Search Results (11,224)

Antibiotic resistance genes (ARGs) are increasingly recognized as a concern in drinking water, yet the factors influencing their persistence from raw to finished water in drinking water treatment plants remain poorly understood. This study investigated the occurrence, removal, and potential factors associated with the persistence of ARGs (sul1, sul2, and tetG) in a full-scale rapid sand filtration drinking water treatment system with intermediate and post-chlorination. ARGs were detected in raw water at a median total concentration of 10⁶ copies/L and remained detectable in finished water at 10⁴ copies/L. Relative ARG abundance increased after treatment despite substantial absolute reductions (2.1–3.6 log). Intermediate chlorination achieved the greatest ARG log reduction value (0.53–2.4 log), likely due to higher chlorine dose and lower pH favoring HOCl formation. By contrast, post-chlorination at higher pH provided limited additional removal, possibly due to predominance of less reactive OCl⁻ and survival of chlorine-tolerant bacteria. Multivariate analyses showed a shift from particle-bound ARGs in raw water to dissolved organic matter (DOM) and fine-particle-associated fractions along the treatment train. These findings suggest that reducing fine particles and DOM, together with optimized disinfection, may help lower ARG-associated risk in finished water. Full article

Ovarian granulosa cells (GCs) ensure proper follicular development and oocyte maturation through gap-junction-mediated intercellular communication. Zearalenone (ZEA), a mycotoxin with estrogen-like activity, specifically targets and impairs ovarian function. Most existing studies have focused on ZEA-induced apoptosis in GCs, but whether ZEA disrupts gap junctions in ovarian GCs remains unclear. Therefore, the aim of this study was to investigate whether and how ZEA induces gap junction injury in ovine ovarian GCs, with a particular focus on the roles of G protein-coupled receptor 30 (GPR30), oxidative stress, and the NLRP3 inflammasome. In the present study, primary ovine ovarian GCs were isolated, cultured, and treated with different concentrations of ZEA to establish a gap junction injury model, and specific inhibitors/antagonists were used to investigate the underlying mechanisms. The results showed that ZEA decreased granulosa cell viability and significantly inhibited the expression of the gap junction proteins Connexin 43 (Cx43) and Connexin 37 (Cx37) in a concentration-dependent manner. ZEA treatment also significantly upregulated the expression of the NOD-like receptor familypyrindomain containing 3 (NLRP3) inflammasome-related proteins (NLRP3, ASC, Cleaved Caspase-1, and the downstream pro-inflammatory cytokine IL-1β) in a concentration-dependent manner. Pretreatment with the NLRP3-specific inhibitor MCC950 significantly reversed ZEA-induced downregulation of Cx43 and Cx37 and effectively blocked NLRP3 inflammasome activation, indicating that NLRP3 is a key target in ZEA-induced gap junction injury. Further experiments confirmed that ZEA treatment significantly increased oxidative stress levels in granulosa cells; pretreatment with the reactive oxygen species (ROS) scavenger N-acetylcysteine (NAC) restored the ZEA-induced downregulation of Cx43 and Cx37 and suppressed NLRP3 inflammasome activation, suggesting that ROS acts as an upstream regulator of NLRP3 inflammasome activation. Moreover, ZEA treatment altered GPR30 expression levels, and pretreatment with the GPR30 antagonist G15 effectively inhibited ZEA-induced ROS production, NLRP3 inflammasome activation, and downregulation of Cx43/Cx37, indicating that ZEA exerts its effects through functional activation of GPR30. Collectively, ZEA activates the GPR30 receptor, induces ROS accumulation in granulosa cells, and subsequently triggers NLRP3 inflammasome activation, ultimately leading to downregulation of Cx43 and Cx37 and gap junction dysfunction. This study reveals a previously unrecognized molecular mechanism by which ZEA induces gap junction injury in ovarian GCs, providing potential therapeutic targets and a theoretical basis for preventing ZEA-induced ovarian dysfunction and improving animal reproductive health. Full article

Periodontitis treatment remains challenging due to incomplete removal of plaque biofilms, increasing antibiotic resistance, and dysregulated host inflammatory responses. In this study, an MPB@ZnPc nanomaterial was constructed to achieve efficient antibacterial activity through the synergistic effects of photothermal therapy (PTT) and photodynamic therapy (PDT), while also exerting immunomodulatory functions under dark conditions. MPB@ZnPc (mesoporous Prussian blue @ zinc phthalocyanine) was synthesized using a polymer-templating method and systematically characterized. The results demonstrated that the nanomaterial exhibited excellent photothermal conversion efficiency and stability under near-infrared (NIR) irradiation. It also showed strong photocatalytic degradation performance toward methylene blue and rhodamine B, accompanied by substantial reactive oxygen species (ROS) generation. In vitro antibacterial assays revealed that MPB@ZnPc achieved significantly enhanced antibacterial efficacy compared with individual components, with bactericidal rates of 99.61 ± 0.52% against Porphyromonas gingivalis and 99.77 ± 0.32% against Fusobacterium nucleatum. The corresponding biofilm removal rates reached 93.60 ± 3.30% and 93.25 ± 3.30%, respectively. Under dark conditions, the nanomaterial exhibited good biocompatibility toward L929 cells and effectively inhibited lipopolysaccharide (LPS)-induced M1 polarization of macrophages, leading to reduced expression of pro-inflammatory cytokines, including IL-1β, IL-6, and TNF-α. Mechanistically, MPB@ZnPc suppressed the activation of the NF-κB signaling pathway. Overall, MPB@ZnPc provides a promising strategy for precise periodontitis treatment by integrating synergistic antibacterial activity with immunomodulatory effects. Full article

TP53 is the most frequently altered tumor-suppressor gene in human cancer, yet efforts to therapeutically target p53 have yielded limited and inconsistent clinical success. We argue that this gap reflects not a lack of druggable biology, but an oversimplified conceptual framework that treats p53 as a binary wild-type versus mutant entity. Here, we synthesize emerging evidence supporting a model in which p53 operates across a spectrum of functional states defined by mutation class, allelic burden, isoform composition, aggregation propensity, post-translational regulation, and cellular context. These states shape distinct biological outputs, including transcriptional activity, dominant-negative and gain-of-function effects, immune modulation, and checkpoint dependency, which collectively determine therapeutic vulnerability. We review current strategies targeting the p53 pathway, including mutant p53 reactivation, targeted degradation, anti-aggregation approaches, immune-directed therapies, restoration of wild-type pathway activity, gene replacement, and synthetic lethal targeting of DNA damage response dependencies. Clinical and preclinical evidence highlights key limitations of each approach, including stoichiometric constraints, mutation specificity, context-dependent efficacy, and adaptive resistance. Notably, emerging evidence from preclinical and correlative clinical studies suggests that therapeutic outcomes may be more closely associated with p53 functional state than with TP53 mutation status alone. We further emphasize the emerging roles of p53 isoforms and the tumor immune microenvironment as critical modifiers of p53 activity and determinants of treatment response. Collectively, these insights support a paradigm shift toward mechanism-matched, biomarker-stratified strategies that align therapeutic modality with the operative p53 network. Future progress will depend on integrating multi-parameter diagnostics with rational combination therapies to fully exploit p53 as a central vulnerability in cancer. Full article

Mastitis is one of the most prevalent diseases in dairy cows, leading to significant economic losses and increased antibiotic usage. The development of safe and effective alternatives is therefore urgently needed. In this study, we investigated the protective effects of Forsythiaside A (FTA), a natural compound, against LPS-induced mastitis in bovine mammary epithelial (MAC-T) cells and a murine model. FTA significantly reduced intracellular reactive oxygen species (ROS), decreased lipid peroxidation, and restored antioxidant capacity. Furthermore, FTA increased the expression of GPX4 and SLC7A11, indicating inhibition of ferroptosis. The ferroptosis inducer RSL3 partially reversed these protective effects, supporting the involvement of GPX4-associated ferroptosis regulation in the protective effects of FTA. In vivo, FTA alleviated mammary tissue injury, reduced inflammatory cell infiltration, and improved redox balance. These findings suggest that FTA may serve as a potential natural therapeutic agent for mastitis, providing a promising alternative to antibiotic-based treatments in dairy production. Full article

Curcumin, a natural polyphenolic compound derived from turmeric, exhibits broad-spectrum anticancer activities, but its ability to induce pyroptosis in osteosarcoma remains unknown. Osteosarcoma is the most common primary malignant bone tumor in children and adolescents, and novel therapeutic strategies are urgently needed to overcome osteosarcoma chemoresistance. Aim: This study aimed to investigate whether curcumin induces pyroptosis-associated molecular changes in human osteosarcoma cells and to explore the underlying molecular mechanisms, focusing on the ROS/NLRP3/CASPASE-1/GSDMD axis and the PI3K/AKT signaling pathway. Methods: Human osteosarcoma U2OS and MG63 cells were treated with curcumin (20–40 μmol·L⁻¹ for 24 h). Cell viability was assessed by CCK-8 assay. Pyroptotic morphology was observed by scanning electron microscopy. Lactate dehydrogenase (LDH) release was measured colorimetrically, and IL-1β/IL-18 secretion was quantified by ELISA. Mitochondrial membrane potential (ΔΨm) and intracellular reactive oxygen species (ROS) levels were analyzed by flow cytometry. Protein expression levels of NLRP3, cleaved CASPASE-1, GSDMD-N, PI3K, AKT, p-AKT, Bax, Bcl-2 and cleaved CASPASE-3 were detected by Western blotting. Pharmacological validation was performed using the pan-caspase inhibitor Z-VAD-FMK. Results: Curcumin significantly inhibited the proliferation of U2OS and MG63 cells in a dose- and time-dependent manner. Scanning electron microscopy revealed characteristic pyroptotic features including cell swelling, membrane pore formation, and rupture. Curcumin treatment markedly increased LDH release and elevated IL-1β/IL-18 secretion. Mechanistically, curcumin induced mitochondrial membrane depolarization and ROS accumulation, upregulated NLRP3, cleaved CASPASE-1, and GSDMD-N expression, and concomitantly reduced PI3K/AKT pathway activity. Additionally, curcumin upregulated pro-apoptotic Bax, downregulated anti-apoptotic Bcl-2, and activated cleaved CASPASE-3. The pan-caspase inhibitor Z-VAD-FMK partially reversed curcumin-induced cytotoxicity, confirming that caspase-dependent apoptosis contributes to the overall anticancer effect. Conclusions: This study provides evidence that curcumin induces both apoptosis and pyroptosis-associated molecular changes in human osteosarcoma cells. The pyroptotic effect involves the ROS/NLRP3/CASPASE-1/GSDMD axis, accompanied by PI3K/AKT suppression, while caspase-dependent apoptosis also plays an important role. These findings uncover a previously unreported mechanism of curcumin’s anti-osteosarcoma activity and suggest that targeting multiple cell death pathways may represent a promising strategy to overcome apoptosis resistance in osteosarcoma. Full article

Pesticides are widely used chemical compounds in agriculture, but their presence in water systems represents a significant environmental and health problem. Due to their stability and toxicity, many pesticides are difficult to remove using conventional water treatment methods, which has led to the development of advanced oxidation processes. Photocatalytic processes are based on the activation of semiconductor materials under light irradiation, leading to the formation of reactive species that degrade pesticides into less harmful products. On the other hand, electrocatalytic processes use electrical energy to generate oxidation and reduction reactions on electrode surfaces, enabling efficient degradation of organic pollutants. Both approaches offer high efficiency and the potential for complete mineralization of pesticides. Nanomaterials play a key role in improving these processes, as they provide a large specific surface area, enhanced conductivity, and increased reactivity. In photocatalysis, nanostructured metal oxides such as TiO₂ and ZnO are commonly used, while in electrocatalysis, advanced nanocomposites and modified electrodes are applied to improve electron transfer efficiency and system stability. This review paper provides an overview of recent research in the field of photocatalytic and electrocatalytic systems for pesticide removal from water, with a particular focus on the role of nanomaterials. Special attention is given to current trends, including the development of new nanostructures, hybrid systems, and energy-efficient technologies. The aim of this paper is to present, in a simple and clear way, the potential of these methods and to contribute to a better understanding of their application in environmental protection. Full article

Epstein–Barr virus (EBV) lytic reactivation contributes to the pathogenesis of EBV-associated epithelial malignancies, including nasopharyngeal carcinoma and gastric carcinoma, highlighting the need for therapeutic strategies targeting viral reactivation. Capsaicin exhibits anticancer and antiviral activities; however, its effects on EBV lytic reactivation remain unclear. This study investigated the effects of capsaicin on EBV lytic reactivation in EBV-positive epithelial cancer models. Capsaicin significantly suppressed the expression of lytic genes, including BZLF1, BRLF1, BMRF1, and BLLF1, and reduced EBV virion production. Proteomic analysis revealed alterations in host cellular pathways associated with metabolism, chromatin organization, and cytoskeletal regulation, whereas metabolomic profiling demonstrated perturbations in nucleotide, amino acid, and polyamine metabolism processes involved in viral DNA replication and protein synthesis. Protein–protein interaction network analysis identified key host proteins, including HSP90AB1, MYH9, and ANXA2, implicated in metabolic reprogramming, cytoskeletal organization, and stress responses. Moreover, upstream regulators associated with EBV lytic activation, including p65, AP-1, HIF-1α, and SP1, were down-regulated following capsaicin treatment. Collectively, these findings demonstrate a multitarget inhibitory effect of capsaicin on EBV lytic reactivation and support its therapeutic potential against EBV-associated epithelial malignancies. Full article

This study investigates the degradation of propranolol, a widely detected beta-blocker in natural water, using an ultraviolet/peracetic acid (UV/PAA) system. The UV/PAA system significantly enhanced the degradation efficiency compared to UV or PAA alone, achieving a 90.67% removal of propranolol after 15 min under optimal conditions. The degradation process was found to follow first-order kinetics, with a rate constant 36 times higher than that of UV. Reactive species such as hydroxyl radicals (^·OH) and organic radicals (RO^·) were identified through quenching experiments and electron paramagnetic resonance (EPR) spectroscopy. The degradation mechanism was further explored using density functional theory (DFT), revealing the molecular sites most susceptible to radical attacks. This study provides new insights into the application of UV/PAA systems for the removal of beta-blockers and contributes to the optimization of advanced oxidation processes in water treatment. Full article

Background: Walnut albumin (WA) possesses a balanced amino acid composition but exhibits poor solubility, limited emulsifying capacity, and low structural stability, restricting its practical applications in food systems. Methods: In this study, bound polyphenols (BPs) from jujube pomace were covalently conjugated with WA through alkaline and radical methods, with or without ultrasound assistance. Four WA–BPs conjugates were prepared, including alkaline-treated (AWA–BPs), ultrasound-assisted alkaline (UAWA–BPs), radical-treated (RWA–BPs), and ultrasound-assisted radical conjugates (URWA–BPs), to investigate the effects of different covalent assembly methods on the structural and functional properties of WA. Results: Covalent conjugation with BPs significantly altered the structural properties of WA, as evidenced by reductions in reactive groups, changes in surface hydrophobicity, fluorescence quenching, and shifts in FTIR spectra. URWA–BPs exhibited the highest grafting degree of 4.46 mg/g dry weight (DW) among the four treatment groups, indicating effective grafting and conformational rearrangement. Moreover, URWA–BPs demonstrated superior functional properties, including improved solubility, emulsifying activity, foaming properties, and antioxidant capacity. The DPPH, ABTS⁺, and FRAP values of URWA–BPs increased by approximately 10–17% compared with WA. In contrast, UAWA–BPs exhibited the lowest in vitro digestibility (54.90 ± 1.60%), indicating enhanced structural stability against gastrointestinal digestion. Molecular docking revealed binding free energies ranging from −5.3 to −7.6 kcal/mol, suggesting stable interactions between BPs and WA. Conclusions: The differences observed between UAWA–BPs and URWA–BPs suggest that, in addition to promoting covalent conjugation, ultrasound exerts distinct regulatory effects during alkaline and radical covalent assembly processes, resulting in different structural and functional properties. This study provides new perspectives for designing functional plant-based protein ingredients and valorizing food-processing by-products. Full article

The detection and quantification of reactive oxygen and nitrogen species (RONS) in plasma-treated water (PTW) are essential for advancing plasma applications in biomedical and agricultural fields. However, RONS characterization remains challenging, as conventional techniques often require chemical reagents that can alter the sample. Electrochemical impedance spectroscopy (EIS) offers a non-destructive alternative by probing the electrical response of aqueous systems and providing information on ionic concentration, charge transfer, and diffusion processes. This study investigates the feasibility of EIS as a diagnostic tool for characterizing physicochemical changes in PTW. Calibration experiments were performed using saline solutions with different ionic concentrations to evaluate the sensitivity of impedance measurements. Impedance spectra were recorded over a frequency range of 0.1 Hz to 10 kHz and analyzed using Nyquist and Bode plots with equivalent circuit modeling. Deionized water was treated with cold atmospheric plasma at different discharge powers (3.53–10.15 W) and treatment times (5–30 min) to generate RONS. The results show that EIS can monitor plasma-induced changes in conductivity and interfacial properties associated with variations in ionic content. In particular, systematic changes in solution resistance and admittance were observed and were correlated with plasma-induced changes in ionic composition. These findings demonstrate that EIS is a sensitive and non-invasive diagnostic method for PTW analysis. Full article

Background: Perioperative immunotherapy has emerged as a promising strategy for improving outcomes in patients with resectable head and neck squamous cell carcinoma (HNSCC). However, its biological rationale, clinical evidence, and optimal implementation remain incompletely defined. Methods: We conducted a narrative review of the current literature, integrating preclinical and clinical evidence on perioperative immune checkpoint inhibitor (ICI) therapy in resectable HNSCC, with particular attention to the immunological impact of surgery, tumor-draining lymph nodes, and treatment sequencing. Results: Neoadjuvant immunotherapy exploits the presence of intact tumor antigen and preserved lymphatic architecture, enabling broad T-cell priming, clonal expansion, and systemic immune memory formation. In contrast, adjuvant immunotherapy primarily targets residual microscopic disease and relies on preexisting tumor-reactive T cells, suggesting that these strategies are biologically distinct. Early-phase clinical trials have demonstrated the safety and feasibility of perioperative ICIs, with evidence of pathological responses. Recent phase III trials, including KEYNOTE-689 and NIVOPOSTOP, have provided practice-relevant evidence supporting the integration of ICIs into perioperative treatment, demonstrating improved event-free survival and clinical outcomes in selected populations. Several challenges remain, including optimal patient selection, lack of validated biomarkers, and treatment sequencing after perioperative ICI exposure. Conclusions: Perioperative immunotherapy represents a promising practice-relevant strategy in resectable HNSCC. Further studies are required to refine patient selection, develop predictive biomarkers, and optimize treatment sequencing to maximize clinical benefit. Full article

To achieve efficient removal and defluorination of perfluorooctanoic acid (PFOA), a visualized micro-scale fused quartz tube reactor (FQTR) was constructed to systematically investigate sub/supercritical water oxidation (SCWO) processes. Under operating conditions of 200–400 °C and 8–27.3 MPa, PFOA underwent rapid degradation with near-complete conversion. The incorporation of γ-MnO₂ markedly enhanced the PFOA degradation at low temperature and achieved faster fluorine removal. At the conditions of 300 °C, 40 min, O/C ratio (oxygen-to-carbon molar ratio) = 1.5, and pH = 7, the degradation and defluorination efficiencies increased by 12.56% and 15.21%, respectively, compared with the non-catalytic system. This enhancement is primarily attributed to the efficient activation of H₂O₂ by γ-MnO₂, which promotes the breaking of C–F bond and accelerates the converting of PFOA into CO₂ and fluoride ions. The SEM, Raman and leaching experiment results demonstrated that γ-MnO₂ exhibits excellent structural stability and reusability. Furthermore, density functional theory (DFT) calculations were performed to identify potential reactive sites and elucidate degradation pathways at the molecular level, providing mechanistic support for the experimental observations. Overall, the γ-MnO₂-catalyzed SCWO exhibits excellent degradation and defluorination performance for PFOA removal, providing useful insight into the treatment of fluorinated wastewater. 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

Glioblastoma multiforme (GBM) is the most aggressive brain tumor in adults. Necrosis, and by inference hypoxia, is a pathognomonic feature of GBM tumors, where hypoxia significantly contributes to chemoresistance, leading to local treatment failure and disease progression. Although temozolomide (TMZ) is the main treatment option, 60–75% of GBM patients do not benefit from it. This study aimed to evaluate the therapeutic potential of Tetrandrine (TET) in combination with or compared to TMZ in treating GBM cells (M010b and U87) under both normoxic and hypoxic conditions. The therapeutic potential was assessed using qRT-PCR, MTT assay, combination index analysis, flow cytometry for apoptosis and cell cycle analysis, scratch assay, gelatin zymography, measurement of mitochondrial membrane potential (ΔΨm), reactive oxygen species (ROS) production, and molecular docking. Under both normoxic and hypoxic conditions, TET showed significant cytotoxicity in both cell lines compared to TMZ. A synergistic effect was observed only under normoxia at 2× IC₅₀ concentrations in M010b cells, and at 4× IC₅₀ concentrations in U87 cells. TET significantly increased the sub-G1 cell population and apoptosis compared to TMZ in both cell lines under normoxic and hypoxic conditions, while TMZ induced G2/M arrest in U87 cells under both conditions. TET significantly increased ROS production in both cell lines under normoxia. Under both conditions, ΔΨm was significantly reduced by TET in M010b cells and by TMZ in both cell lines. TET and TMZ significantly reduced pro-MMP-2 levels in M010b cells under both conditions and in U87 cells under normoxia. In conclusion, given the limited therapeutic potential of TMZ, our findings suggest that TET could be a viable alternative treatment option for GBM. Full article