Search Results (18,548)

While previous studies have extensively demonstrated that summer heat stress (HS) impairs oocyte quality via follicular granulosa cell (GC) mediation, the molecular mechanisms underlying HS-induced GC-mediated oocyte damage—particularly at the multi-omics level—remain poorly understood. This study integrated metabolomic and transcriptomic analyses of GCs from gilts under seasonal thermal stress (winter CON vs. summer HS) to elucidate GC-mediated regulatory networks affecting oocyte quality. Non-targeted metabolomics identified 45 differentially accumulated metabolites (DAMs, p < 0.05), with 69% being lipids/lipid-like molecules enriched in pathways such as glycerophospholipid metabolism, choline metabolism, linoleic acid metabolism, the adipocytokine signaling pathway, and the sphingolipid signaling pathway. Parallel transcriptomics revealed 9085 differentially expressed genes (DEGs, Padj < 0.05), ‌of which the predominant genes were associated with lipid metabolism, hormone synthesis, and cellular senescence pathways. Cross-omics integration highlighted significant correlations between DAMs and DEGs, particularly for lysoPC(20:4) and 1-hexadecyl-2-eicosatrienoyl-sn-glycero-3-phosphocholine, which showed co-regulation with 69 and 48 genes, respectively. Notably, candidate genes like TMEM94, SLIT3, DACT3, and CEBPD, were identified as key regulators of GCs metabolic reprogramming. This study demonstrates for the first time that in vivo HS compromises oocyte developmental competence by disrupting the GC metabolic activities, particularly through lipid metabolism and associated pathways. The identified metabolic signatures and regulatory genes offer mechanistic insights into seasonal infertility and potential biomarkers for thermo-protective strategies in swine reproduction. Full article

Pierce’s disease (PD), caused by the xylem-limited bacterium Xylella fastidiosa, poses a significant threat to global grapevine (Vitis vinifera) production. Despite its economic importance, the dynamic molecular mechanisms underlying grapevine responses to infection remain poorly understood. This study re-analyzed the publicly available RNA-seq dataset GSE152164 to characterize phase-dependent transcriptional reprogramming during PD progression. Differential expression analysis using DESeq2 identified 1093 differentially expressed genes (DEGs) during the early infection phase (Phase I) and 136 in the intermediate phase (Phase II), indicating a strong early defense response followed by transcriptional downregulation as symptoms progressed. Comparative analysis distinguished 991 Phase-I-specific and 34 Phase-II-specific genes, along with 167 infection-specific temporal DEGs, underscoring a coordinated early immune response and subsequent metabolic repression. Protein–protein interaction network analysis identified 21 high-confidence hub genes, including chitinase (VIT_16s0050g02220), thaumatin-like protein (VIT_02s0025g04250), and EDS1 (VIT_17s0000g07560), which represent core regulators of defense and stress adaptation pathways. Collectively, this study elucidates the transcriptional dynamics underlying V. vinifera responses to X. fastidiosa and provides valuable insights for developing disease-resistant cultivars to mitigate Pierce’s disease. Full article

Shewanella putrefaciens is a significant bacterial pathogen causing high mortality in farmed largemouth bass (Micropterus salmoides). This study investigated the molecular immune responses in its primary target organs, the liver and spleen, via transcriptomic profiling at 24 h post-infection. We identified 458 significantly differentially expressed genes (DEGs) in the liver and 1405 in the spleen. Gene Ontology enrichment analysis revealed organ-specific immune strategies: the liver response was characterized by type I interferon signaling pathway, whereas the spleen response centered on the regulation of innate immune response. Furthermore, Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that fatty acid metabolism and cytokine-cytokine receptor interaction were significantly enriched in the liver. In contrast, the C-type lectin receptor signaling pathway and cytokine-cytokine receptor interaction were the most prominent in the spleen. Several key DEGs (e.g., stat1a, rsad2, pglyrp5, pglyrp6, acaca, stat2, lepb) associated with immune response, metabolic adaptation, and cellular stress were identified, suggesting a coordinated host mechanism involving pathogen recognition, immunomodulation, and tissue repair. These results provide crucial insights into the immunomodulatory processes in largemouth bass against S. putrefaciens infection. Full article

This study established an in vitro model to investigate peri- and post-implantation embryo development under heat shock conditions. In Experiment 1, we compared the gene expression profiles of the three germ layers in in vivo mouse embryos with those of mEBs derived from mouse embryonic stem cells. mEBs (Days 1–5) closely resembled developing E5.5–E6.5 embryos, expressing key germ layer markers: nestin (ectoderm), flk-1 (mesoderm), and ttr (endoderm). In Experiment 2, mEBs were randomly allocated to one of the following treatments: a control group (37 °C) or a heat shock group (39 °C or 41 °C) for 12 h or 24 h. Timing of germ layer marker expression, including ttr, was delayed by 1–2 days in the heat-shocked groups compared with the control group. Morphological analysis of mEBs revealed that the peripheral cell layer exhibited signs of disassembly or degeneration and became increasingly apoptotic under heat shock conditions. Additionally, these mEBs showed increased expression of heat shock proteins 70 and 72 in response to elevated temperatures and prolonged heat shock durations. Mouse EBs closely mimic in vivo-developing embryos in their germ layer marker expression profiles. In vitro heat shock delays germ layer marker gene expression and induces heat shock protein 72 expression in mEBs. Full article

Long non-coding RNAs (lncRNAs) are crucial regulators in eukaryotic organisms, yet their roles in filamentous fungi, particularly in environmental adaptation and metabolic changes, remain largely unexplored. Here, we investigated the roles of lncRNAs in salt stress response, morphological differentiation, and metabolic regulation in Eurotium cristatum. Using strand-specific RNA sequencing, we identified lncRNAs in sexual and asexual mycelia of E. cristatum and analyzed their expression profiles. We identified 203 lncRNAs, with 120 significantly differentially expressed (FDR < 0.01; |log₂ (fold change)| ≥ 1) under salt stress, including 57 upregulated and 63 downregulated in the asexual morph compared to the sexual morph. These lncRNAs correlated with physiological indicators like mycelial biomass, polysaccharide content, and melanin production. Target gene prediction and functional enrichment analysis revealed that these lncRNAs influenced morphogenesis and secondary metabolite synthesis in E. cristatum by regulating pathways including carbohydrate metabolism, peroxisome function, and protein ubiquitination. The lncRNA MSTRG.10627.3 showed the highest upregulation (log₂FC = 10.53, FDR < 1 × 10⁻¹⁰⁵), while MSTRG.3124.1 was significantly downregulated in the sexual morph (log₂FC = −4.94, FDR < 1 × 10⁻⁸⁸). A regulatory network of lncRNAs involved in salt stress responses was constructed, providing insights into fungal environmental adaptation mechanisms and potential targets for industrial strain improvement. Full article

Ryanodine receptor 1-related myopathies (RYR1-RM) are caused by RYR1 gene variants and comprise a wide spectrum of histopathological manifestations. Here, we focus on patients carrying RYR1 variants and muscle histopathology consistent with central core disease (CCD) or multi-minicore disease (MmD). RNA-sequencing analyses of skeletal muscle biopsies obtained from both CCD and MmD patients and from healthy controls were performed to better understand the molecular pathways activated by RYR1 variants. Our analyses revealed that, beyond the well-established role of RYR1 in calcium homeostasis, broader cellular pathways are implicated. In CCD, differentially expressed genes were enriched for pathways related to oxidative stress response, SMAD signalling, and apoptosis, consistent with the role of intracellular calcium dysregulation in promoting mitochondrial dysfunction and cell death. In contrast, MmD patients exhibited enrichment of pathways related to immune activation. This was corroborated by the upregulation of GTPase-regulating genes and the down-regulation of transcriptional repressors such as ZFP36 and ATN1. When considering all RYR1-RM patients collectively, Wnt signalling, immune-related pathways, and oxidative phosphorylation emerged as shared enriched pathways, indicating possible convergent mechanisms across histopathological phenotypes. Our study suggests that complex gene regulation driven by RYR1 variants may be a unifying feature in CCD and MmD, offering new insight into potential therapeutic targets. Full article

The non-medicinal parts of Polygonatum sibiricum (P. sibiricum) and Gentiana scabra (G. scabra) are abundant but underutilized in Liaoning Province, China, creating an environmental burden. Solid-state fermentation (SSF) offers a strategy to enhance their bioactivity, yet triple microbial co-fermentation remains underexplored. This study applied a triple microbiota—featuring Aspergillus niger (A. niger), Bacillus subtilis (B. subtilis), and Saccharomyces cerevisiae (S. cerevisiae)—to ferment the stems and leaves of both plants. Antibacterial activity against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) was assessed via the Kirby–Bauer test, while Liquid Chromatography–Tandem Mass Spectrometry (LC–MS/MS)-based non-targeted metabolomics identified differential metabolites and enriched pathways. Co-fermentation significantly increased the inhibition zones to 17.4 ± 0.8 mm for E. coli and 17.7 ± 0.3 mm for S. aureus, a 1.8-fold improvement over the unfermented controls (p < 0.001). Among the 2976 metabolites detected, 1236 were differentially expressed, with Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis highlighting activation of aminoacyl-tRNA biosynthesis, ABC transporter, and phenylalanine–tyrosine–tryptophan pathways. Differential abundance analysis indicated that the aminoacyl-tRNA pathway (DA score > 0.9) is critical for antimicrobial peptide synthesis. Phenylalanine derivatives, including 4-hydroxybenzaldehyde, which increased over 430-fold (Log₂ FC = 8.78), contributed to membrane-disruptive antibacterial effects. Mechanistically, A. niger hydrolyzes cellulose to release precursors, B. subtilis synthesizes antimicrobial peptides, and S. cerevisiae enhances metabolite solubility and excretion, collectively boosting antibacterial activity by 80%, suggesting a potent synergistic interaction among the triple microbiota. This cascade mechanism provides a scalable approach for valorizing approximately 55 million tons of traditional Chinese medicine (TCM) waste annually. Full article

Background/Objectives: Copper-based wood preservatives are widely used to protect timber from fungal decay; however, the emergence of copper-tolerant fungi reduces their long-term effectiveness. This study aimed to elucidate the molecular mechanisms underlying copper resistance in Saccharomyces cerevisiae through adaptive evolution and transcriptomic profiling. Methods: A copper-resistant mutant was developed via stepwise exposure to CuSO₄·5H₂O, and its gene expression profile was compared to the wild-type strain under copper stress and non-stress conditions using Affymetrix GeneChip Yeast Genome 2.0 arrays. Results: Differential expression analysis revealed upregulation of key genes involved in copper transport (ATX1 and CTR1), the oxidative stress response (RCK1 and SOD1), and metal ion detoxification (FRE3 and SLF1). Functional enrichment analysis highlighted the significant activation of pathways related to protein folding, mitochondrial function, and transcriptional regulation. Conclusions: These findings provide insights into the adaptive strategies employed by S. cerevisiae to tolerate copper stress and suggest potential gene targets for the development of more effective wood preservatives capable of mitigating fungal resistance. Full article

Killer-cell immunoglobulin-like receptors (KIRs) play a crucial role in the cytotoxic activity of natural killer (NK) cells, encompassing both inhibitory and activating types. A higher ratio of cytotoxic to inhibitory receptors may harm successful pregnancies by disrupting the uterine environment. Ongoing debates surround the impact of KIR gene variations on recurrent pregnancy loss (RPL) and infertility across populations. This study aimed to explore KIR gene polymorphisms in RPL and infertility among the Venezuelan admixed population. The Venezuelan population exhibits a genetic mix of Caucasian, African, and local Amerindian ancestry, distinguishing it from other Latin American admixed populations. This study included 100 controls and 86 patients: 73 women with idiopathic RPL (53 primary and 20 secondary) and 13 infertile patients (4 primary and 9 secondary). The frequency of activating receptors KIR2DS2 and KIR2DS3 was significantly lower (p < 0.05) in the whole patient group compared to controls. However, when analyzing the haplotypes and genotypes, the significance between patients and controls was lost. When comparing RPL and infertile patients, KIR2DS2, KIR2DL3, 2DL5, and 3DL1 were significantly less frequent in infertile women. In infertile women, KIR2DS3 frequency was increased compared to controls and RPL. The results suggest that the frequency of inhibitory receptors may differentiate patients with RPL and infertility. Further studies should ascertain the expression and function of KIRs in uterine NK cells in patients with RPL and infertility. Full article

Alzheimer’s disease (AD) is the leading cause of dementia and is often prefaced by mild cognitive impairment (MCI). Detection of AD-related changes via blood-based biomarkers would enable critical therapeutic interventions early in disease progression. Neuronal enriched extracellular vesicle (NEEV) miRNAs regulate peripheral genes as a response to early AD brain changes and hence may have biomarker potential. Plasma NEEVs were captured from plasma samples of Mexican Americans (MAs) and Non-Hispanic Whites (NHWs) using an antibody against the neuronal surface marker CD171. miRNAs isolated from NEEVs were sequenced and analyzed using miRDeep2/DEseq2 and QIAGEN RNA-seq portal for differential expression between cognitively impaired (CI) and cognitively unimpaired controls. hsa-miR-122-5p was significantly underrepresented in the CI group in both MAs and NHWs compared to the healthy control. Other population-specific miRNAs (MAs: hsa-miR-26a-5p, hsa-let-7f-5p, and hsa-miR-139-5p, NHWs: hsa-miR-133a-3p, hsa-miR-125b-5p, and hsa-miR-100-5p) identified may have biomarker potential in AD precision medicine. Some of these differentially expressed miRNAs were associated with key AD-related comorbidities such as APOE genotype, age, and metabolic burden and were predicted to target genes within NF-κB -regulated inflammatory pathways. Together, these findings suggest that dysregulated miRNA networks may serve as a mechanistic link between comorbidity burden and AD-related neuroinflammation and neurodegeneration. Full article

Potato virus Y (PVY) is a major threat to global potato production, causing yield losses of nearly 90%. This emphasizes the urgent need to explore the genetic factors underlying resistance mechanisms. Developments in transcriptomics and plant genomes have shed significant light on the genetic underpinnings of PVY resistance. This review summarizes current knowledge on PVY biology and structure, its impacts, key hypersensitive resistance (HR) and extreme resistance (ER) genes and their associated molecular markers, genomic strategies for discovering resistance genes and improving resistance breeding, and challenges. Genetic resistance is a key strategy for controlling PVY, primarily through HR and ER, which are governed by specific genes: the Ny gene for HR and the Ry gene for ER. Our understanding of the molecular mechanisms underlying this resistance has increased significantly due to the advancement of high-throughput sequencing methods, including RNA and whole-genome sequencing. More than 10 PVY resistance genes have been identified in potato, including well-characterized ER genes such as Ry_sto, Ry-f_sto, Ry_adg, Ry_chc, and Ry(o)_phu, as well as HR genes such as Ny-1, Ny-2, and Ny-Smira, which are discussed in this review. Transcriptomic analyses have revealed the involvement of small RNAs and other regulatory molecules in modulating resistance responses. Transcriptomic studies have also identified 6071 differentially expressed genes (DEGs) in potato cultivars infected with PVY, highlighting strong defense responses influenced by strain, cultivar, and environmental conditions. The identification of these resistance genes facilitates the development of PVY-resistant cultivars through marker-assisted selection and gene pyramiding, offering significant opportunities to enhance PVY management and promote sustainable potato production under the challenges posed by climate change. Full article

Background/Objectives: Galectins contribute to the pathogenesis of osteoarthritis (OA) by amplifying inflammatory and catabolic signaling, yet targeted therapeutic approaches remain limited. Three Dimensional (3D) models offer a promising platform to study human OA pathophysiology and evaluate novel interventions. Methods: We established 3D pellet cultures derived from human OA chondrocytes to investigate galectin-induced extracellular matrix (ECM) remodeling and the chondroprotective potential of phytochemicals. OA pellets were stimulated with individual galectins (Gal-1, -3, -4, -8) or a Gal-1/-3/-8 mixture, followed by co-treatment with Brazilin, Diacerein, Quercetin, Resveratrol, or Avocado-Soybean Unsaponifiables (ASU). Morphological, histological, biochemical, and gene expression analyses were performed to assess tissue integrity and molecular responses. Results: Galectin treatment induced pronounced pellet shrinkage, matrix depletion, and upregulation of matrix-degrading enzymes (MMP-1, MMP-3, MMP-13, ADAMTS-4), while suppressing matrix synthesis markers (COL2A1, COL1A1), highlighting their cooperative catabolic effects. Co-treatment with phytochemicals conferred differential protection: Brazilin and Diacerein most consistently preserved pellet size, reduced matrix-degrading gene expression, and attenuated pro-MMP-13 secretion. Resveratrol restored histological matrix density but failed to suppress pro-MMP-13 secretion. Notably, no phytochemical fully restored COL2A1 expression under galectin-induced stress. Conclusions: Our study identifies Brazilin, Diacerein, and Resveratrol as promising modulators of galectin-driven cartilage degeneration and demonstrates the translational potential of patient-derived chondrogenic pellets as a human-relevant platform for preclinical drug evaluation in OA. The 3D culture effectively recapitulates key aspects of OA pathophysiology and offers a robust system to advance therapeutic discovery targeting ECM remodeling. Full article

This study systematically explored the regulatory mechanisms of uterine function across four reproductive stages: sexual maturity sow (SMS), low-yield sow (LYS), high-yield sow (HYS), and culled sow (CS) in Large White (LW) pigs through integrated transcriptomic, proteomic, and metabolomic analyses. Twelve healthy LW sows were selected, and uterine tissues were collected for multi-omics detection. Combined with bioinformatics analysis, molecular regulatory networks were constructed. Results showed that transcriptomics identified 12 types of alternative splicing and 1243 novel genes, which were enriched in energy metabolism and signal transduction pathways. Proteomics revealed 430 differentially co-expressed proteins, indicating high protein synthesis activity in the SMS stage and extracellular inflammatory characteristics in the CS stage. Metabolomics detected numerous differential metabolites, among which XTP and DHA ethyl ester were associated with high fecundity and aging, respectively. Integrated multi-omics analysis identified hub genes such as PLA2G4A, which influence reproductive performance by regulating inflammatory and metabolic balance, and clarified stage-specific “gene–protein–metabolite” modules. This study provides a molecular map for understanding dynamic changes in uterine function in Large White pigs and offers a theoretical basis for optimizing reproductive lifespan and breeding strategies. Full article

Background: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder with unclear pathogenic mechanisms. Dysregulated zinc metabolism contributes to AD pathology. This study aimed to identify zinc metabolism-related hub genes to provide potential biomarkers and therapeutic targets for AD. Methods: We performed an integrative analysis of multiple transcriptomic datasets from AD patients and normal controls. Differentially expressed genes and weighted gene co-expression network analysis (WGCNA) were combined to identify hub genes. We then conducted Gene Set Enrichment Analysis (GSEA), immune cell infiltration analysis (CIBERSORT), and receiver operating characteristic (ROC) curve analysis to assess the hub gene’s biological function, immune context, and diagnostic performance. Drug-gene interactions were predicted using the DrugBank database. Results: We identified a single key zinc transporter–related hub gene, SLC30A3, which was significantly downregulated in AD and demonstrated potential diagnostic value (AUC 0.70–0.80). Lower SLC30A3 expression was strongly associated with impaired synaptic plasticity (long-term potentiation, long-term depression, calcium signaling pathway, and axon guidance), mitochondrial dysfunction (the citrate cycle and oxidative phosphorylation), and pathways common to major neurodegenerative diseases (Parkinson’s disease, AD, Huntington’s disease, and amyotrophic lateral sclerosis). Furthermore, SLC30A3 expression correlated with specific immune infiltrates, particularly the microglia-related chemokine CX3CL1. Zinc chloride and zinc sulfate were identified as potential pharmacological modulators. Conclusions: Our study systematically identifies SLC30A3 as a novel biomarker in AD, linking zinc dyshomeostasis to synaptic failure, metabolic impairment, and neuroimmune dysregulation. These findings offer a new basis for developing targeted diagnostic and therapeutic strategies for AD. Full article

Leishmaniasis and Chagas disease, caused by Leishmania spp. and Trypanosoma cruzi, are neglected tropical diseases with significant global health burden, particularly in resource-limited regions. Despite their impact, diagnosis and treatment remain challenging due to limited diagnostic tools and the toxicity of available therapies. Our objective is to propose the incorporation of markers for the diagnosis of leishmaniasis and Chagas disease using ncRNA. This narrative review evaluates studies published between 2010 and 2024 (PubMed, Scopus, Google Scholar) using the SANRA scale to assess the potential of non-coding RNAs (ncRNAs) as biomarkers for these infections. Both parasites release small RNAs via extracellular vesicles that modulate host–pathogen interactions and gene expression. Although RNA interference machinery is absent in T. cruzi and most Leishmania species, it persists in early-diverging lineages. In leishmaniasis, distinct miRNA expression profiles—including miR-155-5p, miR-5011-5p, miR-6785-5p, and miR-361-3p—demonstrate high diagnostic accuracy for detecting infection (AUC up to 1.0). Serum long ncRNAs such as MALAT1 and NUTM2A-AS1 show potential diagnostic value, though clinical validation remains pending. For Chagas disease, the available evidence on ncRNAs primarily addresses the diagnosis of clinical manifestations rather than initial infection. Host miRNAs, including miR-21, miR-145, miR-146a/b, and miR-19a-3p, correlate with cardiac involvement, immune dysregulation, and inflammation during chronic T. cruzi infection. Circulating miRNAs exhibit modest sensitivity (57–67%) and specificity (57–80%) for diagnosing chronic Chagas cardiomyopathy, indicating their utility in assessing disease progression and organ damage rather than detecting early infection. This review distinguishes between ncRNAs that diagnose infection and those that evaluate disease severity or organ involvement. Altered ncRNA expression profiles represent promising biomarkers for species differentiation, treatment monitoring, and assessing cardiac complications in Chagas disease, with broader diagnostic applications emerging for leishmaniasis. Full article