Search Results (2,325)

(1) Background: Mopeia–Lassa reassortant ML29 virus is an investigational, reassortant virus vaccine for the prevention of Lassa fever caused by Lassa virus (LASV). (2) Methods: The vaccine virus ML29-SF was prepared in Vero cells using a serum-free culture medium under Good Manufacturing Practice. A 2-week repeat dose toxicity study was performed in guinea pigs under Good Laboratory Practice (GLP) regulations to assess the local and systemic toxicological effects. (3) Results: Following an intramuscular (IM) or subcutaneous (SC) injection of 10⁴ PFU of ML29-SF LASV vaccine at the start of the study, with a second dose 15 days later, no toxicological response attributable to the vaccine was observed. Vaccine-related effects were not observed in any in-life or post-mortem parameter evaluated, including clinical observations, injection site observations, body temperature, body weight, food consumption, ophthalmology, immunology, hematology, clinical chemistry, gross anatomical pathology, organ weights, and histopathology. An immunogenic response, as measured by the elicitation of IgG antibodies against major LASV immunogens, nucleocapsid and glycoprotein precursor, was observed in all vaccine-treated animals prior to the booster dose (Study Day 15) which endured through the end of the study (Study Day 42). There was no evidence of viral shedding in any vaccinated animal. (4) Conclusions: Overall, this single-dose vaccine was locally and systemically well tolerated even after a two-dose repeat administration, confirming the high level of safety of ML29-SF vaccination and supporting the future evaluation of this LASV vaccine, including in clinical trials. Full article

Poplar is a vital ecological and economic tree species. In recent years, poplar plantations in China have been increasingly threatened by the fall webworm (Hyphantria cunea). Developing resistant varieties through genetic engineering is an environmentally friendly and cost-effective approach to controlling this pest. Although some exogenous toxic genes have been used in insect-resistant poplar breeding, endogenous defense genes remain scarce. This study focused on tannins, key defensive metabolites in poplar, and explored the role of PagLAR3, a gene encoding a crucial enzyme in condensed tannin biosynthesis, in poplar’s defense against the fall webworm. The findings revealed that overexpression of PagLAR3 significantly increased levels of catechin, gallocatechin, procyanidin B3, and procyanidin C2 in poplar leaves. Feeding assays with fall webworm larvae demonstrated that, compared with an 84 K (P. alba × P. glandulosa) control, transgenic lines overexpressing PagLAR3 significantly reduced larval and pupal weight, prolonged larval duration, and caused a decrease in adult emergence. Development retardation caused by overexpression of PagLAR3 in fall webworm is expected to effectively control the pest population, thereby mitigating damage to poplar trees. PagLAR3 represents a potential target for enhancing poplar resistance to the fall webworm. Full article

Background and Aims: Preterm newborns are particularly susceptible to hypovitaminosis D, potentially impairing bone mineralization. In Thailand, data on its prevalence and standardized supplementation protocols remain limited. This study aimed to compare the efficacy of two vitamin D3 dosages (400 IU/day vs. 800 IU/day) in improving serum vitamin D concentrations and metabolic bone parameters in preterm newborns. Methods: A randomized controlled trial was conducted in preterm newborns born at ≤32 weeks’ gestation or with birth weight ≤1500 g. Preterm newborns were randomized to receive either 400 IU or 800 IU/day of vitamin D3. Serum 25-hydroxyvitamin D (25(OH)D) was measured using electrochemiluminescence immunoassay (ECLIA). Metabolic bone parameters—including calcium, phosphorus, alkaline phosphatase, and albumin—were assessed at baseline and again at six weeks of age. Results: Of the 38 enrolled infants, baseline 25(OH)D levels were comparable between groups (14.8 ± 4.8 ng/mL in the 800 IU/day group vs. 14.7 ± 6.9 ng/mL in the 400 IU/day group). At six weeks, the 800 IU group demonstrated significantly higher 25(OH)D levels (47.3 ± 21.0 ng/mL vs. 32.0 ± 14.2 ng/mL; p = 0.013), with a large effect size (Cohen’s d = 0.85) and the difference-in-differences of +15.7 ng/mL. The prevalence of hypovitaminosis D declined from 89% to 5% in the 800 IU/day group and from 74% to 32% in the 400 IU/day group (p = 0.036). No significant differences in metabolic bone parameters or signs of toxicity were observed. Conclusions: Vitamin D3 supplementation at 800 IU/day significantly improved vitamin D status and reduced hypovitaminosis D in preterm newborns, without observed toxicity. Full article

Many kinds of silicones are a wide family of hybrid inorganic–organic polymers which have valuable physical and chemical properties and find plenty of practical applications, not only industrial, but also numerous medical and pharmaceutical ones, mainly due to their good thermal and chemical stability, hydrophobicity, low surface tension, biocompatibility, and bio-durability. The important biomedical applications of silicones include drains, shunts, and catheters, used for medical treatment and short-term implants; inserts and implants to replace various body parts; treatment, assembly, and coating of various medical devices; breast and aesthetic implants; specialty contact lenses; and components of cosmetics, drugs, and drug delivery systems. The most important achievements concerning the biomedical and pharmaceutical applications of silicones, their copolymers and blends, and also silanes and low-molecular-weight siloxanes have been summarized and updated. The main physiological properties of organosilicon compounds and silicones, and the methods of antimicrobial protection of silicone implants, have also been described and discussed. The toxicity of silicones, the negative effects of breast implants, and the environmental effects of silicone-containing personal care and cosmetic products have been reported and analyzed. Important examples of the 3D printing of silicone elastomers for biomedical applications have been presented as well. Full article

Cervical cancer remains a major threat to women’s health, with advanced cases often exhibiting recurrence and metastasis due to cancer stem cells driving therapy resistance. This study evaluated fenbendazole (FBZ), a repurposed veterinary anthelmintic, for its antitumor activity dual targeting cervical cancer cells (CCCs) and cervical cancer stem cells (CCSCs). CD133⁺CD44⁺ CCSCs were isolated from HeLa and C-33 A cell lines via immunomagnetic sorting and validated for stemness. Cell proliferation, cell cycle and apoptosis, and protein expression were detected by MST assay, flow cytometry, and Western blot analysis, respectively. FBZ dose-dependently inhibited proliferation, induced G2/M arrest, and triggered apoptosis in both CCCs and CCSCs. Mechanistically, FBZ upregulated cyclin B1 and phosphorylation of cdc25C-Ser198, while downregulating Wee1, phosphorylation of CDK1, and phosphorylation of cdc25C-Ser216, collectively enforcing G2/M blockade. In vivo, FBZ (100 mg/kg) significantly suppressed tumor growth in xenograft models without weight loss, contrasting with cisplatin-induced toxicity. Survival analysis revealed 100% survival in FBZ-treated mice versus 40% in cisplatin and 0% in untreated controls. These findings demonstrate FBZ’s unique ability to simultaneously target bulk tumor cells and therapy-resistant CCSCs via cell cycle disruption, supported by its preclinical safety and efficacy, positioning it as a promising therapeutic candidate for cervical cancer. Full article

Magnesium-based coronary stents have gained significant interest due to their excellent biocompatibility, biodegradability, and mechanical properties. However, a key limitation of magnesium in biomedical applications is its low corrosion resistance, which compromises its structural integrity and mechanical strength over time. Polymeric coatings can overcome this challenge, enhancing magnesium-based implants’ corrosion resistance and overall performance. This study applied a polylactic acid (PLA) nanofiber coating to WE43 magnesium (Mg) stents via electrospinning to reduce their corrosion rate. Both uncoated and coated stents underwent in vitro immersion tests in Hank’s solution for 1, 3, 7, and 14 days. The effectiveness of the PLA coating was evaluated through morphological analysis, chemical composition assessment, corrosion behavior (weight change), magnesium ion release, and in vitro biocompatibility. The corrosion observed in the uncoated WE43 stents indicates that protective coatings are necessary to regulate degradation rates over extended implantation periods. The results demonstrated that coated stents exhibited improved performance, maintaining the integrity of the PLA coating for up to 14 days. The coated stents demonstrated reduced surface damage and lower weight loss resulting from lower magnesium release. In our study, the coated stents demonstrated a reduced corrosion rate (0.216 ± 0.013 mm/year) compared with the uncoated stents (0.312 ± 0.010 mm/year), both after 14 days. Additionally, in vitro biocompatibility results confirmed the non-toxic nature of PLA-coated stents, which enhances cellular proliferation and contributes to a more favorable environment for vascular healing. These findings suggest that PLA coatings can effectively prolong the functional durability of WE43 Mg stents, offering a promising solution for enhancing the performance of biodegradable stents in cardiovascular applications. Full article

Selenium (Se) is an essential trace element required for various physiological functions in agriculture. Nanotechnology is applied to produce selenium nanoparticles (SeNPs) that offer new advantages, enhancing their bioavailability and reducing toxicity. To further improve the stability of Se nanoelements in the poultry industry, the grey form of Se was recently offered as a potential alternative. However, its impact on bioaccessibility, metabolism, and overall animal efficiency remains undetermined. This study investigates the impact of red and grey SeNPs on Se content in the liver, blood cellular fraction (BCF), kidney, testis, and eyes, as well as the feed intake (FI) and growth performance, of adult Japanese quails. Adult quails were randomly assigned to five groups: a control (C0) and four groups receiving either red or grey Se nanoparticles (SeNPs) at 0.05 or 0.5 mg/kg, in addition to the basal diet which already contained 0.042 mg/kg Se from the premix, resulting in total Se contents of approximately 0.092 and 0.542 mg/kg in the treatment groups (T1–T4), with four replicates per group. The growth performance of quails fed with nano-Se-supplemented diets showed significant variation across groups (p < 0.05), with body weight differing by up to 20% between the highest performing group (T2) and the lowest (T1). FI showed no significant differences across groups. The results indicated that Se accumulation differed significantly between treatments. The selenium levels in the liver increased in a dose-dependent manner, with the highest accumulation observed in T4 (0.5 mg/kg grey SeNPs), at 42% above control levels. This pattern suggests that the liver is a primary organ for selenium storage and metabolism. The greatest Se content in BCFs was recorded in the groups that received grey selenium (T3 and T4) and red selenium at high concentrations (T2), while the group given red selenium at low concentrations (T1) and the control (C0) had the lowest Se accumulation. In the kidney tissues and testis, the Se content exhibited no significant differences between the treated groups and the control. The observed variations in the eye and breast muscle Se content among treatment groups reflect the differences in selenium bioavailability, metabolism, and tissue-specific regulatory mechanisms. These findings demonstrate that grey SeNPs can significantly elevate Se bioavailability in quails, particularly in target organs, and enhance the growth performance without notable changes in feed intake. This highlights the potential of SeNPs in enhancing quail nutrition, although further research is needed to establish optimal dosing strategies for safe, effective use. Full article

An alternative to conventional methods for mine tailings disposal is stabilization with alkali-activated binders (AABs), developed from agro-industrial waste. Despite increasing interest in this topic, there is still a lack of studies focusing on the stabilization of iron ore tailings (IOTs) using AABs, particularly those that combine the characterization of cementitious gels with an evaluation of leaching behavior. This study assessed the strength, mineralogy, and leaching performance of IOTs stabilized with AABs formulated from rice husk ash (RHA) and hydrated eggshell lime (HEL), using sodium hydroxide as the alkaline activator. Tests included unconfined compressive strength (UCS), X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), and metal leaching analyses. The IOT–AAB mixture with the highest AAB content and dry unit weight achieved an average UCS of 2.14 MPa after 28 days of curing. UCS increased with AAB content, followed by dry unit weight and curing time, the latter showing a non-linear influence. The formation of C–S–H gel was confirmed after 28 days, while N–A–S–H gel was detected as early as 7 days of curing. The cemented IOT–AAB mixtures showed no metal toxicity and effectively encapsulated barium originating from the RHA. Full article

Mineral elements can either be pollutants or essential dietary components. Monitoring their levels in the environment and living organisms is crucial because excessive amounts can become toxic. Dogs, due to their proximity to humans, shared habitats, and similar organ structures, can be effective indicators of environmental pollution by toxic elements. This study aimed to assess the levels of 11 mineral elements in 80 dog carcasses (49 males and 31 females), aged between 2 and 16 years, from the Ionian-Etnean volcanic region of the province of Catania, where the dogs had died under unknown circumstances. A direct mercury analyzer (DMA-80) was used to measure Hg, and an inductively coupled plasma mass spectrometer (ICP-MS) was used for the other elements. A one-way ANOVA, followed by Bonferroni’s multiple comparison for post hoc analysis, was conducted to evaluate significant differences between the organ samples and different minerals and between the weight and metal levels. The statistical significance was set at p < 0.05. The study indicates that high concentrations of metals like cadmium, mercury, lead, and chromium are present in the liver, kidneys, and other organs. These elevated concentrations suggest that the local volcanic emissions contribute to soil, water, and atmospheric contamination. The data showed differences in the metal concentrations between the sexes, which could be attributed to biological and environmental factors. Full article

Oil spills represent a significant environmental threat due to the toxicity of hydrocarbons, particularly in aquatic environments where oil rapidly spreads across the surface. Sustainable sorbents are needed for an efficient and eco-friendly response to oil spills. Cellulose aerogels produced from recycled paper and cardboard exhibit promising properties such as buoyancy, light weight, biocompatibility, and recyclability. Mechanical stability and reusability can be enhanced using cross-linkers such as starch. This study evaluated the impact of starch on cellulose aerogel morphology, sorption capacity for various petroleum products (crude oil, marine diesel, and lubricating oil), and reusability using scanning electron microscopy (SEM) and elemental mapping. Aerogels containing 0.5 and 1 wt% starch showed higher porosity, sorption capacity, and reusability. Starch did not affect hydrophobization or significantly alter nitrogen and carbon levels, indicating limited influence on surface chemistry and adsorption performance. Full article

Phyllotreta striolata is a major pest of Brassica chinensis, with chemical pesticides being the primary method for pest control. However, their negative impact on crop growth and environmental risks have prompted the search for low-toxicity, environmentally friendly alternatives. This study systematically evaluates the control effectiveness of two commonly used chemical pesticides, Zu Jia^® and Jie Tiao^®, along with their impact on the growth characteristics of B. chinensis and compares them to the biopesticide Bacillus thuringiensis (Bt) strain G033A. The control efficacy was assessed by measuring the insect population reduction rate and plant physiological indicators (weight, plant height, chlorophyll content, and root length). The differences between biopesticide and the two chemical pesticide treatments were analyzed. The results indicated that both Bt strain G033A and the chemical pesticides significantly controlled P. striolata. However, chemical pesticides (Zu Jia^® and Jie Tiao^®) significantly reduced the chlorophyll content, plant height, and weight of B. chinensis (p < 0.05), whereas Bt strain G033A had no significant adverse effects on these plant traits (p > 0.05). The colonization characteristics of the Bt strain suggest potential for sustained pest control, while chemical pesticides exhibited rapid pest suppression effects. The findings highlight a novel IPM strategy that integrates the long-lasting efficacy of Bt biopesticides with the rapid action of chemical pesticides, offering a more sustainable and balanced approach to P. striolata management in B. chinensis cultivation. Full article

As the average age of the population increases, memory impairment has become an increasingly prevalent issue. This study investigates the effects of 14 days of oral birch sap administration on memory functions in healthy rats using the Morris water maze (MWM) test and explores the underlying mechanisms. A compositional analysis revealed that birch soap is rich in polysaccharides, specifically a low-molecular weight polysaccharide (MW 1.29 kDa), and exhibits no hepatotoxicity or renal toxicity at the tested dose. The results from the MWM test demonstrated that the time and distance required to reach the platform were significantly shorter in the birch sap-treated group compared to the control group, suggesting that birch sap supports memory preservation. Moreover, rats treated with birch sap showed improved cerebral blood flow compared to the control rats. Additionally, in hippocampal nerve terminals (synaptosomes), rats treated with birch sap exhibited a significant increase in evoked glutamate release, as well as elevated levels of presynaptic proteins, including vesicular glutamate transporter 1 (VGluT1), synaptophysin, synaptobrevin, synaptotagmin, syntaxin, synapsin I, and the 25 kDa synaptosome-associated protein (SNAP-25). Transmission electron microscopy also revealed a notable increase in the number of synaptic vesicles in hippocampal synaptosomes of the birch-sap-treated rats. These findings suggest that birch sap enhances hippocampal presynaptic glutamatergic functions and cerebral blood flow, contributing to its memory-preserving effects in rats. Full article

As an emerging endocrine-disrupting agent and structural analog of bisphenol A (BPA), bisphenol B (BPB) raises significant concerns due to its potential to induce male reproductive toxicity. Despite its presence in maternal bodily fluids, the effects of BPB exposure on the reproductive system and its mechanisms in adult male offspring are poorly understood. By establishing a maternal BPB exposure model in mice, we found that the exposure reduced the relative weights of seminal vesicles and preputial glands, decreased the thickness of the seminiferous epithelium, enlarged the lumen area of seminiferous tubules, and lowered testosterone concentration and synthesis, as well as sperm count in 10-week-old male offspring. Bioinformatic analyses revealed that the differentially expressed genes were significantly associated with major histocompatibility complex I (MHC I)-mediated immunological processes, including immune system processes, antigen processing and presentation of exogenous peptide antigens via MHC class I, and interleukin-2 production. Importantly, molecular docking proposed a potential mechanistic model wherein BPB bound to estrogen receptor α (ERα) suppressed its testicular expression and triggered MHC class I gene overexpression, potentially promoting macrophage infiltration, CD4+/CD8+ T cell activation, and pro-inflammatory cytokine production. Our findings provide critical insights into the adverse effects of maternal BPB exposure on male reproductive development, suggesting that impairments in testicular morphology and spermatogenesis may be attributed to MHC I-mediated immunological responses and hormonal imbalances resulting from inhibited ERα signaling. These results underscore not only the toxicological risks associated with BPB but also potential therapeutic targets for mitigating male reproductive dysfunction. Full article

Introduction: Hyperbilirubinemia in newborns can lead to kernicterus, a severe form of neonatal encephalopathy caused by bilirubin toxicity. Despite timely interventions such as exchange transfusion, kernicterus can still develop, especially in high-risk infants. MRI is crucial for detecting early and evolving signs of bilirubin-induced brain damage. Case Report: We report a term newborn who developed severe hyperbilirubinemia and kernicterus despite receiving exchange transfusion. The infant presented on day 3 of life with jaundice, hypotonia, and feeding difficulties and had a bilirubin level of 51 mg/dL. After exchange transfusion, bilirubin levels normalized, but neurotoxicity persisted. Initial MRI at one month showed mild T1 hyperintensity in the hippocampi with no changes in the basal ganglia. At two months, T1 hyperintensities in the hippocampi partially resolved. By six months, MRI revealed T2 hyperintensities in the globus pallidus and hippocampal atrophy, consistent with kernicterus. Magnetic resonance spectroscopy (MRS) showed reduced N-acetylaspartate (NAA) levels, indicating neuronal loss. Discussion: MRI is essential in monitoring bilirubin-induced brain injury. In this case, early MRI findings showed mild hippocampal T1 hyperintensity, which resolved partially. At six months, T2 hyperintensities in the globus pallidus confirmed chronic bilirubin encephalopathy. MRS demonstrated a reduction in N-acetylaspartate, indicative of neuronal loss. Susceptibility-Weighted Imaging (SWI) showed no abnormalities, likely due to the myelination process in neonates. Conclusions: This case highlights the importance of repeated MRI in detecting bilirubin-induced brain damage. Early neuroimaging enables timely interventions and improves long-term neurodevelopmental outcomes in infants with severe hyperbilirubinemia. Full article

Background: The FDA-cleared antimicrobial quaternary ammonium silane K21 is recognized for its antimicrobial properties. This study explored potential applications of the K21 molecule in human health protection, disease prevention, and treatment using the zebrafish model. Method: A multi-dimensional approach was utilized to assess the toxicity, tolerance, and optimal dosage of K21 through serial dilutions at various concentrations. Acute and chronic exposure studies were performed at different developmental stages (embryonic, larval, juvenile, and adult) to evaluate its efficacy and toxicity in wild-type (WT), Casper (transparent skin mutant), and transgenic zebrafish lines. Results: Significant weight gain was observed in the F1 generation following K21 treatment, a trend that continued into the F2 and F3 generations. The effects of K21 on lipopolysaccharide-induced inflammation were also examined in Casper NFkB:GFP transgenic lines. Treatment with K21 reduced inflammation, indicating anti-inflammatory properties. Improved hatching rates, accelerated larval development, an increased adult mass, and modest reductions in embryonic motility (less than 20%) suggested positive developmental influences. Single-cell RNA sequencing further validated the biological impacts of K21, revealing the potential activation of a novel pathway that accelerates zebrafish growth. Summary and Conclusions: These findings position K21 as a promising candidate for biomedical applications and aquaculture, warranting further investigation into its underlying molecular mechanisms. Our additional study on the effect of K21 on the artemia (brine shrimp) hatching process provide strong evidence of better hatching ratio of 90% for brine shrimp in the group with K21 drug treatment as compared to 70% in the group without the K21 drug at 24 h of treatment; the K21 drug helps the early hatching process, as observed the 90% hatching rate in 20 h K21 treatment group hatching while in the group without K21, only 40% of brine shrimps hatched. Full article