Search Results (1,435)

Urbanization generates large quantities of arsenic-contaminated excavated soils that pose environmental risks due to arsenic volatilization during high-temperature sintering processes. While these soils have potential for recycling into construction materials, their reuse is hindered by arsenic release. This study demonstrated calcium hydroxide (Ca(OH)₂) as a highly effective additive for suppressing arsenic volatilization during soil sintering, while simultaneously improving material properties. Through comprehensive characterization using inductively coupled plasma-mass spectrometry (ICP-MS), scanning electron microscopy (SEM) and X-ray microtomography (μCT), energy dispersive spectroscopy (EDS), X-ray diffraction (XRD), Fourier Transform Infrared Spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS), results demonstrated that Ca(OH)₂ addition (0.5–2 wt.%) reduces arsenic volatilization by 57% through formation of thermally stable calcium arsenate (Ca₃(AsO₄)₂). Ca(OH)₂ acted via two mechanisms: (a) chemical immobilization through Ca-As-O compound formation, (b) physical encapsulation in a calcium-aluminosilicate matrix during liquid-phase sintering, and (c) pH buffering that maintains arsenic in less volatile forms. Optimal performance was achieved at 0.5% Ca(OH)₂, yielding 9.14 MPa compressive strength (29% increase) with minimal arsenic leaching (<110 ppb). Microstructural analysis showed Ca(OH)₂ promoted densification while higher doses increased porosity. This work provides a practical solution for safe reuse of arsenic-contaminated soils, addressing both environmental concerns and material performance requirements for construction applications. Full article

Most botulinum toxin A (BoNT-A) products for esthetic use require reconstitution before administration. Ready-to-use relabotulinumtoxinA is a liquid manufactured using Precipitation-free Extraction and Activity-preserving, Refined Liquid (PEARL™) Technology from a proprietary C. botulinum type A1 strain. We examined the in vitro characteristics of relabotulinumtoxinA. The specific BoNT-A1 potency remained consistent throughout drug substance manufacturing (1.9 × 10⁸–2.2 × 10⁸ LD₅₀ mouse potency units/mg of BoNT-A1, four fractions sampled). Using glabellar line (GL) on-label doses, relabotulinumtoxinA liquid product was compared with powder onabotulinumtoxinA using the following: BoNT-A1 amount based on ELISA; specific enzyme activity based on SNAP-25 cleavage by a fluorescence resonance energy transfer-based assay (BoTest^®); biological activity (binding, internalization, and SNAP-25 cleavage over time) using a cell-based assay. RelabotulinumtoxinA contained more BoNT-A1 per on-label GL dose (0.27 ng) than onabotulinumtoxinA (0.18 ng), had higher enzyme activity (53 vs. 29 BoTest^® units) per GL dose, and had higher specific activity per pg BoNT-A, with onabotulinumtoxinA displaying 81% of the specific activity of relabotulinumtoxinA. In vitro, relabotulinumtoxinA demonstrated higher biological activity and earlier onset of SNAP-25-cleavage than onabotulinumtoxinA. PEARL^TM Technology thus produces high-quality BoNT-A1 with high specific enzyme and biological activities, which may explain the clinical performance of relabotulinumtoxinA in Phase 3 clinical trials examining treatment of GLs and/or LCLs. Full article

The study aimed to evaluate the effect of betanin—a bioactive, natural pigment found in beetroot and prickly pear—on cognitive function, motor performance, and neurotransmission in a mouse model of Parkinson’s disease (PD). Aged mice with PD-like symptoms induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) were pretreated with betanin (50 or 100 mg/kg b.w./day) via drinking water. Behavioural tests assessed motor skills, anxiety-related behaviour, and spatial memory. Biochemical analyses of central nervous system structures were conducted using high-performance liquid chromatography (HPLC) to determine neurotransmitter levels and metabolites. Betanin improved motor and cognitive functions in MPTP-treated mice. While learning ability remained unchanged, the 50 mg/kg dose alleviated spatial memory deficits. Biochemically, betanin moderately limited dopamine depletion and significantly influenced dopamine metabolism and serotonin levels. These findings suggest that betanin, as a functional food component, may exert neuroprotective effects and support cognitive and motor function in neurodegenerative conditions such as PD. Full article

Background: Parkinson’s disease (PD) is a neurodegenerative disorder for which no curative therapies currently exist. Experimental models employing 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) reproduce PD features such as striatal dopaminergic dysfunction and motor deficits. Various MPTP dosing regimens are used to screen drug candidates for PD, but their validity is limited because of the predominant use of young male animals. Sex bias is another issue that is underrepresented in PD research, since females are more susceptible to this pathology. Here, we studied the model of bolus administration of MPTP (30 mg/kg) in aged female mice and assessed its sensitivity to the antioxidants fullerene C₆₀ and fullerenol C₆₀(OH)₂₄, given that oxidative stress is a key contributor to PD. Methods: 12-month-old female C57BL/6 mice received fullerene (0.1 mg/kg/day, via diet) or fullerenol (0.15 mg/kg/day, via drinking water). On day 10, mice were injected with MPTP. We studied tremor, piloerection, and behavior in the pole test, rotarod, pole test, and open field. High-performance liquid chromatography (HPLC) was employed to study dopaminergic neurotransmission, and the expression levels of its molecular regulators and nitric oxide synthase (NOS)-related targets were investigated using RT-PCR in the striatum and cortex. Results: MPTP-challenged mice displayed profound impairment in markers of dopaminergic neurotransmission and cellular distress, and showed disrupted motor behavior and vegetative functions. Antioxidant-treated animals that received a bolus injection of MPTP demonstrated partial preservation of tremor response, dopaminergic parameters, and iNOS and nNOS gene expression, although motor performance in the pole test was only modestly improved. Fullerenol appeared more effective in decreasing MPTP-induced neurochemical changes. Conclusions: The applied MPTP model showed its validity in mimicking PD features and was sensitive to low doses of antioxidants, suggesting its usefulness for screening drugs that target oxidative and nitrosative stress. The neuroprotective effects of fullerene-based compounds suggest their potential utility in the treatment of PD. Full article

The hybrid Sechium edule H387 07, commonly known as chayote, has shown potential as an antiproliferative, cytotoxic, and pro-apoptotic agent in the murine leukemia cell lines P388 (macrophagic) and J774 (monocytic) and in the myelomonocytic leukemia cell line WEHI-3. However, despite these reported bioactivities, its pharmacokinetic profile remains largely unexplored. Understanding the absorption, distribution, and elimination of this hybrid is critical for addressing unmet therapeutic needs and for advancing the development of natural product-based therapies. These effects are attributed to the presence of phenols, flavonoids, and cucurbitacins in its organic extracts. In this study, the pharmacokinetic parameters of secondary metabolites from methanolic extracts of Sechium H387 07 were evaluated after oral administration in mice, while its segregant H387 M16 was subjected to complementary phytochemical characterization. Methanolic extracts of Sechium edule H387 07 were orally administered to mice at doses of 8, 125, and 250 mg/kg, and plasma, liver, and urine samples were collected at 1, 6, 24, and 48 h post-treatment. High-performance liquid chromatography (HPLC) identified polyphenols and cucurbitacins, notably cucurbitacin B (CuB) and cucurbitacin IIA (CuIIA), in the biological samples, and pharmacokinetic variables such as the maximum plasma concentration (C_max), time to reach maximum concentration (T_max), half-life (T_1/2), and volume of distribution (V_d) were determined. For instance, CuB exhibited a C_max of 37.56 µg/mL at 1 h post-dose after oral administration of 125 mg/kg, confirming its rapid absorption and systemic distribution. Notably, the presence of CuIIA in plasma was documented for the first time, along with the pharmacokinetic profiles of apigenin, phloretin, CuB, CuE, and CuI. In parallel, the segregant H387 M16 was characterized via colorimetric assays, thin-layer chromatography (TLC), HPLC, and antioxidant activity tests, which revealed high levels of flavonoids, phenols, and cucurbitacins, with an antioxidant activity of approximately 75% at the highest tested dose (1 mg/mL), supporting its suitability for future bioassays. Overall, these findings not only provide novel pharmacokinetic data for key metabolites of the H387 07 hybrid but also establish the phytochemical and antioxidant profile of its segregant H387 M16. This dual characterization strengthens the evidence of the therapeutic potential of Sechium genotypes and provides a valuable foundation for future studies aiming to develop standardized protocols and explore translational applications in drug development and natural product-based therapies. Full article

Tomato leaves, typically discarded during harvest, are a rich yet underutilized source of bioactive compounds. This study aimed to valorize tomato leaves by optimizing the extraction of their phenolic compounds using a water-based method and response surface methodology. The optimal conditions, notably heating a mixture of 1:50 solid-to-liquid ratio at 71 °C for 29 min, yielded the most total phenolic content and antioxidant activity. The biological activities of the lyophilized tomato leaf extract (TLE) were then assessed. TLE showed dose-dependent antimicrobial activity against Escherichia coli and Candida albicans, but neither against Pseudomonas aeruginosa nor Staphylococcus aureus. In addition, it demonstrated moderate cytotoxicity against MCF-7 breast cancer cells with an IC₅₀ value of 114.5 µg/mL. Interestingly, the extract significantly reduced intracellular reactive oxygen species levels in RAW 264.7 macrophages, supporting its anti-inflammatory potential. LC-MS analysis identified rutin (45.21%), 4-hydroxycoumarin (13.60%), and α-tomatine (12.37%) as the major chemical constituents in TLE, suggesting contributing effects behind the observed bioactivities. These results support the potential of tomato leaf extract as an eco-friendly source for functional ingredients, transforming agricultural waste through green extraction into valuable applications for nutraceuticals and sustainable product development. Full article

The urinary bladder is a primary target organ for environmental toxicants such as arsenic. The objects of this study were two-fold. First, we constructed a novel 3D urinary bladder mucosa model (3D-UBMM) composed of an overlying epithelium and a supporting subepithelial layer. Primary human bladder urothelial and fibroblast cells were immortalized by introducing the human CDK4^R24C and TERT genes. The construction of the 3D-UBMM involved incorporating immortalized fibroblast cells into a collagen raft, while immortalized urothelial cells were cultured at the air-liquid interface. This 3D-UBMM closely resembles the human bladder epithelium in terms of morphology and marker protein expression, including uroplakin 1b, P63, and cytokeratin 5. Second, using the 3D-UBMM we investigated the cytotoxicity of sodium arsenite (iAs^III) and dimethylarsenic acid (DMA^V). Exposure to iAs^III and DMA^V resulted in increased urothelial necrosis, increased γ-H2AX-positive cells, and reduced P63-positive cells, all in a dose–response manner. These findings affirm that this novel 3D-UBMM resembles the human bladder epithelium and offers a practical in vitro model for evaluating bladder toxicants and carcinogens, identifying mechanisms of carcinogenesis, and supporting hazard identification and risk assessment. Full article

Background: Lung cancer remains the leading cause of cancer-related mortality globally, largely due to delayed diagnosis in its early stages. While conventional diagnostic tools like low-dose CT and tissue biopsy are routinely used, they suffer from limitations including invasiveness, radiation exposure, cost, and limited sensitivity for early-stage detection. Liquid biopsy, a minimally invasive alternative that captures circulating tumor-derived biomarkers such as ctDNA, cfRNA, and exosomes from body fluids, offers promising diagnostic potential—yet its sensitivity in early disease remains suboptimal. Recent advances in Artificial Intelligence (AI) and radiomics are poised to bridge this gap. Objective: This review aims to explore how AI, in combination with radiomics, enhances the diagnostic capabilities of liquid biopsy for early detection of lung cancer and facilitates personalized monitoring strategies. Content Overview: We begin by outlining the molecular heterogeneity of lung cancer, emphasizing the need for earlier, more accurate detection strategies. The discussion then transitions into liquid biopsy and its key analytes, followed by an in-depth overview of AI techniques—including machine learning (e.g., SVMs, Random Forest) and deep learning models (e.g., CNNs, RNNs, GANs)—that enable robust pattern recognition across multi-omics datasets. The role of radiomics, which quantitatively extracts spatial and morphological features from imaging modalities such as CT and PET, is explored in conjunction with AI to provide an integrative, multimodal approach. This convergence supports the broader vision of precision medicine by integrating omics data, imaging, and electronic health records. Discussion: The synergy between AI, liquid biopsy, and radiomics signifies a shift from traditional diagnostics toward dynamic, patient-specific decision-making. Radiomics contributes spatial information, while AI improves pattern detection and predictive modeling. Despite these advancements, challenges remain—including data standardization, limited annotated datasets, the interpretability of deep learning models, and ethical considerations. A push toward rigorous validation and multimodal AI frameworks is necessary to facilitate clinical adoption. Conclusion: The integration of AI with liquid biopsy and radiomics holds transformative potential for early lung cancer detection. This non-invasive, scalable, and individualized diagnostic paradigm could significantly reduce lung cancer mortality through timely and targeted interventions. As technology and regulatory pathways mature, collaborative research is crucial to standardize methodologies and translate this innovation into routine clinical practice. Full article

Pre-clinical animal studies evaluating the ‘flash effect’ caused by ultra-high dose rate (≥40 Gy/s) favorably spares normal tissue from radiation-caused toxicity while maintaining anti-tumor effects like conventional (CONV) radiation. The goal of this study is to leverage an immune response resulting from the treatment combination of flash radiotherapy (Flash-RT) and LIFE (liquid immunogenic fiducial eluter) biomaterial incorporating an anti-mouse CD40 monoclonal antibody to enhance the therapeutic ratio in pancreatic cancer. Methods: A small animal FLASH radiation research platform (FLASH-SARRP) was utilized to deliver both ultra-high and CONV dose-rate irradiation to treat syngeneic subcutaneous pancreatic tumors generated in 8–10-week-old male and female C57BL6 mice. The efficacy of FLASH versus CONV radiotherapy (RT) at varying doses of 5, 8, 10, and 15 Gy delivered in a single fraction was evaluated by assessing tumor growth and mice survival over time or comparing tumor weight at 10 days post-treatment. Results: Similar tumor control capability was observed by the high-dose rate and conventional RT related to the control group. Nevertheless, longer survival was observed for the FLASH group at 5 Gy compared to CONV and control at either 5 Gy, 10 Gy, or 15 Gy doses. Multiplex immunofluorescence and immunohistochemistry results showed higher T-cell infiltration within the combination of RT (either FLASH or CONV) and LIFE biomaterial-treated tumors compared to the control cohort. Conclusions: This animal study serves as an impetus for future studies leveraging the immune response using the combination of FLASH and LIFE Biomaterial to enhance the efficacy of pancreatic cancer treatment. Full article

Fetal alcohol spectrum disorder (FASD/FAS) is a chronic inflammatory process of the fetal brain induced by alcohol and mediated by pro-inflammatory (PILM) and pro-resolving (PRLM) lipid mediators of inflammation. DHA (docosahexaenoic acid) is an essential precursor of PRLM. A study examining the response of lipid mediators of inflammation to alcohol insult and DHA supplementation can provide vital information on the pathogenesis of FASD/FAS and the potential ameliorative role of DHA. Four groups of timed pregnant rats were studied: control, low-dose (1.6 g/kg/day) and high-dose (2.4 g/kg/day) alcohol, and high-dose alcohol (2.4 g/kg/day) + DHA (1250 mg/kg/day). The pups were delivered on day 20, and their whole brain was examined for lipid mediators by liquid chromatography mass spectroscopy. The following biomarkers of brain lipid mediators were studied, namely, PILM (LTB4, PGE2, PGF2α, TXB2) and PRLM (LXA5, 4-HDoHE, 17-HDoHE, and MaR1n-3, DPA). The brain PILM and PRLM concentrations decreased significantly (p < 0.001) with high-dose alcohol. However, high-dose alcohol + DHA resulted in a significant (p < 0.001) increase in PRLM levels, viz., LXA5, MaR1n-3 DPA, 17-HDoHE, and a threefold increase in 4-HDoHE. We conclude that DHA supplementation in alcohol-exposed pregnant rats significantly increased levels of brain pro-resolving lipid mediators in the offspring, suggesting a potential role in modulating the inflammatory response. Full article

Antibodies are indispensable for protection against biological toxins and pathogens, yet their conventional liquid formulations impose severe constraints, including dosing inaccuracy caused by residual fluid remaining in the syringe and limited user convenience such as pain caused by fluid-induced tissue distension and nerve stimulation as well as instability in ambient temperature, and the requirement for low-temperature storage and logistics. These limitations critically impair rapid deployment during golden hour following acute exposure. Here, we report an antibody-integrated solid-to-gel microfilm—demonstrated with a 100 µg anti-BoNT/A dose—jet-printed and low-temperature dried directly onto metal needles for consistent, on-demand use. Upon intradermal insertion, the microfilm fully dissolves within 5 min, driven by hydration-induced swelling of a hyaluronic acid (HA) support layer and rapid release of the antibody. Time-resolved microscopy and UV–vis analysis showed a decrease in residual solid from 2.34 mm³ to 0 over 300 s, with a concomitant rise at 187 nm indicative of complete dissolution. The solid formulation maintained ambient-temperature stability for 3–6 months with pharmacokinetics comparable to conventional subcutaneous liquid injections. In a lethal BoNT/A challenge, treated mice achieved 100% survival for 12 days, whereas controls succumbed within 16 h. Full article

In the present study three composite materials based on iron in combination with bismuth, copper or lithium carbonates FeNO₃@Li₂CO₃ (SFL), FeNO₃@CuCO₃ (SFC), and FeNO₃@(BiO)₂CO₃ (SFB) were synthesized by coprecipitation. The purpose was to obtain materials that possess targeted adsorbent properties for the recovery of silver ions from aqueous solutions. After synthesis, to emphasize the adsorptive qualities of materials for the recovery of silver ions, the synthesized composite materials, as well as those doped with silver ions following the adsorption process (SFL-Ag, SFC-Ag, and SFB-Ag), were characterized and several adsorption-specific parameters were examined, including temperature, contact time, pH, adsorbent dose, and the initial concentration of silver ions in solution. Subsequently, the ideal adsorption conditions were determined to be as follows: pH > 4, contact time 60 min, temperature 298 K, and solid–liquid ratio (S–L) of 0.1 g of adsorbent to 25 mL of Ag (I) solution for all three materials. The Langmuir model properly fits the experimental equilibrium data of the adsorption process; however, the Ho–McKay model closely represents the adsorption kinetics. The maximum adsorption capacities of the materials, 19.7 mg Ag(I)/g for SFC, 19.3 mg Ag(I)/g for SFB, and 19.9 mg Ag(I)/g for SFL, are comparable. The adsorption mechanism is physical in nature, as evidenced by the activation energies of 1.6 kJ/mol for SFC, 4.15 kJ/mol for SFB, and 1.32 kJ/mol for SFL. The highest Ag(I) concentration used for doping all three materials in the study was 150 mg Ag(I)/L. The process is endothermic, spontaneous, and takes place at the interface between the adsorbent and the adsorbate, according to thermodynamic theory. Subsequently, the antimicrobial activity against Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Candida albicans microorganisms was evaluated by rate of inhibition assessment. The SFC-Ag material showed a percentage of 100% inhibition with respect to the positive control for each microorganism. All synthetized materials have better efficiency as antifungal agents. Full article

The necessity to produce new biodegradable polymeric materials, to overcome the economic model, based on the linear economy, and to apply the circular economy model is a global problem. As a result, components unutilized derived from industrial processes are becoming increasingly valuable and useful to create new materials. This work focuses on the production of bioplastics based on poly (vinyl) alcohol (PVA) that have been modified with flavonoid fraction, liquid fraction obtained after digestion with cellulase and pectinase, and the solid material remaining after enzyme treatment, obtained from Citrus bergamia by-product (the so-called “pastazzo”). This last one is an almost completely unutilized product, although it is a potential rich source of biological active compounds. Enzymatic and non-enzymatic green extraction protocol have been employed to separate the different fractions and to make it more suitable to functionalize the PVA, suppling new properties to the bioplastics in a dose-dependent manner. Morpho-functional analysis was conducted by SEM, XRD, colorimetry, UV–visible and ATR-FTIR spectroscopy. Regarding optical properties, the obtained results show that transparency of the film in terms of light transmittance (T%) for PVA alone is very high, but when functionalized it had a reduced T%. From the data obtained, the functionalized films acquire antioxidant activity, as well as good mechanical properties, making them good candidates for biodegradable packaging for preserving the shelf life of different fruits and vegetables as confirmed by the food fresh-keeping test performed on apple samples. Full article

Background/Objectives: Watermelon (Citrullus lanatus) is a natural dietary source of L-citrulline and L-arginine, the two amino acids involved in nitric oxide (NO) production and vasodilation. Pre-clinical and clinical studies using isolated amino acids or watermelon extracts suggest blood pressure (BP)-lowering potential; however, limited research has been conducted on the impact of watermelon flesh (WM) on BP in adults at risk for hypertension. Therefore, the primary objective of this study was to assess the effect of daily WM intake for four weeks on 24 h ambulatory BP in adults with elevated blood pressure. The secondary outcomes of this study include changes in glucose and insulin markers, lipid profile, NO, L-citrulline, L-arginine, asymmetric dimethylarginine (ADMA) concentrations, and the L-arginine/ADMA ratio. Methods: In this randomized, placebo controlled parallel study design, 39 adults (age: 41 ± 14 years, BMI: 31 ± 6 kg/m², mean ± SD) with elevated BP were randomly assigned to one of three groups for a 4-week intervention: control (0 g WM), WM-1 cup (152 g/day), or WM-2 cups (304 g/day). Ambulatory BP was measured over 24 h at baseline and the end of the intervention period. Fasting plasma samples were analyzed for metabolic biomarkers on a clinical analyzer and NO using a colorimetric assay. L-citrulline, L-arginine, and ADMA were analyzed using an ultra-high-performance liquid chromatography triple quadrupole mass spectrometer (UHPLC-QQQ-MS/MS). Statistical analyses were conducted using SPSS software (IBM SPSS Statistics, Version 29.0.0). Results: After 4 weeks, mean 24 h ambulatory BP was 130.2 ± 3.9 mm Hg (control), 130 ± 3.2 mm Hg (WM-1 cup), and 124.9 ± 3.9 mm Hg (WM-2 cups), with no statistically significant differences between study interventions (p > 0.05). Similarly, no significant changes were observed in fasting plasma glucose, insulin, lipid profile, or NO concentrations. However, plasma L-arginine concentrations and L-arginine/ADMA ratios significantly increased in the WM groups compared to the control (p = 0.009) after adjusting for age, BMI, race, and gender in the statistical model. Conclusion: Overall, BP was not significantly different after two different doses of watermelon compared to control; however, improvements in NO synthesis pathway precursors (L-arginine, ADMA) suggest potential for dietary modulation to support endothelial function and BP regulation. Full article

Deoxynivalenol (DON) is one of the most common trichothecene mycotoxins found in cereals, posing a significant hazard to food and feed safety. Insects, especially the yellow mealworm (Tenebrio molitor), offer promising alternative protein sources; however, their capacity to metabolise mycotoxins and the nutritional implications are still not fully understood. In this study, T. molitor larvae were reared for two weeks on diets containing DON at 663 or 913 µg/kg, and their biomass was analysed using Liquid Chromatography–Quadrupole Time-of-Flight Mass Spectrometry (LC-QTOF) for DON metabolites and free amino acids, as well as Gas Chromatography–Flame Ionization Detector (GC-FID) for fatty acid profiles. Larvae metabolised DON via multiple pathways, including sulfonation, glucuronidation, sulfation, glucosylation, and de-epoxidation, with a time- and dose-dependent shift towards glucosylation and de-epoxidation. DON exposure significantly reduced the levels of essential amino acids such as methionine, lysine, phenylalanine, and isoleucine, and lowered metabolic intermediates like aspartic and glutamic acid. Conversely, prolonged DON exposure increased linoleic acid levels in larval fat, indicating altered lipid metabolism. These findings demonstrate that T. molitor larvae detoxify DON but incur measurable metabolic costs, leading to changes in amino acid and fatty acid profiles. The dual effect—reduction of toxin levels and nutritional shifts—highlights both the potential and the challenges of using insects for sustainable feed production. Full article