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The influence of natural and synthetic blue food colorants on the human body, including the cardiovascular system, is a complex and not fully understood topic. Considering that various papers have demonstrated that oxidative stress is a crucial step in the development of cardiovascular diseases (CVDs), our experiments on the pro- or antioxidant action of three blue food colorants (one natural colorant—genipin—and two synthetic colorants—brilliant blue FCF and patent blue V) focused on two aspects that are important for the development of CVDs: the level of biomarkers of oxidative stress induced by H₂O₂/Fe²⁺ (the donor of hydroxyl radicals—one of the most aggressive reactive oxygen species produced in humans) in human blood platelets and human plasma, as well as the arachidonic acid cascade in blood platelets stimulated by thrombin (in vitro). Our results demonstrated that two tested blue colorants—genipin and brilliant blue FCF (at four used concentrations: 2, 10, 20, and 200 µM)—reduced plasma lipid peroxidation induced by H₂O₂/Fe²⁺. Moreover, all tested blue colorants (genipin, brilliant blue FCF, and patent blue V; at the concentrations 2, 10, 20, and 200 µM) inhibited lipid peroxidation in blood platelets treated with H₂O₂/Fe²⁺. In contrast, only genipin (at the highest used concentration—200 µM) statistically significantly reduced plasma protein carbonylation induced by H₂O₂/Fe²⁺ (inhibition of this process: about 25%). However, all tested food colorants decreased blood platelet protein carbonylation stimulated by H₂O₂/Fe²⁺, but their action was not always statistically significant. In addition, we noted that all used blue food colorants (1–200 µM) have protector effects on the change in the level of thiol groups in plasma proteins stimulated by H₂O₂/Fe²⁺, but these tested colorants change the level of thiol groups in blood platelets treated with H₂O₂/Fe²⁺ only at the highest used concentration—200 µM. In conclusion, the present study provides the first data on the antioxidant potential of genipin, brilliant blue FCF, and patent blue V in selected elements of blood treated with H₂O₂/Fe²⁺. Earlier and current studies have indicated the promising potential of these blue food colorants, especially genipin (without cytotoxicity toward human blood platelets), which can modify the oxidative stress of platelets and plasma in vitro at concentrations (1–200 µM) which can be obtained in blood during its administration. However, the presented results have limitations, especially concerning the mechanistic clarity surrounding the antioxidant properties of the tested blue food colorants. Therefore, further in vivo experiments are needed to provide a better understanding of their antioxidant potential. Full article

The current study describes the synthesis and preliminary anticancer assessment of a novel series of C3/C28-bis-1,2,4-triazolyl-sulfanylacetate-betulin (AP1–5) derivatives to identify potent agents for clinical development. The cytotoxicity of AP1–5 was evaluated using the Alamar blue assay against MCF-7, A375, PANC-1 (cancer cells) and HaCat (human keratinocytes) cells. Moreover, the molecular mechanisms responsible for cytotoxicity were investigated through in vitro (DCFDA/H₂DCDFA assay, caspase-3/7 assay, and morphological analysis) and in silico assays (network pharmacology, molecular docking, molecular dynamics simulation, and ADMET predictions). The result highlighted AP5, containing unsubstituted 1,2,4-triazoles, as the lead derivative of the series with increased potency against MCF-7, with an IC₅₀ value of 7.41 μM compared to its phenyl-substituted analogs (AP1–4). The derivatives induced apoptosis, marked by fragmented nuclei, round cells, disorganized cytoskeletons, and activation of caspases-3/-7 through a ROS-decreasing mechanism. The network pharmacology assessment predicted AP5 may interact with key proteins in the PI3K/Akt pathway, such as MAP2K1, MDM2, IGF1, JAK2, IL2 and FGFR1, as well as ESR1, PGR and MMP2. Molecular docking suggested MMP-2 is the most favorable target for AP5 among the validated proteins, while molecular dynamics simulations supported the predicted AP5–MMP-2 interaction. Moreover, the ADMET profiling of AP5 showed acceptable intestinal absorption, non-glycoprotein-P substrate status, and reduced hepatic metabolism compared to betulin. However, the ADMET analysis also highlighted some potential toxicity risks such as DILI, genotoxicity, carcinogenicity and skin sensitization that need to be further investigated. Altogether, these promising findings support the further exploration of AP5 as a promising drug candidate for breast cancer in vivo to assess its potency and toxicity. Full article

Global climate warming has intensified in recent years, with extreme weather events occurring more frequently and severely impacting ecosystems and social production. According to the “China Climate Change Blue Book (2023),” China’s temperature rise rate exceeds the global average, with increasingly significant impacts on ecosystems. Hyphantria cunea, an invasive forest pest first discovered in China in 1979, has spread widely, causing serious damage to forestry and agriculture and posing a significant threat to China’s ecological security. To address this threat, this study employed seven modeling algorithms (GLM, GBM, CTA, ANN, SRE, FDA, MARS, RF, and MaxEnt) from the R Biomod2 package to develop an ensemble model. The core research objective of this work is to quantify climate-driven range shifts of H. cunea under ongoing global climate change. Previous nationwide SDM studies on invasive forest pests have consistently demonstrated that climatic variables dominate broad-scale nationwide suitable habitat patterns at the macro-regional level. Supplementary topographic, vegetation cover, and human land-use disturbance layers were incorporated to capture fine-scale habitat filtering effects and long-distance pest dispersal facilitated by human activities, which together fully characterize the suitable regional environments of this pest. By integrating climate, topography, vegetation, and human disturbance data, we predicted the potential geographical distribution of H. cunea in China under four future climate scenarios (SSP1-2.6, SSP2-4.5, SSP3-7.0, and SSP5-8.5). The ensemble model achieved excellent performance with TSS and ROC values of 0.901 and 0.984, respectively. Currently, highly suitable areas for H. cunea are concentrated in 12 provinces, including Shandong, Jiangsu, Hebei, Henan, and Anhui, covering 56.33 × 104 km², with Shandong showing the highest proportion (25.48%). The suitable habitat range is projected to expand northeastward, with significant increases under high emission scenarios (SSP5-8.5). Analysis of environmental variables reveals that nighttime light brightness, precipitation in the warmest season, the seasonal temperature variation coefficient, and average temperature in the driest season are key factors influencing H. cunea distribution. Nighttime light brightness shows the highest contribution (27.7%), indicating significant human impact on species spread. Response curves suggest that H. cunea favors warm, humid areas with pronounced seasonal changes. This study demonstrates that climate change will increase H. cunea expansion risk, necessitating strengthened cross-regional monitoring and biological control techniques. These findings provide a scientific foundation for understanding H. cunea spatiotemporal distribution patterns under future climate scenarios and for developing effective prevention and control strategies. Full article

Chronic inflammation is a key contributor to the pathogenesis of numerous diseases, including cardiovascular, metabolic, and neurodegenerative disorders. Nutraceutical strategies targeting inflammatory pathways are of increasing interest, particularly those based on omega-3 fatty acids. The objective of this study was to evaluate the anti-inflammatory effects of two omega-3-based nutraceutical formulations, Omega 3 Plus and Omega 3 Orange, in primary human monocytes. Primary human monocytes were isolated from peripheral blood of a healthy donor and cultured under standardized conditions. Cells were pre-treated with different concentrations of the test formulations and subsequently stimulated with lipopolysaccharide (LPS, 10 ng/mL) for 24 h. Cell viability was assessed using the AlamarBlue assay. The release of pro-inflammatory mediators, including TNF-α, IL-1β, IL-6, MCP-1, IL-8, and prostaglandin E2 (PGE2), as well as the anti-inflammatory cytokine IL-10, was quantified using ELISA. Both formulations were well tolerated at concentrations up to 2.5%, with no significant cytotoxic effects. LPS stimulation induced a robust increase in inflammatory mediator release. Pre-treatment with Omega 3 Plus and Omega 3 Orange resulted in a significant, dose-dependent inhibition of pro-inflammatory cytokines, including TNF-α, IL-1β, and IL-6 (up to ~70% reduction). MCP-1 was moderately reduced, whereas IL-8 was only minimally affected. Notably, Omega 3 Orange exhibited a pronounced inhibition of PGE2 production (up to ~95%), while Omega 3 Plus reduced PGE2 levels by approximately 80%. Neither formulation induced IL-10 production in unstimulated cells. These findings demonstrate that both omega-3-based nutraceutical formulations exert potent anti-inflammatory effects in primary human monocytes, primarily through the inhibition of pro-inflammatory cytokines and PGE2. The strong suppression of PGE2 is consistent with a possible modulation of pathways involved in prostaglandin synthesis. These results support the potential application of such formulations in inflammation-associated conditions and warrant further mechanistic and clinical investigation. Full article

Reflectance by yellow to red carotenoid-based plumages in birds with ultraviolet-sensitive (UVS) color vision typically shifts to redder (longer) wavelengths as carotenoid consumption (Diet_c) increases. This apparent asymmetric red-shift response implies an overall bias against conceivable shifts to bluer (shorter) wavelengths. However, recent studies among species of Piciformes–Coraciiformes (e.g., woodpeckers, barbets, toucans, bee-eaters, and allies) with violet-sensitive (VS) color vision discovered two kinds of blue shifts between the same plumage and dietary traits. Compared to UVS absolute red shifts (positive slopes at higher Diet_c), VS express absolute (negative slopes at higher Diet_c for yellow and orange plumages) or relative (zero slope for red plumages) blue shifts. These contrasting patterns for different color vision systems suggest that generalized symmetry concepts of opposite (plumage shift) patterns that maintain invariant (Diet_c, perception) processes can be abstracted from physical to biological systems, with positive versus negative responses formalized as “antisymmetries” and relative responses formalized as “broken symmetries”. A subset of VS “true woodpecker” (Picinae) species with known yellow and red plumage-carotenoid chemistries demonstrated similar blue shifts for the main reflectance bands and their independence from phylogeny, sex, and specimen collection year, thus providing key chemical details to further test generalized plumage symmetries. Juxtapositions were facilitated because both yellow and red plumages in true woodpeckers contained comparatively blue- and red-shifted carotenoid types. Despite this parallel, each plumage deployed chemical variations in radically different ways. Yellow plumage contained only chemically defined yellow carotenoids, including intrinsically more red-shifted natives (i.e., hydroxy-xanthophylls) widespread among birds through their diets, and intrinsically more blue-shifted picofulvins (i.e., 7,8-di- and tetra-hydro-carotenoids) probably characteristic of and metabolized by VS birds. Higher absolute and relative (to natives) picofulvin concentrations were significant predictors of absolute blue shifts in yellow plumage reflectance, and were significantly predicted by higher Diet_c. Transitivity implied Diet_c ⟶ native ⟶ picofulvin ⟶ reflectance, such that picofulvins caused absolute blue shifts at higher Diet_c, and natives caused absolute red shifts at lower Diet_c. Moreover, opposite trends for picofulvin and native concentrations in feathers were consistent with the proposed endogenous synthesis of picofulvins from natives. Yellow plumages comprised mainly of picofulvins at very low (from very low Diet_c from ants and termites) or high (from very high Diet_c from fruits) concentrations were especially distinctive for some of these and other interrelationships, suggesting some heterogeneity in yellow pigmentation strategies from dietary idiosyncrasies. Red plumages contained only relatively low concentrations of yellow dietary natives (hydroxy-xanthophylls), but varied widely in the concentration of metabolites of comparatively intermediate (4-oxo-keto-carotenoids) or extreme (4,4′-oxo-keto-carotenoids) redness. However, different red chemistries lacked any corresponding significant relationships with variations in reflectance or Diet_c. Variations in reflectance based on chemical compositions were more visible to humans for yellow than red plumage types, setting minimum salience levels for the more discriminating diurnal avian color visions. Therefore, VS yellow plumage chemistries that emphasize deposition of easily obtained (cheaper) dietary natives at low Diet_c, and of more deliberately synthesized (costly) picofulvin metabolites at higher Diet_c were consistent with several forms of honest signaling in UVS from resource limitations based on Diet_c, including through potential costs and benefits and their trade-offs. Conversely, the diverse chemical compositions and costs of red plumages of similar physical reflectance properties, and evidence that intrinsically orange carotenoids intermediate between red and yellow ones were actively excluded from plumage, suggested that true woodpecker reds were under selection for a convergent appearance. In light of true woodpecker biology, sensory bias, and social and aposematic mimicry are likely mechanisms promoting resemblance. These results extend to the chemical level earlier interpretations of opposite shift patterns as antisymmetries of invariant processes and relative shift patterns as broken symmetries of altered processes for VS vis-à-vis UVS carotenoid-based systems. Full article

While the influence of the urban built environment on public emotions has garnered extensive attention, existing studies predominantly focus on temperate climates or warmer seasons. As a result, they rarely extend their scope to winter-specific emotions in cold-region cities, thereby overlooking the complex human–environment emotional interactions under extreme climates. To bridge this seasonal research gap, this study develops an innovative analytical framework integrating Large Language Models (LLMs) with Multiscale Geographically Weighted Regression (MGWR). Drawing on social media data, this framework leverages the powerful zero-shot reasoning capabilities of LLMs to precisely quantify the two-dimensional emotional characteristics of Valence and Arousal. Concurrently, by incorporating the multi-scale spatial modeling strengths of MGWR, it thoroughly investigates the spatial patterns and driving mechanisms of public emotions within the winter context of typical cold-region cities. The results indicate that, first, extreme climates do not lead to urban emotional suppression; instead, frozen rivers transform into vibrant emotional corridors, with the public demonstrating a high degree of thermal-psychological adaptability. Second, by incorporating winter-specific environmental variables, the research reveals a cold-region paradox of emotional valence. Specifically, under snow cover, lower winter Land Surface Temperature (LST) and winter Normalized Difference Vegetation Index (NDVI) paradoxically evoke positive emotions by reconstructing the aesthetic experience of ice-snow landscapes. Furthermore, the impact of urban service facilities on emotional arousal exhibits a significant pattern of diminishing marginal utility. Overall, the LLMs-MGWR framework achieves a closed loop of high-throughput, multi-dimensional semantic decoding and multi-scale spatial interpretation, demonstrating exceptional cross-regional generalizability. Ultimately, this study not only provides a novel paradigm for understanding human–environment interactions in complex environments but also offers transferable planning guidelines for microclimate design, facility decentralization, and the reshaping of winter blue-green infrastructure in global cold-region cities. Full article

Dopamine dysregulation is connected to several neurological disorders, including Parkinson’s disease, Huntington’s disease, and addiction. A new, precise, accurate, and specific reversed-phase high-performance liquid chromatographic method was developed for dopamine determination in different biological media (human/mouse plasma and mouse brain homogenate). The chromatographic assay was performed using Avantor ACE^® RP-18 (250 × 4.6 mm, 5 µm) column equipped with a suitable ODS pre-column. The temperature was ambient, and the mobile phase was composed of 10 mM potassium dihydrogen phosphate buffer (pH = 3) with 0.25 g/L sodium octanesulfonate, methanol, and acetonitrile at a volume-to-volume ratio of 75:20:5. Isocratic elution mode, flow rate 1.0 mL/min, and ultraviolet detection (280 nm) were applied. The procedure was validated for linearity, and all calibration curves were linear over the selected range with determination coefficients greater than 0.998. Intraday repeatability, expressed as the coefficient of variation, did not exceed 4.88% for the plasma and 3.32% for the mouse brain homogenate samples across all tested concentration levels. The proposed chromatographic method was evaluated in terms of greenness, whiteness, and blueness using three ecological metrics (the Analytical Greenness software, White Analytical Chemistry model, and Blue Applicability Grade Index). The optimized procedure was proven to be suitable for implementation in the routine analytical practice. Full article

Tit species (Paridae) are an important part of urban settlements during winter. We counted wintering tit species from 31 urban settlements along a 920 km latitudinal gradient in Finland during four winters between 1991 and 2020. We observed a total of five tit species, the Great Tit (Parus major), Eurasian Blue Tit (Cyanistes caeruleus), Coal Tit (Periparus ater), Willow Tit (Poecile montanus), and Crested Tit (Lophophanes cristatus) during the surveys. The most common and abundant species were the deciduous forest preferring Great Tit and Eurasian Blue Tit, whereas the coniferous forest preferring species exhibiting a hoarding behavior, the Coal Tit, Willow Tit, and the Crested Tit, were seldom observed, and no Siberian Tits were detected. These results indicated that food-hording coniferous preferring tit species avoided urban areas. The numbers of Great Tit and Eurasian Blue Tit were greater at the end of the study period than in the first two winters studied. The average growth rate (λ) of the Great Tit and Eurasian Blue Tit increased during the winters studied. Our data indicated a greater increase rate of the Great Tit and Eurasian Blue Tit than the Finnish winter bird monitoring work, probably because we only surveyed tits within human settlements. There was a positive correlation between the average growth rate of the Great Tit and the latitude. There was a negative correlation between the changes in average growth rate (λ) of the Eurasian Blue Tit and the changes in built-up area cover within the study areas between winters 1991/1992 and 2019/2020, and vice versa, indicating that the Eurasian Blue Tit population suffered from the increase in built-up area cover. Despite the fact that the total number of winter-feeding sites decreased during the study period, changes in their numbers were not associated with the growth rates of any tit species. The abundance of the Great Tit was negatively associated with building cover and positively associated with winter temperature. The abundance of the Eurasian Blue Tit was negatively associated with building cover and negatively associated with latitude. When controlling for the latitude, the growth rate of the Great Tit increased with the temperature in winter months, indicating that the Great Tit populations have increased in colder study sites. Our results indicated that population trends of tit species may differ regionally, and that changes in urban settlements may modify the abundance of tit species during winter. We did not detect any correlation in population growth rates between species. We recommend conducting more long-term tit research both during the winter and breeding seasons to understand the population dynamics and population trends of tit species across diverse types of habitats in more detail. Full article

Background: Neutrophil dysregulation drives inflammatory pathologies through mechanisms such as matrix metalloproteinase-9 (MMP-9) release. High-value bioprospecting of agro-industrial residues offers a sustainable strategy to identify novel bioactive compounds. In this study, the immunomodulatory effects of seed oils (SOs) obtained via supercritical fluid extraction from Passiflora edulis and Rubus glaucus byproducts on human neutrophil responses was evaluated. Methods: SO lipid profiles were characterized via GC-MS. Human neutrophils were isolated using Percoll gradients and treated with the SOs (10–50 µg/mL). Cytocompatibility was assessed via MTT and trypan blue assays. MMP-9 activity and ERK1/2/p38 phosphorylation were determined via zymography and Western blotting, respectively. Results of GC-MS revealed matrices rich in unsaturated lipids: R. glaucus SO was dominated by linoleic (50.02%) and α-linolenic (29.84%) acids, whereas P. edulis SO contained linoleic (58.91%) and oleic (19.75%) acids. Both oils were highly biocompatible up to 50 µg/mL. Both SOs significantly increased MMP-9 release; notably, R. glaucus induced a dose-dependent response and a potential priming effect at 10 µg/mL. Interestingly, neither oil induced the phosphorylation of ERK1/2 or p38. Conclusions: Supercritical fluid-extracted SOs from P. edulis and R. glaucus byproducts modulate early neutrophil responses by increasing MMP-9 release through pathways independent of classical MAPK phosphorylation. Further functional and in vivo validation is needed to clarify the precise regulatory roles of these specialized lipid matrices in human inflammation resolution and their potential as bioactive ingredients for nutraceutical or pharmaceutical applications. Full article

Traditional acupoint localization methods rely heavily on manual operation, resulting in high subjectivity and limited accuracy. To improve the precision and stability of acupoint detection, this study integrates machine vision technology with in situ projection to achieve automated recognition and real-time visualization of human acupoints. First, an automatic calibration method based on image processing is proposed for back acupoints. Spinal features are extracted from the blue channel, enhanced using adaptive histogram equalization, and processed through region of interest extraction, minimum-threshold binarization, and morphological operations. Key spinal curve points are then fitted using Bézier functions. Canny edge detection is used to extract the human silhouette, locate the acromion, and derive the pixel scale of the “cun” measurement, enabling coordinate computation for 141 back acupoints. In the deep learning component, an improved YOLOv8-Pose model is developed for acupoint localization. Unlike existing methods that use local attention or the original Object Keypoint Similarity (OKS) loss, we introduce two innovations: a non-local attention module for global dependency modeling, and a novel Efficient Object Keypoint Similarity (EOKS) loss function that incorporates geometric constraints—namely, width, height, and center distance—in addition to Euclidean distance. A non-local attention mechanism is incorporated into the backbone to enhance global feature extraction, and the EOKS loss function is designed to improve spatiogeometric regression accuracy. An inference mechanism is further introduced to derive the remaining acupoints from 49 detected keypoints; experiments demonstrate that the improved model achieves 95.0% detection accuracy, outperforming the baseline by 2.62%, with an inference time of 14.5 ms. Finally, an in situ projection platform is constructed, combining camera calibration, four-point proportional scaling, and an OpenCV 4.5.4-based interactive interface. The system supports real-time translation, rotation, and scaling, enabling accurate projection of detected acupoints onto the human body. Full article

Background: Pituitary adenylate cyclase-activating polypeptide (PACAP) functions as an anti-atherogenic neuropeptide. Maxadilan, a PAC1 receptor agonist, offers atheroprotection by acting downstream of vascular inflammation caused by hypercholesterolemia. This study aims to explore how PACAP and Maxadilan influence migration and apoptosis in human coronary artery smooth muscle cells (HCASMCs). Methods: To investigate the role of PACAP deficiency in the pathogenesis of atherosclerosis under standard chow (SC) in vivo, PACAP^−/−-mice were crossed with ApoE^−/−-mice to generate PACAP^−/−/ApoE^−/−-mice. The whole aorta was isolated and stained with OilRedO (ORO). Atherosclerotic lesions and lumen stenosis in the brachiocephalic trunk were quantified using ImageJ 1.54p (Fiji). To further investigate the role of PACAP and Maxadilan in the pathogenesis of atherosclerosis with special respect to HCASMC under a lipid-enriched environment, HCASMCs were treated with oxLDL, with or without PACAP or Maxadilan. Uptake and accumulation of oxLDL were analyzed using Bodipy^TM493/503, and cell viability was assessed with PrestoBlue^®. Cell migration was evaluated using the scratch assay and the MRI wound-healing tool in ImageJ (Fiji). Mitochondrial morphology was examined with MitoTracker Green and the MiNA tool in ImageJ (Fiji). Apoptotic processes were analyzed by Western blot, immunocytofluorescence staining, and ELISA. Results: In vivo, PACAP^−/−/ApoE^−/−-mice showed increased lumen stenosis and decreased plaque burden compared with ApoE^−/−-mice. In vitro, PACAP enhanced the viability of oxLDL-treated HCASMCs, while neither PACAP nor Maxadilan influenced lipid content in HCASMCs, regardless of oxLDL presence. Both oxLDL and PACAP slowed cell migration, but Maxadilan increased migration in oxLDL-treated HCASMCs. The protein level of the proliferation marker Ki67 was reduced in cells treated with oxLDL and Maxadilan. Additionally, BAX, which promotes intrinsic apoptosis, was elevated in HCASMCs stimulated with Maxadilan and oxLDL. Investigations of mitochondrial morphology indicated that oxLDL and PACAP increased the individual and network structures, with a decrease in branches per network. Conclusion: Our data highlight the complex role of the PACAP/PAC1 system in vascular pathology and suggest that selective modulation—such as targeted PAC1 activation or PACAP supplementation—could lead to new strategies for stabilizing atherosclerotic plaques. In the long term, this could improve the balance between plaque formation and vascular function. Full article

Urban mangroves are increasingly recognized for their important blue-carbon functions, yet their long-term aboveground carbon dynamics under climate extremes and human disturbances remain poorly understood. Here, we developed an integrated framework that combines multi-source satellite observations, field survey and LiDAR-constrained modeling to reconstruct annual species composition, canopy structure, and aboveground carbon dynamics from 1990 to 2022 in Shenzhen Bay, which is the only mangrove ecosystem within a megacity in China. Total aboveground carbon increased from 1820 (95% CI: 1386–2199) Mg C in 1990 to 6006 (95% CI: 5280–6618) Mg C in 2022, with habitat expansion accounting for most of the increase. Aboveground carbon accumulation was affected by coastal reclamation, estuarine engineering, and management-driven removal of introduced stands. Species composition emerged as a key determinant of ecosystem response to disturbance and long-term carbon dynamics. Native mangroves remained dominant and exhibited relatively stable canopy greenness during the 2008 extreme cold event. But the introduced Sonneratia apetala experienced a 42.9% drop in greenness and then took about five years to return to the level before the disturbance. By linking long-term changes in species composition, canopy structure, and aboveground carbon storage, this study provides a transferable foundation for monitoring urban blue-carbon ecosystems and evaluating the long-term consequences of disturbance, restoration, and management under accelerating urbanization and climate change. Full article

Contemporary Blue Planetary Health frameworks frequently approach marine degradation primarily as a technical management problem while insufficiently addressing the relational, ethical, and political–economic conditions driving ocean collapse. The framework proposes that dominant marine governance paradigms continue to reproduce anthropocentric and extractivist assumptions that reduce oceans to economic assets rather than recognizing them as living multispecies relational systems. In response, the study develops the Blue Stratified Relational Responsibility Framework (BSRRF), an interdisciplinary model integrating multispecies ethics, marine psychophysiology, environmental humanities, political ecology, Indigenous relational ontologies, and ocean governance. The framework advances three central claims: marine sustainability requires relational rather than purely instrumental governance; humans possess asymmetrical ecological responsibility due to their technological and institutional power; and meaningful Blue Planetary Health transformation requires simultaneous shifts in moral imagination, affective perception, governance systems, and political economy. The study further critiques dominant Blue Economy paradigms for reproducing extractivist and colonial dynamics under narratives of sustainability and innovation. Ultimately, the framework argues that although the ocean crisis manifests ecologically, its underlying drivers are simultaneously epistemological, political, economic, and civilizational. Consequently, advancing Blue Planetary Health requires integrated transformations in education, governance, public policy, and multispecies ethical responsibility. Full article

Introduction: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), such as liraglutide (LIR), are widely used in humans to treat type 2 diabetes mellitus, obesity, and non-alcoholic fatty liver disease. In mammals, GLP-1 RAs have been shown to influence hepatic lipid metabolism, although the underlying mechanisms remain unclear. In fish, GLP-1 also plays an important role in regulating hepatic processes, including glycogenolysis, gluconeogenesis, and lipolysis. However, the effects of GLP-1 RAs on liver lipid metabolism in fish remain largely unexplored. Objective: This study aimed to evaluate the effects of LIR on lipid target genes using primary hepatocytes from brown trout as an in vitro model. Methodology: After 24 h, a hepatocyte monolayer culture was established, and cells were exposed for 24 and 48 h to supplemented L-15 medium (control), 0.1% dimethyl sulfoxide in supplemented L-15 medium (solvent control), and five single exposures to LIR at 1, 10, 100, 500, and 1000 nM. After 24 and 48 h, cell viability was assessed using the trypan blue exclusion assay. Gene expression was analysed by real-time qPCR, targeting genes involved in lipogenesis, lipid transport, and cholesterol efflux. Results: No concentration-dependent effects on cell viability were observed. Gene expression analysis showed that LIR exposure modulated the mRNA levels of lipid-related genes, including acetyl-CoA carboxylase (ACC), acyl-CoA long-chain synthetase 1 (Acsl1), and fatty acid synthase (FAS), with time being the main influencing factor. Overall, expression levels were higher at 48 h compared to 24 h. Additionally, dose-dependent effects were observed for ACC expression, with higher LIR concentrations showing significant differences compared to controls. Conclusions: These findings indicate that LIR modulates lipid-related gene expression in primary hepatocytes of brown trout without affecting cell viability. The results suggest that GLP-1 receptor activation may influence key pathways involved in hepatic lipid metabolism, with time-dependent effects playing a predominant role. Overall, this study supports the use of brown trout primary hepatocytes as a suitable in vitro model for investigating hepatic lipid responses to LIR and other GLP-1 receptor agonists, while providing initial insight into their potential effects in fish. Full article

Background: Persistent intraradicular infection and biofilm survival remain major challenges in endodontic treatment, particularly because residual microorganisms may remain within dentinal tubules despite chemomechanical preparation. The antimicrobial efficacy of sealers may be insufficient against resistant bacteria. This study evaluated the effect of incorporating red and black iron oxide nanoparticles into BioRoot RCS on its antimicrobial activity and cytocompatibility. Methods: BioRoot RCS was modified with red or black iron oxide nanoparticles at 0.5 wt% and 2.0 wt%, generating 5 groups: unmodified sealer, 0.5% red, 2.0% red, 0.5% black, and 2.0% black. Surface morphology was analyzed using scanning electron microscopy, while elemental composition was determined by energy-dispersive X-ray spectroscopy. Antibacterial activity against Enterococcus faecalis and Fusobacterium nucleatum was assessed using a direct contact test, antibiofilm activity by colony-forming unit reduction on infected dentin discs, and cytocompatibility using human gingival fibroblasts and the AlamarBlue assay. Results: Iron was detected in the modified formulations, and elemental mapping showed homogenous distribution of calcium and iron. The 2.0% formulations showed significantly higher antibacterial and antibiofilm effects than the corresponding 0.5% groups (p < 0.05), with 2.0% black showing the lowest bacterial counts. Cytocompatibility differed at 1 and 3 days but not at 7 days, and all groups remained close to the control level with no significant difference (p > 0.05). Conclusions: Within the limitations of this in vitro study, experimental modification of BioRoot RCS with iron oxide nanoparticles, particularly at 2.0 wt%, improved the antimicrobial and antibiofilm efficacy of BioRoot RCS while maintaining acceptable cytocompatibility. However, physicochemical and handling properties must be evaluated before the clinical relevance of this modification can be determined. Full article