Search Results (293)

Background: Long COVID is a heterogeneous post-viral condition in which persistent neurological, autonomic, cognitive, and psychometric symptoms often occur without clear isolated biomarker abnormalities. This mismatch suggests that disease persistence may be driven not only by changes in individual markers, but by longitudinal reorganization of biological and clinical interactions. Materials and Methods: This observational longitudinal study evaluated patients with persistent symptoms after confirmed SARS-CoV-2 infection at 3 and 6 months. Clinical assessment included neurological examination, Hospital Anxiety and Depression Scale, Beck Depression Inventory, and COMPASS-31. Biomarkers representing hypoxia signaling, oxidative/redox stress, endothelial and renin–angiotensin system activity, glycation-related processes, and complement regulation were analyzed. Correlation analysis, association-level biomarker–clinical network modeling, and complementary Graphical LASSO-based sparse network estimation were used to compare network density, community organization, centrality, and edge rewiring between time points. Results: Conventional paired analysis identified HIF-1$\alpha$ as the only continuous variable with a statistically significant longitudinal change (Wilcoxon statistic = 610.0, $p=0.000350$), whereas association-level network analysis revealed a broader systems-level signal. The association-level biomarker–clinical network preserved a similar global size at 3 and 6 months, with 16 nodes, 27 versus 26 edges, and densities of 0.225 versus 0.217. However, this apparent stability concealed substantial rewiring: 19 edges were shared, 8 were lost, and 7 emerged. Complementary Graphical LASSO analysis with 1000 bootstrap resamples supported this pattern by identifying a conservative sparse conditional-dependency core, including seven shared conditional-dependency edges across time points and selective weakening of four early conditional dependencies. The C3–C4 relationship reversed from negative to positive correlation ($r=-0.618$ to $r=0.618$), indicating marked remodeling of complement-associated regulation. A psychometric–autonomic module involving Beck, HADS I, HADS II, and COMPASS-31 remained stable across both assessments. Conclusions: Long COVID progression was characterized by dynamic remodeling of immune, endothelial/RAS, oxidative-redox, hypoxia-related, autonomic, and psychometric interactions. Longitudinal network analysis identified a systems-level interaction structure that was not captured by isolated biomarker comparisons alone and that was further supported by complementary sparse conditional-dependency analysis. Full article

Asthma is a heterogeneous chronic airway disease in which oxidative stress (OS) plays a central mechanistic role beyond classical immune-mediated inflammation. Reactive oxygen and nitrogen species (ROS/RNS), generated by recruited inflammatory cells and activated airway structural cells, drive epithelial injury, mucus hypersecretion, airway remodeling, and modulate key transcription factors including nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways. This review synthesizes current evidence on the multilevel redox-based determinants of asthma severity, spanning from genetic polymorphisms to circulating biomarkers. We examine serum antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), peroxiredoxins (PRDXs), and the thioredoxin (Trx) system as dynamic indicators of systemic redox status and disease severity, alongside oxidative enzymes including NADPH oxidases and dual oxidases (NOX/DUOX), xanthine oxidase (XO), and myeloperoxidase (MPO) that serve as upstream sources of airway oxidant burden. Functional genetic polymorphisms in antioxidant genes (SOD2, CAT, glutathione S-transferase mu 1/glutathione S-transferase theta 1 (GSTM1/GSTT1), heme oxygenase-1 (HO-1), NAD(P)H quinone dehydrogenase 1 (NQO1), nuclear factor erythroid 2-related factor 2/Kelch-like ECH-associated protein 1 (Nrf2/KEAP1)) and oxidative enzyme genes including nitric oxide synthase 1/2/3 (NOS1/2/3), MPO, cytochrome b-245 alpha chain (CYBA), and xanthine dehydrogenase (XDH) are reviewed as modulators of individual redox capacity and asthma susceptibility, with particular attention to gene–environment interactions. We further discuss oxidative damage biomarkers, including malondialdehyde (MDA), 8-isoprostanes, 4-hydroxynonenal, 8-oxo-7, 8-dihydro-2′-deoxyguanosine, protein carbonyls, 3-nitrotyrosine, and advanced oxidation protein products as indicators of lipid, DNA, and protein oxidation that correlate with disease activity and control. The roles of micronutrient cofactors in modulating antioxidant enzyme function and their potential as contextual biomarkers are also addressed. Additionally, emerging evidence on microRNAs (miRNAs) linked to OS biology in asthma is presented. Finally, we critically evaluate the challenges limiting clinical translation, including biomarker non-specificity, analytical variability, gene–environment complexity, and the absence of standardized reference ranges. This integrated framework supports the development of multilevel redox prognostic panels combining genetic, enzymatic, and oxidative damage readouts for improved asthma phenotyping, severity stratification, and personalized therapeutic approaches. Full article

Aging is the dominant risk factor for most chronic diseases, yet the mechanisms driving this relationship remain poorly integrated across biological scales. Existing frameworks have catalogued key hallmarks of aging but do not explain how these processes converge to produce organism-level decline and multimorbidity. A systems-level framework is introduced in which aging is conceptualized as progressive destabilization of interacting regulatory networks. Mitochondrial quality control, nutrient-sensing pathways, and chronic inflammatory signaling form a putative high-centrality network core: mitochondria coordinate redox balance, bioenergetics, and transcriptional adaptation, while NAD⁺-dependent signaling and NLRP3 inflammasome activation propagate perturbations across regulatory layers. This architecture provides a mechanistic basis for the convergence of neurodegenerative, cardiovascular, metabolic, and oncological phenotypes as emergent consequences of shared network instability. Reframing the hallmarks as coupled network nodes shifts the explanatory focus from isolated mechanisms to system-level resilience and non-linear dynamics. This narrative and conceptual review integrates evidence across mitochondrial biology, metabolic signaling, and inflammatory pathways to develop these arguments, with explicit acknowledgment that the proposed framework is hypothesis-generating rather than formally validated. Interventions targeting high-centrality nodes, including mTOR modulation, NAD⁺ restoration, mitophagy activation, and anti-inflammatory strategies, may exert system-wide effects by reconfiguring network dynamics rather than correcting individual pathways. This perspective suggests that biomarker-stratified, network-calibrated interventions may offer a broader systems-level therapeutic rationale than single-pathway approaches. Full article

Heart failure (HF) is fundamentally a disease of energetic insufficiency, in which impaired mitochondrial efficiency, maladaptive metabolic remodeling, and disrupted intercellular signaling converge at the organ level to limit cardiac performance. Despite advances in pharmacologic and device-based therapies, current treatment paradigms largely modulate hemodynamics or neurohormonal pathways rather than directly restoring myocardial bioenergetic capacity. Emerging evidence positions extracellular vesicles (EVs) as endogenous regulators of cardiac energy homeostasis, capable of orchestrating coordinated metabolic and mitochondrial adaptations across cardiac and non-cardiac cell populations. This review advances a system-level framework in which EVs are conceptualized as bioenergetic therapeutics, i.e., active biological agents that reprogram cellular energy utilization, substrate flexibility, and mitochondrial efficiency, rather than passive carriers of isolated molecular cargo. We synthesize preclinical evidence demonstrating EV-mediated modulation of oxidative phosphorylation, glycolytic balance, redox signaling, and mitochondrial dynamics, and examine how these effects scale from cellular and small-animal models to clinically relevant heart failure phenotypes. Importantly, we highlight organ-level integration, wherein EV signaling interfaces with vascular, immune, and metabolic networks to reshape myocardial energetic demand and supply. By bridging mechanistic insights with translational considerations, this review addresses the central question of how EV-driven bioenergetic reprogramming can be deployed within contemporary HF treatment paradigms. We propose EV-based strategies as complementary or synergistic interventions capable of restoring energetic resilience, reframing heart failure therapy beyond structural repair toward systemic metabolic renewal. Full article

Postoperative wound complications remain a major cause of morbidity, prolonged hospitalization, increased healthcare costs, and reduced quality of life. While traditional wound dressings functioned primarily as passive barriers against contamination and exudate, advances in wound biology have transformed surgical wound management. Tissue repair is now recognized as a dynamic immunometabolic process involving coordinated interactions among immune cells, stromal populations, extracellular matrix remodeling, mechanotransduction, mitochondrial function, redox balance, microbial ecology, and bioelectrical signaling. Consequently, modern wound dressings are increasingly designed as bioactive systems capable of actively modulating the wound microenvironment. Recent developments in biomaterials science, immunoengineering, nanotechnology, extracellular vesicle biology, bioelectronics, and artificial intelligence have enabled the creation of advanced wound platforms, including stimuli-responsive hydrogels, immunomodulatory biomaterials, nanozyme-based dressings, conductive scaffolds, oxygen-generating matrices, extracellular vesicle-loaded systems, and biosensor-integrated interfaces. Therapeutic strategies are progressively shifting from antimicrobial-focused approaches toward immune-regenerative modulation targeting chronic inflammation, mitochondrial dysfunction, ferroptosis, cellular senescence, and impaired mechanobiological signaling. This review examines emerging surgical wound dressings from mechanistic, translational, and biomaterial perspectives, highlighting current innovations, translational challenges, and future directions. Collectively, these technologies may enable intelligent therapeutic systems capable of sensing and directing tissue regeneration in real time. Full article

While vanadium redox flow batteries (VRFBs) are considered a promising technology for grid-scale energy storage, the combined influence of electrical load and electrolyte flow rate on overall system performance is often simplified in existing models. A MATLAB/Simulink-based system-level model of a 1 kW vanadium redox flow battery (VRFB) was developed to investigate the influence of load variation and electrolyte flow rate on battery performance. The model accounts for the flow-dependent behavior of key electrochemical parameters, including open-circuit voltage, internal resistance, and polarization losses. State of charge (SOC) is estimated using the Coulomb counting method, and a lumped first-order thermal model is included to represent stack temperature dynamics. The impact of auxiliary pump power is also considered to provide a realistic assessment of system efficiency. Results show that increasing the electrolyte flow rate from 5 LPM to 30 LPM reduces concentration polarization and improves voltage stability, leading to an increase in stack-level electrical efficiency from approximately 85% to more than 92.5%. However, the improvement in overall system efficiency becomes less pronounced at higher flow rates because of the nonlinear increase in pump power consumption.Thermal analysis indicates that stack temperature rise is mainly influenced by electrical loading, whereas higher electrolyte flow contributes to enhanced heat removal and produces only a slight reduction in overall stack temperature. The study highlights the importance of considering both electrochemical performance and auxiliary energy consumption when evaluating VRFB systems and provides useful insights into the coordinated operation of load and electrolyte flow conditions. Full article

Burn wound healing is a complex and dynamic process involving coordinated regulation of inflammation, oxidative stress, angiogenesis, and tissue remodeling. Polygonum cuspidatum, a traditional Chinese medicinal herb widely used for trauma- and inflammation-related disorders, represents an important source of bioactive compounds for tissue repair. Piceatannol (PIC), a naturally occurring stilbene constituent of P. cuspidatum, possesses potent anti-inflammatory and antioxidant activities; however, its therapeutic potential in burn wound healing remains insufficiently understood. In the present study, the therapeutic effects and underlying mechanisms of topical PIC were investigated using a murine deep second-degree burn model combined with multiple skin-related cellular models, including keratinocytes, fibroblasts, endothelial cells, and macrophages. PIC markedly accelerated wound closure and improved histological architecture, as evidenced by reduced inflammatory infiltration, enhanced collagen organization, and increased neovascularization. Mechanistically, PIC suppressed NF-κB activation and modulated KEAP1/NRF2-associated redox signaling, thereby alleviating inflammation–oxidative stress crosstalk during wound healing. In keratinocyte–fibroblast co-culture systems, PIC inhibited fibroblast-to-myofibroblast transition, reduced α-smooth muscle actin (α-SMA) expression, and attenuated excessive collagen deposition, suggesting anti-fibrotic activity. In addition, PIC promoted endothelial tube formation through activation of the STAT3–VEGF signaling axis. Collectively, these findings demonstrate that PIC facilitates burn wound repair through coordinated anti-inflammatory, antioxidative, pro-angiogenic, and anti-fibrotic effects. This study provides pharmacological support for the therapeutic potential of P. cuspidatum-derived compounds in burn management and highlights PIC as a promising candidate for topical treatment of burn injuries. Full article

Prostate cancer remains a major therapeutic challenge, particularly after progression to castration-resistant disease, where persistent androgen receptor signaling, metabolic adaptation, immune escape, and treatment resistance jointly limit clinical benefit. Regulated cell death (RCD) is increasingly recognized not only as an endpoint of tumor cell elimination but also as a dynamic regulator of prostate cancer progression, therapeutic vulnerability, and tumor–immune interactions. In this review, we propose an immunometabolic framework in which androgen receptor signaling, lipid and redox metabolic reprogramming, oxidative stress, and therapeutic pressure converge to shape the susceptibility of prostate cancer cells to distinct RCD modalities. We focus on autophagy and ferroptosis as two extensively studied and translationally relevant pathways, while also discussing emerging roles of necroptosis, pyroptosis, and cuproptosis. Particular attention is given to how RCD-associated signals, including damage-associated molecular patterns, inflammatory mediators, and lipid peroxidation products, may remodel the tumor immune microenvironment and influence the transition between immune-cold and immune-inflamed phenotypes. We further summarize RCD-targeted therapeutic strategies, including ferroptosis induction, autophagy inhibition, nanodrug delivery systems, rational combination therapy, and biomarker-guided patient stratification. Finally, we discuss key translational barriers, including context-dependent biological effects, limited clinical validation, tumor heterogeneity, adaptive resistance, and insufficient predictive biomarkers. By integrating cell death biology with metabolic reprogramming, immune remodeling, and therapeutic resistance, this review highlights RCD as a promising but context-dependent therapeutic vulnerability in advanced prostate cancer. Full article

Abiotic stresses, including drought, salinity, alkalinity, temperature extremes, flooding, heavy metals, and emerging pollutants, challenge plant growth and productivity by disturbing water relations, ion balance, redox homeostasis, membrane stability, energy metabolism, and developmental progression. Although substantial progress has been made in the identification of stress-responsive hormones, second messengers, kinases, transcription factors, transporters, and metabolic regulators, plant stress adaptation cannot be fully explained by linear signaling cascades or single tolerance genes. A major unresolved question is how early molecular events are reorganized into coordinated physiological and developmental outputs that support survival, recovery, and productivity. In this review, we propose an intermolecular interaction-driven adaptive remodeling framework for plant abiotic stress responses. This framework emphasizes that stress tolerance emerges from dynamic changes in receptor–ligand recognition, protein–protein interactions, calcium decoding, redox-sensitive modification, phosphorylation networks, transcriptional regulation, chromatin-associated control, and metabolite-mediated feedback. We further emphasize ROS as integrative redox switches that connect stress sensing, defense activation, senescence-related transitions, and recovery, and chromatin-associated mechanisms as regulators that may stabilize primed or memory-like adaptive states. We discuss how these interaction networks converge on core signaling hubs, including abscisic acid, reactive oxygen species, Ca²⁺, and kinase/phosphatase systems, and how they remodel stomatal behavior, root architecture, ion and pH homeostasis, redox buffering, metabolism, development, and reproductive resilience. We further highlight how natural variation, multi-omics, genome editing, high-throughput phenotyping, and field validation can translate interaction-centered stress biology into crop resilience. This perspective provides a conceptual bridge between molecular stress perception, network behavior, physiological adaptation, and climate-resilient agriculture. Full article

Aqueous zinc–manganese dioxide (Zn–MnO₂) batteries are undergoing a paradigm shift from traditional ion-insertion mechanisms to a reversible deposition/dissolution process. By leveraging a two-electron transfer (Mn²⁺/MnO₂), this electrolytic system achieves a high theoretical capacity of 616 mAh g⁻¹ and a theoretical operating voltage of 1.99 V. However, the accumulation of dead Mn, electrically isolated inactive phases, and dynamic interfacial pH fluctuations remain critical barriers to cycle life and practical energy density. This review systematizes a trinitarian strategy to overcome these bottlenecks, focusing on interfacial engineering, redox mediator-assisted recovery, and advanced electrode architectures. We evaluate how anion engineering and pH-buffering stabilize reaction pathways, and how diverse mediators (e.g., halogens, metal ions, and organic molecules) chemically rescue inactive manganese. Furthermore, we examine the integration of 3D carbon networks and low-cost hybrid electrodes to sustain high-areal-capacity deposition. To elucidate these complex mechanisms, we highlight multiscale analytical approaches combining synchrotron X-ray techniques and density functional theory (DFT). Finally, we outline a roadmap for applications ranging from grid-scale flow batteries to flexible wearable electronics. This work provides a comprehensive perspective on realizing sustainable, safe, and high-performance zinc-based energy storage. Full article

The increasing penetration of renewable energy sources introduces significant variability, low-inertia behaviour, and operational uncertainty into modern power systems, resulting in frequent frequency deviations and degraded dynamic stability. Conventional Load Frequency Control (LFC) approaches based on fixed-parameter PID controllers often exhibit limited disturbance rejection capability under nonlinear and stochastic operating conditions. This study proposes an enhanced LFC framework that integrates a PID controller optimised using the Flower Pollination Algorithm (FPA) with support from a Unified Power Flow Controller (UPFC) and a Redox Flow Battery (RFB) to improve frequency regulation, damping, and robustness in renewable-integrated low-inertia power systems. This study developed a MATLAB/Simulink single-area power system model comprising governor, turbine, and generator-load dynamics to evaluate controller performance under a 0.01 pu step disturbance, stochastic load variations, renewable energy fluctuations, and ±20% parameter uncertainty conditions. The FPA optimally tuned the PID controller gains using the Integral Time Absolute Error criterion to enhance transient response and disturbance rejection capability. Comparative analyses were conducted against conventional PID and fuzzy-based controllers using settling time, overshoot, RMS deviation, ITAE, and mean frequency deviation indices. Simulation results demonstrate that the proposed FPA–PID + UPFC framework significantly outperforms the conventional PID controller by achieving approximately 66.6% settling-time reduction, 72.1% RMS reduction, and 75.5% ITAE reduction. The proposed framework reduced settling time from 18.46 s to 6.16 s and substantially improved damping performance under stochastic disturbances. The coordinated integration of the UPFC and RFB further enhanced transient stability through dynamic power-flow regulation and rapid active-power compensation during disturbances. Sensitivity analysis under parameter uncertainty and stochastic operating conditions confirmed stable and reliable operation under stochastic disturbances and parameter uncertainty conditions. The proposed architecture, therefore, provides an effective, practically applicable solution for secondary frequency regulation in renewable-rich smart grids, low-inertia transmission systems, microgrids, and future distributed power networks. Full article

Microplastics and nanoplastics (MNPLs) are increasingly recognized as dynamic vectors capable of transporting a wide range of environmental contaminants, as well as acting as physical particulates. Their small size, high surface reactivity and strong sorption capacity allow them to carry metals, pesticides, pharmaceuticals and endocrine-active compounds into biological systems. This narrative review examines how these particle-contaminant complexes influence oxidative stress, inflammatory signaling and endocrine function during early development. Relevant literature was identified through structured searches of PubMed, Scopus, Web of Science and Google Scholar, with a focus on the physicochemical properties of plastics, sorption mechanisms, gut barrier physiology and developmental toxicology. Early developmental stages are particularly sensitive, as immature mucus layers, permeable epithelial junctions and underdeveloped detoxification pathways facilitate the uptake and systemic distribution of MNPLs. Once internalized, these particles and their chemical cargo promote the generation of reactive oxygen species through redox-active contaminants, surface-catalysed reactions and mitochondrial dysfunction. The resulting oxidative imbalance activates stress-responsive pathways, including Nrf2–Keap1 signaling, and promotes lipid peroxidation, DNA damage and cellular dysfunction. MNPLs also stimulate inflammatory cascades by activating pattern-recognition receptors, altering cytokine profiles and disrupting epithelial homeostasis. These responses are intensified in the presence of sorbed pollutants, leading to sustained inflammatory states that can be particularly detrimental during organogenesis and immune maturation. Endocrine function is likewise affected, as MNPLs transport hormonally active chemicals and can interfere with hormone-responsive pathways through oxidative and inflammatory mechanisms. These interactions may disrupt thyroid signaling, metabolic regulation and the development of the reproductive axis, with potential long-term physiological consequences. Integrating evidence from polymer chemistry, contaminant behavior and developmental physiology, this review shows that MNPLs act as biologically active vectors that may increase oxidative, inflammatory and endocrine disturbances during early development. These findings highlight the importance of considering particle–contaminant interactions as a critical component of early-life risk assessment. Full article

The efficient conversion of methane into hydrogen-rich syngas is essential for sustainable energy; however, integrating methane partial oxidation (POM) with the water–gas shift (WGS) reaction remains a significant challenge due to thermal and kinetic mismatches. This research presents a spatially decoupled dual-bed reactor configuration, utilizing Ni/GDC and Cu/GDC catalysts, to achieve synergistic hydrogen production. Unlike conventional physically mixed systems, which suffer from thermal hotspots and the unintended promotion of the endothermic Reverse Water–Gas Shift (RWGS) reaction, the dual-bed architecture effectively segregates the reaction zones. Advanced characterization, including O₂-TPO and Raman spectroscopy, reveals that the GDC support acts as a critical oxygen buffer via the Mars-van Krevelen mechanism, modulating the dynamic redox state of the active metal sites to prevent deep oxidation and carbonaceous deactivation. Furthermore, macroscopic performance and carbon–oxygen mass balance analyses confirm that this rational architectural design facilitates a seamless integration of POM and WGS pathways, resulting in significantly maximized H₂ yield. From a broader engineering perspective, this dual-bed strategy offers a practical, low-complexity alternative to intensive integrated technologies such as sorption-enhanced reforming (SER) or chemical looping, providing a robust and scalable framework for durable, high-efficiency hydrogen production. Full article

Groundwater contamination by redox-sensitive elements (RSEs) such as arsenic (As), chromium (Cr), vanadium (V), and selenium (Se) pose a critical challenge in alluvial aquifers, where seasonal hydrological forcing drives dynamic hydrogeochemical and redox conditions. This study investigates the seasonal evolution of groundwater hydrogeochemistry and multi-metal behavior in shallow aquifers of the Mid-Gangetic Plain, India, with particular emphasis on the role of seasonal redox decoupling. Monsoon conditions were dominated by strongly reducing environments (ORP: −150 to −70 mV), predominantly Ca–Mg–SO₄ and Na–Cl type facies. Under these conditions, significant correlations among RSEs in particular (As–V, As–Se) indicated coupled mobilization governed by the reductive dissolution of Fe–Mn (oxyhydr)oxides. Monsoon groundwater also exhibited strong associations between RSEs and agronomic indicators (NO₃⁻, SO₄²⁻), suggesting the influence of recharge-mediated agricultural inputs on redox-sensitive geochemical processes. In contrast, post-monsoon conditions showed a clear transition to sub-oxic states (ORP up to +121 mV) and were dominated by Ca–Mg–HCO₃ facies, accompanied by substantial increases in bicarbonate (~372%), electrical conductivity (~62%), and total dissolved solids (~21%). Despite the partial oxidation of the aquifer system, redox-sensitive metals did not respond uniformly. Instead, inter-element correlations weakened or disappeared, indicating a transition from coupled to decoupled contaminant behavior. Arsenic concentrations increased up to 20.8 µgL⁻¹, whereas Cr and V displayed variable enrichment controlled by alkali-induced desorption and carbonate-mediated surface interactions. This transition reflects seasonal redox decoupling, whereby seasonal redox shifts lead to metal-specific rather than coordinated multi-metal behavior. We propose a Seasonal Redox Decoupling Framework (SRDF) to explain the shift from coupled reductive release during monsoon conditions to selective mobilization pathways in the post-monsoon period. These findings demonstrate that seasonal redox shifts control not only metal concentrations but also inter-element relationships, leading to metal-specific risk profiles. This underscores the need for seasonally adaptive monitoring and management strategies in hydrologically dynamic alluvial aquifers. Full article

The flooded rice rhizosphere is a continuous reactive interface composed of sediment, porewater, root-surface oxic microdomains, and iron plaque, where redox processes and Fe cycling regulate Cd/As speciation, bioavailability, and plant accumulation. Engineered nanomaterials (ENMs) have shown potential for reducing Cd/As uptake in rice, but the coupled roles of microbial community responses, iron-plaque gating, and cross-interface elemental migration remain insufficiently integrated. This review synthesizes the current evidence on ENM transformation and partitioning at flooded rhizosphere microinterfaces, focusing on front-end speciation changes, root-surface retention, microbial functional regulation, and plant sequestration or transport. Correlative evidence suggests that rhizosphere microorganisms are associated with altered redox conditions, Fe cycling, As methylation potential, and metabolite secretion, which may influence Cd/As partitioning and cross-interface migration. However, direct causal validation of the complete ENM transformation–microbial response–Fe cycling–Cd/As flux–grain accumulation sequence within a single integrated system remains lacking. We further discuss how elevated CO₂, micro-/nanoplastics, Fe/DOM dynamics, and water management regimes may modify this framework, and we identify Sb as a theoretical boundary case because direct ENM–rice evidence remains limited. Finally, we highlight the need to integrate spatial tracing and imaging methods, including persistent luminescence tracing, LA-ICP-MS, NanoSIMS, and µ-XRF/µ-XANES, with metaomics to connect particle localization, microbial function, and contaminant fate. Full article