Search Results (1,900)

Ultra-high-temperature ceramic (UHTC) coatings offer a promising route to extending cutting tool service life under severe conditions. This work evaluates the tribological behaviour and wear regime transitions of ZrB₂–SiC/ZrO₂ coatings, deposited by physical vapour deposition (PVD) onto ASSAB-17 high-speed steel tool bits, during dry turning of Ti-6Al-4V. Structural, microstructural, mechanical, and tribological characterisation was performed by X-ray diffraction (XRD), scanning electron microscopy (SEM), nanoindentation, and pin-on-disc testing under three pressure–velocity (PV) severity levels, with worn surfaces analysed by SEM and profilometry. The coating exhibited a nanostructured ZrB₂/β-SiC/t-ZrO₂ architecture with a hardness (H) of 24 ± 3 GPa, a hardness-to-reduced-elastic-modulus ratio (H/Er) of 0.100, and an elastic resistance to plastic deformation (H³/Er²) of 0.240 GPa. Three tribological regimes were identified: running-in, steady-state sliding, and progressive degradation, with the highest severity (PV = 6.0 N·m/s) triggering degradation beyond approximately 620 m, a more than one-order-of-magnitude rise in wear rate, and the only case exceeding the tool-life criterion of maximum flank wear (VBmax = 0.30 mm) according to ISO 3685. The main advantage of the proposed approach is that it condenses tool-life-relevant behaviour into a single, easily measurable severity parameter, the PV product, directly applicable to coating design and the selection of safe machining-condition windows. The overall behaviour is consistent with a mechanism governed by the stability and regeneration capacity of a protective tribofilm. As the composition of this layer was not directly characterised, this mechanism is proposed as a phenomenological interpretation, from which a PV threshold is derived as a design criterion for UHTC coatings. Full article

Cardiovascular diseases remain the leading cause of mortality worldwide, and endoplasmic reticulum (ER) stress has emerged as an important molecular mechanism underlying myocardial injury and heart failure. This study investigated the expression of the ER stress-related genes GRP78, PERK, and CHOP in peripheral whole blood obtained from patients with acute cardiovascular diseases. A total of 300 participants were enrolled, including 200 patients with ST-segment elevation myocardial infarction (STEMI, n = 55), non-ST-segment elevation myocardial infarction (NSTEMI, n = 88), decompensated heart failure (DHF, n = 40), or unstable angina pectoris (USAP, n = 17), and 100 healthy controls. Relative mRNA expression levels were quantified using quantitative real-time PCR. Intergroup comparisons were performed using the Kruskal–Wallis test followed by Dunn’s post hoc test with Bonferroni adjustment. Significant differences in GRP78, PERK, and CHOP expression were observed among the study groups (all p < 0.001). GRP78 and PERK expression levels were highest in the STEMI and DHF groups, whereas CHOP expression was highest in the STEMI group. Significant positive correlations were identified between troponin and CHOP (r = 0.48), GRP78 (r = 0.42), and PERK (r = 0.39) (all p < 0.001), while weaker but significant associations were observed between inflammatory markers (CRP and NLR) and ER stress-related gene expression. Exploratory receiver operating characteristic (ROC) analysis showed that CHOP demonstrated the highest discriminatory performance for distinguishing patients with acute cardiovascular disease from healthy controls. These findings indicate that peripheral whole-blood ER stress-related gene expression is associated with acute cardiovascular disease and correlates with established biomarkers of myocardial injury and inflammation. Further prospective studies are required to determine the clinical significance of these findings. Full article

(1) Background: This study aimed to assess how two different adhesive solvent evaporation techniques affect the microtensile bond strength (µTBS) of a universal adhesive to dentin, as well as the enzymatic activity of dentinal matrix metalloproteinases (MMPs) at baseline and after 6-month aging under simulated pulpal pressure. (2) Methods: Middle-depth dentin surfaces of 32 sound extracted human molars were bonded under simulated pulpal pressure using a universal adhesive (Clearfil Universal Bond Quick) in either etch-and-rinse (ER) or self-etch (SE) mode. Two solvent evaporation approaches were compared: evaporation with a disposable air/water syringe (air) and with a disposable suction device (suction), yielding four experimental groups (n = 8): ER/air, ER/suction, SE/air, and SE/suction. After light-curing for 10 s, a 4 mm composite build-up was created. Specimens were stored in distilled water under simulated pulpal pressure at 37 °C for either 24 h (T0) or 6 months (T6) and then sectioned into sticks and subjected to µTBS testing. Fracture surfaces were examined by scanning electron microscopy (SEM). An additional subset of teeth from each group (n = 3) underwent in situ zymographic analysis, in which bonded sticks were ground and exposed to fluorescein-conjugated gelatin, with enzymatic activity quantified by confocal microscopy. Statistical analysis was performed at a significance threshold of p < 0.05. (3) Results: Air-drying yielded significantly higher µTBS values than suction drying, irrespective of adhesive application mode (p < 0.05). At T6, SE groups retained bond strength values comparable to baseline (p > 0.05), whereas ER groups showed a significant reduction in bond strength with aging (p < 0.05). The ER mode and suction were associated with significantly increased MMP activity at T0 (p < 0.05), while there were no differences between SE/ER at T6 (p > 0.05), and air increased MMP activity (p < 0.05). (4) Conclusions: When using an ethanol-based universal adhesive under pulpal pressure, evaporation with a disposable air syringe combined with the self-etch application mode appears to offer greater bonding reliability and stability. Full article

Background/Objective: Root canal debridement is limited by complex anatomy and the apical vapor lock phenomenon, reducing smear layer removal. This study evaluated the effect of a 5 µm zirconia microparticle suspension used with sonic, passive ultrasonic irrigation (PUI), or erbium, chromium-doped yttrium scandium gallium garnet (Er,Cr:YSGG) laser activation on smear layer removal across the root canal thirds. Methods: Sixty single-rooted human teeth were prepared to size F4 (40/0.06) using 5.25% NaOCl and randomly assigned to six groups (n = 10) combining activation modality (sonic, PUI, or Er,Cr:YSGG laser) and irrigant type (distilled water or 5 µm zirconia suspension) over a 5 min interrupted cycle. Smear layer removal was scored using scanning electron microscopy (SEM) and the Hülsmann grading system. Data were analyzed via Kruskal–Wallis and Friedman tests with post hoc pairwise comparisons (α = 0.05). Results: Inter-rater reliability was strong (Cohen’s κ = 0.736–0.822; p < 0.001). Smear layer removal varied significantly across root thirds (p < 0.001). Ultrasonic + Zirconia demonstrated superior removal in the middle third compared with Sonic + Distilled Water (p = 0.005), and in the coronal third compared with Laser + Distilled Water (p = 0.003) and Sonic + Distilled Water (p = 0.026). Coronally, Ultrasonic + Distilled Water outperformed Laser + Distilled Water (p = 0.041). No significant differences occurred apically (p > 0.05). Conclusions: Incorporating 5 µm zirconia microparticles with passive ultrasonic activation improved smear layer removal, particularly in the coronal and middle thirds of the root canal under the conditions of this ex vivo study. Full article

Canonical signal peptides (SPs) are short N-terminal sequences that direct nascent proteins into the secretory pathway, but their role extends far beyond protein targeting. Advances in sequencing and computational tools have enabled their systematic identification across proteomes, highlighting SPs as critical regulators of protein biogenesis, including endoplasmic reticulum (ER) targeting, translocation, folding, and proteostasis. Clinically, mutations affecting SP function underlie a distinct group of human disorders, while SP-derived fragments are emerging as diagnostic biomarkers and therapeutic targets. In biotechnology, SPs are engineered to enhance recombinant protein production and serve as molecular tags for intracellular delivery. Together, these developments position SPs at the intersection of fundamental cell biology, medicine, and biotechnology. While this review primarily focuses on canonical SPs, it also considers selected non-canonical targeting and topogenic sequences whose dysfunction contributes to protein misfolding, impaired ER translocation, disrupted degradation pathways, and altered intracellular trafficking in neurodegenerative diseases. Aberrations involving both conventional SPs and alternative targeting/topogenic elements contribute to pathological protein aggregation, a hallmark of major neurodegenerative disorders, including Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington Disease (HD), prion diseases, and amyotrophic lateral sclerosis/frontotemporal dementia (ALS/FTD); in multiple sclerosis (MS) is primarily an inflammatory demyelinating disease, where abnormal protein exposure, potentially linked to misprocessed SPs, can activate immune responses. By synthesizing current knowledge, the review explores how alterations in targeting determinants influence key proteostasis pathways, acting as upstream modulators of disease-relevant molecular cascades. It further discusses the emerging concept that SP-derived fragments may participate in intercellular communication, adding an additional layer of regulatory complexity. Full article

Liver involvement is frequent in rheumatoid arthritis (RA) and may progress from steatosis to fibrosis, cirrhosis, or hepatocellular carcinoma. Liver fibrosis (LF) in RA is multifactorial, but the available data are limited and the impact of methotrexate (MTX) remains controversial. In this cross-sectional study, 51 RA patients (46 females; mean age of 48.8 ± 8.2 years; and a median disease duration of 12 years) were enrolled. LF was assessed using non-invasive indices (the aspartate aminotransferase-to-platelet ratio index [APRI] and fibrosis-4 index [FIB-4]) and liver stiffness measurement (LSM) using shear wave elastography. Serum endothelin-1 (ET-1) and selected organokines (namely myostatin, resistin, and osteoprotegerin) were quantified by the ELISA. Associations of the APRI, FIB-4, and LSM with organokines and endothelin-1 were analyzed using univariable and multivariable linear regression, whereas correlations with the RA-specific cardiovascular (CV) risk score (ERS-RA) and echocardiographic parameters of left ventricular diastolic dysfunction (LVDD) were assessed using Spearman’s rank correlation. Myostatin and resistin showed a significant positive and significant negative association with LSM, respectively, while FIB-4 was negatively correlated with lateral and medial e’ velocities and positively with the ERS-RA. MTX use, mean weekly dose, cumulative dose, and endothelin-1 were not associated with the APRI, FIB-4, LSM, or LVDD. These exploratory findings support the potential role of myostatin and resistin in LF-related phenotypes and suggest that FIB-4 may capture aspects of both hepatic and cardiovascular risk in RA. RA patients with elevated FIB-4 values may require echocardiographic assessment and comprehensive CV risk evaluation. In this cohort, MTX exposure and endothelin-1 were not associated with LF or LVDD. Full article

Background/Objectives: Pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) is an important prognostic marker in HER2-positive breast cancer (BC). However, reliable pre-treatment predictors based on routinely available clinical data remain limited. This study evaluated whether clinicopathologic and baseline magnetic resonance imaging (MRI) variables could predict NAC response using classical machine learning (ML) approaches. Methods: A retrospective cohort of 112 patients with HER2-positive BC treated with NAC was analysed, including 57 patients who achieved pCR and 55 who did not. Fourteen pre-treatment variables were evaluated, including hormone receptor (HR) status, tumour grade, ER and PR expression, Ki67, nodal status, age, and baseline MRI characteristics. Seventy ML classifiers were compared using a fully nested leave-one-out cross-validation (LOOCV) framework. Performance was assessed using accuracy, area under the receiver operating characteristic curve (AUROC), Cohen’s kappa, sensitivity, specificity, and F1-score. Results: A support vector machine (SVM) with a radial basis function (RBF) kernel achieved the highest observed accuracy (82.1%) among the 70 evaluated classifiers. The corresponding AUROC was 83.3%, Cohen’s kappa was 64.2%, and sensitivity, specificity, and F1-score were 87.7%, 76.4%, and 83.3%, respectively. HR-related variables, particularly PR and ER expression, together with Ki67 and baseline MRI features, ranked among the most influential predictors. Despite relying exclusively on routinely available pre-treatment variables, the model demonstrated meaningful predictive performance. Conclusions: ML applied to routinely available clinicopathologic and baseline MRI variables showed promising ability to predict pCR before treatment initiation in HER2-positive BC. The proposed approach may support pre-treatment clinical risk assessment using information already generated during routine clinical assessment. Nevertheless, prospective multicentre external validation, calibration assessment, and evaluation of clinical utility are required before implementation in routine clinical practice. Full article

Foamed asphalt mixtures (FAMs) are considered to be among the most environmentally friendly. They are produced at temperatures ranging from 100 °C to 120 °C. In order to produce asphalt mixtures at such a low temperature, it is necessary to produce foamed asphalt binder with high foaming parameters, i.e., maximum expansion (ER) and a half-life (HLa) of the asphalt foam. Consequently, the asphalt binders were modified with a surfactant at a concentration of 0.6% by weight of the binder, prior to its foaming with water. Subsequently, an AC 8 S asphalt mixture was designed using traditional hot-mix asphalt (HMA) technology and with modified foamed asphalt binders in quantities ranging from 5.6% to 6.5% by weight, in increments of 0.3%. To ensure optimal properties of the FAM, hydrated lime was added at levels of 0%, 15%, 30% and 45% by weight as a substitute for filler. The influence of modified foamed asphalt binders and hydrated lime on the void content (Va), resistance to moisture and frost (TSR) and resistance to permanent deformation (WTS_AIR and PRD_AIR) of the FAM was assessed. A key element of the research was the determination of the complex modulus of stiffness E* and resistance to low-temperature cracking R₋₂, σ_cry, T_failure and crack propagation using the SCB methodology. Analysis of the test results using desirability functions enabled the determination of the optimum proportions of foamed asphalt binders and hydrated lime—5.9% and 30% respectively—in the FAM, ensuring that its properties meet all the requirements of the relevant standards and guaranteeing resistance to low-temperature cracking. Full article

Wire arc additive manufacturing (WAAM) enables high-rate fabrication of large metallic components, but spatial variations in thermal history can lead to microstructural heterogeneity that requires efficient process models to evaluate. This study evaluates whether cooling rates extracted from a graph theory model (GTM)-based thermal simulation are consistent with the microstructural evolution observed in an ER70S-6 WAAM wall. Thermal histories from the model were analyzed at selected build heights, and cooling rates were extracted from the final thermal excursion through the austenite phase field. Microstructures at corresponding locations were characterized using electron backscatter diffraction (EBSD) to quantify grain size distributions, and pearlite interlamellar spacing was used as an additional indicator of cooling behavior. The modeled cooling rates were highest near the substrate and generally decreased with build height, consistent with the observed reduction in the fine grain fraction and the progressive shift in the grain size distribution as build height increased. Pearlite spacing trends also supported the modeled cooling rate variation. These results indicate that GTM-derived thermal histories can be post-processed into metallurgically meaningful cooling rate estimates for WAAM steel builds and linked to dataset specific empirical grain size distribution relationships for process–thermal history–microstructure assessment. Full article

Budget overruns driven by unpredictable building material prices are a persistent challenge in emerging economies, yet reliable price forecasting tools for structural materials such as steel reinforcement bar (RFT) remain largely unavailable to building project teams. This study develops an Autoregressive Distributed-Lag (ARDL) model to forecast RFT prices in Egypt using macroeconomic leading indicators. A structured filtering pipeline—stationarity testing, Variance Inflation Factor (VIF) screening, and Granger causality testing—reduced 22 candidate variables to nine predictors: producer price index (PPI), loan rate (LR), discount rate (DR), Egyptian Stock Exchange Index (EGX30), money supply (M0), exchange rate (ER), iron ore prices (ORE), American stock index (S&P500), and Hang Seng Index (HSI). ARDL bounds testing confirmed cointegration across look-back periods (LBP) of 3, 6, and 9 months. Comprehensive diagnostics confirmed model stability, homoscedasticity, and the absence of serial correlation. The ARDL was benchmarked against an Ordinary Least Squares (OLS) baseline and a first-difference vector autoregression (VAR) model. Evaluated as genuine multi-step (dynamic) forecasts over the held-out crisis-period window, the 3-month model achieved an out-of-sample mean absolute error of approximately 5.9% in price terms, retaining a clear advantage over the OLS baseline at that horizon. The proposed framework provides quantity surveyors, cost consultants, and project managers with a practical tool for setting RFT budgets at the tendering stage and optimising procurement timing. It is transferable to other building materials (cement, structural steel sections, glazing) across emerging-market construction economies. Full article

Background: This study evaluated the effect of Erbium:Yttrium–Aluminum–Garnet (Er:YAG) laser irradiation on the fracture load, failure mode, and reliability of monolithic and porcelain-veneered zirconia crowns. Methods: Monolithic ultra-translucent zirconia crowns (5YZ-M, n = 30) and porcelain-veneered zirconia crowns (3YZ-V, n = 30) were divided into control (Ctrl-no surface treatment) and Er:YAG laser irradiation (Las) groups (n = 15). Las was performed on the cementation surface (250 mJ, 10 Hz, 2.5 W for 30 s). Crowns were adhesively cemented onto dentin-analog abutments and subjected to compressive load-to-failure testing. Data were analyzed by two-way ANOVA, Tukey’s post hoc test, and Weibull analysis (α = 0.05). Fractographic analysis was performed. Results: Laser irradiation did not affect the fracture load (p = 0.183). Monolithic crowns (5YZ-M) showed significantly higher fracture load than veneered crowns (3YZ-V) (p < 0.001). There was no effect of the interaction between factors (p = 0.150). The m-values were similar among groups, while the L₀ of 3YZ-V-Ctrl was significantly lower than that of 5YZ-M. Veneered restorations predominantly showed chipping and delamination; whereas, monolithic crowns mainly exhibited catastrophic failures. Fracture origins were mostly located at the occlusal loading area. Conclusions: Er:YAG laser irradiation of the cementation surface did not affect the load-bearing capacity or structural reliability of zirconia crowns. Full article

Short tandem repeat (STR) analysis is the main reference standard in forensic genetics. Despite its reliability, rare genetic anomalies like triallelic patterns and microvariants challenge profile interpretation. This study characterizes an exceptional genetic finding identified during routine casework at the Research Institute of Forensic Science in Sofia, Bulgaria. DNA was isolated from dental remains of an unidentified male corpse and amplified using the Investigator^® ESSplex SE Plus kit targeting 15 autosomal STR loci. A well-balanced male genotype was obtained across 14 loci; however, a rare triallelic anomaly emerged at D19S433 (19q12). Three distinct peaks were identified: standard alleles 13 and 14, and an off-ladder allele at 261.09 bp, designated as microvariant 15.3. Quantitative peak height analysis showed that the combined intensity of alleles 13 and 14 (~1316 RFU) was approximately equal to that of microvariant 15.3 (1054 RFU). This balance confirms a Type I triallelic configuration, indicative of a localized somatic mutation or segmental duplication rather than trisomy or DNA mixture. Global databases (NIST STRBase and STRidER) and regional Bulgarian data confirmed that this specific 13/14/15.3 combination has not been previously documented. Documenting rare STR variations is critical to enriching genomic databases and ensuring maximum accuracy in forensic interpretations. Full article

Cancer cells are able to survive under conditions of high endoplasmic reticulum (ER) stress by activating the adaptive unfolded protein response (UPR), which is closely linked with autophagy. On the other hand, excessive and prolonged ER stress leads to apoptosis. However, the relationships between different UPR branches and apoptosis or autophagy vary in cancer cells of different origins and depend on the extent and nature of the stress signal. This study was designed to establish the role of ER stress sensors protein kinase RNA-like endoplasmic reticulum kinase (PERK) and inositol-requiring enzyme 1 (IRE1α) in apoptosis or autophagy signaling in T-lymphoblastic leukemia MOLT-3 cells via the RNA interference method. The cells were transfected with small interfering RNAs (si-PERK, si-IRE1α, or si-Cont) for 6 h and further cultured under normal conditions for 72 h to provide an insight into chronic effects of the gene silencing. The expression of apoptosis and autophagy effectors at the mRNA and protein levels was compared using RT-PCR and Western blot assays, respectively. Transfection of the cells with PERK siRNA led to a significant decrease in PERK protein and gene expression, and decreased phosphorylation of its downstream effector eukaryotic initiation factor 2α (eIF2α). PERK silencing was accompanied by activation of apoptosis-related genes and proteins—BCL2-associated X (Bax), caspase-3, C/EBP homologous protein (CHOP), while the levels of autophagy markers (Unc-51 like autophagy activating kinase 1 (ULK1), Beclin-1, and microtubule-associated proteins 1A/1B light chain 3 (LC3A/B)) remained stable. In contrast, treatment of the cells with si-IRE1α reduced the content of IRE1α, X-box-binding protein 1 (sXBP1), and glucose-regulated protein 78 (GRP78) proteins, but increased ERN1 gene expression. IRE1α RNA interference did not affect the levels of the pro-apoptotic marker Bax, but suppressed caspase-3, CHOP, c-Jun N-terminal kinase (JNK), and autophagy signaling molecules (ULK1, Beclin-1, LC3A/B) at both the transcriptional and translational levels. These results indicate that the PERK pathway is an important contributor to the survival of MOLT-3 cells under basal ER stress, while PERK depletion compromises the resistance of cells to UPR-mediated apoptosis. The IRE1α UPR branch is directly linked with autophagy-dependent signaling, although IRE1α knockdown exerted a more complicated influence on the cells, probably via activation of multiple pro-death and compensatory pro-survival regulatory mechanisms. Full article

Black soldier fly (Hermetia illucens) larvae meal (BSF meal) has emerged as a promising sustainable protein source in aquafeed formulation. This study examined the effects of graded BSF meal inclusion (0%, 20%, 40%, 60%, 80%, and 100% fishmeal replacement) and die head temperature (80 °C, 100 °C, and 120 °C) on the physical properties of extruded diets for Asian seabass (Lates calcarifer), with particular attention to their interactive effects. Both factors significantly affected most pellet quality parameters (p < 0.05), with the exception that no significant interaction effect was observed for moisture content (p = 0.2817). PDI increased progressively with BSF meal inclusion, peaking at 99.14% at 100% substitution and significantly exceeding the control. Higher BSF meal inclusion levels were associated with reduced expansion ratio (ER), bulk density (BD), and sinking velocity (SV). Notably, pellets produced at 80–100% BSF meal inclusion combined with moderate die temperatures (80–100 °C) achieved complete buoyancy (SV = 0.00 m/s). Processing at 80 °C yielded the highest ER and water absorption index (WAI), while 120 °C was associated with elevated water solubility index (WSI), indicating a higher risk of nutrient leaching. These results suggest that BSF meal can replace fishmeal at up to 100% without compromising pellet durability. Extrusion of BSF-based diets at 60–100% inclusion and 80–100 °C is recommended to achieve an optimal balance of structural integrity, hydration properties, and buoyancy for Asian seabass feeds. Full article

As an important policy tool for promoting green development, environmental regulation (ER) has exerted a profound impact on the employment sector. Using panel data from 106 prefecture-level and above cities in China’s Yangtze River Economic Belt (YREB) from 2011 to 2022, we examine the impact and mechanisms of ER on employment scale and structure. Empirical results reveal that the strengthening of ER has a significant inhibitory effect on employment growth, but a positive impact on the optimization of the employment structure. As regulatory intensity increases, the suppressive effect on employment scale diminishes, while structural optimization strengthens. Moreover, the effects vary across regions. The scale-inhibiting effect is more pronounced in the Upper-Middle Yangtze regions, in areas with initially low regulation intensity, and in large cities. Structural optimization is most significant in the Lower Yangtze regions and in small/medium-sized cities. We also find that ER indirectly changes employment through three channels: industrial structure upgrading (ISU), green innovation (GV), and foreign direct investment (FDI). Our findings underscore the necessity of balancing environmental stringency with social sustainability, and the conclusions of our study are applicable to policymakers in China and other economies. Full article