Search Results (36,006)

Endophytic fungi widely colonize plant tissues without causing severe disease, protect hosts from pathogenic microorganisms, and represent a key potential resource for novel biocontrol agents. To explore the biocontrol potential of endophytic Epichloë fungi and their correlation with alkaloids, 12 Epichloë strains were isolated from six different geographic sites of Festuca sinensis, Achnatherum inebrians, and Hordeum brevisubulatum. The antifungal activity of these strains was evaluated against five phytopathogenic fungi (Alternaria alternata, Bipolaris sorokiniana, Curvularia lunata, Fusarium avenaceum, and Drechslera erythrospila) using dual-culture assays, which measured the inhibition of both colony growth and spore germination. Concurrently, the concentrations of ergonovine and ergine were quantified in the liquid cultures of each Epichloë strain. The results showed that 12 Epichloë strains had varying degrees of inhibitory effects on the colony growth and spore germination of five pathogenic fungi. Among these, strain F2 had the highest inhibition rate on the spore germination of B. sorokiniana (87.73%), while strain H3 had the lowest inhibition rate on F. avenaceum (7.89%). The concentrations of ergonovine and ergine were positively correlated with the inhibition rate of pathogenic fungi, but the degree of these correlations varied among different pathogenic fungi. This study provides further evidence for Epichloë-mediated pathogen inhibition and establishes a basis for their development as biocontrol agents in agricultural systems. Full article

Hydrogen peroxide (H₂O₂) is a key extracellular redox signaling molecule that regulates diverse physiological processes, including immune cell activation and proliferation. However, its role in maintaining extracellular redox balance and mediating intercellular signaling remains underexplored. In this study, we investigated how extracellular depletion of H₂O₂ by catalase modulates intracellular signaling pathways in macrophages. Catalase treatment effectively depleted extracellular H₂O₂ in a concentration- and time-dependent manner, leading to activation of mitogen-activated protein kinase (MAPK) pathways, including extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38, as well as nuclear translocation of the nuclear factor κB (NF-κB) p65 subunit. Perturbation of extracellular redox status resulted in robust upregulation of inflammatory and oxidative stress–related genes, including cyclooxygenase-2 (COX-2), C-C motif chemokine ligand 5 (CCL5), inducible nitric oxide synthase (iNOS), and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. This transcriptional response was accompanied by increased nitric oxide (NO) production and enhanced nuclear translocation and DNA-binding activity of nuclear factor erythroid 2–related factor 2 (Nrf2). Mechanistically, our data suggest that NO-mediated S-nitrosylation contributes to activation of the cellular antioxidant response. In addition, catalase-mediated depletion of extracellular H₂O₂ significantly (p < 0.05) suppressed 5-bromo-2′-deoxyuridine (BrdU) incorporation, indicating inhibition of macrophage proliferation. Together, these findings demonstrate that extracellular H₂O₂ functions as a physiological redox signal that maintains cellular homeostasis, and that its removal triggers a coordinated intracellular response involving both inflammatory activation and antioxidant defense. This study highlights the critical role of extracellular redox balance in shaping macrophage function and provides mechanistic insight into how changes in the oxidative environment regulate downstream immune signaling pathways. Full article

This study examines why consumers intend to visit restaurants recommended by food influencers on social media. Grounded in the Theory of Planned Behavior (TPB) and social influence mechanisms, we test an extended TPB model in which trust in the influencer is incorporated as an additional antecedent of intention and as a mediating mechanism linking influencer–follower identification to visit intention. To obtain information, a structured questionnaire was administered to a sample of 474 Ecuadorian social media users who follow at least one gastronomic influencer. Hypotheses were assessed using partial least squares structural equation modeling (PLS-SEM) and predictive assessment (PLSpredict). The results show that attitude toward recommendations and perceived control exert a significant effect on intention, while subjective norms have a more moderate influence. Trust is projected as an additional facilitator in the transition from evaluation to intention, indicating that parasocial affinity translates into intended behavior only when it is accompanied by perceived credibility. The study contributes to TPB and influencer marketing by clarifying how influencer-mediated digital recommendation contexts reshape the classic TPB mechanism and by specifying trust as the key bridge between identification and behavioral intention in a high-uncertainty gastronomic decision. Full article

This study investigates the combined effect of electrodeposited gold nanoparticles (AuNPs) and AuNP–polypyrrole (PPy)-modified Saccharomyces cerevisiae on electrochemical glucose sensing. AuNPs were deposited onto electrode surfaces by cyclic voltammetry, and the resulting interfaces were characterized using atomic force microscopy, cyclic voltammetry, and electrochemical impedance spectroscopy. AFM analysis confirmed increased surface roughness and height variability after deposition, indicating substantial restructuring of the electrode interface. Electrochemical measurements showed that AuNP deposition altered interfacial charge storage and transfer and increased the measured charge-transfer resistance. Glucose sensing was evaluated in a ferricyanide-mediated system using yeast layers with or without AuNP and PPy modification over a 0–60 mM concentration range. All configurations exhibited saturating, non-linear glucose responses described by Hill fitting. Among the evaluated yeast-modified electrodes, the AuNP–PPy modified yeast produced the strongest glucose-induced current increase and the best low-concentration performance, achieving a limit of detection of 0.540 mM, compared with 1.016 mM and 1.330 mM for single-modified layers and 3.360 mM for unmodified yeast. These results show that combining AuNP electrodeposition with AuNP–PPy yeast modification improves interfacial properties and enhances mediator-assisted electrochemical glucose sensing. Full article

Background/Objectives: Mitochondrial Oxidative Phosphorylation (OXPHOS) is a critical metabolic dependency in many cancers. Targeting OXPHOS through Leucine-Rich PPR Motif-Containing Protein (LRPPRC) degrader-mediated OXPHOS Complex Biogenesis Inhibition (OCBI) has demonstrated promising anti-tumor activity. However, rational combination strategies to enhance therapeutic efficacy remain undefined. This study aims to identify FDA-approved drugs that synergize with LRPPRC inhibition and elucidate the underlying mechanism. Methods: We conducted a high-throughput screen of 1376 FDA-approved compounds using LRPPRC isogenic cancer cell models to identify agents that synergize with LRPPRC degrader-based OCBI therapy. The synergistic effects of the candidate compound were validated in multiple cancer cell lines with either genetic ablation or pharmacological inhibition of LRPPRC. Mechanistic studies were performed to investigate the impact on OXPHOS gene expression from both nuclear and mitochondrial genomes. Results: The clinically approved multi-kinase inhibitor Dasatinib was identified as a robust synergistic candidate, exhibiting heightened sensitivity in cancer cells with either LRPPRC knockout or pharmacological inhibition. Mechanistically, Dasatinib selectively suppressed nuclear-encoded OXPHOS genes, whereas LRPPRC inhibition preferentially impaired mitochondrial DNA-encoded OXPHOS genes, resulting in a coordinated dual-genome blockade of OXPHOS. Conclusions: This study uncovers a previously unrecognized synergistic anti-tumor effect between LRPPRC inhibition and Dasatinib, mediated by complementary suppression of nuclear- and mitochondrial genome-encoded OXPHOS pathways. These findings provide a strong mechanistic and translational rationale for combination therapies targeting LRPPRC-high tumors. Full article

Background: The visceral organs of sea cucumbers belonging to the family Stichopodidae, also known as Stichopodidae Viscus (SV), have been traditionally used for the management of gastrointestinal disorders. Experimental evidence has shown that the ethanol extract of SV (SVE) alleviates ulcerative colitis (UC) symptoms in a mouse model. However, the chemical constituents of SVE and the potential molecular targets mediating its effects in UC remain unclear. Methods: In this study, SVE was prepared from Apostichopus japonicus (Selenka). A reliable and sensitive strategy integrating advanced analytical and informatics tools was employed to profile the chemical components of SVE. Analyses were performed using ultra-performance liquid chromatography coupled with ion mobility spectrometry and quadrupole time-of-flight mass spectrometry operating in high-definition MS^E (UPLC-IMS-Q-TOF-HDMS^E), with data processed using the UNIFI scientific information system. Constituent identification relied on retention time (RT), accurate mass (MS1), experimentally acquired HDMS^E (MS2) spectra, and collision cross-section (CCS). Metabolomics-based approaches were further applied to characterize the in vivo exposure profile of SVE components in mouse serum and colon tissue after oral administration. Subsequently, the putative bioactive constituents and their underlying mechanisms of action were investigated using network pharmacology and molecular docking. Results: Based on the integrated identification strategy, a total of 78 compounds, including saponins, phenolic acids, fatty acids, and amino acids, were annotated in SVE, among which 6 compounds were verified using authentic reference standards to ensure unambiguous identification. Subsequently, 35 features in serum and 24 in the colon were found to be significantly altered following a single oral dose of SVE in mice, and were defined as SVE-related differential constituents. After network pharmacology analyses, 129 shared targets were identified between potential targets of SVE-related components in serum and UC-related targets, including PIK3CA, EGFR, and AKT1. Functional enrichment analysis suggested that SVE might exert its effects in UC through modulation of key nodes within the PI3K-Akt and EGFR signaling pathways, as well as lipid- and atherosclerosis-related pathways. Molecular docking results further indicated moderate binding affinities of representative SVE-related differential components toward PIK3CA, AKT1, and EGFR. Conclusions: This study clarifies the chemical basis and potential UC-related mechanisms of SVE, providing a scientific rationale for the development of SV-derived therapeutic candidates for UC. Full article

Oral squamous cell carcinoma (OSCC) represents a major global health burden and remains one of the most prevalent and aggressive malignancies of the head and neck region. Despite significant advances in surgical techniques, chemotherapy, and radiotherapy, patient outcomes have improved only modestly over recent decades. The high recurrence rate, metastatic potential, and resistance to therapy underscore the complexity of OSCC biology and the limitations of conventional treatment approaches. In recent years, the concept of cancer stem cells (CSCs) has reshaped the understanding of tumor initiation, progression, and therapeutic failure in OSCC. These cells, characterized by self-renewal capacity and phenotypic plasticity, are believed to sustain tumor growth, drive recurrence, and mediate resistance to therapy. Parallel to this, insights into epigenetic regulation, including DNA methylation, histone modifications, and non-coding RNAs, have revealed new layers of molecular heterogeneity and adaptability in oral carcinogenesis. The integration of CSC biology with epigenetic modulation offers a promising foundation for the development of targeted and personalized therapeutic strategies. Novel approaches aim to eradicate CSCs, induce their differentiation, or reprogram their malignant phenotype through the use of epigenetic inhibitors and molecular modulators. This review summarizes current knowledge on the molecular and cellular mechanisms driving OSCC pathogenesis, highlights the emerging role of CSCs and epigenetic regulators, and discusses the challenges and perspectives of translating these findings into effective clinical therapies. Full article

Climate change and tightening resource and environmental constraints are increasing the strategic importance of environmental, social, and governance (ESG) performance for firms’ long-term viability. This study examines whether ESG performance enhances organizational resilience in China and explores the roles of innovation capability and environmental uncertainty. Using an unbalanced panel of 1037 non-financial Chinese A-share listed firms from 2014 to 2022, we estimate panel models and conduct a series of robustness and endogeneity tests. The results show that ESG performance significantly improves organizational resilience. Innovation capability partially mediates this relationship, indicating that ESG enhances resilience in part by strengthening firms’ innovative capacity. Environmental uncertainty also positively moderates the effect of innovation capability on organizational resilience, although the evidence is modest. Further analysis shows that the positive ESG–resilience relationship is stronger among state-owned enterprises and small and medium-sized firms. Overall, the findings suggest that ESG functions not only as a sustainability signal, but also as an organizational capability that supports resilience under uncertainty. Full article

Alzheimer’s disease (AD) is a prevalent chronic neurodegenerative disorder; the progression of this disease is driven by cellular determinants such as oxidative stress and dysregulated neurotrophic signaling. Lavender essential oil is traditionally used in aromatherapy for neuronal regulation and neuroprotection, suggesting its potential neuroprotective effects for chronic neurodegenerative disorders like AD. However, the key active constituents responsible for its benefits and the specific molecular pharmacological mechanisms remain unclear. In this study, we isolated myrtenol from lavender essential oil under the guidance of activity evaluation. Its neuroprotective effects were evaluated in PC12 cells via neurite outgrowth, anti-Aβ/H₂O₂ cytotoxicity, and antioxidant assays. Targets and pathways were explored using inhibitor experiments, cell thermal shift assay (CETSA), drug affinity responsive target stability (DARTS), and Western blot. Myrtenol significantly induced neurite outgrowth in PC12 cells and effectively mitigated cytotoxicity and oxidative stress damage induced by Aβ_25–35 and H₂O₂. Mechanistic studies revealed that myrtenol’s effects are associated with the modulation of tyrosine kinase receptor A (TrkA) and insulin-like growth factor-1 receptor (IGF-1R), activating phospholipase C (PLC)/protein kinase C (PKC) and phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling pathways to jointly mediate neuroprotection effects against the pathology of AD. This study demonstrates that myrtenol as a highly active component of lavender essential oil possesses NGF-like neuritogenic activity and neuroprotective effects. It provides a foundation for understanding the cellular mechanisms of myrtenol as a small-molecule lead for further investigation in neurodegeneration-related research. Full article

Rural revitalization has emerged as a core agenda in the global pursuit of sustainable development, with its success fundamentally hinging on enhancing the resilience of rural households to withstand shocks and restore their livelihoods. In contrast to mainstream research that primarily examines whether Medical Financial Assistance (MFA) reduces medical burden, this paper focuses on MFA as ex-post cash compensation and investigates whether and how it affects the sustainable livelihood recovery of low-income rural households following health shocks, thereby providing empirical evidence for understanding the foundational role of health security in rural revitalization. A quasi-natural experiment is constructed by leveraging the institutional feature that MFA eligibility is activated by exogenous health shocks. Using two-wave balanced panel data (2021–2022) from a nationally designated deep poverty-stricken county in Hebei Province, China, the Propensity Score Matching–Difference-in-Differences (PSM-DID) method and mediation models are employed for causal identification and mechanism testing. The findings indicate that (1) MFA significantly promotes household income recovery. It enables recipient households to recover per capita net income by an average of approximately 13.2% (p < 0.01), demonstrating a protective recovery effect, and simultaneously recovers per capita non-farm labor income by an average of approximately 13.8% (p < 0.05), revealing a developmental recovery effect. The latter is partially mediated by the non-farm labor participation rate (mediation ratio 51.7%, Sobel Z = 2.10). This finding validates the “time release effect,” demonstrating that MFA stimulates endogenous dynamics by restoring health capital and releasing labor previously constrained by family care responsibilities. It thereby extends the application of health capital theory from the individual to the household level. (2) Mechanism analysis shows that the protective recovery effect is fully mediated by the amount of MFA received (mediation ratio 326.7%, Sobel Z = 12.85), providing empirical evidence for precautionary saving theory in the context of targeted social assistance and revealing the potential productive attributes of the social safety net. (3) Heterogeneity analysis reveals clear group targeting and shock thresholds. The protective effect is concentrated among elderly households, while the developmental effect is primarily evident in middle-aged households. Both recovery effects manifest significantly only for households experiencing major disease shocks, confirming the theoretical expectation of “conditional effectiveness,” namely that policy effects are systematically moderated by household life-cycle characteristics and the severity of health shocks. This study demonstrates that MFA serves both as a safety net and an empowerment tool, but its effectiveness is highly contingent upon household characteristics and shock severity. By uncovering the foundational mechanisms through which health security contributes to rural household resilience, this study provides empirical evidence from China for building sustainable poverty prevention systems in the global process of rural revitalization. Full article

Active learning has increasingly been adopted as an evidence-aligned approach to improving learning quality in university physics—a domain characterized by high conceptual abstraction, persistent misconceptions, and substantial variability in student performance. Evidence from physics education research indicates that active-learning designs can outperform lecture-dominant instruction in conceptual learning and student engagement; however, reported effects vary substantially across instructional settings and implementation models. Here, empirical studies and review-level syntheses are integrated to delineate (i) the instructional components that most reliably underpin successful active learning, (ii) the mechanisms through which these components influence learning processes and outcomes, and (iii) the boundary conditions that moderate effectiveness across higher-education contexts. The synthesis is further situated within sustainability-oriented higher education by linking physics active-learning designs to competence development relevant to quality education, climate literacy, and collaborative problem solving. Evidence spanning flipped classroom implementations, peer instruction, collaborative problem solving, inquiry- and project-based approaches, and technology-enhanced formats is organized into a component–mechanism–outcome framework structured along cognitive, affective, and behavioral pathways. Two deliverables are advanced: an integrative mechanism model connecting instructional components to mediating processes, learning outcomes, and sustainability-aligned competencies, and an operational toolbox that translates the evidence into actionable design heuristics, measurement options, and scaling considerations. By redirecting attention from “which strategy works” to “which components work, how, and under what conditions,” the review aims to support instructors, departments, and institutions seeking scalable, evidence-aligned active learning in university physics. Full article

Visual transgenic marker systems enabling rapid and non-destructive transformant detection are crucial for efficient plant genetic transformation and selection. RUBY is a highly effective reporter system based on betalain biosynthesis; however, its application to species outside of the order Caryophyllales (i.e., species lacking betalains) has not been established. In this study, we performed the first systematic evaluation of the RUBY system using Petunia×hybrida lines obtained via Agrobacterium-mediated gene transformation. Stable RUBY transgenic plants were obtained from an optimized transformation and organogenesis system. The transgenic lines displayed a gradient of betalain accumulation, with pigment intensity positively correlated with RUBY expression levels and metabolite contents. In a morphological analysis, there was a negative correlation between RUBY expression and corolla opening, suggesting that RUBY pigment overaccumulation is associated with altered floral development and morphology. RUBY overexpression significantly reduced expression levels of gibberellin biosynthetic genes (PhGA20ox1 and PhGA3ox1) and flowering- and senescence-related regulators (PhNF-YC2 and PhOBF1). These findings indicate that high-level betalain accumulation is associated with changes in floral development and gene expression, highlighting both the utility of the RUBY system as a visual reporter and the importance of carefully evaluating potential developmental effects under strong expression conditions. Full article

Listeria monocytogenes (Lm) is a foodborne pathogen whose virulence depends on the coordinated action of multiple virulence factors. Although deletion of either LIPI-4 or inlB reduces the virulence of Listeria monocytogenes, it remains unknown whether these two factors are functionally or regulatory connected. Therefore, we constructed an inlB deletion mutant and its complemented strain in the Lm928 and ΔLIPI-4 backgrounds. We assessed bacterial growth, biofilm formation, motility, host cell interactions (adhesion, invasion, intracellular proliferation), plaque formation, mouse organ colonization. Growth curve analysis showed no significant differences among strains. qPCR revealed that LIPI-4 modulates inlB expression in a cell-type-specific manner: inlB was downregulated in ΔLIPI-4 under culture and HTR-8 infection, but upregulated during hCMEC/D3 infection—yet functional defects persisted in all cases. Biofilm assays showed that ΔLIPI-4 and the double mutant exhibited enhanced biofilm formation, with the double mutant exceeding ΔLIPI-4, demonstrating synergistic enhancement. Motility assays indicated that LIPI-4 dominates bacterial movement, with ΔLIPI-4 and the double mutant showing identical severe defects. Plaque formation analysis showed that LIPI-4 is essential for cell-to-cell spread, while inlB deletion unexpectedly enhanced plaque formation—an effect completely abolished in the absence of LIPI-4. Host cell assays across Caco-2, HTR-8, and hCMEC/D3 models revealed that LIPI-4 is the core determinant of adhesion, invasion, and intracellular proliferation, whereas inlB contributes in the context of LIPI-4 and its effects vary with the specific cellular process examined. In mice, LIPI-4 was essential for systemic colonization of the liver and spleen, with inlB acting as a co-factor, whereas inlB unexpectedly promoted higher bacterial burdens in the brain, suggesting that inlB modulates LIPI-4-mediated neuroinvasion. Overall, our results establish LIPI-4 as the central determinant of Lm virulence, with inlB acting as a context-dependent co-factor that modulates LIPI-4-mediated pathogenesis in a cell type- and tissue-specific manner. Full article

While breastfeeding is strongly recommended for infant health, uncertainty remains regarding its independent association with early childhood caries after accounting for sugar exposure. Objective: This study aimed to evaluate the controlled direct effect of breastfeeding on dental caries. Methods: Data were drawn from two population-based birth cohort studies: the 2015 Pelotas Birth Cohort Study (Brazil) and the SMILE Study (Australia). The exposure was any breastfeeding at 3, 6, and 12 months, with sugar consumption at 12 and 24 months as the mediator. The outcome was dental caries at ages 4/5, assessed as early childhood caries (ECC), severe ECC, any disease experience, or any decayed teeth. Marginal Structural Models with inverse probability of treatment weight were used to estimate the controlled direct effect of breastfeeding on dental caries, accounting for sociodemographic confounders and sugar consumption. Results: A total of 751 Australian and 3545 Brazilian children were included in at least one sub-analysis. Findings indicate a contextual difference: in Australia, breastfeeding had no effect on dental caries after considering sugar consumption as mediator, whereas in Brazil, children not breastfed had a lower risk of dental caries. For instance, adjusted Brazilian estimates showed a reduced relative risk ranging from 0.63 (95% CI 0.55; 0.72) for ECC to 0.43 (95% CI 0.34; 0.55) for severe ECC. Conclusions: The association between breastfeeding and dental caries appears to vary across socio-environmental contexts. In settings with high caries burden, prolonged breastfeeding may increase caries risk independently of sugar consumption; however, breastfeeding remains strongly recommended given its substantial overall health benefits. These findings highlight the importance of integrating early oral health guidance such as oral health education into breastfeeding support programs. Full article

Lignin nanoparticles (LNPs) offer sustainable alternatives to petroleum-derived nanofillers, yet their industrial application remains limited by poor dispersion control and trade-offs between loading, optical clarity, and mechanical performance. Here, we present a molecular architecture-driven design framework that systematically decouples polymer network physics from nanoparticle dispersion in poly(vinyl alcohol)/LNP nanocomposites. Through eco-friendly self-precipitation, we synthesize uniform LNPs with size tunability, overcoming persistent reproducibility challenges. Systematic investigation across PVA molecular weights and LNP loadings reveals entanglement-controlled dispersion behavior. Combined rheological and small-angle X-ray scattering analyses demonstrate that macroscopic suspension rheology is governed exclusively by polymer chain overlap, remaining invariant across LNP loadings. Conversely, the nanoscale LNP microstructural organization—ranging from depletion-driven clustering in weakly entangled networks to network-confinement stabilization in densely entangled systems—fundamentally dictates the film’s optical clarity and mechanical toughness. This rheology-microstructure decoupling establishes critical processing windows for industrial formulations, where polymer entanglement ensures suspension processability while the LNP dispersion state enables optical–mechanical tunability. The entangled network’s structure-filtering effect provides robust protocols for fabricating sustainable, transparent bio-composites suitable for packaging, optics, and functional films. Our quantitative composition–structure–performance framework advances fundamental understanding of entanglement-mediated interfacial phenomena while delivering practical design rules for next-generation sustainable bio-composites. Full article