Search Results (1,471)

Background and Objectives: Intermittent fasting (IF) has emerged as a nutritional strategy capable of modulating circadian alignment, metabolic efficiency, and neuroendocrine regulation in individuals with obesity. Among the neurobiological mediators potentially involved, Orexin-A—a hypothalamic neuropeptide regulating arousal, appetite, and energy balance—may represent a key link between fasting patterns and metabolic homeostasis. This study aimed to evaluate the long-term metabolic and neuroendocrine effects of two intermittent fasting protocols, time-restricted feeding (16:8) and alternate-day fasting (5:2), compared with a hypocaloric Mediterranean diet used as a reference condition. Materials and Methods: Thirty adults with obesity (aged 20–40 years) were allocated to one of three dietary interventions—low-calorie Mediterranean diet, IF 16:8, or IF 5:2—based on habitual dietary patterns and followed prospectively for 12 months. Anthropometric parameters, metabolic indices, inflammatory markers (CRP, TNF-α, IL-6, IL-10), and circulating Orexin-A concentrations were assessed at baseline and at three-month intervals (T0–T3). Results: Both intermittent fasting protocols induced more rapid improvements in body mass index, adiposity, lipid profile, fasting glucose, and inflammatory markers compared with the Mediterranean diet. Among the IF strategies, the 16:8 regimen showed the most consistent and physiologically coherent pattern of adaptation, characterized by a progressive and sustained increase in Orexin-A levels. This response was strongly associated with enhanced metabolic flexibility, reduced systemic inflammation, and improved energy regulation over time. In contrast, the 5:2 protocol produced more variable metabolic and neuroendocrine responses, likely due to alternating cycles of marked caloric restriction and compensatory intake. Conclusions: Intermittent fasting, particularly the 16:8 time-restricted feeding protocol, appears to be an effective and sustainable chrononutritional strategy for obesity management. By reinforcing circadian organization, improving inflammatory balance, and activating orexinergic pathways, the 16:8 model emerges as a promising intervention to address key metabolic and neuroendocrine dysfunctions associated with obesity. Full article

Electrocatalytic hydrogenation (ECH) represents an environmentally friendly pathway for converting 5-hydroxymethylfurfural (HMF) into the high-value chemical 2,5-bis(hydroxymethyl)furan (BHMF). However, its selectivity and Faradaic efficiency are often constrained by competitive hydrogen evolution at the cathode and insufficient supply of active hydrogen at the surface. To address this challenge, this study developed an Ir-decorated copper oxide nanowire catalyst (denoted as CuIr) featuring a hydrogen-rich adsorption (H_ads) surface. The incorporation of Ir significantly enhances the catalyst’s water dissociation capacity, creating abundant H_ads sources that selectively accelerate HMF hydrogenation while suppressing side reactions. Under a mild applied potential of −0.45 V vs. RHE and a current density of approximately −20 mA cm⁻², the optimal CuIr₄₀ catalyst achieved near-complete conversion of HMF (99%), a BHMF yield of 99%, and a high Faradaic efficiency of 97% within 120 min of electrolysis. Mechanistic studies reveal that this catalytic leap stems from the synergistic functional interaction between Cu and Ir sites in substrate activation and hydrogen supply. This work presents a novel strategy for designing efficient electrocatalysts for biomass hydrogenation by regulating surface H_ads concentration. Full article

Semen cryopreservation is a critical biotechnological approach for preserving superior genetic resources in livestock. Spermatozoa are particularly vulnerable to cryogenic stress during the freeze–thaw process, resulting in impaired structure and function. Therefore, the development of effective cryoprotective additives is essential for improving yak semen cryopreservation. In this study, ginseng peptide (GFREH) was incorporated into the freezing extender at different concentrations (0, 0.25, 0.5, 0.75, and 1.0 mg/mL) to evaluate its effects on post-thaw sperm quality, in vitro fertilization (IVF) capacity, and the underlying regulatory mechanisms. Semen samples treated with 0 and 0.75 mg/mL GFREH were further subjected to proteomic analysis to elucidate the molecular basis of its cryoprotective action. The results demonstrated that GFREH significantly increased total motility (TM), progressive motility (PM), straight-line velocity (VSL), curvilinear velocity (VCL), average path velocity (VAP), as well as plasma membrane and acrosome integrity of frozen–thawed yak spermatozoa (p < 0.05). GFREH also significantly reduced malondialdehyde (MDA) levels while enhancing antioxidant enzyme activities, mitochondrial membrane potential (MMP), and ATP content (p < 0.05). Moreover, GFREH at concentrations of 0.5, 0.75, and 1.0 mg/mL significantly improved IVF and blastocyst formation rates compared with the control (p < 0.05), with the 0.75 mg/mL group exhibiting the highest fertilization and blastocyst rates. Proteomic analysis further revealed that GFREH modulated the PI3K/AKT signaling pathway and downregulated FOXO1 expression. Collectively, these findings indicate that ginseng peptides enhance yak sperm cryotolerance by coordinating oxidative balance, mitochondrial energy metabolism, and survival-related signaling, with 0.75 mg/mL representing an optimal effective concentration within the functional dose range tested. Full article

Medication-related osteonecrosis of the jaw (MRONJ) is a refractory disease for which no established treatment currently exists. Surfactin, a biosurfactant produced by Bacillus subtilis, exhibits antimicrobial activity, anticancer effects, and anti-inflammatory properties, suggesting its potential medical applications. This study aimed to elucidate the ability of surfactin to modulate the immune response induced by lipopolysaccharide (LPS) derived from periodontal pathogens (Aggregatibacter actinomycetemcomitans), clarify the underlying molecular mechanisms, and explore its potential utility in the treatment of MRONJ. Reverse transcription quantitative polymerase chain reaction demonstrated that surfactin suppresses LPS-induced interleukin-6 (IL-6) expression and secretion in J774.1 cells in a concentration-dependent manner. Western blot analysis showed that surfactin inhibited activation of the JNK-c-Jun-AP-1 axis and the JAK/STAT signaling pathways in J774.1 cells. The effects of surfactin administration were further evaluated in an in vivo MRONJ model. Co-treatment with surfactin significantly reduced the extent of LPS-induced bone necrosis. Overall, these findings suggest that surfactin suppresses LPS-induced IL-6 expression in macrophages and inhibits osteonecrosis induced by bisphosphonate preparations and LPS through negative regulation of the JNK-c-Jun-AP-1 axis and inhibition of the JAK/STAT pathway. Hence, surfactin may represent a promising candidate for MRONJ management. Full article

This study provides a quantitative assessment of the combined effects of progressive urbanization and changes in precipitation patterns (PPs) on the urban water cycle. The primary objective was to evaluate historical (1940–2024) and projected (to 2060) changes in total annual surface runoff (TSR) and retention capacity (RC) in the highly urbanized catchment of the Dłubnia River in Cracow, Poland. Simulations were performed using the EPA SWMM hydrodynamic model, supported by digitized historical land-use maps and long-term meteorological records. The results demonstrate that the dominant driver of the observed 6.4-fold increase in TSR and 6.8-fold loss of retention capacity (LRC) over the study period was the progressive increase in impervious surfaces. Although inter-annual variability in the amount and structure of annual precipitation (AP) strongly correlates with annual TSR (r = 0.97), its contribution to the long-term upward trend in TSR is marginal (r = 0.19). Land use and land cover change (LULC) exhibits an extremely strong correlation with the long-term TSR trend (r = 0.998). The study also highlights the high effectiveness of nature-based solutions (NbSs), particularly bioretention cells (BCs)/rain gardens, in mitigating the adverse hydrological effects of excessive surface sealing. Implementation of BCs covering just 3–4% of the total drained roof and road area is sufficient to fully offset the projected combined negative impacts of further urbanization and climate change (CC) in scope Representative Concentration Pathways (RCP4.5 and RCP8.5) projections on catchment retention capacity by 2060. These findings position strategically targeted, relatively small-scale bioretention as one of the most effective and feasible urban adaptation measures in mature, densely developed cities. Full article

The development of efficient spinel oxide catalysts for low-temperature oxidation of volatile organic compounds (VOCs) remains an important research objective. In this work, Ru was doped into a CoMn₂O₄ spinel to enhance its catalytic activity toward toluene oxidation and the underlying promotion mechanism of Ru doping was systematically investigated. The resulting Ru-CoMn₂O₄ catalyst showed remarkable performance, with T₉₀ reaching approximately 224 °C at a WHSV of 60,000 cm³ g⁻¹ h⁻¹ and nearly 100% CO₂ selectivity above 200 °C. Mechanism studies revealed that the reaction followed both Mars–van Krevelen (MvK) and Eley–Rideal (E–R) pathways. The reaction rates were strongly influenced by the oxidizing capacity of the catalyst, the abundance of highly valent surface species (namely Co³⁺, Mn⁴⁺, and Ru⁴⁺), adsorbed toluene, lattice oxygen, gaseous toluene, and adsorbed oxygen. With Ru doping, new Ru–O–Mn and Ru–O–Co chains formed in the CoMn₂O₄ spinel structure, leading to a moderate enhancement in oxidizing ability and a moderate increase in the concentration of highly valent surface species, adsorbed toluene, and lattice oxygen. Although a slight reduction in adsorbed oxygen was observed, Ru doping significantly boosted the overall toluene oxidation activity of CoMn₂O₄. In summary, Ru-CoMn₂O₄ represented a promising catalyst for the efficient oxidation of VOCs. Full article

Non-homologous end joining (NHEJ) is a critical DNA double-strand break (DSB) repair pathway that operates throughout the cell cycle to maintain the genomic stability of the cell. Unlike homologous recombination (HR), NHEJ is capable of repairing DSBs without the need for a homologous template, making it a rapid response mechanism, but potentially prone to errors. Central to NHEJ function and essential for the ligation through the recruitment and activation of additional repair factors, such as Artemis, XRCC4, and DNA ligase IV, is the DNA-dependent protein kinase (DNA-PK) complex. Dysregulation in the NHEJ pathway contributes to genomic instability, oncogenesis, and resistance to genotoxic therapies. Consequently, inhibitors of DNA-PK have emerged as promising therapeutic agents to sensitize tumor cells to radiation and DNA-damaging chemotherapeutics. Inhibiting the DNA-PK ability to recruit the protein complex needed for successful DSB repair promotes cell death through apoptosis or mitotic catastrophe. While inhibitors of DNA-PK can be used to enhance the effects of genotoxic therapies, the field still struggles to address critical problems: how to best exploit the differential DNA repair capacities among tumor subtypes, how to maximize radiosensitization of cancerous cells while sparing normal tissues, and how to translate preclinical studies into clinical benefits. Given that NHEJ constitutes the primary line of defense against radiation-induced damage, rapidly repairing the majority of double-strand breaks throughout the cell cycle, this review concentrates on targeting the DNA-PK complex, as the master regulator of this rapid-response mechanism, highlighting why its inhibition represents a strategic action to overcome intrinsic radioresistance. The implementation of DNA-PK inhibitors into medical practice can enable the stratification of oncologic patients into two categories, based on the tumors’ vulnerability to NHEJ disruptions. Thus, the therapeutic pathways of patients with NHEJ tumors could branch, combining traditional genotoxic therapies (radiation and DNA-damaging chemotherapeutics) with DNA-PK inhibitors to achieve an enhanced effect and improved survival outcomes. Full article

Antibiotics represent a unique and diverse group of drugs, which are known to exert deleterious effects on non-target species and contribute to the phenomenon of antimicrobial resistance. With central inclusion on the EU Surface Water Watch List, and reported known affects in multiple model organisms, the importance of the sufficient monitoring of antibiotics in the aquatic environment has been highlighted. Most studies report the impact of individual antibiotics following exposure for a single generation in animals. In this study, we assessed the impact of four antibiotics with different modes of action (amoxicillin, trimethoprim, erythromycin, and sulfamethoxazole) and their mixture on the sentinel species Daphnia magna over three generations, via biochemical markers and a targeted metabolomic analysis of central metabolic pathways. No mortality was observed at 50 mg/L of each selected antibiotic and their composite mixture. Thus, a working concentration of 1 mg/L was chosen to progress this study. Results indicated that enzyme activity was particularly sensitive to exposure to amoxicillin and the mixture, whereas trimethoprim and the mixture induced the most metabolic changes in glycolysis and the TCA cycle. Additionally, the quaternary mixture had a stronger impact on the first generation of daphnids, altering the activity of β-galactosidase, glutathione S-transferase, and acid and alkaline phosphatase, suggesting that Daphnia can adapt to stress caused by antibiotics. Full article

Recycling water offers a powerful way to lower the environmental water impact of mining activities. Pressure-retarded osmosis (PRO) represents a promising pathway for simultaneous water reuse and clean energy generation from salinity gradients. In this study, the performance of a thin-film nanocomposite (TFN) membrane containing functionalized multi-walled carbon nanotubes (fMWCNTs) within a polyacrylonitrile (PAN) support layer, followed by polydopamine (PDA) surface modification, was investigated under a PRO operation using pretreated gold mining wastewater as the feed solution. Unlike most previous studies that rely on synthetic feeds, this work evaluates the membrane performance under a PRO operation using a real mining wastewater stream. The membrane with fMWCNTs and PDA exhibited a maximum power density of 25.22 W/m² at 12 bar, representing performance improvements of 23% and 68% compared with the pristine thin-film composite (TFC) and commercial cellulose triacetate (CTA) membranes, respectively. A high water flux of 75.6 L·m⁻²·h⁻¹ was also obtained, attributed to enhanced membrane hydrophilicity and reduced internal concentration polarization. The optimized membrane, containing 0.3 wt% fMWCNTs in the support layer and a PDA coating on the active layer, produced a synergistic enhancement in the PRO performance, resulting in a lower reverse salt flux and an improved flux–selectivity trade-off. Furthermore, the ultrafiltration (UF) and nanofiltration (NF) pretreatment effectively reduced the hardness and ionic content, enabling a stable PRO operation with real mining wastewater over a longer period of time. Overall, this study demonstrates the feasibility of achieving both reusable water and enhanced osmotic power generation using modified TFN membranes under realistic mining wastewater conditions. Full article

The Chang 7 shale oil reservoirs of the Yanchang Formation in the Heishui Area of the Ordos Basin display typical tight sandstone characteristics, marked by complex microscopic pore structures and limited flow capacity, which severely constrain efficient development. Using a suite of laboratory techniques—including nuclear magnetic resonance, mercury intrusion porosimetry, oil–water relative permeability, spontaneous imbibition experiments, scanning electron microscopy, and thin section analysis—this study systematically characterizes representative tight sandstone samples and examines the microscopic distribution of remaining oil, flow behavior, and their controlling factors. Results indicate that residual oil is mainly stored in nanoscale micropores, whereas movable fluids are predominantly concentrated in medium to large pores. The bimodal or trimodal T₂ spectra reflect the presence of multiscale pore–fracture systems. Spontaneous imbibition and relative permeability experiments reveal low displacement efficiency (average 41.07%), with flow behavior controlled by capillary forces and imbibition rates exhibiting a three-stage pattern. The primary factors influencing movable fluid distribution include mineral composition (quartz, feldspar, lithic fragments), pore–throat structure (pore size, sorting, displacement pressure), physical properties (porosity, permeability), and heterogeneity (fractal dimension). High quartz and illite contents enhance effective flow pathways, whereas lithic fragments and swelling clay minerals significantly impede fluid migration. Overall, this study clarifies the coupled “lithology–pore–flow” control mechanism, providing a theoretical foundation and practical guidance for the fine characterization and efficient development of tight oil reservoirs. The findings can directly guide the optimization of hydraulic fracturing and enhanced oil recovery strategies by identifying high-mobility zones and key mineralogical constraints, enabling targeted stimulation and improved recovery in the Chang 7 and analogous tight reservoirs. Full article

Background: Uncontrolled diabetes is characterised by a loss of blood glucose control and increased oxidation of fatty acids to produce ATP. Use of metabolic inhibitors to blunt fatty acid oxidation and restore glucose metabolism is a poorly studied intervention for diabetes. Methods: Steptozotocin-induced diabetes was developed in Wistar male rats. A subset was supplemented with mildronate (100 mg/kg—14 days). Exploiting liquid chromatography-mass spectrometry for workflows including ion exchange-, C18-reverse phase- and HILIC-based chromatography methods, metabolite levels were quantified in plasma liver and brain tissue. Using both untargeted and targeted metabolomic analysis changes to the global tissue metabolome and individual metabolic pathways were estimated. Results: We document that an inhibitor of carnitine synthesis, mildronate, decreased plasma (50% p < 0.01) carnitine abundance and decreased plasma glucose concentration by one-third compared to streptozotocin (STZ)-treated rats (p < 0.001). Targeted metabolomic analysis of the liver showed decreased alpha-ketoglutarate abundance (35% p < 0.05) by STZ diabetes that was further decreased following mildronate treatment (50% p < 0.05). For both beta-hydroxybutyrate and succinate levels, STZ diabetes increased hepatic abundance by 50% (p < 0.05 for both), which was restored to control levels by mildronate (p < 0.05 for both). In contrast, brain TCA intermediate abundances were unaffected by either STZ diabetes or mildronate (NS for all). STZ diabetes also decreased abundance of pentose phosphate pathway (PPP) metabolites in the liver (glucose-6-phosphate, 6-phosphogluconolactone, 6-phosphogluconate 50% for all; p < 0.05), which was not restored by mildronate treatment. However, brain PPP metabolite abundance was unchanged by STZ diabetes or mildronate (NS for all). However, mildronate treatment did not affect the increased abundance of brain sorbitol, sorbitol-6-phosphate and glucose-6-phosphate as a result of STZ diabetes. Conclusions: Together, these observations highlight the potential role that metabolic inhibitors, like mildronate, may play in restoring blood glucose for diabetic patients, without a direct effect of tissues that represent obligate consumers of glucose (e.g., brain) whilst manipulating fat oxidation in tissues such as the liver. Full article

Enzymes of the sulfur assimilation pathway represent promising candidates for selective herbicide development. This study investigated the effects of O-benzyl-serine (OBS), a newly identified inhibitor of O-acetylserine(thiol)-lyase (OAS-TL), on two C3 weed species, Ipomoea grandifolia and Euphorbia heterophylla. Plants were cultivated hydroponically for 12 days in the presence of OBS (0–500 µM). OBS inhibited root growth in both species in a dose-dependent manner, with I. grandifolia being more sensitive. OAS-TL activity decreased in the roots of I. grandifolia but increased in the leaves of E. heterophylla. Nutrient profiling revealed significant alterations in sulfur, magnesium, and calcium contents, associated with chlorosis and reduced root and leaf development. While photosynthetic performance appeared unaffected at the lowest OBS concentration tested (62.5 µM), higher doses drastically reduced leaf expansion, preventing further measurements. Given this marked decline in foliar development, it is reasonable to infer that the overall photosynthetic capacity of the plants was also negatively affected under severe OBS exposure. OBS also disrupted apical dominance, promoting lateral shoot formation. These findings demonstrate that OBS differentially affects sulfur metabolism and growth in a species- and organ-specific manner, supporting its potential as a prototype molecule for herbicides targeting novel biochemical pathways. Full article

The Iraqi coastline in the northern Persian Gulf is highly vulnerable to the impacts of future sea level rise. This study introduces a novel approach in the Arc Geographic Information System (ArcGIS) for inundation risk of the 58 km Iraqi coast of the northern Persian Gulf through a combination of multi-data sources, machine-learning predictions, and hydrological connectivity by Landsat. The Prophet/Neural Prophet time-series framework was used to extrapolate future sea level rise with 11 satellite altimetry missions that span 1993–2023. The coastline was obtained by using the Landsat-8 Operational Land Imager (OLI) imagery based on the Normalised Difference Water Index (NDWI), and topography was obtained by using the ALOS World 3D 30 m DEM. Global Land Use and Land Cover (LULC) projections (2020–2100) and population projections (2020–2100) were used as future inundation values. Two scenarios were compared, one based on an altimeter-based projection of sea level rise (SLR) and the other based on the National Aeronautics and Space Administration (NASA) high-emission scenario, Representative Concentration Pathway 8.5 (RCP8.5). It is found that, by the IPCC AR6 end-of-century projection horizon (relative to 1995–2014), 154,000 people under the altimeter case and 181,000 people under RCP8.5 will have a risk of being inundated. The highest flooded area is the barren area (25,523–46,489 hectares), then the urban land (5303–5743 hectares), and finally the cropland land (434–561 hectares). Critical infrastructure includes 275–406 km of road, 71–99 km of electricity lines, and 73–82 km of pipelines. The study provides the first hydrologically verified Digital Elevation Model (DEM)-refined inundation maps of Iraq that offer a baseline, in the form of a comprehensive and quantitative base, to the coastal adaptation and climate resilience planning. Full article

Amid the intensifying global mandate for sustainable aquafeed strategies, this study investigates the functional efficacy and biochemical implications of black soldier fly larvae oil (BLO), extracted via recently approved patent method depending on cold-aqueous process, as a substitute for conventional fish oil (FO) in zebrafish (Danio rerio) diets. The refined extraction technique, representing an advancement over traditional aqueous methodologies, was engineered to selectively preserve bioactive lipid fractions while minimizing environmental footprint and processing residues. Over a 28-day feeding period, adult zebrafish were allocated into triplicate groups and fed diets comprising 0%, 50%, and 100% substitution of FO with BLO and growth, lipid composition, and dietary fatty acid profiles of both diets and flesh were rigorously evaluated. Zebrafish fed the BLO₁₀₀ diet exhibited the most pronounced somatic growth (2.47 ± 0.01 g), significantly elevated specific growth rates (3.88 ± 0.82% day⁻¹), and the most efficient feed conversion, without compromising survival. Flesh lipid analysis revealed a substantial enrichment in saturated fatty acids—most notably lauric acid (C12:0)—corresponding to increasing dietary BLO levels. Although dietary EPA and DHA levels were reduced, DHA concentrations in fish tissues remained comparable to those of the control group, indicating a compensatory capacity mediated by endogenous elongation and desaturation pathways. These findings substantiate the dual potential of BLO as both a nutritionally viable lipid source and a vector for enhancing aquafeed sustainability. The cold-aqueous extraction method demonstrated here underscores a pivotal advancement in green lipid processing, aligning oil quality with ecological stewardship. This integrative approach not only reinforces BLO’s candidacy as a strategic fish oil substitute but also delineates a pathway toward scalable, species-adapted feed innovation. Future investigations should prioritize the modulation of fatty acid profiles through dietary and extraction optimization to fully realize the translational potential of insect-derived lipids in aquaculture. Full article

Background/Objectives: Blood donation is essential to health systems and represents a valuable epidemiological model for studying physiological adaptation to controlled blood loss. Regular blood donors constitute a distinct, health-screened population whose biological responses offer unique insight into mechanisms of resilience and key determinants of population health. Hypoxia-inducible factor 1-alpha (HIF-1α) is a key regulator of erythropoiesis and cellular response to hypoxia, and its modulation following blood donation may inform donor safety and the sustainability of blood donation programs. This study aimed to characterize the sociodemographic, lifestyle, and anthropometric profiles of blood donors in relation to hematopoietic biomarkers (vitamin B12 and folic acid) and to evaluate changes in serum HIF-1α concentration after donation, emphasizing the public health relevance of voluntary blood donation. Methods: A cross-sectional study was conducted among 324 voluntary blood donors (159 regular and 165 occasional). Serum HIF-1α was measured before and 30 min after donation, together with vitamin B12 and folic acid levels. Sociodemographic and lifestyle characteristics (physical activity, smoking, dietary habits) were collected through standardized questionnaires (EHIS-3, FFQ), and anthropometric parameters were assessed. Results: Regular donors were older and predominantly male, with comparable socioeconomic indicators between groups. Both regular and occasional donors showed favorable lifestyle profiles, including low smoking prevalence and moderate physical activity. Skinfold thickness was significantly greater in regular donors (p < 0.001). The main biological finding was a robust post-donation increase in HIF-1α concentrations (≈80%, p < 0.001), independent of donation frequency or lifestyle. No significant associations were found between lifestyle factors and vitamin B12 or folate levels. Conclusions: Blood donation induces a rapid elevation in HIF-1α, reflecting activation of hypoxia-responsive pathways and short-term hematopoietic adaptation. Beyond its biomedical relevance, voluntary blood donation represents a meaningful epidemiological and public health model for studying physiological resilience and the health benefits of altruistic behavior. These findings underscore the importance of donor surveillance and motivation as components of broader preventive health and health equity strategies. Full article