Search Results (3,183)

Poly(ε-caprolactone)-b-polysarcosine (PCL-b-PSar) block copolymers (BCPs) emerge as a promising alternative to conventional poly(ε-caprolactone)-b-poly(ethylene oxide) BCPs for biomedical applications, leveraging superior biocompatibility and biodegradability. In this study, we synthesized two series of PCL-b-PSar BCPs with controlled polymerization degrees (DP of PCL: 45/67; DP of PSar: 28–99) and low polydispersity indexes (Đ ≤ 1.1) and systematically investigated their crystallization-driven self-assembly (CDSA) in alcohol solvents (ethanol, n-butanol, and n-hexanol). It was found that the limited solubility of PSar in alcohols resulted in competition between micellization and crystallization during self-assembly of PCL-b-PSar, and thus coexistence of lamellae and spherical micelles. To overcome this morphological heterogeneity, we developed a modified self-seeding method by employing a two-step crystallization strategy (i.e., T_c1 = 33 °C and T_c2 = 8 °C), achieving conversion of micelles into crystals and yielding uniform self-assembled structures. PCL-b-PSar BCPs with short PSar blocks tended to form well-defined two-dimensional lamellar crystals, while those with long PSar blocks induced formation of hierarchical structures in the PCL₄₅ series and polymer aggregation on crystal surfaces in the PCL₆₇ series. Solvent quality notably influenced the self-assembly pathways of PCL₄₅-b-PSar₂₈. Lamellar crystals were formed in ethanol and n-butanol, but micrometer-scale dendritic aggregates were generated in n-hexanol, primarily due to a significant Hansen solubility parameter mismatch. This study elucidated the CDSA mechanism of PCL-b-PSar in alcohols, enabling precise structural control for biomedical applications. Full article

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver condition globally, strongly linked to obesity, insulin resistance, and type 2 diabetes (T2D). Tirzepatide (TZP), a dual GIP/GLP-1 receptor agonist, improves glycemic control and reduces body weight and the liver fat content in patients with obesity and T2D. However, its effect on liver-specific outcomes such as steatosis and fibrosis remains incompletely characterized. Low-energy ketogenic therapy (LEKT), a nutritional strategy characterized by carbohydrate restriction and nutritional ketosis, may enhance hepatic β-oxidation and reduce hepatic lipogenesis. To date, however, the combination of TZP and LEKT has not been studied in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). This study aimed to compare the hepatic and metabolic effects of TZP combined with either LEKT or a conventional low-calorie diet (LCD) over a 12-week period. Methods: Sixty adult patients with MASLD undergoing TZP therapy were prospectively assigned to either an LEKT or a conventional LCD, with 30 participants per group. As primary endpoints, the controlled attenuation parameter (CAP, an index of hepatic steatosis) and liver stiffness measurement (LSM, an index of liver fibrosis) were assessed at the baseline and after 12 weeks using FibroScan^®. Secondary outcomes included changes in body mass index (BMI), glycated hemoglobin (HbA1c), and liver enzymes. Adherence to both diet and pharmacological treatment, as well as tolerability, were systematically monitored throughout the intervention period. Results: Both groups showed significant reductions in body weight (TZP + LEKT, p = 0.0289; TZP + LCD, p = 0.0278), with no significant intergroup difference (p = 0.665). CAP and LSM improved significantly in both groups, but reductions were greater in the TZP + LEKT group (CAP −12.5%, p < 0.001; LSM −22.7%, p < 0.001) versus LCD (CAP −6.7%, p = 0.014; LSM −9.2%, p = 0.022). Between-group differences were statistically significant for both CAP (p = 0.01) and LSM (p = 0.03). Conclusions: Based on these preliminary findings, we support the hypothesis that the combination of TZP and LEKT may be superior to TZP with an LCD in reducing hepatic steatosis and stiffness in individuals with obesity. Full article

Semi-natural grasslands are some of the most species-rich habitats in Europe and provide important ecosystem services such as biodiversity conservation, carbon sequestration and soil fertility maintenance. This study investigates how different intensities of grassland management affect the composition of functional groups and soil chemical properties. Five grassland management systems were analyzed: Cut3—three cuts per year; LGI—low grazing intensity; CG—combined cutting and grazing; Cut4—four cuts per year; and HGI—high grazing intensity. The functional groups assessed were grasses, legumes and forbs, while soil samples from three depths (0–10, 10–20 and 20–30 cm) were analyzed for their chemical properties (soil organic carbon—SOC; soil total nitrogen—STN; inorganic soil carbon—SIC; soil organic matter—SOM; potassium oxide—K₂O; phosphorus pentoxide—P₂O₅; C/N ratio; and pH) and physical properties (volumetric soil water content—VWC; bulk density—BD; and porosity—POR). The results showed that less intensive systems had a higher proportion of legumes, while species diversity, as measured via the Shannon index, was the highest in the Cut4 system. The CG system tended to have the highest SOC and STN at a 0–10 cm depth, with a similar trend observed for SOC_stock at a 0–30 cm depth. The Cut4, HGI and CG systems also had an increased STN_stock. Both grazing systems had the highest P₂O₅ content. A tendency towards a higher BD was observed in the top 10 cm of soil in the more intensive systems. Choosing a management strategy that is tailored to local climate and site conditions is crucial for maintaining grassland stability, enhancing carbon sequestration and promoting long-term sustainability in the context of climate change. Full article

Microgreens, having short growth cycles and efficient nutrient uptake, are ideal candidates for biofortification. This study investigated the effects of selenium (Se) and zinc (Zn) on photosynthetic performance in four hydroponically grown Brassica microgreens (broccoli, pak choi, kohlrabi, and kale), using direct and modulated chlorophyll a fluorescence and chlorophyll-to-carotenoid ratios (Chl/Car). The plants were treated with Na₂SeO₄ at 0 (control), 2, 5, and 10 mg/L or ZnSO₄ × 7H₂O at 0 (control), 5, 10, and 20 mg/L. The results showed species-specific responses with Se or Zn uptake. Selenium enhanced photosynthetic efficiency in a dose-dependent manner for most species (8–26% on average compared to controls). It increased the plant performance index (PI_tot), particularly in pak choi (+62%), by improving both primary photochemistry and inter-photosystem energy transfer. Kale and kohlrabi exhibited high PSII-PSI connectivity for efficient energy distribution, with increased cyclic electron flow around PSI and reduced Chl/Car up to 8.5%, while broccoli was the least responsive. Zinc induced variable responses, reducing PI_tot at lower doses (19–23% average decline), with partial recovery at 20 mg/L (9% average reduction). Broccoli exhibited higher susceptibility, with inhibited Q_A re-oxidation, low electron turnover due to donor-side restrictions, and increased pigment ratio (+3.6%). Kohlrabi and pak choi tolerated moderate Zn levels by redirecting electron flow, but higher Zn levels impaired PSII and PSI function. Kale showed the highest tolerance, maintaining stable photochemical parameters and total electron flow, with increased pigment ratio (+4.5%) indicating better acclimation. These results highlight the beneficial stimulant role of Se and the dual essential/toxic nature of Zn, thus emphasizing genotype and dose-specific optimizations for effective biofortification. Full article

Background/Objectives: The consumption of refined carbohydrates has increased globally. It is associated with inflammation and oxidative stress, both recognized as risk factors for cardiovascular disease. This study investigated the effects of a refined carbohydrate-rich diet on the vascular reactivity of rat aorta. Methods: We acclimatized adult male Wistar rats for two weeks and then randomly assigned them to two experimental groups: a control (CT) group and a high-carbohydrate diet (HCD) group. The CT group received standard laboratory chow for 15 days, while the HCD group received a diet composed of 45% sweetened condensed milk, 10% refined sugar, and 45% standard chow. After the dietary exposure period, we evaluated the vascular reactivity of aortic rings, gene expression related to inflammation, superoxide dismutase activity, and biochemical parameters, including cholesterol, triglycerides, fasting glucose, and glucose and insulin tolerance. Results: The results demonstrate a reduction in vascular reactivity caused by endothelial alterations, including increased NO production, which was observed as higher vasoconstriction in the presence of L-NAME and aminoguanidine and upregulation of iNOS gene expression. In addition, increased production of free radicals, such as O₂^-, was observed, as well as immune markers like MCP-1 and CD86 in the HCD group. Additionally, the HCD group showed an increase in the TyG index, suggesting early metabolic impairment. GTT and ITT results revealed higher glycemic levels, indicating early signs of insulin resistance. Conclusions: These findings indicate that short-term consumption of a refined carbohydrate-rich diet may trigger oxidative stress and endothelial dysfunction, thereby increasing the risk of cardiovascular complications. Full article

Biochar has emerged as a promising soil amendment for mitigating heavy metal contamination in agricultural systems. This study investigates the effects of biochar on cadmium (Cd) and copper (Cu) uptake, plant growth, oxidative stress, and physiological responses in lettuce (Lactuca sativa L.) plants exposed to different metal concentrations. Results indicate that biochar significantly influenced Cd bioavailability, reducing its accumulation in plant tissues by up to 31.9% and alleviating oxidative stress, with malondialdehyde and proline levels decreasing by up to 51.0% and 60.2%, particularly at higher application rates (5%). Cd-exposed plants treated with biochar exhibited an improved fresh weight (+22.6%), lower malondialdehyde and proline levels, and enhanced the chlorophyll content (+14.9% to 24.1%) compared to untreated plants. The bioaccumulation factor for Cd decreased (up to 31.8%) while the immobilization index (II) increased, confirming the role of biochar in limiting Cd mobility in soil. In contrast, Cu uptake remained consistently low across all treatments, with a significant reduction observed only at higher contamination levels (up to −34.2%). Biochar contributed to Cu immobilization, reflected in increased II values, and enhanced the plant biomass and chlorophyll content under Cu exposure (+15.4% and up to +24.1%, respectively), suggesting a partial alleviation of Cu toxicity. These findings highlight biochar’s potential in heavy metal remediation, particularly for Cd, by reducing bioavailability and improving plant resilience. However, its role in Cu-contaminated soils is mainly through immobilization rather than uptake reduction. Full article

Background/Objectives: This study aimed to evaluate the effects of lung injury induced by insoluble uranium oxide particles on gut microbiota and related metabolites in rats. Methods: The rats were randomly divided into six UO₂ dose groups. A rat lung injury model was established through UO₂ aerosol. The levels of uranium in lung tissues were detected by ICP-MS. The expression levels of the inflammatory factors and fibrosis indexes were measured by enzyme-linked immunosorbent assay. Paraffin embedding-based hematoxylin & eosin staining for the lung tissue was performed to observe the histopathological imaging features. Metagenomic sequencing technology and HM700-targeted metabolomics were conducted in lung tissues. Results: Uranium levels in the lung tissues increased with dose increase. The expression levels of Tumor Necrosis Factor-α (TNF-α), Interleukin-1β (IL-1β), Collagen I, and Hydroxyproline (Hyp) in rat lung homogenate increased with dose increase. Inflammatory cell infiltration and the deposition of extracellular matrix were observed in rat lung tissue post-exposure. Compared to the control group, the ratio of Firmicutes and Bacteroides in the gut microbiota decreased, the relative abundance of Akkermansia_mucinphila decreased, and the relative abundance of Bacteroides increased. The important differential metabolites mainly include αlpha-linolenic acid, gamma-linolenic acid, 2-Hydroxybutyric acid, Beta-Alanine, Maleic acid, Hyocholic acid, L-Lysine, L-Methionine, L-Leucine, which were mainly concentrated in unsaturated fatty acid biosynthesis, propionic acid metabolism, aminoacyl-tRNA biosynthesis, phenylalanine metabolism, and other pathways in the UO₂ group compared to the control group. Conclusions: These findings suggest that uranium-induced lung injury can cause the disturbance of gut microbiota and its metabolites in rats, and these changes are mainly caused by Akkermansia_mucinphila and Bacteroides, focusing on unsaturated fatty acid biosynthesis and the propionic acid metabolism pathway. Full article

Long-term storage may induce lipid oxidation in brown rice and impact its utilization in animal diets. One-day-old male Ross 308 broiler chickens (with an initial body weight of 20 g) were randomly divided into three groups: corn-based diet (Corn), fresh brown rice-based diet (BR1) and stored brown rice-based diet (BR6), with 8 replicates of 10 birds per pen, in a 42-day feeding trial. The results showed that lipid oxidation indexes increased and fatty acid composition changed significantly in BR6 (p < 0.05). The dietary replacement of corn with brown rice showed no effects on growth performance of broilers (p > 0.05). However, palmitic acid and oleic acid increased, and stearic acid, linoleic acid and docosadienoic acid decreased in the broiler breast muscle of the BR1 and BR6 groups (p < 0.05). Ileum antioxidant enzyme activities increased in the BR1 and BR6 groups compared to the Corn group (p < 0.05), and the activities of α-amylase, trypsin, chymotrypsin and lipase decreased in the BR6 group compared to the BR1 and Corn groups (p < 0.05). Also, compared to the BR1 group, the overall expression of metabolites involved in drug metabolism—cytochrome P450, GnRH secretion and the estrogen signaling pathway in broiler ileum were down-regulated in the BR6 group (p < 0.05). In conclusion, the lipid oxidation of stored brown rice decreased digestive enzyme activities and changed metabolic characteristics in the ileum of broilers. While replacing corn with brown rice did not affect broiler growth performance, it reduced the contents of unsaturated and essential fatty acids in breast muscle and enhanced the ileal antioxidant functions of broilers. Full article

Background: Vitiligo, a chronic depigmentation disorder driven by oxidative stress and immune dysregulation, remains poorly understood mechanistically. The Keap1/NRF2/ARE pathway is critical for melanocyte protection against oxidative damage; however, the role of Cullin-3 (CUL3), a scaffold for E3 ubiquitin ligases that regulate NRF2 degradation, and its interplay with inflammatory mediators in vitiligo pathogenesis are underexplored. This study investigates CUL3, NRF2, and the associated regulatory networks in vitiligo, integrating clinical profiling and computational docking to identify therapeutic targets. Methods: A case-control study compared non-segmental vitiligo patients with age-/sex-matched controls. Lesional skin biopsies were analyzed by qRT-PCR for the expression of CUL3, NRF2, miRNA-146a, FOXP3, NF-κB, IL-6, TNF-α, and P53. Molecular docking was used to evaluate vitexin’s binding affinity to Keap1, validated by root mean square deviation (RMSD) calculations. Results: Patients with vitiligo exhibited significant downregulation of CUL3 (0.27 ± 0.03 vs. 1 ± 0.58; p = 0.013), NRF2 (0.37 ± 0.26 vs. 1 ± 0.8; p = 0.001), and FOXP3 (0.09 ± 0.2 vs. 1 ± 0.3; p = 0.001), alongside the upregulation of miRNA-146a (4.7 ± 1.9 vs. 1 ± 0.8; p = 0.001), NF-κB (4.7 ± 1.9 vs. 1 ± 0.5; p = 0.001), IL-6 (2.8 ± 1.5 vs. 1 ± 0.4; p = 0.001), and TNF-α (2.2 ± 1.1 vs. 1 ± 0.3; p = 0.001). P53 showed no differential expression (p > 0.05). Docking revealed a strong binding of vitexin to Keap1 (RMSD: 0.23 Å), mirroring the binding of the control ligand CDDO-Im. Conclusions: Dysregulation of the CUL3/Keap1/NRF2 axis and elevated miRNA-146a levels correlate with vitiligo progression, suggesting a role for oxidative stress and immune imbalance. Vitexin’s high-affinity docking to Keap1 positions it as a potential modulator of the NRF2 pathway, offering novel therapeutic avenues. This study highlights the translational potential of targeting the ubiquitin–proteasome and antioxidant pathways in the management of vitiligo. Full article

Fusaric acid (FSA) is a mycotoxin produced by pathogenic Fusarium species that inhibits the growth of various beneficial microbes. In this study, we investigated the molecular mechanisms by which Trichoderma harzianum NJAU4742 (Th), a beneficial fungus, responds to FSA-induced stress. Here, by combining a transcriptome analysis, a gene knockout, and physiological data measurements, our study investigated the molecular mechanisms underlying the response of Trichoderma harzianum NJAU4742 (Th) to FSA stress. The results showed that FSA can induce severe oxidative stress in Th, and an aldehyde dehydrogenase (Thaldh3) in Th plays a critical role in alleviating FSA stress. Deleting Thaldh3 significantly decreased the γ-aminobutyrate (GABA) content, causing more severe oxidative damage in Th. Furthermore, we also provide evidence demonstrating that Thaldh3 alleviates FSA stress by enhancing the activities of key enzymes involved in the tricarboxylic acid cycle and ATP content. A pot experiment showed that an enhanced tolerance to FSA increased the Th biomass, strengthening its antagonistic capacity against pathogens and reducing the disease index in tomatoes. In conclusion, these observations provide new insight into the role of beneficial microbes in promoting plant health. Full article

The accumulation of nanoparticles (NPs) in the female body has raised global concerns regarding potential effects on the reproductive system. This study aimed to investigate the toxic effects of nano-titanium dioxide (nano-TiO₂) exposure on the ovaries and the underlying mechanisms. By establishing a nano-TiO₂ accumulation model in mice, our research systematically evaluated the effects of different concentrations of nano-TiO₂ exposure on the development and reproductive endocrine functions of mice. The results showed that nano-TiO₂ exposure significantly reduced the littering rate, sex hormone levels, and ovarian index of mice, and the effects were dose-dependent. Studies on the mechanisms involved revealed that nano-TiO₂ induces an excessive production of reactive oxygen species (ROS), leading to the potential collapse of the mitochondrial membrane and an increase in the apoptosis rate of granulosa cells, thereby triggering oxidative stress and inhibiting the expression of ovarian-specific genes and granulosa-cell function genes. This study reveals the “dual blow” mechanism of nano-TiO₂-mediated ovarian morphology and function through oxidative stress in granulosa cells, namely directly disrupting cellular homeostasis and interfering with the reproductive-related gene network, ultimately leading to decreased ovarian function. This provides experimental evidence for assessing the reproductive risks of nanomaterials in women. Full article

Previously, research adopted an ultrasound-assisted extraction method to isolate crude polysaccharide from blackened jujube, followed by preliminary structural identification of the purified polysaccharide (BJP). This manuscript analyzed the accurate structure and immunomodulatory activity of BJP. Further structural identification indicated that BJP was mainly composed of →3)-α-L-Araf-(1→, →3,5)-α-L-Araf-(1→, →3)-β-D-GalpA-(1→, →2,4)-β-D-Galp-(1→, →4)-β-D-GalpA-(1→, →3)-α-L-Rhap-(1→ and →3,4)-α-L-Rhap-(1→. The immunomodulatory effects of BJP were examined using a mouse model with immunosuppression induced by cyclophosphamide. The findings suggested that BJP could relieve the condition of immunosuppressed mice. BJP could inhibit decreases in the body weight and organ index of mice, and HE staining showed that BJP could alleviate the harm to spleen and thymus tissues. BJP enhanced the secretion of interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), interleukin-2 (IL-2), interleukin-6 (IL-6), immunoglobulin A (IgA), and immunoglobulin G (IgG) in serum. It also reduced liver oxidative stress by increasing superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) activities, while lowering malondialdehyde (MDA) levels. Moreover, BJP contributed to the maintenance of gut homeostasis by stimulating the generation of short-chain fatty acids in the cecal contents. The study aims to establish a solid basis for the comprehensive development of blackened jujube and furnish a theoretical framework for its polysaccharides’ role in immune modulation. Full article

The Stability Toolkit for the Appraisal of Bio/Pharmaceuticals’ Level of Endurance (STABLE) is introduced and proposed as a comprehensive tool and software to evaluate the stability of active pharmaceutical ingredients (APIs) under various stress conditions. In the pharmaceutical industry, stability testing is a critical step in the drug development process, ensuring the quality, safety, and efficacy of APIs. Traditional stability tests—such as real-time, accelerated, and forced degradation testing—often face challenges, including inconsistent interpretation and implementation across different regions and organizations. STABLE addresses these challenges by providing a standardized and holistic approach to assessing drug stability across five key stress conditions: oxidative, thermal, acid-catalyzed hydrolysis, base-catalyzed hydrolysis, and photostability. Beyond its role as an evaluation tool, STABLE also serves as a practical guide for chemists, encouraging a more complete and thoughtful approach to stability studies. While many investigations focus solely on acid- and base-catalyzed hydrolysis, other critical conditions—such as photostability—are often underexplored or entirely omitted. By highlighting the importance of evaluating all relevant degradation pathways, STABLE promotes more robust and informed stability testing protocols. The index utilizes a color-coded scoring system to quantify and compare stability, facilitating consistent assessments across different APIs. This paper discusses the methodology of STABLE, including the scoring system and specific criteria applied under each condition. This tool is introduced to reflect intrinsic degradation susceptibility under forced conditions. The software is freely available as an open-source tool at bit.ly/STABLE2025, enabling broader accessibility and implementation across the pharmaceutical research community. Full article

Psoriasis is a chronic inflammatory autoimmune disease that causes significant deterioration of the quality of life, and due to its multifactorial causes, it is often difficult to manage. Apart from genetic and environmental components, an important part of its pathophysiology comprises an oxidative stress induction that the standard antioxidative mechanisms of the human body cannot compensate for. Moreover, in many psoriatic patients, there is a documented imbalance between antioxidant and pro-oxidative factors. Usually, psoriasis is evaluated using the Psoriasis Area and Severity Index (PASI) score. It has been demonstrated that dietary choices can lead to significant modification of PASI scores. Hypocaloric diets that are rich in antioxidants are highly effective in this regard, especially when focusing on vegetables and restricting consumption of animal-derived protein. Specific dietary regimens, namely the Mediterranean diet and potentially the ketogenic diet, are very beneficial, in the former case owing in large part to the omega-three fatty acids it provides and its ability to alter gut microbiome, a factor which seems to play a notable role in the pathogenesis of the disease. Another option is the topical application of vitamin D and its analogues, combined with corticosteroids, which can ameliorate the manifestations of psoriasis at the level of the skin. Finally, oral vitamin D supplementation has a positive impact on psoriatic arthritis and can mitigate the risk of associated comorbidities. Full article

Soil erosion-prone areas require effective microbial treatments to improve soil bacterial communities and functional traits. Understanding the driving effects of different microbial interventions on soil ecology is essential for restoration efforts. Single and combined microbial treatments were applied to soil. Bacterial community structure was analyzed via 16S IRNA high-throughput sequencing, and functional groups were predicted using FAPROTAX. Soil microbial carbon, nitrogen, metabolic entropy, and enzymatic activity were assessed. Microbial Carbon and Metabolic Activity: The Arbuscular mycorrhizal fungi (AMF) and Bacillus mucilaginosus (BM) (AMF.BM) treatment exhibited the highest microbial carbon content and the lowest metabolic entropy. The microbial carbon-to-nitrogen ratio ranged from 1.27 to 3.69 across all treatments. Bacterial Community Composition: The dominant bacterial phyla included Firmicutes, Proteobacteria, Acidobacteria, Bacteroidetes, and Actinobacteria. Diversity and Richness: The AMF and Trichoderma harzianum (TH) (AMF.TH) treatment significantly reduced diversity, richness, and phylogenetic diversity indices, while the AMF.BM treatment showed a significantly higher richness index (p < 0.05). Relative Abundance of Firmicutes: Compared to the control, the AMF, TH.BM, and TH treatments decreased the relative abundance of Firmicutes, whereas the AMF.TH treatment increased their relative abundance. Environmental Correlations: Redundancy and correlation analyses revealed significant correlations between soil organic matter, magnesium content, and sucrase activity and several major bacterial genera. Functional Prediction: The AMF.BM treatment enhanced the relative abundance and evenness of bacterial ecological functions, primarily driving nitrification, aerobic ammonia oxidation, and ureolysis. Microbial treatments differentially influence soil bacterial communities and functions. The AMF.BM combination shows the greatest potential for ecological restoration in erosion-prone soils. Full article