Search Results (8,300)

The yak represents a distinct domestic animal species that predominantly inhabits the Qinghai–Tibet Plateau and adjacent areas, possessing considerable value in both scientific and economic contexts. Compared to animals that mainly dwell on plains, such as cattle, the sperm maturation process in yak exhibits a certain degree of species specificity to adapt to their unique reproductive needs in high-altitude environments. Serving as the main storage site for functionally competent sperm, the cauda epididymis plays an integral role in mediating their post-testicular maturation. MiRNAs are vital regulatory molecules in the epididymis, influencing sperm maturation by modulating gene expression after transcription. To investigate the unique regulatory mechanisms of sperm maturation in yak, this study compared the miRNA expression profiles in the cauda epididymis of yak and cattle using high-throughput small RNA (sRNA) sequencing. The comparative analysis identified and characterized sRNA populations in the cauda epididymis of yak and cattle, revealing a similar length distribution that peaked at 22 nt and a predominance of known miRNAs. Notably, eight miRNAs were found to be highly expressed in both species. Furthermore, the first-nucleotide bias differed significantly between known and novel miRNAs within each species. A total of 31 differentially expressed (DE) miRNAs were identified, with 11 upregulated and 20 downregulated in yak compared to cattle. Among these, bta-miR-1298 exhibited the most significant upregulation, while bta-miR-2344 displayed the most pronounced downregulation. Bioinformatic analysis linked the predicted target genes of these miRNAs to numerous critical signaling pathways, including calcium signaling, the mitogen-activated protein kinase (MAPK) signaling pathway, the Ras-associated protein 1 (Rap1) signaling pathway, and the cyclic guanosine monophosphate-protein kinase G (cGMP-PKG) signaling pathway. Furthermore, eight significantly DE miRNAs, including bta-miR-2443, bta-miR-503-3p, bta-miR-6517, bta-miR-2440, bta-miR-2431-3p, bta-miR-2436-3p, bta-miR-6523a, and bta-miR-6775, were predicted to target genes involved in various aspects of sperm structural and functional maturation. These aspects include flagellum formation, sperm motility, chromatin remodeling, acrosome reaction, acrosome structure, sperm capacitation, chemotaxis, and nuclear chromatin condensation. Multiple miRNAs and their corresponding predicted target genes were analyzed by quantitative real-time PCR (qPCR), demonstrating an inverse correlation between miRNA expression and target gene levels. These findings reveal a distinct, species-specific miRNA signature in the yak cauda epididymis, which suggests a potential contribution to regulating the epididymal luminal environment and the process of sperm maturation. This study provides preliminary foundational data for elucidating the differences in sperm maturation mechanisms between yak and cattle, and offers potential novel targets for improving reproductive efficiency in plateau livestock. Full article

MicroRNA (miRNA) is a type of small non-coding RNA that influences various biological processes by targeting gene expression. However, the roles of microRNA in mediating ruminant mammary cell proliferation and survival remain poorly understood. This study aimed to elucidate how miR-215-5p regulates cell cycle and apoptosis-related genes in goat mammary epithelial cells (GMECs). The effects of miR-215-5p on cell cycle and apoptosis were assessed by flow cytometry. A combination of bioinformatics analysis was conducted to predict the target genes of miR-215-5p; this was followed by experimental validation using techniques such as luciferase reporter assays. The effects of CTCF, the targeting gene of miR-215-5p, on cell cycle and apoptosis were examined by qRT-PCR, Western blot and flow cytometry in GMECs. The study demonstrated that miR-215-5p induced cell-cycle arrest at the G0/G1 phase and promoted apoptosis in GMECs. Mechanistically, miR-215-5p downregulated CTCF expression by directly targeting its 3′-untranslated region (3′UTR). This miR-215-5p-mediated depletion of CTCF inhibits CDK2 and CDK6 activity, consequently downregulating genes involved in cell-cycle progression. Furthermore, the miR-215-5p/CTCF axis was found to promote apoptosis by downregulating the protein expression of Bcl-xL and upregulating the gene expression of Bax. In summary, miR-215-5p suppresses GMEC proliferation and survival through CTCF-dependent histone modifications. Full article

Eukaryotic initiation factor 2 (EIF2) signaling plays a crucial role in regulating mRNA translation and initiating eukaryotic protein synthesis. Computational molecular network pathway analysis of the canonical pathways of the coronaviral infection revealed that EIF2 signaling is inactivated when the coronavirus pathogenesis pathway is activated and vice versa. Our computational analyses indicated that the coronavirus pathogenesis pathway and EIF2 signaling had inverse activation states. Computational investigation of upstream or downstream microRNA (miRNA) revealed that EIF2 signaling directly interacted with miRNAs, including let-7, miR-1292-3p (miRNAs with the seed CGCGCCC), miR-15, miR-34, miR-378, miR-493, miR-497, miR-7, miR-8, and MIRLET7. A total of 36 nodes, including 8 molecules (ATF4, BCL2, CCND1, DDIT3, EIF2A, EIF2AK3, EIF4E, and ERK1/2), 1 complex (the ribosomal 40s subunit), and 1 function (apoptosis) in the coronavirus pathogenesis pathway, overlapped with EIF2 signaling. Alterations in EIF2 signaling may play a role in the pathogenesis of coronavirus. Full article

Background: Zika virus (ZIKV), a mosquito-borne flavivirus, is associated with congenital malformations and neuroinflammatory disorders, highlighting the need to identify host factors that shape infection outcomes. Macrophages, key targets and reservoirs of ZIKV, orchestrate both antiviral and inflammatory responses. Methods: Vitamin D (VitD) has emerged as a potent immunomodulator that enhances macrophage antimicrobial activity and regulates inflammation. To investigate how VitD shapes macrophage responses to ZIKV, we reanalyzed publicly available RNA-seq and miRNA-seq datasets from monocyte-derived macrophages (MDMs) of four donors, differentiated with or without VitD and subsequently infected with ZIKV. Results: Differential expression analysis identified long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and mRNAs integrated into competing endogenous RNA (ceRNA) networks. In VitD-conditioned and ZIKV-infected MDMs, 65 lncRNAs and 23 miRNAs were significantly modulated. Notably, lncRNAs such as HSD11B1-AS1, Lnc-FOSL2, SPIRE-AS1, and PCAT7 were predicted to regulate immune and metabolic genes, including G0S2, FOSL2, PRELID3A, and FBP1. Among the miRNAs, let-7a and miR-494 were downregulated, while miR-146a, miR-708, and miR-378 were upregulated, all of which have been previously implicated in antiviral immunity. Functional enrichment analysis revealed pathways linked to metabolism, stress responses, and cell migration. ceRNA network analysis suggested that SOX2-OT and SLC9A3-AS1 may act as molecular sponges, modulating regulatory axes relevant to immune control and viral response. Conclusions: Despite limitations in sample size and experimental validation, this study provides an exploratory map of ncRNA–mRNA networks shaped by VitD during ZIKV infection, highlighting candidate molecules and pathways for further studies on host–virus interactions and VitD-mediated immune regulation. Full article

Pistachio skin is a by-product that is considered a promising novel feed ingredient for ruminants; however, its role in shaping the lamb gastrointestinal tract microbiota is poorly studied. The present study aimed to investigate, through a metagenomics approach, the effects of integrating pistachio skin into the diet on the faecal and ruminal microbiota of healthy lambs. Faecal samples, collected at the beginning (d0) and 58 days after the start of the dietary treatment (d58), and ruminal samples, collected after slaughter, were subjected to Illumina MiSeq analysis of the 16S rRNA gene. The results revealed that, although temporal variations were observed, the supplementation of pistachio skin did not markedly affect the overall faecal microbiota structure. Conversely, specific rumen taxa were selectively modulated by the experimental diet. In conclusion, the use of pistachio skin as a feed ingredient can be considered a suitable and sustainable dietary strategy that modulates specific rumen microbial groups, thereby preserving the stability of the gut microbiota in lambs. Full article

Soft tissue sarcoma remains challenging to treat due to its heterogeneity, stemness-associated survival programs, and resistance to conventional therapies. Extracellular vesicles (EVs) mediate tumor–stroma communication, yet how stemness-targeted therapies reshape EVs-associated miRNAs networks remains unclear. This study profiled EVs miRNAs cargo from infrapatellar fat pad mesenchymal stem/stromal cells (IFP-MSCs) and sarcoma cells (SCs) under basal conditions and following treatment with a synthetic tyrosine peptide analog (TPA). EVs were isolated, characterized, and subjected to miRNAs profiling and pathway enrichment analyses. TPA induced ≥2-fold regulation of 182 miRNAs, including 49 upregulated and 24 downregulated in IFP-MSC-EVs and 86 upregulated and 23 downregulated in SC-EVs. A conserved core of 149 miRNAs (67.1%) was shared across all EVs groups. Abundant species included miR-3960 and miR-21-5p, while TPA reduced tumor-associated miRNAs such as miR-1246 (~10-fold decrease in IFP-MSC-EVs). Pathway enrichment revealed consistent targeting of cancer, MAPK, Wnt, TGF-β, and immune signaling pathways, with modest increases in mapped gene coverage following TPA treatment. In silico analysis identified distinct EVs miRNA–gene interaction profiles, with VEGFA emerging as a recurrent predicted target. These results demonstrate that stemness-targeted modulation quantitatively reprograms EVs miRNA cargo in a cell-type-dependent manner, reshaping vesicle-mediated signaling networks in sarcoma. Full article

Automatic Music Transcription (AMT) plays a fundamental role in Music Information Retrieval (MIR) by converting raw audio signals into symbolic representations such as MIDI or musical scores. Despite advances in deep learning, accurately transcribing piano performances remains challenging due to dense polyphony, wide dynamic range, sustain pedal effects, and harmonic interactions between simultaneous notes. Existing approaches using convolutional and recurrent architectures, or autoregressive models, often fail to capture long-range temporal dependencies and global harmonic structures, while conventional Vision Transformers overlook the anisotropic characteristics of audio spectrograms, leading to harmonic neglect. In this work, we propose SpectTrans, a novel piano transcription framework that integrates a Spectral Gating Network with a multi-head self-attention Transformer to jointly model spectral and temporal dependencies. Latent CNN features are projected into the frequency domain via a Real Fast Fourier Transform, enabling adaptive filtering of overlapping harmonics and suppression of non-stationary noise, while deeper layers capture long-term melodic and chordal relationships. Experimental evaluation on polyphonic piano datasets demonstrates that this architecture produces acoustically coherent representations, improving the robustness and precision of transcription under complex performance conditions. These results suggest that combining frequency-domain refinement with global temporal modeling provides an effective strategy for high-fidelity AMT. Full article

Background: Gallbladder cancer (GBC) is a highly aggressive malignancy characterized by a poor prognosis, particularly in its advanced stages. While microRNAs (miRNAs) regulate cancer progression, their specific role in the transition from early to advanced GBC is poorly understood. Methods: We performed miRNA expression profiling on 41 formalin-fixed paraffin-embedded (FFPE) tissues, including 10 gallstone disease (GSD) controls, 14 early-stage GBC (stage I and II), and 17 advanced-stage GBC cases (stage III and IV), using the NanoString nCounter platform. Differentially expressed miRNAs (DEMs) were identified followed by miRNA target identification using miRTarBase. Results: We identified 43 significantly dysregulated miRNAs in early-stage and 46 in advanced-stage GBC compared to controls. Based on the literature search, we found EMT-inhibiting miRNAs (miR-200 family) to be overexpressed in early stage and downregulated in advanced stages (miR-574-3p, miR-195-5p) in our study. Pathway analysis revealed significant enrichment of the ‘EGFR tyrosine kinase inhibitor resistance’ pathway in both the stages. The correlation of DEMs with clinicopathological features revealed that the expression of miR-361-3p and miR-423-5p was significantly associated with tumor grade (r = −0.605, p = 0.0003) and lymph node status (r = −0.621, p = 0.0001), respectively. Conclusions: This study identifies distinct miRNA signatures associated with GBC initiation and progression, offering insights into the molecular pathogenesis of the disease. Furthermore, functional studies of the miRNAs implicated in EMT and EGFR-TKI resistance may be conducted using GBC cell lines to dissect the precise roles of key miRNAs and explore their potential as novel therapeutic targets in GBC. Full article

Myocardial infarction (MI) triggers complex pathological processes, including inflammation, hypoxia, and fibrotic remodeling. MicroRNAs (miRNAs) have emerged as promising biomarkers for cardiovascular injury; however, their expression dynamics along processes remain underexplored. We used an in vivo rat model of permanent coronary occlusion to study the molecular alterations associated with MI and its resolution in a temporal mode, including five experimental groups with five animals in each: sham, PO 24 h, PO 72 h, PO 7 d, PO 1 month. Histological analysis, serum biomarkers, and miRNA/gene expression profiles were analyzed in a time-dependent manner post-occlusion. Subsequent analysis revealed early depletion of selected circulating miRNAs (PO 24 h). Transient upregulation in cardiac tissue miRNAs, inflammatory and fibrotic gene expression (Fibronectin, Collagen, Vimentin, E-Cadherin) were observed at PO 72 h. These molecular alterations correlated with histological evidence of myocardial injury and repair. Taken together, our findings delineate the molecular timeline of MI progression and resolution and identify candidate miRNAs as sensitive and time-dependent indicators of myocardial stress, including miR-107, miR-122-5p and miR-221-3p. This integrative approach supports the use of miRNA signatures for noninvasive monitoring of cardiac injury and resolution and unveils potential therapeutic targets to reduce pathological remodeling. Full article

Background: Malva sylvestris (the common mallow) is an herbaceous species widely used in ethnobotanical practices to treat gastrointestinal, hepatic and urinary inflammation. Objectives: Despite these beneficial effects on human health, the antineoplastic potential of this plant has not yet been fully explored. Thus, in the present study, two human colon cancer cell lines (i.e., HCT-116 and Caco-2) were treated with an extract obtained from M. sylvestris flowers (MFE), whose composition in terms of phytochemicals and microRNAs has been recently published by our research group, to explore its potential bioactivity. Methods/Results: MTT and Trypan blue assays demonstrated that MFE reduced tumour cell growth without causing significant cytotoxicity or apoptosis. Following the diphenylboric acid 2-aminoethyl ester-induced fluorescence of some plant metabolites, microscopy analysis proved that MFE components crossed the cell membranes, accumulating into nuclei. Wound assay and transwell tests documented that MFE was also able to reduce cell motility and invasiveness. In both cell lines qPCR experiments demonstrated that MFE caused the over-expression of factors, like VIMENTIN and E-CADHERIN, which negatively influence epithelial–mesenchymal transition in colon cancers. However, the effects of MFE appeared to be time-, dose- and cell type-dependent. In fact, the treatment induced senescence in P53-null Caco-2 cells (i.e., ROS, β-galactosidase and P21^WAF1/Cip1) and a premise of differentiation (i.e., P27^Kip1) in P53-wild-type HCT-116 cells, also via the CDK2/c-MYC/AKT axis, justifying its antiproliferative property. In parallel, the transfection of tumour cells with pure synthetic miR160b-5p—a microRNA identified in M. sylvestris flowers and predicted to target the human CDK2 transcript—resulted in gene silencing, thereby suggesting its central role in mediating the cross-kingdom effects of MFE on the investigated cancer models. Conclusions: Overall, these findings open new perspectives on the common mallow as a source of potential antimetastatic compounds and on the possible use of its plant microRNAs in the development of gene therapies. Full article

Prostate cancer (PCa) is a leading cause of cancer-related mortality in men and is often characterized by aggressive growth and bone metastasis. Angiogenesis plays a central role in tumor progression and dissemination. This study aimed to explore the regulatory roles of long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) in angiogenesis and metastasis during PCa progression. Publicly available RNA-seq datasets were analyzed to identify differentially expressed miRNAs between metastatic (N1) and nonmetastatic (N0) PCa. Bioinformatic tools were used to reconstruct co-regulatory networks involving miRNAs, lncRNAs, and angiogenesis-related mRNAs. RT-qPCR was performed on serum-derived liquid biopsies from N0 and N1 patients and healthy controls to validate the key regulatory axes. Transcriptomic analysis revealed that miRNAs such as hsa-miR-183-5p and hsa-miR-216a-5p were upregulated in N1 PCa and associated with pro-angiogenic signaling, whereas hsa-miR-206 and hsa-miR-184, known for their anti-angiogenic functions, were downregulated. Network analysis identified the LINC00261–miR-206–HIF1A axis as the central regulatory module. RT-qPCR validation confirmed the significant downregulation of LINC00261 and miR-206, along with HIF1A overexpression in N1 samples compared to N0 and controls (p < 0.001), supporting in silico predictions. These findings highlight the role of ncRNA-mediated regulation of PCa angiogenesis and metastasis. The LINC00261–miR-206–HIF1A axis may serve as a promising noninvasive biomarker and potential therapeutic target. The integration of computational and experimental data provides a strong rationale for the further functional validation of advanced PCa. Full article

Rising global temperatures lead to a continuous increase in the frequency and intensity of extreme weather events, such as droughts and floods, posing serious threats to terrestrial homeotherms. However, adaptive changes in respiratory metabolism and molecular mechanisms in lung tissues of small mammals under extreme water shortage conditions remain unclear. This study hypothesized that small desert mammals can adapt to extreme water shortage environments by regulating the plasticity of lung tissue gene expression and respiratory metabolism. Using 29 wild-caught Siberian jerboas (Orientallactaga sibirica) as subjects, we implemented a 12-day complete water deprivation protocol to simulate extreme aridity. Body weight, food intake, and daily energy expenditure (DEE) were monitored throughout the experiment. Whole-transcriptome sequencing of lung tissues was performed to profile mRNA, circRNA, and miRNA expression, with competitive endogenous RNA (ceRNA) network analysis to explore molecular mechanisms underlying lung adaptation to water deprivation. Over the 12-day water deprivation (WS) period, Orientallactaga sibirica (O. sibirica) exhibited a 30.3% reduction in body mass and a 68.1% decrease in food intake relative to the baseline level. DEE during the peak activity period at the end of the experiment was 12.6% lower in the WS group compared to the control group. In lung tissue, structural integrity-related genes (Mybl2, Ccnb1) were downregulated. A key finding was that circ_0015576 exhibits a significant positive correlation with the potassium channel gene Kcnk15 and a robust negative correlation with miR-503-5p—suggesting that circ_0015576 functions as a competing endogenous RNA (ceRNA) to sequester miR-503-5p and thereby derepress Kcnk15 expression. Core regulatory genes (ApoA4, Dusp15 etc.) were also coordinately downregulated. Collectively, these results indicate that O. sibirica reduces overall energy expenditure, which may be associated with lung gene expression plasticity, such as those related with lung cell proliferation, pulmonary function, and gas exchange efficiency. This metabolic downregulation facilitates energy conservation under severe water scarcity. Full article

Fetal growth restriction (FGR) is a major contributor to perinatal morbidity and mortality, most commonly arising from placental dysfunction, with increasing evidence implicating aberrant DNA methylation in its pathogenesis. To identify robust epigenetic alterations associated with FGR, we analyzed placental chorionic villi from an in-house early-onset FGR cohort and compared them with a publicly available dataset (GSE100197). DNA methylation profiling was performed using Illumina EPIC (in-house) and 450K (public) arrays, processed with identical normalization and quality-control pipelines, including adjustment for gestational age and estimation of placental cell-type composition. Differentially methylated positions (DMPs) were identified using linear regression models, revealing 10,427 DMPs in the in-house cohort and 7467 in the public dataset, with 108 shared DMPs showing consistent direction of change across both cohorts. Promoter-associated DMPs were mapped to genes involved in angiogenesis, morphogenesis, immune regulation, and transcriptional control, including EPHA1, ANGPTL6, ITGAX, BCL11B, and CYP19A1, while additional novel candidates such as SLC39A12, YEATS4, and MIR515 family members were also identified. Functional annotation suggests that these methylation changes may influence pathways essential for placental vascular development and structural organization. Overall, this cross-cohort comparison highlights reproducible epigenetic signatures of FGR and underscores the need for standardized approaches to clarify the molecular mechanisms underlying placental insufficiency. Full article

During public health emergencies, individuals typically obtain epidemic-related information through mass media channels and personal social media platforms. This information enables them to monitor epidemic progression and adjust their preventive behaviors accordingly to mitigate infection risks. To capture these processes, this paper proposes a three-layer coupled metapopulation network model that investigates the effects of regional mass media and social information propagation on the spatial spread of epidemic. The mass media layer represents regional outlets that propagate epidemic-related information to individuals within corresponding patches. Migrant individuals not only follow mass media information of the residential patch, but also continue to follow mass media information from their destination patch. The information layer captures the dynamics of information exchange on social media platforms. The epidemic layer depicts the spread of the epidemic within the metapopulation network and simulates the reaction-diffusion dynamics of migrating individuals across different patches through a Migration-Interaction-Return (MIR) mechanism; the coupling between the information layer and the epidemic layer is asymmetric. Theoretical analysis using the Microscopic Markov Chain Approach (MMCA) derives the evolution equation and determines the epidemic thresholds, while Monte Carlo (MC) simulations validate the model and explore factors influencing propagation dynamics. Our research indicates that when migrants simultaneously receive mass media information from both residential and destination patches, it significantly enhances information coverage and promotes protective behaviors, thereby effectively suppressing epidemic spread. Furthermore, promoting information propagation—particularly the communication among individuals within a patch—significantly increases the proportion of aware individuals, reduces the infection scale, and raises the epidemic threshold. Notably, population migration would originally lead to an increase in infection scale, but as the intensity of information propagation strengthens, migration instead has a good effect on controlling epidemic spread. These results provide deeper insights into the role of awareness propagation and human mobility in epidemic containment. Full article

Background/Objectives: Diffuse large B-cell lymphoma (DLBCL) is an aggressive and heterogeneous malignancy, for which predicting clinical outcomes remains challenging. Although immune-checkpoint pathways are known to influence tumor biology, the impact of their germline variants on DLBCL susceptibility and prognosis has not been fully elucidated. Methods: Variants in PD-L1 gene CD274 (rs4143815, rs822336), and miR-155 gene MIR155HG (rs767649, rs1893650), assessed by TaqMan assays in 99 DLBCL patients and 113 age- and sex-matched healthy controls, were associated with clinicopathological features, treatment response, overall survival (OS), relapse-free survival (RFS), and disease susceptibility. Results: The PD-L1 variant rs822336 was significantly associated with relapse status (p = 0.005) and RFS (p = 0.008), with the wild-type GG genotype showing the poorest RFS that remained independent in the multivariate Cox analysis (HR = 2.387, p = 0.003). Conversely, rs4143815 showed a nominal association with treatment resistance (p = 0.026), while patients carrying the GG genotype had worse OS (p = 0.006). In susceptibility analyses, miR-155 variant rs767649 showed a nominal association with DLBCL risk, with the rare AA genotype showing an increased risk of DLBCL (OR = 5.234, p = 0.045), which did not remain significant after Bonferroni correction. Conclusions: In a hypothesis-generating manner, these findings suggest that PD-L1 genetic variants may predominantly influence disease progression and outcomes, while miR-155 variation may contribute to DLBCL susceptibility. These findings highlight germline immunogenetic variants as stable, treatment-independent markers that may inform future studies on risk stratification and prognosis in DLBCL. Full article