Search Results (34,119)

Osteoclast hyperactivity represents a central mechanism in pathological bone destruction, underscoring the importance of discovering novel anti-resorptive compounds. In this study, we present early-stage evidence that 8-Epixanthatin can inhibit osteoclast differentiation induced by receptor activator of nuclear factor kappa-B ligand (RANKL). 8-Epixanthatin exhibited no significant cytotoxicity at the concentrations used for osteoclast differentiation studies. The compound showed concentration-dependent reductions in TRAP-positive multinucleated osteoclasts, with an IC₅₀ value of 2.3 μM. Our mechanistic investigations revealed that 8-Epixanthatin interferes with RANKL-activated signaling networks, particularly nuclear factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPK) cascades. Collectively, these observations identify 8-Epixanthatin as a promising lead structure for anti-osteoclast drug discovery. Full article

In this study, the chemical composition of highland barley (HB), microwave fluidization HB (HB-1), extrusion and puffing HB (HB-2), and ultrafine pulverization HB (HB-3) were investigated based on untargeted metabolomics. In addition, RNA-seq transcriptomics, real-time polymerase chain reaction (qRT-PCR) and Western blot (WB) analysis were used to investigate the lipid metabolism mechanism of HB-1, induced by a high fat and cholesterol diet (HFCD). The results indicated that a total of 1292 metabolites were detected and classified into 78 distinct classes in the untargeted metabolomics analysis including fatty acyls, carboxylic acids and derivatives, glycerophospholipids, organooxygen compounds, prenol lipids, and so on. HB-1, HB-2, and HB-3 all increased the levels of amino acids and their derivatives, phenols, and carboxylic acid and its derivatives compared with HB. Furthermore, RNA-seq transcriptomic results indicated that HB-1 significantly modulated key genes of Cyp2c38, Cyp2b13, and Cyp2b9 related to steroid hormone biosynthesis and CD36, Plin4, and Fabp4 related to the PPAR signaling pathway, which played key roles in lipid metabolism. Moreover, qRT-PCR and WB results indicated that HB-1 obviously enhanced ADIPOQ expression level, while it reduced SCD-1, CD36, Fabp4, and SREBP-1c expression levels, suggesting that the alleviation of lipid metabolic dysregulation by HB-1 in hyperlipidemia mice might be mediated via participating in the PPARγ pathway. This study provided essential theoretical insights for the development and utilization of HB. Full article

Glycosylation is one of the most prevalent post-translational modifications of membrane proteins and plays a central role in regulating their structure and function. Unlike many existing reviews that address glycosylation in a system-wide context, this review focuses specifically on membrane proteins and examines how glycosylation shapes their functional behavior and clinical relevance. Because membrane proteins are exposed to the extracellular environment, glycans on their surface directly influence protein folding, receptor organization, and interactions with ligands and immune components. These diverse effects can be understood within a common mechanistic framework in which glycosylation modulates protein conformation, receptor clustering, and membrane organization, thereby altering signaling, adhesion, transport, and immune recognition. We discuss how N-linked and O-linked glycosylation regulate major classes of membrane proteins across these processes. Particular attention is given to disease-associated alterations in glycosylation, especially in cancer, immune and inflammatory disorders, and metabolic disease. For instance, glycosylation-dependent stabilization of PD-L1 and modulation of receptor signaling, such as EGFR, illustrate how glycan modifications contribute to immune evasion and therapeutic response. We further consider the clinical implications of membrane protein glycosylation, including its roles in biomarker development and as a potential target for therapeutic intervention. Advances in glycoproteomic technologies have enabled increasingly detailed characterization of site-specific glycosylation, although significant analytical challenges remain, particularly for membrane proteins. Overall, this review highlights membrane protein glycosylation as a dynamic regulatory layer that links molecular mechanisms to functional outcomes and clinical applications. Full article

The particle size of aggregate is a key factor affecting the mechanical properties and deformation capacity of cemented gangue filling body. In this study, coal gangue with a particle size range of (0.05, 20) mm was sieved into six groups of aggregate particles. Based on the Talbot gradation theory, cubic specimens with gradation indices n = 0.3, 0.4, 0.5, 0.6, and 0.7 were prepared for acoustic emission (AE) monitoring tests. The microstructure of the filling body was analyzed, and the failure characteristics and damage evolution laws of the cemented gangue filling body with different gradation indices were explored. The results show that the compressive strength reaches its maximum when n = 0.5. As the gradation index increases, the compressive strength of the specimens first increases and then decreases, and the specimens shift from primarily experiencing cleavage failure to shear failure. The curve of cumulative AE ringing count shows a bimodal distribution pattern, with both surge points and fracture points coexisting. The surge points can be regarded as precursor signals of backfill failure. The spatiotemporal evolution of AE events exhibits complex phased changes. An excessively small gradation index tends to form micropores and striped microcracks, reducing the compactness of the microstructure. An excessively large gradation index can lead to the formation of penetrative weak channels. A reasonable gradation index enables the mutual interlocking of aggregate particles, constructing a stable three-dimensional spatial skeleton structure. The dynamic trend of damage in the filling body can be captured based on AE analysis, and reverse guidance can be provided for parameter optimization of Talbot gradation, achieving a dynamic closed loop of “gradation design-AE monitoring-damage assessment-parameter optimization”. This not only enriches the application scenarios of acoustic emission analysis in graded materials, but also provides a new research approach and technical method for gradation design and safety assessment in scenarios where particle sizes are missing in practical engineering. Full article

Vaccinium bracteatum Thunb. leaves (VBTL), a traditional medicinal plant historically consumed as food in certain regions of China, have been documented to possess potent in vitro antioxidant activity. However, its in vivo anti-aging effects and underlying mechanisms remain to be fully elucidated. Therefore, this study aimed to evaluate its anti-aging efficacy to support its potential value as a functional food constituent for healthy aging. Anti-aging efficacy was systematically assessed using D-galactose-induced aging mice, a Caenorhabditis elegans model, and an H₂O₂-induced cellular senescence model. Key active constituents were identified via untargeted metabolomics. In D-galactose-induced aging mice, VBTL extracts effectively ameliorated oxidative stress, significantly increasing the activities of endogenous antioxidant enzymes such as superoxide dismutase (SOD) and catalase (CAT), while reducing malondialdehyde (MDA) levels. In Caenorhabditis elegans, VBTL extended lifespan, reduced lipofuscin accumulation, and demonstrated no reproductive toxicity. Untargeted metabolomics identified xanthotoxol as a key active constituent, which was then selected for mechanistic investigation. In a cellular senescence model, xanthotoxol alleviated H₂O₂-induced oxidative stress, significantly enhanced SOD activity, reduced reactive oxygen species (ROS) and MDA levels, inhibited senescence-associated β-galactosidase (SA-β-gal) activity and the expression of senescence-associated secretory phenotype (SASP) factors (IL-6, MMP1, MMP3), and downregulated the expression of genes in the P53/P21/P16 signaling pathway. Mechanistically, xanthotoxol activated the Nrf2 signaling pathway, promoting the expression of its downstream targets heme oxygenase-1 (HO-1) and NAD(P)H quinone oxidoreductase 1 (NQO1). This study demonstrates that VBTL and its active compound xanthotoxol exert anti-aging effects across multiple models by modulating the Nrf2 pathway, providing both theoretical and experimental foundations for developing VBTL as a novel, safe, and effective natural ingredient in anti-aging functional foods. Full article

This study systematically elucidated the developmental characteristics and molecular regulatory mechanisms of the testis during the critical period of sexual maturation in Kazakh horses by combining histological observation of one- and two-year-old testicular tissues with transcriptomic sequencing. In the testes of one-year-old horses, no obvious lumen was observed, and the interior is mainly comprising supporting cells and spermatogonia on the basement membrane; in contrast, in the testes of two-year-old horses, the tubular lumen was complete with spermatogonia, spermatocytes, and spermatozoa, indicating that spermatogenic function had approached maturity. Transcriptome profiling identified 979 differentially expressed genes (DEGs), with 209 up-regulated genes, including CYP11A1 and CATSPER2, and 770 down-regulated genes, including CD9. Gene Ontology (GO) annotation indicated primary enrichment of DEGs in biological processes related to multicellular organism development, cell membrane composition, and ion binding. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed significant enrichment of DEGs in the calcium signaling pathway, cell adhesion molecules, and neuroactive ligand–receptor interaction, among other key pathways. Protein–protein interaction (PPI) network analysis further highlighted core genes, including TNF, CATSPER2, and CDH13. Validation by RT-qPCR confirmed the reliability of the RNA-Seq data. Our findings reveal the dynamics of testicular development in Kazakh horses through histological and molecular analyses, thereby providing a theoretical framework and candidate genes to further elucidate regulatory mechanisms and guide genetic improvement in reproductive traits. Full article

Antioxidant peptides show significant activity and can be developed into functional foods for treating chronic diseases. Cigarette smoke components can cause damage or even apoptosis of lung cells, eventually leading to chronic lung diseases. Therefore, this study aimed to investigate the protective effects and mechanisms of Skipjack tuna peptides against in vitro cigarette smoke extract (CSE)-induced chronic obstructive pulmonary disease (COPD). The results demonstrated that tuna peptides DVGRG (S1), PHPR (S5), GRVPR (S6), and SVTEV (S7) significantly enhanced the activities of SOD, CAT, and GSH-Px by upregulating the mRNA transcription levels of Keap1 and Nrf2, consequently reducing ROS and MDA levels in CSE-induced COPD model of MLE-12 cells. Molecular docking analysis revealed that S1, S6, and S7 competitively inhibited the Keap1-Nrf2 interaction by binding to the Kelch domain of Keap1, whereas S5 operated through a non-competitive mechanism. These peptides also downregulated p65 mRNA expression and upregulated IκBα mRNA expression, leading to a significant reduction in inflammatory cytokines of IL-1β, IL-6, and TNF-α, thereby alleviating inflammatory responses. Furthermore, these peptides significantly inhibited CSE-induced apoptosis by restoring mitochondrial membrane potential and upregulating the Bcl-2/Bax ratio. Additionally, S1, S5, S6, and S7 promoted MLE-12 cell migration in a concentration-dependent manner, suggesting a role in lung epithelial repair and regeneration. In conclusion, tuna peptides S1, S5, S6, and S7 exert antioxidant, anti-inflammatory, anti-apoptotic, and cell migration-promoting effects through the regulation of the Keap1/Nrf2 and NF-κB signaling pathways, as well as Bcl-2/Bax apoptotic balance, providing a promising strategy for mitigating CSE-induced lung injury. Full article

Classifying power quality disturbances (PQDs) under strong noise conditions remains challenging for existing deep learning models. These models typically separate denoising from feature extraction, often rely on attention mechanisms that operate along only a single dimension, and tend to achieve high accuracy at the cost of high complexity, which limits their performance under low signal-to-noise ratio conditions and hinders practical deployment. To address these limitations, this paper proposes AD-PDAF-Net, which organically integrates three key mechanisms through a co-design strategy. Unlike conventional methods that depend on preprocessing, an adaptive soft thresholding denoising layer is embedded into a lightweight residual network to progressively suppress noise during feature extraction, thereby unifying denoising with feature learning. A parallel dual attention module independently refines features along the channel and temporal dimensions, then adaptively fuses them using learnable weights to capture both frequency domain and temporal characteristics of disturbances. The lightweight network entry replaces aggressive downsampling with small convolutions to preserve transient details, and a bidirectional long short-term memory network (BiLSTM) efficiently captures temporal dependencies. Evaluated on a dataset of 25 disturbance categories defined in IEEE Std 1159-2019, the model achieves a classification accuracy of 97.26% and a Kappa coefficient of 97.02% under 20 dB white Gaussian noise, along with an accuracy of 98.78% under mixed noise conditions. The model has only 0.36 million parameters and a computational cost of just 1.50 GFLOPS. Through this co-design, AD-PDAF-Net achieves both high noise robustness and high classification accuracy with minimal computational overhead, offering an effective solution for time series signal recognition in resource constrained environments. Full article

A keloid is a benign fibroproliferative cutaneous disorder characterized by excessive extracellular matrix deposition, which is driven by persistent fibroblast proliferation and aberrant wound healing. Its complex pathogenesis involves genetic susceptibility, chronic inflammation, mechanical tension and dysregulated cellular signaling, resulting in poor clinical efficacy and high recurrence rates. Cellular senescence has recently become a central focus in exploring keloid pathophysiology, offering a novel perspective for elucidating its initiation, progression and recurrence. This review systematically summarizes the biological roles of cellular senescence in keloid pathology: it elaborates on the basic concepts and core molecular features of cellular senescence, details the spatial heterogeneity of senescent cell accumulation, the activation and pathological effects of senescence-associated secretory phenotype (SASP), and clarifies the molecular link between senescence-resumed proliferation (SRP) and keloid recurrence and treatment resistance. It also summarizes advances in senescence-related markers, the regulatory roles of the p53/p21 and Wnt/β-catenin pathways, and potential senescence-targeted therapies (senolytic, senomorphic, signaling intervention, cell reprogramming). Finally, we discuss the challenges and future perspectives for translating senescence research into clinical keloid treatments, aiming to provide a novel theoretical framework and therapeutic targets for keloid management. Full article

Mastitis is a common inflammatory disease that harms mammary gland health. Its development is closely linked to dysregulated inflammatory signaling. Eicosapentaenoic acid (EPA), an omega-3 polyunsaturated fatty acid, has potential anti-inflammatory effects. However, its molecular mechanism in mastitis prevention remains unclear. In this study, we used both in vivo and in vitro models to evaluate how EPA pretreatment regulates mastitis-related inflammatory signaling. Transcriptome analysis showed that differentially expressed genes after EPA treatment were mainly enriched in the peroxisome proliferator-activated receptor (PPAR) signaling pathway. In an LPS-induced mastitis model, EPA restored the LPS-reduced PPARγ protein level and suppressed NF-κB p65 activation, consistent with reduced nuclear translocation of p65. Similar effects were observed in mammary epithelial cells, where EPA inhibited NF-κB activation at 50 and 100 μM. Functional experiments further showed that a PPARγ agonist mimicked the inhibitory effect of EPA on p65, whereas PPARγ antagonist partially abrogated EPA-mediated inhibition of p65. Collectively, these data indicate that EPA attenuates mastitis-associated inflammation at least in part through the PPARγ–NF-κB axis. Full article

Respiratory infections remain a leading cause of morbidity and mortality worldwide, highlighting the urgent need to better understand host defense mechanisms in the respiratory tract. Recent advances in sequencing technologies have challenged the traditional view of the lungs as sterile organs and revealed the presence of a distinct, low-biomass microbial community known as the lung microbiota. These microbial populations interact closely with airway epithelial cells and immune cells to maintain respiratory homeostasis and regulate host immune responses. In healthy lungs, microbial communities dominated by Firmicutes, Bacteroidetes, and Proteobacteria contribute to immune regulation through interactions with innate and adaptive immune pathways. Microbiota-derived signals are detected by pattern recognition receptors, activating signaling pathways that regulate cytokine production, immune cell recruitment, and T-cell differentiation. In the respiratory mucosa, microbial stimulation can also induce epithelial and antigen-presenting cells to produce B-cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL), which promote immunoglobulin A (IgA) class-switch recombination and support mucosal antibody responses. During pulmonary infection, disruption of microbial communities can lead to dysbiosis that amplifies inflammatory responses, impairs epithelial barrier integrity, and increases susceptibility to secondary bacterial infections. In addition to local microbial interactions, the gut–lung axis represents a key communication pathway linking intestinal microbiota with respiratory immunity through microbial metabolites such as short-chain fatty acids (SCFAs) and immune signaling networks. This review summarizes current insights into microbiota–immune crosstalk in the lung during pulmonary infection and discusses how these interactions may inform mucosal vaccine development. A deeper understanding of host–microbiota interactions may enable microbiome-informed vaccines and therapeutic strategies to improve protection against respiratory diseases. Full article

Background: YES1 is an Src family non-receptor tyrosine-protein kinase that regulates cell growth, migration, survival, and oncogenic signaling. Although YES1 activation mechanisms and substrates have been extensively studied, its phosphosite-specific regulation across diverse biological contexts remains poorly understood. Methods: We performed a large-scale integrative analysis of 3825 publicly available human mass spectrometry-based phosphoproteomic datasets to map YES1 phosphorylation events. Co-modulation, co-occurrence, evolutionary conservation, and disease-association analyses were conducted to characterize the functional and clinical relevance of site-specific YES1 phosphorylation. Results: Y426 emerged as the predominant YES1 phosphosite across diverse biological conditions, localized within the activation loop of the kinase domain and conserved across Src family kinases. Co-modulation analysis identified 421 positively and 102 negatively associated phosphosites enriched in biological processes related to cell cycle regulation, transcription, cytoskeletal remodeling, apoptosis, and carcinogenesis. Among these high-confidence protein phosphosites, we identified 24 binary interactors, 5 upstream regulators, and 8 candidate downstream substrates. Comparison with DisGeNet cancer biomarkers showed overlap between YES1-associated phosphoproteomic signatures and site-specific oncogenic markers across multiple cancers, such as breast cancer, colorectal cancer, leukemia, and lung adenocarcinoma. Conclusions: This study provides a systems-level, phosphosite-focused view of YES1 signaling and supports a central regulatory role for Y426 within global phosphoregulatory and cancer-associated networks. Full article

Accurate classification of rock fracture modes is essential for understanding rock mass instability mechanisms. To address the limitation of traditional acoustic emission (AE) classification methods that treat a single AE signal as a single fracture event, overlooking its composite nature from multiple fracture events and leading to misclassification, this study proposes a novel rock fracture mode classification method based on AE spectral analysis. This study details the development framework, theoretical model, classification criteria, application process, and experimental validation of the new rock fracture mode classification method. Uniaxial compression tests on granite, marble, and limestone, along with rockburst simulation tests on granite, were conducted to validate the classification of fracture modes. In rockburst simulations, shear fracture signals accounted for 48% on average, composite signals 40%, and tensile signals 12%. The method effectively distinguishes multiple fracture events within a single AE signal, accurately classifies fracture modes, and elucidates the dynamic evolution of fracture modes during the rockburst precursor stage, offering significant advantages for rock fracture mode classification and mechanistic insight. Full article

The evolution toward sixth-generation (6G) networks envisions humans as active nodes within a fully interconnected digital ecosystem, supported by data collected from in-body and on-body sensors. Since many of these devices are not equipped to connect directly to 6G networks, Wireless Body Area Networks (WBANs) serve as an essential intermediate layer. However, conventional radio-frequency technologies face limitations in terms of energy efficiency, security, and data integrity, motivating the adoption of lightweight security mechanisms. Physical Layer Security (PLS), and in particular Physical Key Extraction (PKE), offers a promising solution by enabling legitimate devices to derive shared cryptographic keys from the reciprocal properties of the communication channel. Galvanic coupling (GC) communication has recently emerged as an on-body transmission technology alternative to radio-frequency (RF), which exploits low-power electrical signals propagating through biological tissue. Building on prior feasibility studies, this work proposes a PKE framework tailored to GC channels, integrating a lightweight key reconciliation method, based on Hamming (7,4) error-correction codes, and evaluating system performance through dedicated reliability and security Key Performance Indicators (KPIs). Results reveal a trade-off shaped by electrode placement and channel quantization parameters. Among the ones tested, the optimal configuration is achieved with a 3 cm transverse inter-electrode spacing at both transmitter and receiver, and a 3 cm longitudinal separation between transmitter and receiver, by quantizing the channel impulse response with two quantization bits. While this work focuses on validating the method in controlled conditions in order to establish a reliable study framework, future developments will focus on enhanced reconciliation, privacy amplification, and analysis of the GC channel considering physiological and environmental variations. Full article

Acoustic emission (AE) and digital image correlation (DIC) techniques enable real-time capture of damage signals and full-field deformation at anchored rock–concrete interfaces under shear loading, which is critical for quantitatively characterizing freeze–thaw (F-T) degradation and preventing geological disasters in cold regions. This study synchronously monitored full-shear-process AE signals using a broadband AE system (150 kHz resonant frequency, 5 MS/s sampling) and captured high-precision full-field deformation via a 5-megapixel monocular DIC system (25 fps). F-T cycle and direct shear tests were conducted on sandstone–concrete anchored specimens with varying F-T cycles and anchor depths to investigate their effects on shear mechanical properties, AE characteristics and failure modes. Results show that AE peak ring count first decreases by 44.9% then increases by 56.5%, while cumulative ring count exhibits a three-stage evolution. Shear crack proportion first decreases then increases, with tensile failure remaining dominant throughout. DIC reveals that F-T cycles shift failure from crack propagation to surface delamination and interface slip, while different anchor depths induce distinct failure patterns. This study confirms that AE and DIC can accurately characterize F-T degradation, providing a reliable non-destructive monitoring method for cold-region anchorage engineering. Full article