Search Results (949)

Copper pyrithione (CuPT), an emerging biocide used in ship antifouling coatings, may accumulate in marine sediments and pose risks to non-target organisms. However, current research on CuPT toxicity remains limited. Litopenaeus vannamei, one of the world’s most important aquaculture shrimp species, relies heavily on its hepatopancreas for energy metabolism, detoxification, and immune responses. Due to their benthic habitat, these shrimps are highly vulnerable to contamination in sediment environments. This study investigated the toxicological response in the hepatopancreas of L. vannamei exposed to CuPT (128 μg/L) for 3 and 48 h. Terminal deoxynucleotidyl transferase dUTP Nick-End Labeling (TUNEL) fluorescence staining revealed increased apoptosis, deformation of hepatic tubule lumens, and the loss of stellate structures in the hepatopancreas after CuPT 48 h exposure. A large number of differentially expressed genes (DEGs) were identified by transcriptomics analysis at 3 and 48 h, respectively. Most of these DEGs were related to detoxification, glucose transport, and immunity. Metabolomic analysis identified numerous significantly different metabolites (SDMs) at both 3 and 48 h post-exposure, with most SDMs associated with energy metabolism, fatty acid metabolism, and related pathways. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of metabolomics and transcriptome revealed that both DEGs and SDMs were enriched in arachidonic acid metabolism, fatty acid biosynthesis, and glycolysis/gluconeogenesis pathways at 3 h, while at 48 h they were enriched in the starch and sucrose metabolism, amino sugar and nucleotide sugar metabolism, and galactose metabolism pathways. These results suggested that CuPT disrupts the energy and lipid homeostasis of L. vannamei. This disruption compelled L. vannamei to allocate additional energy toward sustaining basal physiological functions and consequently caused the accumulation of large amounts of reactive oxygen species (ROS) in the body, leading to apoptosis and subsequent tissue damage, and ultimately suppressed the immune system and impaired the health of L. vannamei. Our study elucidates the molecular mechanisms of CuPT-induced metabolic disruption and immunotoxicity in L. vannamei through integrated multi-omics analyses, providing new insights for ecological risk assessment of this emerging antifoulant. Full article

Background/Objectives: Dendrobium nobile Lindl. (DNL), a traditional dietary supplement, exhibits therapeutic potential for type 2 diabetes mellitus (T2DM), yet its mechanisms remain unclear. Methods: T2DM was induced in db/db mice. DNL (10 g/kg/d) or metformin (65 mg/kg/d) was administered for 4 weeks. This study integrated pharmacodynamic evaluation and multi-omics to elucidate DNL’s anti-diabetic effects in db/db mice. Results: DNL intervention significantly ameliorated T2DM phenotypes, reducing hyperglycemia, insulin resistance, and renal dysfunction. Metabolomics analysis identified 39 differential metabolites (19 upregulated, 20 downregulated) linked to citrate cycle, oxidative phosphorylation, and glycerophospholipid metabolism, while proteomics revealed 113 differentially expressed proteins, with multi-omics integration highlighting DNL’s modulation of three proteins (Ckm, Ache, Selenbp1) and four metabolites (4-guanidinobutanoic acid, phosphorylcholine, homocysteine, succinic acid) across arginine/proline metabolism, glycerophospholipid metabolism, and sulfur metabolism. Pathway analysis demonstrated DNL’s restoration of dysregulated processes, including inflammation suppression via NF-κB and PI3K-Akt pathways, enhanced insulin sensitivity through glycerophospholipid balance, and mitigation of oxidative stress via sulfur metabolism. Key correlations between metabolites and proteins underscored DNL’s multi-target action. Conclusions: These findings systematically decode therapeutic mechanisms of Dendrobium nobile Lindl., emphasizing its role in rectifying metabolic disorders and inflammatory signaling, thereby providing a molecular basis for its clinical application in T2DM management. Full article

Background/Objective: Oral lichen planus (OLP) is a chronic inflammatory disorder of the oral mucosa with unclear etiology. Increasing evidence implicates oral microbial dysbiosis in its pathogenesis, but little is known about supragingival plaque communities in relation to clinical subtypes. This cross-sectional case–control study aimed to characterize the supragingival plaque microbiota and microbial interaction networks in erosive OLP (E-OLP), non-erosive OLP (NE-OLP), and healthy controls (HCs), to elucidate microbial patterns associated with disease severity. Methods: Supragingival plaque samples were collected from 90 participants (30 per group) and analyzed using 16S rRNA gene sequencing. Alpha and beta diversity metrics, differential abundance, and co-occurrence network analyses were performed. Results: E-OLP exhibited pronounced dysbiosis, including the enrichment of pro-inflammatory taxa (e.g., Prevotella, Parvimonas) and depletion of health-associated commensals (e.g., Rothia, Capnocytophaga). Network analysis revealed the stepwise disintegration of microbial community structure from HC to NE-OLP to E-OLP, with reduced connectivity and increased dominance of pathogenic clusters in E-OLP. These microbial alterations aligned with clinical findings, as E-OLP patients showed significantly higher Reticulation/keratosis, Erythema, and Ulceration (REU) scores for erythema and ulceration compared to NE-OLP. Conclusions: Supragingival plaque dysbiosis and ecological disruption are strongly associated with OLP severity and subtype. This study highlights the utility of plaque-based microbial profiling in capturing lesion-proximal dysbiotic signals, which may complement mucosal and salivary analyses in future diagnostic frameworks. Multi-omics approaches incorporating fungal, viral, and metabolic profiling are warranted to fully elucidate host–microbe interactions in OLP. Full article

The zinc finger protein with KRAB and SCAN domains 3 (ZKSCAN3) has emerged as a critical regulator of diverse cellular processes, including autophagy, cell cycle progression, and tumorigenesis. Structurally, ZKSCAN3 is characterized by its conserved DNA-binding zinc finger motifs, a SCAN domain mediating protein–protein interaction, and a KRAB repression domain implicated in transcriptional regulation. Post-translational modifications, such as phosphorylation and ubiquitination, dynamically modulate its subcellular localization and activity, enabling context-dependent functional plasticity. Functionally, ZKSCAN3 acts as a master switch in autophagy by repressing the transcription of autophagy-related genes under nutrient-replete conditions, while its nuclear-cytoplasmic shuttling under stress conditions links metabolic reprogramming to cellular survival. Emerging evidence also underscores its paradoxical roles in cancer: it suppresses tumor initiation by maintaining genomic stability yet promotes metastasis through epithelial–mesenchymal transition induction. Furthermore, epigenetic mechanisms, including promoter methylation and non-coding RNA regulation, fine-tune ZKSCAN3 expression, contributing to tissue-specific outcomes. Despite these insights, gaps remain in understanding the structural determinants governing its interaction with chromatin-remodeling complexes and the therapeutic potential of targeting ZKSCAN3 in diseases. Future investigations should prioritize integrating multi-omics approaches to unravel context-specific regulatory networks and explore small-molecule modulators for translational applications. This comprehensive analysis provides a framework for advancing our mechanistic understanding of ZKSCAN3 and its implications in human health and disease. This review synthesizes recent advances in elucidating the regulatory networks and functional complexity of ZKSCAN3, highlighting its dual roles in physiological and pathological contexts. Full article

Atherosclerotic cardiovascular disease (ASCVD) remains a leading cause of global morbidity and mortality, prompting significant interest in individualized prevention and treatment strategies. This review synthesizes recent advances in genomic and precision medicine approaches relevant to ASCVD, with a focus on genetic risk scores, lipid metabolism genes, and emerging gene editing techniques. A structured literature search was conducted across PubMed, Scopus, and Web of Science databases to identify key publications from the last decade addressing genomic mechanisms, therapeutic targets, and computational tools in ASCVD. Notable findings include the identification of causal genetic variants such as PCSK9 and LDLR, the development of polygenic risk scores for early prediction, and the use of deep learning algorithms for integrative multi-omics analysis. In addition, we highlight current and future therapeutic applications including PCSK9 inhibitors, RNA-based therapies, and CRISPR-based genome editing. Collectively, these advances underscore the promise of precision medicine in tailoring ASCVD prevention and treatment to individual genetic and molecular profiles. Full article

Background: Immune checkpoint inhibitors (ICIs) have transformed cancer treatment, yet severe immune-related adverse events (irAEs) often necessitate immunotherapy discontinuation and cause life-threatening complications. Circulating plasma proteins, dynamically accessible and functionally linked to immunity, may predict and offer novel targets for irAEs. Methods: Leveraging multi-omics integration, we conducted bidirectional two-sample Mendelian randomization (MR) using protein quantitative trait loci (pQTLs) from 4998 plasma proteins and genome-wide association data of irAE phenotypes. A causal inference framework combining colocalization analysis, multivariable MR (MVMR) adjusting for body mass index (BMI) confounding, and mediation MR elucidated BMI-independent pathways. Systems biology approaches including tissue-specific expression profiling, pathway enrichment, and protein interaction network analysis revealed spatial and functional drivers of irAE pathogenesis. Results: Proteome-wide MR mapping identified eight plasma proteins (CCL20, CSF1, CXCL9, CD40, TGFβ1, CLSTN2, TNFSF12, TGFα) causally associated with all-grade irAEs, and five (CCL20, CCL25, CXCL10, ADA, TGFα) with high-grade irAEs. Colocalization prioritized CD40/TNFSF12 (all-grade) and ADA/CCL25 (high-grade) as therapeutic targets (PPH4 > 0.7). CXCL9/TNFSF12 (all-grade) and CCL25 (high-grade) exerted BMI-independent effects, suggesting intrinsic immune dysregulation mechanisms. Tissue-specific gene expression patterns, CSF1, TGFβ1 in lung, TNFSF12 in the ileum may explain organ-specific irAE vulnerabilities. High-grade irAEs correlated with compartmentalized immune dysregulation and IL-17/immunodeficiency pathway activation. Conclusions: This study establishes the causal atlas of plasma proteins in irAE pathogenesis, bridging biomarker discovery with actionable therapeutic targets. These advances align with next-generation immunotherapy goals: maximizing efficacy while taming the immune storm. Full article

Pear (Pyrus pyrifolia) is an important deciduous fruit tree that requires a specific period of low-temperature accumulation to trigger spring flowering. The warmer winter caused by global warming has led to insufficient winter chilling, disrupting floral initiation and significantly reducing pear yields in Southern China. In this study, we integrated targeted phytohormone metabolomics, full-length transcriptomics, and proteomics to explore the regulatory mechanisms of dormancy in ‘Mixue’, a pear cultivar with an extremely low chilling requirement. Comparative analyses across the multi-omics datasets revealed 30 differentially abundant phytohormone metabolites (DPMs), 2597 differentially expressed proteins (DEPs), and 7722 differentially expressed genes (DEGs). Integrated proteomic and transcriptomic expression clustering analysis identified five members of the dormancy-associated MADS-box (DAM) gene family among dormancy-specific differentially expressed proteins (DEPs) and differentially expressed genes (DEGs). Phytohormone correlation analysis and cis-regulatory element analysis suggest that DAM genes may mediate dormancy progression by responding to abscisic acid (ABA), gibberellin (GA), and salicylic acid (SA). A dormancy-associated transcriptional regulatory network centered on DAM genes and phytohormone signaling revealed 35 transcription factors (TFs): 19 TFs appear to directly regulate the expression of DAM genes, 18 TFs are transcriptionally regulated by DAM genes, and two TFs exhibit bidirectional regulatory interactions with DAM. Within this regulatory network, we identified a novel pathway involving REVEILLE 6 (RVE6), DAM, and CONSTANS-LIKE 8 (COL8), which might play a critical role in regulating bud dormancy in the ‘Mixue’ low-chilling pear cultivar. Furthermore, lncRNAs ONT.19912.1 and ONT.20662.7 exhibit potential cis-regulatory interactions with DAM1/2/3. This study expands the DAM-mediated transcriptional regulatory network associated with bud dormancy, providing new insights into its molecular regulatory mechanisms in pear and establishing a theoretical framework for future investigations into bud dormancy control. Full article

Background/Objectives: Cell–cell communication (CCC) is a critical process within the tumor microenvironment, governing regulatory interactions between cancer cells and other cellular subpopulations. Aiming to improve the accuracy and completeness of intercellular gene-regulatory network inference, we constructed a novel spatial-resolved gene-regulatory network framework (spGRN). Methods: Firstly, the spatial multi-omics data of colorectal cancer (CRC) patients were analyzed. We precisely located the tumor boundaries and then systematically constructed the spGRN framework to study the network regulation. Subsequently, the key signaling molecules obtained by the spGRN were identified and further validated by the spatial-proteomics dataset. Results: Through the constructed spatial gene regulatory network, we found that in the communication with malignant cells, the highly expressed ligands LIF and LGALS3BP and receptors IL6ST and ITGB1 in fibroblasts can promote tumor proliferation, and the highly expressed ligands S100A8/S100A9 in plasma cells play an important role in regulating inflammatory responses. Further, validation of the key signaling molecules by the spatial-proteomics dataset highlighted the role of these genes in mediating the regulation of boundary-related cells. Furthermore, we applied the spGRN to publicly available single-cell and spatial-transcriptomics datasets from three other cancer types. The results demonstrate that ITGB1 and its target genes FOS/JUN were commonly expressed in all four cancer types, indicating their potential as pan-cancer therapeutic targets. Conclusion: the spGRN was proven to be a useful tool to select signal molecules as potential biomarkers or valuable therapeutic targets. Full article

Background/Objectives: Olfactory neuroblastoma (ONB), also known as esthesioneuroblastoma, is a rare neuroectodermal malignancy of the nasal cavity characterized by aggressive local invasion and variable metastatic potential, with diverse clinical behavior, often presenting at advanced stages. ONB poses challenges for targeted therapeutic strategies, despite advances in surgical and multimodal treatment strategies, because of the rarity of this disease and the limited understanding of its molecular pathophysiology. Methods: A comprehensive review of genomic, multi-omic, and molecular studies was performed to integrate known targeted sites in ONB with the current understanding of its pathophysiology. Results: Recent genetic and molecular studies have identified significant epigenetic and signaling pathway alterations that are critical in pathogenesis and treatment resistance and may serve as potential therapeutic targets. Additionally, novel discovered immunohistochemical and transcriptomic markers, such as IDH2, NEUROD1, and OTX2, offer improved diagnostic specificity and prognostication. Multi-genomic platforms (i.e., multi-omics), involving the combined integration of transcriptomics, epigenetics, and proteomics findings, have led to several recent insights, including the subclassification of neural and basal genomic subtypes, the identification of key driver mutations, and new insights into disease development. This review synthesizes current knowledge on the molecular landscape of ONB, including its tumor origin, immune microenvironment, genetic alterations, and key molecular pathways involved in its pathogenesis. Conclusions: Future research may benefit from integrating these findings into precision medicine approaches, enabling earlier diagnosis and more accurate prognosis. Full article

Curcumin is a natural polyphenolic compound known to alleviate follicular developmental abnormalities associated with ovarian dysfunction. However, its precise molecular mechanisms remain to be fully elucidated. In this study, we systematically investigated the regulatory effects of curcumin on bovine ovarian granulosa cells through integrated transcriptomic and metabolomic analyses. A total of 503 and 200 significantly altered metabolites were identified in the positive and negative ion modes, respectively, with enrichment in key pathways such as glutathione metabolism, fatty acid biosynthesis, and the phosphatidylinositol signaling pathway. Transcriptomic profiling revealed 1168 differentially expressed genes (582 upregulated and 586 downregulated) which were significantly enriched in pathways related to glutathione metabolism and cellular senescence. Joint multi-omics analysis further demonstrated that curcumin significantly influenced pathways related to glutathione metabolism, cysteine, and methionine metabolism, as well as multiple forms of programmed cell death, including apoptosis, necroptosis, and ferroptosis. Collectively, these findings suggest that curcumin may enhance the antioxidant capacity and survival of granulosa cells by maintaining redox homeostasis and modulating cell fate. This work provides new insights into the potential cellular mechanisms underlying the protective effects of curcumin on granulosa cell function. Full article

Background/Objectives: Cardiac aging involves the progressive structural and functional decline of the myocardium. Endurance training is a well-recognized non-pharmacological intervention that counteracts this decline, yet the molecular mechanisms driving exercise-induced cardiac rejuvenation remain inadequately elucidated. This study aimed to identify key effector genes and regulatory pathways by integrating human cardiac aging transcriptomic data with multi-omic exercise response datasets. Methods: A systems biology framework was developed to integrate age-downregulated genes (n = 243) from the GTEx human heart dataset and endurance-exercise-responsive genes (n = 634) from the MoTrPAC mouse dataset. Thirty-seven overlapping genes were identified and subjected to Enrichr for pathway enrichment, KEA3 for kinase analysis, and ChEA3 for transcription factor prediction. Candidate effector genes were ranked using ToppGene and ToppNet, with integrated prioritization via the FLAMES linear scoring algorithm. Results: Pathway enrichment revealed complementary patterns: aging-associated genes were enriched in mitochondrial dysfunction and sarcomere disassembly, while exercise-responsive genes were linked to protein synthesis and lipid metabolism. TTN, PDK family kinases, and EGFR emerged as major upstream regulators. NKX2-5, MYOG, and YBX3 were identified as shared transcription factors. SMPX ranked highest in integrated scoring, showing both functional relevance and network centrality, implying a pivotal role in mechano-metabolic coupling and cardiac stress adaptation. Conclusions: By integrating cardiac aging and exercise-responsive transcriptomes, 37 effector genes were identified as molecular bridges between aging decline and exercise-induced rejuvenation. Aging involved mitochondrial and sarcomeric deterioration, while exercise promoted metabolic and structural remodeling. SMPX ranked highest for its roles in mechano-metabolic coupling and redox balance, with X-inactivation escape suggesting sex-specific relevance. Other top genes (e.g., KLHL31, MYPN, RYR2) form a regulatory network supporting exercise-mediated cardiac protection, offering targets for future validation and therapy. Full article

Malignant melanoma (MM) affects not only humans but also animals, with gray horses being particularly predisposed to acquiring the disease. Multiomics have greatly advanced the understanding of human MM. In contrasty little is known regarding the pathogenesis of gray-horse melanoma and the unique phenomenon of melanoma “dormancy” in some animals. To help close this gap in knowledge, melanoma tissue and intact skin collected from gray horses were subjected to transcriptome analysis using RNAseq. In the next step, cultured primary tumor cells and normal skin fibroblasts were established from gray horses, and their protein expression profiles were determined. The obtained data unambiguously identified gray-horse melanoma (ghM) as a malignant tumor, as reflected by the overrepresentation of pathways typically activated in human melanoma and other human cancers. These included the RAS/RAF/MAPK, the IRS/IGF1R, and the PI3K/AKT signaling networks. In addition, the obtained data suggest that the key molecules RAC1, RAS, and BRAF, which are frequently mutated in human melanoma, may also contain activating mutations in ghM, whilst PTEN may harbor loss-of-function mutations. This issue will be subject to downstream analyses determining the mutational status in ghM to further advance the understanding of this frequent disease in gray horses. Full article

Globally, rice cultivation consumes large amounts of fresh water, and urgent improvements in water use efficiency (WUE) are needed to ensure sustainable production, given increasing water scarcity. While stomatal traits have been a primary focus for enhancing WUE, complex interactions between stomatal and non-stomatal leaf traits remain poorly understood. In this review, we present an analysis of stomatal and non-stomatal leaf traits influencing WUE in rice. The data suggests that optimising stomatal density and size will be insufficient to maximise WUE because non-stomatal traits such as mesophyll conductance, leaf anatomy, and biochemical composition significantly modulate the relationship between stomatal conductance and the photosynthetic rate. Integrating recent advances in high-throughput phenotyping, multi-omics technologies, and crop modelling, we suggest that combinations of seemingly contradictory traits can enhance WUE without compromising yield potential. We propose a multi-trait breeding framework that leverages both stomatal and non-stomatal adaptations to develop rice varieties with superior WUE and climate resilience. This integrated approach provides a roadmap for accelerating the development of water-efficient rice cultivars, with broad implications for improving WUE in other crops. Full article

Phytoremediation is a green economic method to address soil cadmium (Cd) pollution, and Solanum americanum is considered a potential phytoremediation candidate. However, the underlying Cd response mechanisms of S. americanum remain unclear. In the current study, a hydroponic experiment with 160 μmol/L Cd stress was conducted, physiological and molecular indices were measured to explore the response of S. americanum leaves to Cd stress at different time points (0, 3, and 7 days). Our findings revealed that Cd stress inhibited plant growth. Moreover, Cd stress significantly increased Cd accumulation, as well as Chla content, Chla/b, activities of SOD and POD, and elevated MDA content in the leaves. Furthermore, transcriptomics, proteomics, and metabolomics analyses revealed 17,413 differentially expressed genes (DEGs), 1421 differentially expressed proteins (DEPs), and 229 differentially expressed metabolites (DEMs). Meanwhile, integrative analyses of multi-omics data revealed key proteins involved in response to Cd stress, including POD, PAL, F5H, COMT, and CAD for phenylpropanoid biosynthesis, as well as GAPA, FBP, and FBA for photosynthesis pathways. Additionally, conjoint analyses highlighted that upregulated phenylpropanoid metabolism and photosynthesis alleviated Cd toxicity, playing vital roles in enhancing Cd tolerance in leaves. A conceptual molecular regulatory network of leaves in the response to Cd toxicity was proposed. This comprehensive study will provide detailed molecular-scale insights into the Cd response mechanisms in S. americanum. Full article

Colorectal cancer (CRC) is one of the most prevalent and lethal oncological diseases worldwide, with a concerning rise in incidence, particularly in developing countries. Recent advances in genetic sequencing have revealed that the gut microbiome plays a crucial role in CRC development. Mechanisms such as chronic inflammation, metabolic alterations, and oncogenic pathways have demonstrated that dysbiosis, a disruption of the gut microbiome, is linked to CRC. Associations have been found between tumor progression, treatment resistance, and pathogenic microbes such as Fusobacterium nucleatum and Escherichia coli. A promising approach for CRC prevention and treatment is microbiome manipulation through interventions such as probiotics, prebiotics, fecal microbiota transplantation, and selective antibiotics. This article explores how gut microbiome alterations influence CRC pathogenesis and examines microbiome modulation strategies currently used as adjuncts to traditional treatments. Advances in artificial intelligence, single-cell and spatial transcriptomics, and large-scale initiatives such as the ONCOBIOME Project are paving the way for the identification of microbiome-derived biomarkers for early CRC detection and personalized treatment. Despite promising progress, challenges such as interindividual variability, causal inference, and regulatory hurdles must be addressed. Future integration of microbiome analysis into multi-omics frameworks holds great potential to revolutionize precision oncology in CRC management. Full article