Search Results (718)

Drug resistance remains a significant challenge in the clinical treatment of acute myeloid leukemia (AML). Therefore, there is an urgent need to develop a novel combinatorial therapy strategy, aiming to overcome drug resistance and improve therapeutic outcomes in AML. Herein, we developed a covalent organic framework bispecific nanosystem, namely glucose oxidase-loaded iron porphyrin covalent organic framework coated with bone marrow stromal cell membrane and functionalized with anti-CD3 and anti-PD-L1 antibodies (abbreviated FeC-G@M-C&P). The fabricated FeC-G@M-C&P displayed good cascade catalytic activity. The bone marrow stromal cell membrane endowed the nanosystem with robust targeting ability, which further triggered abundant reactive oxygen species (ROS) production for chemodynamic therapy. Moreover, bone marrow stromal cell membrane component suppressed the migration and adhesion of C1498 cells by interfering with the CXCR4/CXCL12 axis. Meanwhile, anti-CD3 and anti-PD-L1 antibodies improved T cell activation, relieved immune suppression, and jointly enhanced T cell-mediated immune responses against leukemia cells. Experimental results indicated that the FeC-G@M-C&P plus T cells group showed better anti-leukemia effects compared with other groups, which can be attributed to the integration of chemodynamic therapy, CXCR4/CXCL12 axis blockade therapy and immunotherapy. Collectively, the fabricated nanosystem provided a promising approach for the combined treatment of AML. Full article

Photodynamic therapy (PDT) represents a highly promising modality for cancer treatment; however, its clinical success is significantly restricted by the hypoxic nature of the tumor microenvironment (TME). Hypoxia also upregulates hypoxia-inducible factor-1α (HIF-1α) expression, thereby exacerbating tumor malignancy. To tackle this challenge, we engineered a hypoxia-activatable supramolecular nanoplatform (GH@CyNPs) capable of dual hypoxia reversal and amplification of PDT efficacy. The nanoplatform was constructed via host–guest interactions between a water-soluble pillar[5]arene (WP5) and an azobenzene-linked cyanine/YC-1 conjugate (Cy-G), followed by the co-encapsulation of glucose oxidase (GOx) and catalase (CAT). Upon entering the cancer cells via endocytosis, the azobenzene linker is specifically cleaved by the hypoxic TME, facilitating payload release. Concurrently, the released GOx/CAT pair drives in situ cascade reactions to generate oxygen (O₂), while YC-1 effectively suppresses HIF-1α expression, thereby achieving synergistic alleviation of hypoxia. Under irradiation, the released cyanine acts as a potent photosensitizer, generating abundant reactive oxygen species (ROS) to kill cancer cells. Both in vitro and in vivo evaluations corroborated that GH@CyNPs exhibit preferential tumor accumulation, profound antitumor efficacy, and excellent biocompatibility. This study presents an innovative paradigm for overcoming TME hypoxia to optimize photodynamic oncotherapy. Full article

Mycotoxin contamination in feed poses a major threat to animal health and productivity, particularly in pigeons. This study evaluated the protective effects of three mycotoxin biodegradation agents (MBAs) in pigeons subchronically co-exposed to a mycotoxin-contaminated (MYC) diet for 60 days. The MYC diet was prepared by mixing 3% naturally mold-contaminated corn with 97% basal diet, yielding final dietary concentrations of fumonisin B1 (7829.41 µg/kg), aflatoxin B1 (201.16 µg/kg), zearalenone (1675.46 µg/kg), T-2 toxin (7721.41 µg/kg), and deoxynivalenol (1211.77 µg/kg). Birds were allocated to five groups (n = 18/group): CON (basal diet); MYC (MYC diet alone); and TRT1–TRT3 fed the MYC diet supplemented with 1.5 g/kg of MBA I (Bacillus subtilis + Bacillus licheniformis + Devosia sp.), MBA II (Bacillus licheniformis + Saccharomyces cerevisiae), or MBA III (Bacillus subtilis + glucose oxidase), respectively. Subchronic co-exposure to the MYC diet significantly increased serum pro-inflammatory cytokines (TNF-α, IL-1β, IL-6), whereas all three MBAs effectively attenuated these elevations. Histopathological examination revealed inflammatory infiltration and tissue damage in the jejunum and liver of MYC birds, which were markedly alleviated by MBA supplementation. Gut microbiota analysis showed that mycotoxins decreased Firmicutes and Lactobacillus and increased Proteobacteria and Streptococcus, whereas MBAs partially restored microbial balance. Among the three MBAs, MBA II exhibited the strongest protective effect, as reflected by the greatest improvements in serum biochemistry, intestinal morphology, and microbial composition. Liver transcriptome analysis showed that mycotoxin mainly affected pathways related to cell cycle and DNA replication, whereas MBA II enhanced pathways associated with intestinal immune function and antigen processing and presentation. Collectively, these findings suggest that MBA II offers effective protection against combined mycotoxin-induced toxicity in pigeons and may serve as a promising feed additive for mitigating mycotoxin contamination in poultry production. Full article

Fe₃O₄ magnetic nanoparticles, as typical magnetic nanomaterials, can be functionalized and self-assembled into one-dimensional and two-dimensional structures to obtain new physicochemical properties. However, there are few studies on preparing stable large-sized one-dimensional Fe₃O₄ magnetic nanochains structure by a simple self-assembly method, and its application scope needs to be expanded urgently. In this paper, a large-size Fe₃O₄@SiO₂ one-dimensional nanochains were synthesized and modified by means of different functionalization. On this basis, the application of one-dimensional nanochains in the flow injection chemiluminescence analysis was explored. Glucose oxidase was immobilized on the Fe₃O₄@SiO₂ nanochains, which as a packed stationary phase, was successfully coupled with the flow injection system through the optimization of experimental conditions. As a result, a novel flow injection chemiluminescence analysis of glucose was developed. It has been proven that the one-dimensional nanochains-based packed stationary phase not only retains similar catalytic sites as the free magnetic particles, but also effectively overcomes the problem of poor fluidity of the free fixed phase. Therefore, it is expected to explore more high-performance flow injection analysis systems by strategies of the nanochain-immobilized enzyme-based packed stationary phase. Full article

High-glucose exposure impairs intestinal metabolic homeostasis and barrier integrity in fish, but the transcriptional responses associated with high-glucose adaptation in fish intestinal epithelial cells remain incompletely understood. This study investigated whether exogenous 5-methylcytosine (5MC) alleviates high-glucose-induced metabolic and epithelial stress in grass carp (Ctenopharyngodon Idella) intestinal epithelial cells and whether these responses are associated with changes in DNA methyltransferase 3 beta (dnmt3b) expression and Caudal type homeobox 1b (cdx1b)/Sodium-glucose cotransporter 1 (sglt1)-related transcriptional responses. As exploratory in silico information, molecular docking predicted candidate complex conformations of DNMT3B with CDX1B and SGLT1, with binding energies of −37.2 and −25.9 kcal/mol, respectively. Functionally, dnmt3b knockdown significantly reduced dnmt3b, Interleukin 6 (il6), and Nuclear factor kappa B (nfκb) expression, while increasing cdx1b, sglt1, Solute carrier family 2 member 3a (slc2a3a), 6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase 4a (pfkfb4a), and Amine oxidase copper containing 1 (aoc1) expression (p < 0.05). CDX2/CDX1B-like immunoreactive protein and SGLT1 protein levels were also increased after dnmt3b knockdown (p < 0.05). Under high-glucose stress, exogenous 5MC exerted concentration-dependent effects. Specifically, 6 mM 5MC significantly reduced residual extracellular glucose, lactate dehydrogenase and diamine oxidase activities, and malondialdehyde content, while increasing glutathione content, cell viability, and cell migration (p < 0.05). These effects remained detectable after replacement with high-glucose medium for an additional 12 h. By contrast, 24 mM 5MC markedly increased lactate dehydrogenase activity and reduced cell viability, suggesting potential cytotoxicity (p < 0.05). S-adenosylmethionine (SAM) levels were significantly lower in the NC and 6 mM groups than in the HG, 12 mM, and 24 mM groups, suggesting changes in SAM-related one-carbon metabolic status rather than direct evidence of altered DNA methylation (p < 0.05). Exogenous 5MC, particularly at 6 mM, alleviated high-glucose-induced metabolic and epithelial stress in grass carp intestinal epithelial cells. These effects were accompanied by changes in several glucose metabolism- and inflammation-related genes. However, the cellular uptake, metabolic fate, DNA incorporation, methylation consequences, and causal roles of these gene-expression changes remain to be further verified. Full article

Age-related hyperphosphatemia is increasingly recognized as a contributing factor in sarcopenia. This work studies the metabolic effects of elevated phosphate on muscle. C2C12 cells were differentiated in the absence or presence of 10 mM β-glycerophosphate (BGP), an exogenous phosphate donor. In addition, quadriceps muscles from four experimental groups of male C57BL/6J mice were analyzed: young (5 months) and old (24 months) fed with standard diet; old mice fed with hypophosphatemic diet or supplemented with the phosphate binder Velphoro^®, for the last three months of life. Mice were stratified according to sarcopenia degree based on muscle mass, strength and physical performance. Protein levels were determined by immunoblotting and mRNA expression by RT-qPCR. ATP levels were measured by luminescence and L-lactate production, citrate synthase and cytochrome c oxidase activities by colorimetric assays. Mitochondrial content, membrane potential and reactive oxygen species (ROS) were determined by fluorescence assay. BGP-treated cells showed increased glucose transporter 1 (GLUT1) and decreased NADH Dehydrogenase (CI-NDUFB8) protein expression, elevated hexokinase II (HK2), phosphoglycerate kinase 1 (PGK1) and lactate dehydrogenase A (LDHA) mRNA levels, reduced ATP levels, increased lactate production, and decreased mitochondrial enzyme activities. Moreover, BGP increased ROS, diminished mitochondrial membrane potential, and altered fusion–fission dynamics and mitophagy. In aged quadriceps, oxidative phosphorylation (OXPHOS) subunits and superoxide dismutase 2 (SOD2) expression were reduced. The hypophosphatemic diet improved all parameters, whereas Velphoro^® selectively increased Mitochondrial cytochrome C oxidase subunit 1 (CIV-MTCO1) expression. Several altered mitochondrial markers are associated with sarcopenia degree. Altogether, hyperphosphatemia induces metabolic changes that scale with the sarcopenic degree. Our findings show a relevant association between hyperphosphatemia and mitochondrial dysfunction, and they support the potential benefit of phosphate reduction as a strategy to prevent or mitigate sarcopenia. Full article

Metal oxide nanomaterials tailored at the nanoscale are opening new avenues for advanced electroanalytical sensing devices with enhanced properties, including improved electrocatalytic activity. In this work, a novel Mn₂Mo₃O₈/MnO-MWCNT nanocomposite was employed to modify a screen-printed carbon electrode, enabling the fabrication of an amperometric sensor for H₂O₂ operating at relatively low applied potential due to the catalytic activity of the nanocomposite. Further functionalization of this nanostructured surface with glucose oxidase allowed the construction of an electrochemical glucose biosensor, where the Mn₂Mo₃O₈/MnO-MWCNT material acted as an efficient electrocatalyst for hydrogen peroxide detection. The H₂O₂ sensor exhibited a linear response from 0.06 mM to 3.00 mM, with a sensitivity of (2.22 ± 0.02) µA mM⁻¹ and a detection limit of 22 µM. The glucose biosensor showed a linear response in the range from 0.10 mM to 18.9 mM glucose, with a sensitivity of (0.345 ± 0.005) µA mM⁻¹, and a detection limit of 29 µM. The biosensor displayed excellent selectivity and high stability and was successfully applied to the determination of glucose in lactose-free skimmed milk. Full article

Seasonal fluctuations in open solid-state fermentation drive batch-to-batch variability in Chinese Baijiu Daqu; however, how environmental shifts reshape microbial functional expression and non-volatile flavour precursors in medium-high-temperature Daqu remains poorly resolved. In this study, data-independent acquisition (DIA)-based quantitative metaproteomics and untargeted liquid chromatography–mass spectrometry (LC-MS) metabolomics were integrated to characterise winter and summer Daqu from Luzhou, Sichuan. Among 2904 annotated non-volatile metabolites, orthogonal partial least squares discriminant analysis (OPLS-DA) revealed clear seasonal separation; 1472 differential metabolites (560 up- and 912 downregulated in winter vs. summer; variable importance in projection [VIP] > 1, p < 0.05) were enriched in glycolysis/gluconeogenesis, the tricarboxylic acid (TCA) cycle, amino acid biosynthesis, and starch/sucrose metabolism. DIA-based quantitative metaproteomics further resolved season-specific enzyme expression: summer Daqu exhibited elevated saccharolytic, glycolytic and amino-acid-converting enzymes (β-glucosidase, 6-phosphofructokinase, pyruvate dehydrogenase), whereas winter Daqu was enriched in glucose oxidase, phosphoenolpyruvate carboxykinase and aldehyde dehydrogenase, consistent with a pattern suggestive of carbon-storage prioritisation. Proteome–metabolome integration established a coherent “enzyme protein abundance–inferred metabolic tendency–metabolite accumulation” correlative framework axis: higher hydrolytic and central-carbon enzyme abundance in summer corresponded to increased maltose, lactate, acetate, L-glutamate and L-aspartate. Therefore, production season reshapes Daqu quality chiefly by corresponding to distinct patterns of in situ enzyme protein abundance, providing a DIA quantitative metaproteome-anchored mechanistic framework for screening high-expression starters and stabilising seasonal Daqu quality. Full article

Agaricus bisporus (A. bisporus) is susceptible to rapid postharvest deterioration. Although elevated CO₂ (6%) delays senescence, the metabolic mechanisms remain unclear. In this study, untargeted and targeted metabolomic analyses were employed to explore these pathways in A. bisporus. The results revealed that elevated CO₂ treatment promoted glycolysis by upregulating Hexokinase (HK), Phosphofructokinase (PFK), and Pyruvate Kinase (PK), accumulating Glucose-6-phosphate (G-6-P) and Fructose-6-phosphate (F-6-P). Concurrently, elevated CO₂ treatment upregulated the expression of genes associated with the tricarboxylic acid (TCA) cycle and increased the enzymatic activities of Malate Dehydrogenase (MDH) and Fumarate hydratase (FUM). These changes led to the rapid consumption of key intermediate metabolites (Fumarate (Fum), Malate (Mal), and α-Ketoglutarate (α-KG)), collectively enhancing the efficiency of the TCA cycle. Furthermore, elevated CO₂ treatment significantly suppressed the activities of Glutamine Synthetase (GS) and Xanthine Oxidase (XOD), inhibiting the synthesis of Glutamine (Gln) and Pyroglutamate (pGlu) while promoting the accumulation of Hypoxanthine (Hx). This coordinated reprogramming of amino acid metabolism and purine metabolism contributed to improved energy efficiency and enhanced cellular integrity in postharvest A. bisporus. This study elucidates the specific mechanism by which elevated CO₂ levels regulate the postharvest energy metabolism of A. bisporus from a metabolomics perspective, providing a theoretical basis for developing strategies to control its postharvest quality. Full article

Niacin contents vary significantly among fresh-cut potato cultivars with different browning sensitivities, whereas its role as a browning inhibitor for fresh-cut produce has not been previously reported. In this study, potato slices were soaked in distilled water (control) or 1% food-grade niacin solution for 5 min, then stored at 4 ± 1 °C for 8 days with sampling every 2 days for physiological and molecular analyses. In particular, the optimal niacin (1%) treatment showed higher brightness and lower color change than the control. The activities of polyphenol oxidase (PPO), peroxidase (POD), and phenylalanine ammonia lyase (PAL), and phenol content were reduced. Higher activities of superoxide dismutase (SOD) and catalase (CAT), and greater glutathione accumulation, were observed following niacin treatment. Meanwhile, lower levels of malondialdehyde and reactive oxygen species (ROS), and lower nicotinamide adenine dinucleotide phosphate oxidase (NOX) activity, indicated lower oxidant damage. The contents of NADP and NAD, and activities of nicotinamide adenine dinucleotide kinase (NADK) and glucose-6-phosphate dehydrogenase (G6PDH) were improved. Furthermore, the gene expression patterns of StRBOH, StPPO, and StG6PDH also supported the hypothesis that niacin regulates pyridine nucleotide and ROS homeostasis. Full article

Reagentless glucose biosensors with redox mediator—polymerized 1,10-phenanthroline-5,6-dione (pPD)—were developed and electrochemically investigated. Three types of biosensors based on graphite rod (GR) electrodes modified by (i) 13 nm of gold nanoparticles (AuNPs), (ii) electrochemically synthesized dendritic gold nanostructures (DAuNSs), and (iii) platinum nanostructures (PtNSs) were prepared. All electrodes were modified by glucose oxidase (GOx), and the pPD was polymerized for 2 h. Thus, GR/AuNPs/GOx/pPD, GR/DAuNSs/GOx/pPD, and GR/PtNSs/GOx/pPD electrodes were developed and electrochemically characterized. The electrode without noble metal nanostructures (GR/GOx/pPD) was used as the control. The biosensor based on the GR/DAuNSs/GOx/pPD electrode exhibited the best performance, with the sensitivity of 2.58 μA/(mM cm²), the linear range up to 93.7 mM, the limit of detection 0.182 mM, the reproducibility and repeatability of 4.99 and 4.80%, and the storage stability (50% of initial current responses (t_1/2)) for up to 19 days. The achieved high resistance to interfering materials enabled precise glucose detection in real samples, including human serum and beverages. The technological solutions presented in this paper are anticipated to provide opportunities and benefits of developing novel enzymatic reagentless glucose biosensors based on noble metal nanostructures for use in clinical assays and general diagnostics, including blood glucose monitoring in people with diabetes. Full article

As a promising class of catalysts for enzymatic glucose sensors, Prussian blue analogues (PBAs) exhibit exceptional biomimetic activity. However, their performance is often constrained by poor intrinsic conductivity, which typically limits their sensitivity. To address this limitation, this study presents an effective approach using direct in situ growth of PBAs on the electrode substrates, which enables the effective integration of PBA-based electrochemical systems. A porous Ni framework was first electrodeposited onto a screen-printed gold electrode substrate, followed by the reduction of Pt onto the porous Ni. Subsequently, NiFe PBA was synthesized in situ using the porous Pt/Ni structure as a sacrificial template. Functionalized with glucose oxidase (GO_x), the PBA/Pt/Ni biosensor exhibited excellent performance for glucose detection in buffer solution, with a high sensitivity of 262.6 μA mM⁻¹·cm⁻² and an ultra-low detection limit of 1.45 μM (calculated at a signal-to-noise ratio of 3, S/N = 3). Notably, its sensitivity corresponds to a two-fold enhancement relative to the electrodes modified with commercial Prussian blue using the conventional drop-casting method. Even when tested in human sweat samples, the biosensor achieved a high sensitivity of 236.4 μA mM⁻¹·cm⁻² and a linear detection range of 20–1000 μM, with the broad sensing range fully encompassing the typical physiological concentrations of glucose in human sweat. This excellent performance arises from the high specific surface area of the porous Pt/Ni structure and the tight connection between PBA and the sacrificial Ni anode. This research presents a promising design strategy for advanced, wearable, and non-invasive health-monitoring platforms. Full article

Glucose oxidase (GOD) is a natural enzyme with antioxidant and antimicrobial properties but its effects on sows remain insufficient. This study investigated the effects of dietary GOD supplementation during gestation on inflammatory response, antioxidant capacity, immune function, and gut microbiota of farrowing sows. Twenty-four primiparous sows were randomly assigned to two groups and fed a basal diet or a basal diet supplemented with GOD (300 mg/kg diet) from gestation day 30 to farrowing. GOD supplementation significantly increased triglyceride, superoxide dismutase, and immunoglobulin M levels (p < 0.05), and significantly decreased alanine aminotransferase and interleukin-6 levels in serum (p < 0.05); significantly reduced placental interleukin-1β, malondialdehyde and tumor necrosis factor-α concentrations and NF-κB gene expression (p < 0.05), and elevated glutathione peroxidase activity and relative mRNA expressions of Nrf2, HO-1, GPX1 and SOD2 (p < 0.05). Moreover, GOD supplementation altered the fecal microbial community structure (p < 0.05), significantly reducing Clostridium, dgaA-11_gut_group, Bacteroides, and Prevotellaceae_NK3B31_group abundance (p < 0.05), while enriching Lachnospira, unclassified_f_Erysipelotrichiaceae, and Anaerostipes (p < 0.05). Collectively, 300 mg/kg glucose oxidase supplementation during mid-to-late gestation improved the health status of farrowing sows by improving nutrient utilization, immune function and antioxidant capacity, and altering fecal microbial structure and relative abundances. Full article

Currently, single-modal tumor therapy has significant limitations, while multi-modal combination therapy can overcome this bottleneck and open up new pathways for enhancing the efficacy of tumor therapy. However, it is still difficult to design a functionalized nanocarrier that can simultaneously mediate multiple therapeutic approaches. To tackle this challenge, we developed a multifunctional nano-codelivery system with glucose oxidase (GOx) loaded inside iron-doped zeolitic imidazolate framework-8 (Fe/ZIF-8), abbreviated as GFZ. This system effectively integrates the synergy and complementarity between ferroptosis therapy and starvation therapy (STT). Herein, GFZ innovatively combines the pH sensitivity of the ZIF-8 skeleton with the EPR effect of nanoparticles to achieve on-demand triggered release, significantly improving the accuracy of tumor targeting. Furthermore, GOx-mediated STT effectively alleviates the insufficiency of endogenous H₂O₂ during the ferroptosis process, thereby enhancing and synergizing with ferroptosis therapy. Experiments demonstrated both in vitro and in vivo that GFZ activates antitumor cascade reactions, inhibits tumor recurrence and metastasis, and exhibits excellent biocompatibility. Consequently, given its remarkable potential, GFZ is poised to emerge as a new mode of nano-delivery platform. Full article

Pyranose oxidases (POXs, EC 1.1.3.10) are a class of fungal FAD-dependent oxidoreductases with potential for lignocellulosic bioconversion because they generate H₂O₂ during sugar oxidation. Despite their known catalytic properties, the role of these enzymes in promoting lignocellulose enzymatic saccharification remains largely unexplored. In this study, POXs from Phanerochaete chrysosporium (PcPOX) and Trametes versicolor (TvPOX) were comparatively evaluated through biochemical characterization, kinetic analysis, molecular simulation, and supplementation for lignocellulose hydrolysis. PcPOX exhibited a broader substrate spectrum and a slightly higher optimum temperature, whereas TvPOX demonstrated greater stability under acidic and hydrolysis-relevant conditions and a longer half-life at 50 °C. TvPOX also showed a numerically lower apparent K_m toward D-glucose, while the apparent catalytic efficiencies were comparable between the two enzymes. Molecular simulation results suggested more stable glucose binding in TvPOX. Accordingly, TvPOX was selected for hydrolysis experiments and was shown to increase the measured glucan conversion of phosphoric acid-swollen cellulose, Avicel, and corncob residue. Mixture design analysis further indicated that this positive effect depended on balanced peroxide regulation, with low catalase supplementation providing better performance. These results identify TvPOX as a promising auxiliary enzyme for cellulase-based lignocellulosic saccharification. Full article