Search Results (5,536)

Molecular dynamics simulations were performed to investigate the nanometric cutting of polycrystalline oxygen-free copper using a single-crystal diamond tool. The effects of grain size, tool geometry (rake angle and edge radius), cutting speed, and ambient temperature on atomic migration, dislocation activity, and tool wear were systematically analyzed. The results indicate that material removal is dominated by cutting-induced amorphization and the formation of hcp-coordinated defect structures, while dislocation activity governs plastic deformation and cutting force fluctuations. A damaged subsurface layer, composed of amorphous structures, hcp-coordinated defects, and residual dislocations, is formed beneath the machined surface. Increasing grain size reduces grain-boundary-induced stress concentration and suppresses subsurface damage. A larger rake angle facilitates chip removal and reduces damage, whereas a larger edge radius intensifies dislocation activity and amorphization. Higher cutting speeds reduce lattice distortion and subsurface damage but increase stress concentration on the tool. Elevated temperature enhances atomic mobility, promoting amorphization and subsurface deformation while accelerating tool wear. These findings provide insight into the nanometric cutting behavior of polycrystalline copper and offer guidance for optimizing process parameters to improve surface integrity and tool life. Full article

Metabolic heterogeneity within the cell microenvironment is a key driver of cancer progression and resistance to therapy. However, current approaches lack the spatial and temporal resolution required to capture its dynamics in living systems. While recent advances in 3D cell culture models and metabolomic profiling have improved our understanding of the tumor niche, their integration with real-time optical sensing remains underdeveloped. Here, we present an integrated platform combining a 3D-printed microreactor culture chamber with Raman spectroscopy to enable non-invasive, spatially resolved metabolic monitoring of living cell cultures. Our microreactor platform generates controlled oxygen and nutrient cues while simultaneously acquiring label-free Raman spectra, revealing extracellular metabolic fingerprints linked to cell catabolism (e.g., glucose and lactate shifts) and acidification. Analysis across four cell lines uncovered temporal evolution as the dominant source of metabolic variance, while spatial heterogeneity along oxygen gradients is a secondary factor. In particular, diffusion-limited regions exhibited localized acidification and accumulation of stress biomarkers—such as the release of nucleotides—features that cannot be detected using conventional bulk assays. By providing a versatile platform for real-time mapping, this work enables the mechanistic dissection of cell adaptation to microenvironmental stress and supports the prediction of metabolic signatures underlying drug response and treatment outcomes. Full article

Astaxanthin (AST) is a potent carotenoid renowned for its exceptional antioxidant properties, which has attracted considerable scientific interest due to its broad spectrum of health benefits. This review comprehensively evaluates the therapeutic potential of AST in counteracting age-related decline, oxidative stress, and immune dysfunction, while also examining its beneficial effects on gut and skin health. Current evidence demonstrates that AST effectively mitigates oxidative stress and supports cellular health and longevity by neutralizing free radicals and upregulating endogenous antioxidant systems. In addition, AST modulates immune responses under conditions of immune dysfunction, thereby enhancing resilience against inflammatory disorders and infections. Emerging studies further indicate that AST promotes gut health by improving intestinal barrier integrity and maintaining a balanced gut microbiota, both of which are essential for systemic well-being. Moreover, its capacity to enhance skin elasticity and protect against ultraviolet-induced damage underscores its promising applications in cosmetic and dermatological products. This review highlights the urgent need for additional well-designed clinical trials to fully elucidate the underlying mechanisms, optimal bioavailability, dosage regimens, and long-term safety of AST. By integrating findings across multiple research domains, the present work provides a concise yet comprehensive overview of AST as a promising nutraceutical for promoting health, healthy aging, and the management of chronic diseases. Full article

Dexamethasone induces systemic toxicity, including oxidative stress, inflammation, hematological disturbances, and organ damage, particularly in the lungs and thyroid. Taurine exhibits antioxidant and anti-inflammatory properties, but poor bioavailability limits its efficacy. Nanoparticle delivery may enhance stability and tissue targeting. This study aimed to evaluate the protective effects of taurine-loaded chitosan nanoparticles (Tau–CS NPs) against dexamethasone-induced tissue injury in rats. Forty-eight male Wistar rats were allocated into control, DEXA, DEXA + silymarin, DEXA + taurine, and DEXA + Tau–CS NPs groups. Tau–CS NPs were characterized by TEM, UV–vis, FTIR, encapsulation efficiency, and drug loading. Hematology, oxidative stress markers (CAT, SOD, GSH, MDA), thyroid hormones (T3, T4, TSH, calcitonin), protein profile, lung and thyroid histopathology, and MPO expression were assessed. Tau–CS NPs showed uniform spherical morphology (11–60 nm), high encapsulation (98.2%), and substantial loading (50.36%). Dexamethasone caused hematological, oxidative, thyroidal, and histological disturbances. Tau–CS NPs markedly restored hematological indices, antioxidant defenses, thyroid function, protein profile, and tissue architecture, outperforming free taurine and silymarin. MPO expression was significantly reduced, indicating decreased inflammation. Taurine nanoparticles effectively mitigate dexamethasone-induced systemic and organ-specific toxicity, offering improved bioavailability and targeted delivery, highlighting their therapeutic potential. Full article

In this study the electromechanical response of a cantilever composite beam with surface-bonded piezoelectric patches is examined, focusing on interface stresses that may initiate delamination. A thermodynamically consistent electroelastic framework was specialized to the linear piezoelectric law used in finite element software, and a two-dimensional (2D) finite element model was developed and validated under static actuation. The predicted tip displacement was compared against the analytical Euler–Bernoulli solution across all seven mesh levels of the convergence study; findings indicated that the converged ANSYS 17.1 result (h = 5 × 10⁻⁵ m) differed from the analytical value by 5.8%, a discrepancy attributed to the plane-strain assumption and the neglect of shear deformation in the Euler–Bernoulli formulation. To resolve the delamination-critical behavior, three-dimensional (3D) models were built using SOLID185/SOLID5 and SOLID186/SOLID226 elements. Interfacial peel σ_y and shear τ_xy stresses were evaluated along lengthwise (PATH1) and transverse (PATH2) paths at the patch–core interface, with maximum interface stresses occurring along the transverse PATH2 near the free end, where strong three-dimensional edge effects developed. Both element sets predicted a similar tip displacement, but the SOLID186/SOLID226 elements yielded peak interface stresses approximately 19% higher in peel and 87% higher in shear along the critical transverse PATH2. These findings demonstrate that element choice minimally affects global stiffness but significantly influences local interface stress prediction, providing practical guidance for the selection of appropriate models when assessing the delamination risk in piezoelectric-actuated composite beams. Full article

Purpose: Natural polysaccharides have shown considerable potential in the management of type 2 diabetes mellitus (T2DM) due to their multi-target metabolic regulatory effects. However, their clinical translation is limited by poor oral stability and low intestinal permeability. Snow lotus polysaccharide (SIP), a representative plant-derived polysaccharide, exhibits promising metabolic benefits but suffers from these delivery barriers. This study aimed to develop an oral nanodelivery system to enhance the gastrointestinal stability and intestinal transport of SIP, thereby improving its in vivo efficacy. Methods: SIP-loaded chitosan–tripolyphosphate nanoparticles (SIP@CS-TPP) were prepared via ionic crosslinking and characterized in terms of particle size, surface charge, morphology, and structural features. In vitro release behavior under simulated gastrointestinal conditions was evaluated. Ex vivo intestinal permeation was assessed using an isolated intestinal sac model. The metabolic regulatory effects were further investigated in a high-fat diet/streptozotocin-induced T2DM rat model. Results: SIP@CS-TPP nanoparticles exhibited a uniform particle size of 188.9 ± 12.8 nm, a surface charge of 28.3 ± 5.1 mV, and good stability after freeze-drying. A pH-responsive and diffusion-controlled release profile was observed. Ex vivo studies demonstrated significantly enhanced intestinal transport, with an approximately 3.7-fold increase in apparent permeability compared with free SIP. In vivo, SIP@CS-TPP improved glycemic control, glucose tolerance, insulin resistance, lipid metabolism, oxidative stress, and inflammatory responses more effectively than free SIP at the same dose. Conclusions: The CS-TPP nanodelivery system effectively enhances the oral delivery and metabolic regulatory effects of SIP. This study highlights the potential of a delivery-oriented strategy to improve the in vivo performance of natural polysaccharides and provides a promising approach for their application in metabolic disease management. Full article

Individuals with diabetes mellitus (DM) experience impaired wound healing, where the healing process is often compromised by a complex, hostile microenvironment characterized by persistent inflammation, high oxidative stress, and dysfunctional angiogenesis. The hyperglycemic environment damages the blood vessels and disturbs the normal hypoxia-induced upregulation of vascular endothelial growth factors, causes poor vascularization and insufficient production of new blood vessels, and leads to impaired perfusion and thickened and dysfunctional capillary basement membranes, which reduce blood flow to the wound, leading to delayed wound healing. Mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) are the main effectors of intercellular communication and have emerged as a potent cell-free strategy for the acceleration of tissue repair. MSC-EVs can be isolated from various adult tissues, but increasing evidence suggests that pla Full article

Systemic inflammation is influenced by regular physical activity and diet. While moderate exercise can transiently alter inflammatory markers, high-intensity activity may increase muscle turnover without substantially elevating systemic inflammation. The combined effects of physical activity and dietary inflammatory potential in healthy young men remain poorly defined. In this cross-sectional observational study, 233 healthy men aged 18–30 years were categorized according to physical activity level: low (NA, n = 52), moderate (A, n = 93), and high (S, n = 88). Anthropometry and body composition were assessed using bioelectrical impedance. Dietary intake was recorded over 4 days and used to calculate the Dietary Inflammatory Index (DII). Blood samples were collected and analyzed for complete blood counts, high-sensitivity C-reactive protein (hs-CRP), serum amyloid A (SAA), and creatine kinase (CK). Differences between groups were evaluated using the Kruskal–Wallis test with Dunn’s post hoc correction, and principal component analysis (PCA) was performed to explore multivariate inflammatory patterns. The highest BMI, fat percentage, and DII were observed in low-activity men, whereas fat-free mass and CK activity were greatest in highly active men. Slightly higher systemic inflammatory markers (hs-CRP and SAA) were observed in moderately active men compared to other groups. PCA revealed two principal axes: PC1 representing systemic inflammation and PC2 representing leukocyte distribution. Weak associations were found between DII and these components, indicating a limited link between dietary inflammatory potential and circulating inflammatory biomarkers. Body composition is strongly influenced by physical activity, with high activity promoting lean mass and moderate activity associated with modest elevations in inflammatory markers. Dietary inflammatory potential was only weakly associated with systemic inflammation, suggesting that exercise-induced physiological stress may play a more prominent role in shaping inflammatory profiles in healthy young men. Full article

Poly(amidoamine) (PAMAM) dendrimers are widely recognized as versatile nanocarriers due to their tunable architecture and ability to associate with bioactive molecules. In this study, generation 3 PAMAM dendrimers functionalized with triphenylphosphonium (TPP) were employed to investigate the association of structurally related phenolic compounds—caffeic acid, p-coumaric acid, and cinnamic acid—through either covalent conjugation or non-covalent encapsulation. Physicochemical characterization by NMR, dynamic light scattering, and zeta potential measurements revealed the formation of supramolecular aggregates rather than isolated dendrimer units, with hydrodynamic diameters ranging from 127 to 260 nm and positive surface charge across all formulations. Encapsulation efficiencies determined by HPLC reached 93.8% for caffeic acid, 78.9% for p-coumaric acid, and 71% for cinnamic acid, indicating differential association behavior. Molecular dynamics simulations over 1 μs supported these findings, showing stronger and more stable interactions for polar antioxidants, particularly caffeic acid, driven by hydrogen bonding and electrostatic interactions, while cinnamic acid displayed preferential binding in more hydrophobic dendrimer regions. Radical scavenging assays (DPPH• and ABTS•+) demonstrated that all formulations retained antioxidant capacity, although dendrimer association modulated scavenging kinetics. In cellular assays under oxidative stress, free caffeic acid exhibited the strongest immediate reduction of intracellular reactive oxygen species, whereas dendrimer-associated systems showed reduced but significant activity, consistent with decreased solvent accessibility and slower release predicted by simulations. Overall, these results highlight a trade-off between molecular retention and immediate biological efficacy, demonstrating that the mode of association governs antioxidant accessibility and performance. This combined experimental and computational approach provides a mechanistic framework for the rational design of dendrimer-based delivery systems aimed at balancing stability and functional activity. Full article

Alcohol-related liver disease (ALD) and ALD-related mortality are associated with hemolysis, increased erythrophagocytosis, and disturbed iron homeostasis. While macrophage-mediated erythrophagocytosis is well established, we investigated the contribution of liver sinusoidal endothelial cells (LSECs) to handling oxidatively damaged or ethanol-primed red blood cells (RBCs) in ALD. Live-cell imaging demonstrated that damaged RBCs were rapidly taken up by SK-HEP1 cells, an endothelial cell line with LSEC-like characteristics, and RBC uptake was associated with induction of heme oxygenase-1 (HO-1) and activation of its upstream regulator Nrf2. siRNA-mediated knockdown of the scavenger receptor Stabilin-1 attenuated RBC-induced HO-1 expression, supporting a role for Stabilin-1 in efferocytic signaling. Exposure of RBCs to ethanol concentrations as low as 25 mM induced phosphatidylserine externalization and rendered erythrocytes efferocytosis-competent. Lysed RBCs and free hemin elicited comparable oxidative stress responses. In murine models of hemolysis and chronic ethanol feeding, hemoglobin-derived signals were detected within sinusoidal structures showing a diffuse CD206-positive distribution pattern consistent with the sinusoidal scavenger compartment. Similar signals were observed in sinusoidal endothelial regions in human heavy drinkers with clinical signs of hemolysis. Together, these data suggest that LSECs may represent an additional component of RBC clearance in ALD, alongside macrophages and hepatocytes, with implications for hepatic iron handling. Full article

Introduction: Late functional outcomes remain major determinants of quality of life after robot-assisted radical prostatectomy (RARP). Although several baseline and perioperative factors have been linked to postoperative stress urinary incontinence (SUI) and erectile dysfunction (ED), their cumulative effect remains incompletely characterized in large real-world cohorts. Materials and Methods: This retrospective single-center study included 862 consecutive patients undergoing RARP for localized prostate cancer. All endpoints were assessed at a fixed 12-month follow-up visit; therefore, a median follow-up beyond this predefined time point was not applicable. Outcomes were derived from patient-reported information documented during routine follow-up and comprised pad use, ED, and urethral anastomotic stricture. Age, body mass index (BMI), console time, estimated blood loss, and prostate weight were selected a priori based on clinical relevance and uniform availability and were analyzed using univariable and multivariable logistic regression. A simple exploratory composite risk score (0–5 points) was constructed by assigning one point for each predefined adverse factor. Results: At 12 months, 50.0% of patients were pad-free, 85.6% achieved social continence (0–1 pad/day), 14.5% had clinically significant incontinence (>1 pad/day), 71.5% had chart-documented ED, and 1.0% developed urethral anastomotic stricture. In multivariable analysis, age (OR 1.039, 95% CI 1.018–1.059) and prostate weight (OR 1.011, 95% CI 1.004–1.018) independently predicted SUI, while age was the only independent predictor of ED (OR 1.029, 95% CI 1.007–1.050). No predictor of stricture was identified. The composite score showed an exploratory dose–response association with SUI (OR 1.364 per point, 95% CI 1.208–1.541; AUC 0.597) and a weaker association with ED (OR 1.149, 95% CI 1.007–1.313; AUC 0.540). Conclusions: A simple composite score may provide pragmatic exploratory grouping of SUI risk after RARP, but discrimination is modest and interpretation is limited by non-validated outcome assessment and the absence of major confounders, including nerve-sparing status and baseline functional measures. Full article

This study investigates the stress–strain state of rocks subjected to the impact of penetrators with diverse configurations, employing numerical simulations in the ANSYS Workbench Static Structural module. The research focuses on the interaction between roller cone drill bit teeth and rock formations during blast hole drilling. Through finite element modeling using a linear elastic constitutive model, the influence of penetrator geometry, position relative to borehole walls, angle of attack, and distance to open surfaces on rock fracture parameters is analyzed. Key quantitative findings include: the relative breaking force near the borehole wall reaches 2.8 for soft rocks (siltstones) with a 10 mm tooth diameter, and decreases to approximately 1.0 at a distance of 1.5d from the wall; the optimal angle of attack ranges from 60° to 90° depending on rock hardness; and the proximity to a free surface reduces fracture resistance to as low as 0.23 of the baseline value. Six sets of parabolic regression equations (R² > 0.95) are derived for relative breaking forces across three rock hardness groups and two tooth diameters. Optimal parameters for tooth placement, borehole bottom shapes, and operational conditions are proposed. Implementation of the recommended parameters is estimated to increase drilling efficiency by 10–20% and extend tool service life by 15–30%. The findings provide a scientific foundation for designing advanced roller cone drill bits suitable for rocks with Protodyakonov hardness indices ranging from f = 5 to f = 18. Full article

Background: Liquid biopsy-based biomarkers provide valuable insights into tumor biology, dynamics, burden, relapse prediction and therapeutic responsiveness. The stress-inducible heat shock protein 70 (Hsp70), which is frequently overexpressed in highly aggressive solid tumors and is presented on the cell membrane of tumors but not normal cells, is found in the circulation either as a free protein originating from dying cells or in the context of extracellular vesicles (EVs) that are actively released by viable tumor cells. This study demonstrates the potential value of circulating Hsp70 (eHsp70) levels across multiple solid tumor entities as an entity- and stage-dependent diagnostic biomarker reflecting tumor burden and disease stage. Methods: Circulating eHsp70 levels, as determined using the Hsp70-exo ELISA which detects free and EV-associated Hsp70, in plasma samples collected from patients with different tumor entities (n = 389) prior to the initiation of any oncological therapy and healthy controls (n = 108) between 2021 and 2025, were analyzed retrospectively. Tumor stages were categorized as early, locally advanced, or metastatic. The Kruskal–Wallis test was used for group comparisons and the Receiver Operating Characteristic (ROC) curve was used to evaluate the diagnostic performance of eHsp70 levels. DeLong’s test was used to calculate differences between AUC values. Results: In tumor patients (n = 389), circulating eHsp70 levels were significantly higher than those in healthy controls (n = 108) (Kruskal–Wallis, p < 0.001). eHsp70 levels progressively increased from early-stage to locally advanced and metastatic disease in a stage-dependent manner. Although ROC analysis demonstrated the limited discriminatory performance of eHsp70 levels in early-stage disease (AUC 0.569), increased discrimination was apparent in locally advanced disease (AUC 0.751), metastatic tumors (AUC 0.784) and combined advanced tumor diseases (AUC 0.765; significant by DeLong’s Test comparing early-stage to locally advanced and metastatic tumors), irrespective of the tumor entity with the highest AUC values in metastatic breast cancer (AUC 0.872), sarcoma (AUC 0.861) and non-small cell lung cancer (NSCLC) (AUC 0.835). Apart from minor entity-specific differences, the correlation of eHsp70 levels with the tumor stage remained consistent across all measured tumor entities. Conclusions: Circulating eHsp70 levels are markedly elevated in patients with highly malignant solid tumors and show a consistent, stage-dependent increase across multiple tumor types. These findings suggest that circulating eHsp70, as an indicator of tumor-associated cellular stress and overall tumor burden, represents a valuable biomarker for assessing disease stage, monitoring disease progression, and evaluating therapeutic responses. Full article

Background: Right ventricular (RV) dysfunction is a key contributor to morbidity and mortality in systemic sclerosis (SSc), emerging from the combined effects of microvascular disease, myocardial fibrosis, interstitial lung involvement, and increasing pulmonary vascular load. Conventional echocardiography frequently fails to detect early RV impairment, prompting growing interest in deformation-based parameters such as RV free-wall longitudinal strain (RV-FWS), global longitudinal strain (RV-GLS), and RV–pulmonary artery (PA) coupling indices. Although natriuretic peptides reflect myocardial stress and are widely used in cardiopulmonary diseases, their integration with advanced RV imaging has been inconsistently reported in SSc. This systematic review synthesizes available evidence on RV strain, RV–PA coupling, and their relationship with clinical outcomes and biomarkers in SSc. Methods: A systematic search was conducted to identify clinical studies evaluating RV strain (RV-FWS, RV-GLS), right atrial strain, or RV–PA coupling indices in adult patients with SSc or SSc-associated pulmonary arterial hypertension (SSc-PAH). Eligible studies included those using speckle-tracking echocardiography or cardiac magnetic resonance feature-tracking. Study selection and data extraction were performed in accordance with PRISMA guidelines. Results: Seven studies met the eligibility criteria. Across unselected SSc cohorts, early disease without pulmonary hypertension (PH), and right-heart-catheterization-confirmed SSc-PAH, RV strain consistently detected myocardial impairment even when conventional echocardiographic indices remained normal. RV-FWS and RV-GLS were commonly reduced, and longitudinal data demonstrated progressive deterioration independent of standard measures. Strain-derived RV–PA coupling, particularly RV-FWS/PASP, significantly improved prognostic stratification when added to established PAH risk models. Two studies identified impaired RV deformation as a predictor of mortality, and CMR-derived right atrial strain provided additional prognostic value. Biomarker integration was limited, with only one study reporting an association between natriuretic peptide elevation (NT-proBNP) and impaired RV–PA coupling suggesting that biomarkers may reflect the hemodynamic load, although evidence remains limited captured by strain abnormalities. Conclusions: RV strain and RV–PA coupling indices are more sensitive than conventional echocardiography for detecting early RV dysfunction, monitoring disease progression, and predicting adverse outcomes in SSc. Although biomarker evidence remains limited, available data suggest that natriuretic peptides may provide complementary information to deformation-based assessment, although current evidence remains limited by reflecting combined myocardial and pulmonary vascular load. Standardized prospective studies including both strain imaging and biomarkers are needed to clarify the integrated diagnostic and prognostic value of advanced RV assessment in SSc. Full article

6063 aluminum alloy has broad application prospects in aerospace and microelectronic thermal management systems due to its good thermal conductivity and moderate strength. However, its extremely high hot cracking susceptibility during the laser powder bed fusion (LPBF) process limits the direct manufacturing of complex components. This study proposes a strategy combining material composition modification with advanced structural design. By introducing TiH₂ nanoparticles (1.0~4.5 wt.%) to modify the 6063 aluminum alloy powder, Diamond-type porous structures based on triply periodic minimal surfaces (TPMS) were successfully fabricated using LPBF technology. The results show that the introduction of TiH₂ significantly suppresses the solidification cracking of the aluminum alloy. The underlying mechanism is that the L1₂-structured Al₃Ti particles, generated by the in situ decomposition of TiH₂ in the melt pool, provide high-density heterogeneous nucleation sites. This leads to a drastic decrease in the average grain size from 30.46 μm to 0.75 μm (a reduction of 97.5%), achieving a remarkable columnar-to-equiaxed transition (CET). In terms of mechanical properties, the 3.0 wt.% TiH₂ addition group exhibits excellent plateau stress (28.5 MPa) and energy absorption capacity, which is mainly attributed to the synergistic effect of fine-grain strengthening and Orowan dispersion strengthening. Thermal tests reveal that the thermal conductivity of the 3.0 wt.% group reaches 123 W/(m·K) at 100 °C. The healing of cracks reconstructs the macroscopic heat conduction paths, resulting in a significant improvement in thermal conductivity compared with the unmodified group. This work provides a theoretical reference for the development of high-performance, crack-free, and multi-functional integrated aluminum alloy components via additive manufacturing. Full article