Search Results (8,856)

The increasing demand for plant-based beverages as alternatives to dairy milk requires rapid and reliable methods to assess their composition and authenticity. This study investigated the feasibility of mid-infrared (MIR) and near-infrared (NIR) spectroscopy for classifying plant-based beverages and predicting their nutritional profile. A total of 57 commercial beverages from five categories (oat, almond, soybean, rice, and coconut) were analyzed. Canonical discriminant analysis was used to discriminate among beverage categories, and modified partial least-squares regression models were developed using reference chemical analyses and spectral data to predict protein, fat, sugars, ash, acidity traits, minerals, and amino acid composition. Both MIR and NIR successfully discriminated among the five beverage categories. Quantitative prediction models were generally more accurate with MIR than with NIR. The most robust MIR models were obtained for protein, fat, glucose, ash, and selected minerals (P and K), reaching accuracy levels suitable for quality-control applications. Protein was predicted with excellent accuracy by both technologies. The most robust prediction models were achieved for amino acid composition, with all amino acids except phenylalanine showing satisfactory predictive performance, particularly with MIR spectroscopy. In conclusion, these results demonstrate the feasibility of infrared spectroscopy for the authentication and compositional assessment of plant-based beverages. In particular, MIR spectroscopy showed considerable potential for integration into routine quality-control workflows, similar to those currently implemented for dairy milk analysis. Full article

Background: MicroRNAs are key post-transcriptional regulators of gene expression and contribute to cancer progression, tumor heterogeneity, and context-dependent regulatory rewiring. However, most computational approaches rely on sequence-based target prediction or bulk expression association and are not designed to jointly model regulatory priors, expression context, and heterogeneous cancer states, particularly when matched single-cell microRNA/mRNA co-profiling data are scarce. Methods: We developed a context-aware graph transformer framework for microRNA–gene regulatory analysis across biological resolutions. The framework represents microRNAs, genes, and biological contexts as a heterogeneous graph, where contexts correspond to individual cells in single-cell data and tumor samples or subtype-defined profiles in bulk cohorts. Heterogeneous graph transformer learning generated regulatory embeddings, Bayesian topology optimization refined candidate microRNA–gene interactions, and a dominance-based competition layer with Dominance Share scoring identified master regulators and cooperative target modules. Results: We applied miR-CellMap to matched single-cell miRNA/mRNA co-sequencing data from K562 leukemia cells and paired bulk cancer datasets spanning pan-cancer and subtype-specific cohorts, including breast, colon, glioblastoma, lower-grade glioma, and ovarian cancer. The framework identified recurrent and dataset-specific miRNA regulatory programs, including regulators such as miR-186-5p, miR-214-3p, miR-27a-3p, and let-7 family members. Embedding-derived context analysis showed that predicted miRNA target programs were consistently closer to observed context-specific gene programs than random matched gene programs across all seven datasets. Dominance Share analysis further identified cooperative target modules and co-repressed target programs, supporting the use of miR-CellMap for interpretable cancer-focused miRNA regulatory discovery. Conclusions: This framework provides an interpretable strategy for mapping conserved, cancer-specific, and context-dependent microRNA–gene regulatory programs across single-cell and bulk cancer datasets. Full article

Heat stress negatively affects bovine fertility and embryonic development, while cryopreservation imposes additional cellular stress that may impair embryo survival. The present study investigated whether controlled heat treatment applied during the early morula stage could influence subsequent blastocyst development, molecular stress responses, and post-thaw survival of bovine embryos. In vitro-produced bovine embryos were exposed to controlled thermal treatment involving gradual elevation in temperature from 38.8 °C to 40.0 °C followed by subsequent cooling. Blastocyst formation, post-thaw survival after slow freezing, and the expression of stress-associated genes and microRNAs were evaluated. Heat treatment did not significantly affect blastocyst formation rates or post-thaw embryo survival compared to the control groups. However, significant alterations in the expression of stress-associated markers were observed. The expression of HSP90AA1 and HSPB11 was significantly reduced following heat treatment, while cryopreservation induced increased expression of these markers compared to embryos exposed only to heat treatment. Significant alterations were also detected in the expression of several stress-associated microRNAs. These findings suggest that controlled heat exposure during the morula stage may induce molecular changes associated with the embryonic response to heat stress without compromising developmental competence or cryosurvival. The results contribute to a better understanding of the molecular mechanisms underlying embryonic responses to thermal and cryogenic stress and may support future optimization of embryo production and cryopreservation strategies. Full article

IGF2-H19 locus is important for normal development and growth, and its deregulation has been implicated in various cancers, with conflicting data in oral cancer. IGF2 and H19 expression was analyzed in oral cancer (SCC-25, SCC-15) and normal keratinocytes (HaCaT) cell lines, as well as in cancer tissue and adjacent non-cancerous tissues from 55 patients with oral cancer. The expression of IGF2 and H19 was increased in oral cancer cell lines compared with control cell line. In clinical samples, expression of the IGF2-H19 locus and its associated hsa-miR-675-5p was significantly lower in cancer tissue compared with adjacent non-cancerous tissue. IGF2, H19, and hsa-miR-675-5p demonstrated moderate ability to discriminate between oral cancer and non-cancerous tissues, while the combined analysis of all three molecules improved diagnostic performance. Our results suggest that IGF2-H19 and hsa-miR-675-5p may have potential as molecular biomarkers for discriminating between oral cancer and non-cancerous tissue, but do not appear to have prognostic value. Full article

The beta-site amyloid precursor protein (APP)-cleaving enzyme 1 (BACE1) is a promising and rational target for Alzheimer’s disease (AD), but current clinical trials have been disappointing. Consequently, utilizing the intrinsic regulatory mechanisms of BACE1 during AD pathogenesis might provide valuable insights into the treatment of this devastating disease. In this study, we proposed a combination of AAV delivery and microRNA therapeutics targeting AD at its root by sustained and spatial inhibition of BACE1 with a single therapeutic injection. We demonstrate that upregulation of BACE1 is correlated with downregulation of miR-143-3p in the hippocampus of individuals with AD, and miR-143-3p can directly target BACE1 to inhibit Aβ generation. In the brains of 5×FAD model mice, BACE1 levels are found to be elevated with age in the cornu ammonis 1 (CA1) subfield of the hippocampus. AAV-mediated miR-143-3p restoration in the hippocampal CA1 subfield of AD mice can improve cognitive performance, attenuate BACE1 expression, reduce Aβ levels, induce microglia polarization toward the anti-inflammatory phenotype, modulate neural-related genes including Gal3, and promote synaptic functions. Collectively, the AAV-mediated microRNA gene therapy approach developed for spatial suppression of BACE1 can effectively enhance cognitive performance in AD model mice, offering an attractive therapeutic option for AD treatment with long-lasting efficacy. Full article

Biological aerosols represent a significant challenge for modern CBRN defense due to their potential for long-range dispersion and the need for rapid threat assessment. Current stand-off detection systems are effective in recognizing anomalous aerosol clouds but often lack the molecular specificity required for reliable agent identification. This review examines the role of mid-infrared (MIR) spectroscopy as an emerging approach for chemically resolved stand-off bioaerosol sensing. The physical principles of MIR detection are discussed, including molecular vibrational fingerprints, differential scattering (DISC), and circular intensity differential scattering (CIDS), together with their relationship to aerosol optical properties and Mie resonance effects. Existing and emerging sensing architectures are reviewed, ranging from operational CO₂ laser-based DISC systems to semiconductor-based platforms utilizing tunable differential absorption lidar (DIAL), Quantum Cascade Lasers (QCLs), and dual-comb spectroscopy. The analysis highlights the ability of MIR sensing to access biomolecular signatures associated with proteins, lipids, nucleic acids, and bacterial spores, while also addressing challenges related to atmospheric attenuation, biological variability, and signal interpretation. The reviewed literature indicates that MIR spectroscopy offers a promising pathway toward improved stand-off identification of hazardous bioaerosols, supporting early threat detection and enhanced situational awareness in applications including CBRN defense, critical infrastructure protection, environmental monitoring, public health surveillance, and emergency response. Full article

Inflammation is essential for host defense, but, when dysregulated, it contributes to tissue damage and chronic disease. MicroRNA-146a (miR-146a) is a well-recognized negative regulator of inflammatory signaling, primarily through suppression of the NF-κB pathway; however, its broader proteomic impact under inflammatory conditions remains incompletely defined. In this study, we overexpressed an miR-146a mimic in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages and applied quantitative mass spectrometry to characterize global protein abundance changes. Functional overexpression was supported by reduced mRNA abundance of the established miR-146a targets TRAF6 and IRAK1 under LPS-stimulated conditions. Proteomic analysis identified 1232 proteins showing differential abundance under the predefined exploratory criteria, including proteins related to NF-κB activity, inflammasome components, nitric oxide synthesis, and IL-6-associated pathways. Proteins linked to interferon-related signaling were also altered. Targeted validation by quantitative RT-PCR and parallel reaction monitoring supported changes in selected inflammatory mediators, including PTGS2, NOS2, MAPKAPK2, and IRF3. Functionally, miR-146a overexpression was associated with reduced LPS-induced nitric oxide and IL-6 production. Together, these findings provide an exploratory proteomic overview of pathways associated with miR-146a overexpression in activated macrophages and suggest that miR-146a is associated with modulation of multiple inflammatory signaling networks under inflammatory conditions. Full article

Background/Objectives: Rhabdomyosarcoma (RMS), the most common pediatric soft tissue sarcoma, includes two main subtypes, embryonal (eRMS) and alveolar (aRMS), each with distinct molecular and clinical characteristics. Although cellular processes underlying RMS and differences between PAX3-FOXO1 fusion-positive and fusion-negative tumors are well known, the contribution of long noncoding RNAs (lncRNAs) remains poorly understood. Methods: Here, we reannotated publicly available microarray datasets to comprehensively profile lncRNA expression and reconstruct lncRNA–miRNA–mRNA regulatory networks in RMS. Results: We identified several lncRNAs with subtype-specific differential expression, including HOTAIR as a potential sponge for miR-206, DSCR8 for miR-885-5p, and PRKCQ-AS1 for miR-515-5p in eRMS. Database-supported interaction analyses identified putative regulatory relationships between these lncRNAs and cancer-related miRNAs and mRNAs. Validation using the St. Jude Cloud PeCan platform confirmed distinct lncRNA expression signatures across RMS subtypes and other pediatric solid tumors, supporting subtype-specific regulation. Conclusions: Our findings provide an updated characterization of the lncRNA landscape in RMS and identify candidate lncRNA–miRNA–mRNA regulatory networks that may contribute to disease biology. The proposed regulatory interactions are hypothesis-generating and require experimental validation. Overall, our findings provide a resource for future functional studies and support the investigation of lncRNAs as potential biomarkers and therapeutic targets in RMS. Full article

LncRNA NR_003508 has been implicated in lipopolysaccharide (LPS)-induced acute respiratory distress syndrome. Yet, the involvement of LncRNA NR_003508 in Pseudomonas aeruginosa (PA)-induced autophagy remains elusive. This study aims to reveal the underlying mechanisms of LncRNA NR_003508 in PA-induced autophagy, thereby enhancing the basic research content of the pathogenesis of PA infection. Fluorescence in situ hybridization (FISH) probes and q-PCR revealed that PA infection induced macrophage autophagy accompanied by increasing LncRNA NR_003508, suggesting that LncRNA NR_003508 may participate in competing endogenous RNA (ceRNA)-mediated regulatory networks. Concurrently, autophagic clearance of PA requires LncRNA NR_003508. Then, we used the Gene Expression Omnibus (GEO) database to find that LC3 was considered a core protein in PA-infected autophagy. Furthermore, LncRNA NR_003508 promoted the formation of autophagosomes, which played a positive role in PA clearance. Functionally, bioinformatics analysis and luciferase reporter assays demonstrated that LncRNA NR_003508 promotes the conversion of LC3I to LC3II by sponging miR-344i and facilitates p62 degradation by binding to miR-344g-5p. Taken together, our data established that LncRNA NR_003508 enhanced the formation of autophagosomes induced by PA infection via the miR-344i/LC3 and miR-344g-5p/p62 axes, partly boosting the clearance of PA and providing a theoretical basis and experimental support for understanding the mechanisms underlying PA infection. Full article

Introduction: Bronchopulmonary dysplasia (BPD) remains the most significant complication of extreme prematurity, affecting long-term respiratory outcomes. Because current diagnostic criteria identify only established lesions at 36 weeks postmenstrual age, early non-invasive biomarkers are needed. This pilot study aimed to identify a candidate salivary miRNA panel associated with BPD risk and to explore its pathogenetic relevance through in silico analysis. Methods: Saliva was collected from 20 preterm infants (10 with BPD and 10 controls), and miRNA expression was profiled using the GeneChip™ miRNA 4.1 Array Plate. Discriminatory performance was explored by ROC analysis within this discovery cohort, together with power and Spearman correlation analyses. Results: Expression of hsa-let-7b-5p, hsa-let-7c-5p, and hsa-miR-4454 was significantly elevated in the BPD group (p < 0.05, log₂FC ≥ 1.0), with no significant correlation with gestational age or birth weight. Bootstrap-corrected AUC values ranged from 0.905 to 0.937 and were supported by leave-one-out cross-validation. All three miRNAs showed very large effect sizes exceeding the minimum detectable effect at 80% power. Conclusions: In this pilot study, salivary miRNAs represent a hypothesis-generating candidate biomarker signal for BPD that requires external validation in larger, independent cohorts before any diagnostic or prognostic application can be considered. Full article

MicroRNAs are important regulators of melanoma progression; however, their relationship with cellular senescence remains poorly understood. To address this gap, a systematic review was conducted following PRISMA 2020 guidelines and prospectively registered in the International Prospective Register of Systematic Reviews (PROSPERO) under registration number CRD420251155760. A comprehensive search of PubMed, Scopus, Embase, and Dimensions identified studies evaluating melanoma-associated microRNAs and their effects on cell cycle regulation. Risk of bias was assessed using the SYRCLE tool and an adapted version of ToxRTool, with the included studies classified as having low, moderate, or high risk of bias. Fifteen studies met the eligibility criteria. Most studies reported that microRNA modulation reduced melanoma proliferation through cell cycle arrest; however, only two directly assessed senescence-associated markers. Of the fifteen identified microRNAs, seven had predicted targets and were included in the bioinformatic analysis. Integration of these predictions with genes downregulated in high-risk melanoma and underexpressed during cellular senescence identified 158 shared genes. Subsequent analysis identified predicted targets within this gene set only for hsa-miR-195-5p, and hsa-miR-425-5p, highlighting RNF138, and SYNCRIP as candidate regulatory genes. Collectively, these findings suggest a potential link between microRNA-mediated regulation and senescence-associated pathways during melanoma progression. Full article

Quince (Cydonia oblonga Mill.) is an important fruit crop, yet a systematic quality evaluation framework is lacking. This study comprehensively characterized multiple germplasms from distinct production areas. An integrated strategy combining physicochemical analysis, FT-MIR (Fourier transform mid-infrared spectroscopy), electronic nose (E-nose), headspace solid-phase microextraction–gas chromatography–mass spectrometry (HS-SPME-GC-MS), and chemometrics was employed. Significant variations were observed among accessions: certain varieties were observed to exhibit the highest pectin (1.86%) and total phenolic content (143.40 mg/100 g), while others showed superior firmness and titratable acidity. β-Damascenone in one accession was found to have an exceptionally high odor activity value (OAV) of 265.05. Multivariate analysis, including PLS-DA and OPLS-DA, effectively discriminated among quince accessions, with PLS-DA achieving 100% classification accuracy, and tentatively identified 18 key markers (VIP > 1) for accession discrimination. Loading scatter plot analysis further validated the contribution of these markers to the separation between accessions. However, due to the limited sample size (n = 18) and partial confounding between cultivar and origin, these findings should be considered exploratory and require validation in larger independent studies. This work provides preliminary insights into the diversity and geographical patterns of quality and flavor traits in quince germplasm, offering a preliminary foundation for germplasm evaluation and targeted utilization. Full article

Background/Objectives: Type 2 diabetes mellitus (DM) and carotid atherosclerosis are established risk factors for cardiovascular disease (CVD). However, their relative and combined prognostic significance in individuals without known CVD remains uncertain. This study aimed to evaluate the independent and combined associations of carotid plaques and DM with cardiovascular events and mortality in a high-cardiometabolic-risk primary prevention cohort. Methods: This prospective cohort study followed 6138 participants (3571 men [57%] and 2567 women [43%]; median age 53 years, IQR 48–58) enrolled in the Lithuanian High Cardiovascular Risk (LitHiR) primary prevention program from 2006 to 2023. All individuals underwent clinical assessment and carotid ultrasonography. Participants were stratified by DM status and the presence of carotid plaques. Associations with cardiovascular events, major adverse cardiovascular events (MACE, including non-fatal ischaemic stroke, non-fatal myocardial infarction, and cardiovascular death), and all-cause mortality were evaluated using Cox proportional hazards models. Results: During follow-up (median 6.5 years, IQR 4.5–9.0), 954 participants (16%) experienced composite cardiovascular events (MACE, including non-fatal ischaemic stroke, non-fatal myocardial infarction, and cardiovascular death). Bilateral carotid plaques were more common in individuals with cardiovascular events (23.3% vs. 19.4%; p = 0.007). Individuals with both DM and carotid plaques had the highest risk of MACE (HR = 1.696; 95% CI: 1.346–2.136; p < 0.001), myocardial infarction (MI; HR = 4.089; 95% CI: 1.590–10.516; p = 0.003), and all-cause mortality (HR = 1.802; p = 0.015). The presence of carotid plaques without DM was independently associated with increased risk of MACE (HR = 1.234; 95% CI: 1.062–1.433; p = 0.006) and MI (HR = 2.492; 95% CI: 1.176–5.278; p = 0.017), but not all-cause mortality (HR = 0.986; 95% CI: 0.689–1.413; p = 0.941). In contrast, DM without carotid plaques was not significantly associated with any outcome examined. Conclusions: In this high-cardiometabolic-risk primary prevention cohort, carotid plaques were independently and more strongly associated with cardiovascular outcomes than diabetes alone. Individuals with both carotid plaques and diabetes showed the highest observed risk of adverse cardiovascular events and all-cause mortality. These findings are associational and apply to a high-risk metabolic syndrome cohort; extrapolation to the general population requires further study. The results support the prognostic value of carotid plaque assessment as an adjunctive tool in cardiovascular risk evaluation. Full article

Background: Thoracic aortic aneurysm (TAA) is a potentially life-threatening degenerative disease whose principal danger arises from progressive aortic dilation with the attendant risk of rupture and dissection and which is characterized by extracellular matrix breakdown, smooth muscle loss, and endothelial dysfunction. Caveolae, plasma membrane microdomains built from caveolins (CAV1-3) and cavins (CAVIN1-4), govern nitric oxide (NO) signaling, endocytosis, and mechanotransduction. We hypothesized that downregulation of caveolae-associated genes, driven in part by microRNAs, contributes to endothelial failure and vascular remodeling in TAA. Methods: Normalized transcriptomic expression values for five caveolae-associated genes were retrieved from the GSE26155 dataset (43 TAA and 43 control aortas) using GEO2R. Differential expression was assessed for CAV1, CAV2, CAV3, CAVIN1, and CAVIN2, and Spearman correlation with Deming regression explored inter-gene relationships. Functional enrichment (Enrichr) and experimentally validated microRNA-target interactions (miRTarBase) were used to infer regulatory and mechanistic networks. CpG island mapping and gene-gene interactome construction (GeneMANIA) complemented the analyses. Results: CAV1 and CAV2 were downregulated in TAA at nominal significance (CAV1, p = 0.0225; CAV2, p = 0.0361); after Benjamini–Hochberg correction across the five candidate genes both differences attenuated to a consistent trend (q approximately 0.09), while the two caveolins were strongly co-expressed (Spearman r = 0.527, p < 0.001; Deming CAV2 = 1.881 × CAV1-0.892), indicating coordinated transcriptional regulation. Network analysis linked both genes to NOS3, NOSTRIN, EGFR, HRAS, and RAC1, consistent with impaired endothelial nitric oxide and GTPase signaling. Gene Ontology enrichment highlighted endothelial proliferation, nitric oxide metabolism, calcium homeostasis, vesicle organization, and MAPK regulation. Database-supported analysis (miRTarBase) identified miR-93-5p, miR-199a-3p, miR-203a-3p, and the miR-29 family as experimentally validated candidate repressors of CAV1/CAV2. Conclusions: This integrative transcriptomic and microRNA analysis identifies coordinated CAV1 and CAV2 downregulation as a candidate molecular event in thoracic aortic aneurysm, associated with caveolar loss, endothelial dysfunction, and disrupted nitric oxide homeostasis. The CAV1/CAV2-microRNA axis represents a candidate mechanistic signature warranting further investigation as a potential therapeutic target in aortic disease. Full article