randomly allocated into two groups (eight replicates/group, one piglet/replicate) and fed with standard formula milk powder (CON) and goat milk formula powder (GMF). The formal experiment lasted for 14 days. Results showed that compared with the CON group, the GMF group showed a significant increase (p < 0.05) in the final weight, the serum levels of immunoglobulin A (IgA), IgG, IgM and C-reactive protein (CRP4), and intestinal trypsin content. Additionally, the GMF group had higher (p < 0.05) serum essential and non-essential amino acid and fatty acid levels, and had trends toward upregulation (0.05 < p < 0.1) in hepatic mRNA expression of spermine N1-acetyltransferase 1 (SAT1), duodenal peptide transporter 1 (PePT1), and jejunal cationic amino acid transporter 1 (CAT1). Microbiome sequencing revealed that GMF enhanced intestinal microbial richness and diversity and increased concentrations of acetic and propionic acids (p < 0.05). In conclusion, GMF suggests a potential improvement in the growth performance by enhancing immunity, amino acid and fatty acid metabolism and optimizing intestinal microbiota composition in neonatal piglets. These findings further support the favorable nutritional properties and tolerability of GMF in early-life nutrition. Full article

Spermidine/spermine N1-Acetyltransferase 2 (SAT2), belonging to the spermidine/spermine N1-Acetyltransferase family, has been increasingly recognized for its potential effects on tumor occurrence and development. Nonetheless, little is known about its biological function and clinical value for pancreatic cancer (PC). The present work focused on investigating its expression pattern, prognostic value, molecular mechanisms, and immune relevance in PC. SAT2 expression within PC samples and its prognostic significance were analyzed by retrieving the relevant data from the TCGA, CPTAC, and HPA databases. The biological function of SAT2 was investigated through GO and KEGG enrichment analyses. The association of SAT2 with immune cell infiltration in tumors was assessed by CIBERSORT. Additionally, in vitro experiments were performed to examine how SAT2 expression affected the PC cell proliferation, invasion, and migration abilities. An in vivo xenograft tumor model was employed for investigating how SAT2 expression affected the PC cell-derived tumor growth. The expression of SAT2 within the PC tissue exhibited a significant decrease in comparison with a non-carcinoma sample. Such observation was validated within PC cells. In addition, SAT2 expression showed a close relation to both tumor growth (T stage) and prognosis. SAT2 primarily participates in pathways, including the PI3K/Akt and MAPK pathways. Furthermore, we demonstrated a significant association between SAT2 expression and immune cell infiltration into tumors. The in vitro experiments confirmed that elevated SAT2 expression significantly suppressed PC cell viability, invasion, and migration through modulating the PI3K/Akt and MAPK pathways. The in vivo experimental results suggested the role of SAT2 overexpression in inhibiting xenograft tumor growth. Our investigation confirms the role of SAT2 in PC development through involvement in the PI3K/Akt and MAPK pathways. The correlation between SAT2 expression levels, immune infiltration, and checkpoint regulation provides valuable insights for immunotherapy strategies targeting PC. Full article

N-terminal acetylation, catalyzed by N-terminal acetyltransferase (NAT) complexes, is one of the most prevalent protein modifications in eukaryotic cells, yet its role in heart development remains poorly understood. Here, we use Drosophila as an in vivo platform to investigate the functions of NAT complex components in cardiac development and congenital heart disease (CHD). Focusing on the NatA complex, we showed that cardiac-specific knockdown of each of its three subunits (Naa15-16, vnc, and san) led to developmental lethality, structural disorganization, fibrosis, and impaired cardiac function in Drosophila. Remarkably, human NAA16 completely rescued the cardiac defects in Naa15-16 silenced Drosophila, whereas a CHD-associated variant (NAA16-R70C) failed to do so, providing direct functional evidence of its pathogenicity. Together, these findings suggest the NatA complex as a critical regulator of heart development and provide functional validation linking variants in NatA complex genes to CHD. Further studies in mammalian models will be required to provide additional supporting evidence. Full article

Alzheimer’s disease (AD) is a progressive neurological condition with limited effective pharmaceutical treatments, often accompanied by side effects. This has increased interest in plant-based alternatives. This study examined the cognitive effects of a Natural Polyherbal Extract (NPX) on scopolamine-induced memory deficits in mice. Male C57BL/6 mice (10 weeks old, n = 36) were divided into four groups: control (saline), scopolamine (1 mg/kg, i.p.), tacrine (10 mg/kg, oral), and NPX (1000 mg/kg, oral). NPX and tacrine were administered daily by oral gavage for two weeks. Cognitive function was assessed weekly using the Y-maze task. Brain tissues were collected for biochemical analysis, including AChE activity and immunohistochemical detection of neurodegeneration-related markers. Results: Mice treated with NPX demonstrated improved spontaneous alternation behavior compared to the scopolamine group. NPX also significantly reduced acetylcholinesterase activity. Immunohistochemistry revealed decreased expression of amyloid-beta (Aβ) and caspase-3, with enhanced choline acetyltransferase levels. These outcomes were comparable to those observed in the tacrine-treated group. Conclusions: NPX alleviated scopolamine-induced memory impairment through enhancement of cholinergic signaling and mitigation of neurodegenerative markers. The findings suggest that NPX may serve as a promising plant-derived candidate for managing memory-related disorders, including AD. Full article

This study examined twenty-eight N-methylimidazolium ionic liquids (ILs) with various substituents and anions to assess their impact on the activity of Carnitine Acetyltransferase (CAT), an indispensable enzyme in human metabolism. In vitro experiments demonstrated that these compounds inhibited CAT in a concentration-dependent manner, with IC₅₀ values ranging from 0.93 to 30.8 mM. Structural analysis of the ILs revealed the following structure–activity relationships: (i) the length of the hydrocarbon chain at N3 markedly affects CAT activity, with longer chains resulting in stronger inhibition; (ii) the degree of unsaturation and the presence of polar groups are not essential for increased activity; (iii) the effect of the anion aligns with the Hofmeister series. One of the most potent compounds, 1-decyl-3-methylimidazolium bromide [C₁₀C₁im]Br, was identified as a mixed inhibitor of CAT with a K_i of 0.77 mM. These findings raise concerns about the biocompatibility of commonly used imidazolium ILs, as they may interfere with fatty acid oxidation by inhibiting their cellular transport. Full article

Plant melatonin is widely recognized as a pleiotropic regulator. As a growth-regulating hormone, it extensively participates in various growth and developmental processes and has significant functions in stress responses and disease resistance. Plant melatonin is synthesized primarily through the catalytic actions of five enzymes: TDC (tryptophan decarboxylase), T5H (tryptamine-5-hydroxylase), SNAT (serotonin N-acetyltransferase), ASMT (N-acetylserotonin methyltransferase), and COMT (caffeic acid-O-methyltransferase). There are multiple genes for each of these five enzymes in citrus genomes, however, with the exception of COMT5—whose function has recently been elucidated—and SNAT, which has only been preliminarily identified, the remaining genes have not been unequivocally characterized or functionally annotated. Hence, we carried out a genome-wide analysis of melatonin biosynthesis enzyme-related gene families in trifoliate orange (Poncirus trifoliata), one of the most common citrus rootstock varieties. Through bioinformatics approaches, we identified 96 gene family members encoding melatonin biosynthetic enzymes and characterized their protein sequence properties, phylogenetic relationships, gene structures, chromosomal distributions, and promoter cis-acting elements. Furthermore, by analyzing expression patterns in different tissues and under various stresses, we identified multiple stress-responsive melatonin synthase genes. These genes likely participate in melatonin synthesis under adverse conditions, thereby enhancing stress adaptation. Specifically, PtCOMT5, PtASMT11, and PtTDC9 were significantly induced by low temperature; PtSNAT1, PtSNAT14, PtSNAT18, and PtTDC10 were markedly responsive to drought; and PtASMT15, PtSNAT15, PtASMT16, and PtSNAT3 were strongly induced by ABA. Among them, PtASMT23 expression was induced up to 120-fold under low temperature, while PtSNAT18 showed over 100-fold upregulation under dehydration treatment. These findings strongly suggest that PtASMT23 and PtSNAT18 play critical roles in regulating melatonin biosynthesis in response to cold and drought stress, respectively. Collectively, these findings pinpoint novel genetic targets for enhancing stress resilience in citrus breeding programs and lay the foundation for the functional characterization of specific melatonin biosynthesis pathway gene family members in citrus and other horticultural crop species. Full article

A complex microbial community gives the possibility to produce biogenic amines in traditional fermented foods. In this study, the metabolism mechanisms of biogenic amines during fermentation of fermented mandarin fish Chouguiyu were revealed based on the metabolic pathways and correlation analysis. Functional genes based on KEGG orthology related to biogenic amine metabolism were selected from the metagenome and were used to construct the biogenic amine metabolic pathways in Chouguiyu. A total of 91 and 75 genera were related to the synthesis and degradation of biogenic amines, respectively. High concentrations of cadaverine and putrescine were observed, while the other biogenic amines were detected in relatively low concentrations. The metabolic mechanisms of various biogenic amines were illuminated by correlation network maps between biogenic amines and microbial synthesis/degradation enzymes. Lactococcus, Flavobacterium, Tessaracoccus, and Yoonia could only degrade and not produce biogenic amines. Acinetobacter and Enterococcus possessed more abundant enzymes for degradation than synthesis. Amine oxidase (K00276), diamine N-acetyltransferase (K00657), and gamma-glutamylputrescine synthase (K09470) were the main biogenic amine degradation enzymes in the microbial community. Lactococcus garvieae, Flavobacterium gelidilacus, Tessaracoccus antarcticus, Yoonia vestfoldensis, Acinetobacter haemolyticus, and Enterococcus ureasiticus were the main microbial species for biogenic amine degradation and could be isolated as the potential strains for biogenic amine degradation in fermented foods. Full article

Down syndrome (DS), stemming from the triplication of human chromosome 21, results in intellectual disability, with early mid-life onset of Alzheimer’s disease (AD) pathology. Early interventions to reduce cognitive impairments and neuropathology are lacking. One modality, maternal choline supplementation (MCS), has shown beneficial effects on behavior and gene expression in neurodevelopmental and neurodegenerative disorders, including trisomic mice. Loss of basal forebrain cholinergic neurons (BFCNs) and other DS/AD relevant hallmarks were observed in a well-established trisomic model (Ts65Dn, Ts). MCS attenuates these endophenotypes with beneficial behavioral effects in trisomic offspring. We postulate MCS ameliorates dysregulated cellular mechanisms within vulnerable BFCNs, with attenuation driven by novel gene expression. Here, choline acetyltransferase immunohistochemical labeling identified BFCNs in the medial septal/ventral diagonal band nuclei of the basal forebrain in Ts and normal disomic (2N) offspring at ~11 months of age from dams exposed to MCS or normal choline during the perinatal period. BFCNs (~500 per mouse) were microisolated and processed for RNA-sequencing. Bioinformatic assessment elucidated differentially expressed genes (DEGs) and pathway alterations in the context of genotype (Ts, 2N) and maternal diet (MCS, normal choline). MCS attenuated select dysregulated DEGs and relevant pathways in aged BFCNs. Trisomic MCS-responsive improvements included pathways such as cognitive impairment and nicotinamide adenine dinucleotide signaling, among others, indicative of increased behavioral and bioenergetic fitness. Although MCS does not eliminate the DS/AD phenotype, early choline delivery provides long-lasting benefits to aged trisomic BFCNs, indicating that MCS prolongs neuronal health in the context of DS/AD. Full article

In this study, we investigated the mitochondrial defects resulting from the deletion of GCN5, a lysine-acetyltransferase, in the yeast Saccharomyces cerevisiae. Gcn5 serves as the catalytic subunit of the SAGA acetylation complex and functions as an epigenetic regulator, primarily acetylating N-terminal lysine residues on histones H2B and H3 to modulate gene expression. The loss of GCN5 leads to mitochondrial abnormalities, including defects in mitochondrial morphology, a reduced mitochondrial DNA copy number, and defective mitochondrial inheritance due to the depolarization of actin filaments. These defects collectively trigger the activation of the mitophagy pathway. Interestingly, deleting CSN5, which encodes to Csn5/Rri1 (Csn5), the catalytic subunit of the COP9 signalosome complex, rescues the mitochondrial phenotypes observed in the gcn5Δ strain. Furthermore, these defects are suppressed by exogenous ergosterol supplementation, suggesting a link between the rescue effect mediated by CSN5 deletion and the regulatory role of Csn5 in the ergosterol biosynthetic pathway. Full article