Search Results (16,298)

Natural fungal polysaccharides are increasingly explored as bioactive compounds capable of orchestrating complex regenerative responses during tissue repair. This study aimed to evaluate the in vivo wound-healing efficacy and molecular mechanisms of a topical polysaccharide formulation derived from Bovistella utriformis (Calvatin 2%) using complementary murine, zebrafish, and proteomic approaches. Phylogenetic analysis based on ITS sequences confirmed the taxonomic identity of the Chilean specimen. In a murine full-thickness excisional wound model, Calvatin 2% significantly accelerated wound contraction and re-epithelialization compared to both saline and base-cream controls, achieving near-complete closure by day 10. Label-free quantitative proteomic analysis of wound tissue by UHPLC-HRMS identified 2432 high-confidence proteins, with 171 upregulated and 153 downregulated proteins in the Calvatin versus control comparison (p < 0.01). Functional enrichment revealed strong activation of innate immune response, complement activation, coagulation cascades, and acute-phase response pathways, while lipid metabolism, mitochondrial energy production, and muscle-related processes were significantly downregulated. KEGG pathway analysis further highlighted complement and coagulation cascades and neutrophil extracellular trap formation as the most prominently affected pathways. In a zebrafish laser-induced wound model, Calvatin induced early and sustained regenerative responses, reaching over 93% wound closure by 18 days post-lesion, significantly outperforming both PBS and vehicle-treated groups. Chronic oral administration of polysaccharides did not induce major hepatic inflammatory responses, supporting systemic safety. Overall, these findings indicate that B. utriformis polysaccharides are associated with modulation of immune- and repair-related pathways together with tissue reprogramming processes that may contribute to accelerated cutaneous regeneration, positioning Calvatin as a promising bioactive formulation for wound-healing applications. Full article

Soil salinization is a major threat to global crop production. Tartary buckwheat (Fagopyrum tataricum), valued for its hardiness in marginal environments, provides an excellent system for studying plant salt tolerance. Using an integrated multi-omics approach, we deciphered the physiological, metabolic, and transcriptional responses of Tartary buckwheat to prolonged NaCl stress. Physiological profiling confirmed membrane damage alongside osmotic adjustment via proline accumulation and a phased antioxidant response. Metabolomics revealed extensive reprogramming, with dynamic enrichment in pathways of flavonoid biosynthesis, lipid metabolism, and the TCA cycle. Transcriptomics delineated a time-specific cascade from early signaling to late defense activation. Critical regulators within ABA and MAPK signaling pathways showed fine-tuned, divergent expression; for instance, SnRK2.3 was suppressed while specific PP2Cs were induced, and FtMAPK10 was dramatically up-regulated. Integrated analysis demonstrated coordinated induction of osmoprotectant synthesis (e.g., galactinol and betaine pathways) and a rewiring of central carbon metabolism. Our findings reveal a sophisticated, multi-layered adaptation strategy in Tartary buckwheat, integrating enhanced osmolyte production, antioxidant defense, membrane remodeling, and metabolic reprogramming, orchestrated by key signaling networks. This study provides a comprehensive molecular framework for salt tolerance and identifies valuable genetic targets for improving crop resilience. Full article

Chronic d-galactose (d-gal) treatment is a model to induce accelerated aging-like phenotypes in rodents. However, the sex differences in behavioral and musculoskeletal manifestations of this model are not well understood. Heme oxygenase-1 (HO-1) is a cytoprotective protein that may have anti-aging properties. The goal of this study was to better understand the sex differences in the behavioral and musculoskeletal effects of chronic d-gal treatment in C57BL/6J mice, as well as the role of HO-1 induction or inhibition. Eight-week-old male and female mice received daily saline or d-gal injections (500 mg/kg, s.c.) for 12 weeks. After this time, mice in the d-gal group were randomized into three groups (n = 6/group/sex): d-gal, d-gal + cobalt protoporphyrin (CoPP) (5 mg/kg, s.c. weekly), and d-gal + zinc deutroporphyrin bisglycol (ZnBG) (42 mg/kg, i.p. triweekly) for a period of 4 weeks. Open-field, novel-object recognition, Barnes maze, grip strength, micro-computed tomography (µ-CT), histology, and protein analysis were performed. Chronic d-gal treatment resulted in a sexual dimorphic response, with female mice being more prone to develop deficits in both short- and long-term spatial memory as well as in non-spatial memory. Male mice exhibited deficits only in long-term spatial memory when treated chronically with d-gal. Inhibition of HO-1 was protective in both females and males. Chronic d-gal treatment did not accelerate the development of osteoporosis or sarcopenia in either males or females. Our results demonstrate a sexual dimorphic response to the chronic effects of d-gal treatment on aging, with greater effects in females than in males, which is dependent on HO-1. Full article

Exosomes (EXs) mediate intercellular communication in the tissue microenvironment. We previously demonstrated that endothelial progenitor cell-derived exosomes (EPC-EXs) from exercised mice protect neurons and cerebral endothelial cells from hypoxia- and hypertension- induced injury ex vivo, suggesting their therapeutic potential in hypertensive ischemic injury. Here, we investigated whether exercise-conditioned EPC-EXs (ET-EPC-EXs) confer protection against acute ischemic injury. Hypertensive transgenic mice were divided into donor and recipient groups. Donor mice underwent treadmill exercise to generate ET-EPC-EXs. Recipient mice was subjected to middle cerebral artery occlusion and received ET-EPC-EXs via tail vein injection (2 × 10⁸/100 μL saline) two hours after stroke onset. Cerebral blood flow (CBF) was assessed, and brains were collected on day two for histological and molecular analyses. Our data showed that ET-EPC-EXs were robustly taken up by cerebral cells, predominantly in the penumbra in the ipsilateral hemisphere. ET-EPC-EXs reduced cell death and microglia activation and restored tight-junction proteins. Moreover, ET-EPC-EX treatment preserved CBF and improved sensorimotor function on day two post-stroke. Mechanistically, ET-EPC-EXs suppressed p38 activation, accompanied by reduced matrix metalloproteinase-3 and cytochrome c levels in the ipsilateral brain. Collectively, these findings demonstrate that EPC-EXs from exercise mice improve sensorimotor functions and confer protection in hypertensive ischemic brain injury, likely through attenuation of neuroinflammation and preservation of vascular integrity via modulation of the p38 signaling. Full article

Despite their vital physiological roles, oxidative imbalance caused by reactive oxygen, nitrogen, sulphur, and chlorine species damages essential body macromolecules such as proteins, lipids, and nucleic acids through oxidative stress. This stress is strongly associated with cancer, inflammation, neurological and cardiovascular disorders, and other chronic human diseases. Therefore, antioxidants, natural or synthetic, that counteract oxidative damage are important, with increasing interest in their use within the pharmaceutical, food, and cosmetic industries. However, due to toxicity concerns with the synthetic variants, natural antioxidants are increasingly preferred. Extremophile-derived antioxidants, such as superoxide dismutases, catalases, peroxidases, carotenoids, and melanin, are of renewed interest due to their remarkable stability, robustness, and potency under extreme conditions of temperature, pH, and salinity. These make them better than many mesophile-derived antioxidants and excellent candidates for cost-effective biotechnological, research, and industrial processes that require high operational efficiency. This review summarises key classes of selected enzymatic and pigment antioxidants, their mechanisms of action, and their industrial relevance, with a focus on extremophilic microalgae, bacteria, and fungi. The benefits of extremophilic antioxidants are discussed alongside their current applications and existing challenges, including the need to develop efficient delivery systems, scalability issues, and limited characterisation. Full article

Background/Objectives: Fibroblast activation protein (FAP) has emerged as a promising target for oncologic molecular imaging due to its high expression in cancer-associated fibroblasts and low presence in healthy tissues. Among available FAP ligands, [⁶⁸Ga]Ga-FAPi-46 has shown rapid tumor accumulation, low background uptake, and broad tumor applicability. This study reports the successful translation of [⁶⁸Ga]Ga-FAPi-46 from preclinical development to routine clinical radiopharmacy practice, detailing automated synthesis, quality control performance, radiochemical stability, and the first clinical imaging results. Methods: Automated radiolabeling of FAPi-46 with gallium-68 was performed using a synthesis module. Quality control included radiochemical purity assessments by iTLC, SPE, and RP-HPLC (pH, appearance, endotoxin levels, and membrane integrity testing). Radiochemical stability was evaluated in saline (up to 6 h) and human serum (up to 90 min). In vitro characterization included the partition coefficient and serum protein binding determination. A clinical evaluation was conducted in a woman with newly diagnosed lung adenocarcinoma who underwent both [¹⁸F]FDG PET/CT and [⁶⁸Ga]Ga-FAPi-46 PET/CT. Results: Automated synthesis of [⁶⁸Ga]Ga-FAPi-46 achieved a high radiochemical yield (87.9 ± 1.3%) and radiochemical purity greater than 98%. All batches met release specifications for sterility, apyrogenicity, and physicochemical parameters. The radiotracer demonstrated high stability in saline and human serum, with radiochemical purity consistently above 95% at all evaluated time points. The compound showed a hydrophilic profile (LogP = −3.32 ± 0.14) and 40–60% serum protein binding. Clinically, [⁶⁸Ga]Ga-FAPi-46 PET/CT provided superior lesion delineation compared to [¹⁸F]FDG, revealing additional mediastinal, supraclavicular, and brain metastases. Conclusions: [⁶⁸Ga]Ga-FAPi-46 can be reliably synthesized using automated procedures under routine radiopharmacy conditions, meeting regulatory quality standards and demonstrating excellent stability. Its enhanced lesion detectability compared with [¹⁸F]FDG in the first patient case supports its potential value for oncological staging and clinical implementation. Full article

The desert ecosystem harbors a resilient microbial community that sustains plant life under extreme stress. Understanding the endophytic microbiota of desert flora provides key insights into how these microorganisms enable plant survival and maintain ecological balance in arid landscapes. To date, the endophytic bacterial communities of dominant desert plants in the Arabian Peninsula have not been comprehensively characterized. Here, we investigated the endophytic microbiota of five co-adapted desert species, namely, Schweinfurthia papilionacea, Sesuvium verrucosum, Ochtocloa compressa, Helianthemum nummularium, and Convolvulus arvensis. These plants coexist in hyper-arid habitats and exhibit exceptional tolerance to drought, salinity, and nutrient scarcity. We hypothesized that, despite their phylogenetic divergence, these plants host functionally convergent microbial communities shaped by desert selection pressures. Using 16S rRNA gene amplicon sequencing, we obtained 3.4 million high-quality reads from 25 samples. Clustering at 97% similarity revealed 35 phyla and 17 dominant genera, highlighting notable microbial richness and ecological complexity. Alpha-diversity indices showed comparable species richness across hosts, while beta-diversity indicated community differentiation driven by environmental filtering. The dominant phyla included Pseudomonadota, Actinomycetota, Cyanobacteriota, and Bacillota, reflecting microbial adaptation to extreme desert conditions. Functional pathway prediction revealed enrichment of genes associated with DNA repair and protein turnover, suggesting metabolic flexibility and enhanced survival under stress. Overall, this study provides a comparative metagenomic insight into the endophytic bacterial communities of five desert plant species, uncovering a consistent pattern of functional convergence across diverse hosts. The findings suggest the presence of shared functional traits among the endophytic microbiota examined here, offering preliminary evidence for microbial contributions to plant resilience in arid environments. Full article

Heart failure (HF) affects approximately 64 million people globally. HF often coexists with chronic kidney disease. HF may affect the heart during diastolic filling, systolic ejection, or both. Conventionally, HF is categorized by left ventricular ejection fraction (LVEF). One of the leading causes of death in chronic kidney disease (CKD) patients of cardiovascular origin increase hospitalizations and worsen quality of life by causing fluid and electrolyte overload. As kidney function declines, increases risk of development of HF in CKD, with a negative impact and worse prognosis in these patients. This narrative review provides healthcare professionals—including nephrologists, car-diologists, internists, and general practitioners—with evidence-based strategies to iden-tify and manage this complex comorbidity, aiming to reduce hospitalization and mor-tality in CKD patients. By synthesizing recent findings on risk stratification, diagnostic modalities, and individualized treatment—particularly for patients undergoing renal replacement therapy—clinicians can enhance volume management and optimize patient outcomes. Considering the increasing prevalence of chronic kidney disease and associated cardiovascular comorbidities, this review addresses pathogenic mechanisms, diagnostic approaches, pharmacological treatments, and dialytic therapy modifications. Full article

Saline-alkaline (SA) soils pose a serious threat to soybean production worldwide. Although severe saline-alkaline stress can reduce yield by up to 30%, the mechanisms underlying saline-alkaline-induced inhibition of root growth remain unclear. In this study, two soybean cultivars with contrasting tolerance, Chang Nong 26 (CN26) and Jiyu 441 (JY441), were exposed to saline-alkaline stress induced by NaHCO₃ and Na₂CO₃ at Na⁺ concentrations of 0, 21, and 45 mmol·L⁻¹. The effects on seed germination, early seedling growth, antioxidant responses, and root DNA damage were systematically examined. High-level saline-alkaline stress significantly inhibited germination and root elongation in both cultivars. Superoxide dismutase (SOD) and peroxidase (POD) activities increased markedly under stress, indicating activation of antioxidant defenses. Catalase (CAT) and ascorbate peroxidase (APX) to scavenge ROS and maintain cellular redox balance. Nevertheless, oxygen-free radicals (OFRs) accumulated to a significantly greater extent in the root tips of CN 26 than in JY441, suggesting lower tolerance in CN 26. Random amplified polymorphic DNA (RAPD) analysis revealed pronounced DNA damage in root tips under saline-alkaline stress, with more polymorphic bands detected in CN 26 than in JY441. Furthermore, qRT-PCR analysis demonstrated that the expression of DNA damage repair-related genes (RAD51, OGG1, RAD4, and ATM) was downregulated in CN 26 roots under stress, whereas E2FA and WEE1 expression was upregulated. In contrast, these DNA repair genes in JY441 were significantly induced during the early stage of stress exposure and subsequently declined. Collectively, this study demonstrates that saline-alkaline stress inhibits soybean growth through the induction of oxidative DNA damage and cell cycle arrest in roots. The reduced capacity for DNA repair in CN 26 likely contributes to its greater sensitivity to saline-alkaline stress. This study provides mechanistic insights into saline-alkaline stress-induced growth inhibition in soybean and offers a theoretical basis for breeding stress-tolerant cultivars. Full article

Background: Hypothermic machine perfusion (HMP) has been associated with reduced delayed graft function compared with static cold storage (SCS). However, the molecular mechanisms underlying these differences during cold preservation remain incompletely understood. This study compared cold-storage-related biochemical and histological changes in kidneys preserved by HMP versus SCS using a Lewis rat model prior to transplantation. Methods: Following isolation, rat kidneys were flushed with cold saline (4 °C). Left kidneys were preserved by HMP at constant flow using Belzer’s machine perfusion solution (MPS) at 4 °C, while right kidneys were stored using SCS in University of Wisconsin solution at 4 °C. After four hours of preservation, kidneys were processed for biochemical and histological analysis. Fresh biopsies were evaluated for mitochondrial complex respiration. Western blotting was performed to assess expression of NDUFS3, a complex I subunit. Histological staining for nitrotyrosine and kidney injury markers was compared across groups. Results: Mitochondrial complex respiration did not differ significantly between the SCS and HMP groups. Western blot analysis demonstrated significantly increased NDUFS3 expression in HMP-preserved kidneys compared with SCS and control kidneys. Histological evaluation revealed elevated tubular staining of nitrotyrosine and kidney injury markers in SCS kidneys relative to controls, whereas HMP preservation markedly attenuated these increases. Conclusions: HMP mitigates cold-storage-induced oxidative stress and reduces expression of kidney injury markers after four hours of preservation. These molecular findings suggest a protective effect of HMP during cold preservation. Future studies with longer preservation times and transplantation models are needed to determine whether these improvements translate into enhanced post-transplant kidney function. Full article

Water scarcity compels wastewater reuse, but lax discharge standards generate a regulatory mirage, misleading the public about safety. Here, “regulatory mirage” refers to situations where formal compliance with discharge standards creates a false perception of safety while ecological risks and degradation persist. Despite formal compliance, treated effluent severely harms Iran’s effluent-dependent Kashaf River, driving eutrophication, salinization, and the downstream transport of unregulated contaminants of emerging concern, including fluorinated substances (PFAS) and pharmaceuticals. These pressures extend beyond the river channel to adjacent natural wetlands, which act as de facto nature-based treatment systems yet are progressively transformed into sacrificial sinks for excess nutrients, salts, heavy metals, and micropollutants. By benchmarking the Iranian Wastewater Discharge Standards (IWDS) against international guidelines (WHO, EU, FAO), this study quantifies a “Permissibility Gap” frequently greater than 10 for key parameters such as BOD₅, nutrients, and trace metals, revealing how concentration-based limits ignore cumulative mass load and mixture toxicity at the basin scale. The Kashaf River case demonstrates that current end-of-pipe regulation undermines both natural wetlands and planned nature-based solutions, including constructed wetlands, in arid regions where effluent reuse is unavoidable. The study argues that aligning discharge standards with global benchmarks, adopting mass-based permits, and explicitly regulating contaminants of emerging concern are prerequisites for truly safe wastewater reuse and for protecting wetland ecosystems in effluent-dependent basins. This study shows that permissive, concentration-based discharge standards in effluent-dependent basins create a regulatory mirage that accelerates river and wetland degradation, and that stricter, mass-based limits are essential for safe wastewater reuse. Full article

Aquaculture wastewater (AWW) contains elevated concentrations of nitrogen, phosphorus, and salts, in addition to many micropollutants that may cause environmental pollution if discharged untreated. This study evaluated the potential of the halophilic microalga Dunaliella salina for simultaneous phycoremediation of AWW and production of biodiesel-oriented biomass. Microalgal growth and biochemical composition were compared between AWW and synthetic f/2 medium under controlled laboratory conditions. Results showed that AWW supported efficient microalgal growth, showing a biomass yield of 1.32 g L⁻¹ with a productivity of 0.09 g L⁻¹ d⁻¹, representing 40.88% and 18.42%, respectively, over that obtained in f/2 medium. Cultivation in wastewater also enhanced the volumetric productivity of lipids, proteins, and carbohydrates by 26.20%, 12.46%, and 26.38%, respectively. Significant nutrient removal from AWW was achieved, with high reduction efficiencies for nitrate, nitrite, ammonium, phosphate, and sulfate within the range 76.80–94.10%, along with a decrease in salinity by 29.70%. The lipid fraction was dominated by fatty acid methyl esters suitable for biodiesel production, representing 94.10% of the total lipids. Biodiesel properties met the international fuel standards and were even improved when the microalga was cultivated in AWW. These findings demonstrate that AWW can serve as an effective culture medium for halophilic microalgae, enabling simultaneous wastewater treatment and sustainable biofuel feedstock production. Full article

The impacts of climate change on Mediterranean weed flora were investigated to inform future weed management strategies. Projections indicate that rising temperatures and increased atmospheric CO₂ concentrations are likely to favor ruderal species characterized by rapid phenological development and high dispersal capacity. Enhanced abiotic stressors—such as elevated temperatures, water scarcity, and increased UV-B radiation—are expected to affect crops more severely than weeds, given the latter’s greater evolutionary potential to develop stress-tolerant biotypes. Moreover, the increased frequency and intensity of extreme events (e.g., drought, flooding, and soil salinization) may reduce weed community diversity, potentially leading to dominance by a limited number of highly competitive species and consequently intensifying reliance on chemical weed control. Simplification of weed communities may also increase vulnerability to the introduction and establishment of alien species, particularly those originating from hot and arid regions, some of which may be parasitic, toxic, or allergenic. Climate change-induced phenological mismatches between flowering plants and pollinators are likely to favor wind-pollinated weed species, further compromising the aesthetic and ecological quality of agricultural landscapes. Additionally, increased production of wind-dispersed allergenic pollen, together with the anticipated rise in herbicide applications, may pose significant risks to human health. An effective agronomic strategy to address future weed scenarios should include the genetic improvement in crops to enhance adaptive plasticity, exploiting germplasm from ancestral lines and related wild species. Full article

In this work, we assessed the impacts of biostimulant application on pot-grown Sonchus oleraceus L. plants under saline conditions. The biostimulant products tested were an experimental formulation based on humic and fulvic acids (HF) and the commercial product Sipfol Star^® (SS), which comprises amino acids (mainly glutamic acid, alanine, and aspartic acid). Our results highlight that biostimulants mitigated the negative impacts of high salinity only on specific morphological traits, such as the dry matter of leaves. Accordingly, the HF treatment reduced the fat and protein content (under low and high salinity, respectively) and energetic value (under high salinity), while the carbohydrate content increased under high salinity for the SS treatment and the untreated plants compared to the respective treatment under low salinity. The nitrogen content of leaves was negatively affected by biostimulant application at high salinity, whereas the HF and SS treatments induced the accumulation of sodium and potassium under high salinity compared to the untreated plants. The total flavonoid content also increased in biostimulant-treated plants under high salinity, whereas no effects on total phenol content were recorded. Moreover, the plants treated with biostimulants under low salinity conditions showed higher antioxidant activity for the ferric reducing antioxidant power (FRAP) assay than the respective treatments at high salinity and the control treatment. The content of oxidative markers, such as malondialdehyde (MDA) and hydrogen peroxide (H₂O₂), was higher under low-salinity levels, whereas biostimulant-treated plants showed the lowest content under high salinity. Overall, the application of biostimulants showed promising results in mitigating the adverse impacts of high salinity on S. oleraceus plants. However, further research is needed on more biostimulatory products and application regimes (e.g., different doses and application times) to elucidate the mechanisms of action and bolster the positive effects of this sustainable agronomic tool. Full article

Ocean temperature and salinity structures are crucial in understanding ocean circulation and heat–salt transport processes. However, the high cost and limited spatiotemporal coverage of in situ observations make it difficult to reconstruct high-resolution three-dimensional temperature–salinity (T-S) fields. To address these limitations and the strong spatiotemporal heterogeneity of T-S structures in the South China Sea (SCS), the Smart Synthetic Ocean Profile (SSOP) model is proposed, which is a two-stage machine learning-based inversion framework for reconstructing subsurface T-S profiles from satellite surface data. The framework integrates localized training, adaptive model selection, and an error correction strategy. Using climate-state grids with a consistent spatiotemporal resolution as a baseline, multiple candidate regression models are independently trained for each grid point–depth layer–month combination, and the optimal model is selected through performance validation to generate initial T-S profiles. An error correction module is then introduced to refine temperature profile deviations, improving profile consistency and overall accuracy. Experiments using three independent observational periods from the SCS show that SSOP reliably reconstructs vertical T-S structures, particularly in the upper ocean and thermocline. Comparisons with in situ observations indicate that SSOP achieves improved accuracy relative to the Modular Ocean Data Assimilation System and climatology. Full article