Search Results (3,773)

Nuclear transport is a vital system that mediates movement of essential biomolecules between the nucleus and cytoplasm. It is tightly regulated by the Importin (IMP) superfamily to maintain separation of cellular compartments. Cellular stress in various forms, particularly oxidative, can suspend nuclear transport and lead to cell death. Prolonged oxidative stress manifests in myriad conditions, including cancer, viral infection and metabolic disease. An IMP protein, Importin-13 (IMP13), retains function under stress, while all other IMP family members tested to date do not. Phylogenetic and structural analysis revealed Transportin-3 (TNPO3) as the closest homologue of IMP13, suggesting it may also retain its function under stress. Subcellular localisation studies indicated that TNPO3 maintained its typical subcellular localisation, even in the presence of stress, unlike most IMP family members. Also, fluorescence recovery after photobleaching (FRAP) demonstrated that TNPO3 shuttling is unaffected under stress. Co-immunoprecipitation studies examining cargo binding revealed the capacity of TNPO3 to bind its cargo in the presence of stress. This demonstrated for the first time that TNPO3 retains functionality under stress conditions, in contrast to other IMPs, but similar to IMP13. Furthermore, both IMP13 and TNPO3 appear to protect against the potentially critical mislocalisation of Ran, a key molecule involved in the maintenance of the nuclear transport system. Full article

To address the surface wear issues of tungsten alloys in die-casting mold applications—where low hardness coupled with severe service conditions involving high-pressure impact from molten metal, thermal cycling, and component counter-friction—this study employed three techniques: laser cladding, plasma spraying, and vacuum surface carburization. Three distinct strengthening coatings were prepared on a tungsten heavy alloy (WHA) substrate. X-ray diffraction (XRD), scanning electron microscopy (SEM), a Vickers hardness tester, and block-on-ring friction and wear tests were employed to characterize the phase composition, microstructure, hardness, and wear resistance of the coatings. The results indicate that all three coatings significantly enhanced the hardness of the substrate, albeit through different strengthening mechanisms. The hardness increase in the laser-clad coating is attributed to the combined strengthening effect of rapid solidification-induced fine grains and dispersed WC particles. The enhanced hardness of the plasma-sprayed coating is due to the intrinsic hardness of WC and its dense layered structure. The carburized layer exhibits the highest hardness, resulting from the continuous WC phase formed via in situ reaction and an interface-free gradient transition with the substrate, which eliminates interfacial weak zones. Under loads of 50 N and 100 N, the plasma-sprayed coating demonstrated the best wear resistance, with wear volumes of 0.16% and 0.18% of that of the substrate, and wear depths of 4.57% and 3.50% of that of the substrate, respectively. It also exhibited the optimal load adaptability, making it a preferred solution for surface strengthening of tungsten alloy die-casting molds. Full article

Laser-induced microjet-assisted ablation is an emerging technology in the field of laser processing. However, the influence of solid boundaries on jet behavior and the associated material removal mechanism remains unclear after observing and analyzing the ablation process. To address this, the present study systematically investigates the effect of the incidence angle on the processing efficiency and material removal mechanism in laser-induced microjet ablation. By controlling the laser power and liquid layer thickness, the dynamic behavior of the microjet, material removal performance, and surface morphology evolution under different inclination angles were explored. Based on video analysis and OpenCV processing, the regulation of jet morphology and impact mode by the incidence angle was revealed. Combined with white light interferometry and ultra-depth-of-field three-dimensional microscopy, the ablation depth and material removal rate were quantitatively characterized. The results showed that under normal incidence, the maximum material removal rate of 0.092 mm³/s was achieved at 9 W, while further increases in power led to a decrease in removal rate due to bubble aggregation. When the sample was tilted to 15°, the material removal rate reached 0.163 mm³/s, representing a 106.30% improvement compared to that at 0°, and the ablation depth also peaked with an average maximum depth of 12.32 ± 0.58 μm and a single-point maximum of 54.36 μm. Furthermore, scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDS) were employed to elucidate the microstructural features and elemental distribution under different process parameters. Through multi-parameter experiments, this study achieved process parameter optimization and clarified the material removal mechanism influenced by different incidence angles, providing both a process reference and theoretical basis for efficient micro-machining of aerospace materials. Full article

Pulse repetition frequency (PRF) controls pulse off-time and, therefore, the extent of thermal accumulation, melt expulsion, and dielectric recovery in finishing electrical discharge machining (EDM). This study clarifies how PRF modifies crater evolution and surface integrity in finishing EDM of 4Cr13 martensitic stainless steel, a corrosion-resistant mold steel used in precision dies and molds. A 2D axisymmetric electro-thermo-fluid model was established in COMSOL, where Gaussian current density, heat-flux, and plasma pressure were periodically imposed at PRFs of 25–100 kHz, while pulse-on time (6 μs) and peak current (8 A) were kept constant. The simulations tracked the transient pressure, heat-flux, velocity, and temperature fields over a common elapsed time of 25 μs. Finishing experiments were then carried out on flat 4Cr13 coupons at 50, 75, and 100 kHz using a copper electrode and deionized water, followed by characterization by laser confocal microscopy, SEM/EDS, and X-ray diffraction using the cosα method. Increasing PRF localized the coupled pressure-heat-flow fields near the crater rim, but shortened off-time and intensified inter-pulse heat accumulation. Accordingly, the surface roughness decreased from Ra = 1.18 μm at 50 kHz to 0.63 μm at 75 kHz, and then slightly increased to 0.71 μm at 100 kHz because of crater overlap, re-melting, and incomplete gap recovery. SEM observations confirmed large irregular craters with cracks at 50 kHz, more uniform fine craters at 75 kHz, and overlapping re-solidified traces at 100 kHz. The residual stress remained compressive for all tested conditions (−341 to −409 MPa). Overall, 75 kHz offers the best compromise between crater uniformity, roughness, and compressive stress for finishing EDM of 4Cr13 steel. Full article

Under the conditions of laser power of 1500 W, scanning speed of 5 mm/s, spot diameter of 3.5 mm, and powder feeding rate of 10 r/min, this study systematically investigated the influence of different tempering temperatures (200 °C and 600 °C) on the microstructure, friction and wear properties, and corrosion resistance of laser cladding Ni25 coatings, as well as the underlying mechanisms. The phase composition, microstructure, chemical composition, wear resistance, and corrosion resistance of the coatings were characterized and analyzed using X-ray diffraction (XRD), scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), pin-on-disk friction and wear tests, and electrochemical workstations. The results showed that the as-clad coating was composed of γ-Ni supersaturated solid solution and various metastable borides/carbides (such as Cr₃B₄), presenting fine-grained and non-equilibrium features. Tempering at 200 °C mainly achieved stress relaxation, enhancing and shifting the diffraction peaks to the left without changing the phase composition, while tempering at 600 °C drove significant diffusion-type phase transformation, leading to the decomposition of metastable Cr₃B₄ and the precipitation of stable phases such as Ni₂Si, accompanied by grain growth and microstructure coarsening. Friction tests indicated that the coating tempered at 600 °C exhibited the lowest average friction coefficient (0.679) and wear volume (0.0582 mm³) due to stable microstructure and hard phase strengthening, demonstrating the best wear resistance. However, electrochemical tests revealed a “trade-off” effect: the fine-grained microstructure of the as-clad coating, with its uniform composition, had the lowest corrosion current density (8.10 × 10⁻⁵ A/cm²) in 3.5% NaCl solution, showing the best resistance to uniform corrosion, while tempering, especially at 600 °C, caused grain growth, coarsening of the second phase, and micro-galvanic effects, slightly reducing the anodic dissolution resistance and increasing the corrosion current. This study clarified that heat treatment can significantly enhance the mechanical and tribological properties of Ni25 coatings by regulating their transformation from metastable to stable states, but at the potential cost of some corrosion resistance, providing a theoretical basis for optimizing post-treatment processes for different service conditions (wear resistance or corrosion resistance). Full article

Titanium and its alloys are widely used in orthopedic and dental implantology for their corrosion resistance and biocompatibility supporting osseointegration; however, their usage is accompanied by release of wear debris that may induce inflammatory responses. The necessity of formation of multifunctional coatings that accelerate osseointegration and provide long-term mechanical stability of titanium implants remains highly relevant. We propose a new simple and scalable coating method based on the laser shock processing technique, with TiO₂ and SrCO₃ powder mix used as an absorption layer. Our results show that this treatment created an approximately 158.3 ± 35.8 μm thick coating consisting of a mixed SrTiO₃-TiO₂ phase. The hardness of this coating evaluated by Vickers microhardness measurements showed a hardness increase of 3.3 times compared to the initial titanium substrate. Piezoelectric force microscopy (PFM) analysis revealed the presence of a reverse piezoelectric effect in the obtained structure confirming the highly likely successful synthesis of coating impregnated with SrTiO₃. This piezoelectric coating can be readily deposited onto titanium substrates using the proposed method, enabling exploration of potential biomedical applications in future research. Full article

Metal substrates were preprocessed via picosecond laser surface texturing (PLST, 532 nm) to fabricate interfacial microgrooves for tribological performance optimization prior to deposition of a magnesium silicate hydroxide (MSH)/graphite/MoS₂–PI solid lubricant coating. By tuning the PLST parameters (average laser power: 0.2–0.5 W, scan passes: 3–5, hatch spacing: 0.005–0.1 mm), three representative texture geometries (linear, circular, and square) were produced, and the resulting coating performance was compared with conventional mechanical polishing and sandblasting pretreatments. Among the three laser textures, the linear texture exhibited the most excellent tribological performance and interfacial adhesion, outperforming the circular and square counterparts. Ball-on-disk tests in a kerosene-contaminated environment (10 N, 800 rpm) showed that the linear-textured sample reached the lowest steady-state friction coefficient (0.038), lower than polished (0.048) and sandblasted (0.052) controls, together with reduced wear scar dimensions. Progressive-load scratch tests indicated a pronounced adhesion enhancement, with the critical failure load increasing from 7.05 N (polished) to 26.05 N for the linear-textured interface, which is higher than 21.21 N (circular) and 23.78 N (square) textures. Cross-sectional microscopy and EDS mapping reveal that the laser-defined microgrooves (~15 μm depth, ~120 μm width, ~500 μm spacing) act as a parameter-controlled interfacial architecture that promotes mechanical interlocking and provides lubricant-rich reservoirs. This laser-enabled interfacial design suppresses delamination, supports transfer film stability, and ultimately enhances the coating’s tribological performance by reducing friction and wear. Full article

In a previous study, we demonstrated that a novel surface treatment applied to laser-melted Ti6Al4V substrates supports osteoblast-like cell adhesion, proliferation, and the activation of early osteogenic pathways. Building on these preliminary findings, the present work aimed to further investigate the ability of the same surface to promote extracellular matrix (ECM) deposition, organization, and osteogenic maturation, which are critical events for the establishment of a stable bone–implant interface in subperiosteal dental implants. Human osteoblast-like MG-63 cells were cultured on Ti6Al4V discs subjected to different surface treatments, including a proprietary surface modification (ATcs) specifically designed for subperiosteal applications. ECM formation and maturation were evaluated through scanning electron microscopy coupled with energy-dispersive spectroscopy, immunofluorescence, and semiquantitative analyses of osteogenic markers type I collagen (COL1A1), secreted protein acidic and rich in cysteine (SPARC), and dentin matrix protein 1 (DMP1) through Western blotting. The results showed that, while all tested surfaces supported cell adhesion, the ATcs surface promoted a distinct osteogenic profile characterized by enhanced DMP1 expression, organized collagen deposition, and the formation of calcium–phosphate–rich mineralized structures. Compared to surfaces that primarily stimulated cell proliferation or early matrix production, ATcs appeared to favour progression toward late-stage osteogenic maturation and matrix mineralization. Taken together, these findings extend our previous observations and indicate that this novel surface treatment not only supports osteoblast viability and early differentiation but also promotes extracellular matrix maturation, a key prerequisite for effective osseointegration. Although further in vivo studies are required, the present data provide additional biological rationale for the use of ATcs-treated Ti6Al4V surfaces in next-generation custom-made subperiosteal implant designs. Full article

Streptococcus mutans (S. mutans), one of the main etiological pathogens of dental caries, forms dental plaque biofilms that drive tooth decay. Although bacterial membrane vesicles (MVs) are increasingly recognized as modulators of biofilm biology, little is known about MVs generated by S. mutans. The objective of this study is to investigate the role of S. mutans-derived MVs in the development of S. mutans biofilms formed under static conditions in plates or confocal dishes. Transmission electron microscopy and nanoparticle tracking analysis revealed that the MVs were cup-shaped with bilayered membranes and averaged 80.49 $\pm$ 32.24 nm in diameter. The addition of ≥5 µg/mL MVs enhanced biofilm formation during the initial adhesion stage (0 to 6 h), as demonstrated by crystal violet staining and XTT assays. Confocal laser scanning microscopy and scanning electron microscopy confirmed the incorporation of PKH26-labeled MVs into S. mutans biofilms and showed that supplemental MVs increased bacterial viability and extracellular polysaccharide biomass. Furthermore, RT-qPCR analysis revealed upregulated expression of genes related to adhesion and quorum-sensing systems in MV-treated biofilms. In conclusion, these findings indicate that S. muants MVs are integral biofilm components that promote biofilm establishment at the early stage of biofilm formation. Full article

Background/Objectives: Photobiomodulation Therapy (PBMT) is widely used in musculoskeletal rehabilitation. Although its clinical use continues to expand, the dose-dependent metabolic responses on specific musculoskeletal cell populations remain undefined. This study assessed the effects of 1064 nm PBMT on primary human tenocytes and bursa-derived cells across varying fluence and irradiance. Methods: Primary tenocytes and bursa-derived cells were cultured in 24-well plates and exposed to Hiro TT 1064 nm laser at fluences ranging from 1.5 to 6.0 J/cm² and irradiance levels of 90 or 125 mW/cm². Treatments were administered once daily for three consecutive days. Cellular activity was assessed using an XTT assay and bright field microscopy was performed to assess cell morphology and confluency. Statistical analysis was compared to evaluate dose-dependent effects. Results: PBMT demonstrated tissue-dependent effects on cellular metabolic activity and proliferation. In tenocytes, moderate fluence (4.5–6.0 J/cm²) significantly increased metabolic activity compared with control. In contrast, bursa-derived cells exhibited smaller magnitude changes, with most treatment groups demonstrating neutral or modest deviations from control. Conclusions: PBMT of 1064 nm wavelenght produced distinct dose-dependent responses in musculoskeletal cell types, with tenocytes demonstrating a threshold-dependent response and bursa-derived cells showing attenuated effects. These findings support the need for tissue-specific parameters when applying PBMT in clinical tendon-related applications. Full article

Glioblastoma (GBM) remains the most aggressive primary malignant brain tumor in adults, with poor survival largely driven by diffuse cellular infiltration, profound heterogeneity, and near-universal recurrence following standard therapy. Although maximizing the extent of resection is a key determinant of patient outcome, current clinical imaging modalities lack the spatial resolution necessary to detect microscopic tumor invasion and therapy-resistant cell populations. Emerging in vivo imaging technologies capable of cellular and near-single-cell resolution have therefore become a major focus in preclinical neuro-oncology research, with growing relevance for surgical guidance, treatment adaptation, and translational discovery. This review evaluates multiple optical imaging modalities, including multi-photon microscopy, near-infrared II fluorescence imaging, bioluminescence imaging, photoacoustic imaging, optical coherence tomography, confocal laser endomicroscopy, Raman spectroscopy, autofluorescence microscopy, and fluorescence macroscopy with a focus on their ability to detect residual GBM cells. Despite significant advances, these approaches remain constrained by limitations in molecular target availability, probe delivery across the blood–brain barrier, and signal variability within heterogeneous tumor regions. The biological complexity of GBM further challenges detection, as residual tumor cells are spatially dispersed and phenotypically diverse, limiting the effectiveness of single-marker or single-modality strategies. Together, these findings highlight the need for integrated, biologically informed imaging approaches to improve detection of residual disease and guide surgical decision making. Full article

Liquid infant formula has garnered increasing attention due to its mild thermal processing and superior retention of bioactive nutrients. Within such matrices, the lipid source is a critical determinant of protein digestion behavior, yet its influence on peptide bioavailability and intestinal homeostasis remains undefined. Given that efficient peptide absorption is vital for the systemic delivery of bioactivity in infants, understanding the lipid–protein synergy is essential for formula optimization. Moreover, excessive oxidative stress is closely associated with impaired intestinal health and developmental disorders in infants, making the regulation of oxidative stress crucial for maintaining intestinal function. The present study evaluated the effects of three distinct lipid sources—soybean oil (SM), bovine milk fat (BM), and goat milk fat (GM)—on the physicochemical stability, proteolytic digestion, peptide release, intestinal absorption, and oxidative stress modulation of goat-milk-based infant formula. An integrated approach combining physicochemical characterization, in vitro simulated infant digestion, and a Caco-2 intestinal epithelial cell model was employed. we demonstrate that all three lipids (3% w/w) formed stable emulsions with uniform spherical structures and mean particle diameters of 117–300 nm, as visualized by laser confocal microscopy. Following in vitro simulation of infant gastrointestinal digestion, the SM group exhibited the most extensive protein hydrolysis, yielding the highest total peptide content (4.28 ± 0.10 mg/mL) and generated the highest number of peptides identified by LC-MS/MS (474 types). Bioinformatic analysis predicted that peptides from all groups possess potential antihypertensive, hypoglycemic, and immunomodulatory activities. The Caco-2 monolayer cell model demonstrated that although the GM group produced fewer identified peptide species than the SM group (365 types), it achieved significantly higher intestinal peptide absorption rate (55.34 ± 1.05%). Furthermore, the GM digests provided superior protection against H₂O₂-induced oxidative stress in Caco-2 cells, markedly reducing reactive oxygen species levels and suppressing the expression of pro-inflammatory cytokines TNF-α and IL-6. Collectively, these findings reveal that while soybean oil promotes more extensive proteolysis, the use of homologous goat milk lipid enhances peptide bioaccessibility and confers potential cytoprotective effects on intestinal epithelial cells, underscoring its potential as a preferred lipid source in infant formula formulations. Full article

The methodical work describes all the necessary steps for establishing a stable oral ex vivo biofilm using saliva and crevicular plaque samples from periodontal healthy donors. First, cover slips were preconditioned with saliva supernatants and subsequently inoculated with crevicular plaque suspensions. Ex vivo biofilm formation was characterized by confocal laser scanning microscopy (cLSM) after 1, 4, 24, 48 and 72 h of anaerobic cultivation. Exemplarily, the inhibitory characteristics of blackcurrant fruit extracts [all-fruit juice (AFJ); alcoholic fraction from berry skins (AFBS)] were observed on 1, 4 and 24 h-aged ex vivo biofilms. Chlorhexidine (CHX, 0.2%) served as positive control. After direct contact (3 min), biofilms were dispersed, plated onto agar and anaerobically cultivated for 24 h. Early ex vivo biofilms (1 h-biofilm) showed scattered microbial colonies. After 4 h of cultivation, a multilayered biofilm was formed. Biofilm mass gradually increased, displaying a complex polymicrobial structure after 24 h. At 72 h, the biofilms had a dense three-dimensional appearance. Treatment with AFJ and CHX was more efficient in inhibiting biofilm growth compared to AFBS. Early biofilms (1 h, 4 h) were more susceptible to AFJ and CHX compared to 24 h-biofilms. The introduced model can be recommended for testing the efficiency of plaque-controlling agents. Full article

Background: Total glycosides of peony (TGP) have therapeutic potential for immune-related and inflammatory skin diseases, but their skin absorption is not satisfactory. This study aims to investigate how Evodia rutaecarpa volatile oil (VO-ER) enhances the permeability of TGP. Methods: Safety assessment was conducted through cell delivery and skin erythema tests. The chemical composition of VO-ER was identified via GC-MS. The study was conducted using modified Franz diffusion cells, microdialysis, confocal laser scanning microscopy (CLSM), attenuated total reflection–Fourier transform infrared spectroscopy (ATR-FTIR), molecular docking and molecular dynamics simulations (MD), laser Doppler flowmetry (LDF), and the western blotting method. Results: The study found that VO-ER promotes the permeation of total glycosides of peony in a concentration-dependent manner by disrupting the intercellular lipid tissue structure, downregulating the expression of claudin-1, claudin-7, and occludin, and improving local microcirculation, thereby promoting the absorption of TGP. Conclusions: VO-ER enhances the transdermal absorption of TGP through multiple mechanisms, such as disrupting the skin lipid barrier, downregulating tight junction proteins, and improving local skin microcirculation. This study provides a theoretical basis for VO-ER as a safe and effective new transdermal penetration enhancer, offering support for the development of topical preparations containing Evodia rutaecarpa and Paeonia lactiflora. Full article

This study proposes an innovative spacer design for use in spiral-wound membrane filtration systems as a high-performance alternative to conventional woven spacers. By eliminating interwoven filaments, this structure fundamentally reshapes flow patterns while maintaining mechanical support. A novel aspect of this methodology is the inaugural application of coupled computational fluid dynamics (CFD) and the discrete phase model (DPM) for modeling microbial particle transport and deposition dynamics, which has been a critical gap in prior studies that focused solely on hydrodynamic analysis without addressing biocolloid dynamics. Numerical simulations demonstrated that the novel design reduces stagnant zones by a significant amount compared to standard woven spacers and achieves a greater velocity uniformity. For all eight configurations of the novel design, the DPM-derived microbial distribution maps revealed a reduction of circa 65% in particle colonization density on the spacer surface, and this reaches a 77% reduction for the optimal design. These measurements directly linking structural geometry to antifouling efficacy provide mechanistic insight unattainable through conventional velocity field analysis alone. Experimental validation using optical coherence tomography (OCT) revealed a 40% reduction in TOC deposition, while confocal laser scanning microscopy (CLSM) quantified a 54% decrease in biofilm viability through adenosine triphosphate (ATP) measurements. The incorporation of the optimal spacer in the plate-and-frame test module demonstrated that the lower degree of fouling caused both a 23% increase in permeation flux together with 76% lower energy consumption compared to the commercial design. Full article