Search Results (1,505)

Quarry dust (QD) landfill causes environmental issues that cannot be ignored. In this study, we systematically explore its potential application as a supplementary cementitious material (SCM) in cemented paste backfill (CPB), revealing the activated mechanism of modified QD (MQD) and exploring the hydration process and workability of CPB containing QD/MQD. The experimental results show that quartz, clinochlore and amphibole components react with CaO to form reactive dicalcium silicate (C₂S) and amorphous glass phases, promoting pozzolanic reactivity in MQD. QD promotes early aluminocarbonate (M_c) formation through CaCO₃-derived CO₃²⁻ release but shifts to hemicarboaluminate (H_c) dominance at 28 d. MQD releases active Al³⁺/Si⁴⁺ due to calcination and deconstruction, significantly increasing the amount of ettringite (AFt) in the later stage. With the synergistic effect of coarse–fine particle gradation, MQD-type fresh backfill can achieve a 161 mm flow spread at 20% replacement. Even if this replacement rate reaches 50%, a strength of 19.87 MPa can still be maintained for 28 days. The good workability and low carbon footprint of MQD-type backfill provide theoretical support for—and technical paths toward—QD recycling and the development of low-carbon building materials. Full article

This study evaluated the effects of maternal supplementation with rumen-protected methionine (RPM), alone or combined with rumen-protected choline (RPC) and betaine (RPB), during the periconceptional and prepartum periods on reproductive outcomes and offspring performance in Chios ewes. One hundred synchronized ewes were assigned to three groups—control (no supplementation), M (5.50 g RPM/day), and MCB (3.50 g RPM, 1.60 g RPC, 0.49 g RPB/day)—from day −14 to +14 relative to mating. Blood was collected on days −14, 0, and +14 for ABTS (2,2′-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid), ferric-reducing ability (FRAP), and malondialdehyde (MDA), on days 18 and 21 for progesterone, and on day 26 for pregnancy-associated glycoprotein (PAG) detection. Thirty days before and up to lambing, the ewes were further divided into C-C, C-M, C-MCB, M-M, M-C, MCB-MCB, and MCB-C subgroups. Embryonic loss did not differ between groups. FRAP was higher (p < 0.001) in MCB ewes, and ABTS was lower (p < 0.05) in M ewes, in the periconceptional period. Offspring in the C-M, C-MCB, M-M, M-C, and MCB-MCB groups had higher birth weights (p < 0.01), along with increased MDA levels (p < 0.05). The results suggest that maternal methyl donor supplementation during early and/or late gestation enhances antioxidant status, supports embryonic development, and increases birth weight. Full article

Microchannel heat sinks (MCHSs) have emerged as an alternative for dissipating high heat rates. However, manufacturing MCHSs can be expensive, so exploring low-cost additive manufacturing using 3D printing is warranted. Before fabrication, the entropy minimization method helps to optimize MCHSs, enhancing their cooling capacity while maintaining their power consumption. We employed this method through computational simulation of laminar water flow in rectangular microchannels ($\mathsf{\mu }$C) and minichannels (mC), considering two heat fluxes (10 and 50 kW/m²). The results showed that the frictional entropy is only appreciable in the smallest and largest channels. These computational results enabled the fabrication of the optimal $\mathsf{\mu }$C and mC, whose experimental implementation validated the computational findings. Moreover, we computationally studied the effect of using rGO-Ag water-based nanofluids as a coolant. In general, a reduction in total entropy generation was observed at a heat flux of 50 kW/m². Although at lower heat flux (10 kW/m²), mC was the best option. Channels with lower heights were more effective at higher heat fluxes (≥50 kW/m²). Our findings offer a cost-effective strategy for fabricating high-performance cooling systems while also highlighting the interplay among heat flux, entropy generation, and nanofluid-enhanced cooling. Full article

Background/Objectives: The resistance mutations EGFR^{L858R/T790M/C797S} in epidermal growth factor receptor (EGFR) are key factors in the reduced efficacy of Osimertinib. Predicting the inhibitory effects of Osimertinib derivatives against these mutations is crucial for the development of more effective inhibitors. This study aims to predict the inhibitory effects of Osimertinib derivatives against EGFR^{L858R/T790M/C797S} mutations. Methods: Six models were established using heuristic method (HM), random forest (RF), gene expression programming (GEP), gradient boosting decision tree (GBDT), polynomial kernel function support vector machine (SVM), and mixed kernel function SVM (MIX-SVM). The descriptors for these models were selected by the heuristic method or XGBoost. Comprehensive learning particle swarm optimizer was adopted to optimize hyperparameters. Additionally, the internal and external validation were performed by leave-one-out cross-validation ($Q_{LOO}^2$), 5-fold cross validation ($Q_{5-fold}^2$) and concordance correlation coefficient (CCC), $Q_{F1}^2$, and $Q_{F2}^2$. The properties of novel EGFR inhibitors were explored through molecular docking analysis. Results: The model established by MIX-SVM whose kernel function is a convex combination of three regular kernel functions is best: $R^2$ and RMSE for training set and test set are 0.9445, 0.1659 and 0.9490, 0.1814, respectively; $Q_{LOO}^2$, $Q_{5-fold}^2$, CCC, $Q_{F1}^2$, and $Q_{F2}^2$ are 0.9107, 0.8621, 0.9835, 0.9689, and 0.9680. Based on these results, the IC₅₀ values of 162 newly designed compounds were predicted using the HM model, and the top four candidates with the most favorable physicochemical properties were subsequently validated through PEA. Conclusions: The MIX-SVM method will provide useful guidance for the design and screening of novel EGFR^{L858R/T790M/C797S} inhibitors. Full article

Epigenetic regulation, particularly DNA methylation, plays a crucial role in embryonic development by controlling gene expression patterns. The disruption of this regulation by environmental factors can have long-lasting consequences. Opioid drugs, such as morphine, are known to cross the placental barrier and affect the developing central nervous system, yet their precise epigenetic effects during early development remain unclear. This study aimed to elucidate the impact of chronic morphine exposure on the DNA methylation landscape and gene expression in mouse embryonic stem cells (mESCs). mESCs were chronically exposed to morphine (10 μM for 24 h). Genome-wide bisulfite sequencing was performed to identify DNA methylation changes, while RNA sequencing (RNA-Seq) assessed corresponding gene expression alterations. Global levels of 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) were quantified using mass spectrometry. Morphine exposure induced global DNA hypomethylation and identified 16,808 differentially methylated genes (DMGs) related to development, cell signalling, metabolism, and transcriptional regulation. Integrative transcriptomic analysis with RNA-Seq data revealed 651 overlapping genes, including alterations in key epigenetic regulators involved on DNA methylation machinery. Specifically, Tet1 was upregulated with promoter hypomethylation, while Dnmt1 was downregulated, without changes in promoter methylation after morphine exposiure. Mass spectrometry results confirmed a global decrease in 5mC levels alongside increased 5hmC, indicating the involvement of both passive and active demethylation pathways. These findings demonstrate for the first time that morphine disrupts the epigenetic homeostasis of mESCs by promoting global and gene-specific DNA demethylation, which might be key to the phenotypic changes that occur in adulthood. This work provides novel mechanistic insights into how opioid exposure during early development may lead to persistent epigenetic alterations, with potential long-term implications for neurodevelopment and disease susceptibility. Full article

The phase transformations of Crucible Particle Metallurgy (CPM) American Iron and Steel Institute (AISI) M4 steel were studied during heat treatments using a CALPHAD-based method. The calculated results were compared with experimental observations. The optimum austenitizing temperature was determined to be about 1120 °C using Thermo-Calc software (2024b). Air-cooling and quenching treatments led to the formation of martensite with a hardness of 63–65 Rockwell C (HRC). The annealing treatment promoted the formation of the equilibrium ferrite and carbide phases and resulted in a hardness of 24 HRC. These findings with regard to phases and microconstituents are in agreement with the predictions derived from a Thermo-Calc-calculated time–temperature–transformation diagram at 1120 °C. Additionally, the primary carbides, MC and M₆C, which formed prior to the heat treatment and had a minor influence on the quenched hardness. In contrast, the tempering process primarily led to the formation of fine secondary M₆C carbides, which hardened the tempered martensite to 57 HRC. The present work demonstrates the application of a CALPHAD-based methodology to the design and microstructural analysis of tool steels. Full article

Background: Traumatic fractures of the cervical spine pose significant challenges in management, particularly in young patients, where preserving mobility is crucial. Patient Characteristics: A 30-year-old woman presented with a C3 lateral mass and pedicle fracture following a motor vehicle collision. Initial conservative management with a rigid cervical collar for three months failed to reduce the diastasis, and the debilitating neck pain worsened. Preoperative imaging confirmed fracture instability without spinal cord compression. Intervention and Outcome: Preoperative screw trajectory planning was conducted with the My Spine MC system (Medacta), and fine-tuning was achieved on a 3D-printed model of the vertebra. A posterior midline approach was employed to expose the C3 vertebra, and a Herbert screw was inserted under fluoroscopic guidance. Imaging at three months demonstrated significant fracture reduction and early bone fusion. The patient achieved substantial improvement in functional mobility without complications. Conclusion: Herbert screw fixation holds potential as a less-invasive alternative to conventional posterior stabilization for selected cervical fractures. This technical note provides the reader with the required information to support surgical planning and execution. Full article

Nero Siciliano (NS) is an autochthonous pig breed reared in northeastern Sicily; despite its high-quality meat products, NS is currently endangered. This study aimed to evaluate the genetic variability at nine loci within candidate genes for meat traits—Melanocortin 4 Receptor (MC4R), Ryanodine Receptor 1 (RYR1), Class 3 Phosphoinositide 3-Kinase (PIK3C3) and Leptin (LEP)—to provide useful information for preservation and exploitation of the NS pig breed. Distribution of the genetic variants was assessed in a representative sample of 87 pigs (18 boars and 69 sows) collected in nine farms located in the original breeding area. Genotypes have been determined using PCR-RFLP and Sanger sequencing. Alleles linked to different growth rates and back fat deposition showed high frequencies (MC4R c.175C—0.93; LEP g.3469T—0.91) in the whole sample. Deviations from Hardy–Weinberg equilibrium and different allele distribution in boars and sows were observed. The RYR1 g.1843T allele, associated with Malignant Hyperthermia and Pale Soft Exudative meat defect, was reported in seven heterozygote pigs (q = 0.04) with one farm exhibiting a frequency of 0.29. Our results suggest the need for continuous monitoring of the genetic variants in NS both to maintain high meat quality and eradicate the RYR1 g.1843T allele. Full article

GTD 111 has been employed in first-stage blades in different gas turbines. The study of microstructural evolution is essential for the lifetime assessment and development of turbine blades. The microstructural stability of a 130 MW gas turbine first-stage blade at 800 °C was studied. The microstructure’s evolution was analyzed using scanning electron microscopy (SEM), transmission electron microscopy (TEM), and thermodynamic calculation. As thermal exposure time increases, the shape of γ′ precipitates changes from square to spherical. During thermal exposure, MC particles formed and coarsened along the grain boundaries, and primary MC carbide decomposed into the η phase and M₂₃C₆. The stability of MC carbide at the grain boundaries was lower than that within the grains. MC carbide precipitated at the grain boundaries tends to grow along the boundaries and eventually forms elongated carbide. High-resolution transmission electron microscopy (HRTEM) images indicate that the orientation of the γ′ precipitate changes during the coarsening process. The GTD 111 alloy can be deformed through dislocation shearing at 800 °C. The hardness value initially increases, then decreases with further exposure, which is related to the reduced precipitation strengthening by γ′ precipitates and the reduction in the hardness of the γ matrix. Full article

In this paper, cultivable actinobacteria were isolated, cultured, and identified from the heavily algal-bloomed waters of Taihu Lake using 16S rRNA gene sequencing. Among the isolates, a single strain exhibiting vigorous cyanocidal activity against Microcystis aeruginosa FACHB-905 was selected for further investigation. The cyanocidal efficacy and underlying mechanisms of this strain, designated TH05, were assessed through using chlorophyll content, cyanobacterial inhibition rate, and cyanobacterial cell morphology measurements. In addition, oxidative stress responses, expression of key functional genes in FACHB-905, and variations in microcystin concentrations were comprehensively evaluated. Cyanobacterial blooms caused by Microcystis aeruginosa pose serious ecological and public health threats due to the release of microcystins (MCs). In this study, we evaluated the cyanocidal activity and mechanism of a novel actinomycete strain, Streptomyces sp. TH05. Optimization experiments revealed that a light–dark cycle of 12 h/12 h, temperature of 25 °C, and pH 7 significantly enhanced cyanocidal efficacy. Under these conditions, TH05 achieved an 84.31% inhibition rate after seven days of co-cultivation with M. aeruginosa. Scanning electron microscopy revealed two distinct cyanocidal modes: direct physical attachment of TH05 mycelia to cyanobacterial cells, causing cell wall disruption, and indirect membrane damage via extracellular bioactive compounds. Biochemical analyses showed increased levels of malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT) during the first five days, peaking at 2.47-, 2.12-, and 1.91-fold higher than control levels, respectively, indicating elevated oxidative stress. Gene expression analysis using elf-p as a reference showed that TH05 modulated key genes associated with photosynthesis (PsaB, PstD1, PstD2, RbcL), DNA repair and stress response (RecA, FtsH), and microcystin biosynthesis (McyA, McyD). All genes were upregulated except for RbcL, which was downregulated. In parallel, microcystin content peaked at 32.25 ng/L on day 1 and decreased to 16.16 ng/L by day 9, which was significantly lower than that of the control group on day 9 (29.03 ng/L). These findings suggest that strain TH05 exhibits potent and multifaceted cyanocidal activity, underscoring its potential for application in the biological control of cyanobacterial blooms. Full article

Although emerging evidence suggests that epigenetic mechanisms contribute to the pathogenesis and progression of type 2 diabetes mellitus (T2DM), data remain limited for patients with suboptimal metabolic control. The aim of this study was to assess global DNA methylation in patients with poorly controlled T2DM and to identify diabetes-related factors associated with DNA methylation levels. The study included 107 patients and 50 healthy controls. Global DNA methylation (5mC) was measured by UHPLC-DAD method. Pro-oxidant and antioxidant biomarkers, advanced glycation end-products, high-sensitivity C-reactive protein (hsCRP) and complete blood count were determined and leukocyte indices calculated. Patients had a significantly lower 5mC than controls (3.56 ± 0.31% vs. 4.00 ± 0.68%; p < 0.001), with further reductions observed in those with longer disease duration and diabetic foot ulcers. Oxidative stress and inflammatory biomarkers were higher in the patient group. DNA hypomethylation was associated with a higher monocyte-to-lymphocyte ratio and hsCRP, pro-oxidant–antioxidant balance, ischemia-modified albumin, and advanced oxidation protein products levels. Conversely, 5mC levels showed positive correlations with total antioxidant status and total sulfhydryl groups. Principal component analysis identified five key factors: proinflammatory, pro-oxidant, aging, hyperglycemic, and antioxidant. The pro-oxidant factor emerged as the sole independent predictor of global DNA hypomethylation in T2DM (OR = 2.294; p = 0.027). Our results indicate that global DNA hypomethylation could be a biomarker of T2DM progression, reflecting the complex interactions between oxidative stress, inflammation, and epigenetic modifications in T2DM. Full article

This study presents a comprehensive case analysis of pyrite-hosted solid inclusions and their metallogenic significance in the Bainaimiao porphyry Cu deposit in NE China, which is genetically linked to the early Silurian granodiorite intrusion and porphyry dykes. Solid inclusions in pyrite from the deposit’s southern ore belt were analyzed across distinct mineralization stages. Using Electron Probe Micro-Analysis (EPMA) and in situ sulfur isotope analysis (MC-ICP-MS), inclusion assemblages in pyrite were identified, including pyrrhotite-chalcopyrite solid solutions, biotite, and dolomite. The results demonstrate that these inclusions primarily formed through coprecipitation with pyrite during crystal growth. Early-stage mineralizing fluids exhibited extreme temperatures exceeding 700 °C, coupled with low oxygen fugacity (fO₂) and low sulfur fugacity (fS₂). Sulfur isotope compositions (δ³⁴S: −5.85 to −4.97‰) indicate a dominant mantle-derived magmatic sulfur source, with contributions from reduced sulfur in sedimentary rocks. Combined with regional geological evolution, the Bainaimiao deposit is classified as a porphyry-type deposit. Its ore-forming materials were partially derived from Mesoproterozoic submarine volcanic exhalative sedimentary source beds, which were later modified and enriched by granodiorite porphyry magmatism. Full article

Crash boxes play a crucial role in automotive safety by absorbing impact energy during collisions. The advancement of additive manufacturing (AM), particularly Fused Deposition Modeling (FDM), has enabled the fabrication of geometrically complex and lightweight crash boxes. This study presents a comparative evaluation of the crashworthiness performance of five FDM materials, namely, PLA+, PLA-ST, PLA-LW, PLA-CF, and PETG, across four structural configurations: Single-Cell Circle (SCC), Multi-Cell Circle (MCC), Single-Cell Square (SCS), and Multi-Cell Square (MCS). Quasi-static axial compression tests are conducted to assess the specific energy absorption $\left(SEA\right)$ and crush force efficiency $\left(CFE\right)$ of each material–geometry combination. Among the materials, PLA-CF demonstrates superior performance, with the MCC configuration achieving an $SEA$ of 22.378 ± 0.570 J/g and a $CFE$ of 0.732 ± 0.016. Multi-cell configurations consistently outperformed single-cell designs across all materials. To statistically quantify the influence of material and geometry on crash performance, a two-factor ANOVA was performed, highlighting geometry as the most significant factor across all evaluated metrics. Additionally, a comparative test with aluminum 6063-T5 demonstrates that PLA-CF offers comparable crashworthiness, with advantages in mass reduction, reduced $PCF$, and enhanced design flexibility inherent in AM. These findings provide valuable guidance for material selection and structural optimization in FDM-based crash boxes. Full article

Glaucoma is a leading cause of irreversible blindness worldwide, yet early detection can prevent vision loss. This paper proposes a novel deep learning approach that combines two ophthalmic imaging modalities, fundus photographs and optical coherence tomography scans, as paired images from the same eye of each patient for automated glaucoma detection. We develop separate convolutional neural network models for fundus and optical coherence tomography images and a fusion model that integrates features from both modalities for each eye. The models are trained and evaluated on a private clinical dataset (Bangladesh Eye Hospital and Institute Ltd.) consisting of 216 healthy eye images (108 fundus, 108 optical coherence tomography) from 108 patients and 200 glaucomatous eye images (100 fundus, 100 optical coherence tomography) from 100 patients. Our methodology includes image preprocessing pipelines for each modality, custom convolutional neural network/ResNet-based architectures for single-modality analysis, and a two-branch fusion network combining fundus and optical coherence tomography feature representations. We report the performance (accuracy, sensitivity, specificity, and area under curve) of the fundus-only, optical coherence tomography-only, and fusion models. In addition to a fixed test set evaluation, we perform five-fold cross-validation, confirming the robustness and consistency of the fusion model across multiple data partitions. On our fixed test set, the fundus-only model achieves 86% accuracy (AUC 0.89) and the optical coherence tomography-only model, 84% accuracy (AUC 0.87). Our fused model reaches 92% accuracy (AUC 0.95), an absolute improvement of 6 percentage points and 8 percentage points over the fundus and OCT baselines, respectively. McNemar’s test on pooled five-fold validation predictions (b = 3, c = 18) yields ${\chi }^2=10.7$ (p = 0.001), and on optical coherence tomography-only vs. fused (b_o = 5, c_o = 20) ${\chi }_o^2=9.0$ (p = 0.003), confirming that the fusion gains are significant. Five-fold cross-validation further confirms these improvements (mean AUC $0.952\pm 0.011$. We also compare our results with the existing literature and discuss the clinical significance, limitations, and future work. To the best of our knowledge, this is the first time a novel deep learning model has been used on a fusion of paired fundus and optical coherence tomography images of the same patient for the detection of glaucoma. Full article

Microcystis, a potentially toxigenic cyanobacterium known to form extensive blooms in eutrophic lakes globally, was investigated in the cold oligotrophic Lake Baikal. We report the isolation of two Microcystis strains, Microcystis aeruginosa and M. novacekii, and document the presence of the latter species in Lake Baikal for the first time. In M. aeruginosa strain BN23, we detected the microcystin synthetase gene mcyE. Liquid chromatography-mass spectrometry revealed the presence of two microcystin variants in BN23, with microcystin-LR, a highly potent toxin, being the dominant form. The concentration of MC-LR reached 540 µg/g dry weight. In contrast, M. novacekii strain BT23 lacked both microcystin synthesis genes and detectable toxins. The habitat waters were characterized as oligotrophic with minor elements of mesotrophy, exhibiting low phytoplankton biomass dominated by the chrysophyte Dinobryon cylindricum (76–77% of biomass), with cyanobacteria contributing 8–10%. The contribution of Microcystis spp. to the total phytoplankton biomass could not be quantified as they were exclusively found in net samples. The water temperature at both sampling stations was ~19 °C, which is considerably lower than optimal for Microcystis spp. and potentially conducive to enhanced microcystin production in toxigenic genotypes. Full article