Search Results (281)

Cadmium (Cd) is a potentially toxic element that impairs plant growth and threatens food safety and human health. This study aimed to investigate the effects of sulfur (S) supplementation on Cd uptake and tolerance in rice under hydroponic conditions. Rice seedlings were exposed to Cd stress and treated with S at different concentrations. Physiological traits, oxidative damage markers, thiol compounds, and ionomic profiles in rice plants were assessed. S supplementation reduced Cd-induced growth inhibition, restoring plant biomass. Although Cd accumulation increased with S treatment, it was accompanied by enhanced antioxidant responses, scavenging reactive oxygen species (ROS) and malondialdehyde. S application increased the production of thiol-containing compounds, including γ-glutamylcysteine, glutathione, and phytochelatins, which helped chelate Cd and sequester it in vacuoles, particularly in roots. Additionally, S supplementation altered the essential nutrient composition in rice tissues, particularly the uptake of N, P, and K, while influencing levels of Ca, Mg, and other essential elements. S supplementation enhanced rice tolerance to Cd stress by reestablishing ROS balance, activating thiol-based detoxification pathways, and regulating mineral nutrient balance. Furthermore, sulfur (S) exhibited a dual effect in plants, enhancing cadmium (Cd) uptake while also promoting its detoxification, underscoring its role in improving crop resilience in contaminated soils. Full article

The widespread occurrence of macrolide antibiotics (MLs) in aquatic environments poses potential ecological risks; however, the interactive effects of MLs, especially combined MLs on microalgae and their removal mechanisms, remain poorly understood. This study investigated the removal efficiency, physiological–biochemical responses, and molecular mechanisms of Chlorella pyrenoidosa under single and combined exposure to erythromycin (ERY) and roxithromycin (ROX) over 14 days. The results demonstrated that antibiotic removal efficiency was concentration-dependent and higher in low-concentration treatment. The removal rates of ERY (0.15 mg/L) and ROX (0.02 mg/L) reached 100% and 66.86%, respectively. Notably, in the combined low-concentration group, the presence of ROX promoted the degradation of ERY, with the removal being 11.06–14.77% higher than in single treatment. Conversely, in high-concentration combined treatments (1.63 mg/L ERY + 0.5 mg/L ROX), the removal of ERY was inhibited and the removal of ROX was comparable with the corresponding single treatment. High-concentration treatment groups and combined-treatment groups significantly inhibited microalgae growth and total chlorophyll content, modified the chlorophyll composition, and induced severe oxidative stress. Correlation analysis revealed that antibiotic removal was positively correlated with cell density, chlorophyll content, CAT, CYP450, and GST activities while negatively correlated with SOD, ROS, and MDA. Transcriptomic analysis revealed significant disruption of xenobiotic metabolism pathways, photosynthesis-related processes, and DNA replication/mismatch repair pathways. Key genes involved in stress signaling (e.g., MKK3, MPK3), detoxification (e.g., CYP97, GSTP), and photosynthesis (e.g., HemL) were differentially regulated, providing molecular evidence for the observed physiological responses and removal behaviors. These findings provide valuable insights for the ecological risk assessment of antibiotic mixtures and the development of microalgae-based wastewater treatment technologies. Full article

Titanium dioxide (TiO₂) has evolved from a conventional photocatalyst into a sophisticated nano-platform that bridges environmental sustainability and biomedicine. This paper proposes a unified interfacial redox design framework that links the electronic-structure engineering of the TiO₂ with the spatial control of its reactive oxygen species (ROS). In the environmental sector, we highlight advances in photocatalytic detoxification, such as the cleavage of organophosphates via Ag-modified TiO₂, driven by doping and metal–support interactions. In the biomedical domain, TiO₂ is framed as an active bio-interface capable of coordinative protein binding. We specifically examine the “moonlighting” protein dihydrolipoamide dehydrogenase (DLDH) as a model for stable, oriented biofunctionalization. By integrating RGD-targeting motifs, these hybrid systems enable integrin-directed, localized photodynamic effects. We further address critical toxicological considerations, emphasizing that TiO₂ behavior is context-dependent and governed by particle size, crystallinity, and surface state. By synthesizing insights from catalysis and redox biology, this manuscript outlines principles for the rational design of safer, application-specific TiO₂ technologies. This convergence supports a transition from non-selective oxidation toward predictable, spatially confined redox outcomes in both complex environmental matrices and physiological systems. This review outlines key mechanistic insights and proposes design principles for controlled and context-dependent TiO₂ activity. Full article

Background/Objectives: Many chronic diseases, including cancer, can be developed in conjunction with excessive intracellular oxidative stress and persistent inflammation. The importance of preventive strategies is highlighted by the potential of phytochemical interventions to mitigate these diseases. The purpose of this study was to investigate how Citrus depressa leaf (CDL) extracts can prevent 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced carcinogenesis in JB6 P+ mouse skin epidermal cells. Methods: CDL extracts were prepared and characterized for their phenolic and flavonoid contents. Effects of the potent extract on cell viability, TPA-induced colony formation, intracellular reactive oxygen species (ROS) levels, and nuclear factor erythroid 2–related factor 2 (Nrf2)-related protein and mRNA expression, mediated by epigenetic modifications, were evaluated in JB6 P+ cells. Results: Both the water extract (CDL-WE) and the 95% ethanol extract (CDL-95EE) contain abundant flavonoids that inhibit TPA-induced cell transformation and colony formation without minimal cytotoxicity. Mechanistic studies indicated that CDL-95EE increased the gene expression of Nrf2-related detoxification and antioxidant enzymes, such as UDP-glucuronosyltransferase 1A (UGT1A) and heme oxygenase-1 (HO-1), and decreased intracellular ROS accumulation. Furthermore, CDL-95EE reduced the expression of epigenetic modifiers, including DNA methyltransferases (DNMTs) and histone deacetylases (HDACs), suggesting involvement in epigenetic regulation. Conclusions: These findings indicate that CDL, an agricultural by-product, may be useful in cancer prevention through antioxidant and epigenetic mechanisms. Full article

Apis cerana is widely managed in apiculture in Southern China but experiences substantial colony losses during prolonged summer heat. Developing effective strategies to support colony over-summering is therefore critical. This study demonstrates that dietary supplementation with melatonin significantly enhances thermal tolerance and extends worker lifespan in A. cerana under heat stress. Laboratory bioassays revealed that melatonin supplementation (20 µg/mL) markedly improved worker survival at both 35 °C and 37 °C, with the most pronounced effect at 37 °C, where mortality was significantly reduced. Consistently, field trials demonstrated that melatonin supplemented colonies gained significantly more weight during summer heatwaves than colonies without melatonin supplementation. Mechanistically, melatonin orchestrates a biphasic adaptive response. In an early phase (day 4), melatonin rapidly upregulates heat shock proteins (HSC70-4, CRYAA, l(2)efl) and detoxification enzymes (GST-like), accompanied by reduced reactive oxygen species (ROS) accumulation and enhanced proboscis extension response (PER), indicative of preserved sensory function. This is followed by a later maintenance phase (day 11), characterized by sustained upregulation of fatty acyl-CoA reductases (FAR1, FAR11-like, FARwat) and peroxisomal components (PMP34), which promote lipid remodeling and membrane stabilization. RNA-seq analysis identified differentially expressed genes (DEGs) significantly enriched in pathways related to redox homeostasis, lipid metabolism, detoxification (GSTs, CarEs, CYP450s), and longevity. These molecular responses were associated with enhanced antioxidant capacity, reduced oxidative damage, and sustained foraging activity under thermal stress. Collectively, these results indicate that melatonin serves as a potent nutritional intervention that reprograms redox metabolic networks to mitigate heat-induced damage, extend worker longevity, and enhance colony productivity under climate warming. These findings highlight melatonin’s potential as a practical tool to reduce summer colony losses in apiculture. Full article

ZmSIG2A is a nuclear-encoded plastid sigma factor 2A in maize (Zea mays L.) that is essential for plastid gene transcription and chloroplast biogenesis. As a key regulator of chloroplast development and function, ZmSIG2A may also contribute to the coordination of plant growth and environmental adaptation; however, its roles in root development and stress responses remain largely unclear. We compared two ZmSIG2A mutants, eal1-1 (hypomorphic) and ems110 (nonsense). eal1-1 had increased root number and longer roots, while ems110 had normal root number but shorter roots and failed to mature. The zmsig2a^Val480del transcript was upregulated in eal1-1, and the root-promoting effect of OsSIG2A in rice suggests a conserved role in monocot root growth. DAP-seq indicated that zmsig2a^Val480del targets are involved in metabolism, transport, signaling, and antioxidants, with Chr4 peak clustering near multiple LRR-RLKs, suggesting a ZmSIG2A–LRR-RLK module in root development and stress integration. Physiologically, eal1-1 showed increased antioxidant enzyme activities and reduced MDA, indicating enhanced ROS scavenging, while ems110 exhibited decreased enzyme activities and elevated MDA, indicating compromised ROS detoxification. Upstream, Y1H and dual-luciferase assays demonstrated that the Mediator subunit ZmMed31 positively regulates transcription from the ZmSIG2A promoter. Given Mediator’s role in bridging transcription factors and the core transcriptional machinery, ZmMed31 likely links hormone-responsive transcription factors to the ZmSIG2A regulatory network. Collectively, we propose a stress-responsive ZmMed31–ZmSIG2A–LRR-RLK module that underpins maize root development and drought adaptation, offering mechanistic insight and potential targets for stress-resilient breeding. Full article

Selenium (Se) is a trace element with a narrow margin between beneficial effects and stress from toxic effects. The determinants of the transition from selenium adequacy to toxicity remain unknown. Moreover, the roles of selenoproteins and other adaptive responses also remain unclear. The effects of dynamic and localized redox fluctuations on survival and neurodegeneration also require further investigation. To better understand the underlying mechanisms, several studies utilized the nematode Caenorhabditis elegans (C. elegans) as a model. This review systematically addresses pivotal mechanistic controversies. Thioredoxin reductase-1 (TRXR-1) is the only protein in a small amount of the selenoproteome, and it also has a fully conserved selenocysteine insertion mechanism. Moreover, this systematic review also incorporates the current understanding of the molecular factors that determine selenium homeostasis, ranging from neurotoxicological diseases to biosynthetic circumstances. TRXR-1 supports health benefits such as enhance lipid metabolism, longevity, and stress response. During acute selenium toxicity, TRXR-1 is not needed for survival. Instead, cells defend against adverse effects by using the HIF-1 pathway. Reactive oxygen species (ROS) and hydrogen sulfide (H₂S) inhibit the prolyl hydroxylase EGL-9 in high-selenium conditions, stabilizing HIF-1 and initiating a transcriptional detoxification process independent of the selenoprotein mechanism. Finally, this review also discuss selective neurotoxicity, a condition in which degeneration that occurs solely in cholinergic ventral cord motor neurons plays a distinctive and precarious role among trace elements. Full article

Background/Objectives: Lung cancer remains a major global health burden, largely driven by cigarette use. Although electronic cigarettes (e-cigarettes) are viewed as safer alternatives due to their reduced chemical load, growing evidence shows their vapor can disrupt cellular transcriptomes, including long noncoding RNAs (lncRNAs). In this study, we examined the regulation and function of vape-associated lncRNA transcript 1 (VALT1), a novel transcript upregulated in the oral transcriptomes of e-cigarette users and similarly elevated in non-small-cell lung cancer (NSCLC) tumors. Methods: Publicly available RNA-seq datasets were analyzed, and VALT1 was identified as an e-cigarette-responsive lncRNA. Its dose-dependent induction by e-cigarette smoke extract (eCSE) and cytoplasmic localization were confirmed via RT-qPCR. Its effects on cancer-associated phenotypes including proliferation, ROS detoxification, resistance to apoptosis, migration, cytoskeletal disorganization, and nuclear remodeling were assessed through overexpression and siRNA-mediated knockdown in A549 and BEAS-2B cells. Results: Acute eCSE exposure induced a biphasic, dose-dependent increase in VALT1 expression, accompanied by enhanced proliferation, ROS detoxification, apoptosis resistance, migration, cytoskeletal disorganization, and nuclear remodeling in A549 cells. VALT1 overexpression reproduced these phenotypes in both cell lines without eCSE treatment, whereas knockdown attenuated them. VALT1 promoted survival under cytotoxic stress in A549 but not BEAS-2B cells. Conclusions: These findings support an active role for VALT1 as an e-cigarette vapor-upregulated transcript that contributes to its phenotypic readout and enhances cellular survival under extracellular chemical stress—thereby aggravating tumorigenic phenotypes even in the absence of mutations that contribute to malignant transformation. Full article

Heat stress is a key environmental factor that adversely affects plant growth, development, and productivity. Nitrate reductase (NR), encoded by AtNIA1 and AtNIA2, plays a crucial role in nitric oxide (NO) biosynthesis, which mediates stress responses in plants. In this study, we investigated the roles of AtNIA1 and AtNIA2 in regulating plant heat stress tolerance. Under heat stress conditions, Arabidopsis thaliana plants maintained higher relative water content and chlorophyll levels, whereas atnia1 and atnia2 mutants exhibited greater physiological damage. Oxidative stress markers such as MDA and H₂O₂ accumulated to higher levels in nitrate reductase mutants than in Col-0, indicating increased heat sensitivity. Gene expression analysis further revealed a pronounced late-phase induction of MBF1c in atnia2 plants, accompanied by altered expression of heat shock proteins. These results suggest that nitrate reductase-dependent pathways contribute to heat stress tolerance by regulating water status, membrane stability, ROS detoxification, and heat shock gene expression. This study provides new insights into NR-mediated NO signaling in thermotolerance and highlights potential targets for improving crop resilience under rising temperatures. Full article

Abiotic stresses disrupt redox homeostasis and reduce crop productivity. Antioxidant networks support resilience by limiting excess reactive oxygen species (ROS) and maintaining redox signalling for stress perception, gene expression, and metabolic reprogramming. We summarize advances (2000–2025) in ROS generation, detoxification mechanisms, and signalling across organelles, including chloroplasts, mitochondria, peroxisomes, and the apoplast. This includes compartmentalized enzymes—superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase (APX), glutathione peroxidase (GPX), and glutathione reductase (GR)—as well as the peroxiredoxin–thioredoxin system and non-enzymatic buffers like ascorbate, glutathione, tocopherols, carotenoids, and flavonoids. We uniquely synthesize these findings in a compartment-resolved “redox rheostat” model, linking ROS concentration–time windows (signaling vs. damage) to antioxidant network design (kinetic tiers, compartmentation, and trade-offs) and identifying intervention points for breeding, genome editing, and field-scale priming. We emphasize constraints, such as NADPH supply and antioxidant recycling capacity, that lead to context-dependent outcomes. We evaluate omics, transgenic strategies, genome editing (CRISPR and Cas systems), exogenous applications, and plant–microbe associations. This synthesis clarifies how antioxidant systems protect photosynthetic and respiratory machinery while supporting signalling, thus outlining routes to climate-resilient, yield-stable crops across varied environments and stresses. Full article

Ovarian cancer progression is strongly influenced by tumour hypoxia and associated oxidative stress. Experimental evidence indicates that cysteine availability supports ovarian cancer cell fitness under hypoxic conditions, yet the quantitative integration of cysteine metabolism, redox control, and energetic maintenance remains incompletely understood. We present a reduced mechanistic mathematical model describing intracellular cysteine allocation between glutathione (GSH) synthesis and hydrogen sulfide production under experimentally imposed hypoxia. The model integrates extracellular cysteine uptake, GSH-dependent reactive oxygen species (ROS) detoxification, hypoxia-amplified ROS generation, and redox-modulated ATP maintenance. Parameter estimation was performed using experimentally derived extracellular metabolite fluxes measured over a 24 h interval. Uncertainty was assessed via bootstrap resampling, and variance-based sensitivity analysis was conducted within (patho)physiologically constrained parameter domains. The calibrated model reproduces extracellular fluxes with relative deviations below 7% and identifies GSH synthesis capacity as the dominant determinant of ATP maintenance within experimentally supported ranges. Hydrogen sulfide (H₂S) production exerts a secondary stabilising influence, whereas hypoxia-driven ROS amplification negatively impacts energetic state. Numerical continuation across hypoxia levels reveals distinct qualitative response regions but does not imply a formal bifurcation structure. Importantly, intracellular metabolite dynamics are inferred as latent variables consistent with extracellular constraints and established biochemical knowledge; the model does not uniquely identify intracellular pool sizes or enzyme kinetics. The framework therefore provides flux-consistent mechanistic plausibility rather than direct intracellular validation. This systems-level analysis supports cysteine allocation as a quantitatively influential control point in hypoxic adaptation and establishes a constrained modelling framework for subsequent metabolic network expansions and experimental validation. Full article

Soil salinization poses a major constraint to global agriculture. Apocynum venetum, a salt-tolerant halophyte, provides an effective model for investigating salt-adaptive strategies; however, the temporal dynamics of its tolerance-associated genes and metabolites remain unclear. In this study, integrated transcriptomics, metabolomics (UHPLC-MS), physiological assays, and weighted gene co-expression network analysis (WGCNA) were conducted to characterize early (7-day) and late (18-day) responses to 200 mM NaCl stress. NaCl stress significantly reduced chlorophyll content while increasing Na⁺ accumulation, MDA levels, antioxidant enzyme activities (SOD and CAT), and total flavonoid content. Early responses (NaCl7) were marked by accumulation of ferulic acid, rhamnetin, and 3,4-dihydrocoumarin, with activation of plant hormone (ABA, auxin, zeatin) and MAPK signaling pathways. Late responses (NaCl18) exhibited increased accumulation of scopoletin, formononetin, and caffeyl-alcohol, with enrichment of phenylpropanoid biosynthesis, glutathione metabolism, and photosynthesis-related pathways. WGCNA identified early-response hub genes, including AOC, MAPKKK17/18, CYP98A, and CCoAOMT, coordinating stress signaling and antioxidant metabolism. Late stress responses involved genes like CPK, GST, CYCD3, and ARF, modulating calcium signaling and ROS detoxification. Genes shared across phases included CYP90C1, HD-ZIP, HSP20, and PP2C, regulating protein stabilization and stress signaling. These findings reveal a two-phase salt tolerance strategy in A. venetum, integrating early signaling and late metabolic adaptation. Full article

A new category of polyphenolic compounds, like flavonoids, phenolic acids, phenylpropanoids, terpenoids, and others, referred to as food nutrients, may counteract the harmful effects of micro- and nanoplastics (MNPs) by enhancing cellular stress resilience response and overall human health. These compounds found in functional food help mitigate the cellular damage, inflammation, and oxidative stress caused by MNP exposure, which can contribute to pathological conditions, including diabetes. Importantly, specific food nutrients are able to activate, at the minimum dose, the nuclear factor erythroid-derived 2-like 2 (Nrf2) to prevent or block MNP-induced damage. The Nfe2l2 gene encodes the Nrf2 transcription factor, acting as a master regulator of redox homeostasis by inducing antioxidant response element (ARE)-driven resilience genes, which in turn, promote the expression of detoxification enzymes like heme oxygenase-1 (HO-1), NAD(P)H: quinone oxidoreductase 1 (NQO1), and glutathione S-transferase (GST) to scavenge reactive oxygen species (ROS) and shield cells from environmental damage and toxicity. Deregulation of the Nfe2l2 gene due to the accumulation of MNP pollutants may exacerbate the inflammatory conditions associated with diabetes and its chronic complications by rendering cells more sensitive to oxidative stress, apoptosis, and pyroptosis. Furthermore, epigenetic modifications influence gene regulation; chromatin remodeling directly impacts DNA accessibility, allowing or limiting transcription factor access to regulate gene expression. This mechanism may also play a pivotal role in the progression of oxidative stress-related diseases, as it modulates the Nrf2 pathway and the expression levels of its target genes. In contrast to the current literature, which has only addressed the pathological mechanisms induced by MNPs, this research explores, for the first time, how food nutrients interacting with the Nfe2l2 gene can combat or reverse the toxic effects of MNPs in cells, tissues, and organs. The goal is to improve health by attenuating MNP toxicity, which is influenced by individual genetic variations and cellular stress resilience. Full article

Soil salinization, as a key constraint to global agricultural sustainable development, has threatened over one billion hectares of farmland, posing severe challenges to staple crop production. Therefore, this review summarizes important advances in the molecular mechanisms of salt–alkali tolerance from the model plant Arabidopsis thaliana to staple crops (rice, maize, and wheat) and compares the commonalities and differences in physiological structure and molecular regulatory networks among these species. Studies have shown that plants respond to saline–alkali stress mainly through conserved mechanisms, including salt overly sensitive (SOS) signaling pathway-mediated ion homeostasis, accumulation of osmoprotectants, reactive oxygen species (ROS) scavenging, and coordination of multiple hormone signals. However, different species have evolved unique adaptive strategies: Arabidopsis has revealed core regulatory pathways, but its simple root system limits direct application in crops; rice employs root barriers and a stem node “ion filter” to precisely regulate Na⁺ transport; maize utilizes the C4 photosynthetic pathway along with efficient osmotic adjustment and tissue compartmentalization to enhance tolerance; and wheat achieves ion detoxification through TaHKT allele variation and vacuolar sequestration. Looking forward, future breeding for salt–alkali tolerance should adopt a “crop-centric” approach, focusing on the mining and molecular design of superior alleles, combined with gene editing and multi-trait integration, to provide a theoretical basis and strategic support for developing high-yield and stable crop varieties adapted to saline–alkali lands. Full article

Hepatocellular carcinoma (HCC) remains one of the leading causes of cancer-related mortality worldwide, with limited therapeutic options and poor clinical outcomes. Mounting evidence suggests that targeting cancer-specific metabolic and redox adaptations represents a promising therapeutic strategy. Peroxiredoxin 1 (PRDX1), a key antioxidant enzyme that is frequently overexpressed in HCC, enables tumor cells to neutralize excessive reactive oxygen species (ROS), thereby sustaining survival and conferring therapeutic resistance. In this study, using human hepatocellular carcinoma HepG2 cells as an in vitro model, we identify ginsenoside Rg5 (Rg5) as a previously unrecognized small-molecule inhibitor of PRDX1. Structural and functional analyses demonstrate that Rg5 directly binds to the Asn145 residue of PRDX1, effectively suppressing its peroxidase activity. Mechanistically, this inhibition disrupts ROS detoxification in HepG2 cells, leading to mitochondrial ROS accumulation, activation of the intrinsic apoptotic pathway, and consequent HepG2 cell death. Additionally, Rg5 not only suppresses HepG2 cell survival but also acts synergistically with doxorubicin, a first-line chemotherapeutic agent, to markedly enhance antitumor efficacy and potentially mitigate chemoresistance. Collectively, these findings suggest that PRDX1 inhibition may represent a broadly exploitable vulnerability in liver cancer and establish Rg5 as a promising candidate for developing targeted and combinatorial therapies against HCC. Full article