Search Results (2,839)

Mastitis severely hinders dairy farming, with Streptococcus agalactiae (S. agalactiae) serving as a major causative pathogen. Prolonged antibiotic administration promotes the emergence of multidrug-resistant strains, thereby compromising mastitis control. Consequently, novel natural antibacterial agents are urgently needed. In this study, bacteriostatic assays identified the MIC of rosmarinic acid (RA) against S. agalactiae as 8 mg/mL. At the MIC, RA reduced the adhesion capacity of S. agalactiae by 16.6% and inhibited biofilm formation by 25.09%. RA also disrupted bacterial membrane architecture and markedly downregulated the expression of virulence factors. A mouse model of mastitis treated with varying doses of RA (25, 50, and 100 mg/kg) indicated that RA attenuated pathological damage to the mammary duct architecture and ameliorated inflammatory responses in S. agalactiae-infected mice. ELISA revealed that RA significantly reduced pro-inflammatory mediators, including IL-1α, IL-1β, IL-6, and TNF-α. RT-qPCR results indicated that mRNA expression levels of TLR2, NF-κB, AKT, and PI3K were substantially reduced following RA treatment, whereas apoptosis-related genes p53, RUNX1, and Bim exhibited distinct expression patterns. Western blotting analysis further indicated that RA modulated the phosphorylation of Bim, RUNX1, and p53 in mastitis tissues, suppressed the TLR2/NF-κB inflammatory signaling pathway, and regulated the PI3K/AKT cascade. By targeting multiple pathways, RA suppressed S. agalactiae proliferation and attenuated mammary gland inflammation, highlighting its potential as a green therapeutic agent for sustainable animal husbandry. Full article

Background/Objectives: Tumor progression is often accompanied by sialylation of cell-surface N-glycan glycoproteins with α2-6-linked sialic acids by the sialyltransferase ST6GAL1. Moreover, a hallmark of human cancers is heterogeneity in ST6GAL1 expression among cancer cells, yet the mechanisms and significance of this variability remain poorly understood. Here, we investigate whether epigenetic changes in ST6GAL1 DNA methylation, which affect intracellular ST6GAL1 and cell-surface α2,6-sialylation of glycoproteins, are associated with the biology of human breast cancer (BCa) cells. Methods: We analyzed CpG island methylation across spatially distinct regions of the human ST6GAL1 promoter (P2 and P3) and the associated loss of ST6GAL1 expression in primary human breast tumors compared with adjacent normal tissue controls. Epigenetic changes in ST6GAL1 DNA methylation and patient progression-free survival (PFS) were evaluated. Small-molecule epigenetic inhibitors (5-aza-dC and MS-275) were used to assess ST6GAL1 transcriptional reactivation and its effects on intracellular ST6GAL1, cell-surface α2,6-sialylation, and cell adhesion to collagen I in cultured BCa cell models. Results: In estrogen receptor (ER)+ and human epidermal growth factor receptor 2 (HER2)+ primary BCa tissues, ST6GAL1 P3-promoter hypermethylation, but not P2-promoter methylation, significantly correlated with loss of ST6GAL1 expression compared with adjacent normal controls. Higher promoter methylation was significantly associated with improved PFS in ER+ and HER2+ BCa subtypes compared with triple-negative breast cancer (TNBC). ST6GAL1 protein expression and relative transcript levels are higher in adjacent normal controls or human normal breast epithelial cells than in human BCa tissue or cultured cells. In BCa cells, native ST6GAL1 is sensitive to degradation by cycloheximide or MG-132 and even to sialidase treatment. Pharmacological reactivation with 5-aza-dC or MS-275 restored intracellular ST6GAL1 expression and functional cell-surface α2,6-sialylation, thereby enhancing BCa cell adhesion to collagen I. Since ST6GAL1 is also released into the extracellular milieu by cancer cells, and extracellular ST6GAL1 (exoST6) may contribute to cancer cell-surface protein α2,6-sialylation, we also found that 5-aza-dC increased exoST6 levels released in the form of exosome vesicles. Conclusions: Our results suggest that ST6GAL1 promoter methylation, together with copy-number alterations, drives loss of expression and phenotypic heterogeneity in human BCa, thereby reducing α2,6-sialylation and correlating with improved PFS in the ER+ and HER2+ subtypes. Demethylating agents restore both endogenous ST6GAL1 expression and exosomal exoST6 release in BCa cells, highlighting this targetable epigenetic axis as a promising prognostic biomarker and therapeutic strategy to improve patient survival in progressive diseases. Future studies will focus on evaluating the functional outcomes of targeting cell-native ST6GAL1 versus the exoST6/sialylation pathways and on defining ST6GAL1’s role in driving disease progression in vivo. Full article

Polymeric membrane systems have emerged as an effective approach for water separations due to their high separation efficiency, simplicity, and adaptability to a wide range of water treatment applications. However, traditional membrane fabrication processes often rely on toxic organic solvents, such as N-methyl-2-pyrrolidone (NMP) and dimethylacetamide (DMAc), which pose environmental and health risks. Eco-friendly solvents have been investigated as an alternative to traditional toxic solvents. This study investigates the fabrication and performance of polymeric membranes using eco-friendly solvent systems, with a focus on bilayer membranes designed to improve separation performance over traditional single-layer membranes. Membranes were fabricated using eco-friendly solvents, Rhodiasolv© PolarClean and gamma-valerolactone in combination with polymers polysulfone (PSf) and poly(vinylidene fluoride-co-hexafluoropropylene) (PVDF-HFP). Membranes were fabricated using nonsolvent-induced phase separation (NIPS) through doctor blade extrusion (DBE) and slot-die coating (SDC) methods in order to compare traditional laboratory-scale casting methods (DBE) with scalable fabrication techniques (SDC). Bilayer membranes were investigated to address limitations presented by single-layer membranes, with polydopamine (PDA) incorporated as an adhesion-promoting additive. Membrane characterization included scanning electron microscopy (SEM), contact angle measurements, and tensile testing, along with water permeability and solute rejection tests. Results showed that polymer concentration and casting method influenced permeability and solute rejection, with the SDC bilayers reaching the highest initial BSA rejection. Filtration used deionized water and model aqueous feeds containing 100 ppm NaCl, 100 ppm CaCl₂, and 100 ppm bovine serum albumin (BSA). Full article

Candida tropicalis has emerged as one of the most clinically relevant non-albicans Candida species, owing to its increasing global prevalence, high mortality associated with invasive infections, and rising rates of antifungal resistance. Although traditionally considered an opportunistic pathogen, growing evidence indicates that its remarkable adaptive capacity is driven by the coordinated regulation of multiple biological processes that promote host colonization, persistence, and immune evasion. In this review, we summarize current knowledge on the epidemiology, biology, genomic organization, virulence factors, and host–pathogen interactions of C. tropicalis. Particular emphasis is placed on recent advances in comparative genomics and functional studies that have expanded our understanding of the molecular determinants underlying adhesion, biofilm formation, morphogenesis, extracellular hydrolytic enzyme production, thermotolerance, cell wall remodeling, and immune evasion. We also integrate orthology analyses identifying putative C. tropicalis homologs of well-characterized Candida albicans virulence genes, highlighting the evolutionary conservation of key pathogenic mechanisms while emphasizing species-specific adaptations that remain functionally unexplored. Finally, we discuss current knowledge of antifungal resistance and the emerging relationship between genomic plasticity, stress adaptation, and pathogenicity. Together, this review provides an updated and comprehensive overview of the biological mechanisms that contribute to the success of C. tropicalis as an emerging opportunistic pathogen and identifies key areas requiring further investigation to improve diagnosis, treatment, and the development of novel antifungal strategies. Full article

Diabetes mellitus prevalence is rising globally, linked to persistent hyperglycemia and endothelial dysfunction. Extracellular vesicles (EVs) play a role in diabetes pathology, involving complex intercellular communication that influences endothelial response. However, the mechanisms by which EVs contribute to endothelial dysfunction under hyperglycemia remain unknown. To investigate the effect of glucose-altered EVs on endothelial cells, we isolated EVs from HBMECs and THP-1 cells under normal- and high-glucose conditions (5.5 and 33 mM). We used NTA, electron microscopy, and LC-MS/MS for EV characterization. HBMECs in RPMI’s default glucose (11 mM) were exposed to 100 ng/mL of each EV condition, and adherent THP-1 CFSE+ cells were quantified. Long-term high glucose activated HBMECs without altering cell viability. Glucose level altered EV secretion, content, and function. For HBMECs, high glucose decreased EV release but shifted their cargo toward metabolism, barrier disruption, and neuronal protein content. For THP-1 cells, high glucose kept the EV release rate and shifted the cargo toward an inflammatory activation profile. Functionally, high-glucose EVs (mainly THP-1-derived) showed a pro-adhesive effect on endothelial cells. Here, we describe the impact of glucose on EV biology and how glucose-altered EVs can influence inflammation and endothelial responses, highlighting the importance of glycemic control in diabetic patients. Full article

Alpha-latrotoxin (α-LTX) is the principal vertebrate-specific neurotoxin in widow spider (Latrodectus) venom and a powerful presynaptic secretagogue. Although its receptors, pore-forming activity and stimulation of neurotransmitter release have been studied extensively in central and motor neurons, its relationship to the severe, persistent pain of latrodectism remains poorly understood. This focused review re-examines α-LTX from a nociceptive perspective. The available evidence supports a model in which α-LTX binds adhesion G protein-coupled receptor L1 (ADGRL1; latrophilin-1) and neurexin-1α on susceptible sensory neurons; inserts a large cation-permeable pore; and promotes membrane depolarisation, calcium entry and release of pain-associated neuropeptides. The transcript-level gene expression of α-LTX receptor genes in dorsal root ganglion neurons and evidence of toxin-evoked neuropeptide release provide a molecular basis for direct nociceptor activation, although functional validation in defined nociceptor subclasses remains necessary. A comparison with the nociceptive ion channels transient receptor potential vanilloid 1 (TRPV1) and transient receptor potential ankyrin 1 (TRPA1) highlights their convergence on calcium-dependent sensory excitation, while distinguishing α-LTX from toxins that modulate endogenous channels. We propose that the pain of latrodectism is a composite state in which direct nociceptor activation complements muscle spasm and tissue-derived signalling, positioning α-LTX as a distinctive probe of pain pathways. Full article

Rabbit odontogenic abscesses are among the most challenging chronic infections encountered in exotic animal medicine because of their polymicrobial etiology, biofilm-associated persistence, and poor response to conventional antimicrobial therapy. Biofilm formation plays a central role in disease pathogenesis by promoting bacterial adhesion, extracellular polymeric substance (EPS) production, quorum sensing (bacterial cell-to-cell communication), metabolic heterogeneity, and the persister-cell formation (transiently antibiotic-tolerant bacterial subpopulations), collectively reducing antimicrobial susceptibility and contributing to treatment failure and recurrence. In addition to biofilm-mediated tolerance, antimicrobial resistance (AMR) further complicates disease management through mechanisms including horizontal gene transfer, efflux pump activation, enzymatic antibiotic degradation, reduced membrane permeability, and target modification. This review summarizes current knowledge on the microbiology, biofilm dynamics, and resistance mechanisms associated with rabbit odontogenic infections while examining recent advances in molecular diagnostics, including culture-independent sequencing technologies, metagenomics, and advanced imaging approaches. Current and emerging anti-biofilm strategies, such as local antimicrobial delivery systems, enzymatic biofilm disruption, quorum-sensing inhibitors, bacteriophage therapy, antimicrobial peptides, photodynamic therapy, and nanotechnology-based approaches, are critically discussed in the context of their potential application in rabbits. Comparative evidence from human endodontic infections and other veterinary biofilm-associated diseases highlights the translational relevance of rabbit odontogenic abscesses as a naturally occurring model for chronic polymicrobial infections. Finally, key research gaps are identified, emphasizing the need for standardized experimental models, integrated multi-omics analyses, combining genomic, transcriptomic, proteomic, and metabolomic data, longitudinal clinical investigations, and evidence-based antimicrobial stewardship. By integrating microbiology, biofilm biology, antimicrobial resistance, and One Health concepts, this review provides a comprehensive framework to support future research and improve the diagnosis, treatment, and prevention of rabbit odontogenic infections. Full article

Wearable electronics, particularly dry epidermal electrodes, provide human-connected interfaces for recording biopotential signals. However, their practical utility is often hindered by their limited operational longevity and the resulting environmental burden of electronic waste, as most conventional electrodes are discarded after a single use because of performance degradation. Herein, a reusable, soft, and conductive epidermal electrode is reported, fabricated through the precise incorporation of functional additives. By intentionally modulating the polymer chain architecture, a homogeneous composite is developed that exhibits exceptional flexibility, high conductivity (~100 S/cm), softness (~649 kPa), and stretchability (~234%). This molecular-level design promotes strong intermolecular interactions at the skin–electrode interface, facilitating persistent adhesion and conformability to challenging surfaces, including wet, wrinkled, and stretched skin. These properties enable reliable electrocardiography acquisition through 50 repeated attachment and detachment cycles, over which a commercial Ag/AgCl gel electrode became unmeasurable after 20. The applicability of the electrode to human–machine interfaces is further demonstrated by capturing clear electromyography signals of muscle activity during a rock–paper–scissors game. This low-modulus electrode platform offers a route towards repeated-use wearable healthcare systems and soft-robotics applications, with the potential to reduce the waste associated with single-use electrodes. Full article

To mitigate the deterioration of the tribological performance of end-face friction pairs under low-speed conditions, this study investigated a water-lubricated CF/PEEK–316L stainless steel end-face friction pair. Surface micro-textures with different depth-to-diameter ratios and texture area ratios were fabricated on the 316L stainless steel surface to evaluate the effects of texture parameters and sliding speed on tribological performance. The results showed that appropriately designed micro-textures effectively reduced the coefficient of friction and improved the wear characteristics of the friction pair. Among the tested conditions, the CF/PEEK–316L stainless-steel tribo-pair with a 316L counterface textured at ε = 0.05 and s = 10% exhibited the lowest average friction coefficient. At 200 rpm, this textured tribo-pair exhibited an average friction coefficient approximately 34.8% lower than that of the untextured tribo-pair. Furthermore, laser micro-textures suppressed interfacial material transfer and mitigated adhesive wear and three-body abrasive wear by capturing wear debris. Gear-pump prototype tests further showed that the textured surface improved flow-delivery and volumetric-efficiency performance, while promoting more uniform end-face wear morphology, indicating its potential application in practical gear-pump components. The findings provide guidance for surface-texture design and tribological-performance optimization of polymer/metal end-face friction pairs. Full article

Portable handheld bioprinters represent a transformative advancement in personalized skin regeneration, bypassing the logistical constraints of stationary lab-based systems by enabling real-time, in situ fabrication of bioengineered constructs directly within the wound bed. This review aims to evaluate the current state of their development and clinical translation. One of the foci is placed on the stringent physicochemical requirements for bioinks, where we examined the critical balance between bioadhesion—facilitated by functional groups—and mechanical cohesion necessary for maintaining structural integrity during deposition, while RGD motifs are considered primarily as promoters of integrin-mediated cell adhesion. Preclinical studies have demonstrated promising effects of bioprinted constructs on wound healing and tissue organization; however, human evidence for handheld and direct in situ skin bioprinting remains limited, and clinical efficacy has yet to be established in controlled studies. Nevertheless, widespread adoption is hindered by inferior printing fidelity relative to stationary counterparts, a lack of standardized GMP-compliant bioink production, and regulatory ambiguity that impedes clear classification as either medical devices or biologics. Practical barriers, including intraoperative sterility assurance and operator training, also remain unresolved. Looking ahead, we discuss how the convergence of, in particular, artificial intelligence for real-time wound morphometry, closed-loop process control, and smart, self-healing biomaterials promises to surmount these obstacles. We conclude that these synergistic innovations may propel handheld bioprinters from experimental prototypes toward clinical tools with the potential to reshape reconstructive surgery and emergency wound care, although their clinical value will require validation in appropriately designed human studies. Full article

The clinical success rate of titanium (Ti) implants is significantly reduced in elderly patients and by implant-associated bacterial infections. Thus, Ti surfaces were modified using sandblasted large-grit alkaline etching (SLA), argon-nonthermal plasma treatment, and recombinant human secretory leukocyte protease inhibitor (rhSLPI) coating. This study evaluated surface characteristics, human fetal osteoblast (hFOB 1.19) activities, and antibacterial efficacy. The modified surfaces exhibited increased roughness and hydrophilicity compared to Ti. The SBPTi-rhSLPI enhanced 7-day protein retention on the surface. While Ti promoted higher cell proliferation, the modified groups demonstrated superior cell adhesion and mineralization. Specifically, SBPTi-rhSLPI showed the highest cytoplasmic spreading, adhesion-related gene expression (Itg$\alpha$1, Itg$\alpha$2, Itg$\alpha$5, and Itg$\beta$1), and mineralization. Additionally, rhSLPI-coated groups effectively reduced the adhesion of both S. aureus and E. coli. In conclusion, combining SLA modification, argon plasma treatment, and rhSLPI coating provides enhanced effects. This combined approach significantly enhances osteoblast adhesion and mineralization while possessing antibacterial potential, which could be a promising strategy to improve implant success rates. Full article

The mechanical properties of continuous-fiber-reinforced composites in FDM-3D printing are significantly influenced by process parameters. However, research in this area is constrained by printing equipment, control software, and material preparation. This study examines how the tensile and interlaminar shear properties of CCF/PA and CF/PEEK are affected by continuous-fiber nozzle temperature, platform temperature, and printing speed. Studies indicate that enhancing the nozzle temperature can notably improve mechanical properties by enhancing material flowability, ensuring consistent fiber encapsulation and reducing pore defects. Increasing the platform temperature initially boosts both tensile strength and ILSS, but, beyond a certain point, these properties decline. Inadequate platform temperature can result in uneven infiltration and diffusion among deposited CCF/PA paths, leading to void defects. Conversely, excessive platform temperature can cause semi-molten CCF/PA layers to be vulnerable to nozzle pressure and scraping, resulting in continuous-fiber debonding and interlayer tearing. Furthermore, lower printing speeds extend the melt wetting time between adjacent paths, promoting diffusion and adhesion for enhanced performance. Following an experimental investigation, the optimal parameters are identified as a nozzle temperature of 295 °C, a platform temperature of 240 °C, and a printing speed of 3 mm/s. This research provides valuable guidance for the practical production of continuous-fiber-reinforced composites using FDM-3D printing. Full article

The role of Fusobacterium nucleatum (F. nucleatum) in regulating exosome-mediated communication between oral squamous cell carcinoma (OSCC) cells and lymphatic endothelial cells (LECs) remains poorly understood. Here, we confirmed the presence of F. nucleatum in OSCC tissues and showed that it induced inflammation- and vesicle-associated transcriptional changes in OSCC cells. Exosomes were isolated by differential ultracentrifugation, and quantitative analyses demonstrated that F. nucleatum stimulation increased exosome yield from OSCC cells. In vitro, pretreatment of LECs with exosomes derived from F. nucleatum-stimulated OSCC cells (Fn-Exo) enhanced OSCC cell adhesion to LEC monolayers. Fn-Exo upregulated intercellular adhesion molecule 1 (ICAM1) expression in LECs, and ICAM1 blockade partially reduced Fn-Exo-induced OSCC cell adhesion to LECs. Fn-Exo increased intracellular reactive oxygen species (ROS) accumulation and promoted NF-κB p65 phosphorylation and nuclear translocation in LECs. N-acetyl-L-cysteine (NAC) attenuated Fn-Exo-induced ROS accumulation and NF-κB activation, and both NAC and the NF-κB inhibitor BAY 11-7082 reduced ICAM1 upregulation and partially attenuated the enhanced adhesion of OSCC cells to Fn-Exo-treated LECs. These pharmacological inhibition experiments support the involvement of ROS/NF-κB/ICAM1 signaling in the Fn-Exo-induced pro-adhesive phenotype. Collectively, these findings indicate that F. nucleatum is associated with increased exosome yield from OSCC cells and that Fn-Exo enhances the adhesive interaction between OSCC cells and LECs. Full article

Intrauterine adhesion (IUA) is a fibrotic disorder resulting from aberrant repair following injury to the endometrial basal layer, leading to menstrual abnormalities, infertility, recurrent miscarriage, and pregnancy complications. Although hysteroscopic adhesiolysis remains the primary clinical treatment, the rate of postoperative re–adhesion is still high, especially in patients with moderate–to–severe IUA. Moreover, mechanical separation alone is often insufficient to restore intact endometrial architecture and reproductive function. Hydrogels, with their hydrated three–dimensional networks, extracellular matrix (ECM)–mimicking properties, injectability, biodegradability, tissue adhesion, and tunable delivery capacity, have evolved from passive barrier materials into multifunctional therapeutic platforms capable of regulating the pathological microenvironment and promoting tissue regeneration. Recent advances in responsive, self–healing, adhesive, antioxidant, and bioactive cargo–loaded hydrogels have expanded their applications from preventing adhesion formation toward functional endometrial reconstruction. In this review, we summarize recent progress in hydrogel–based IUA therapy, focusing on material composition, structural design, functional modification, therapeutic mechanisms, and translational considerations. Particular emphasis is placed on disease–informed hydrogel engineering strategies that integrate the unique anatomical characteristics of the uterine cavity, injury–associated microenvironment, and dynamic stages of endometrial repair. This perspective provides insights into the development of next–generation hydrogel systems for preventing re–adhesion and restoring reproductive function. Full article

De-escalation of axillary surgery has resulted in the loss of pathologic nodal information, yet the extent of lymph node involvement remains an important determinant of treatment decisions in estrogen receptor-positive (ER+)/HER2− disease. We examined whether primary tumors differed molecularly according to the extent of this regional dissemination. Genome-wide DNA methylation profiling of primary ER+/HER2− tumors from 47 patients with pN1 (n = 29) vs. >pN1 (n = 18) disease showed differences concentrated at promoters of developmental and cell-adhesion genes. By integrating methylomes with transcriptomes from the TCGA-BRCA cohort (n = 148) and clinical outcomes from KM Plotter (RFS, n = 1154; OS, n = 442; DMFS, n = 423), we identified four genes (ARL10, RIC3, CXCL14, KCNH2) showing concordant molecular and clinical associations, from which we derived the Lymph-node Involvement Outcome Numerator (LION) score. Lower LION scores were observed in metastatic lesions from the AURORA US cohort (n = 45). In SCAN-B (n = 3969), lower scores were associated with shorter distant recurrence-free intervals (HR = 0.38; 95% CI 0.23–0.62); this association persisted after adjustment for age, nodal and tumor category but was lost after adjustment for histological grade (HR = 0.83; 95% CI 0.48–1.44), indicating that the score and grade capture overlapping biology. These findings suggest that primary tumors already display coordinated epigenetic and transcriptional alterations associated with the extent of metastatic dissemination. Full article