Search Results (14,701)

Background/Objectives: Branched-chain fatty acids (BCFAs) exhibit a range of biological activities; however, their limited natural abundance and high cost have constrained in vivo research. Lanolin represents a promising source for enriching BCFAs. Nevertheless, the in vivo application, safety, and dose-effect relationship of BCFAs derived from lanolin (BCFAs-DFL) remain unassessed. Methods: In this study, the acute toxicity in C57BL/6J mice was first evaluated for 7 days by a single oral administration of 5000 mg/kg BW of BCFAs-DFL. Subsequently, 40 mice were divided into four groups (control group, low dose of 100 mg/kg BW, medium dose of 300 mg/kg BW, and high dose of 600 mg/kg BW) and were continuously administered by gavage for 28 days to study the effects of BCFAs-DFL on the growth, blood biochemistry, intestinal morphology, and intestinal flora of the mice. Results: In the acute toxicity test, BCFAs-DFL exhibited no lethality or abnormalities in mice, indicating its non-toxic nature. Throughout the 28-day trial, mice in the medium- and high-dose groups experienced a notable decrease in average daily feed intake (p < 0.05), yet their weight gain remained unaffected (p > 0.05). Hemoglobin and hematocrit levels declined in the high-dose group (p < 0.05). Conversely, serum aspartate aminotransferase and total bilirubin levels escalated in the medium- and high-dose groups, while triglycerides and urea nitrogen levels decreased (p < 0.05). The serum’s total antioxidant capacity and immunoglobulin levels (IgA, IgG) rose in proportion to the dosage (p < 0.05). BCFAs-DFL notably enhanced the villus height of the jejunum and ileum in mice (p < 0.05). Gut microbiota analysis indicated no significant impact on overall α and β diversity. Conclusions: The 28-day intervention revealed that BCFAs-DFL can modulate feeding behavior, TG, T-AOC, and immunoglobulin levels in mice. Additionally, it promotes the development of intestinal villi. Based on various indicators, a dosage of 100 mg/kg BW effectively induces beneficial metabolic regulation, such as the reduction of triglycerides, without causing a burden on liver metabolism. This dosage may represent a more suitable application for potential use. Full article

Background/Objectives: Apple pomace, a major by-product of juice production, represents both an environmental burden and an underutilized resource. This study aimed to enhance the nutritional value of apple pomace via solid-state fermentation (SSF) to develop a functional feed ingredient and systematically evaluate its effects on growth, metabolism, and intestinal health in weaned piglets. Methods: Apple pomace was fermented using a multi-species consortium (Geotrichum candidum, Saccharomyces cerevisiae, Rhizopus oryzae, Bacillus subtilis, and Trichoderma viride). A total of 180 weaned piglets were fed iso-nitrogenous diets containing 0, 2, 4, 6, 8, or 10% fermented apple pomace for 35 days. Growth performance, serum biochemical and immuno-antioxidant indices, diarrhea incidence, jejunal morphology, and fecal microbiota were analyzed. Results: Dietary fermented apple pomace supplementation showed dose-dependent effects. The 8% fermented apple pomace group exhibited optimal growth performance, with increased average daily gain and feed intake and reduced feed-to-gain ratio (p < 0.05). Serum analysis indicated enhanced protein synthesis, antioxidant capacity (T-AOC, SOD, GSH-Px), and immunoglobulin levels (IgA, IgG, IgM), along with reduced urea nitrogen and oxidative stress marker MDA. This group also had the lowest diarrhea rate, associated with improved jejunal villus morphology. Microbiota analysis revealed that 8% fermented apple pomace effectively increased α-diversity, promoted beneficial bacteria (e.g., lactic acid bacteria and butyrate-producing Clostridium sensu stricto_1), and suppressed pathogens (Escherichia coli, Salmonella, Streptococcus). Conclusions: Multi-species SSF successively enhanced the nutritional profile of apple pomace. Inclusion at 8% showed the most favorable response in terms of growth performance, metabolic profile, and immune–antioxidant status in weaned piglets, mediated through improved intestinal morphology and targeted modulation of the gut microbiota toward a more diverse and beneficial ecosystem. These findings support the high-value, functional utilization of apple pomace as a feed additive in swine nutrition. Full article

The family Arenaviridae encompasses zoonotic, rodent-borne pathogens (e.g., Lassa, Machupo, and Junín viruses) that cause severe viral hemorrhagic fevers with high case fatality rates. The current therapeutic landscape is severely limited, underscoring the urgent need for novel antiviral strategies. A promising approach involves combining directly acting antivirals with host-targeted antivirals. A compelling host-targeted antiviral target is the aryl hydrocarbon receptor (AHR). This ubiquitous ligand-activated transcription factor is a recognized pro-viral host factor across multiple viral families. Building on prior work with Junín and Tacaribe viruses, we investigated whether the AHR inhibitor CH223191 could enhance the virus-directed antiviral activity of favipiravir against these viruses. First, we evaluated the toxicity and antiviral potential of CH223191 against a lethal Junín virus infection in male and female hTfR1 mice. After demonstrating substantial protection, we conducted preliminary assays to study the antiviral effects of combining CH223191 and favipiravir on Tacaribe virus (TCRV) infections in the Vero cell culture model. We observed synergistic interaction with all four models (ZIP, Loewe, Bliss, and HSA). We next determined the sub-optimal dose of favipiravir and conducted an antiviral combination study in the male and female AG129 mouse model infected with TCRV. The combination effectively protected mice from a lethal TCRV infection and showed cooperative effects, reducing weight loss and viral loads. Overall, these results show that the AHR is a promising pharmacological target for the development of novel antivirals. Furthermore, we discovered a cooperative interaction between the activities of favipiravir and CH223191. Full article

Dendrobium officinale Kimura et Migo (D. officinale) is a traditional Chinese medicinal herb with recognized anti-inflammatory, antioxidant, and immunomodulatory properties. This study evaluated whether dietary supplementation with D. officinale leaf powder could influence bone mass, mechanical strength, and molecular markers of bone metabolism in caged laying hens. A total of 192 healthy 19-week-old Jinghong No. 1 hens were randomly assigned to three dietary groups: a control group fed a basal diet and two treatment groups supplemented with 1200 or 3600 mg/kg of D. officinale leaf powder for 16 weeks. Tibial and femoral bone strength and mineral density did not differ significantly among treatments (p > 0.05). However, tibial breaking strength displayed upward trends in both supplemented groups (p = 0.08), and similar tendencies were observed for femoral bone mineral content and bone density (p = 0.08). At the molecular level, dietary supplementation produced selective changes in gene expression. The low-dose diet significantly increased VEGFA expression (p < 0.05), whereas the high-dose diet resulted in significantly higher TGF-β1 expression (p < 0.05). Several other genes related to bone formation, bone resorption, or cytokine signaling exhibited numerical increases but did not reach statistical significance. These findings indicate that D. officinale leaf powder may modulate bone metabolic processes at the transcriptional level, although these molecular alterations were not accompanied by significant improvements in bone mass. Full article

Listeria monocytogenes is a high-risk pathogenic bacterium associated with ready-to-eat foods and poses a potential threat to consumer health. This study aimed to investigate the prevalence, characterization and genetic diversity of L. monocytogenes in ready-to-eat raw salmon and trout products obtained from physical stores and online stores in China. Out of 150 samples analyzed, 23 (15.3%) were positive for L. monocytogenes. Among these positive samples, three (12%) were from Japanese restaurants, four (16%) from farmers markets, one (2.9%) from large supermarkets and fifteen (30%) from e-commerce platforms, and only one sample showed a contamination level exceeding 100 most probable number (MPN)/g. The isolates from positive samples demonstrated a concrete public health risk through several findings: twenty-three L. monocytogenes exhibited varying degrees of cytotoxicity, ranging from 7.6% to 71.8%. Compared with the reference strain ATCC 19115, five of these isolates were highly cytotoxic, a result that was validated by mouse survival rate experiment, which also confirmed their high virulence at tested dose. All isolates were resistant to cefuroxime sodium, ceftriaxone, cefepime and nalidixic acid, and 13% showed resistance to sulphamethoxazole-trimethoprim. Three serogroups were identified, with serogroup Ⅰ.1 (1/2a, 3a) being the most prevalent (65.2%). These isolates were grouped into eight sequence types, with ST8 (34.8%) and ST87 (30.4%) dominating. All isolates carried virulence genes associated with LIPI-1 andmultiple internalin genes (inlA, inlB, inlJ and inlK), confirming their potential pathogenicity. Additionally, the isolates harbored antimicrobial resistance genes lin and FosX. The five highly virulent isolates exhibited the highest genetic similarity to J2-031 (GCA_000438645.1) and C1-387 (GCA_000438605.1). The results provided valuable information for Chinese regulatory authorities to strengthen the risk monitoring of L. monocytogenes in ready-to-eat raw salmon and trout products. Full article

Aeroponics has emerged as a key technology for sustainable and resource-efficient food production, particularly under intensifying constraints on water availability, land use, and greenhouse gas (GHG) emissions. This review synthesizes recent advances in water–energy–nutrient integration, highlighting operational parameters—humidity (50–80%), temperature (18–25 °C), nutrient solution pH (5.5–6.5), and electrical conductivity (1.5–2.5 mS cm⁻¹)—that critically influence system performance. Evidence indicates that closed-loop water recirculation and AI-assisted monitoring for environmental control and nutrient dosing can stabilize system dynamics and reduce water consumption by more than 90%. Reported yield improvements ranged from 45% to 75% compared with conventional soil-based cultivation. Moreover, systems powered by renewable energy demonstrated up to an 80% reduction in GHG emissions. Life-cycle assessment studies further suggest that aeroponics, coupled with low-carbon electricity in controlled-environment agriculture (CEA), can outperform traditional agricultural supply chains in climate and resource efficiency metrics. Additional technological innovations—including multi-tier vertical rack architectures, optimized misting intervals, and micronutrient-enriched fertigation formulations containing N, P, Ca, Mg, and K—were found to enhance spatial productivity and crop quality. Overall, aeroponics represents a promising pathway toward net-zero, high-performance agricultural systems. Full article

Soil salinity is recognized as a critical abiotic stress that limits plant growth on marginal lands. The cup plant (Silphium perfoliatum L.), a perennial bioenergy species with high biomass potential, has been proposed for cultivation on saline-degraded soils; however, its physiological responses to different types of salinity stress, particularly alkaline and neutral salt stress, remain insufficiently characterized. In the present study, the physiological responses of the cup plant to neutral (NaCl) and alkaline (NaHCO₃) salt stress at concentrations of 100, 200, and 300 mM were evaluated in a pot experiment conducted under controlled conditions. The assessed indicators included relative chlorophyll content (CCI), chlorophyll fluorescence parameters (F_v/F_m, F_v/F₀, PI), and gas exchange characteristics, namely net photosynthetic rate (P_N), stomatal conductance (g_s), transpiration rate (E), and intercellular CO₂ concentration (C_i). Salinity reduced most physiological parameters, although some, such as maximum photochemical efficiency of PSII (F_v/F_m) and transpiration rate (E), did not show a clear dose-dependent response. Alkaline salt stress induced more pronounced reductions in the physiological parameters than neutral salt stress. At the first measurement, at the highest salt concentration, the chlorophyll content decreased by 49.0% and the P_N parameter by 77.8% under NaHCO₃ treatment, whereas under NaCl conditions the decreases were 29.0% and 51.3%, respectively, compared to the control. At 300 mM NaHCO₃, the chlorophyll content and photosynthetic rate were substantially reduced compared with those recorded under the corresponding NaCl treatment. Even at the moderate salinity level of 100 mM NaHCO₃, reductions in photosynthetic performance were detected relative to the control. Overall, photosynthetic efficiency and gas exchange in the cup plant were markedly impaired by salinity, particularly under conditions of high bicarbonate concentration. The results offer a deeper understanding of the physiological limitations of S. perfoliatum under acute salt stress and demonstrate that alkaline salinity, associated with elevated pH due to HCO₃⁻, exacerbates stress effects beyond the osmotic and ionic impacts of neutral salinity. These results highlight the potential of S. perfoliatum for sustainable biomass production on salt-affected soils, supporting renewable energy generation and environmentally responsible land use. Full article

4-hydroxy-TEMPO is a water-soluble nitroxide radical with potent antioxidant and redox-modulating properties. Its small molecular weight and membrane permeability enable it to act as a superoxide dismutase mimetic, efficiently scavenging reactive oxygen species and mitigating oxidative damage. In this study, we investigated the physiological and transcriptomic effects of 4-hydroxy-TEMPO in Saccharomyces cerevisiae, using wild-type and mutant strains deficient in key redox and DNA repair pathways (sod1Δ, sod2Δ, yap1Δ, rad52Δ). RNA-Seq analysis revealed widespread transcriptional reprogramming. Treatment with 4-hydroxy-TEMPO impaired cell growth, induced accumulation of cells with 1C (G1 phase) DNA content, and modulated chronological aging in a strain-dependent manner. Notably, low concentrations delayed aging in wild-type, yap1Δ, and rad52Δ strains, while accelerating it in sod1Δ mutants, consistent with a hormetic response. Unlike TEMPO, 4-hydroxy-TEMPO exhibited markedly reduced translational toxicity, preserved polysome structure at high doses, and triggered a non-canonical, redox-dependent transcriptional program characterized by induction of stress-response genes together with unexpected up-regulation of multiple ribosomal protein genes. This was accompanied by a biphasic, genotype-specific hormetic response and a measurable genoprotective effect. RT-qPCR confirmed key transcriptional changes, linking transcriptome remodeling to functional outcomes. Full article

Reversed-phase high-performance liquid chromatography (RP-HPLC) remains one of the most widely applied analytical techniques in the development and quality control testing of finished pharmaceutical products. The combination of gradient chromatographic methods with diode-array detection (DAD) enhances selectivity, ensuring accuracy and reliability when testing drugs with diverse chemical properties in a single dosage form (i.e., fixed-dose combination (FDC) products). In this study, an RP-DAD-HPLC method was developed for the quantitative analysis of clofazimine (CFZ) and pyrazinamide (PZA) for inclusion in an FDC topical drug delivery system. Chromatographic separation was achieved using a C18 column (4.6 mm × 150 mm, 5 µm particle size) with gradient elution at 1 mL/min, employing 0.1% aqueous formic acid and acetonitrile (mobile phases). PZA and CFZ were detected at 254 nm and 284 nm, respectively. The method was validated in accordance with ICH Q2 guidelines, assessing specificity (considering interference from solvents, product matrix, and degradation products), linearity (7.8–500.0 µg/mL, r² = 0.9999), system repeatability (%RSD ≤ 2.7%), and intermediate precision (25–500 µg/mL, %RSD ≤ 0.85%). Method robustness was evaluated using a three-level Box–Behnken design (BBD) with response surface methodology (RSM) to assess the effects of variations in detection wavelength, mobile phase flow rate, and column temperature. Full article

Background/Objectives: While new vaccines are in development; one strategy to increase influenza vaccine coverage is to repurpose current influenza vaccines for intranasal delivery. Methods: To address this goal; mice were vaccinated intranasally with either a split inactivated virus vaccine (Fluzone) or a recombinant HA vaccine (Flublok) at one of two doses (1 μg high dose or 0.1 μg low dose). Both vaccines were adjuvanted with either a STING agonist; c-di-AMP (CDA); or a combination of a synthetic toll-like receptor (TLR) 4 and TLR7/8 agonist (TRAC478). Results: Mice vaccinated with either vaccine plus adjuvant had higher hemagglutination-inhibition titers than mice administered unadjuvanted vaccines. Mice vaccinated with either vaccine plus CDA had on average higher numbers of H3 and influenza B hemagglutinin (HA)-specific antibody-secreting cells (ASCs); whereas mice vaccinated with vaccine plus TRAC478 had on average higher number of H1 HA-specific ASCs. All vaccinated mice challenged with the H1N1 influenza virus were protected against both morbidity and mortality with no detectable virus in their lungs. Mice challenged with the H3N2 influenza virus all lost weight over the first 5 days of infection. Adding TRAC478 with either a high or low dose vaccine resulted in 80–100% survival following challenge. Almost all mice vaccinated with Flublok plus CDA died from H3N2 influenza virus challenged with ~2 logs higher viral lung titers than mice administered Flublok only or Flublok plus TRAC478. Conclusions: Overall; Fluzone and Flublok can effectively be used for intranasal vaccination. Full article

Oocytes cultured in vitro are exposed to high oxygen tension and lack follicular antioxidants, leading to redox imbalance. Eicosapentaenoic acid (EPA), a marine long-chain n-3 polyunsaturated fatty acid, possesses strong antioxidant activity. Here, using pigs as a model, we examined the effects of EPA on oocyte in vitro maturation (IVM) and subsequent developmental competence. Cumulus–oocyte complexes were cultured with EPA, followed by assessment of nuclear and cytoplasmic maturation and embryonic development; transcriptomic and proteomic analyses were conducted to explore underlying mechanisms. Supplementation with 10 µM EPA significantly improved maturation and blastocyst rates by reducing spindle defects, facilitating a more uniform organization of cortical granules and mitochondria. EPA increased resolvin E1 accumulation and reduced cumulus-cell apoptosis through downregulation of TNF-α and BAX and upregulation of BCL2. In MII oocytes, EPA lowered apoptosis, DNA damage, and ROS levels while enhancing SOD2 and GPX4 expression. Mitochondrial quality and turnover were improved via upregulation of PPARGC1A, NDUFS2, PINK1, LC3, FIS1, MUL1, and OPA1, alongside strengthened ER–mitochondria contacts. These findings demonstrate that EPA alleviates oxidative stress, optimizes mitochondrial function, and enhances porcine oocyte maturation and developmental competence in a parthenogenetic model, highlighting its potential as a marine-derived functional additive for reproductive biotechnology. Future studies will be required to validate these effects under fertilization-based embryo production systems and to further refine dose–response relationships using expanded embryo-quality endpoints. Full article

Glucocorticoids are widely applied intra-articularly to alleviate inflammation and pain in osteoarthritis (OA). However, repeated administration and high local concentrations can lead to crystal deposition on the cartilage surface, contributing to chondrocyte damage and extracellular matrix (ECM) degradation, potentially accelerating OA progression. Calcium-dependent mechanosensors play a critical role in mediating catabolic responses in chondrocytes, but it remains unclear whether glucocorticoids affect chondrocyte mechanosensitivity or biomechanical properties. This in vitro study examined the dose-dependent effects of triamcinolone acetonide (TA) on chondrocyte biomechanics and mechanosensitivity. Primary human chondrocytes (N = 23) were cultured for one week with TA (2 µM–2 mM) or control medium. Cytoskeletal organization was visualized by F-actin staining (N = 6), and cellular elasticity (N = 5) was quantified via atomic force microscopy (AFM). Mechanotransduction was analyzed by Ca²⁺ imaging (Fluo-4 AM) upon AFM-based indentation (500 nN). Expression of matrix-related and mechanosensitive genes (N = 9) was assessed by qPCR. TA exposure induced a concentration-dependent reorganization of the F-actin cytoskeleton, pronounced at 0.2 mM, accompanied by a significant increase in the elastic modulus (p < 0.001). TA further augmented Ca²⁺ fluorescence intensity under basal conditions and during mechanical stimulation. Blocking cationic mechanosensitive channels with GsMtx4 (N = 3) markedly reduced the TA-evoked Ca²⁺ influx (p < 0.0001). Significant reduction in MMP1 was observed on the transcriptional level (N = 9) after TA-treatment (p < 0.05). In summary, TA enhances chondrocyte stiffness through cytoskeletal condensation and amplifies Ca²⁺-dependent mechanotransduction but reduces MMP1 expression, indicating a dual biomechanical response of chondrocytes to OA under exposure of potent corticosteroid. Full article

Recurrent brain tumors—including high-grade gliomas, brain metastases, and aggressive meningiomas—continue to carry a poor prognosis, with high mortality despite therapeutic advances. The aim of this narrative review is to summarize and critically discuss the current evidence on the role of intra-arterial radioligand therapy (RLT) in the treatment of recurrent brain tumors. RLT, a targeted form of radionuclide therapy, has gained increasing attention for its potential theranostic applications in neuro-oncology. A literature search was conducted using PubMed and Scopus, including clinical studies evaluating intra-arterial radioligand delivery in central nervous system tumors. Recent research has explored intra-arterial administration of radioligands targeting somatostatin receptors and prostate-specific membrane antigen (PSMA). Somatostatin receptors are overexpressed in meningiomas, while PSMA is highly expressed in the neovasculature of glioblastomas and brain metastases; both targets can be addressed using lutetium-177 (¹⁷⁷Lu)- or actinium-225 (²²⁵Ac)-labeled radiopharmaceuticals, traditionally delivered intravenously. Available evidence indicates that the intra-arterial route achieves markedly higher radionuclide uptake on ⁶⁸Ga-PSMA-11 and ⁶⁸Ga-DOTATOC PET, as well as increased absorbed doses in dosimetric models. Dosimetric analyses consistently show greater tracer accumulation compared with intravenous administration, without evidence of significant peri-procedural toxicity. Uptake in healthy brain tissue is minimal, and no relevant differences have been reported in liver or salivary gland accumulation between intra-arterial and intravenous RLT. Although based on heterogeneous and limited data, intra-arterial RLT appears to be a promising therapeutic strategy for recurrent brain tumors. Future research should focus on improving radioligand delivery beyond the blood–brain barrier and enhancing effective tumor targeting. Full article

The tomato leafminer, Tuta absoluta (Meyrick) (Lepidoptera: Gelechiidae), is one of the most destructive pests of tomato crops worldwide. Its high reproductive potential and increasing resistance to conventional insecticides have made the development of sustainable management strategies essential. Biological control using entomopathogenic fungi (EPF), particularly when established as endophytes, has emerged as a promising approach. This study investigated the endophytic colonization capacity and greenhouse performance of three commercially available EPF formulations: Beauveria bassiana (Velifer^®), Lecanicillium lecanii (Lecan^®), and a Beauveria bassiana–Metarhizium anisopliae mixture (Metab^®), for the suppression of T. absoluta in tomato. Our experiment was conducted under commercial greenhouse conditions using soil drench applications at manufacturer-recommended doses. Endophytic colonization was assessed through surface-sterilized leaf assays, while pest suppression was evaluated via weekly measurements of larval mine length, infestation incidence, and survival dynamics. B. bassiana (Velifer^®) exhibited the highest endophytic colonization frequency and consistently reduced mine length and infestation levels compared with untreated plants. Survival analysis using Cox proportional hazards revealed significant reductions in infestation risk for Velifer^® (hazard ratio, HR = 0.420), Metab^® (HR = 0.480), and Lecan^® (HR = 0.599), relative to the negative control, whereas the chemical positive control provided the strongest overall suppression (HR = 0.287). Our findings demonstrate that commercial EPF formulations can significantly reduce T. absoluta infestation under greenhouse conditions and represent a valuable component of integrated pest management programs. Full article

Optimizing planting density and mepiquat chloride (MC) is essential for simplified, machine-harvestable cotton production in the Yangtze River Basin. A two-year field experiment was conducted to explore the synergistic regulatory mechanisms of MC and planting density on plant architecture, physiology, and yield in short-season direct-seeding cotton. A split-plot design was employed with varying gradients of MC dosage and planting density. The results indicate that density and MC function complementarily in shaping plant architecture: MC primarily controls vertical growth (“dwarfing”), while density elevates the initial fruiting node (“elevation”), with no antagonistic interaction between the two. Regarding canopy structure, increasing density is the primary driver for improving the leaf area index (LAI), while MC optimizes light distribution during the critical boll stage. In terms of yield formation, high density significantly enhances seed cotton yield by increasing the number of bolls per unit area, which effectively overcompensates for the reduction in bolls per plant. Notably, a dose-dependent synergistic effect was observed where high MC dosage maximized the yield potential of high-density populations. Furthermore, fiber quality remained stable across treatments, driven primarily by interannual climate factors rather than agronomic regulation. Consequently, an independent synergistic optimization strategy is recommended, combining high density to secure population yield with medium-to-high MC dosage to shape an ideal machine-harvestable architecture. This approach provides a theoretical basis and technical pathway for high-yield and efficient cotton cultivation in the region. Full article