Search Results (4,981)

Prostaglandin E₂ (PGE₂) plays a critical role in regulating uterine endometrial function and supporting embryonic development during early pregnancy in ruminants. However, its precise roles in shaping the uterine microenvironment remain unclear. Herein, 1 mg PGE₂ was infused daily into the uterus of dairy heifers from days 12 to 14 of the estrus cycle. ULF was subsequently collected for integrated proteomic, metabolomic, and targeted lipidomic analyses. In addition, bovine endometrial epithelial cells were used to evaluate the effects of PGE₂ on epithelial adhesion and responsiveness to interferon tau (IFNT). PGE₂ infusion resulted in 909 differentially abundant proteins (DAPs), which are primarily associated with early embryonic development, immune regulation, and cell adhesion. Untargeted metabolomics analysis identified 587 altered metabolites, which were enriched in sphingolipid, arachidonic acid, phenylalanine, and tryptophan metabolism. Proteomic–metabolomic analyses showed that these alterations were primarily associated with early embryonic development, immune regulation, and cell adhesion. Targeted lipidomic analysis showed a global reduction in lipid accumulation, with glycerophospholipid metabolism and choline metabolism most significantly affected. In vitro, PGE₂ reduced epithelial microvilli density, increased osteopontin (OPN) expression, and decreased the expression of junctional proteins (zona occludens-1 (ZO-1), E-cadherin (CDH1), and fibronectin 1 (FN1)). Moreover, PGE₂ enhanced the responsiveness of bEECs to IFNT by interferon alpha/beta receptor 1 (IFNAR1) and IFNAR2, and prostaglandin E receptor 4 (PTGER4) was identified as the primary receptor mediating this response. Collectively, these findings suggest that PGE₂ may modulate lipid metabolism and adhesion-related processes in the endometrium and influence endometrial responsiveness to IFNT, providing insights into molecular mechanisms associated with pregnancy establishment in dairy cows. Full article

Background: The optimal timing of adjuvant chemotherapy after cytoreductive surgery in epithelial ovarian cancer remains uncertain, and perioperative wound-healing responses may transiently create a pro-tumorigenic and drug-resistant microenvironment. This study aimed to characterize time-dependent wound-induced transcriptomic alterations and to identify pharmacologic agents capable of reversing these responses. Methods: An ID8 murine ovarian cancer model was used to compare no treatment, anesthesia alone, and anesthesia plus surgical wounding mimicking futile laparotomy. Tumors were collected at baseline, 1 day (T1), 1 week (T2), and 2 weeks (T3) after intervention. RNA sequencing was performed, and wound-specific differentially expressed genes (WsDEGs) were defined by excluding anesthesia- and progression-related signatures. Functional enrichment analyses were conducted, followed by transcriptome-based drug repurposing using the REMEDY platform to identify compounds predicted to reverse wound-induced gene expression profiles. Results: Surgical wounding significantly increased tumor burden at T1. Transcriptomic analyses revealed distinct, time-dependent wound-associated programs. At T1, WsDEGs were enriched in inflammatory signaling, coagulation, angiogenesis, and immune cell migration, with Vorinostat and Homoharringtonine identified as top candidates to counteract these signatures. At T2, pathways related to cell survival, adhesion, and morphogenesis predominated, with LY-2090314, Artesunate, and Birinapant emerging as potential modulators. At T3, cell-cycle regulation and lipid metabolic pathways were dominant, and Fulvestrant, Atorvastatin, Imatinib, and ABT-737 were predicted to inhibit these processes. Conclusions: Perioperative surgical wounding induces dynamic, stage-specific transcriptomic programs that may promote ovarian cancer progression and alter drug responsiveness. These findings support time-adapted perioperative pharmacologic strategies to optimize postoperative cancer therapy. Full article

A dual-mode electrical–optical nanocomposite hydrogel is developed by integrating carboxyl-modified upconversion nanoparticles (UCNPs-COOH) and quaternized chitosan (CQAS) into a polyacrylamide (PAAm) covalent network. The hydrogel exhibits high optical transparency (>90% in the visible region), excellent mechanical properties (fracture strain of 1742%, tensile strength of 0.85 MPa, toughness of 6.57 MJ/m³), and robust adhesion to various substrates. The synergistic covalent–noncovalent hybrid network enables efficient energy dissipation, while CQAS-enhanced dispersion of UCNPs significantly improves upconversion luminescence intensity and stability, as evidenced by prolonged fluorescence lifetime from 0.564 ms to 0.691 ms at 539 nm. Leveraging distinct electrical and optical signal transduction pathways, the hydrogel functions as a highly sensitive resistive strain sensor with multistage gauge factors up to 13.85 and excellent cyclic stability over 1200 loading–unloading cycles at 100% strain for human motion monitoring. It also serves as a ratiometric optical pH sensor over a broad range (pH 1–13) based on phenolphthalein-sensitized upconversion luminescence, with excellent repeatability. By integrating real-time resistance responses with optical readouts within a single soft material, this work demonstrates a reliable dual-mode sensing strategy for simultaneous mechanical and chemical monitoring, holding promise for wearable electronics, smart healthcare, and environment-responsive sensing systems. Full article

The use of marginal sedimentary aggregates in pavement construction remains a major challenge in mountainous regions due to their high porosity, weak lamination planes, and susceptibility to moisture-induced deterioration. This study investigates the potential of low-density polyethylene (LDPE) plastic waste to enhance the engineering performance of laminated Miocene soft rock aggregates used in bituminous concrete. Aggregates sourced from the Surma Group (Bhuban Formation) in Mizoram, India, were characterized through physico-mechanical, geochemical, and mineralogical analyses to evaluate their durability and moisture sensitivity. X-ray fluorescence (XRF) analysis revealed elevated feldspar and total alkali contents (≈5.15%), indicating a mineralogical composition prone to hydrophilic behavior and stripping within bituminous mixtures. To mitigate these limitations, aggregates were coated with varying proportions of LDPE plastic using the dry process. An optimum LDPE content of 9% by weight of aggregate produced significant improvements in aggregate performance, resulting in a 70.03% reduction in Aggregate Impact Value (from 17.72% to 5.31%), a decrease in Los Angeles Abrasion Value from 42.93% to 31.45%, and an 89.82% reduction in water absorption (from 4.52% to 0.46%). The polymer coating effectively sealed lamination planes and reduced moisture ingress within the sedimentary structure. Bituminous concrete mixtures incorporating LDPE were further evaluated using Marshall stability and indirect tensile strength tests. The addition of 1.1% LDPE by weight of mix significantly enhanced moisture resistance. For mixtures with nominal maximum aggregate sizes (NMASs) of 13 mm and 19 mm, the Tensile Strength Ratio (TSR) increased from 52.59% and 58.58% in the control mixtures to 82.81% and 87.10%, respectively, thereby satisfying the minimum requirement of 80% specified by MoRTH. The results indicate that LDPE functions as a hydrophobic barrier and structural sealant that improves binder–aggregate adhesion and prevents stripping along weak lamination planes. The findings demonstrate that LDPE-modified bituminous concrete provides a sustainable and technically viable strategy for upgrading marginal sedimentary aggregates into durable pavement materials while simultaneously promoting the beneficial reuse of plastic waste. Full article

The interface between biomaterials and biological systems is crucial for medical implants and tissue engineering. Surface modifications are a key strategy for controlling interactions. Synthetic glycopolymers offer a versatile toolbox, mimicking the structure and function of natural glycoconjugates like mucins. This review highlights the significance of glycopolymers for targeted surface modifications of established biomaterials, such as silicones and poly(meth)acrylates. Controlled polymerization techniques, like the reversible-addition-fragmentation chain-transfer (RAFT) polymerization, enable the synthesis of well-defined glycopolymer architectures. Glycopolymeric surface functionalization creates tailored interfaces for different biological responses, from preventing protein and cell adhesion to promoting specific cell-type binding. The focus lies on using single, well-characterized polymeric base materials and tuning their surface properties through glycopolymer coatings to achieve various and specific functions. This approach opens new dimensions in the development of advanced biomaterials for applications like contact lenses, drug delivery systems, and biosensors and also possesses potential regulatory advantages by leveraging the safety profiles of existing materials. Full article

Background/Objectives: Severe and recurrent infections due to multidrug-resistant (MDR) Pseudomonas aeruginosa necessitate alternative antimicrobial strategies. Fermented cacao beans represent a niche microbial ecosystem with the potential to harbor beneficial lactic acid bacteria (LAB). This study aimed to isolate and characterize LAB strains from fermented cacao beans in southern Thailand and to evaluate their probiotic potential and antimicrobial activity against MDR P. aeruginosa. Methods and Results: Five Lactiplantibacillus plantarum isolates were identified via MALDI-TOF MS and whole-genome sequencing (WGS). All strains demonstrated antimicrobial activity against 17 clinical MDR P. aeruginosa isolates and CR14 exhibited the largest inhibition zone. The isolates displayed robust probiotic traits, including survival under simulated gastrointestinal conditions. Acid tolerance (pH 2.0) reached 61.15 ± 7.75%, while resistance to pepsin, pancreatin, and bile salts exceeded 88%, 91%, and 92%, respectively. Strong adhesion was confirmed via auto-aggregation (55.02 ± 1.75%), hydrophobicity (45.58 ± 0.96%) and Caco-2 cell attachment (up to 98.11 ± 3.28%). WGS revealed multiple plantaricin-encoding clusters. Coarse-grained molecular dynamic simulations showed that two-peptide plantaricins (plnJ/K and plnNC8-αβ) self-assembled and formed stable pores in bacterial membrane models, confirming a pore-forming antimicrobial mechanism. The strains lacked acquired resistance genes and virulence factors, confirmed by in silico safety assessments. Conclusions: Thus, these L. plantarum strains are promising probiotics for managing MDR P. aeruginosa via functional foods or adjunct therapies. Full article

Bcakground: Hepatocellular carcinoma (HCC) is a prevalent malignancy with limited therapeutic options. Drug repurposing offers an attractive strategy to accelerate anticancer discovery. The pleuromutilin class of antibiotics, including the human-approved agent lefamulin and the veterinary drug tiamulin, has shown preliminary anticancer potential, but its efficacy and mechanism in HCC remain unexplored. Methods: The anti-tumor effects of lefamulin and tiamulin were evaluated in HCC cell lines, patient-derived organoids, and a C57BL/6 mouse subcutaneous tumor model. Safety was assessed in a human normal hepatocyte cell line and by histopathological examination of major organs in treated mice. Mechanistic investigations were performed using RNA-sequencing, RT-qPCR, immunohistochemistry (IHC), filipin staining, pharmacological rescue assays, and shRNA-mediated gene silencing. Results: In this study, we found that both lefamulin and tiamulin markedly inhibited HCC cell proliferation in vitro and significantly suppressed tumor growth in vivo (lefamulin vs. control, p = 0.014; tiamulin vs. control, p = 0.021), without causing significant toxicity. RNA-sequencing analysis revealed consistent downregulation of the cholesterol transporter Abca1 (ATP-binding cassette transporter A1) and alterations in cell adhesion molecule pathways. Functional studies confirmed that treatment reduced ABCA1 protein levels, leading to intracellular cholesterol accumulation and aberrant distribution. Furthermore, treated tumors exhibited a significant increase in CD8⁺ T-cell infiltration, with CD4⁺ T cells and macrophage infiltration remained unchanged, indicating a specific modulation of the tumor immune microenvironment. Conclusions: These findings suggest that lefamulin and tiamulin are promising therapeutic candidates for HCC. Full article

Functionally graded nickel-based coatings represent an advanced surface engineering approach designed to enhance the performance of components operating in high-temperature and harsh environments. Unlike conventional coatings with uniform composition, functionally graded coatings exhibit gradual variations in composition and microstructure across their thickness, enabling improved adhesion, reduced residual stresses, and enhanced multifunctional performance. This review provides a comprehensive overview of recent developments in nickel-based functionally graded coatings, focusing on substrate materials, coating compositions, and manufacturing technologies. Particular attention is given to coatings designed for high-temperature applications and harsh service conditions, including carbide-reinforced composite coatings and MCrAlY-type systems used for oxidation and corrosion protection. Various fabrication methods, including laser cladding, additive manufacturing, electrodeposition, and thermal spraying, are critically discussed in terms of their advantages and limitations. The current state of the art is analyzed with emphasis on coating performance in high-temperature and aggressive environments. Finally, key challenges and future research directions are identified, highlighting the need for improved long-term performance evaluation, advanced manufacturing approaches, and the development of multifunctional gradient coating architectures. Full article

This study investigated the surface characteristics and wettability behaviour of grey poplar (Populus × canescens) compared with spruce (Picea abies) in order to evaluate its potential as an alternative raw material for bonded structural wood products. Surface roughness was analysed on freshly planed radial surfaces using amplitude and functional roughness parameters, complemented by multivariate factor analysis and dynamic contact angle measurements. The results showed that grey poplar sapwood exhibited roughness values comparable to spruce (R_a ≈ 6–7 μm; R_z ≈ 35–40 μm). Grey poplar heartwood showed slightly higher roughness and greater variability, which can be attributed to its heterogeneous anatomical structure characterised by larger vessel elements and higher extractive content. Hybrid roughness parameters indicated favourable bonding-related surface characteristics in sapwood due to lower R_pk values, suggesting fewer protruding fibres, while higher R_vk values reflected the diffuse-porous anatomical structure of poplar. Static contact angle measurements revealed higher initial values for grey poplar (37.9° for heartwood and 41.9° for sapwood) compared with spruce (31.7°), indicating lower initial wettability with polar liquids. However, dynamic measurements demonstrated faster early-stage spreading in grey poplar heartwood (Δθ = 26.1° within the first second) compared with sapwood (16.8°) and spruce (17.5°), suggesting that vessel-driven capillary uptake may facilitate liquid penetration once wetting begins. Overall, the results indicate that grey poplar—particularly its sapwood fraction—exhibits surface characteristics comparable to spruce after planing. Despite slightly lower initial wettability, its spreading behaviour and surface morphology indicate favourable conditions for adhesive interaction. These findings support the potential use of grey poplar as an alternative raw material for laminated structural products such as glulam or bonded panels, provided that adhesive application parameters are properly adjusted. Full article

Myogenic mechanobiology governs how mechanical cues regulate myocyte organization, alignment, and functional maturation; however, in vitro platforms that enable quantitative control and real-time readout of myogenic mechanical microenvironments remain limited. Here, we engineered a pneumatic-driven organ-on-a-chip platform integrating six parallel culture units and a bead-embedded flexible PDMS membrane to deliver cyclic mechanical strain and enable quantitative stress–strain mapping in cardiomyocytes and skeletal muscle cells. Finite element-guided optimization ensured effective membrane deformation, and the platform generated stable and tunable cyclic strain with a strong linear relationship between applied negative pressure (50–700 mbar) and membrane stress and strain. Plasma treatment combined with type I collagen coating restored myogenic cell adhesion and growth on PDMS to levels comparable to standard culture conditions. Under 13% cyclic strain, both cardiomyocytes and skeletal muscle cells exhibited pronounced and highly uniform alignment, with cellular polarity oriented perpendicular to the stretch axis. Moreover, cyclic loading significantly enhanced the expression of contractile maturation markers, including MYH7 in cardiomyocytes and MYH6 in skeletal muscle cells (all p < 0.05), whereas expression of the differentiation regulator MyoG remained unchanged, indicating that mechanical stimulation preferentially promotes structural organization and contractile maturation rather than lineage commitment. Collectively, this quantitatively programmable organ-on-a-chip represents a bioengineered microdevice for studying myogenic mechanobiology, revealing conserved mechanosensitive alignment and maturation responses across myogenic lineages and providing a versatile framework for biomedical engineering research, disease modeling, and mechanotherapeutic screening. Full article

Background/Objectives: Nature-inspired therapeutic strategies that promote biological regenerative mechanisms and replicate the native structural microenvironment conductive to formation of healthy tissue are increasingly recognized as a promising platform for skin tissue regeneration and wound healing. This study proposes an innovative design of novel multifunctional scaffolds composed entirely of natural components—gelatin, L-ascorbic (ASA) acid and allantoin—as a bioinspired approach for skin tissue regeneration through pro-regenerative, antimicrobial, and keratinocyte-supportive properties. Methods: The biocompatible, skin-adhesive scaffolds were prepared via a simple and environmentally friendly heat-induced crosslinking of gelatin with varying ASA contents, and by enriching the system with allantoin. The influence of ASA content on scaffold properties was investigated through characterization of their morphology, porosity, swelling behavior, skin tissue adhesion, and allantoin release potential. Biocompatibility was evaluated in vitro using human keratinocyte (HaCaT) cells, while antibacterial activity was assessed against Escherichia coli and Staphylococcus epidermidis. Results: The scaffolds revealed a highly porous, interconnected structure with tunable porosity (87.37–92.39%) and soft-tissue-matched mechanical properties (0.81–1.47 MPa). Incorporation of allantoin into the scaffolds enhanced their mechanical performance and swelling capacity. All scaffolds demonstrated antibacterial activity against both tested bacteria, supported keratinocyte viability and provided sustained release of allantoin for up to 76 h, confirming their multifunctional pro-regenerative potential. Conclusions: The novel gelatin/ascorbic acid scaffolds enriched with allantoin combine a porous replicated structure of native extracellular matrix, fluid absorption capacity, soft-tissue-like mechanical properties, stable skin tissue adhesion, cytocompatibility and antibacterial functionality with the pro-regenerative properties of allantoin, thereby representing a multifunctional and biologically inspired platform for advanced skin tissue regeneration and wound-healing applications. Full article

Chronic exposure to benzo[a]pyrene (BaP), a Group 1 IARC carcinogen, is a major driver of lung carcinogenesis; however, how sustained subcytotoxic exposure reprograms bronchial epithelium toward preneoplastic states remains poorly defined. Here, we subjected BEAS-2B human bronchial epithelial cells to 12 weeks of continuous BaP at environmentally relevant concentrations (0.1 and 1.0 µM) and interrogated the resulting phenotypes using an integrated multi-scale framework encompassing functional toxicology, RT-qPCR, RNA-seq, phospho-kinase/NF-κB arrays, and organotypic air–liquid interface (ALI) cultures. Cells maintained metabolic competence throughout, evidenced by sustained CYP1A1 and CYP1B1 induction at both acute (4 h) and chronic (12-week) timepoints, while accumulating genotoxic stress as demonstrated by dose-dependent nuclear γ-H2AX foci formation and ATM phosphorylation (Ser1981). RNA-seq revealed a dose-dependent transcriptional shift: 0.1 µM BaP yielded 119 differentially expressed genes (DEGs; |log2FC| ≥ 1, FDR < 0.05), whereas 1.0 µM generated 255 DEGs. Downregulated transcripts were enriched for extracellular matrix and cell-adhesion programs (COL14A1, ADAMTS2, CSMD3, CADM3), while upregulated genes encompassed inflammatory, calcium-signaling, and vesicle-trafficking modules (NFATC4, CSF2RA, SYT1, PCLO). Phospho-kinase/NF-κB arrays confirmed a p53/NF-κB signaling nexus, with concurrent activation of MAPK/ERK (Thr202/Tyr204) and PI3K/Akt (Ser473) pathways. Despite persistent genotoxic stress, cells did not acquire anchorage-independent growth and remained non-tumorigenic in vivo. Critically, ALI organotypic cultures derived from BaP-exposed cells exhibited histological dysplasia, nuclear pleomorphism, and disrupted apical-basal polarity. These findings mechanistically link chronic BaP exposure to an initiation-like preneoplastic state and establish a validated 2D/3D multi-omics platform for PAH-driven lung carcinogenesis research. Full article

The development of inks with suitable rheological, physicochemical, mechanical, and biological properties is crucial for the successful fabrication of functional scaffolds via extrusion-based 3D printing. In this study, collagen/chitosan hydrogels with varying polymer ratios were developed and characterized to evaluate their printability and suitability for cartilage tissue engineering. Rheological analyses revealed that all samples exhibited shear-thinning behavior and solid-like viscoelasticity, with the formulation of an 80:20 COL/CHI ratio (20CHI) demonstrating optimal filament formation and dimensional stability. Physicochemical analyses confirmed the preservation of the collagen triple helix and the formation of hydrogen bonding between chitosan and collagen. 20CHI scaffolds showed swelling capacity and high cohesiveness. In vitro studies confirmed the cytocompatibility of the scaffolds with murine fibroblasts and the ability of the scaffolds to promote adhesion, proliferation, and extracellular matrix production of both chondrocytes and adipogenic mesenchymal stem cells (aMSCs). Quantification of sulfated glycosaminoglycan (sGAG) indicated sustained matrix deposition over 28 days, particularly by chondrocytes. These findings demonstrate that 20CHI hydrogel is a promising candidate for 3D printing of biomimetic scaffolds for cartilage regeneration. Full article

A major drawback of many proposed biobased alternatives of the most commonly used petroleum-based packaging materials is their relatively poor physical properties. In order to develop more viable alternative packaging materials, these properties need to be modified, while maintaining and improving the other desired characteristics. An investigation was done on corona-charged curcumin-containing PLA films to determine how the addition of the polyphenol impacts its physical properties. Measurements of the surface potential of the films were performed, as was the impact of low pressure on the electret properties. The effect of the corona discharge treatment on the physicochemistry of the surface of composite PLA films was investigated systematically using some complementary surface analytical techniques, such as surface wettability and morphology by scanning electron microscopy. The mechanical properties and conductance of the films were also investigated. A dependency of the decay of the surface potential on the film type and the polarity of the corona was found. It was also established that modifying the surface of the films with corona discharge can cause an increase in their wettability and surface free energy, while also improving their adhesion properties. This is caused by the creation of polar functional groups on the film surface during the charging process. It was also determined that the introduction of curcumin in the PLA films decreases their stiffness, which may be caused by a decrease in intramolecular cohesion. Full article

Mechanical signals play key roles in the regulation of epidermal homeostasis and regeneration after injury. Integrins are key components of focal adhesions, and these complexes are major contributors to mechanotransduction. In keratinocytes, integrin-linked kinase (ILK) modulates essential processes for epidermal homeostasis and wound repair. However, its functions in the transduction of mechanical stimuli have remained virtually unexplored. In this study, we characterized epidermal tissues and primary keratinocytes from mice with epidermis-restricted inactivation of the Ilk gene (ILK-KO). ILK-deficient epidermis exhibits abnormalities in key components of mechanotransduction cascades, including disruptions in hemidesmosomal Collagen XVII immunoreactivity at the dermal–epidermal junction, and marked reduction in the nuclear localization of the mechanosensitive transcriptional regulator YAP. In wild-type (ILK+), but not in ILK-KO-cultured keratinocytes, exposure to cyclic bidirectional strain induced marked F-actin cytoskeletal rearrangements, characterized by the assembly of thick cortical actin bundles and stress fibers, as well as YAP nuclear translocation and transcriptional activity. Exposure to mechanical strain was additionally accompanied by differential changes in miRNA expression between ILK+ and ILK-KO cells. These findings reveal multiple and previously unappreciated key regulatory roles for ILK in epidermal keratinocyte responses to mechanical signals. Full article