Search Results (7,440)

Nearly all eukaryotic proteins are turned over by the ubiquitin (Ub)-26S proteasome system (UPS). Despite its broad cellular roles, only a handful of UPS members, particularly the Ub E3 ligases that specifically recognize a protein for ubiquitylation, have been characterized in plants to date. The challenge arises from the transient recognition and rapid degradation of ubiquitylation substrates by the UPS. To tackle this challenge, the emerging biotinylation-based proximity labeling (PL) offers an exciting tool for enriching transient interactors of Ub E3 ligases. In this study, we examined the efficacy of TurboID in identifying substrates of Arabidopsis Skp1-cullin1-F-box (SCF) ligases. We demonstrate that the Arabidopsis Skp1 Like (ASK)1-TurboID is not fully functioning in planta, which led us to discover a novel antagonism between biotinylation and ubiquitylation in regulating protein stability in vivo. This discovery lowers the effectiveness of PL in ubiquitylome studies. However, using one long-known SCF substrate, phytochrome A, we succeeded to apply its TurboID fusion for complementing the far-red-light response of the phyA-211 null mutant allele, suggesting an efficacy of PL in characterizing single ubiquitylation pathways. This study highlighted a limitation of PL in ubiquitylome studies, discovered a new antagonistic pathway of biotinylation, and developed a theoretical guidance for future PL-based characterization of ubiquitylation pathways. Full article

Nuclear factor erythroid 2-related factor 2 (NRF2) serves as a master transcriptional regulator of cellular antioxidant responses through orchestration of cytoprotective gene expression, establishing its significance as a therapeutic target in cerebral pathophysiology. Classical electrophilic NRF2 activators, despite potent activation potential, exhibit paradoxically reduced therapeutic efficacy relative to single antioxidants, attributable to concurrent oxidative stress generation, glutathione depletion, mitochondrial impairment, and systemic toxicity. Although emerging non-electrophilic pharmacological activators offer therapeutic potential, their utility remains limited by bioavailability and suboptimal potency, underscoring the imperative for innovative therapeutic strategies to harness this cytoprotective pathway. Non-pharmacological interventions, including neuromodulation, physical exercise, and lifestyle modifications, activate NRF2 through non-canonical, non-electrophilic pathways involving protein–protein interaction inhibition, KEAP1 degradation, post-translational and transcriptional modulation, and protein stabilization, though mechanistic characterization remains incomplete. Such interventions utilize multi-mechanistic approaches that synergistically integrate multiple non-electrophilic NRF2 pathways or judiciously combine electrophilic and non-electrophilic mechanisms while mitigating electrophile-induced toxicity. This strategy confers neuroprotective effects without the contraindications characteristic of classical electrophilic activators. This review comprehensively examines the mechanistic underpinnings of non-pharmacological NRF2 modulation, highlighting non-electrophilic activation pathways that bypass the limitations inherent to electrophilic activators. The evidence presented herein positions non-pharmacological interventions as viable therapeutic approaches for achieving non-electrophilic NRF2 activation in the treatment of cerebrovascular and neurodegenerative pathologies. Full article

This study reports an investigation of the synergistic extraction of dysprosium (Dy(III)) from aqueous media using a low-concentration, binary carrier mixture of Cyanex 272 and D2EHPA within an emulsion liquid membrane (ELM). Within the tested formulations, the one containing 0.42% (w/w) Cyanex 272 and 0.28% (w/w) D2EHPA yielded the best results. The impact of process factors that maximize recovery efficiency and minimize emulsion breakdown was also examined. A Span 80 loading of 0.75% (w/w) achieved 97.5% extraction with minimal breakage (less than 2.1%). An external phase pH of 5.8 achieves an optimal balance of high-throughput Dy(III) recovery and membrane stability; 0.2 N HNO₃ as the stripping phase strikes the optimal balance, providing strong initial uptake with minimal emulsion degradation. As the initial Dy(III) loading increases, extraction efficiency decreases. Increasing the temperature from 15 to 45 °C accelerates mass transfer, achieving near-complete extraction in under 15 min. However, above 45 °C, emulsion breakage spikes, causing a collapse in efficiency. Similarly, increasing NaCl levels suppresses Dy(III) uptake and promotes coalescence. This reduces recovery from seawater to just over 70%. Nevertheless, the balanced mineral content of Zamzam water preserves emulsion integrity and enables 100% extraction. The activation energy was found to be 26.16 kJ/mol, suggesting that mass transfer, rather than the chemical reaction at the interface, controls the process. The results of this study highlight the synergistic efficiency advantage of the ELM system at lower carrier concentrations, even in complex water sources. Full article

Accurate State of Health (SOH) estimation is critical for ensuring the safe operation of lithium-ion batteries. However, current data-driven approaches face significant challenges: insufficient feature extraction and ambiguous physical meaning compromise prediction accuracy, while initialization sensitivity to noise undermines stability; the inherent nonlinearity and temporal complexity of battery degradation data further lead to slow convergence or susceptibility to local optima. To address these limitations, this study proposes an enhanced CNN-BIGRU model. The model replaces conventional random initialization with a Hiking Optimization Algorithm (HOA) to identify superior initial weights, significantly improving early training stability. Furthermore, it integrates an Attention mechanism to dynamically weight features, strengthening the capture of key degradation characteristics. Rigorous experimental validation, utilizing multi-dimensional features extracted from the NASA dataset, demonstrates the model’s superior convergence speed and prediction accuracy compared to the CNN-BIGRU-Attention benchmark. Compared with other methods, the HOA-CNN-BIRGU-Attention model proposed in this study has a higher prediction accuracy and better robustness under different conditions, and the RMSEs on the NASA dataset are all controlled within 0.01, with R2 kept above 0.91. The RMSEs on the University of Maryland dataset are all below 0.006, with R2 kept above 0.98. Compared with the CNN-BIGRU-ATTENTION baseline model without HOA optimization, the RMSE is reduced by at least 0.15% across different battery groups in the NASA dataset. Full article

In this study, 10% nitric acid was employed to remove the aluminum coating on the cobalt-based superalloy K6509, with a focus on elucidating the corrosion mechanism and evaluating the effect of ultrasonic on the removal process. The results shows that ultrasonic treatment (40 kHz) significantly improves coating removal efficiency, increasing the maximum corrosion rate by 46.49% from 2.5413 × 10⁻⁷ g·s⁻¹·mm⁻² to 4.7488 × 10⁻⁷ g·s⁻¹·mm⁻² and reducing removal time from 10 min to 6 min. This enhancement is attributed to cavitation effect of ultrasonic bubbles and the shockwave-accelerated ion diffusion, which together facilitate more efficient coating degradation and results in a smoother surface. In terms of corrosion behavior, the difference in phase composition between the outer layer and the interdiffusion zone (IDZ) plays a decisive role. The outer layer is primarily composed of β-(Co,Ni)Al phase, which is thermodynamically less stable in acidic environments and thus readily dissolves in 10% HNO₃. In contrast, the IDZ mainly consists of Cr₂₃C₆, which exhibit high chemical stability and a strong tendency to passivate. These characteristics render the IDZ highly resistant to nitric acid attack, thereby forming a protective barrier that limits acid penetration and helps maintain the integrity of the substrate. Full article

The clinical use of 1,25-dihydroxycholecalciferol (1,25D3), the active form of vitamin D₃, is limited by its calcemic side effects and rapid metabolic degradation. To overcome these limitations, we designed novel vitamin D analogs with extended, rigidified, and branched side chains. Among them, PRI-1938, featuring a 5,6-trans triene system and 22,24-all-trans side-chain geometry, demonstrated markedly enhanced resistance to enzymatic catabolism. In vitro assays revealed that metabolic conversion of PRI-1938 by the nonselective cytochrome P450 3A4 (CYP3A4) enzyme was ca. 4-fold lower than that of the previously obtained PRI-1906 and over 9-fold lower than 1,25D3. All new analogs, including PRI-1927 and PRI-1937, exhibited significantly higher stability toward mitochondrial cytochrome P450 24A1 (CYP24A1), the vitamin D-selective catabolic enzyme, than that of 1,25D3. Molecular modeling and quantum mechanical calculations indicated that PRI-1938 adopts a highly stable conformation in the CYP24A1 active site, stabilized by four hydrogen bonds and multiple hydrophobic interactions. The spatially optimized interaction network reduces access to the catalytic heme, resulting in the lowest observed metabolic conversion. These findings highlight the critical role of the side-chain geometry in modulating metabolic stability and support the further development of PRI-1938 as a promising anticancer vitamin D analog. Full article

Fatigue damage failure is a process where the mechanical properties of different materials continuously degrade under the action of cyclic loads. The cumulative analysis of fatigue damage has a significant impact on the service structure of major equipment. This paper starts from the mechanism of fatigue damage evolution, comprehensively considers the influence of the order of high-low cycle load mixed cyclic loading on the fatigue life performance, and based on the Manson-Halford nonlinear fatigue damage accumulation theory and the mechanism of relative cumulative damage, a new nonlinear damage accumulation fatigue life model is established, and a fatigue damage accumulation influencing factor D_cr is introduced to improve the prediction accuracy of the model. The new model proposed in this paper is verified through multi-level fatigue load data. By comparing the prediction results with other models under the same experimental conditions, the fatigue life prediction error precision of the new model is the best in similar cases, generally with an error precision between 10% and 20%, which proves the effectiveness and accuracy of the nonlinear damage accumulation model proposed in this paper. At the same time, the improved method in this paper has better stability while ensuring prediction accuracy. Full article

The persistence of pharmaceutical pollutants such as ciprofloxacin (CIP) in aquatic environments represents a critical environmental threat due to their potential to induce antimicrobial resistance. Photocatalysis using TiO₂-based materials offers a promising solution for their mineralization; however, the limited visible-light response of TiO₂ and charge carrier recombination restricts its overall efficiency. In this study, Nb-doped TiO₂ nanoparticles were synthesized via the sol–gel method, incorporating Nb⁵⁺, ions into the TiO₂ lattice to modulate the structural and electronic properties of TiO₂ to enhance its photocatalytic performance for CIP degradation under UV and visible irradiation. Comprehensive structural, morphological, and optical analyses revealed that Nb incorporation stabilizes the anatase phase, reduces particle size (from 21.42 nm to 10.29 nm), and induces a slight band gap widening (from 2.85 to 2.87 eV) due to the Burstein–Moss effect. Despite this blue shift, Nb-TiO₂ exhibited significantly improved photocatalytic activity under visible light, achieving 86% CIP degradation with a reaction rate 16 times higher than that of undoped TiO₂. This enhancement was attributed to improved charge separation and higher hydroxyl radical (^•OH) generation, driven by excess conduction band electrons introduced by Nb doping. Density Functional Theory (DFT) calculations further elucidated the electronic structure modifications responsible for this behavior, offering molecular-level insights into Nb dopant-induced property tuning. These findings demonstrate how targeted doping strategies can engineer multifunctional nanomaterials with superior photocatalytic efficiencies, especially under visible light, highlighting the synergy between experimental design and theoretical modeling for environmental applications. Full article

With the rapid development of advanced machining technologies such as high-speed cutting, dry cutting, and ultra-precision cutting, as well as the widespread application of various difficult-to-machine materials, the surface degradation problems such as wear, oxidation, and delamination faced by tools in the service process have become increasingly prominent, seriously restricting the performance and service life of tools. Nanocoatings, with their distinct nano-effects, provide superior hardness, thermal stability, and tribological properties, making them an effective solution for cutting tools in increasingly demanding working environments. For example, the hardness of the CrAlN/TiSiN nano-multilayer coating can reach 41.59 GPa, which is much higher than that of a single CrAlN coating (34.5–35.8 GPa). This paper summarizes the most common nanocoating material design, coating deposition technologies, performance evaluation indicators, and characterization methods currently used in cutting tools. It also discusses how to improve nanocoating performance using modulation analysis of element content, coating composition, geometric structure, and coating thickness. Finally, this paper considers the future development of nanocoatings for cutting tools in light of recent research hotspots. Full article

This study investigates the development of a sustainable flame-retardant treatment for cotton fabrics using a hybrid coating composed of chitosan, phytic acid, APTES, and eggshell powder at concentrations of 2% and 4%, applied in one and two cycles. FTIR confirmed the deposition of the organic–inorganic layer through the appearance of characteristic bands. Thermogravimetric analysis (TGA/dTGA) revealed enhanced thermal stability for all treated samples, with increased char yield and a shift in the main cellulose degradation peak. Vertical flammability tests demonstrated that all coated fabrics achieved self-extinguishing behavior within 12 s, meeting NFPA 701 criteria. The 2% eggshell formulation with two applications (S2%-II) exhibited the best balance between flame retardancy and mechanical performance. Tensile tests indicated improved fiber cohesion for treated samples, while SEM micrographs confirmed uniform coating deposition and particle integration. Colorimetric analysis showed that the treatment did not cause a significant change in the natural color of the cotton. Although washing resistance remains a limitation due to the natural origin of the components, the samples remained stable over time without microbial growth or staining, suggesting potential for upholstery and covering fabrics not subjected to domestic washing. The results highlight the feasibility of using agro-industrial waste to create eco-friendly flame-retardant finishes for cotton textiles. Full article

Strawberries are highly perishable despite their popularity, as their limited shelf life compromises both freshness and market value. The study investigated the effects of 1-methylcyclopropene (1-MCP), modified atmosphere packaging (MAP), and their combined treatments on the quality and flavor of strawberries during cold storage and simulated shelf life. 1-MCP was applied by enclosing strawberry fruits in a hermetically sealed container and exposing them to 250 nL/L 1-MCP at 20 °C for 18 h. Three initial MAP gas compositions were tested: MAP1 (5% O₂, 15% CO₂, 80% N₂), MAP2 (10% O₂, 10% CO₂, 80% N₂), and MAP3 (15% O₂, 5% CO₂, 80% N₂), with MAP1 identified as optimal based on strawberry postharvest quality metrics. The results showed that all treatments could inhibit the deterioration of strawberry quality, and the 1-MCP + MAP treatment had the best fresh-keeping effect. Untargeted Gas Chromatography-Mass Spectrometry (GC-MS) analysis identified 85 volatile compounds, and sensory correlation analysis revealed that 1-MCP + MAP-treated strawberries maintained the highest consumer acceptability, with odor characteristics closely resembling those of pre-storage controls. Further studies demonstrated that the combined treatment uniquely suppressed the generation of fatty acid oxidation-derived volatiles while stabilizing critical aroma-active esters, thereby decelerating flavor degradation. Collectively, these findings highlight the potential of 1-MCP + MAP as a postharvest strategy to delay the postharvest senescence of strawberries and maintain their storage quality. GC-MS provided a scientific method for the flavor quality evaluation of this preservation technology. Full article

This study reports the development of a simple and sensitive electrochemical sensor based on activated screen-printed electrodes modified by electrodeposition of nickel(II) tetrasulfonated phthalocyanine film (poly-NiTSPc), denoted SPE-A-polyNiTSPc, for the direct determination of BPA in landfill leachate samples. BPA concentrations in raw landfill leachate solutions and in residual solutions after a reverse osmosis (RO) treatment were determined, using differential pulse voltammetry (DPV) on SPE-A-polyNiTSPc, to be 29.7 mgL⁻¹ and 6.4 µgL⁻¹, respectively. The obtained BPA concentrations were very close to those found by the accredited lab in the same samples, which were 29.6 mgL⁻¹ and 6.0 µgL⁻¹, respectively. The applicability of SPE-A-polyNiTSPc for BPA bioremediation was investigated in landfill leachate samples using Trichoderma harzianum fungus in a microbial fuel cell (MFC), where the kinetics data were modeled. The first results showed an IC₅₀ of 175 mgL⁻¹ BPA, indicating that the inhibition factor could be negligeable for MFC experiments at 30 mgL⁻¹ BPA. The biodegradation kinetics was found to be of first order, with a kinetic constant of 0.795 h⁻¹ at 22 °C and a half-degradation time of 0.872 h for an initial concentration of 29 mgL⁻¹. The developed MFC displayed higher stability, offering a maximum power of 100 mWm⁻³. Full article

This paper presents a detailed analysis of the severe structural anomalies that led to the urgent rehabilitation of the Eduardo Caldeira Bridge in Machico, Madeira. Situated in a challenging coastal environment with complex volcanic geology, the bridge exhibited a critical failure of its bearing devices, which were assigned the highest defect severity rating (Grade 5). A multidisciplinary diagnostic methodology, combining visual inspection data, non-destructive testing, and geotechnical analysis, was employed to identify the root causes of this degradation. The investigation concluded that the bearing failure was not due to widespread material deterioration but was directly linked to significant lateral structural displacements, exacerbated by localized geotechnical instabilities. This paper details the data-driven rehabilitation strategy that was subsequently implemented, including the complete replacement of the bearings and substructure stabilization measures. The study provides a valuable case study of a complex, mechanics-driven failure mode and demonstrates that for such critical infrastructure, a proactive management model integrating advanced technologies like Structural Health Monitoring (SHM) and Building Information Modelling (BIM) is essential for ensuring long-term safety and resilience. Full article

This study presents a high-performance external strengthening strategy for reinforced concrete (RC) beam–column joints, integrating near-surface mounted (NSM) Carbon Fiber Reinforced Polymer (C-FRP) ropes with externally bonded C-FRP sheets. The X-shaped ropes, anchored diagonally on both principal joint faces and complemented by vertical ropes at column corners, provide enhanced core confinement and shear reinforcement. C-FRP sheets applied to the beam’s plastic hinge region further increase flexural strength and delay localized failure. Three full-scale, shear-deficient RC joints were subjected to cyclic lateral loading. The unstrengthened specimen (JB0V) exhibited rapid stiffness deterioration, premature joint shear cracking, and unstable hysteretic behavior. In contrast, the specimen strengthened solely with X-shaped C-FRP ropes (JB0VF2X2c) displayed a markedly slower rate of stiffness degradation, delayed crack development, and improved energy dissipation stability. The fully retrofitted specimen (JB0VF2X2c + C-FRP) demonstrated the most pronounced gains, with peak load capacity increased by 65%, equivalent viscous damping enhanced by 55%, and joint shear deformations reduced by more than 40%. Even at 4% drift, it retained over 90% of its peak strength, while localizing damage away from the joint core—a performance unattainable by the unstrengthened configuration. These results clearly establish that the combined C-FRP rope–sheet system transforms the seismic response of deficient RC joints, offering a lightweight, non-invasive, and rapidly deployable retrofit solution. By simultaneously boosting shear resistance, ductility, and energy dissipation while controlling damage localization, the technique provides a robust pathway to extend service life and significantly enhance post-earthquake functionality in critical structural connections. Full article

Lung cancer is the leading cause of cancer mortality worldwide, with a poor prognosis driven by late diagnosis, systemic toxicity of existing therapies, and rapid development of multidrug resistance (MDR) to agents such as paclitaxel and cisplatin. MDR arises through multiple mechanisms, including overexpression of efflux transporters, alterations in apoptotic pathways, and tumour microenvironment-mediated resistance. The application of nanotechnology offers a potential solution to the aforementioned challenges by facilitating the enhancement of drug solubility, stability, bioavailability, and tumour-specific delivery. Additionally, it facilitates the co-loading of agents, thereby enabling the attainment of synergistic effects. Halloysite nanotubes (HNTs) are naturally occurring aluminosilicate nanocarriers with unique dual-surface chemistry, allowing hydrophobic drug encapsulation in the positively charged lumen and functionalisation of the negatively charged outer surface with targeting ligands or MDR modulators. This architecture supports dual-delivery strategies, enabling simultaneous administration of phytocannabinoids and chemotherapeutics or efflux pump inhibitors to enhance intracellular retention and cytotoxicity in resistant tumour cells. HNTs offer additional advantages over conventional nanocarriers, including mechanical and chemical stability and low production cost. Phytocannabinoids such as cannabidiol (CBD) and cannabigerol (CBG) show multitarget anticancer activity in lung cancer models, including apoptosis induction, proliferation inhibition, and oxidative stress modulation. However, poor solubility, instability, and extensive first-pass metabolism have limited their clinical use. Encapsulation in HNTs can overcome these barriers, protect against degradation, and enable controlled, tumour-targeted release. This review examined the therapeutic potential of HNT-based phytocannabinoid delivery systems in the treatment of lung cancer, with an emphasis on improving therapeutic selectivity, which represents a promising direction for more effective and patient-friendly treatments for lung cancer. Full article