Search Results (12,015)

Around 85% of all land plants have symbiotic relationships with arbuscular mycorrhizal (AM) fungi, microscopic soil fungi that build extensive filamentous network in and around the roots. These links strongly influence plant development, water uptake, mineral nutrition, and defense against abiotic stresses. In this context, the use of AMF as a biological instrument to enhance plant drought resistance and phenotypic plasticity, through the formation of mutualistic associations, seems like a novel strategy for sustainable agriculture. This review synthesizes current understanding on the mechanisms through which AMF alleviates drought stress in agriculture. We focus on how AMF help maintain nutrient and water homeostasis by modulating phytohormones and signaling molecules, and by orchestrating associated biochemical and physiological responses. Particular emphasis is placed on aquaporins (AQPs) as key water-and stress-related channels whose expression and activity are modulated by AMF to maintain ion, nutrient, and water balance. AMF-mediated host AQP responses exhibit three unique patterns under stressful conditions: either no changes, downregulation to limit water loss, or upregulation to promote water and nutrient uptake. Nevertheless, little is known about cellular and molecular underpinnings of AMF effect on host AQPs. We also summarize evidence that AMF enhance antioxidant defenses, osmotic adjustment, soil structure, and water retention, thereby jointly improving plant drought tolerance. This review concludes by outlining the potential of AMF to support sustainable agriculture, offering critical research gaps, such as mechanistic studies on fungal AQPs, hormonal crosstalk, and field-scale performance, which propose future directions for deploying AMF in drought-prone agroecosystems. Full article

This experiment evaluated the application effects of the dietary substitution of maize silage with mixed silage prepared with Pennisetum giganteum and rice straw on fattening lambs. Forty-eight male Hu lambs with similar body weights and ages were randomly divided into four groups. The maize silage in the diet was replaced with Pennisetum giganteum and rice straw mixed silage in proportions of 0 (CON), 25% (PR1), 50% (PR2) and 75% (PR3). The average daily gain of the PR3 group was lower (p < 0.05) than that of the other groups. The highest substitution level increased (p < 0.05) ruminal ammonia nitrogen concentration and acetate-to-propionate ratio in lambs compared with the CON and PR1 groups. Moreover, dry matter and neutral detergent fiber digestibility in PR3 lambs were lower (p < 0.05) than in PR1 lambs. Compared with the CON group, the concentrations of serum catalase and total antioxidant capacity were increased (p < 0.05) in the PR2 and PR3 groups. Overall, the dietary substitution of maize silage with Pennisetum giganteum and rice straw mixed silage at a 50% level did not show a negative influence on growth performance of fattening lambs but displayed positive effects on their fiber digestibility and antioxidative capacity. Full article

The cosmetics industry is experiencing dynamic growth, which poses significant environmental challenges, primarily due to the accumulation of cosmetic ingredients in aquatic and soil ecosystems. In response, sustainable solutions aligned with the principles of the circular economy and the concept of “clean beauty” are increasingly sought. One promising approach is the use of bioferments obtained through the fermentation of plant raw materials from the Asteraceae family as alternatives to conventional extracts in cosmetic formulations. This literature review provides up-to-date insights into the biotechnological transformation of Asteraceae plants into cosmetic bioferments, with particular emphasis on fermentation processes enabling enzymatic hydrolysis of glycosylated flavonoids into aglycones, followed by their conversion into low-molecular-weight phenolic acids. These compounds exhibit improved local skin penetration (i.e., higher local bioavailability within the epidermal barrier) compared to their parent glycosides, thereby enhancing antioxidant activity. The analysis includes evidence-based data on the enzymatic hydrolysis of glycosidic flavonoids into free aglycones and their subsequent conversion into low-molecular-weight phenolic acids, which exhibit improved antioxidant potential compared to unfermented extracts. Furthermore, this narrative review highlights the role of lactic acid bacteria and yeast in producing bioferments enriched with bioactive metabolites, including lactic acid (acting as a natural moisturizing factor and preservative), while emphasizing their biodegradability and contribution to minimizing the environmental impact of cosmetics. This review aims to provide a comprehensive perspective on the technological, dermatological, and environmental aspects of Asteraceae-based bioferments, outlining their potential as sustainable and functional ingredients in modern cosmetics. Full article

Trametes polyzona is a white-rot basidiomycete with increasing relevance in environmental biotechnology due to its ligninolytic enzymes, biodegradation capacity, and versatile metabolic responses to diverse substrates. To provide an integrated and updated understanding of its biotechnological potential, we conducted a systematic review following PRISMA guidelines. A total of 46 studies published between 1991 and 2024 were analyzed, covering enzymatic production profiles, degradation of xenobiotics, extraction of bioactive metabolites, and experimental conditions influencing performance. Across the literature, T. polyzona consistently exhibits high ligninolytic activity, including laccase specific activities reported up to 1637 U/mg, together with efficient transformation of dyes, pesticides, and phenolic pollutants, and promising antioxidant and antimicrobial properties. However, substantial methodological heterogeneity was identified, particularly in strain characterization, fermentation parameters, and analytical approaches used to quantify enzymatic and biodegradation outcomes. These inconsistencies limit cross-study comparability and hinder process standardization. This review integrates current evidence; highlights critical gaps, such as limited ecotoxicological assessment of degradation products and scarce multi-omics characterization; and identifies key opportunities for process optimization in submerged/solid-state fermentation, bioreactor scaling, and the valorization of fungal metabolites. Overall, T. polyzona remains an underutilized resource with distinct advantages for applied mycology, environmental remediation, and industrial biotechnology. Full article

Soil salinization poses a significant threat to global agricultural productivity. Salt-tolerant plant growth-promoting bacteria (ST-PGPB) have shown great potential in enhancing crop resilience under saline stress, yet the molecular basis of their intrinsic tolerance remains incompletely understood. To address this, we employed an integrated genomic, transcriptomic, and biochemical approach to investigate the salt tolerance strategies of Pantoea sp. EEL5, an endophytic ST-PGPB isolated from Elytrigia elongata. The results demonstrated that EEL5 exhibited remarkable salt tolerance and efficiently removed Na⁺ via extracellular adsorption and intracellular accumulation. Genomic analysis identified key genes responsible for Na⁺ efflux, betaine synthesis and transport, and typical plant growth-promoting traits. Under salt stress, transcriptomic profiling revealed a marked upregulation of genes involved in Na⁺ extrusion, antioxidant enzymes, betaine biosynthesis and transport, arginine and proline catabolism, TCA cycle, and electron transport chain, concomitant with a downregulation of genes governing energy-intensive flagellar assembly and chemotaxis. These coordinated responses facilitated Na⁺ exclusion, enhanced antioxidant capacity, accumulated compatible solutes (betaine, glutamate, and GABA), increased energy production, and conserved energy via motility reduction, collectively conferring salt tolerance in EEL5. Our findings elucidate the multi-level salt adaptation mechanisms of EEL5 and provide a genetic foundation for a comprehensive understanding of ST-PGPB. Full article

Astaxanthin, a potent antioxidant, has attracted growing interest for its applications in the food, pharmaceutical, and cosmetic industries. This study aims to optimize the green extraction of astaxanthin from shrimp (Parapenaeus longirostris) by-products using ultrasound-assisted extraction (UAE) with extra virgin olive oil (EVOO) as a sustainable solvent, and explore its application in trahana fortification, a traditional Greek fermented cereal-based product. Response Surface Methodology (RSM) was applied to optimize astaxanthin extraction conditions (extraction time, liquid-to-solid (L/S) ratio, and ultrasound amplitude). Fatty acid analysis was performed with gas chromatography (GC-FID), and sensory analysis was conducted using a 7-point hedonic scale for sensory attributes. The optimal UAE conditions for astaxanthin, determined by RSM, were 228 min extraction time, a 65:1 liquid-to-solid ratio, and 41% ultrasound amplitude, predicting 83.50 μg astaxanthin/g by-product. At the optimal conditions, the experimentally obtained yield of 76.75 ± 1.17 μg astaxanthin/g by-product fell within the 95% confidence interval of the predicted value. The enriched trahanas retained nutritionally relevant levels after cooking (46.35 ± 0.60 μg astaxanthin per 60 g serving). Accelerated storage testing at 65 °C for six days was used to assess the thermal stability of astaxanthin in enriched trahanas. Based on first-order degradation kinetics and Arrhenius-based extrapolation of literature-derived activation energy values, astaxanthin retention above 80% at 25 °C was estimated to be maintained for approximately 27–51 days. Thereafter, progressive degradation is expected, with the estimated half-life ranging from 85 to 159 days. GC-FID analysis revealed favorable incorporation of bioactive lipids, including omega-3 fatty acids (EPA and DHA). Sensory evaluation demonstrated enhanced consumer acceptability, with enriched samples scoring significantly higher in appearance, aroma, and overall acceptance compared to traditional trahanas. These findings highlight UAE as an efficient and environmentally friendly strategy for recovering astaxanthin from seafood by-products and for developing functional cereal-based foods that align with sustainability. This work demonstrates the effective use of extra virgin olive oil as a green extraction solvent that also serves as a nutritional carrier, enabling the enrichment of trahanas with astaxanthin. The approach ensures both nutritional stability and consumer acceptability, providing a practical pathway for the development of sustainable, functional cereal-based foods. Full article

Opophytum forskahlii has a well-established ethnopharmacological significance. This study aimed to assess the skin anti-aging and hair growth-promoting activities of O. forskahlii seed oil (OFSO) and the underlying mechanism. GC-MS profiling revealed high levels of unsaturated fatty acids, linoleic acid (55.46%), and oleic acid (38.54%). The skin anti-aging activity of OFSO (3.125–100 µg/mL) was evaluated in normal human dermal fibroblasts (NHDFs) using MTT and enzyme inhibition assays. OFSO was non-cytotoxic and enhanced fibroblast proliferation in a dose-dependent manner, reaching 145.5% of control at 100 µg/mL (p < 0.05). OFSO significantly (p < 0.05) inhibited collagenase (48%), hyaluronidase (53%), elastase (57%), and tyrosinase (55%). The oil showed anti-inflammatory activity by inhibiting COX-1 and COX-2 (0.01–100 µg/mL) with IC₅₀ = 0.125 and 0.014 µg/mL, respectively. The hair growth promoting efficacy was assessed using adult male Wistar rats, randomly divided into control, OFSO-treated, and 2% minoxidil-treated groups (5 rats/group). Hair growth was assessed through visual scoring over 14 days of topical application and confirmed by histological examination and hair follicle counting. On day 14, the OFSO-treated group displayed almost complete hair coverage (score about 5.0), exceeding minoxidil (about 4.0), and significantly increased hair follicle number (14.0 ± 1 vs. 9.2 ± 0.8, p < 0.05). Histology confirmed that OFSO promoted hair follicle growth, differentiation, and transition from the telogen to the anagen phase. Network pharmacology analysis, integrating targets predicted via SwissTargetPrediction and disease-associated genes from GeneCards, identified PPARG, ESR1, and IL6 as key hub genes underlying OFSO’s effects. PPARG enhances antioxidant defenses, anti-inflammatory responses, and sebaceous gland function; ESR1 supports collagen production, skin elasticity, and follicle vascularization; and IL6 modulates inflammation and triggers the anagen phase of hair growth. Functional enrichment revealed modulation of PPAR, estrogen, prolactin, and arachidonic acid metabolism pathways, suggesting that OFSO may regulate lipid metabolism, inflammation, hormonal signaling, and tissue regeneration. OFSO demonstrated promising anti-aging and hair growth activities, supporting further development and testing of cosmetic formulations. Full article

Background/Objective: Neuroimmune and metabolic dysregulation have been increasingly implicated in the cognitive heterogeneity of autism spectrum disorder (ASD). However, it remains unclear whether anti-inflammatory diets engage distinct biological and cognitive pathways in autistic and neurotypical children. This study examined whether a 12-week anti-inflammatory dietary protocol produces group-specific neuroimmune–metabolic signatures and cognitive responses in autistic children, neurotypical children receiving the same diet, and untreated neurotypical controls. Methods: Twenty-two children (11 with ASD, six a on neurotypical diet [NT-diet], and five neurotypical controls [NT-control]) completed pre–post assessments of plasma IFN-γ, CXCL1, RANTES (CCL5), trimethylamine-N-oxide (TMAO), and an extensive ENI-2/WISC-IV neuropsychological battery. Linear mixed-effects models were used to test the Time × Group effects on biomarkers and cognitive domains, adjusting for age, sex, and baseline TMAO. Bayesian estimation quantified individual changes (posterior means, 95% credible intervals, and posterior probabilities). Immune–cognitive coupling was explored using Δ–Δ correlation matrices, network metrics (node strength, degree centrality), exploratory mediation models, and responder (≥0.5 SD domain improvement) versus non-responder analyses. Results: In ASD, the diet induced robust reductions in IFN-γ, RANTES, CXCL1, and TMAO, with decisive Bayesian evidence for IFN-γ and RANTES suppression (posterior P(δ < 0) > 0.99). These shifts were selectively associated with gains in verbal learning, semantic fluency, verbal reasoning, attention, and visuoconstructive abilities, whereas working memory and executive flexibility changes were heterogeneous, revealing executive vulnerability in individuals with smaller TMAO reductions. NT-diet children showed modest but consistent improvements in visuospatial processing, attention, and processing speed, with minimal biomarker changes; NT controls remained biologically and cognitively stable. Network analyses in ASD revealed a dense chemokine-anchored architecture with CXCL1 and RANTES as central hubs linking biomarker reductions to improvements in fluency, memory, attention, and executive flexibility. ΔTMAO predicted changes in executive flexibility only in ASD (explaining >50% of the variance), functioning as a metabolic node of executive susceptibility. Responders displayed larger coordinated decreases in all biomarkers and broader cognitive gains compared to non-responders. Conclusions: A structured anti-inflammatory diet elicits an ASD-specific, coordinated neuroimmune–metabolic response in which suppression of CXCL1 and RANTES and modulation of TMAO are tightly coupled with selective improvements in verbal, attentional, and executive domains. Neurotypical children exhibit modest metabolism-linked cognitive benefits and minimal immune modulation. These findings support a precision-nutrition framework in ASD, emphasizing baseline immunometabolic profiling and network-level biomarkers (CXCL1, RANTES, TMAO) to stratify responders and design combinatorial interventions targeting neuroimmune–metabolic pathways. Full article

The role of alternative nucleic acid structures (ANS) in biology is an area of increasing interest. These non-canonical structures include the Z-DNA and Z-RNA duplexes (ZNA), the three-stranded triplex, the four-stranded G-quadruplex (GQ), and i-motifs. Previously, the biological relevance of ANS was dismissed. Their formation in vitro often required non-physiological conditions, and there was no genetic evidence for their function. Further, structural studies confirmed that sequence-specific transcription factors (TFs) bound B-DNA. In contrast, ANS are formed dynamically by a subset of repeat sequences, called flipons. The flip requires energy, but not strand cleavage. Flipons are enriched in promoters where they modulate transcription. Here, computational modeling based on AlphaFold V3 (AF3), under optimized conditions, reveals that known B-DNA-binding TFs also dock to ANS, such as ZNA and GQ. The binding of HLH and bZIP homodimers to Z-DNA is promoted by methylarginine modifications. Heterodimers only bind preformed Z-DNA. The interactions of TFs with ANS likely enhance genome scanning to identify cognate B-DNA-binding sites in active genes. Docking of TF homodimers to Z-DNA potentially facilitates the assembly of heterodimers that dissociate and are stabilized by binding to a cognate B-DNA motif. The process enables rapid discovery of the optimal heterodimer combinations required to regulate a nearby promoter. Full article

Moringa oleifera, widely recognized as the horseradish tree or drumstick tree, is classified within the Moringaceae family, which comprises 13 species predominantly distributed across tropical and subtropical regions. The plant possesses a variety of therapeutic, nutritional, and beneficial health properties, including its potential to enhance the immune system. The present work provides extensive bibliographic research addressing the chemical composition of Moringa oleifera and its immunomodulatory properties with a focus on the cellular and molecular mechanisms involved in the regulation of immune function, which is crucial in unchecked cell proliferation and metastasis. The chemical composition of Moringa oleifera, including kaempferol, chlorogenic acid, quercetin, and niazimicin, varies between different biological parts of the plant (seeds, leaves, roots, and stems). The presence of these various chemical compounds contributes to the plant’s effect on the immune response via different pathways. Several studies indicate that Moringa oleifera mitigates inflammation by suppressing key pro-inflammatory mediators, such as TNF-α, IL-1β, inducible nitric oxide synthase (iNOS), prostaglandin E2 (PGE-2), and cyclooxygenase-2 (COX-2), while simultaneously enhancing anti-inflammatory mediators through activation of PPAR-γ. Furthermore, the immunomodulatory properties and possible application in health promotion and disease prevention, especially in cancer therapy, are discussed. Studies indicate that Moringa oleifera can modulate the tumor microenvironment (TME) by reducing Treg polarization, enhancing NK cell cytotoxicity, and prompting the proliferation and clonal expansion of CD8⁺ and CD4⁺ T lymphocytes. Together, Moringa oleifera could be considered for the treatment of conditions related to immune dysregulation, such as cancer. Full article

Essential oils (EOs) are complex volatile mixtures that exhibit antioxidant activity through both chemical and biological pathways. Phenolic constituents act as efficient chain-breaking radical-trapping antioxidants, whereas some non-phenolic terpenes operate through distinct mechanisms. Notably, γ-terpinene functions via a “radical export” pathway, generating hydroperoxyl radicals that intercept lipid peroxyl radicals and accelerate chain termination. Recent methodological advances, such as inhibited autoxidation kinetics, oxygen-consumption assays, and fluorescence-based lipid peroxidation probes, have enabled more quantitative evaluation of these activities. Beyond direct radical chemistry, EOs also regulate redox homeostasis by modulating signaling networks such as Nrf2/Keap1, thereby activating antioxidant response element–driven enzymatic defenses in cell and animal models. Phenolic constituents and electrophilic compounds bearing an α,β-unsaturated carbonyl structure may directly activate Nrf2 by modifying Keap1 cysteine residues, whereas non-phenolic terpenes likely depend on oxidative metabolism to form active electrophilic species. Despite broad evidence of antioxidant efficacy, molecular characterization of EO–protein interactions remains limited. This review integrates radical-chain dynamics with redox signaling biology to clarify the mechanistic basis of EO antioxidant activity and to provide a framework for future research. Full article

Lichens are a source of diverse compounds with a wide range of biological activities, making them of significant interest for novel drug development. In this study, metabolites were extracted from Lobariaceae lichens, and their antioxidant and antibacterial properties were experimentally investigated and explained using various computational approaches. Specifically, four lichen metabolites were analyzed using three methods to assess their antioxidant capacity. Antibacterial activity assays were conducted against four pathogens, and the minimum inhibitory concentrations (MICs) of the most promising compounds were determined. Ab initio studies were performed to evaluate radical stability. A pharmacological target responsible for the antibacterial effect was identified, and possible binding sites and modes were studied in silico. Metabolite IX, physciosporin, exhibited the highest antioxidant activity, which was associated with the theoretical stability of the radical. Additionally, IX exhibited an MIC of 0.97 μg/mL against S. pyogenes, surpassing the potency of streptomycin. The RecA protein was identified as a potential target, and a possible binding site and pattern of interactions at that site were described. Finally, IX showed low cytotoxicity in human cancer cell lines and was predicted to have favorable oral absorption properties, supporting its potential as a promising antioxidant and antibacterial agent against S. pyogenes. Full article

The widespread presence of polystyrene microplastics (PS-MPs) and agricultural pollutants such as avermectin (AVM) in aquatic environments poses a significant threat to aquatic organisms. However, the combined toxic effect of PS-MPs and AVM on cardiac development remains poorly understood. This study aimed to investigate the cardiac toxicity of AVM co-exposed with two sizes of MPs (large MPs, LMPs, 20 µm; small MPs, SMPs, 80 nm) in both larval and adult zebrafish. Firstly, under the co-exposure conditions of MPs and AVM, we observed significant cardiac developmental toxicity, including decreased survival rate, body length, and hatching rate, as well as a significant reduction in the number of myocardial cells. Secondly, the number of neutrophils and antioxidant enzyme activities such as CAT and SOD were greatly decreased, while inflammatory cytokines such as TNF-α and IL8 were significantly increased after co-exposure in larval zebrafish. Thirdly, there was severe disorganization of cardiomyocytes and interstitial edema in adult zebrafish hearts under the co-exposure by histopathological examination. Our results suggest that cardiomyocyte proliferation was suppressed, but heart apoptosis level and anti-apoptotic genes were significantly increased in the AVM+MPs co-exposure. Additionally, transcriptome sequencing and bioinformatics analysis revealed that significant changes in differentially expressed genes in the AVM+SMPs co-exposure group, particularly in the processes related to oxidation–reduction, inflammatory response, and the MAPK signaling pathway in the adult zebrafish heart. Furthermore, our pharmacological experiments demonstrated that inhibiting ROS and blocking the MAPK signaling pathway could partially rescue the heart injury induced by AVM and MPs co-exposure in both larval and adult zebrafish. In summary, this study suggested that co-exposure to AVM and MPs could induce heart toxicity mainly via the ROS-mediated MAPK signaling pathway in zebrafish. The information provided important insights into the potential environmental risk of microplastic and pesticide co-exposure on aquatic ecosystems. Full article

This review synthesizes research on nuclear factor erythroid 2-related factor 2 (Nrf2) in intestinal health across human, livestock, and mouse models. The Nrf2 signaling pathway serves as a master regulator of cellular antioxidant defenses and a key therapeutic target for intestinal inflammatory disorders, including ulcerative colitis and Crohn’s disease. The interplay between oxidative stress, Nrf2 signaling, and NF-κB inflammatory cascades represents a critical axis in the pathogenesis and resolution of intestinal inflammation. Under normal physiological conditions, Nrf2 remains sequestered in the cytoplasm by Kelch-like ECH-associated protein 1 (Keap1), which facilitates its ubiquitination and proteasomal degradation. However, during oxidative stress, reactive oxygen species (ROS) and electrophilic compounds modify critical cysteine residues on Keap1, disrupting the Keap1-Nrf2 interaction and enabling Nrf2 nuclear translocation. Once in the nucleus, Nrf2 binds to antioxidant response elements (ARE) in the promoter regions of genes encoding phase II detoxifying enzymes and antioxidant proteins, including heme oxygenase-1 (HO-1), NAD(P)H quinone oxidoreductase 1 (NQO1), and glutamate-cysteine ligase. This comprehensive review synthesizes current evidence demonstrating that activation of Nrf2 signaling confers protection against intestinal inflammation through multiple interconnected mechanisms: suppression of NF-κB-mediated pro-inflammatory cascades, enhancement of cellular antioxidant capacity, restoration of intestinal barrier integrity, modulation of immune cell function, and favorable alteration of gut microbiota composition. We systematically examine a diverse array of therapeutic agents targeting Nrf2 signaling, including bioactive peptides, natural polyphenols, flavonoids, terpenoids, alkaloids, polysaccharides, probiotics, and synthetic compounds. The mechanistic insights and therapeutic evidence presented underscore the translational potential of Nrf2 pathway modulation as a multi-targeted strategy for managing intestinal inflammatory conditions and restoring mucosal homeostasis. Full article

Background: Frostbite injury creates an ischemic, hypoxic, and acidic microenvironment that often triggers severe oxidative stress and inflammation. Current therapeutic approaches are limited by low drug delivery efficiency and an inability to adequately regulate multiple pathological pathways. Although oxyresveratrol (OR) exhibits excellent antioxidant and anti-inflammatory activities, its application is hampered by poor aqueous solubility and low stability. Methods: We constructed Oxyresveratrol@Zeolitic Imidazolate Framework-8 nanoparticles (OR@ZIF-8) and further embedded them in a sodium hyaluronate (HA) matrix to form an OR@ZIF-8@HA composite hydrogel. The physicochemical properties and pH-responsive drug release behavior of the system were characterized. Its antioxidant activity, ability to promote cell migration, and capacity to modulate macrophage polarization were evaluated in cellular assays. The therapeutic efficacy was further investigated using a mouse frostbite model, with wound repair analyzed via histological staining. Results: The OR@ZIF-8 nanoparticles achieved a cumulative release rate of 75.46 ± 3.68% under acidic conditions within 36 h. In vitro experiments demonstrated that the formulation significantly scavenged TNF-α and IL-6, by 161.85 ± 19.43% and 125.37 ± 12.65%, respectively, and increased the level of IL-10 by 44.97 ± 4.57%. In a scratch assay, it promoted wound healing, achieving a closure rate of 97.55 ± 2.77% after 36 h. In vivo studies revealed that the OR@ZIF-8@HA treatment group achieved a wound healing rate of 96.14 ± 4.12% on day 14. Conclusions: The OR@ZIF-8@HA composite hydrogel effectively overcomes the limitations of OR application via intelligent pH-responsive delivery. Through synergistic multi-mechanistic actions, it significantly accelerates frostbite wound healing, offering a novel and efficient therapeutic strategy for frostbite management. Full article