Search Results (30,469)

Intracellular alkalosis and extracellular acidosis are two pathological features associated with malignant cells. They offer advantages in terms of invasiveness and proliferation. Extracellular acidification is the consequence of intracellular metabolic changes associated with a higher metabolic rate of cancer cells, potentially inducing dangerous intracellular acidification. To overcome this menace, malignant cells adapt themselves to export hydrogen ions. Therefore, it is reasonable that targeting intracellular alkalinization and extracellular acidification to prompt the reversal of such a pH gradient towards a condition comparable to normal, untransformed cells may represent a strategy helping to contrast malignant behavior. In the present study, we investigated in vitro, in prostate cancer cell models, the biological activity towards intracellular, extracellular and organelle pH of systems of molecules of vegetal origin. A few of these systems were shown to promote intracellular acidification in vitro, whereas others were shown to prevent extracellular acidification and promote lysosomal alkalinization in a cell type-dependent manner. This result clearly indicates that these systems may function as agents interfering with malignant cells inverted pH gradient. Further analysis would be necessary to unravel the cell type specificity of their effects, as well as their mechanism of action. Nevertheless, our proof-of-principle study provides evidence that such systems of molecules can be considered interesting agents in co-adjuvating anti-cancer therapies. Full article

Homologous recombination deficiency (HRD) is a pivotal biomarker in precision oncology, driving therapeutic strategies for ovarian and breast cancers through impaired DNA double-strand break repair. This narrative review synthesizes recent advances (2021–2025) in HRD’s biological basis, prevalence, detection methods, and clinical implications, focusing on high-grade serous ovarian carcinoma (HGSOC; ~50% HRD prevalence) and triple-negative breast cancer (TNBC; 50–70% prevalence). HRD arises from genetic (BRCA1/2, RAD51C/D, PALB2) and epigenetic alterations (e.g., BRCA1 methylation), leading to genomic instability detectable via scars (LOH, TAI, LST) and mutational signatures (e.g., COSMIC SBS3). Advanced detection integrates genomic assays (Myriad myChoice CDx, Caris HRD, FoundationOne CDx), functional assays (RAD51 foci), and epigenetic profiling, with tools like HRProfiler and GIScar achieving >90% sensitivity. HRD predicts robust responses to PARP inhibitors (PARPi) and platinum therapies, extending progression-free survival by 12–36 months in HGSOC. However, resistance mechanisms (BRCA reversion, SETD1A/EME1, SOX5) and assay variability (60–70% non-BRCA concordance) pose challenges. We propose a conceptual framework in ^{Section 10}, integrating multi-omics, methylation analysis, and biallelic reporting to enhance detection and therapeutic stratification. Regional variations (e.g., Asian cohorts) and disparities in access underscore the need for standardized, cost-effective diagnostics. Future priorities include validating novel biomarkers (SBS39, miR-622) and combination therapies (PARPi with ATR inhibitors) to overcome resistance and broaden HRD’s applicability across cancers. Full article

Sb-based anodes have great potential in lithium-ion batteries because of their relatively high theoretical capacities. However, in general, their volume changes (>150%) during charge and discharge process have a significant impact, which affects their electrochemical performances. In this paper, nano-alloy FeSb wrapped in three-dimensional honeycomb graphite carbon (FeSb@C) was prepared by the freeze-drying method using sodium chloride as a template. The three-dimensional carbon can buffer the volume change in the reaction process, increasing the contact area between the electrode and electrolyte. Furthermore, the addition of metallic iron also increases the overall specific capacity and improves its electrochemical performance. As the anode of a lithium-ion battery, the optimized FeSb@C shows excellent electrochemical performance with a specific capacity of 193.0 mAh g⁻¹ at a high current density of 5 A g⁻¹, and a reversible capacity of 607.8 mAh g⁻¹ after 600 cycles of 1 A g⁻¹. It provides an effective strategy for preparing high-performance lithium-ion batteries anode materials. Full article

Numerical simulations were performed using the RANS (Reynolds-averaged Navier–Stokes) approach to analyze the flow field around an aircraft during the landing rollout phase with thrust reversers deployed. The objective was to characterize the flow structure modifications induced by the reversed jet flow and to assess its impact on the aerodynamic performance of various control surfaces. The results demonstrate that the reverse jet flow introduces significant disturbances to the flow field, substantially altering the aerodynamic load distribution over the airframe and causing a marked reduction in overall lift. High-lift devices are particularly susceptible to these effects: the pressure distributions on both the leading-edge slats and trailing-edge flaps are severely disrupted, resulting in a notable degradation of their lift augmentation capabilities. The rudder retains a generally linear response characteristic, though a slight reduction in effectiveness is observed. In contrast, the elevator exhibits a pronounced asymmetry in control effectiveness, with significantly greater degradation under positive deflection compared to negative deflection. This study elucidates the complex interference mechanisms associated with thrust reverser-induced flows and provides valuable insights for the optimization of thrust reverser system design and the enhancement of flight control strategies during the landing phase. It further delivers the first quantitative evaluation of elevator response asymmetry and accompanying lift degradation caused by reverse jet plumes, supplying design-ready metrics for reverser integration. Full article

A two-level model-based control system for energy-optimal operation of a two-stage reverse osmosis (RO) membrane desalination system was developed and field demonstrated. The control scheme was based on the specific energy consumption (SEC) framework accounting for pump efficiencies, physical system constraints, and temporal variability of feed salinity. The SEC framework consisted of a higher-level (supervisory) control system that guided a lower-level controller for real-time SEC optimization. The supervisory controller combined real-time plant data and the SEC model to determine the energy-optimal first-stage water recovery and the overall permeate water recovery (unless specified), and membrane permeability for a target permeate production. The derived operating state was then applied to control the RO plant operation through the lower-level control system, consisting of three separate feedback loops regulating the RO feed flow rate, first-stage RO pressure, and the second-stage RO pressure via control of the first-stage and second-stage RO feed pumps, and the RO concentrate valve. The two-level control system was demonstrated for a mobile brackish water desalination plant capable of permeate productivity up to 98 m³/day. Field testing demonstrated robust simultaneous control of the dynamically coupled control variables and effective energy-optimal operation. Full article

The natural resistance-associated macrophage proteins (NRAMPs) gene family represents a group of membrane transporter proteins with wide distribution in plants. This family of membrane transporters plays a pivotal role in mediating plant responses to metal stress by coordinating ion transport processes and maintaining cellular metal homeostasis, thereby effectively mitigating the detrimental effects of metal ion stress on plant growth and development. This study conducted a comprehensive genome-wide analysis of the NRAMP gene family in A. tauschii using integrated bioinformatics approaches, as well as the expression pattern when exposed to heavy metal-induced stress. By means of phylogenetic investigation, eleven AetNRAMP proteins were categorized into five distinct subgroups. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis revealed that the majority of NRAMP genes exhibited marked differential expression patterns under specific stress treatments. Subsequently, yeast cells were employed to validate the functions of AetNRAMP1 and AetNRAMP3. It was confirmed that AetNRAMP1 functioned in copper transport, and AetNRAMP3 showed an increase in its expression level under manganese stress. These findings establish a molecular foundation for elucidating the functional specialization of NRAMP gene family members in A. tauschii’s heavy metal detoxification pathways, providing critical genetic evidence for their stress-responsive regulatory networks. Nevertheless, significant knowledge gaps persist regarding its functions in A. tauschii. Research on metal stress resistance in this wheat progenitor species may establish a theoretical foundation for enhancing wheat tolerance and developing improved cultivars. Full article

This review aims to advance quartz processing technology by examining the surface properties, flotation behavior, and selective flotation mechanisms of quartz mineral. Characterized by a strong negative charge over a wide pH range and an isoelectric point around pH 2, quartz surfaces allow physical adsorption of cationic collectors, particularly amines, which render the quartz surface hydrophobic and enhance bubble–particle interactions. In contrast, flotation with anionic collectors requires prior surface activation via multivalent metal cations such as Ca²⁺. The pH value of the medium plays a critical role in both collector adsorption and flotation selectivity. Both direct and reverse flotation strategies can be used, depending on whether quartz is targeted as a valuable mineral or a gangue mineral. In direct flotation, depressants like carboxymethyl cellulose and starch are used to depress gangue minerals, while in reverse flotation, quartz is depressed using chemicals such as fluoride ions and cationic polymers. To improve the efficiency and selectivity of quartz flotation, further research is needed on surface chemistry, collector adsorption mechanisms, and the transition from laboratory-scale experiments to industrial applications. Full article

With the rapid advancement of new energy electric vehicles, high-capacity nickel-rich layered oxides have emerged as predominant cathode materials in lithium-ion battery systems. However, their widespread implementation necessitates rigorous investigation into cycling stability. We synthesized nickel-manganese-aluminum hydroxide precursors as raw materials by co-precipitation method, and synthesized ultrathin Al₂O₃-coated LiNi_0.9Mn_0.05Al_0.05O₂ cathode materials by hydrolysis reaction. The cathode material was uniformly covered by an Al₂O₃ layer with an average thickness of 5–10 nm by high resolution transmission electron microscopy (HRTEM). Electrochemical performance tests showed that the modified cathode material exhibited significantly enhanced reversible capacity, cycling stability, and rate performance, and a more favorable differential capacity curve. In particular, the LNMA-2 samples were able to maintain 90.6% and 88.3% of their initial capacity after 100 cycle tests (with cutoff voltages of 4.3 and 4.5 V, respectively) at 0.5 C charge/discharge rate. These improved electrochemical properties are mainly attributed to the advantages offered by the unique Al₂O₃ coating structure. This study provides significant theoretical value for designing and optimizing the production of high-nickel cobalt-free cathode materials with high cycling performance. Full article

China has adopted extensive restoration practices to improve ecosystem function. The efficiency of these restoration efforts remains unclear, which may hinder the supply of ecosystem services (ESs). In this context, this study first employed InVEST models to clarify spatio-temporal changes in five key ESs. The static and dynamic efficiencies of ecosystem service production in 130 cities from 2015 to 2021 in the Yangtze River Economic Belt (YREB) were then measured using the Super-SBM-Malmquist model, with ESs considered as outputs. The results indicated that water conservation (WC), water purification (WP), and soil retention (SR) exhibited overall declining trends, decreasing by 28.32%, 3.22%, and 10.00%, respectively, while carbon storage (CS) and habitat quality (HQ) remained steady. More than 70% of studied cities exhibited static efficiency levels below 50%, which were attributed to inefficient utilization of labor, capital, and technology. Significant spatial heterogeneity was observed, with high-efficiency cities mainly located in mountainous areas and low-efficiency cities concentrated in flat regions. The downward trend in dynamic efficiency has been reversed from a 39.02% decline in 2015–2018 to a 38.31% increase in 2018–2021, despite being adversely affected by technological regression. Finally, several policy implications are proposed, including optimizing resource allocation, introducing advanced technology and setting the intercity cooperation and complementarity mechanisms. Full article

Preeclampsia (PE) is a leading cause of maternal and fetal morbidity that affects 2–8% of pregnancies worldwide, driven by placental dysfunction and systemic inflammation. Growth arrest-specific protein 6 (Gas6) and its receptor AXL play pivotal roles in PE pathogenesis, promoting trophoblast impairment and vascular dysregulation. This study investigated the transcriptomic reversal effects of AXL Receptor Tyrosine Kinase (AXL) inhibition in a Gas6-induced rat model of PE using RNA sequencing (RNA-seq). Pregnant rats were administered Gas6 to induce PE-like symptoms such as hypertension and proteinuria; a subset also received the AXL inhibitor R428. RNA-seq of placental tissues revealed 2331 differentially expressed genes (DEGs) in Gas6-AXLi versus Gas6 (1277 upregulated, 1054 downregulated). Protein–protein interaction networks and Gene Ontology enrichment highlighted upregulated mitochondrial functions, including electron transport chain components (e.g., NDUFC2, COX5A), suggesting enhanced energy metabolism. In the secondary analysis that compared Gas6 to Control, Gas6-upregulated extracellular matrix proteins (e.g., COL4A1, LAMC1) linked to fibrosis were reversed by AXL inhibition, indicating ameliorated placental remodeling. AXL inhibition activated compensatory pathways beyond Gas6 blockade, unveiling novel mechanisms for PE resolution. These findings position AXL inhibitors as promising therapeutics, offering insights into mitochondrial and fibrotic targets to mitigate this enigmatic disorder. Full article

The growing scarcity of freshwater worldwide has increased interest in forward osmosis (FO) membranes as a promising solution for water desalination and wastewater treatment. This study investigates the enhancement of thin-film composite (TFC) FO membranes via the incorporation of carboxyl-functionalized multiwalled carbon nanotubes (COOH-MWCNTs) into the polyethersulfone (PES) support layer. The membranes were fabricated using a combination of phase inversion and interfacial polymerization techniques, with COOH-MWCNTs incorporated into the membrane support layers at different concentrations (0–0.75 wt.%). Comprehensive characterization was carried out using various analytical methods and mechanical testing to evaluate the physicochemical and structural properties of the membranes. The modified membranes demonstrated improved hydrophilicity, enhanced mechanical and thermal stability, and improved surface charge properties. Performance tests using a 1 M NaCl draw solution showed that the optimized membrane (0.5 wt.% COOH-MWCNTs) attained a 161% enhancement in water flux (7.48 LMH) compared to the unmodified membrane (2.86 LMH), while also reducing internal concentration polarization (ICP). The antifouling properties were also significantly improved, with a flux recovery rate of 91.92%, attributed to enhanced electrostatic repulsion as well as surface and microstructural modifications. Despite a moderate rise in reverse solute flux, the specific reverse solute flux (J_s/J_w) remained within acceptable limits. These findings highlight the potential of COOH-MWCNT-modified membranes in enhancing FO desalination performance, offering a promising option for next-generation water purification technologies. Full article

Lithium/carbon fluoride (Li/CF_x) batteries are promising for specialized applications due to their high theoretical capacity (>865 mAh·g⁻¹) and energy density. However, their practical deployment is hindered by the intrinsically low conductivity of CF_x and sluggish reaction kinetics. While conventional conductive additives improve electron transport, their physical mixing with active materials yields weak interfacial contacts and fails to catalytically facilitate C–F bond cleavage. To address these dual limitations, this study proposes a dual-functional conductive-catalytic additive strategy. We engineered zinc-nickel/carbon nanotube (ZnNi/CNT) composites modified with transition metal dopants (Fe, W, Cu) to integrate conductive networks with nanoscale-dispersed catalytic sites. Fe-doped ZnNi/CNT (ZnFeNiC) emerged as the optimal system, delivering a discharge plateau of 2.45 V and a specific capacity of 810.3 mAh·g⁻¹ at 0.1 C. This performance is attributed to Fe-doping accelerates Li⁺ diffusion, and promotes reversible Ni redox transitions (Ni²⁺↔Ni⁰) that catalyze C–F bond dissociation. This work establishes a design paradigm for high-performance Li/CF_x batteries, bridging the gap between conductive enhancement and catalytic activation. Full article

Ecological security evaluation serves as the cornerstone for ecological management decision-making and spatial optimization. This study focuses on the Dongping Lake Basin. Based on the Pressure–State–Response (PSR) model framework, it integrates ecological risk, ecosystem health, and ecosystem service indicators. Utilizing methods including Local Indicators of Spatial Association (LISA), Transition Matrix, and GeoDetector, it analyzes the spatio-temporal evolution characteristics and driving mechanisms of watershed ecological security from 2000 to 2020. The findings reveal that the Watershed Ecological Security Index (WESI) exhibited a trend of “fluctuating upward followed by periodic decline”. In 2000, the status was “relatively unsafe”. It peaked in 2015 (index 0.332, moderately safe) and experienced a slight decline by 2020. Spatially, a significantly clustered pattern of “higher in the north and lower in the south, higher in the east and lower in the west” was observed. In 2020, “High-High” clusters of ecological security aligned closely with Shandong Province’s ecological conservation red line, concentrating in core protected areas such as the foothills of the Taihang Mountains and Dongping Lake Wetland. Level transitions were characterized by “predominant continuous improvement in low levels alongside localized reverse fluctuations in middle and high levels,” with the “relatively unsafe” and “moderately safe” levels experiencing the largest transfer areas. Geographical detector analysis indicates that the Human Interference Index (HI), Ecosystem Service Value (ESV), and Annual Afforestation Area (AAA) were key drivers of watershed ecological security change, influenced by dynamic interactive effects among multiple factors. This study advances watershed-scale ecological security assessment methodologies. The revealed spatio-temporal patterns and driving mechanisms provide valuable insights for protecting the ecological barrier in the lower Yellow River and informing ecological security strategies within the Dongping Lake Watershed. Full article

Obstructive sleep apnea (OSA), characterized by intermittent hypoxia (IH), is strongly associated with metabolic syndrome and metabolic dysfunction-associated steatotic liver disease (MASLD). IH exacerbates MASLD progression through oxidative stress, inflammation, and lipid accumulation. This study aims to investigate the impact of oxygen normalization on metabolic dysfunction in OSA patients using continuous positive airway pressure (CPAP) therapy, and in mice exposed to IH followed by a reoxygenation period. In the clinical study, 76 participants (44 OSA patients and 32 controls) were analyzed. OSA patients had higher insulin resistance, triglycerides, very low density lipoprotein (VLDL) content, and liver enzyme levels, along with a higher prevalence of liver steatosis. After 18 months of CPAP therapy, OSA patients showed significant improvements in insulin resistance, lipid profiles (total cholesterol and VLDL), liver function markers (AST and albumin), and steatosis risk scores (Fatty Liver Index and OWLiver test). In the experimental study, IH induced hepatic lipid accumulation, oxidative stress, and inflammation, and reoxygenation reversed these deleterious effects in mice. At the molecular level, IH downregulated fatty acid oxidation (FAO)-related genes, thus impairing the FAO process. Reoxygenation maintained elevated levels of lipogenic genes but restored FAO gene expression and activity, suggesting enhanced lipid clearance despite ongoing lipogenesis. Indeed, serum β hydroxybutyrate, a key marker of hepatic FAO in patients, was impaired in OSA patients but normalized after CPAP therapy, supporting improved FAO function. CPAP therapy improves lipid profiles, liver function, and MASLD progression in OSA patients. Experimental findings highlight the therapeutic potential of oxygen normalization in reversing IH-induced liver damage by FAO pathway restoration, indicating a metabolic reprogramming in the liver. Full article

Introduction: Extrinsic skin damage is often a result of oxidative stress caused by exposure to environmental factors such as ultraviolet (UV) radiation, ozone (O₃), and various pollutants. As a result, topical antioxidants have been evaluated for their effectiveness in mitigating or reversing skin damage caused by environmental factors. Topical antioxidants containing a combination of l-ascorbic acid, tocopherol, and ferulic acid have significantly improved markers of skin health after exposure to environment-induced skin damage. However, research suggests that l-ascorbic acid and tocopherol tend to be relatively unstable, possibly affecting their efficacy against outdoor stressor damage. It has been shown that ferulic acid significantly improves the stability of both l-ascorbic acid and tocopherol, but its long-term stabilization effects on these antioxidants are relatively unknown. Material and Methods: This study evaluated the time-dependent effectiveness of a topical antioxidant mix containing 15% l-ascorbic acid, 1% tocopherol, and 0.5% ferulic acid (AOX) on UV-induced skin damage. Skin biopsies (12 mm, n = 60) were placed in a 6-well plate with medium and incubated at 37 °C and 5% CO₂ overnight. The day after, skin samples were pretreated with 10 µL of differently aged AOX (0-, 6-, 12-, and 36-month-old) and then exposed to different doses of UV light (100, 200, 400 mJ/cm²) daily over four days. AOX formulations were stored in a cool, dry, and dark place at approximately 20–22 °C during the whole study. This study evaluated 4-hydroxynonenal (4-HNE) and 8-hydroxy-2′-deoxyguanosine (8-OHdG) as oxidative damage and skin DNA damage markers, Collagen1 and Filaggrin as skin structure, and IL-8 and Nrf2 as inflammatory and defensive response. Results: UV exposure significantly increased oxidative and inflammatory markers in human skin explants affecting also filaggrin and collagen levels. However, pre-treatment with the antioxidant formulation, particularly in its younger formulations (0-, 6-, and 12-month-old), significantly reduced the damaging effect of UV. Additionally, all antioxidant formulations effectively mitigated UV-induced damage across all doses. Conclusions: Our results indicate that pre-treatment with this formulation consistently reduces UV-induced oxidative damage and DNA damage in human skin explants, regardless of the formulation age and the discoloration state. Although effective, the protective capacity of aged formulations may be reduced only when extreme UV exposure is tested, a condition that is unlikely to occur under typical environmental conditions. These results support ferulic acid as a stabilization agent for topical antioxidant mixtures. Full article