Search Results (1,670)

Cadmium (Cd), a toxic and mobile heavy metal, poses significant risks to agricultural systems due to industrial pollution. Tea plants (Camellia sinensis L.) efficiently absorb and accumulate Cd from soil, leading to contamination in leaves. Chronic consumption of Cd-laden tea can cause severe health issues, including neurological, reproductive, and immunological disorders, as well as increased cancer risk. Despite growing concerns, the molecular mechanisms of Cd stress response in tea plants remain poorly understood. Current research highlights key physiological adaptations, including activation of antioxidant defenses and modulation of secondary metabolite pathways, which influence tea quality. Cd disrupts photosynthesis, induces oxidative stress, and alters the biosynthesis of flavor-related compounds. Several critical genes involved in Cd transport (e.g., CsNRAMP5, CsHMA3, CsZIP1), sequestration (CsPCS1), and stress regulation (CsMYB73, CsWRKY53, CsbHLH001) have been identified, offering insights into molecular responses. This review systematically examines Cd dynamics in the soil-tea plant system, its effects on growth, photosynthesis, and quality, and the physiological and biochemical mechanisms underlying Cd tolerance. By consolidating recent findings on Cd-responsive genes and regulatory pathways, this study provides a theoretical foundation for breeding Cd-resistant tea varieties and ensuring production safety. Furthermore, it identifies future research directions, emphasizing the need for deeper mechanistic insights and practical mitigation strategies. These advancements will contribute to safer tea consumption and sustainable cultivation practices in Cd-contaminated regions. Full article

Personalizing therapy using medical marijuana (MM) is based on understanding the pharmacogenomics (PGx) and drug–drug interactions (DDIs) involved, as well as identifying potential epigenetic risk markers. In this work, the evidence regarding the role of variants in phase I (CYP2C9, CYP2C19, CYP3A4/5) and II (UGT1A9/UGT2B7) genes, transporters (ABCB1), and selected neurobiological factors (AKT1/COMT) in differentiating responses to Δ⁹-tetrahydrocannabinol (THC) and cannabidiol (CBD) has been reviewed. Data indicating enzyme inhibition by CBD and the possibility of phenoconversion were also considered, which highlights the importance of a dynamic interpretation of PGx in the context of current pharmacotherapy. Simultaneously, the results of epigenetic studies (DNA methylation, histone modifications, and ncRNA) in various tissues and developmental windows were summarized, including the reversibility of some signatures in sperm after a period of abstinence and the persistence of imprints in blood. Based on this, practical frameworks for personalization are proposed: the integration of PGx testing, DDI monitoring, and phenotype correction into clinical decision support systems (CDS), supplemented by cautious dose titration and safety monitoring. The culmination is a proposal of tables and diagrams that organize the most important PGx–DDI–epigenetics relationships and facilitate the elimination of content repetition in the text. The paper identifies areas of implementation maturity (e.g., CYP2C9/THC, CBD-CYP2C19/clobazam, AKT1, and acute psychotomimetic effects) and those requiring replication (e.g., multigenic analgesic signals), indicating directions for future research. Full article

Hydrolysable tannins (HTs) are polyphenolic compounds extracted from plants consisting of a sugar core, esterified with phenolic acids, such as gallic or ellagic acid. These phenolic acids are responsible for their well-known antioxidant, anti-tumor, antimicrobial, and anti-inflammatory properties. This study investigated the potential protective role of HTs against bisphenol A (BPA), an environmental pollutant known to have toxic effects. Zebrafish embryos were exposed to BPA at 25.0 µM alone and in combination with HTs at 5.0, 10.0, and 20.0 µgL⁻¹ for 72 h. The results showed that HTs at 20.0 µgL⁻¹ improved hatching and heart rate affected by BPA and reduced the phenotypic alterations caused by BPA. In addition, molecular analysis of genes involved in development showed that the down-regulation of cd63, zhe1, klf4, hand2, sox9b, and gata4 genes in the BPA group were improved with HTs 20.0 µgL⁻¹. Furthermore, HTs were able to reduce the increased lipid content caused by exposure to BPA. These results demonstrate that HTs have a protective effect on the development of zebrafish exposed to BPA, suggesting that they could potentially exert protective effects in response to other environmental stressors. Full article

Background: Individual differences in immune responses to African swine fever virus (ASFV), whether induced by vaccination or natural infection, may be linked to genetic variation in the genes involved in antigen presentation. Methods: A total of nine pigs from the 112-population were selected for RNA-seq analysis. To pinpoint key transcription factors (TFs) regulating gene expression in the lymph nodes, weighted Kendall’s Tau rank correlation analysis was performed to link the TF binding potential with the extent of differential expression of target genes. Results: CD8⁺ T cells expressing a specific epitope of the ASFV p72 protein (ACD8⁺) accounted for 41% of the total CD8⁺ T cells in peripheral blood. A total of 2062 transcripts were identified as differentially expressed across the nine pigs (q-value < 1 × 10⁻⁸). Differential expression levels of the target genes for MECP2, ETS1, ZBTB33, ELK4, and E2F4 were significantly correlated with their TF binding potential (p < 0.05). Six SNPs were identified in the promoter region of ELK4. Analysis of the 112-pig population revealed that SNPs at S.-404A>G and S.-668C>T loci were significantly associated with ACD8⁺ levels (q-value < 0.01). Individuals with the AA genotype at S.-404A>G had significantly higher ACD8⁺ counts compared to those with AG and GG genotypes (q-value < 0.05). At the S.-668C>T locus, ACD8⁺ levels were highest in the CC genotype, followed by CT and TT genotypes, with CC showing notably higher ACD8⁺ counts (q-value < 0.05). Notably, the S.-404A>G site overlaps with potential binding sites for TFs FOXA2, GATAs, and TRPS1, while the S.-668C>T site lies within the binding regions for NR1H3, RARA, VDR, and NR1I3. Conclusion: These mutations may disrupt TFs binding to the ELK4 promoter, potentially reducing ELK4 expression and impairing antigen processing and presentation. Full article

Background: Sarcoidosis is a systemic granulomatous disease of unknown etiology. Pulmonary sarcoidosis with extrapulmonary lesions (EPL) confers poor prognoses. The transcriptomic features of peripheral blood mononuclear cells (PBMCs) could be crucial in sarcoidosis pathogenesis. However, the gene expression characteristics associated with EPL development remain unknown. Methods: Bulk PBMCs were collected from 26 healthy controls and 14 patients with pulmonary sarcoidosis stratified into those with (n = 9) or without (n = 5) EPL. None of the participants were receiving immunosuppressive agents. PBMC transcriptomic analysis was conducted using RNA sequencing. Results: Principal component analysis (PCA) revealed a clear distinction between pulmonary sarcoidosis and healthy control groups, with 227 differentially expressed genes (88 upregulated, 139 downregulated), including upregulated (CLEC7A, GBP5, JAK2, IL15, IL1B, CXCL8, and CXCL10) and downregulated (TNFRSF13C, CD40LG, CD28, and ID3) genes in pulmonary sarcoidosis group. Enrichment analysis revealed upregulated immunological pathways related to granuloma formation in pulmonary sarcoidosis PBMCs, including T helper 17 and tumor necrosis factor-alpha signaling pathways, IL-1B, IL-6, and IL-17 production, and response to external stimuli. Furthermore, patients with and without EPL showed 206 differentially expressed genes (131 upregulated, 75 downregulated), including upregulated (IFNG and IFNLR1) and downregulated (SOCS3, MMP9, and CXCL10) genes. Gene ontology (GO) analysis revealed that interleukin 6 (IL-6) and IL-23 production were upregulated in patients with EPL. Conclusions: These findings elucidate the mechanisms underlying granuloma formation in sarcoidosis and demonstrate the differential transcriptomic features of PBMCs in patients with and without EPL. The upregulation of IFNG and IFNLR1 may be related to EPL development and could serve as potential therapeutic targets for sarcoidosis. Full article

The exon junction complex (EJC) is a central mediator of post-transcriptional regulation in eukaryotes. A comprehensive, systematic analysis of EJC core genes has been lacking in Phyllostachys edulis (P. edulis). Here, we identified 147 EJC core genes across 17 plant species spanning the major green plant lineages. Phylogenetic analyses supported each family as a monophyletic clade consistent with established taxonomic relationships. Synteny analyses indicated that segmental duplication is the principal driver of EJC core gene expansion in P. edulis (Moso bamboo). Transcriptome profiling further showed that nearly all PedEJCs were engaged during rapid shoot growth, with PedY14b-D, PedY14c-D, and PedY14d-C displaying the most pronounced expression changes. During shoots’ post-harvest senescence process, PedEIF4A3s, PedY14s, and PedMAGOs were progressively downregulated, whereas PedBTZs were upregulated, indicating distinct module-level responses among EJC subunits. Only a small subset of PedEJCs responds to phytohormones and abiotic stresses. Furthermore, cis-regulatory element composition in promoter region likely shapes PedEJCs transcriptional regulation. Collectively, these findings lay the groundwork for in-depth functional dissection of PedEJCs in Moso bamboo. Full article

Child maltreatment (MALT) is a devastating form of early-life adversity (ELA) and a primary risk for mental and physical illness. It is difficult to disentangle postnatal caregiving effects from heritable factors. Here we investigated the long-term effects of maternal care using a cross-fostering design to control for biological/heritable factors on immune function and inflammation during adolescence in a translational and naturalistic macaque model of MALT. We studied the impact of MALT on the immunophenotype of peripheral blood mononuclear cells (PBMCs) and assessed glucocorticoid receptor expression and function during adolescence. MALT was associated with elevated expression of NR3C1, the gene that encodes for the glucocorticoid receptor, in PBMCs. Glucocorticoid receptor function was not altered by MALT when examined for response to dexamethasone (DEX). In addition, MALT led to a reduction in the percentage of naïve CD4⁺ T cells and an increase in the percentage of central memory (Tcm) CD4⁺ T cells. These results suggest that MALT-exposed adolescents show residual effects of MALT on CD4⁺ T cells and increased expression of NR3C1 without demonstration of increased function of the glucocorticoid receptor. Taken together, these results suggest that ELA has enduring implications for cellular glucocorticoid receptor biology and CD4⁺ T cells. Full article

Reservoirs are hotspots for the coupling of nutrients and heavy metals, and they substantially modify the compositions and spatiotemporal distributions of microorganisms in fluvial systems. However, relatively few studies have been performed that investigate the microbial mechanisms driving interactions among heavy metals and nutrients in reservoirs. The Goupitan Reservoir, a seasonal stratified reservoir located within the Wujiang River catchment, was chosen as the research subject. The temporal and spatial variations in heavy metals and nutrients, and the metagenomic composition of the reservoir water were analyzed in January, April, July, and October 2019. The results revealed that As, Ni, Co, and Mn were derived primarily from mine wastewater, whereas Zn, Pb, Cd, and Cr were related to domestic and agricultural wastewater discharge. The study area was dominated by Proteobacteria, Actinobacteria, Cyanobacteria, and Bacteroidetes, with the proportion of dominant phyla reaching 90%. Decreases in the dissolved oxygen (DO) concentration and pH in the bottom water during July and October were conducive to increases in the abundance of the anaerobic bacterial groups Planctomycetes and Acidobacteria. The functional genes norBC and nosZ associated with denitrification (DNF), the key gene nrfAH involved in the dissimilatory nitrate reduction to ammonium (DNRA) process, the functional genes aprAB and dsrAB responsible for sulfate reduction/sulfide oxidation, as well as the thiosulfate oxidation complex enzyme system SOX, all exhibit high abundance in hypoxic water bodies and peak in the redoxcline, highlighting the significance of related nitrogen (N) and sulfur (S) metabolic processes. In addition, the concentrations of heavy metals significantly affected the spatial differentiation of the planktonic bacterial community structure, with Mn, Co, Fe, Ni, As, and Cu making relatively high individual contributions (p < 0.01). This study is important for elucidating the sources and microbiological mechanisms influencing heavy metals and nutrients in seasonally stratified subtropical reservoirs. Full article

Background/Objectives: Soft tissue sarcomas (STS) remain a therapeutic challenge due to their limited response to radiation and conventional chemotherapies. While recent advances in immunotherapy have improved outcomes in several cancers, these strategies have been largely disappointing in STS patients. Naturally occurring STS in dogs have been suggested as a spontaneous, immunocompetent model of human STS, but further characterization of its tumor immune microenvironment is needed to validate its relevance. This study aimed to identify the shared immune-related components of canine and human STS and to determine how these factors influence the tumor biology, progression, and prognosis. Results: Data from 75 dogs with STS was analyzed. In addition, we characterized the tumor immune microenvironment using immunohistochemistry and compared gene expression between canine and human STS. Progression-free survival and time to metastasis was significantly longer in castrated males in comparison to females. In addition, dogs with appendicular tumors had better progression- and recurrence-free survival, whereas tumor recurrence following surgical excision was associated with a shorter time to metastasis. Immunohistochemistry revealed infiltration of CD204⁺ cells in most of the tumors examined, and disease-free intervals were shorter in dogs with tumors exhibiting FOXP3⁺ cell infiltration. Gene expression profiling demonstrated similarities between canine STS and human undifferentiated pleomorphic sarcomas, with MYC dysregulation emerging as a poor prognostic indicator for dogs. Conclusions: The comparative analysis between the human and canine STS microenvironment offers a valuable insight into the clinical behavior and immune landscape of canine STS, underscoring its potential as a relevant preclinical model for the translation and development of future immunotherapies. Full article

Despite advances in blood-based screening tests for colorectal cancer (CRC), most existing assays focus on DNA-based biomarkers, which predominantly reflect tumor-derived fragments released at later disease stages. In contrast, whole-blood transcriptomic profiling can capture systemic immune responses and tumor–host interactions, offering a complementary strategy for earlier disease detection. However, clinically validated whole-blood transcriptomic signatures remain limited. Here, we investigated a whole-blood RNA-based biomarker discovery strategy by integrating multi-cohort transcriptomic resources. Public GEO datasets (GSE164191 and GSE11545) were harmonized and analyzed, yielding 956 differentially expressed genes (DEGs). Multi-layer biological filtering incorporating PPI networks, transcription factors, CRC-related GWAS variants, whole-blood eQTL signals, DigSeE, and CoReCG disease associations refined these to 375 high-confidence transcripts (WB-PADs). In parallel, RNA-seq analysis of a Korean cohort (10 CRC vs. 10 controls) identified 217 DEGs (WB-K). Cross-dataset convergence highlighted seven overlapping transcripts, and five candidates (DLG5, CD177, SH2D1B, NQO2, and KRT73) were selected for validation. RT-qPCR in an independent clinical cohort (106 CRC and 123 healthy controls) confirmed four transcripts with significant discriminatory ability. A multivariable logistic regression model derived from the five-transcript signature achieved an AUC of 0.952 (95% CI 0.884–1.000), with sensitivities of 0.889 and 0.667 at fixed specificities of 90% and 95%, respectively, demonstrating strong applicability for screening-relevant thresholds. Notably, the model retained high accuracy in early-stage CRC (Stage I–II: AUC 0.929, 95% CI 0.868–0.989). Overall, this study provides a robust analytic framework for reproducible whole-blood RNA biomarker discovery and establishes a multi-gene signature with promising translational potential for minimally invasive and early CRC detection. Full article

Background: Exercise is a promising non-pharmacological intervention for cocaine addiction but molecular mechanisms of exercise-related genes in addiction remain unclear. This study aimed to identify exercise-related signature genes for cocaine addiction and to assess the potential causal relationship between exercise and cocaine addiction using two-sample Mendelian randomization (MR) analysis. Methods: Midbrain transcriptomic data were analyzed for differentially expressed genes (DEGs) and intersected with exercise-related genes. Functional enrichment, protein-protein interaction (PPI) and immune infiltration analyses explored their roles while signature genes were screened via LASSO/Random Forest and validated by ROC curves. GSEA explored pathways and MR confirmed exercise’s causal effect. Results: A total of 244 DEGs were identified, including 27 exercise-related, and six signature genes (CALM3, CCL2, CD44, CLIC1, JUN, VCAM1) showed AUC values between 0.714 and 0.868 in distinguishing cocaine-addicted individuals from controls. Functional analyses revealed enrichment in immune-inflammatory pathways, metabolic processes and neuro-immune interactions and immune infiltration analysis showed cocaine addicts had elevated pro-inflammatory cells, reduced regulatory cells and signature genes correlated with immune dysregulations. MR analysis suggested a statistically significant protective association between genetically proxied higher levels of exercise and cocaine addiction risk (p < 0.05). Conclusions: These six genes may be potential biomarkers and therapeutic targets, and exercise may protect against cocaine addiction by regulating immune-inflammatory responses, metabolic pathways and neuroplasticity, although further validation in larger, independent cohorts and experimental models is required. Full article

Background: Rabies virus (RABV) causes approximately 59,000 human deaths annually. Current pre- and post-exposure vaccination relies on inactivated vaccines (INVs) with limited yield and immunogenicity. We engineered a dual-cationic LNP-based nucleocapsid-like nanostructure (NLS) that co-encapsulates RABV G-mRNA and recombinant RABV-N to engage MHC-I/II pathways and enhance protection. Methods: A pVAX-RABV-G plasmid containing 5′/3′UTRs, Kozak, and poly(A) was transcribed in vitro. RABV-N with an N-terminal 6× His tag was expressed in E. coli BL21(DE3) and purified by Ni-Sepharose affinity chromatography. Dual-cationic LNPs (DHA, DOTAP Cl, mPEG-DTA2K, DOPC) were formulated by microfluidics at a 4:1 (G-mRNA:RABV-N) mass ratio. Vaccine quality was assessed by encapsulation efficiency, DLS, PDI, zeta potential, and TEM. Mice received empty LNPs, INV, G-mRNA, or NLS under varied schedules and doses. ELISA measured RABV-G/N-IgG; RFFIT determined neutralizing antibody (nAb) titers; ELISPOT quantified CTL response; qPCR assessed T-cell activation genes. On day 35 after the first immunization of vaccines, mice were challenged intramuscularly with 25 LD₅₀ of CVS-24. Results: G-mRNA purity was >95% and drove strong RABV-G expression in 293T cells. Purified RABV-N was approximately 52 kDa, >90% pure, and reactive to anti-His and anti-N antibodies. NLS achieved >95% encapsulation, a diameter of 136.9 nm, PDI 0.09, and a +18.7 mV zeta potential. A single dose yielded approximately 10 IU mL⁻¹ nAb by day 7; two doses peaked at approximately 1000 IU mL⁻¹. Mice showed 100% survival and no viral rebound in brain, spinal cord, and sciatic nerve. NLS induced stronger MHC-I/II-linked cellular immunity and higher RABV G/N-specific IFN-γ spot frequencies than G-mRNA or INV. Conclusions: The dual-antigen NLS vaccine co-delivering G-mRNA and RABV-N via dual-cationic LNPs robustly activates MHC-I/II, rapidly generates high-titer nAb (≥10 IU mL⁻¹ within 1 week), and sustains potent CD8⁺ CTL and CD4⁺ Th responses. A two-dose regimen (days 0 and 21) conferred complete protection, supporting the NLS platform as a next-generation rabies vaccine candidate. Full article

Previous studies have reported that Enterovirus A71 (EV-A71) infection could activate STING-related signaling pathways in vitro, but the role of STING in EV-A71 infection in vivo and the associated immune regulatory mechanisms remain unclear. Here, we used the STING-specific agonist diABZI to activate STING and STING-knockout mice to jointly study the role and mechanism of regulating STING on EV-A71 infection in vivo. The results showed that activating STING could inhibit the in vivo replication of EV-A71, alleviate clinical symptoms in infected mice, and increase the survival rate. Conversely, STING knockout significantly promoted viral replication in vivo and increased the lethality and severity of EV-A71 infection. Mechanistic studies further revealed that STING activation exerts its antiviral effects by stimulating interferon signaling pathways, upregulating the expression of interferon-stimulated genes (ISGs). Additionally, STING activation also modulated the serum cytokine response profile. Moreover, STING activation drove the expansion of diverse immune cell populations, including T cells, natural killer (NK) cells and myeloid cells. In contrast, STING knockout not only reduced the proportion of thymic T cells and impeded T cell developmental progression from double-positive (DP) to single-positive (SP) stages, but also impaired the effector functions of CD8+ T cells and NK cells during viral infection. In summary, this study demonstrates that STING activation effectively suppresses EV-A71 replication and mitigates infection symptoms by modulating immune and inflammatory responses. These findings provide a foundational framework for understanding how STING coordinates antiviral immunity and inform future investigations into STING-targeted therapies for viral infections. Full article

Pleomorphic rhabdomyosarcoma is a rare soft-tissue tumor that occupies an uncertain middle ground between rhabdomyosarcoma and undifferentiated pleomorphic sarcoma. With its relative rarity, aggressiveness, and lack of detailed characterization, it presents a challenging task for therapeutic treatment. In this case study, we use single-cell transcriptomics to investigate the heterogeneous landscape of pRMS and the tumor microenvironment. We demonstrate that the tumor populations in pRMS have a clear division into myogenic and non-myogenic clusters, with the non-myogenic clusters having more numerous communication links with the immune populations. All pRMS tumor clusters use the MIF-CD74 pathway to suppress the immune response, while APP, PTN, and CXCL12 signaling are employed predominantly by the non-myogenic tumor clusters. The cytotoxic T cells in pRMS bear markers of exhaustion (LAG3, HAVCR2, EOMES), and the macrophages express myeloid checkpoint-related genes (SIGLEC1, SIRPA, CSF1R, HAVCR2). This transcriptomic data suggests that targeting MIF and APP signaling in pRMS may have therapeutic potential; however, studies on multiple-patient cohorts, protein verification, and in vitro and in vivo validation are still needed for clinical actionability. Full article

Pearl millet (Pennisetum glaucum (L.) R. Br.) is widely recognized for its high tolerance to marginal environments. However, a systematic understanding of its organ-specific transcriptional adaptation mechanisms under individually applied abiotic stresses remains limited. In this study, we conducted a comparative transcriptome analysis of leaves and roots subjected to six distinct stress treatments (Ion stress: CdCl₂/NaCl; Water stress: PEG/Waterlogging; Temperature stress: Heat/Cold), revealing fundamental differences in defense strategies between the two organs. Across all stresses, leaves showed more differentially expressed genes (DEGs) (213) than roots (118), yet the transcriptional responses were largely stress-specific. Carotenoid biosynthesis was the only pathway co-activated in leaves under both water and temperature stress. In contrast, roots exhibited a robust and conserved strategy, with significant enrichment of phenylpropanoid and flavonoid biosynthesis pathways consistently observed across all six stresses. This cross-stress synergistic response involved more than 300 enzyme genes in roots, including key enzymes such as peroxidases (128) and shikimate O-hydroxycinnamoyltransferases (33), which collectively contribute to root-specific cell wall reinforcement and oxidative stress defense. Interaction network analysis further revealed that the MYB transcription factor family serves as a central regulatory hub in root stress responses, with key nodes PMF4G04191 and PMF5G01787 frequently interacting with pathway genes under all stress conditions. This study elucidates the organ-specific and cross-stress defense mechanisms in pearl millet, providing valuable transcriptomic resources and candidate genes for molecular-assisted breeding of multi-stress-tolerant varieties. Full article