Search Results (4,914)

Baicalin, a natural plant-derived compound, holds promise in addressing clinical bacterial resistance when combined with antibiotics. This study evaluated the antibacterial activity of the combination of baicalin and cefotaxime and explored its mechanism of action on the cell wall and biofilm of multidrug-resistant Pseudomonas aeruginosa (MRPA). The results showed that the combination of baicalin and cefotaxime exerted a synergistic inhibitory effect on the growth of MRPA, with a fractional inhibitory concentration index (FICI) of 0.28. Mechanistically, compared with cefotaxime alone, the combination of baicalin and cefotaxime enhanced the permeability of the cell membrane and cell wall of MRPA, thereby increasing cell damage. It also exhibited stronger antibiofilm activity by inhibiting numerous virulence factors (pyocyanin, elastase, lectin), reducing cellular metabolic activity, and downregulating the expression of biofilm genes (pslA, pelA, algD) and quorum-sensing genes (lasl, lasR, rhll, rhlR, pqsA, pqsR). The molecular docking results revealed that baicalin could stably bind to wbpE, LasR, and RhlR. Therefore, this interaction may indirectly influence the processes related to antibiotic resistance and biofilm formation in bacterial cells. Metabolomic analysis revealed that the combination of baicalin and cefotaxime upregulated 863 metabolites and downregulated 587 metabolites. These metabolites mainly included amino acids, lipids, nucleotides, carbohydrates, and secondary metabolites. The combination primarily enriched key pathways such as amino acid metabolism, lipid metabolism (sphingolipid metabolism) and secondary metabolite biosynthesis. Through these pathways, it triggers significant metabolic reprogramming, thereby interfering with the supply of cell wall synthesis precursors, membrane structural stability, and the generation of biomembrane matrix. Ultimately, it synergistically enhances the effects of cell wall damage and biomembrane inhibition. In conclusion, this study confirms that the combination of baicalin and cefotaxime exerts significant synergistic antibacterial activity against MRPA. It also reveals the mechanism of action of the combination on the cell wall and biofilm of MRPA at the metabolic level, providing theoretical support for the development of novel strategies to combat MRPA. Full article

The particle size of aggregate is a key factor affecting the mechanical properties and deformation capacity of cemented gangue filling body. In this study, coal gangue with a particle size range of (0.05, 20) mm was sieved into six groups of aggregate particles. Based on the Talbot gradation theory, cubic specimens with gradation indices n = 0.3, 0.4, 0.5, 0.6, and 0.7 were prepared for acoustic emission (AE) monitoring tests. The microstructure of the filling body was analyzed, and the failure characteristics and damage evolution laws of the cemented gangue filling body with different gradation indices were explored. The results show that the compressive strength reaches its maximum when n = 0.5. As the gradation index increases, the compressive strength of the specimens first increases and then decreases, and the specimens shift from primarily experiencing cleavage failure to shear failure. The curve of cumulative AE ringing count shows a bimodal distribution pattern, with both surge points and fracture points coexisting. The surge points can be regarded as precursor signals of backfill failure. The spatiotemporal evolution of AE events exhibits complex phased changes. An excessively small gradation index tends to form micropores and striped microcracks, reducing the compactness of the microstructure. An excessively large gradation index can lead to the formation of penetrative weak channels. A reasonable gradation index enables the mutual interlocking of aggregate particles, constructing a stable three-dimensional spatial skeleton structure. The dynamic trend of damage in the filling body can be captured based on AE analysis, and reverse guidance can be provided for parameter optimization of Talbot gradation, achieving a dynamic closed loop of “gradation design-AE monitoring-damage assessment-parameter optimization”. This not only enriches the application scenarios of acoustic emission analysis in graded materials, but also provides a new research approach and technical method for gradation design and safety assessment in scenarios where particle sizes are missing in practical engineering. Full article

Metal anodes offer substantially higher specific and volumetric capacities than conventional anode materials such as graphite in lithium-ion batteries or hard carbon in sodium-ion batteries. However, the integration of metal anodes into solid-state batteries poses significant challenges, particularly with respect to processing, interfacial stability, and cell assembly. Anode-free solid-state batteries (AFSSBs) address these challenges by eliminating the pre-installed metal anode, instead forming the metal in situ during the initial charging (formation) step. In anode-free solid-state batteries, the quality of the interfacial contact is particularly critical, as insufficient contact can lead to locally increased current densities. Consequently, the initial metal plating during the formation step plays a decisive role in determining the homogeneity and stability of the anode interface. Furthermore, conventional battery-grade copper foils (~10 µm) are considerably thicker than required for the targeted C-rates and are difficult to use as stand-alone anode-free current collectors, thereby hindering the industrial production of anode-free solid-state batteries. In this publication, we demonstrate the application of atmospheric plasma spraying (APS) to fabricate thin copper current collectors directly on the ceramic solid electrolytes LAGP (lithium aluminium germanium phosphate) and BASE (beta-alumina solid electrolyte) with superior interface contact. No mechanical damage or diffusion of copper into the solid electrolyte nor formation of secondary phases at the interfaces were observed in SEM or EDS despite the elevated process temperature. LAGP with a thickness as low as 300 µm was successfully coated and subsequently used for plating/stripping experiments. Finally, dense sodium metal was plated at the copper-substrate interface of a 1.4 mm thick BASE sample. Full article

Natural fracture development in tight-sand gas reservoirs is strongly controlled by tectonic evolution yet remains difficult to characterize using conventional seismic interpretation due to limited resolution. This study presents a damage-mechanics-based approach that integrates 2D seismic data, well logs, and drilling information to construct a 3D geological model and simulate tectonically induced fracture development under regional orogenic loading. The approach is applied to the Permian formation in the Ordos Basin. Modeled damage zones, interpreted as areas of enhanced natural fracture development, show strong spatial correspondence with high-productivity wells. The results demonstrate that damage mechanics provides an effective framework for linking tectonic processes with fracture distribution in tight-sand reservoirs and offers new insights into fracture-controlled gas accumulation and productivity. This case demonstrates the applicability and effectiveness of the technology of continuum damage mechanics for 3D natural fracture distribution based on sets of 2D seismic data plus drilling data. Although sets of 2D seismic data cannot replace real 3D seismic data for all its usage, it can produce numerical results of natural fractures with reasonable accuracy for calculation of natural fractures with damage mechanics method. Full article

The high prevalence of biofilm-associated multidrug-resistant (MDR) Escherichia coli infections in older adults calls for novel control strategies. This study compared fecal E. coli carriage, antimicrobial resistance, and biofilm formation among community-dwelling older adults with different self-reported immune statuses (lower vs. normal), and evaluated the antibiofilm activity of five Lactobacillus cell-free supernatants (CFSs). Fecal samples from 20 older adults were analyzed. E. coli was enumerated, and isolates were characterized for antimicrobial susceptibility and biofilm formation. Five Lactobacillus strains were screened for antibiofilm activity using crystal violet assay, with further evaluation of extracellular polymeric substance (EPS) production and biofilm morphology. After removing the redundant isolates, 70 isolates were reported, with significantly higher counts in the lower-immunity group (7.89 vs. 6.04 log MPN/g). The lower-immunity group had significantly higher antimicrobial resistance (97.3% vs. 60.6%), and higher MDR prevalence (91.7% vs. 24.2%). Biofilm formation was observed in 62.9% of isolates, with significantly higher prevalence among MDR isolates and in the lower-immunity group. L. paracasei L475 CFS showed the strongest antibiofilm activity against a representative MDR isolate (L5-1), with inhibition and eradication rates of 82.9% and 75.0%, respectively. Mechanistically, L475 CFS reduced extracellular polymeric substance components, with a 92.3% reduction in proteins and 41.3% in polysaccharides. Microscopy confirmed disrupted biofilm architecture, membrane damage, and cell lysis. In conclusion, these preliminary findings indicate a potential association between self-reported immune function and E. coli resistance/biofilm formation in older adults. L. paracasei L475 CFS demonstrates promising in vitro antibiofilm activity against an MDR E. coli isolate from this population, supporting its potential as a postbiotic candidate. Full article

Alcohol-associated Hepatitis (AH) is a rare acute injury caused by alcohol consumption, which can lead to one of the most severe manifestations of liver disease. It is part of the alcohol-related liver diseases (ArLD) spectrum, which represents a major global health burden, with oxidative stress and inflammation serving as central, interconnected pathogenic mechanisms. Chronic alcohol (ethanol) consumption induces hepatic reactive oxygen species (ROS) generation through multiple pathways, including cytochrome P450 2E1 (CYP2E1) induction, mitochondrial dysfunction, and NADPH oxidase activation. These oxidative insults trigger a cascade of cellular damage encompassing lipid peroxidation, protein adduct formation, DNA damage, and endoplasmic reticulum stress, ultimately leading to hepatocyte dysfunction and multiple forms of cell death, including apoptosis, necroptosis, pyroptosis, and ferroptosis. The inflammatory response, orchestrated primarily by Kupffer cells and infiltrating neutrophils through Toll-like receptor (TLR) signalling and inflammasome activation, not only amplifies hepatic injury but also promotes fibrogenesis through hepatic stellate cell activation. Neutrophils, characterised by elevated lipocalin-2 expression and spontaneous NETosis in AH, exhibit a paradoxical role by driving both tissue damage and repair. Current therapeutic strategies include corticosteroids, which remain the first-line treatment for severe AH, while emerging therapies targeting the gut–liver axis, hepatic regeneration, and specific molecular targets show promise in clinical trials. This review comprehensively examines the molecular crosstalk between oxidative stress and inflammation in the pathogenesis of AH to highlight current and investigational therapeutic approaches targeting these interconnected pathways. Full article

(1): Endotoxins are components of Gram-negative bacteria. Uptake can induce allergies, nausea, or sepsis. These responses are triggered by an activation of the immune system. Endothelial cells, lining blood vessels, are the first to be exposed to circulating LPA. Activation can dramatically affect the blood system, such as the formation of thrombi. This study aimed to clarify whether the activation of primary human venous endothelial cells (HUVECs) by LPA could be reduced by the addition of an Arthrospira platensis (AP) extract. (2): HUVECs were cultured for 24 h in cell culture medium supplemented with different concentrations of AP (50, 100, 200 µg/mL). Then 2.5 µg/mL of LPA was added. Cell morphology, viability, cell proliferation, cell membrane integrity, cell metabolism, and cell function were examined after two and four days. (3): Treatment with LPA alone negatively affected HUVEC growth, viability, cell membrane integrity, and metabolic activity. Adding AP to the culture medium had a positive influence on these effects, with 100 µg/mL proving to be the most effective dose. (4): The results clearly revealed that an extract of AP has the potential to reduce the damage to the venous endothelium when exposed to lipopolysaccharides, in particular at a concentration of 100 µg/mL. Full article

Endovascular therapies have transformed cardiovascular medicine, yet restenosis, thrombosis, and device failure remain common and poorly predictable complications. Increasing evidence suggests that immunothrombotic processes critically shape vascular recovery after device implantation. This includes neutrophil extracellular trap (NET) formation, innate immune polarization, and endothelial damage responses. Concurrently, advances in artificial intelligence (AI) are increasingly enabling continuous multimodal monitoring and adaptive clinical decision-making throughout the medical device life cycle. Here, we propose the concept of immunologically adaptive endovascular devices: a closed-loop paradigm in which patient immune status informs device selection, device–tissue interactions are interpreted via mechanistic biomarkers, and real-world monitoring dynamically updates risk and management. The study introduces (i) an immune–device interaction phenotype taxonomy linking device design features to measurable thrombo-inflammatory trajectories, (ii) a mechanistic framework defining interface signaling processes that enhance or resolve NET-driven responses, (iii) a minimum evidence model encompassing preclinical testing, clinical validation, and post-market surveillance, and (iv) a reference AI architecture for risk prediction, drift detection, and safety monitoring. This study also outlined testable predictions and a translational roadmap toward precision endovascular intervention and next-generation adaptive cardiovascular devices. Full article

Purpose: Cannabidiol (CBD) is a primary bioactive, non-intoxicating cannabinoid found in the cannabis plant. Studies have shown that CBD causes anticancer activity by inhibiting the expression of growth factors and inducing apoptosis, leading to cell cycle arrest. In this study, we aimed to determine how CBD influences the expression of genes that affect cancer pathways in doxorubicin-sensitive (MCF-7) and doxorubicin-resistant (MCF-7/Adr) breast cancer cells. Materials and Methods: IC₅₀ concentrations of CBD in MCF-7 and MCF-7/Adr cell lines were determined by the MTT cell cytotoxicity assay. RNA isolation and subsequent cDNA synthesis were performed for qPCR experiments with the determined IC₅₀ values. The effects of CBD on the cell cycle and apoptosis were studied using flow cytometry. IC₅₀ values of CBD were determined in MCF-7 and MCF-7/Adr breast cancer cell lines at eight different concentrations and at three different incubation periods (24 h, 48 h, and 72 h) with different doses. RT-qPCR was used to investigate the molecular mechanisms underlying the expression of genes involved in cancer pathway analysis. Results: Treatment with CBD at concentrations of 17.57 μM (MCF-7) and 11.41 μM (MCF-7/Adr) for 48 h decreased colony formation, induced apoptosis, and inhibited cell invasion in both cell lines. In addition, we observed significant alterations of angiogenesis, apoptosis, cell cycle, cellular senescence, DNA damage and repair, epithelial-to-mesenchymal transition, hypoxia, metabolism, telomeres, and telomerase in both cell lines. Conclusions: Our research indicates that CBD could be an effective natural bioactive compound for breast cancer treatment, inhibiting tumor cell proliferation and inducing apoptosis. Full article

Background/Objectives: Diabetic wound healing faces significant challenges due to the harsh microenvironment of wounds such as high blood glucose levels, excessive inflammation, persistent infection, upregulated reactive oxygen species (ROS), and damaged new blood vessels. Therefore, developing hydrogel dressings with microenvironmental regulation functions has become an important strategy in treating diabetic wounds. Methods: In this study, an ultraviolet in situ crosslinked hydrogel (D@H/E) was developed using methacrylic anhydride modified hyaluronic acid (HA-MA) and glycidyl methacrylate modified ε-polylysine (EPL-GMA), loaded with the iron chelating agent desferrioxamine (DFO). The physicochemical and biochemical properties of the hydrogel were comprehensively characterized, and its efficacy as a dressing for diabetic wounds was evaluated in a STZ-induced hyperglycemic mouse model. Results: This hydrogel demonstrated remarkable multidimensional effects by alleviating oxidative stress damage, inhibiting bacterial infection, regulating inflammatory responses, mitigating ferroptosis, and promoting cell migration and tubule formation. Specifically, the DFO-loaded hydrogel achieved a high DPPH radical scavenging efficiency of 80.8% and exhibited excellent antibacterial activity, with over 99.8% inhibition against both S. aureus and E. coli. In streptozotocin (STZ)-induced diabetic mice, the hydrogel accelerated wound closure to near completion by day 14. Mechanistically, it significantly upregulated CD206 expression to promote M2 macrophage polarization, upregulated the expression of angiogenesis-related factors to promote angiogenesis at the wound site, and enhanced GPX4 expression to alleviate ferroptosis. Conclusions: By orchestrating multi-dimensional synergy that combines ROS scavenging, infection control, immune regulation, and anti-ferroptosis, this D@H/E hydrogel system effectively remodels the harsh diabetic wound microenvironment, offering a promising platform for chronic wound management. Full article

This study aims to evaluate the therapeutic efficacy of emodin (EMO) in rheumatoid arthritis (RA) and to verify whether its underlying mechanism involves the blockade of pathological angiogenesis via the inhibition of the nuclear factor-kappa B (NF-κB)/hypoxia-inducible factor-1α (HIF-1α)/vascular endothelial growth factor (VEGF) signaling axis. Bovine type II collagen-induced arthritis (CIA) mouse models and lipopolysaccharide (LPS)-stimulated EA.hy926 endothelial cells were utilized in this study. The effects of EMO on joint pathological alterations, the expression of NF-κB/HIF-1α/VEGF axis proteins, inflammatory cytokines (tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1 beta (IL-1β)), and angiogenic capacity were assessed using histopathological analysis, Western blotting, immunohistochemistry (IHC), immunofluorescence, and tube formation assays. Furthermore, small interfering RNA (siRNA) interference targeting key molecules was employed to validate the molecular mechanisms underlying the therapeutic effects of EMO. In the CIA model group, the ankle joints of mice exhibited pronounced inflammatory infiltration, synovial hyperplasia, and bone destruction. Compared with the model group, both the EMO and methotrexate (MTX) treatment groups demonstrated attenuated synovial hyperplasia and cartilage destruction, along with significantly downregulated expression levels of key NF-κB pathway proteins, HIF-1α, and VEGF in joint tissues (p < 0.001). In vitro experiments revealed that EMO treatment significantly reduced the LPS-induced secretion of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β) (p < 0.001), and decreased both the number and total length of tubular structures formed by endothelial cells compared to the control (p < 0.001). Notably, siRNA-mediated knockdown of p65 resulted in decreased intracellular protein levels of HIF-1α and VEGF, accompanied by a significant reduction in tube formation (p < 0.001). This study demonstrates that EMO alleviates pathological damage in RA by inhibiting the activation of the NF-κB signaling pathway, which subsequently downregulates pathological angiogenesis and inflammatory responses mediated by the HIF-1α/VEGF axis. These findings provide a robust experimental basis for the potential application of EMO as a therapeutic agent for RA. Full article

The cement plug-casing interface is critical for long-term wellbore integrity in well abandonment to prevent fluid channeling. However, traditional cement easily debonds under long-term in situ stress and fluid exposure, causing seal failure and safety risks. To address this issue and overcome the limitations of conventional cement, a three-dimensional finite element model was established based on stress-seepage coupling theory. A systematic comparative analysis of the interface debonding mechanisms for three materials—cement, resin, and alloy—and their different combination sequences was conducted. The entire process of interface damage was quantified. The effects of material combination, formation elastic modulus, and injection rate on sealing performance were analyzed. Results show that the stiffness gradient dominates the failure mode, and the “cement–resin–alloy” configuration best suppresses damage propagation, reducing failure height by about 30%. Additionally, interface integrity is sensitive to formation constraints and operational parameters: the interface failure height decreases as the formation elastic modulus increases, and increases as the injection rate rises. The findings of this study can provide a theoretical basis and engineering reference for the optimal design of composite plugging barriers in demanding operational conditions, such as those encountered in carbon sequestration wells. Full article

The dense passivation film (DPF) formed on the surface of martensitic stainless steel effectively improves corrosion resistance, but it also hinders the adsorption and diffusion of active nitrogen atoms during gas nitriding. In this work, the influence of the DPF of 1Cr11Ni2W2MoV stainless steel on gas nitriding was overcome by controlling the cooling rate during stainless steel solution treatment, thereby enabling the successful formation of a nitrided layer. The effects of nitrogen potential on the microstructure, phase constitution, and tribological performance of the nitrided layer were systematically investigated. A dense passivation film formed at a solid-solution cooling rate of 110 ± 5 °C/s effectively inhibited nitrogen diffusion, resulting in the absence of a nitrided layer. However, when the cooling rate during solid solution was reduced to 80 ± 5 °C/s, the precipitation of chromium carbide along the grain boundaries damaged the density and integrity of the DPF, thereby enabling the formation of a nitrided layer during gas nitriding. A high nitrogen potential enhanced nitrogen diffusion and increased the nitrided layer thickness. However, an excessively high nitrogen potential led to nitrogen enrichment along grain boundaries, resulting in microcracking and reduced mechanical integrity of the compound layer. When the nitrogen potential was 1.0, a uniform and crack-free nitrided layer with a surface hardness exceeding 1000 HV_0.1 was obtained. Tribological tests combined with SEM observations of the worn surfaces showed that gas nitriding significantly reduced the friction coefficient and wear rate compared with the matrix sample. Among the nitrided samples, H-10 exhibited the lowest friction coefficient and wear rate, whereas H-23 showed relatively inferior wear resistance due to microcrack-related brittleness. The dominant wear mechanism changed from severe abrasive–adhesive wear in the matrix sample to mild abrasive wear in the nitrided samples. These results indicate that regulating passivation film integrity through heat treatment, together with optimizing nitrogen potential, is an effective strategy for achieving high-quality gas nitriding and improved tribological performance in martensitic stainless steel. Full article

Background/Objectives: The medial meniscus is crucial for load transmission and knee stability. Meniscal tears disrupt joint biomechanics, increasing the risk of cartilage degeneration. However, few studies have quantitatively compared how different tear types affect stress and contact mechanics using finite element analysis (FEA). This study aims to analyze stress distributions for various meniscal tear types and develop a predictive model for meniscal stress behavior. This study investigates how stress distributions differ between healthy and torn medial menisci under identical loading conditions. The study examines which meniscal tear type produces the highest stress concentrations. The effects of different tear types on penetration, gap formation, pressure distribution, and sliding distance at the meniscus interface are also analysed. Materials and Methods: The FEA model of the knee joint, including femoral and tibial cartilage and the medial meniscus, was developed. Simulations were conducted for a healthy meniscus and for menisci with radial, horizontal and complex tears. Stress, penetration, gap, pressure, and sliding distance were calculated, and a mathematical model describing their relationships was established. Results: All torn menisci exhibited significantly higher stresses than the healthy meniscus (p < 0.001). Radial tears generated the highest stress concentrations (p < 0.001). Pressure was mainly influenced by meniscal geometry, while the gap remained nearly constant. Penetration increased slightly (p < 0.05). The predictive model demonstrated a strong correlation between meniscal stress and interface parameters (R² > 0.9). In a healthy meniscus, stress distribution is homogeneous (≈26 MPa). Stress concentration increases depending on the tear type: limited in a horizontal tear (≈26.5 MPa), significant in a vertical tear (≈30.8 MPa), and highest in a radial tear (≈40.6 MPa). These results indicate that as the tear progresses, the load-bearing capacity of the meniscus decreases, and stresses concentrate at the tear edges. Conclusions: Meniscal tears, especially radial ones, substantially alter knee biomechanics and elevate tissue stress. These biomechanical insights highlight the importance of early diagnosis and targeted rehabilitation strategies to prevent further cartilage damage and osteoarthritis progression. Full article

Glycation of superoxide dismutase 1 (SOD1) has been shown to modulate the cytosolic levels of phosphorylated TAR DNA-binding protein 43 (TDP-43), a hallmark of amyotrophic lateral sclerosis (ALS) pathology. In this study, we investigated the interaction between TDP-43 and SOD1 and assessed how methylglyoxal (MGO)-induced glycation and the ALS-associated G93A SOD1 mutation affect this interplay in H4 cells. MGO exposure reduced SOD1 activity and TDP-43 phosphorylation in cells expressing WT SOD1, but not in those expressing G93A SOD1. Both WT and mutant SOD1 interacted with TDP-43 in the nucleus and cytosol; however, cytosolic interactions were more prevalent in G93A-expressing cells. Although MGO did not significantly alter the overall interaction between TDP-43 and WT SOD1, it induced cytosolic inclusion formation at 0.4 mM, a concentration associated with reduced cell viability. These inclusions did not colocalize with stress granules, indicating alternative aggregation pathways. Treatment with cyclosporin A, which inhibits the phosphatase calcineurin, decreased both TDP-43–WT SOD1 inclusions and cytosolic interactions between TDP-43 and G93A SOD1. Together, these findings suggest that SOD1 damage, induced by glycation or ALS-linked mutation, may affect TDP-43 phosphorylation status and promote its cytosolic mislocalization and aggregation, providing new insights into ALS-associated proteinopathy. Full article