Search Results (694)

Using a three-factor orthogonal design, we investigated the transcriptomic and histological responses of triploid rainbow trout (Oncorhynchus mykiss) gills across three salinities (10, 20, and 30 ppt) over 60 days, with temperature and body size as background conditions. Results showed that 20 ppt was associated with extensive transcriptional reprogramming, with 3333 differentially expressed transcripts (DETs), whereas 30 ppt induced only 120 DETs; WGCNA further identified salinity-correlated modules involved in ion transport and ribosome biogenesis. Histological alterations remained within physiological ranges with no salinity-dependent severity gradient, as confirmed by semi-quantitative scoring. These findings demonstrate that triploid rainbow trout gills employ distinct molecular strategies at medium versus high salinity. Within the 10–30 ppt range examined, 20 ppt was the salinity at which transcriptional reprogramming was most active, suggesting that this intermediate salinity warrants further investigation as a potential acclimation stage. Full article

Objectives: Heart failure (HF) arises from multiple interrelated pathological processes. Among these, lysosomal impairment and loss of autophagic homeostasis are increasingly recognized as important contributors to myocardial damage and ventricular remodeling. This study sought to identify lysophagy-associated signature genes in HF and to define their biological roles, cellular origins, and potential diagnostic relevance. Methods: Bulk myocardial transcriptome datasets, including GSE16499, GSE57338, and GSE76701, were integrated with the human cardiac single-cell dataset GSE145154. Differential expression analysis was first performed to identify lysophagy-related differentially expressed genes (DEGs). Candidate hub genes were then screened using support vector machine-recursive feature elimination (SVM-RFE) and least absolute shrinkage and selection operator (LASSO) regression. Functional enrichment analysis, Gene Set Enrichment Analysis (GSEA), immune infiltration assessment, single-cell transcriptomic mapping, and regulatory network analysis were subsequently conducted. The expression profiles of the selected genes were validated in a murine HF model, and VAMP8 overexpression assays were performed in H9c2 cells. Results: Five hub genes, namely VAMP8, STX2, MCOLN1, DERL1, and PTP4A2, were consistently and markedly decreased in failing myocardial tissue. These genes were mainly linked to SNARE-dependent vesicle trafficking and lysophagy regulation. A diagnostic model incorporating these hub genes demonstrated good discriminatory performance in both the training dataset and a small independent validation cohort, supporting further evaluation of their potential diagnostic value. Single-cell analysis further indicated that these genes were primarily enriched in cardiac FOLR2⁺ tissue-resident macrophages (TRMs). Pseudotime and cell–cell communication analyses associated this module with FOLR2⁺ TRM cell states and predicted interactions with cardiac stromal cells. In the HF mouse model, the mRNA levels of all five hub genes were decreased, with concurrent reductions in VAMP8, MCOLN1 and DERL1 protein expression. In Ang II/LLOMe-induced H9c2 cells, VAMP8 overexpression was associated with reduced cardiomyocyte injury, attenuation of changes in the abundance of lysosome- and autophagy-related proteins, and fewer ultrastructural abnormalities, suggesting a potential cardioprotective effect. Conclusions: VAMP8, STX2, MCOLN1, DERL1, and PTP4A2 were identified as candidate molecular markers of HF that reflect alterations in a lysophagy- and vesicular-transport-related program associated with FOLR2⁺ tissue-resident macrophages. These findings provide new insights into immune-microenvironment remodeling in HF and suggest potential directions for mechanistic and therapeutic investigations. Full article

Impaired amyloid-β (Aβ) clearance across the blood–brain barrier (BBB) is a major contributor to Aβ accumulation in Alzheimer’s disease (AD). P-glycoprotein (P-gp) has been identified as a key BBB efflux transporter involved in Aβ clearance, whereas emerging evidence suggests that organic anion transporting polypeptide 1A2 (OATP1A2) and its rodent counterparts, such as Oatp1a4, may participate in the influx component of Aβ transport. Nuclear factor erythroid 2–related factor 2 (Nrf2) and pregnane X receptor (PXR) are important transcriptional regulators of oxidative stress responses, xenobiotic metabolism, and transporter expression and may therefore modulate OATP1A2 and P-gp expression at the BBB. However, the mechanisms by which Nrf2–PXR crosstalk may regulate OATP1A2/P-gp expression in BBB endothelial cells under AD-relevant pathological conditions, as well as the consequences of this regulation for Aβ transport homeostasis, remain incompletely understood. This review summarizes current evidence linking P-gp, OATP1A2/Oatp1a4, Nrf2, and PXR to BBB transporter homeostasis in AD. A “net-effect” model is further proposed, in which Nrf2–PXR crosstalk may shift the BBB transporter balance toward enhanced P-gp-mediated efflux and reduced OATP1A2-associated influx. Because several key components of this model, particularly OATP1A2-mediated Aβ influx and BBB-specific Nrf2–PXR regulation, remain insufficiently validated, this model should be regarded as a mechanistic framework for future experimental investigation rather than as an established pathogenic pathway. Clarifying this regulatory axis may provide new insights into BBB dysfunction and impaired Aβ clearance in AD and may help identify potential molecular targets for therapeutic intervention. Full article

Auxin response factors (ARFs) are key transcription factors regulating plant growth and development, but their functions and molecular mechanisms in stem elongation of cucurbit crops remain unclear. In this study, we identified a nuclear-localized ARF member, ClARF4, in watermelon. ClARF4 knockout lines were generated using CRISPR-Cas9 technology and exhibited significant reductions in plant height, internode number, and internode length. Cytological analysis indicated that the dwarf phenotype resulted from inhibited longitudinal cell elongation in stems. Transcriptome analysis revealed that ClARF4 modulates cell size by regulating the expression of genes involved in auxin signaling and response pathways. Furthermore, using yeast two-hybrid screening, we identified ClPetC, a component of the photosynthetic electron transport chain, as an interacting protein of ClARF4; bimolecular fluorescence complementation (BiFC) assays further confirmed their direct interaction in the plant nucleus. This study not only reveals the key role of ClARF4 in regulating plant height in watermelon, but also provides important insights into the function of chloroplast–nucleus signaling crosstalk in plant architecture establishment by identifying the interaction between ClARF4 and the chloroplast protein ClPetC in the nucleus. Full article

Abdominal fat deposition is an important economic trait in meat ducks, but the molecular mechanisms underlying individual variation in abdominal fat rate remain unclear. In this study, abdominal fat traits were measured in 316 male Pekin ducks, from which six ducks with high abdominal fat rates and six ducks with low abdominal fat rates were selected for transcriptomic and metabolomic analyses of abdominal adipose tissue. Considerable individual variation in abdominal fat rate was observed in the population, providing a phenotypic basis for divergent group selection. Transcriptomic analysis identified 549 differentially expressed genes, including 181 upregulated and 368 downregulated genes in the LF group relative to the HF group. Functional enrichment analysis revealed that these genes were mainly involved in lipid metabolism, fatty acid metabolism, glycerolipid and glycerophospholipid metabolism, triglyceride metabolism, cholesterol metabolism, lipid transport, and the PI3K-Akt signaling pathway. Among the representative candidate genes, FASN, AGPAT1, ELOVL4, PEMT, PLTP, LCAT, LIPA, and LIPG were upregulated, whereas FABP5 and FABP6 were downregulated in the HF group relative to the LF group. Metabolomic analysis detected 222 differential metabolic features. The putatively annotated metabolites among these features were mainly associated with cholesterol metabolism, primary and secondary bile acid biosynthesis, bile secretion, steroid biosynthesis, alpha-linolenic acid metabolism, PPAR signaling, and adipocytokine signaling pathways. Integrated transcriptomic and metabolomic analysis further highlighted potential gene–metabolite modules related to lipid synthesis/remodeling, cholesterol–bile acid metabolism, and lipid signaling. Overall, these findings provide an exploratory molecular framework for subsequent validation of abdominal fat deposition in Pekin ducks. The proposed candidate genes and putatively annotated metabolites require validation in independent duck populations and further functional studies. Full article

Peroxisome proliferator-activated receptors (PPARs) are ligand-activated nuclear transcription factors comprising three isoforms—PPARα, PPARγ, and PPARβ/δ—that regulate hepatic lipid metabolism, glucose homeostasis, inflammation, bile acid synthesis, and fibrogenesis. Because liver diseases involve overlapping metabolic, inflammatory, cholestatic, and fibrotic pathways, PPAR agonists have emerged as a versatile therapeutic class across a spectrum of hepatic conditions. PPARα agonists (e.g., fenofibrate) promote fatty acid β-oxidation and suppress de novo lipogenesis; PPARγ agonists (e.g., pioglitazone) improve insulin sensitivity and exert anti-inflammatory and antifibrotic effects; and PPARδ agonists (e.g., seladelpar) regulate bile acid and cholesterol metabolism. Dual agonists (elafibranor [PPARα/δ] and saroglitazar [PPARα/γ]) and pan-PPAR agonists (lanifibranor [PPARα/γ/δ] and bezafibrate) aim to simultaneously address multiple pathogenic mechanisms. In primary biliary cholangitis (PBC), elafibranor and seladelpar received accelerated FDA approval in 2024 based on phase 3 trials (ELATIVE and RESPONSE, respectively), demonstrating significant biochemical response rates of 51% and 62% versus 4% and 20% with the placebo. Long-term open-label extension data from the ELATIVE trial have demonstrated sustained improvements in cholestatic biomarkers and stabilization of fibrosis markers over three years, with durable benefits on fatigue and pruritus. The ASSURE open-label study has confirmed the durability of seladelpar’s effects on biochemical response and pruritus through up to two years of treatment. Saroglitazar, a dual PPARα/γ agonist, has shown positive topline phase 3 results in the EPICS-III trial and received an FDA priority review designation. Bezafibrate has shown a survival benefit in large retrospective analyses and is used as a second-line therapy in Europe and Japan; notably, bezafibrate functions as a dual PPAR/pregnane X receptor (PXR) agonist, inducing CYP3A4 and efflux transporters that contribute to bile acid detoxification. In metabolic dysfunction-associated steatotic liver disease (MASLD)/metabolic dysfunction-associated steatohepatitis (MASH), pioglitazone remains the most extensively studied PPAR agonist, with meta-analytic evidence supporting MASH resolution and fibrosis reduction regardless of diabetes status. Lanifibranor demonstrated histological improvement in the phase 2b NATIVE trial and is currently in phase 3 development (NATiV3). PPAR agonists have also demonstrated therapeutic effects on liver fibrosis inhibition through direct modulation of hepatic stellate cell activation and suppression of fibrogenic signaling. This narrative review synthesizes the molecular pharmacology of PPAR isoforms; the available clinical and preclinical evidence for mono-, dual-, and pan-PPAR agonists; and their therapeutic applications across MASLD/MASH, alcohol-associated liver disease (ALD), PBC, primary sclerosing cholangitis (PSC), intestinal failure-associated liver disease (IFALD), and advanced chronic liver disease (ACLD). The evolution from single-isoform to multi-isoform PPAR agonism reflects the recognition that overlapping pathogenic mechanisms in liver diseases may require broader receptor coverage for optimal therapeutic efficacy. Full article

Breast cancer remains a leading cause of cancer-related mortality worldwide, highlighting the need for novel therapeutic strategies that selectively target tumor cells while minimizing systemic toxicity. Dietary ammonium hydroxide enhancement (AHE) has previously been shown to modulate metabolic pathways in animal studies. However, its potential as a localized anticancer therapy has not been investigated. In the present study, we evaluated the antitumor efficacy and systemic safety of NH₄OH using complementary in vitro and orthotopic breast cancer xenograft models. MDA-MB-231 breast cancer cells and non-tumorigenic MCF10A mammary epithelial cells were treated with increasing concentrations of NH₄OH (2.5–225 µM) to assess dose-dependent effects on cell proliferation, viability, and apoptosis. Following this, MDA-MB-231 cells were orthotopically xenografted into female athymic nude mice and treated by intratumoral injection with NH₄OH using a stepwise dose-escalation regimen (0.01%, 0.1%, and 0.5%; total volume of 20 μL per tumor divided between two injection sites) or phosphate-buffered saline (PBS). Differences between treatment groups of mammary tumors and kidney tissues were analyzed molecularly and histologically. NH₄OH significantly suppressed MDA-MB-231 cell growth and metabolic activity, with minimal effects on MCF10A cells, and induced apoptosis in MDA-MB-231 cells without detectable apoptotic induction in MCF10A cells. In vivo, although tumor volume only showed a non-significant downward trend, histological and molecular analyses demonstrated substantial alterations in tumor biology. NH₄OH treatment induced molecular changes consistent with an antitumor response, including increased Caspase-3 and p53 expression, reduced BCL2 and Ki-67 expression, and attenuation of TNFα, IL-6, and TLR4 inflammatory signaling. Furthermore, the tumor architecture in T-NH tumors displayed increased pale eosinophilic regions and reduced cellular density, suggestive of treatment-associated tumor tissue disruption. Histological analysis of kidney tissue showed no evidence of overt renal toxicity. Indeed, localized NH₄OH administration was associated with reduced renal inflammatory and apoptotic signaling, preserved renal morphology, and increased expression of the ammonia transporters RHBG and RHCG. Cross-sectional morphometric measurements showed decreased area for the distal convoluted tubules in NH₄OH-treated samples. Although this initial preclinical study was limited by a relatively small sample size, further studies are warranted to validate these findings and define the molecular mechanisms underlying NH₄OH-mediated antitumor activity. Collectively, these findings suggest that intratumoral NH₄OH modulates tumor metabolic, inflammatory, and apoptotic pathways associated with a less aggressive tumor phenotype while showing no overt molecular or histological evidence of renal injury, supporting further investigation as a localized metabolic intervention targeting molecular and histological drivers of breast cancer progression. Full article

Xylem, a critical vascular tissue extensively distributed in stems and roots, plays indispensable roles in horticultural plant development. It facilitates water and mineral transport, provides mechanical support through secondary cell wall lignification, and precisely modulates ion homeostasis (e.g., Na⁺/K⁺ balance), thereby enhancing plant resilience to abiotic stresses. Consequently, xylem function directly impacts crop yield and quality. Recent breakthroughs in molecular biology have significantly advanced our understanding of the regulatory networks governing xylem development, including key transcription factors, hormonal signaling pathways (particularly auxin, cytokinin, and brassinosteroids), and their interactions with environmental cues. This review systematically summarizes current progress on the molecular mechanisms underlying xylem differentiation, secondary wall biosynthesis, and stress-responsive vascular adaptation in horticultural species. We further discuss emerging research frontiers, existing technical challenges, and prospective directions, aiming to provide a theoretical framework for genetic improvement and precision cultivation of horticultural crops. Full article

Liposomes are among the most extensively studied delivery systems owing to their biocompatibility, structural versatility, and ability to improve the stability and bioavailability of bioactive compounds. Meanwhile, edible fungal polysaccharides (EFPs), particularly β-glucans and heteropolysaccharides, have attracted increasing interest because of their antioxidant, immunomodulatory, prebiotic, and health-promoting properties. The integration of EFPs with liposomal systems has emerged as a promising strategy for developing multifunctional nanocarriers with enhanced physicochemical stability and biological performance. However, current research remains fragmented, and the mechanisms by which EFP molecular structures influence liposome assembly, stability, gastrointestinal fate, and delivery efficiency are poorly understood. Moreover, existing reviews primarily focus on liposomes or fungal polysaccharides independently, without systematically addressing their interfacial interactions, structure-function relationships, and translational applications. This review provides a comprehensive and critical overview of EFP liposomes, highlighting the interactions between fungal polysaccharides and lipid bilayers, including hydrogen bonding, electrostatic interactions, hydrophobic association, and surface conjugation. The effects of EFPs on liposomal physicochemical properties, encapsulation performance, membrane stability, gastrointestinal protection, mucoadhesion, cellular uptake, and biological activity are further discussed. Emerging applications in targeted delivery, oral delivery, gut microbiota modulation, gut–brain axis regulation, and functional foods are also critically evaluated. Importantly, this review identifies key research gaps, including the lack of quantitative structure-function relationships, limited understanding of biological transport mechanisms, insufficient investigation of microbiota-mediated effects, and challenges in scalable manufacturing. By integrating glycobiology, nanotechnology, and food science, this review establishes a unified framework for the rational design and future development of EFP-based liposomal delivery systems. Full article

Salt stress severely limits plant growth, particularly in woody species. In this study, a time-course transcriptomic analysis (0–24 h NaCl treatment) revealed a clear time-dependent transcriptional reprogramming pattern in Betula platyphylla, characterized by rapid early activation followed by gradual stabilization. The response can be divided into three phases: early stress perception and signaling (1–3 h), mid-stage metabolic and hormonal reprogramming (5–9 h), and late-stage homeostasis and physiological adaptation (12–24 h). Early responses are dominated by signal transduction, the middle phase by metabolic reorganization and enhanced translation, and the late phase by redox and cellular homeostasis. Compared to the limited role of the Dehydration-Responsive Element-Binding protein (DREB) pathway, Abscisic acid (ABA) and Jasmonic acid (JA) signaling appear to play more central regulatory roles. Further analyses revealed the coordinated temporal activation of Reactive oxygen species (ROS), Salt Overly Sensitive (SOS), and ABA pathways: ROS shows an early burst followed by antioxidant activation; the SOS pathway regulates ion homeostasis via the Calcineurin B-like protein (CBL)-CBL-interacting protein kinase (CIPK) module; and ABA signaling progresses from biosynthesis to downstream transcriptional regulation. Protein interaction network analysis further identifies ABA signaling as a central hub integrating Ca²⁺ signaling, ROS metabolism, and ion transport. Overall, B. platyphylla responds to salt stress through a temporally coordinated regulatory network, providing new molecular insights into salt tolerance mechanisms in woody plants. Full article

Variegated sweetpotato leaves are of interest for ornamental and functional-food applications, yet the molecular and metabolic basis of their coloration remains poorly understood. A sweetpotato accession with variegated leaves was found incidentally in the field, with rare and vivid Pink-purple coloration in the apical leaves. To investigate the mechanism underlying this interesting phenotype, this material was maintained in the laboratory, and variegated and normal green leaves from this plant were analysed by transcriptome profiling, miRNA sequencing and metabolome analysis. By integrating differential mRNA expression analysis, target-gene prediction, miRNA sequencing and metabolite identification, we screened candidate miRNA-mRNA modules associated with this leaf-colour formation. Using FDR < 0.05 and |log₂FC| ≥ 1 as thresholds, 49 differentially expressed miRNAs and 692 regulatory relationships involving differentially expressed target mRNAs associated with these miRNAs were identified. Functional annotation indicated that the iba_638_x1- G10133|TU16655 and iba_730_x1- G3592|TU5891 modules were associated with anthocyanin/flavonoid biosynthesis and vacuolar transport, respectively. Metabolome analysis showed that the total relative abundance of flavonoids in Pink leaves was 2.98-fold higher than that in CK, and 28 flavonoids accumulated to more than 2-fold higher levels in Pink than in CK. The differentially accumulated metabolites mainly included anthocyanin glycosides, such as petunidin-3-O-glucoside, delphinidin-3-O-glucoside and cyanidin-3,5-O-diglucoside, and flavonol glycosides, such as quercetin-3-O-sophoroside, isorhamnetin-3-O-glucoside and kaempferol-3-O-sophoroside-7-O-glucoside. These results indicate that the variegated phenotype of Pink leaves is mainly associated with differential accumulation of anthocyanin glycosides and flavonol glycosides. Full article

Surgical procedures create dynamic interfaces between tissues, fluids, gases, and applied materials. Failure to control these interfaces can cause leakage, postoperative adhesion, scar tethering, poor tissue integration, maladaptive host responses, or loss of mechanical support. Hydrogels are attractive surgical materials because their hydrated polymer networks can be engineered for wet-tissue conformity, adhesion, transport, degradation, mechanical compatibility, and local biological activity. However, many hydrogel systems are still evaluated by polymer chemistry, stimulus type, or isolated physicochemical properties rather than by the operative function required at a defined surgical boundary. This narrative review proposes a function-based framework for designing and evaluating programmable hydrogels in surgical-interface control. Four principal functions—sealing, separation, protection, and integration/reinforcement—are linked to dominant failure modes, design priorities, endpoints, and comparator requirements. Hemostatic and other biological activities are treated as primary clinical claims or adjunct programs when they support these interface functions. Responsiveness is distinguished from clinically meaningful programmability using five operational criteria: input relevance, encoded transition, baseline and off-target stability, interface-level output, and matched-control comparison. DNA-based hydrogels are discussed as molecular modules for recognition, assembly, crosslinking, degradation, actuation, and release, mainly within mechanically robust hybrid systems. This framework emphasizes time-resolved, function-specific evaluation under procedure-relevant conditions. Full article

Crohn’s disease (CD) is a chronic inflammatory bowel disease with a rising incidence and prevalence worldwide. It is associated with Mycobacterium avium subspecies paratuberculosis (MAP). Current CD treatment strategies are based on anti-inflammatory therapies, including anti-TNF-α drugs. These treatment options provide short-term benefits and are associated with numerous side effects in CD patients. Manuka honey is distinguished from other honey by its high content of methylglyoxal (MGO). MGO, a reactive metabolite, is also generated endogenously in macrophages during infection through glycolysis; however, the amount is insufficient to neutralize the ongoing infection and subsequent tissue damage. This study examined whether exogenous, low-dose MGO can modulate MAP-driven inflammatory and glycolysis- and lactate-associated markers in infected macrophages. THP-1 macrophages were infected with the CD-associated MAP strain and then treated with MGO doses at defined time intervals. We measured markers of M1-/M2-like phenotype polarization, monocarboxylate transporters, lactate export, antioxidant responses, cytokines, and selected glycolysis- and lactate-associated markers at both the mRNA and protein levels. MGO reduced M1 signaling markers CXCL10 (p < 0.05), TNF-α (p < 0.0001), IL-1β (p < 0.01), and IL-6 (p < 0.0001). Simultaneously, MGO promoted M2 shift, elevating CD206 by 1.20-fold and IL-10 by 7-fold. Low-dose MGO administration was associated with increases in Nrf-2 (1.4-fold), HO-1 (1.4-fold), and IL-1Ra (1.5-fold), while the pro-inflammatory cytokines decreased. Metabolically, MGO downregulated MCT4 (p < 0.01) and reduced lactate export by 30%. These changes were coupled with higher PHD2 (1.4-fold) and decreases in GLUT1 (0.9-fold), PKD1 (0.8-fold), and IL-1β, consistent with attenuated glycolysis- and lactate-associated inflammatory signaling. These results suggest that hormetic concentration of MGO mitigates MAP-induced inflammatory activation while altering glycolysis- and lactate-related signaling markers in infected macrophages. Most importantly, we unraveled the predicted molecular mechanism by which MGO suppresses inflammation and modulates oxidative damage. Full article

Endocrine-disrupting pesticides (EDPs) are environmental toxicants capable of perturbing hormonal homeostasis through multiple molecular and cellular mechanisms. Growing evidence indicates that these compounds contribute to a broad spectrum of adverse health outcomes extending beyond classical endocrine dysfunction. This review critically synthesizes current knowledge on the toxicological mechanisms of EDPs and evaluates epidemiological evidence linking exposure to human disease. Mechanistically, EDPs act through modulation of nuclear hormone receptors, disruption of membrane-associated signaling pathways, interference with hormone synthesis, metabolism, and transport, induction of oxidative stress and mitochondrial dysfunction, and epigenetic reprogramming. These molecular events converge on shared biological pathways that affect multiple organ systems and life stages. Human and experimental evidence associates EDP exposure with reproductive dysfunction, endocrine-related cancers, metabolic disorders, thyroid abnormalities, and neurodevelopmental impairments. Particular concern surrounds exposure during critical windows of susceptibility, especially prenatal development and early childhood, when endocrine systems are highly vulnerable to disruption and developmental programming. Across disease endpoints, recurring mechanisms, including endocrine receptor perturbation, oxidative stress, inflammation, and epigenetic alterations, support a unifying toxicological framework linking diverse adverse outcomes. Despite substantial progress, important uncertainties remain regarding chronic low-dose exposure, non-monotonic dose–response relationships, cumulative effects of pesticide mixtures, and the translation of mechanistic findings into human risk assessment. Future research should integrate repeated biomonitoring, advanced mixture modeling, mechanistic biomarkers, and multi-omics approaches within longitudinal life-course studies. Improved integration of toxicological and epidemiological evidence will strengthen causal inference, refine hazard characterization, and support more protective regulatory strategies for reducing the human health burden associated with endocrine-disrupting pesticides worldwide. Full article

Water availability, light spectral composition, and phytohormones jointly regulate plant morphogenesis and photosynthesis. Light quality can modify stress responses by altering endogenous regulators such as melatonin. However, it remains unclear whether light spectrum modulates melatonin-mediated protection under osmotic stress. Here, we investigated the effects of 1 μM melatonin on cucumber (Cucumis sativus L.) subjected to polyethylene glycol 6000 (PEG-6000)-induced osmotic stress under three distinct photosynthetically active radiation (PAR) spectral compositions. Our results indicate that PAR spectral composition determines both the magnitude and the primary physiological targets of the melatonin response. Under red-enriched illumination, melatonin predominantly enhanced photosystem II performance, evidenced by increased effective quantum yield of PSII [Y(II)] and electron transport rate (ETR), reduced lipid peroxidation, and altered expression of genes involved in antioxidant defense, melatonin biosynthesis, and auxin signaling. Specifically, expressions of SOD, APX, and ARF were upregulated, while SNAT expression was downregulated. Under blue-enriched illumination, melatonin effects were mainly associated with stomatal regulation: stomata remained more open, stomatal area and density increased, proline accumulated, and guaiacol peroxidase activity rose, collectively supporting water balance and gas exchange. These findings suggest that melatonin functions as a light-dependent regulator of cucumber responses to PEG-induced osmotic stress, with its physiological and molecular effects being modulated by the spectral quality of PAR. Full article