Vitamin D signaling has emerged as a significant modulator of neurobiological processes implicated in major depressive disorder (MDD). Beyond its classical functions in calcium homeostasis and bone health, accumulating evidence highlights antioxidant, neurotrophic, and anti-inflammatory effects mediated by vitamin D-dependent pathways in the central nervous system. By influencing neurotransmitter synthesis, neuroinflammatory and redox pathways, as well as neuroplasticity, vitamin D signaling may contribute to mechanisms underlying depressive symptoms. Therefore, this review aims to provide a comprehensive overview of preclinical studies examining the association between vitamin D status or vitamin D-related interventions and antidepressant-like effects in rodent models, exploring the molecular mechanisms potentially involved, and highlighting the role of vitamin D-dependent signaling pathways in modulating key neurobiological targets implicated in MDD. It may contribute to establishing the relevance of vitamin D-related mechanisms to MDD pathophysiology and identifying promising targets for future translational studies.

Arthrospira platensis (Spirulina) has been traditionally consumed in Africa, Asia and Central America as a nutrient-rich restorative food associated with metabolic balance and gastrointestinal health. Its longstanding ethnopharmacological use suggests biological activities related to antioxidant and anti-inflammatory effects, which are relevant in conditions associated with metabolic disorders. This study investigated whether A. platensis supplementation prevents the reduction in ileal relaxant reactivity induced by a hypercaloric diet (HCD) in rats and explored the involvement of prostanoid, nitric oxide and NADPH oxidase pathways in this response. Male Wistar rats were fed standard or hypercaloric diets for eight weeks and treated with A. platensis (25mgkg-1·day-1). Isolated ileum segments were subjected to cumulative concentration-response curves to verapamil in the absence or presence of indomethacin, tempol, L-NAME, 1400W, apocynin or combined L-NAME plus apocynin. Relaxant reactivity was assessed by maximal effect and potency parameters. The hypercaloric diet markedly reduced verapamil-induced relaxant potency, whereas A. platensis supplementation completely prevented this dysfunction without altering responses in healthy animals. In HCD-fed rats, indomethacin, tempol, L-NAME, 1400W and apocynin each fully restored relaxant potency, demonstrating the contribution of prostanoid overactivity, oxidative stress, excessive iNOS-derived nitric oxide and NADPH oxidase-dependent reactive oxygen species to the observed impairment. In supplemented animals, relaxant responses were fully or partially preserved across all pharmacological conditions. These findings provide mechanistic support for the traditional use of A. platensis, demonstrating that its protective effects on intestinal smooth muscle function are mediated by the modulation of convergent inflammatory and redox pathways. The results highlight A. platensis as an ethnopharmacologically relevant natural product with potential for preventing obesity-associated gastrointestinal dysmotility.

Peripheral cannabinoid receptor activation attenuates frostbite-induced chronic pain via modulation of TRP channels, neuroinflammation, and autophagy.

7-ketocholesterol (7-KC) is a highly abundant and biologically active lipid oxidation product that perturbs membrane integrity, sterol homeostasis, mitochondrial function, and redox balance. In parallel, tamoxifen, a cornerstone therapy for estrogen receptor-positive breast cancer, induces not only estrogen receptor antagonism but also pronounced metabolic and organelle-associated stress. Here, we investigated transcriptional responses of breast cancer cell line models to tamoxifen, 7-KC, and their combination. Tamoxifen elicited a shared antiproliferative response in MCF-7 and BT-20 cells, characterized by suppression of cell cycle progression, DNA replication, and mitosis. However, the downstream stress responses diverged markedly between the two models. MCF-7 cells activated adaptive programs, including unfolded protein response, autophagy, and metabolic reprogramming toward glycolysis, consistent with cytostatic survival. In contrast, BT-20 cells exhibited suppression of metabolic and redox pathways accompanied by inflammatory and apoptotic signaling, indicating impaired stress adaptation. Combined tamoxifen and 7-KC treatment further amplified these divergent stress-response phenotypes. Analysis of the correlation of 16 oppositely regulated genes with clinical data of breast cancer patients validated ST8SIA6 as the main candidate associated with adaptive stress tolerance. Overall, our findings indicate that the capacity to integrate metabolic and redox stress determines tumor cell type-specific responses to combined endocrine and oxysterol-induced stress in breast cancer.

Therapeutic potential of nicorandil vs nebivolol in attenuating PKC/P38MAPK signaling via PPARγ/KLOTHO/CREB pathway signaling: molecular docking and experimental validation in rat model of unilateral ureteric obstruction.

BackgroundHypoxia-inducible factors (HIF1α, HIF2α) influence radiotherapy responses in non-small cell lung cancer (NSCLC) and glioblastoma (GBM), tumors characterized by oxygen and HIF expression heterogeneity. As the function of HIFs in normoxic metabolic function remained unexplored, we investigated how loss of HIF1α or HIF2α affects metabolism, redox homeostasis, and radiotherapy sensitivity in normoxia, aiming to identify opportunities for combined metabolic inhibition.MethodsNSCLC HIF1α or HIF2α knockout (KO) and HIFα wildtype (WT) models were analyzed using 13C-glucose mass spectrometry tracing before and after radiotherapy treatment. Metabolic phenotypes were validated using serine/glycine (ser/gly) synthesis enzyme expression by immunoblot and quantitative PCR, redox by ROS flow cytometry analysis, and DNA methylation by 5mC dot-blot assessment. Pharmacological inhibition of ser/gly metabolism was performed in both NSCLC and GBM models using the repurposed serine-glycine conversion inhibitor sertraline using incucyte confluency monitoring.ResultsBoth HIF1α and HIF2α KO cells displayed reduced glycolysis and compensatory ser/gly pathway hyperactivation. HIF1α KO cells channeled ser/gly into nucleotide (particularly TTP) synthesis and glutathione (GSH)-mediated antioxidant defense, conferring radiotherapy resistance. In contrast, HIF2α KO cells preferentially used serine for α-ketoglutarate (α-KG) production, the enhanced NADH/methionine-dependent redox system and the methionine cycle to support enhanced DNA methylation. Subsequently, following irradiation, only the radiation resistant HIF1α KO cells further enhanced ser/gly metabolism, increasing AMP/ATP and GSH/GSSG (oxidized GSH) ratios, whereas HIF2α KO cells failed to adapt and accumulated oxidative stress. HIF1α KO cells were more sensitive to pharmacological inhibition of ser/gly metabolism by sertraline, particularly in combination with irradiation, which abrogated their radioresistant phenotype in both NSCLC and GBM models.ConclusionsHIF1α-deficient cells rely on ser/gly synthesis for nucleotide production and antioxidant defense, promoting radiotherapy resistance while creating vulnerability to sertraline plus irradiation. HIF2α-deficient cells favor α-KG production and methionine-driven alternative redox and methylation pathways. Targeting ser/gly synthesis may overcome HIF-gradient–dependent radiotherapy resistance.Graphical abstractSupplementary InformationThe online version contains supplementary material available at 10.1186/s40170-026-00433-6.

From rapid reduction to stable immobilization: A regenerative 4D FeMgAl layered double hydroxide-microbial strategy for chromium remediation.

MXenes have gathered immense scientific attention due to their unique combination of high electronic conductivity, hydrophilicity, and reduced dimensionality. While considerable advances in synthetic methodologies, achieving rapid, high-yield production of dispersible monolayer MXenes with controllable in-plane structure remains a daunting challenge. Herein, we report an ultrafast radical-intensified selective etching (RISE) tactic that enables one-step mild synthesis of monolayer Ti3C2Tx MXene bearing customized in-plane nanoholes with near-quantitative etching efficiency (∼99.9%) within merely 3h. By fine-tuning the dosage of H2O2, which generates hydroxyl radicals (·OH) in situ, defect-lean monolayer MXene was made in a high yield of 81.6%. Liters of such colloidal dispersion of monolayer MXene were obtained within hours, which could be readily processed into conductive films with improved oxidation resistance. Mechanistic studies reveal that the RISE protocol follows a radical-driven redox pathway fundamentally distinct from traditional proton-mediated etching routes. As a proof of concept, holey MXene-derived conductive films demonstrated an exceptional desalination capacity of 32.71mg g-1 in capacitive deionization, outperforming most pure MXene-based electrode materials. Our method can potentially revolutionize the prevailing wet chemical etching protocol used for a decade for yielding monolayer MXene and establishes a swift pathway toward customizable MXene architectures for energy and environmental applications.

Graphite cathodes enable high-voltage operation in dual-ion batteries but are intrinsically constrained by a single-electron chemistry and sluggish anion intercalation. Here, an iron-chloride-intercalated graphite stabilized by oxygen functional groups is shown to establish a pre-activated, cascade multi-electron redox pathway. Sequential oxidation of iron and chlorine at intermediate potentials simultaneously expands interlayer spacing and redistributes electronic density, creating a favorable host for high-voltage PF6 - intercalation. This synergistic activation enables an average transfer of 2.61 electrons per redox event, breaking the intrinsic one-electron limit of graphite. As a result, the cathode delivers up to 5V (vs. Na/Na+) with a stable capacity of 52 mAh g-1 at 3 A g-1, significantly outperforming conventional graphite cathodes (15 mAh g-1). By integrating multi-electron redox chemistry with anion storage, this approach unlocks a new direction for high-power electrochemical energy storage.

Abstract Adolescent depression is increasingly prevalent, and the ongoing neurodevelopmental remodeling of the adolescent brain confers heightened vulnerability to stress. Accumulating evidence indicates that stress acts as a primary upstream driver that converges on synaptic dysfunction through tightly interconnected metabolic, inflammatory, and redox pathways. Across prenatal, early-life, and adolescent stress models, stress exposure disrupts synaptic maturation and emotional regulation, with maternal stress and intergenerational effects further amplifying risk during adolescence. At the mechanistic level, stress-induced mitochondrial dysfunction and impaired energy metabolism initiate oxidative imbalance, leading to excessive reactive oxygen species accumulation and weakened antioxidant capacity. These metabolic disturbances synergize with neuroimmune activation—characterized by microglial reactivity, inflammasome signaling, and pro-inflammatory cytokine release—to destabilize synaptic structure and plasticity. Concurrently, dysregulated iron homeostasis exacerbates oxidative damage and ferroptosis-related processes, reinforcing a self-propagating pathological loop that converges on impaired synaptic plasticity, including deficits in long-term potentiation/long-term depression, dendritic spine maintenance, and neurogenesis. Together, these findings support a unified stress–metabolism–inflammation–iron–synapse cascade underlying adolescent depression. Future studies should focus on resolving causal relationships, delineating developmental stage–dependent amplification effects, and integrating multi-omics with clinical evidence to inform early, mechanism-guided interventions and prevention strategies.

The clinical management of non-small cell lung cancer (NSCLC) is of major challenge due to the contribution of ALDH-positive non-small cell lung cancer to tumor aggressiveness, metastasis, and resistance to therapy. The FDA-approved alcohol aversion agent disulfiram (DSF) has been shown to be promising in preclinical models aiming to treat tumor in the animal model but its efficacy in vivo is limited by poorly understood molecular targets in ALDH+NSCLC. Our hypothesis is that DSF will act on important nodes within the oncogenic (EGFR/MAPK), inflammatory (COX-2) and redox pathways which maintain ALDH+stemness. To evaluate this, network pharmacology was used and determined 137 common targets to exist between DSF and NSCLC-related genes. Analysis of protein-protein interaction has identified the following central hubs: EGFR, PTGS2 (COX-2), and MAPK1. These targets were found to bind DSF with very high affinity (7.45 -6.15 -6.65kcal/mol, respectively) in comparison to reference inhibitors (Erlotinib, Celecoxib, Sorafenib). The RMSD values remaining below 2.1Å, MMGBSA analysis, and consistent energy gyration profiles, supporting the stability of the DSF-target complexes. DSF (IC50=2.5μM) experimentally caused a significant decrease in phosphorylation of EGFR, ERK1 (MAPK1) and COX-2 in NSCLC cells. The article presents mechanistic support to the multi-target effect of DSF in ALDH+NSCLC through inhibition of EGFR, COX-2, and MAPK1, potent agents of stemness and resistance to drugs. It is believed that the reuse of DSF would be effective in treating NSCLC therapeutic resistance and promote its use in practice.

Electrochemical sensor-based analysis of NRF2/SLC7A11/GPX4 redox pathways in high-glucose conditions: Implications for Salidroside-mediated osteoporosis protection

Abstract Background Pulmonary hypertension (PH) causes chronic elevation of right ventricular (RV) afterload, driving progressive remodeling associated with poor clinical outcomes. Cardiac fibroblasts regulate extracellular matrix (ECM) composition and fibrosis, yet their temporal and regional transcriptional programs during RV adaptation remain poorly defined. We hypothesized that RV fibroblasts display temporally regulated transcriptional programs during hypoxia-induced pulmonary hypertension that are not shared with fibroblasts from the left ventricle (LV) or septum. Methods C57BL/6 mice were exposed to hypobaric hypoxia (18,000 ft) for 3, 7, or 21 days (n = 2 males and females each timepoint). RV, LV, and septum were analyzed by single-cell RNA sequencing (10X Genomics Chromium Fixed RNA Profiling). Fibroblasts were examined using the SLIDE (Significant Latent Factor Interaction Discovery and Exploration) framework to identify latent transcriptional programs across three intervals: normoxia-3 days (early), 3-7 days (intermediate), and 7-21 days (chronic). Gene ontology and clustering analyses were performed to define dynamic pathways of fibroblast activation. Results Following hypoxia, fibrosis-associated genes (Postn, Col1a1, Tgfb1, Acta2, Meox1) were selectively upregulated in the RV with a 7-day peak, indicating region-specific activation despite equivalent exposure across cardiac chambers (Figure 1). From normoxia-3 days, RV fibroblasts displayed a uniform stress-response characterized by cytokine-STAT3 (Osmr, Stat3, Tlr3), ER-stress (Hspa5, Manf, Hsp90aa1), and early matrix-remodeling (Eln, Loxl2, Adamtsl2, Col1a1, Col3a1) pathways. From 3-7 days, SLIDE analysis identified two distinct fibroblast populations: one cluster enriched for 3-day fibroblasts exhibited higher expression of stress-adaptive programs consistent with acute activation of redox and proteostatic pathways, while a second cluster composed of roughly equal proportions of 3- and 7-day fibroblasts showed lower expression of antioxidant and ER-stress-response genes (Mt1, Mt2, Hspa5, Manf, Hyou1), suggesting a transition from early stress-responsive fibroblasts to a matrix-oriented, lower-stress phenotype by day 7. From 7-21 days, fibroblasts further diversified into eight transcriptionally distinct subtypes with dominant antioxidant, proteostatic, metabolic, stress-inflammatory, contractile, matrix-modulating, and biosynthetic programs. Conclusions Although all cardiac regions experienced the same hypoxic stimulus, RV fibroblasts uniquely activated profibrotic gene programs, revealing intrinsic regional susceptibility that may underlie the selective remodeling seen in PH. SLIDE analysis revealed dynamic transitions in RV fibroblasts: an early stress-response phase, a transitional phase with divergence into stress-adaptive and matrix-producing populations, and a late phase composed of specialized phenotypes. Distinct from identity-based clustering, SLIDE uncovered latent transcriptional programs that define progressive shifts in fibroblast states during hypoxia-PH RV remodeling, identifying potential therapeutic windows for selective modulation of fibroblast activation. This abstract is funded by: Janssen Pharmaceutical Companies of Johnson and Johnson ATS Early Career Investigator Award in Pulmonary Vascular Disease Program

Melaleuca alternifolia (Australian tea tree) sits at a rare intersection of ethnomedicine and modern pharmacology. Rooted in Bundjalung Aboriginal practice for respiratory, dermatologic, and wound care, its essential oil (TTO) has since been validated as a multi-target agent. We synthesize advances spanning cultivation ecology, chemistry, mechanisms, and translation. Chemotyped oils (ISO 4730) are dominated by terpinen-4-ol-supported by γ-/α-terpinene, 1,8-cineole, and selected sesquiterpenes-whose coordinated actions destabilize microbial membranes, impair energy metabolism, modulate redox and inflammatory pathways (PPAR-γ, Nrf2-ARE), and, in cancer models, trigger mitochondrial apoptosis and autophagy. Across pathogens, TTO displays antibacterial, antifungal, antiviral, and antiparasitic activity, including effects on drug-resistant biofilms and ectoparasites (e.g., Demodex, scabies, head lice). Inflammation and oxidative stress are dampened via NF-κB/MAPK restraint and antioxidant support, aligning with clinical signals in dermatology and wound care. Crucially, nanotechnology (nanoemulsions/nanoemulgels, chitosan-alginate hydrogels, lipid nanocarriers, electrospun fibers) converts volatile, irritancy-prone oil into a controllable payload with improved stability, targeted release, and safety, while enabling co-delivery with standard drugs for dose-sparing synergy. Remaining gaps include chemotype standardization, exposure-response definition at target sites, and adequately powered, indication-specific trials with patient-centered endpoints. We outline priorities for quality control, rational combinations, and engineered delivery, and note how data-driven tools (e.g., composition-activity modeling) can accelerate optimization. Altogether, TTO exemplifies how cultural knowledge, ecological stewardship, and formulation science can converge to yield a next-generation phytotherapeutic for anti-infective, wound, dermatologic, and emerging anticancer applications.

Integrative Astral-DIA proteomics and transcriptomics reveal candidate salt-tolerance genes in the halophyte Hordeum marinum.

Cardiac ischemia induces substantial metabolomic reprogramming, which dysregulates cardiomyocytes (CMs) and non-myocyte stromal cell populations. The stromal cells derived from epicardial adipose tissue (EAT) and ventricle are critical for extracellular matrix (ECM) remodeling, paracrine signaling, and myocardial homeostasis. However, the metabolomic content and responses of EAT-derived stromal cells (EATDS) and ventricular stromal cells (VSCs) remain unknown. This study employed untargeted liquid chromatography-mass spectrometry (LC-MS)-based metabolomics to characterize ischemia-driven metabolic reprogramming in EATDS and VSCs harvested from swine hearts. Ischemia was simulated using the standard ischemic buffer (pH 6.2) for 2h. Metabolomic screening revealed 65 and 68 metabolites, respectively, for EATDS and VSCs. Results revealed extensive downregulation of amino acid biosynthesis, redox pathways, and mitochondrial metabolism, alongside selective upregulation of glycolytic and cofactor-associated metabolites. Pathway enrichment analyses indicated significant suppression of the TCA cycle, one-carbon metabolism, glutathione cycling, and branched-chain amino acid degradation, reflecting impaired bioenergetic and antioxidant capacity. Adaptive responses included the enrichment of glycolysis, β-alanine, and glyoxylate/dicarboxylate metabolism, consistent with metabolic plasticity under hypoxic conditions. Network-based analyses linked these metabolic shifts to inflammatory pathways. Functional assays demonstrated that sarcosine, pyroglutamic acid, and 3-hydroxypropionic acid modulate the gene expression of cardiac regenerative biomarkers, including GATA4, Nkx2.5, TROP-I, LGALS1, TBX5, and IRX4. These findings suggest that ischemia-induced metabolomic changes exert transcriptional control over cardiac remodeling programs, emphasizing the regulatory potential of metabolite-gene interactions. Such an integrated metabolomic transcriptional response highlights novel therapeutic targets for modulating cellular resilience and heart regeneration following ischemic heart disease.

Glyphosate is one of the most widely used herbicides worldwide and has been increasingly reported in aquatic environments, including riverine, estuarine, and coastal systems. However, information on its intestinal effects in benthic marine invertebrates remains limited. In this study, we investigated dose-dependent intestinal responses of the sea cucumber Apostichopus japonicus following acute waterborne glyphosate exposure using integrated transcriptomic and metabolomic analyses. Sea cucumbers were exposed for 24 h to four nominal glyphosate concentrations: 0, 9.23, 46.15, and 230.77 mg/L. Mortality occurred only in the highest-concentration group, allowing phenotypic stratification of this group into high-dose survivors (HL) and high-dose dead individuals (HD) for downstream multi-omics comparisons. Principal component analysis and orthogonal partial least-squares discriminant analysis indicated clear exposure- and phenotype-associated shifts in intestinal molecular profiles. Differential expression analysis and pathway enrichment showed that low-dose exposure was mainly associated with metabolic and digestion-related adjustments, whereas higher exposure levels were characterized by broader perturbation of immune regulation, stress-response signaling, proteostasis-related processes, and cell fate-associated pathways. Metabolomic profiling further revealed progressive remodeling of lipid, amino acid, energy, redox, and transport-related pathways, with the most extensive alterations observed in HD. Integrated transcriptome-metabolome analysis supported increasingly structured cross-omics covariation with rising exposure severity, highlighting coordinated intestinal system disruption under high-dose glyphosate stress. Overall, these findings demonstrate that acute waterborne glyphosate exposure induces dose-dependent intestinal molecular reprogramming in A. japonicus, with marked divergence between surviving and dead individuals at the highest exposure level. This study provides mechanistic evidence for early intestinal responses to glyphosate in a representative marine deposit-feeding invertebrate and offers a basis for future studies linking controlled exposure experiments with environmentally relevant marine risk scenarios.

HighlightsWhat are the main findings?Punicic acid shows greater cytotoxicity in ovarian cancer cells than in normal cells and may enhance the effects of cisplatin.Punicic Acid induces ferroptosis, alters lipid metabolism, modulates mitochondrial function, and reprograms redox and ferroptosis-associated pathways in ovarian cancer cells.What are the implications of the main findings?This study suggests that combining punicic acid with cisplatin may allow lower chemotherapy doses while maintaining or enhancing antitumor efficacy, potentially improving clinical tolerability.These findings propose mechanisms that may underly punicic acid’s preferential toxicity, providing insight into ovarian cancer cell vulnerabilities.Ovarian cancer (OC) remains the deadliest gynecological malignancy, with aged tumor microenvironments linked to poorer outcomes. Our prior work identified reduced levels of free fatty acids (FFAs) within tumor-surrounding adipose tissue of aged OC xenograft rats compared to younger counterparts. In this study, we investigated the therapeutic potential of one such FFA, punicic acid (PunA). We evaluated PunA’s effects on OC and normal cell viability and compared its activity with that of its structural isomer, α-eleostearic acid (α-ESA). Both compounds decreased OC cell viability; however, α-ESA was cytotoxic to normal cells, whereas PunA selectively impaired OC cell viability while sparing normal cells. Additionally, PunA enhanced cisplatin efficacy, demonstrating its potential for use in combination therapy to reduce cisplatin dosage and toxicity without compromising antitumor activity. Mechanistically, PunA induced ferroptosis in OC cells while sparing normal cells by differently modulating lipid peroxidation, fatty acid oxidation, and mitochondrial function. Transcriptomic profiling further revealed coordinated gene expression changes associated with oxidative stress and ferroptosis in PunA-treated OC and normal cells. In a preliminary C57BL/6J-ID8 OC mouse model, PunA suppressed tumor growth. Collectively, these findings identify PunA as a promising therapeutic candidate for OC, acting through ferroptosis and mitochondrial dysfunction, and enhancing cisplatin efficacy while sparing normal cells.

Abstract Background Plants are continuously challenged by diverse abiotic stresses, which compromise growth, photosynthesis, and nutrient homeostasis. This review aims to elucidate the roles of antioxidant systems and mineral nutrients in stress adaptation, and to highlight the potential of multi-omics approaches to enhance crop resilience. Methods A comprehensive synthesis of current research on enzymatic and non-enzymatic antioxidant mechanisms, nutrient interactions, and stress physiology was performed. Multi-omics datasets—including genomics, transcriptomics, proteomics, metabolomics, ionomics, and miRNomics were analyzed to assess nutrient acquisition, redistribution, and signaling under stress. Genotype-specific responses, stress memory, and ROS–Ca 2 ⁺–hormone cross-talk were emphasized. High-throughput phenotyping and genome-editing strategies were also considered. Results Evidence shows that plants employ integrated antioxidant systems to maintain redox balance and mitigate reactive oxygen species (ROS)-induced damage. Mineral nutrients act as enzymatic cofactors, regulate antioxidant activity, and modulate osmotic adjustment and signaling pathways. In addition, interactions between essential and toxic metals involve both competitive and protective mechanisms that influence metal uptake, transport, and detoxification. Multi-omics studies highlight genotype- and stress-history-dependent responses and reveal complex ROS–Ca 2 ⁺–hormone signaling networks. Conclusions The integration of antioxidant defenses, nutrient homeostasis, and signaling networks is critical for plant resilience under abiotic stress. Multi-omics and advanced phenotyping provide actionable insights for developing nutrient-efficient, stress-tolerant crops. Coordinating redox and nutrient signaling pathways represents a promising strategy to translate molecular basis into agronomic solutions for sustaining productivity under climate change.

Understanding how thermal history influences redox evolutionandchemical fractionation is essential for characterizing high-temperaturecondensation in complex materials, including nuclear debris. Here,we tested the hypothesis that distinct thermal regimes in a plasmaflow reactor influence redox pathways and elemental partitioning internary U/Ce/Cs systems. A configurable plasma flow reactor was modifiedwith an external tube furnace to impose two distinct thermal gradients:continuous ambient cooling and a furnace-assisted thermal hold-upnear 1400 K followed by rapid cooling. Transmission electron microscopycharacterized phase identity, morphology, and nanoscale element distributions,while inductively coupled plasma-mass spectrometry quantified bulkelemental ratios. Across both thermal regimes, uranium and ceriumcondensed as UO2 and CeO2 as dominant refractoryoxide products. Uranium partially oxidized to α-UO3 during extended ambient cooling, while furnace-assisted hold-uppreserved UO2 and produced partial reduction of ceriumto Ce2O3. Cesium remained volatile upstreamand condensed later in the reactor, forming Cs2O and Cs-uranatephases with the highest incorporation after thermal hold-up. BulkICP-MS measurements supported these observations. U/Ce ratios remainedcomparatively stable and Cs displayed delayed and apparent transientenrichment that matched the nanoscale measurements. This integratedapproach provides a quantitative method for linking thermal gradientsto redox evolution and volatility-driven fractionation. These resultsshow how the plasma flow reactor can identify where equilibrium descriptionsremain adequate and where kinetic effects from residence time andtemperature history must be considered when interpreting condensationbehavior in multicomponent systems.