Search Results (2,379)

Hormone-dependent breast cancer, particularly in its treatment-resistant forms, remains a significant therapeutic challenge. In this study, we applied a fully computational strategy to design steroid-based compounds capable of simultaneously targeting three key receptors involved in disease progression: progesterone receptor (PR), estrogen receptor alpha (ER-α), and HER2. Using a robust 3D-QSAR model (R² = 0.86; Q²_LOO = 0.86) built from 52 steroidal structures, we identified molecular features associated with high anticancer potential, specifically increased polarizability and reduced electronegativity. From a virtual library of 271 DFT-optimized analogs, 31 compounds were selected based on predicted potency (pIC₅₀ > 7.0) and screened via molecular docking against PR (PDB 2W8Y), HER2 (PDB 7JXH), and ER-α (PDB 6VJD). Seven candidates showed strong binding affinities (ΔG ≤ −9 kcal/mol for at least two targets), with Estero-255 emerging as the most promising. This compound demonstrated excellent conformational stability, a robust hydrogen-bonding network, and consistent multitarget engagement. Molecular dynamics simulations over 100 nanoseconds confirmed the structural integrity of the top ligands, with low RMSD values, compact radii of gyration, and stable binding energy profiles. Key interactions included hydrophobic contacts, π–π stacking, halogen–π interactions, and classical hydrogen bonds with conserved residues across all three targets. These findings highlight Estero-255, alongside Estero-261 and Estero-264, as strong multitarget candidates for further development. By potentially disrupting the PI3K/AKT/mTOR signaling pathway, these compounds offer a promising strategy for overcoming resistance in hormone-driven breast cancer. Experimental validation, including cytotoxicity assays and ADME/Tox profiling, is recommended to confirm their therapeutic potential. Full article

Allergic contact dermatitis (ACD) is an immunologic reaction to a dermal chemical exposure that, once triggered in an individual, will result in an allergic response following subsequent encounters with the allergen. Air Force epidemiological consultations have indicated that aircraft structural maintenance workers may experience ACD at elevated rates compared to other occupations. We aimed to better understand the utility of non-animal testing methods in characterizing the sensitization potential of chemicals used during Air Force operations by evaluating the skin sensitization hazard of Air Force-relevant chemicals using new approach methodologies (NAMs) in a case study. We also evaluated the use of NAM data to develop preliminary candidate surface guidelines (PCSGs, maximum concentrations of chemicals on workplace surfaces to prevent induction of dermal sensitization) for chemicals identified as sensitizers. NAMs for assessing skin sensitization, including in silico models and experimental assays, were leveraged into an integrated approach to predict sensitization hazard for 19 chemicals. Local lymph node assay effective concentration values were predicted from NAM assay data via previously published quantitative models. The derived values were used to calculate PCSGs, which can be used to compare the presence of these chemicals on work surfaces to better understand the risk of Airmen developing ACD from occupational exposures. Full article

Steel is an important product in many engineering sectors; however, steelmaking remains one of the largest ${\mathrm{CO}}_2$ emitters. Therefore, new governmental policies drive the steelmaking industry toward a cleaner and more sustainable operation such as the gas-based direct reduction–electric arc furnace process. To become carbon neutral, utilizing more scrap is one of the feasible solutions to achieve this goal. Addressing knowledge gaps regarding scrap heterogeneity (size, shape, and composition) is essential to evaluate the effects of increased scrap ratios in basic oxygen furnace (BOF) operations. This review systematically examines heat and mass transfer correlations relevant to scrap melting in BOF steelmaking, with a focus on low Prandtl number fluids (thick thermal boundary layer) and dense particulate systems. Notably, a majority of these correlations are designed for fluids with high Prandtl numbers. Even for the ones tailored for low Prandtl, they lack the introduction of the porosity effect which alters the melting behavior in such high temperature systems. The review is divided into two parts. First, it surveys heat transfer correlations for single elements (rods, spheres, and prisms) under natural and forced convection, emphasizing their role in predicting melting rates and estimating maximum shell size. Second, it introduces three numerical modeling approaches, highlighting that the computational fluid dynamics–discrete element method (CFD–DEM) offers flexibility in modeling diverse scrap geometries and contact interactions while being computationally less demanding than particle-resolved direct numerical simulation (PR-DNS). Nevertheless, the review identifies a critical gap: no current CFD–DEM framework simultaneously captures shell formation (particle growth) and non-isotropic scrap melting (particle shrinkage), underscoring the need for improved multiphase models to enhance BOF operation. Full article

Addressing the need for contact load detection in wind turbine main bearings during service, a roller contact load measurement method is proposed. An analytical model characterizes the contact load-to-inner bore strain mapping relationship. To overcome the inherent low sensitivity of direct bore strain measurement, bore-to-measurement-point sensitivity analysis was optimized. Multiple structurally optimized sensor brackets were designed to enhance strain measurement sensitivity, and their performance was comparatively evaluated via simulation. To mitigate sensitivity fluctuations caused by roller rotation phase variations, a strain–phase–load calculation method incorporating real-time phase compensation was developed and verified through simulation analysis. A dedicated roller contact load testing system was constructed and experimental validation was conducted. Results demonstrate 95% accuracy in contact load acquisition. This method accurately obtains roller contact loads in wind turbine main bearings, proving crucial for studying bearing mechanical behavior, predicting fatigue life, optimizing structural design, and enhancing reliability. Full article

This paper creates a global similarity network between city-level dialects of English in order to determine whether external factors like the amount of population contact or language contact influence dialect similarity. While previous computational work has focused on external influences that contribute to phonological or lexical similarity, this paper focuses on grammatical variation as operationalized in computational construction grammar. Social media data was used to create comparable English corpora from 256 cities across 13 countries. Each sample is represented using the type frequency of various constructions. These frequency representations are then used to calculate pairwise similarities between city-level dialects; a prediction-based evaluation shows that these similarity values are highly accurate. Linguistic similarity is then compared with four external factors: (i) the amount of air travel between cities, a proxy for population contact, (ii) the difference in the linguistic landscapes of each city, a proxy for language contact, (iii) the geographic distance between cities, and (iv) the presence of political boundaries separating cities. The results show that, while all these factors are significant, the best model relies on language contact and geographic distance. Full article

This study proposes a vibration-based approach for detecting and quantifying sub-slab corner voids in airport cement concrete pavement. Scaled down slab models were constructed and subjected to controlled moving load simulations. Acceleration signals were collected and analyzed to extract time–frequency domain features, including power spectral density (PSD), skewness, and frequency center. A finite element model incorporating contact and nonlinear constitutive relationships was established to simulate structural response under different void conditions. Based on the simulated dataset, a random forest (RF) model was developed to estimate void size using selected spectral energy indicators and geometric parameters. The results revealed that the RF model achieved strong predictive performance, with a high correlation between key features and void characteristics. This work demonstrates the feasibility of integrating simulation analysis, signal feature extraction, and machine learning to support intelligent diagnostics of concrete pavement health. Full article

To address the wear life prediction challenge of Guide Cones in passive compliant connectors under dynamic loads within specialized equipment, this study proposes a dynamic wear modeling and life assessment method based on the improved Archard model. Through integrated theoretical modeling, finite element simulation, and experimental validation, we establish a bidirectional coupling framework analyzing dynamic contact mechanics and wear evolution. By developing phased contact state identification criteria and geometric constraints, a transient load calculation model is established, revealing dynamic load characteristics with peak contact forces reaching 206.34 N. A dynamic contact stress integration algorithm is proposed by combining Archard’s theory with ABAQUS finite element simulation and ALE adaptive meshing technology, enabling real-time iterative updates of wear morphology and contact stress. This approach constructs an exponential model correlating cumulative wear depth with docking cycles (R² = 0.997). Prototype experiments demonstrate a mean absolute percentage error (MAPE) of 14.6% between simulated and measured wear depths, confirming model validity. With a critical wear threshold of 0.8 mm, the predicted service life reaches 45,270 cycles, meeting 50-year operational requirements (safety margin: 50.9%). This research provides theoretical frameworks and engineering guidelines for wear-resistant design, material selection, and life evaluation in high-reliability automatic docking systems. Full article

Sepsis is a fetal disease that requires a clear diagnostic biomarker for timely antibiotic treatment. Recent research has identified a pyroptosis-inducing epitope known as P5-5 in tetranectin (TN), a plasma protein produced by monocytes. Previously, we produced a 12F1 monoclonal antibody against the P5-5 and discovered that it could not only diagnose the presence but also monitor the progress of sepsis in the clinic. In the current study, we further investigated the structure site of the P5-5 and the recognition mechanism between the 12F1 mAb and the P5-5 epitope. To this end, 10 amino acids (NDALYEYLRQ) in the P5-5 were individually mutated to alanine, and their binding to the mAb was tested to confirm the most significant antigenic recognition sites. In the meanwhile, the spatial conformation of 12F1 mAb variable regions was modeled, and the molecular recognition mechanisms in detail of the mAb to the P5-5 epitope were further studied by molecular docking. Following epitope prediction and experimental verification, we demonstrated that the motif “DALYEYL” in the epitope sequence position 2−8 of TN-P5-5 is the major binding region for mAb recognition, in which two residues (4L and 8L) were essential for the interaction between the P5-5 epitope and the 12F1 mAb. Therefore, our study greatly narrowed down the previously reported motif from ten to seven amino acids and identified two Leu as critical contact residues. Finally, a single-chain variable fragment (scFv) from the 12F1 hybridoma was constructed, and it was confirmed that the identified motif and residues are prerequisites for the strong binding between P5-5 and 12F1. Altogether, the data of the present work could serve as a theoretic guide for the clinical design of biosynthetic drugs by artificial intelligence to treat sepsis. Full article

To remove nickel (II) from an aqueous solution, cellulose nanocrystals (CNCs) were modified as an adsorbent. The FTIR and SEM were used to characterise the properties of CNCs. In addition to how well they predicted reaction (adsorption capacity), the central composite design was used. The response surface model method performs well, according to statistical data. Four operational variables were studied: The initial concentration of the nickel (II) solution in mg/L, the pH, the contact period in minutes, and the adsorbent dose in g/100 mL. The removal percentage (%) was the result. The percentage removal was 98% after 178 min of contact, a starting concentration of 110 mg/L, an adsorbent dosage of 9.3 g, and an initial pH of 3.5. The R² was 0.996, the adjusted R² was 0.921, and the predicted R² was 0.945. The quadratic equation was determined using central composite design. The FTIR examination revealed that the functional groups, hydroxyl groups (OH), peaked around 3300–3500 cm^−1, and carboxyl groups (COOH) peaked around 1700 cm⁻¹. Full article

The inferior electrical conductivity and elevated hardness of AgSnO₂ electrical contact materials have impeded their development. To investigate the effects of Co, Bi, and La doping on the stability and electrical properties of AgSnO₂, this study established interfacial models of doped AgSnO₂ based on first-principles calculations initiated from the atomic structures of constituent materials, subsequently computing electronic structure parameters. The results indicate that doping effectively enhances the interfacial stability and bonding strength of AgSnO₂ and thereby predicted improved electrical contact performance. Doped SnO₂ powders were prepared experimentally using the sol–gel method, and AgSnO₂ contacts were fabricated using high-energy ball milling and powder metallurgy. Testing of wettability and electrical contact properties revealed reductions in arc energy, arcing time, contact resistance, and welding force post-doping. Three-dimensional profilometry and scanning electron microscopy (SEM) were employed to characterize electrical contact surfaces, elucidating the arc erosion mechanism of AgSnO₂ contact materials. Among the doped variants, La-doped electrical contact materials exhibited optimal performance (the lowest interfacial energy was 1.383 eV/Ų and wetting angle was 75.6°). The mutual validation of experiments and simulations confirms the feasibility of the theoretical calculation method. This study provides a novel theoretical method for enhancing the performance of AgSnO₂ electrical contact materials. Full article

The exponential increase in electronic waste (e-waste) from end-of-life electrical and electronic equipment presents a growing environmental challenge. E-waste contains high concentrations of rare earth elements (REEs), which are classified as critical raw materials (CRMs). Their removal and recovery from contaminated systems not only mitigate pollution but also support resource sustainability within a circular economy framework. The present study proposed the use of hazelnut shells as a biosorbent to reduce water contamination and recover REEs. The sorption capabilities of this lignocellulosic material were assessed and optimized using the response surface methodology (RSM) combined with a Box–Behnken Design (three factors, three levels). Factors such as pH (4 to 8), salinity (0 to 30), and biosorbent dose (0.25 to 0.75 g/L) were evaluated in a complex mixture containing 9 REEs (Y, La, Ce, Pr, Nd, Eu, Gd, Tb and Dy; equimolar concentration of 1 µmol/L). Salinity was found to be the factor with greater significance for REEs sorption efficiency, followed by water pH and biosorbent dose. At a pH of 7, salinity of 0, biosorbent dose of 0.75 g/L, and a contact time of 48 h, optimal conditions were observed, achieving removals of 100% for Gd and Eu and between 81 and 99% for other REEs. Optimized conditions were also predicted to maximize the REEs concentration in the biosorbent, which allowed us to obtain values (total REEs content of 2.69 mg/g) higher than those in some ores. These results underscore the high potential of this agricultural waste with no relevant commercial value to improve water quality while providing an alternative source of elements of interest for reuse (circular economy). Full article

This paper proposes an improved wave function asperity elastic–plastic model. A cosine function that could better fit the geometric morphology was selected to construct the asperity, the elastic phase was controlled by the Hertz contact theory, the elastoplastic transition phase was corrected by the hyperbolic tangent function, and the fully plastic phase was improved by the projected area theory. The model broke through the limitations of the spherical assumption and was able to capture the stress concentration and plastic flow phenomena. The results show that the contact pressure in the elastic phase was 22% higher than that of the spherical shape, the plastic strain in the elastoplastic phase was 52% lower than that of the spherical shape, and the fully plastic phase reduced the contact area error by 20%. The improved hyperbolic tangent function eliminated the unphysical oscillation phenomenon in the elastoplastic phase and ensured the continuity and monotonicity of the contact variables, with an error of <5% from the finite element analysis. Meanwhile, extending the proposed model, we developed a rough surface contact model, and it was verified that the wavy asperity could better match the mechanical properties of the real rough surface and exhibited progressive stiffness reduction during the plastic flow process. The model in this paper can provide a theoretical basis for predicting stress distribution, plastic evolution, and multi-scale mechanical behavior in the connection interface. Full article

In this paper, MXene nanosheets were used as nano additives for the preparation of MXene-modified polyvinyl chloride (PVC) mixed max membranes (MMMs) for the rejection of lead (Pb²⁺) ions from wastewater. MXene nanosheets were introduced into the PVC matrix to enhance membrane performance, hydrophilicity, contact angle, porosity, and resistance to fouling. Modeling and optimization techniques were used to examine the effects of important operational and fabrication parameters, such as pH, contaminant concentration, nanoadditive (MXene) content, and operating pressure. Predictive models were developed using experimental data to assess the membranes’ performance in terms of flux and Pb²⁺ rejection. The ideal circumstances that struck a balance between long-term operating stability and high removal efficiency were found through multi-variable optimization. The optimized conditions for the best rejection of Pb²⁺ ions and the most stable permeability over time among the membranes that were manufactured were the initial metal ions concentration (2 mg/L), pH (7.89), pressure (2.99 bar), and MXene mass (0.3 g). The possibility of combining MXene nanoparticles with methodical optimization techniques to create efficient membranes for the removal of heavy metals in wastewater treatment applications is highlighted by this work. Full article

Ferrocene (Fc), a redox-active organometallic scaffold, has attracted significant attention in medicinal chemistry due to its favorable physicochemical and pharmacological properties. The present study explores the therapeutic potential of novel Fc-functionalized analogues of imatinib and nilotinib, aimed at targeting BCR-ABL1+ chronic myeloid leukemia (CML) cells. A series of Fc-based derivatives (compounds 6, 9, 14, and 18) were synthesized by systematically substituting key pharmacophoric regions of the parent tyrosine kinase inhibitors with Fc units. The antiproliferative activity of these compounds was evaluated against four BCR-ABL1-positive leukemia cell lines (K-562, BV-173, AR-230, and LAMA-84), with imatinib serving as a reference drug. Biological assays revealed distinct structure–activity relationships. Compounds 6 and 9 demonstrated superior activity against the K-562 cell line, while compounds 14 and 18 exhibited enhanced potency and higher ligand efficiencies (LEs) against BV-173 and AR-230 cells compared to imatinib. Selectivity assays further indicated favorable toxicity profiles of compounds 9 and 14 toward malignant versus non-malignant cells. Molecular docking studies supported these findings, showing that Fc substitution alters binding interactions within the c-Abl kinase ATP-binding site while retaining key stabilizing contacts. Computationally predicted LEs showed strong correlation with experimental data, especially for K-562 and LAMA-84 cells, confirming the kinase as a relevant target. Full article

Natural polymers, polysaccharides, demonstrate piezoelectric behavior suitable for force sensor manufacturing. Carrageenan hydrogel film with α-iron oxide particles can act as a piezoelectric polysaccharide-based force sensor. The mechanical impact on the hydrogel caused by a falling ball shows the impact response time, which is measured in milliseconds. Repeating several experiments in a row shows the dynamics of fatigue, which does not reduce the speed of response to impact. Through the practical experiments, we sought to demonstrate how theoretical knowledge describes the hydrogel we elaborated, which works as a piezoelectric material. In addition to the theoretical basis, which includes the operation of the metal and metal oxide contact junction, the interaction between the metal oxide and the hydrogel surfaces, the paper presents the practical application of this knowledge to the complex hydrogel film. The simple calculations presented in this paper are intended to predict the hydrogel film’s characteristics and explain the results obtained during practical experiments. Carrageenan, as a low-cost and already widely used polysaccharide in various industries, is suitable for the production of low-cost force sensors in combination with iron oxide. Full article