Search Results (26,643)

The flower color of Michelia odora, an important landscape tree plant, shows significant ornamental value, but its regulatory mechanisms remain to be further explored. The present work integrated metabolomic with transcriptomic analyses for elucidating the anthocyanin biosynthesis mechanisms in light pink and deep pink M. odora flowers. Our metabolomic analysis identified 13 differentially expressed anthocyanins, 11 of which, especially cyanidins, were significantly accumulated within deep pink petals versus light pink ones. As revealed by our transcriptomic analysis, 33 differential genes were related to flavonoid and anthocyanin biosynthesis. Further, transcription factor genes, encompassing three MoMYB alongside two MobHLH genes, were likely the hub genes that modulated anthocyanin biosynthesis. Quantitative real-time PCR validation indicated that certain genes, like MoPAL, MoC4H, Mo4CL, MoCHS, MoCHI, MoUGT75C1, MoMYB3, MobHLH1, and MobHLH3, displayed concurrent expression with anthocyanin accumulation within deep pink petals. Collectively, these results indicate the role of anthocyanin accumulation in deep pink color, and the effect of upregulated genes on increasing anthocyanin levels. Our results shed novel light on color change mechanisms underlying M. odora, and provide a theoretical basis for flower breeding. Full article

Fusobacterium nucleatum (F. nucleatum) is a key periodontal pathobiont associated with oral inflammation. This bacterium forms biofilms and expresses adhesins that facilitate its adhesion to and invasion of gingival epithelial cells. These processes disrupt the epithelial barrier and trigger oral inflammation, and in some cases, systemic inflammation. Conventional antimicrobial strategies predominantly depend on the utilization of antibiotics. Nevertheless, this can result in the proliferation of drug-resistant strains and the disruption of the oral microbiome equilibrium. As the predominant human milk oligosaccharide, 2′-Fucosyllactose (2′-FL) demonstrates considerable promise in inhibiting pathogenic bacterial adhesion and fortifying epithelial barrier function, mediated by its characteristic structural and bioactive attributes. In this study, we showed that 2′-FL attenuates the expression of virulence genes in F. nucleatum, reduces biofilm formation, and suppresses the bacterium’s ability to adhere to human gingival epithelial cells (HGECs). Furthermore, at the transcriptional level, 2′-FL suppressed F. nucleatum-induced inflammatory cytokine overexpression in both HGECs and RAW 264.7 macrophages, and upregulated barrier-related proteins (ZO-1, Occludin) and MUC-1 gene expression in HGECs. In vivo studies demonstrated the inhibitory effect of 2′-FL on F. nucleatum-induced periodontal injury in Balb/c mice. Furthermore, 16S rRNA sequencing analysis demonstrated that 2′-FL modulated oral microbiota composition of healthy volunteers and significantly reduced the abundance of Fusobacterium. Full article

Lignin deposition in fruit trees represents a fundamental physiological trade-off: essential for structural integrity and stress adaptation, yet excessive or mistimed activation compromises fruit texture, palatability, and market value. This review synthesizes advances in lignin biosynthesis and its multilayered regulation in commercial fruit species. We describe how abiotic (drought, salinity, temperature extremes) and biotic (pathogens, pests) stresses trigger lignification through transcriptional, post-transcriptional, hormonal, and epigenetic mechanisms, centered on the conserved NAC-MYB cascade. This core module integrates WRKY/ERF transcription factors (TFs), microRNA networks, and hormone signaling. Transcriptional programs are further refined by microRNAs, alternative splicing, DNA methylation, histone acetylation, and phytohormone crosstalk (abscisic acid, ABA; jasmonic acid, JA; salicylic acid, SA; and brassinosteroids, BRs). We emphasize molecular crosstalk integrating abiotic and biotic stress signaling via shared TFs, reactive oxygen species (ROS), and epigenetic memory. We critically examine lignification’s dual nature during development and postharvest storage, contributing to desirable traits (stone formation and skin toughness) but also driving defects (stone cell gritty texture and chilling-induced wooliness). Finally, we propose a strategic framework leveraging molecular breeding, targeted gene editing, and precision horticulture to fine-tune lignification, enabling climate-resilient cultivars without compromising fruit quality. Full article

Oxidative stress is a major challenge in weaned piglet production because it impairs intestinal health, nutrient utilization, and growth performance; however, the effects of dietary epigallocatechin-3-gallate (EGCG) on intestinal dysfunction under oxidative stress conditions have not been fully elucidated. This study examined whether dietary EGCG supplementation could improve intestinal function in weaned pigs subjected to Diquat-induced oxidative stress. Thirty-two weaned piglets were allocated to four treatments according to a 2 × 2 factorial arrangement involving dietary EGCG supplementation (0 or 50 mg/kg) and exposure to saline or Diquat (50 mg/kg body weight). Diquat exposure impaired intestinal morphology and antioxidant status and altered the transcription of genes associated with epithelial barrier integrity and redox regulation. Dietary EGCG supplementation partially attenuated these alterations, as reflected by improvements in villus architecture, intestinal antioxidant indices, and the mRNA expression of barrier- and antioxidant-related genes. These findings indicate that dietary EGCG supplementation was associated with improved intestinal function in weaned pigs exposed to oxidative stress. These beneficial effects may be related, at least in part, to changes in redox status, inflammatory responses, epithelial barrier-related gene expression, and selected gut microbial populations. This study supports EGCG as a potential bioactive dietary factor for maintaining intestinal health under oxidative stress conditions. Full article

Vitis heyneana Roem. et Schult. var. adenoclada (Hand.-Mazz.) is an important wild grapevine resource with unique berry traits and wine quality characteristics; yet the molecular mechanisms governing its phenolic biosynthesis remain to be further elucidated compared with cultivated Vitis vinifera. This study aimed to systematically characterize the transcriptional and metabolic regulation of phenolic compound accumulation in V. heyneana var. adenoclada using integrated metabolomics and transcriptomics. At the metabolic level, V. heyneana var. adenoclada exhibited significantly higher contents of phenolic acids (caffeic and ferulic acids), resveratrol, flavonols (quercetin and myricetin), flavan-3-ols (catechin and epicatechin), and anthocyanin diglucosides compared with V. vinifera cv. Cabernet Sauvignon. The two tested V. heyneana varieties showed distinct developmental accumulation profiles: Guiheizhenzhu No. 6 accumulated more ferulic acid, resveratrol, myricetin, and anthocyanins at maturity, whereas Yeniang No. 2 showed higher quercetin and flavan-3-ols at the green stage. Integrated multi-omics correlation analyses revealed that the elevated phenolic content is driven by the coordinated upregulation of key structural genes mediated by a complex MYB regulatory network. Specifically, MYB12 (MYBF1) positively correlated with COMT, CHI, DFR, and LAR. MYB5, MYBS3, and MYB61 promoted quercetin synthesis by activating FLS. MYB06, MYB4, and MYB36 enhanced STS transcription to drive resveratrol biosynthesis, whereas MYB1 and MYB5 cooperatively regulated UFGT, 5GT, and GST4, facilitating efficient synthesis and transport of anthocyanin diglucosides. These findings provide comprehensive mechanistic insights into phenolic metabolism in V. heyneana var. adenoclada and establish a valuable theoretical foundation for improving the flavor quality and regional utilization of wild grape wines. Full article

The ketogenic diet (KD) has demonstrated anti-proliferative effects across multiple tumor types, yet the underlying metabolic and transcriptomic mechanisms remain incompletely understood. This study employed integrated multi-omics analysis combining targeted metabolomics and RNA sequencing to elucidate KD-induced metabolic reprogramming in BRAF/NRAS wild-type, BRAF mutant, and NRAS mutant melanoma xenografts, which showed delayed tumor growth when treated with the KD. Despite pronounced metabolic and transcriptional heterogeneity across models with minimal overlap in individual KD-responsive genes, pathway-level analysis revealed convergent biological signatures. Using VIP score-based integration and supervised latent variable modeling (mixOmics DIABLO), we identified consistent KD-associated alterations in cancer-related pathways including the PI3K-Akt, MAPK, sphingolipid as well as HIF-1 signaling pathways. The KD enhanced sphingomyelin and ceramide levels and additionally induced transcriptional signatures, indicating increased ceramide synthesis and reduced ceramide breakdown. Moreover, the KD reduced transcript levels of genes encoding critical tumor regulators, including PI3K, AKT, HIF, MEK, and ERK. These findings demonstrate that despite metabolic and transcriptomic heterogeneity, the KD drives coordinated metabolic reprogramming at the pathway level, indicative of shifting lipid metabolism toward pro-apoptotic ceramides and attenuating key oncogenic signaling cascades. Our results provide insights into the KD’s anti-tumor efficacy and identify metabolic nodes amenable to therapeutic intervention in melanoma. Full article

Objectives: This study aimed to identify and characterize macrophage-associated inflammatory regulatory signatures in ulcerative colitis (UC) by integrating bulk and single-cell transcriptomic data, and to explore their potential regulatory and pharmacological relevance. Methods: Two colonic bulk microarray datasets (GSE179285 and GSE87466) and one single-cell RNA-sequencing dataset (GSE231993) were analyzed. Differential expression analysis, area under the recovery curve-based single-cell gene-set scoring (AUCell) scoring, macrophage high-dimensional Weighted Gene Co-Expression Network Analysis (hdWGCNA), and three machine learning algorithms were combined to prioritize candidate genes. Their expression and diagnostic performance were externally validated. Macrophage trajectory analysis, cell–cell communication analysis, virtual perturbation, transcription factor activity inference, compound prediction, and molecular docking were further performed. Results: Single-cell preprocessing retained 30,737 high-quality cells, and macrophages exhibited relatively high innate immune cell barrier-related gene activity. Integrated screening identified CCL3, CCL4, JUNB, and FOS, whereas machine learning consensus retained CCL3, CCL4, and JUNB as the final signatures. These genes were consistently upregulated in UC, with validation area-under-the-curve values of 0.917, 0.958, and 0.888, respectively. Their expression varied along an inferred macrophage inflammatory state continuum, and UC showed remodeled macrophage-centered communication, including CXCL8–ACKR1 signaling. Virtual perturbation linked CCL3 and CCL4 to chemotaxis and lysosomal programs and JUNB to antigen processing and major histocompatibility complex (MHC) class II pathways; RFX5 was prioritized as a potential upstream regulator. CID11879209 was predicted as a shared candidate compound, with docking energies of −6.55, −6.31, and −4.50 kcal/mol for CCL3, CCL4, and JUNB, respectively. Conclusions: CCL3, CCL4, and JUNB constitute a macrophage-associated inflammatory signature connecting tissue-level UC dysregulation with macrophage state remodeling. These findings provide testable molecular and pharmacological hypotheses requiring further experimental and clinical validation. Full article

Excessive fructose consumption is associated with metabolic syndrome (MS). This study evaluated the effect of two coffee by-products, coffee pulp (CP) and coffee silverskin (SK), on fructose-induced intestinal changes. Sprague–Dawley rats were assigned to six groups (n = 6/group) for 10 weeks: Control, Fructose (FRU; 20% fructose in drinking water), CP, CP + FRU, SK, and SK + FRU. CP and SK were administered by oral gavage (250 mg/kg/day) using corn oil as vehicle. Intestinal morphology, gene expression (RT-qPCR), and gut microbiota composition (16S rRNA sequencing) were assessed. Fructose significantly increased jejunal expression of the glucose transporters SGLT1 and GLUT2. CP and SK reversed SGLT1 and GLUT2 overexpression and reduced GLUT5 expression relative to the FRU group. Fructose also markedly increased expression of sweet taste receptors TAS1R2 and TAS1R3 and the transcription factors SREBP-1c and ChREBP. Both CP and SK normalized TAS1R2 and TAS1R3 expression, whereas SK additionally prevented SREBP-1c and ChREBP overexpression. Both by-products restored fructose-induced reductions in microbial richness and alpha diversity. CP also modified beta diversity and increased the abundance of the genus Blautia compared with FRU. In conclusion, CP and SK reversed several fructose-induced intestinal alterations, namely in the jejunal expression of sugar-sensing and absorption-related genes. Additionally, CP showed microbiota-modulating effects, whereas SK modulated the jejunal expression of key transcription factors (SREBP-1c and ChREBP) involved in carbohydrate and lipid metabolism. Overall, these findings suggest that CP and SK may represent promising candidates for mitigating fructose-induced intestinal alterations. Full article

Background: Lung infections represent a major cause of morbidity and mortality in patients with cystic fibrosis (CF) and are predominantly associated with chronic infection by Pseudomonas aeruginosa. The clinical management of CF lung disease is increasingly compromised by the emergence of multidrug-resistant strains, biofilm formation, and the expression of multiple virulence determinants. Antimicrobial peptides (AMPs), evolutionarily conserved effectors of innate immunity, have emerged as promising therapeutic candidates due to their ability to exert both bactericidal and anti-virulence activities. In this study, we investigated the antimicrobial and mechanistic effects of Ranalexin-1G, an AMP derived from the skin secretion of Rana grylio, against P. aeruginosa, for which its antibacterial activity has not previously been reported in the literature. Methods: Antibacterial activity was determined against the reference strain and three clinical isolates of P. aeruginosa by broth microdilution assays, time-kill kinetics and anti-biofilm assays, while peptide-mediated modulation of virulence was evaluated through transcriptional analysis of key virulence-associated genes by RT-PCR. The impact of Ranalexin-1G on host–pathogen interactions was further assessed using bacterial invasion assays in human bronchial epithelial cells (BEAS-2B). Results: Ranalexin-1G exerted a rapid bactericidal effect within 6 h at non-cytotoxic concentrations and displayed modest anti-biofilm effects, with greater efficacy in inhibiting biofilm formation. Mechanistically, peptide treatment resulted in a reduction in the expression of selected genes involved in biofilm formation and virulence, including those associated with alginate biosynthesis and type III secretion system-mediated cytotoxicity. Consistently, Ranalexin-1G markedly impaired bacterial invasion of epithelial cells, indicating interference with early host–pathogen interaction processes. Notably, the peptide displayed robust antimicrobial activity against multidrug-resistant P. aeruginosa clinical isolates from CF patients. Conclusions: Collectively, these findings suggest that Ranalexin-1G acts through a dual mechanism involving direct bactericidal activity and modulation of selected virulence pathways, supporting further investigation of its potential as an anti-virulence and host-directed approach for the treatment of chronic P. aeruginosa infections in cystic fibrosis. Full article

Ectropis obliqua nucleopolyhedrovirus (EcobNPV) is an important biocontrol agent against Ectropis obliqua and E. grisescens. A previously isolated strain, EcobNPV-QF4, exhibits significantly higher virulence than the original strain EcobNPV-QV, yet the molecular basis for this difference remains unclear. Leaf-dipping bioassays demonstrated that EcobNPV-QF4 caused significantly higher larval mortality than EcobNPV-QV from 10 dpi onward, reaching 97.9% versus 33.8% at 16 dpi, and higher pupal mortality (100% versus 47.3%), confirming its superior virulence across both larval and pupal stages. To investigate the transcriptional dynamics underlying virulence variation, we performed a comparative time-course transcriptomic analysis of E. grisescens infected with either strain at 0, 2, 6, 12, 24, 36, and 48 h post-infection. The reliability of the RNA-seq data was validated by qRT-PCR for selected expressed genes. The results showed that, relative to EcobNPV-QV, the EcobNPV-QF4 strain exhibits a transcriptional strategy characterized by comprehensive and accelerated activation: the transcriptional initiation of its functional modules is globally advanced by approximately 6 h compared with EcobNPV-QV, and genes associated with midgut escape, virion assembly, and viral DNA replication are preferentially and coordinately expressed, resulting in a more synchronized transcriptional profile. Based on these findings, we hypothesize that the enhanced virulence of EcobNPV-QF4 is not attributable to a single factor but rather reflects a synergistic, multitiered acceleration of transcriptional progression that may compress the infection cycle and enhance viral dissemination efficiency. These findings provide critical insights into the molecular mechanisms that may underlie baculovirus virulence and provide a basis for future mechanistic studies. Full article

Despite the growing demand for sustainable agricultural systems, the long-term effects of tillage practices remain controversial. No-tillage (NT) systems offer several potential benefits, including improved soil structure, enhanced soil biological activity, and reduced environmental stress, but their application can also be associated with challenges such as difficulty in weed control or variable crop yield. Although previous studies have extensively investigated the effects of NT systems on soil and crop, limited knowledge is available about the cellular adaptation mechanisms of plants, especially gene expression and biochemical responses. The aim of this study was to compare the effects of conventional tillage (CT) and NT systems in sunflower plants using an integrated transcriptomic and biochemical approach. We performed genome-wide transcriptomic analysis based on next-generation sequencing on leaf samples from three different field sites, supplemented by measurements of biochemical parameters related to selected metabolic processes. Exploratory transcriptomic analysis indicated that several gene expression changes related to primary metabolic processes occurred in plants grown in the NT system compared to the CT system. These included processes related to photosynthesis, cellular respiration, carbohydrate metabolism and the biosynthesis of some amino acids. In parallel, we observed transcriptional patterns indicating increased activity of several secondary metabolic pathways, which may be related to adaptation mechanisms to environmental stress. Determination of total soluble sugar, crude protein, total phenolics and total flavonoids provided independent biochemical support for the changes indicated by the transcriptomic results. Our results suggest that the tillage system affects the cellular regulatory processes of sunflower. During adaptation to a no-tillage environment, plants can simultaneously maintain basic metabolic processes and activate defense mechanisms that may contribute to adaptation to changed growing conditions. Our study contributes to a better understanding of the molecular and physiological consequences of tillage systems in plants. Full article

Major depressive disorder (MDD) has been linked to oxidative stress, mitochondrial dysfunction, and impaired neuronal plasticity, but the reproducibility of related transcriptomic alterations across postmortem brain cohorts remains uncertain. We performed a targeted cross-platform analysis of a prespecified 14-gene panel spanning antioxidant defense, mitochondrial-redox regulation, cellular stress responses, neurotrophic signaling, synaptic plasticity, and polyamine metabolism across seven postmortem dorsolateral prefrontal cortex cohorts comprising 146 MDD cases and 179 controls. Primary support required Fisher-combined evidence, Benjamini–Hochberg correction across the panel, and concordant MDD-minus-control direction across all available cohorts. NPTX2, EGR1, VGF, BDNF, and SAT1 met these criteria, with lower expression in MDD. The same five-gene pattern was supported by weighted signed Stouffer analysis, one-stage generalized least-squares models, random-effects meta-analysis, and 200,000 disease-label permutations; none produced at least five genes meeting the complete primary-support criterion (empirical p = 5.0 × 10⁻⁶). The most robust cross-cohort finding was a convergent lower-expression pattern across genes supporting redox-linked stress adaptation, polyamine homeostasis, neurotrophic signaling, activity-dependent transcription, and synaptic plasticity. This pattern suggests impaired molecular capacity for neuronal stress resilience and adaptive plasticity in MDD. Full article

Fusarium oxysporum f. sp. radicis-cucumerinum (Forc) V03-2g and Fusarium oxysporum f. sp. radicis-lycopersici (Forl) ZUM2407 both cause foot and root rot in cucumber, but differ in host range. Forc V03-2g possesses Secreted in Xylem (SIX) effector genes, whereas Forl ZUM2407 does not, raising questions about their distinct infection strategies on this host. Using comparative transcriptomic analysis (in cucumber at 7 and 14 days post-inoculation (dpi) and in tomato at 2 dpi) we show that Forl ZUM2407 induces a delayed defense response in cucumber compared to Forc V03-2g. In turn, Forc V03-2g rapidly activates accessory chromosome effectors on cucumber, while Forl ZUM2407 initially deploys core chromosome genes, activating distinct from Forc V03-2g accessory genes only by 14 dpi. Thereby, Forc V03-2g and Forl ZUM2407 use distinct accessory gene repertoires (unique to each strain) and distinct core gene transcription strategies to infect the same host. Full article

Obesity and type 2 diabetes mellitus (T2DM) are multifactorial disorders characterized by insulin resistance, chronic low-grade inflammation, adipose tissue dysfunction, and multi-organ metabolic impairment. MicroRNAs (miRNAs) act as post-transcriptional gene regulators and play critical roles in metabolic homeostasis, the modulation of insulin signaling, adipogenesis, inflammatory pathways, and energy balance in key insulin-target tissues, including liver, skeletal muscle, and adipose tissue. This review summarizes mechanistic and translational insights into miRNA regulation in obesity, insulin resistance, and T2DM, integrating data from human studies and experimental models on miRNA sequence codes and extracellular vesicle sorting pathways. We focus on the tissue-specific and systemic roles of miRNAs, highlighting their contribution to inter-organ communication and metabolic network regulation. In addition, we emphasize their emerging roles as predictive biomarkers, modulators of treatment response, and promising targets for RNA-based interventions. Advances in sequence-specific miRNA sorting and extracellular vesicle-mediated delivery may provide avenues for therapeutic intervention. However, challenges related to delivery efficiency, tissue specificity, off-target effects, and variability in miRNA quantification remain important barriers to clinical translation. Addressing these limitations may help define the clinical utility of miRNAs as biomarkers and therapeutic targets in metabolic disorders. Full article

Down feathers and contour feathers are two distinct feather types with vastly different structures and functions coexisting in the same individual. However, the molecular mechanism underlying these differences remains unclear. In this study, skin tissue containing intact feather follicles was collected from four anatomically defined regions of healthy Beijing ducks (Anas platyrhynchos domesticus) for transcriptomic sequencing: the breast and abdomen, which generate down feathers, and the wingtips and rump, which produce contour feathers. To mitigate bias arising from site-specific effects, we established paired comparisons between contour feathers and down feathers across different regions. Across all comparisons, 36 core differentially expressed genes (DEGs) were consistently identified. These encompassed nine HOX family transcription factors across three paralogous clusters, ZIC family members (ZIC1 and ZIC4), WNT4, TBX4, BMP5, cytoskeletal and sarcomeric genes (MYOZ2, ACTN2, DES, SMPX), extracellular matrix regulators (ASPN, MGP, FMOD), and lipid metabolism-related genes (MOGAT2, PNPLA2), among others. Pathway enrichment analysis revealed that transcriptomic variations in different feather follicles involve gene modules functioning in positional identity, cytoskeletal organization, extracellular matrix remodeling and lipid metabolism, with potential neuroendocrine modulation. The transcriptomic dataset established here facilitates future studies on the molecular mechanisms of feather differentiation and offers a reference for molecular breeding to enhance down feather yield and quality of Beijing ducks. Full article