Search Results (23,207)

Porcine Reproductive and Respiratory Syndrome (PRRS) causes significant economic losses in the swine industry. Circular RNAs (circRNAs), a class of stable non-coding RNAs, are increasingly recognized as regulators in immune responses and host–virus interactions. This study investigated the genome-wide circRNA responses in porcine alveolar macrophages (PAMs), key cell targets of PRRSV, following treatment with a modified live virus (MLV) vaccine or two interferon (IFN) subtypes (IFN-α1, IFN-ω5). Using RNA sequencing, we identified over 1000 differentially expressed circRNAs across treatment groups, revealing both conserved and distinct expression profiles. Gene Ontology and KEGG pathway analyses indicated that circRNA-associated genes are significantly enriched in immune-related processes and pathways, including cytokine signaling and antiviral defense. Notably, IFN-ω5 treatment induced a pronounced circRNA response, aligning with its potent antiviral activity. We further explored the regulatory potential of these circRNAs by predicting miRNA binding sites, revealing complex circRNA-miRNA interaction networks. Additionally, we assessed the coding potential of differentially expressed circRNAs by identifying open reading frames (ORFs), internal ribosome entry sites (IRESs), and N6-methyladenosine (m⁶A) modification sites, suggesting a subset may undergo non-canonical translation. These findings provide a comprehensive landscape of circRNA expression in PAMs under different antiviral conditions, highlighting their potential roles as immune regulators and novel players in interferon-mediated antiviral responses, particularly downstream of IFN-ω5. This work contributes to understanding the non-coding RNA landscape in the PRRSV-swine model and suggests circRNAs as potential targets for future antiviral strategies. Full article

Modern distributed computing systems and applications with strict privacy requirements demand robust data confidentiality. A primary challenge involves enabling parties to exchange data or perform joint computations. These interactions must avoid revealing private information about the data. Protocols with the obliviousness property, known as oblivious protocols, address this issue. They ensure that no party learns more than necessary. This survey analyzes the security and performance of post-quantum oblivious protocols, with a focus on oblivious transfer and oblivious pseudorandom functions. The evaluation assesses resilience against malicious adversaries in the Universal Composability framework. Efficiency is quantified through communication and computational overhead. It identifies optimal scenarios for these protocols. This paper also surveys related primitives, such as oblivious signatures and data structures, along with their applications. Key findings highlight the inherent trade-offs between computational cost and communication complexity in post-quantum oblivious constructions. Open challenges and future research directions are outlined. Emphasis is placed on quantum-resistant designs and formal security proofs in stronger adversarial models. Full article

This study aims to elucidate the neurodevelopmental toxicity and molecular mechanisms of endocrine-disrupting chemicals (EDCs) in neurodevelopmental disorders (NDDs) through a network toxicology approach, using triclosan exposure as a case example. Potential targets of triclosan were identified via comparative analysis of toxicogenomics databases such as the Comparative Toxicogenomics Database (CTD), Similarity Ensemble Approach (SEA), SwissTargetPrediction, and TargetNet. NDD-related targets were retrieved from GeneCards, Disease Gene Network (DisGeNET), and Online Mendelian Inheritance in Man (OMIM), resulting in 633 overlapping genes associated with disease pathology and triclosan effectors. Protein–protein interaction networks were constructed using STRING and Cytoscape, applying median-based algorithms to identify six core genes: AKT1, TP53, EGFR, FN1, SRC, and ESR1. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses via Metascape revealed that triclosan-induced NDDs are primarily associated with endocrine signaling disruption and activation of the PI3K-Akt pathway. Molecular docking with CB-Dock2 demonstrated strong binding affinities between triclosan and the core targets, while YASARA molecular dynamics simulations confirmed stable interactions, notably with EGFR, exhibiting high binding stability. Collectively, these findings delineate the potential molecular mechanisms underlying triclosan-induced NDDs and underscore the utility of network toxicology, molecular docking, and molecular dynamics simulations in assessing neurotoxicity and related molecular pathways. This research provides novel insights for future investigations, enhances understanding of the potential impact of neurodevelopmental disorders on health, and lays a scientific foundation for the development of preventive and therapeutic strategies. Full article

The growth plate is a specialized cartilage structure near the ends of long bones that orchestrates longitudinal bone growth during fetal and postnatal stages. Within this region reside a dynamic population of growth plate skeletal stem cells (gpSSCs), primarily located in the resting zone, which possess self-renewal and multilineage differentiation capacity. Recent advances in cell-lineage tracing, single-cell transcriptomics, and in vivo functional studies have revealed distinct subpopulations of gpSSCs, which are defined by markers such as parathyroid hormone-related protein (PTHrP), CD73, axis inhibition protein 2 (Axin2), forkhead box protein A2 (FoxA2), and apolipoprotein E (ApoE). These stem cells interact intricately with their niche, particularly after the formation of the secondary ossification center, through stage-specific regulatory mechanisms involving several key signaling pathways. This review summarizes the current understanding of gpSSC identity, behavior, and regulation, focusing on how these cells sustain growth plate function through adapting to biomechanical and molecular cues. Full article

Background: Cancer stem cells (CSCs) are key drivers of tumorigenesis and metastasis. However, the precise roles of CSC-associated genes in these processes remain unclear. Methods: This study integrates cancer stem cell biomarkers and clinical data from The Cancer Genome Atlas (TCGA) specific to bladder cancer (BLCA). By combining differentially expressed genes (DEGs) from TCGA-BLCA samples with CSC-related biomarkers, we conducted comprehensive functional analyses and developed an 8-gene prognostic signature through Cox regression, least absolute shrinkage and selection operator (LASSO) analysis, and multivariate Cox regression. This model was validated with GEO datasets (GSE13507 and GSE32894), and the single-cell RNA seq dataset GSE222315 was subsequently analyzed to characterize the signature genes and elucidate their interactions. And a nomogram was created to stratify TCGA-BLCA patients into risk categories. The ‘oncoPredict’ algorithm based on the GDSC2 dataset assessed drug sensitivity in BLCA. Result: From the TCGA cohort, 665 CSC-related genes were identified, with 120 showing significant differential expression. The 8-gene signature (ALDH1A1, CBX7, CSPG4, DCN, FASN, INHBB, MYC, NCAM1) demonstrated strong predictive power for overall survival in both TCGA and GEO cohorts, as confirmed by Kaplan–Meier and ROC analyses. The nomogram, integrating age, tumor stage and risk scores, demonstrated high predictive accuracy. Additionally, the oncoPredict algorithm indicated varying drug sensitivities across patient groups. Based on retrospective data, we identified a novel CSC-related prognostic signature for BLCA. This finding suggests that targeting these genes could offer promising therapeutic strategies. Full article

Background: Breast cancer remains a predominant malignancy among females globally, and the tumor microenvironment (TME) exerts a pivotal role in its progression. Despite notable advancements in diagnostic and therapeutic modalities, resistance to conventional therapies persists as a critical hurdle, underscoring the necessity of exploring TME-related prognostic biomarkers. Methods: To elucidate the role of the TME in breast cancer progression and identify potential prognostic biomarkers, we analyzed RNA-seq data from 1081 breast cancer cases and 99 normal controls to assess tumor-infiltrating immune cells (TICs) and stromal components. Differential gene expression analysis identified genes correlated with ImmuneScore and StromalScore. A protein–protein interaction (PPI) network was constructed, followed by univariate Cox regression to pinpoint survival-associated genes. JCHAIN, significantly linked to survival outcomes, was selected for further investigation. Gene Set Enrichment Analysis (GSEA) and TIC correlation analyses were performed to explore its associations with immune pathways. Additionally, immunohistochemistry (IHC) and multiplexed immunofluorescence (mIF) were performed on 61 clinical samples. Results: High ImmuneScore was associated with improved survival. Joining chain of multimeric IgA and IgM (JCHAIN) expression was notably reduced in tumor tissues, with low expression correlating with poorer prognosis. GSEA highlighted immune-related pathways enriched in high JCHAIN expression groups. TIC analysis revealed positive correlations with CD8+ T cells and M1 macrophages. IHC and mIF validations further confirmed decreased JCHAIN protein expression in tumor tissues, and higher JCHAIN expression was associated with increased M1 macrophage density. Conclusions: JCHAIN serves as a promising prognostic biomarker in breast cancer, reflecting immune activity within the TME, providing valuable insights into immune-stromal interactions and the therapeutic potential of JCHAIN. Full article

Age-related impaired wounds often become infected with bacteria, leading to substantial mortality and morbidity in the elderly. The decline in androgen levels with increasing age is believed to exacerbate inflammation during wound infections. Despite its well-documented anti-inflammatory activities in wound repair, little is known about the effect of age-related androgen deprivation on bacterial phagocytosis in impaired chronic wounds. The aim of this study was to investigate the effect of age-related testosterone deprivation on the phagocytic functions of THP-1 monocyte-derived macrophages to eliminate Gram-positive and Gram-negative bacteria in vitro. Host–pathogen interaction experiments were conducted to quantify the macrophage-mediated clearance of two common wound-associated bacteria, methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa, under in vitro environments that model testosterone levels representative of those found in elderly males, healthy young adults and testosterone replacement therapy (TRT). Testosterone and its metabolite 5α-dihydrotestosterone (DHT) significantly dampened the macrophage-mediated phagocytosis of both MRSA and P. aeruginosa in a dose-dependent manner (p < 0.05). Blockade of the androgen receptor (AR) using enzalutamide confirmed that testosterone mediates bacterial clearance through binding to the AR. Blocking the conversion of testosterone to DHT through stimulation of macrophages with the 5-α-reductase inhibitor finasteride reversed the testosterone-mediated effects on bacterial clearance, which confirmed that testosterone could potentially dampen the innate phagocytic responses in macrophages through conversion to DHT. Novel findings in this study suggest that the selective manipulation of the AR and/or blockade of testosterone–DHT conversion may provide effective therapeutic treatments to combat wound infections in the elderly. Full article

Background: To overcome the esthetic limitations of dental monolithic zirconia restorations, multichromatic systems were developed to combine improved structural integrity with a natural shade gradient that mimics the optical properties of natural teeth. In response to the clinical demand for time-efficient, i.e., chairside fabrication of zirconia restorations, rapid sintering protocols have become necessary to adjust clinical efficiency along with material performance. This study addresses the challenges of a rapid sintering protocol related to optical performance and phase transformation of the final restoration and the zirconia–cell interaction. Methods: The influence of a rapid sintering protocol on the color stability of the final dental restoration was evaluated by the CIE L*a*b* color space. Phase transformation was assessed through X-ray diffraction analysis. Cellular behavior was evaluated by measuring wettability, the material’s surface energy, and a cell mitochondrial activity assay on human gingival fibroblasts. Results: Optical measurements demonstrated that the total color change in all layers after rapid sintering was above the perceptibility threshold (ΔE* > 1.2), while only the polished enamel layer (ΔE* = 3.01) exceeded the acceptability threshold (ΔE* > 2.7), resulting in a clinically perceptible mismatch. Results of X-ray diffraction analysis, performed for fixed occupancy at Z_0.935Y_0.065O_0.984, revealed that rapid sintering caused a decrease in the cubic (C-) phase and an increase in the total amount of tetragonal (T-) phases. Conventionally sintered zirconia consists of 54% tetragonal (T-) and 46% cubic (C-) phase, whereas in the speed-sintered specimens, an additional T1 phase was detected (T = 49%; T1 = 27%), along with a reduced cubic fraction (C = 24%). Additionally, a small amount of the monoclinic (M) phase is noticed. Although glazing as a surface finishing procedure resulted in increased hydrophilicity, both polished and glazed surface-treated specimens showed statistically comparable cell adhesion and proliferation (p > 0.05). Conclusions: Rapid sintering induced perceptible color changes only in the enamel layer of multichromatic zirconia, suggesting that even layer-specific alterations may have an impact on the overall esthetic outcome of the final prosthetic restoration. Five times higher heating and cooling rates caused difficulty in reaching equilibrium, leading to changes in lattice parameters and the formation of the metastable T1 phase. Full article

Animal studies show that sleep regulation depends on subcortical networks, but whether the connectivity between subcortical areas contributes to human sleep variability remains unclear. We investigated whether the effective connectivity between the LC and hypothalamic subparts during wakefulness relates to sleep electrophysiology. Thirty-three younger (~22 y, 27 women) and 18 late middle-aged (~61 y, 14 women) healthy individuals underwent 7-Tesla functional MRI during wakefulness to assess LC–hypothalamus effective connectivity. Additionally, sleep EEG was recorded at night in the lab to examine the relationships between effective connectivity measures and REM sleep theta energy as well as sigma power prior to REM. Connectivity analyses revealed strong mutual positive influences between the LC and both the anterior–superior and posterior hypothalamus, consistent with animal studies. Aging was negatively associated with the connectivity from the anterior–superior hypothalamus (including the preoptic area) to the LC. In late middle-aged adults, but not younger adults, stronger effective connectivity from the anterior–superior hypothalamus to the LC was associated with lower REM theta energy. This association extended to other low-frequency bands during REM and NREM sleep. These findings highlight the age-dependent modulation of LC–hypothalamus interactions and their potential roles in sleep regulation, providing new insights into neural mechanisms underlying age-related sleep changes. Full article

Irregular rooting in vitro is a major problem in the micropropagation of culinary rhubarb (Rheum rhaponticum), a vegetable crop rich in bioactive compounds. To date, little is known about the factors and mechanisms underlying adventitious root (AR) formation in rhubarb under in vitro conditions. Here, we studied the effects of indole-3-butyric acid (IBA) and its interaction with ethylene (ET) on AR development in rhubarb ‘Raspberry’ selection. To evaluate the ET-effect, we applied a precursor of ET biosynthesis—1 aminocyclopropane-1-carboxylic acid (ACC); an inhibitor of ET synthesis—aminoethoxyvinylglycine (AVG); and an inhibitor of ET action—silver nitrate (AgNO₃). The best results (96.9% rooting frequency, 12.7 roots/shoot) were obtained after adding ACC to the IBA-containing medium. The positive effect of ET was linked to decreased levels of cytokinin and auxins in the rhubarb shoot bases at the initiation and expression stages of rooting. Moreover, the enhanced expression levels of genes involved in auxin signalling and homeostasis (IAA17, GH3.1) and ABA catabolism (CYP707A1) were observed. The blocking of ethylene synthesis significantly increased JA production, and the rooting frequency decreased to 29.8%. The presence of AgNO₃ in the auxin medium resulted in a significant reduction in root number, which was consistent with the enhanced levels of ABA and the expression of genes related to ABA biosynthesis and signalling (PP2C49 and CBF4), as well as ET synthesis (ACO5). Full article

Background: Whether therapeutic albumin (ThHSA) can serve as a defense tool in Candida species (spp.) infections is still a matter of debate, although many physicians are in the habit of infusing ThHSA to restore the physiological concentration of endogenous human serum albumin (HSA). Given the need for innovative anti-Candida strategies, we assessed in vitro the role of ThHSA alone or in combination with voriconazole (VCZ) in combating Candida spp. growth and the role of bovine serum albumin (BSA)—used as a substitute for HSA—with two endogenous bovine antimicrobial peptides in combating C. albicans and other microbes. Results: The combination of ThHSA with VCZ enhanced the antifungal effect on C. albicans, sensitive C. tropicalis, sensitive C. glabrata, and C. lusitaniae. However, for resistant C. tropicalis, the combination of ThHSA with VCZ promoted yeast growth, and VCZ tended to suppress the antimicrobial effect of ThHSA on resistant C. glabrata. As to the possible transposition of ThHSA-type properties to BSA (as regards the growth inhibition of other pathogens), we tested combinations of BSA with two physiological chromogranin A-derived antimicrobial peptides (catestatin and cateslytin). BSA enhanced significantly the activity of catestatin (but not cateslytin) in combating C. albicans, A. fumigatus, and M. luteus, but was inactive against S. aureus and E. coli. Conclusions: Our experiments support the fact that albumins display intrinsic antimicrobial properties, with an unpredictable growth inhibitory effect on various microbes. ThHSA can thus be an adjunctive tool for more efficient care of some, though not all, infections. The interaction of BSA with catestatin and cateslytin is related to their structure, with BSA significantly enhancing the effect of catestatin but not that of cateslytin. Full article

Background: Exercise duration at maximum oxygen uptake ($\dot{\mathrm{V}̇}$O₂max) appears to be influenced not only by metabolic factors but also by the interplay between brain dynamics and ventilatory regulation. This study examined how cortical activity, assessed via electroencephalography (EEG), relates to performance and acute fatigue regulation during a constant-load cycling test. We hypothesized that oscillatory activity in the theta, alpha, and beta bands would be associated with ventilatory coordination and endurance capacity. Methods: Thirty trained participants performed a cycling test to exhaustion at 90% maximal aerobic power. EEG and gas exchange were continuously recorded; ratings of perceived exertion were assessed immediately after exhaustion. Results: Beta power was negatively correlated with time spent at $\dot{\mathrm{V}̇}$O₂max (r = −0.542, p = 0.002). Theta and Alpha power alone showed no direct associations with endurance, but EEG–metabolic ratios revealed significant correlations. Specifically, the time to reach $\dot{\mathrm{V}̇}$O₂max correlated with Alpha/$\dot{\mathrm{V}̇}$O₂ (p < 0.001), Alpha/$\dot{\mathrm{V}̇}$CO₂ (p < 0.001), and Beta/$\dot{\mathrm{V}̇}$CO₂ (p = 0.002). The time spent at $\dot{\mathrm{V}̇}$O₂max correlated with Theta/$\dot{\mathrm{V}̇}$O₂ (p = 0.002) and Theta/$\dot{\mathrm{V}̇}$CO₂ (p < 0.001). The time-to-exhaustion was correlated with Theta/$\dot{\mathrm{V}̇}$CO₂ (p < 0.001) and Alpha/$\dot{\mathrm{V}̇}$CO₂ (p < 0.001). Conclusions: These findings indicate that cortical oscillations were associated with different aspects of acute fatigue regulation. Beta activity was associated with fatigue-related neural strain, whereas Theta and Alpha bands, when normalized to metabolic load, were consistent with a role in ventilatory coordination and motor control. EEG–metabolic ratios may provide exploratory indicators of brain–metabolism interplay during high-intensity exercise and could help guide future brain-body interactions in endurance performance. Full article

Background: Lung cancer is the leading cause of cancer-related mortality globally, with lung adenocarcinoma (LUAD) as the most common subtype. Dysbiotic intratumoral mycobiomes drive LUAD pathogenesis, and Aspergillus sydowii (A. sydowii) acts as a key oncogenic fungal species. Ginseng polysaccharides (GPs), bioactive phytochemicals with immunomodulatory and oncostatic properties, counteract fungal infections and restore immunosurveillance in LUAD. Methods: Subcutaneous and orthotopic LUAD murine models were established by implanting Lewis lung carcinoma (LLC) cells. Subcutaneous tumors were infected intratumorally and orthotopic models via nasal inoculation. GPs (200 mg/kg/day) were orally administered to evaluate tumor growth. Metagenomic and targeted bile acid metabolomic profiling of fecal and tumor tissues was performed, with Spearman correlations analyzed using R packages. Results: GPs significantly inhibited A. sydowii-induced tumor growth in both models. In subcutaneous tumors; GPs reduced volume (p < 0.05) and weight vs. infected controls. In orthotopic models, GPs decreased pathological nodules and lung weight, with micro-CT/H&E confirming attenuated hyperplasia. Metagenomics showed GPs restored gut homeostasis by enriching Lactobacillus/Muribaculum intestinale and suppressing pro-inflammatory Alistipes. Targeted metabolomics revealed reduced β-Hyodeoxycholic Acid (3β-HDCA), Chenodeoxycholic acid 24-acyl-b-D-glucuronide (CDCA-24G) and 3β-hydroxychol-5-en-24-oic acid (5-isoLCA) after GP treatment. Network analysis confirmed significant microbe–bile acid interactions. Conclusions: GPs exert antitumor effects against A. sydowii-induced LUAD by modulating gut microbiota and bile acid metabolism. This identifies GPs as a promising therapy for mycobiome-influenced cancers, with dual targeting of fungal infection and metabolic reprogramming. Full article

Background: Suicide attempts often co-occur with bipolar disorder (BD), major depressive disorder (MDD), and schizophrenia (SCH). Although impairments of the serotonin (5-HT) system have been associated with suicide attempts, it remains unclear whether these alterations reflect suicidal behavior or are confounded by underlying psychiatric diagnosis. This study used a genotype-informed dynamic model of the 5-HT presynapse to disentangle the effects of suicide attempts and psychiatric diagnosis. Methods: We applied a personalized dynamic model of the 5-HT presynapse to 392 psychiatric patients (with BD, MDD, or SCH), categorized by suicide attempt status, and 140 unaffected individuals. The model incorporated five variants across TPH2, SLC6A4, and MAOA genes simulating individual-specific concentration changes of five 5-HT-related molecular species. Model outputs were summarized by six statistical measures (mean, median, maximum, standard deviation, skewness, and kurtosis) and compared across groups. Results: No significant differences were found across groups defined by suicide attempt status and unaffected individuals. However, diagnosis significantly influenced 5-hydroxyindoleacetic acid (5-HIAA) mean, median, maximum, and standard deviation (all p < 0.05). BD patients had lower 5-HIAA levels than SCH patients (mean: p = 0.013; median: p = 0.013; maximum: p = 0.014; standard deviation: p = 0.014). MDD patients also showed lower 5-HIAA levels than SCH patients for the same measures, with differences approaching significance. No significant difference was observed between BD and MDD patients. A diagnosis-by-suicide attempt status interaction was observed for 5-HIAA skewness (p = 0.013). Conclusions: Model-derived 5-HT profiles were shaped primarily by diagnosis, while temporal dynamics of 5-HIAA, rather than its absolute levels, was associated with suicide attempt status. Thus, personalized dynamic modeling incorporating genetic variants may aid in detecting subtle molecular signatures across diagnoses and suicidal behavior. Full article

This study focuses on tourist-oriented urban historic districts. In recent years, many such districts have experienced commercial intensification and homogenization, placing pressure on sustainable development. The prior work is largely descriptive and offers limited mechanism-level guidance for governance. In response, this study employs Tianzifang as an empirical case and proposes an online-review-driven mechanism-identification framework. Drawing on 3005 online reviews, a quantitative–qualitative mixed approach was adopted: word-frequency and semantic-network analyses of the full corpus mapped topics and their relational structure; guided by these structures, grounded-theory coding was conducted on a negative-review subsample (n = 602); the results indicate a double-helix interaction between culture–commerce and expectation–reality, associated with lower perceived authenticity, affective disconnect, stronger negative word-of-mouth, and perceived declines in attractiveness. The main contributions are: a mechanism identification framework with a replicable quantitative–qualitative integration workflow; the construction of a double-helix mechanism coupling culture–commerce and expectation–reality; and, on this basis, a governance strategy framework to support fine-grained management and the sustainable renewal of urban historic districts. Full article