Search Results (2,935)

Background: African swine fever (ASF) is a highly contagious and often deadly disease that poses a major threat to swine production worldwide. The lack of a commercially available vaccine underscores the critical need for innovative immunization strategies to combat ASF. Methods: Six ASFV antigenic proteins (K78R, A104R, E120R, E183L, D117L, and H171R) were fused with the Lactiplantibacillus plantarum WCFS1 surface anchor LP3065 (LPxTG motif) to generate recombinant Lactiplantibacillus plantarum NC8 (rNC8) strains. The surface expression was confirmed using immunofluorescence and Western blotting assays. Additionally, the dendritic cell-targeting peptides (DCpep) were co-expressed with each antigen protein. Mice were immunized at a dosage of 10⁹ colony-forming units (CFU) per strain per mouse via intragastric (I.G.), intranasal (I.N.), and intravenous (I.V.) routes. The bacterial mixture was heat-inactivated by boiling for 15 min to destroy viable cells while preserving antigenic structures. I.V. administration caused no hypersensitivity, confirming the method’s safety and effectiveness. Results: Following I.G. administration, rNC8-E120R, rNC8-E183L, rNC8-K78R, and rNC8-A104R induced significant levels of secretory immunoglobulin A (sIgA) in fecal samples, whereas rNC8-H171R and rNC8-D117L failed to induce a comparable response. Meanwhile, rNC8-D117L, rNC8-K78R, and rNC8-A104R also elicited significant levels of sIgA in bronchoalveolar lavage fluid (BALF). Following I.N. immunization, rNC8-E120R, rNC8-K78R, and rNC8-A104R significantly increased sIgA levels in both fecal and BALF immunization. In contrast, I.V. immunization with heat-inactivated rNC8-K78R and rNC8-A104R induced robust serum IgG titers, whereas the remaining antigens elicited minimal or insignificant responses. Flow cytometry analysis revealed expanded CD3⁺CD4⁺ T cells in mice immunized via the I.N. and I.G. and CD3⁺CD4⁺ T cells only in those immunized via the I.N. route. Th1 responses were also significant in the sera of mice immunized via the I.G. and I.N. routes. Conclusions: The rNC8 multiple-antigen cocktail elicited strong systemic and mucosal immune responses, providing a solid foundation for the development of a probiotic-based vaccine against ASF. Full article

A total of 24 novel steroidal derivatives were synthesized, including 1,3,4-thia(selena)diazolines and structurally unique spirothiadiazolines, obtained through intramolecular cyclization under standard acetylation conditions. This strategy was further extended to the construction of a novel dimeric compound bearing a thiadiazoline linker. Seleno- and thiosemicarbazone precursors were derived from various functionalized steroidal monomers and dimers via straightforward synthetic protocols. Key intermediates included aldehyde 7 and ketones 16, 19, and 24. Rotameric equilibria were observed in certain thiosemicarbazones, attributed to partial double-bond character in the N–CS bond. Cyclization yielded heterocyclic systems as epimeric mixtures, and in some cases, inseparable mixtures of isomers were obtained due to low diastereoselectivity. Full structural elucidation of epimeric pairs was achieved using 2D NMR and IR spectroscopy, with compounds 2, 3, 5, 11, 17, 27, 28a, and 28b further confirmed by single-crystal X-ray diffraction. Preliminary antiproliferative assays against human cancer cell lines revealed GI₅₀ values below 10 µM for compounds 21, 22, and 27. Full article

Skin sensitization is a complex biological process induced by a wide range of chemicals, from single molecules to complex mixtures and finished products. While single chemical entities were used to design and validate sophisticated safety assessment assays, complex chemistries have proven challenging to test in practice using these methods. These assays range from in silico and in chemico methods to cell-based and reconstructed tissues-based approaches and target the key events now grouped within the Adverse Outcome Pathway. We focused our analysis on the use of New Approach Methodologies for skin sensitization assessments of complex mixtures, botanicals, medical and wearable devices, agrochemicals, and pollutants. We present the defined approaches that integrate these technologies, aligning with the principles of the replacement, reduction, and refinement of animal testing. We also detail the known challenges posed by these product classes in terms of testing and data interpretation. Our analysis indicates that validated and non-validated NAMs have shown some success in predicting skin sensitization potential across the product categories reviewed. Full article

Lopezia racemosa Cav., commonly known as “cancer herb” in indigenous communities, has long been used for its medicinal properties. The biotechnological production of its bioactive compounds through genetic transformation represents a valuable approach for obtaining pharmacologically relevant substances. The initial focus of this study was to identify compounds previously reported in the species; however, phytochemical analysis by HPLC and NMR led to the isolation and identification of two pentacyclic triterpene esters not previously described in L. racemosa: 3-O-[(E)-feruloyl]-maslinic acid (1) and 3-O-[(E)-feruloyl]-corosolic acid (2), identified as constituents of fraction 33. The LRTC3.1 callus line was obtained from hairy roots generated by infecting L. racemosa leaf explants with Agrobacterium rhizogenes strain ATCC15834/pTDT. The crude extract, specific fractions, and the mixture of these compounds demonstrated significant anti-inflammatory and cytotoxic activities. Anti-inflammatory activity was evaluated using the carrageenan-induced mouse paw edema model, where the crude extract achieved 51.02% inhibition of inflammation compared to meloxicam (30.86%). Cytotoxicity was assessed against three human cancer cell lines: breast carcinoma (MCF7), cervical carcinoma (SiHa), and colon carcinoma (HCT-15). Fractions FD (28–29) and 33 exhibited potent cytotoxic effects, with IC₅₀ values of 0.508 and 1.345 µg/mL against SiHa cells, and 0.053 and 2.693 µg/mL against MCF-7 cells, respectively. These findings suggest that transformed L. racemosa cultures represent a promising source of bioactive compounds for potential therapeutic development. Full article

Fuel cells have become a fundamental technology in the development of clean energy systems, playing a vital role in the global shift toward a low-carbon future. With the growing need for sustainable hydrogen production, perfluoro sulfonic acid (PFSA) ionomer membranes play a critical role in optimizing green hydrogen technologies and fuel cells. This study aims to investigate the effects of different environmental and solvent treatments on the chemical and physical properties of Nafion N−115 membranes to evaluate their suitability for both hydrogen production in proton exchange membrane (PEM) electrolyzers and hydrogen utilization in fuel cells, supporting integrated applications in the local and global green hydrogen economy. To achieve this, Nafion N−115 membranes were partially dissolved in various solvent mixtures, including ethanol/isopropanol (EI), isopropanol/water (IW), dimethylformamide/N-methyl-2-pyrrolidone (DN), and ethanol/methanol/isopropanol (EMI), evaluated under water immersion and thermal stress, and characterized for chemical stability, mechanical strength, water uptake, and proton conductivity using advanced electrochemical and spectroscopic techniques. The results demonstrated that the EMI-treated membrane showed the highest proton conductivity and maintained its structural integrity, making it the most promising for hydrogen electrolysis applications. Conversely, the DN-treated membrane exhibited reduced stability and lower conductivity due to solvent-induced degradation. This study highlights the potential of EMI as an optimal solvent mixture for enhancing PFSA membranes performance in green hydrogen production, contributing to the advancement of sustainable energy solutions. Full article

Although chlorpromazine is primarily used in psychiatry, it has been shown since its introduction to influence the course of neoplastic diseases. According to the strategy of drug repurposing, chlorpromazine has been successfully tested for its potential antitumor effects on multiple cancer cell lines. This effect is consistent with the overlap of molecular pathways observed for years between schizophrenia and cancer. The main objective of this work was to evaluate the lipophilicity of 17 previously synthesized tetracyclic chlorpromazine analogues exhibiting diverse anticancer and antimicrobial activity using thin-layer chromatography and computational methods. For a compound to become an effective drug, it must have a favorable ADMET profile, which determines its pharmacokinetic properties as a drug candidate. Lipophilicity is one of the key parameters widely employed in designing new bioactive compounds as potential therapeutic agents. In this article, chromatographic plates precoated with silica gel 60 RP-18F₂₅₄ and a mixture of acetone and TRIS buffer were used as the mobile phase. The chromatographic parameter of lipophilicity (R_M0) of the investigated compounds determined by means of the Soczewinski–Wachtmeister formula was useful to obtain the values of the experimental lipophilicity parameter expressed as logP_TLC. The results of logP_TLC were compared with theoretical values of logP obtained using different algorithms (iLOGP, XLOGP3, WLOGP, MLOGP, SILCOS-IT, and ClogP). Furthermore, the online platforms, such as SwissADME and pkCSM, allowed the determination of the remaining ADME parameters of the quinoline derivatives of chlorpromazine. The study of lipophilicity and ADME factors enabled confirmation that the tested compounds demonstrated favorable properties. Therefore, they can be considered as promising starting structures for further studies. Full article

Grape pomace is a major by-product of winemaking and a rich source of phenolic compounds with antioxidant potential. The Carménère variety, emblematic of Chilean viticulture, remains underutilized despite its high anthocyanin and flavanol content. This study aimed to develop a cost-effective method to recover and stabilize bioactive compounds from Carménère grape pomace. Five extracts were obtained using ethanol–water mixtures (0–100%) and characterized by HPLC-DAD and antioxidant assays (DPPH, FRAP, ORAC-FL). The 80% ethanol extract (EET-80) showed the highest antioxidant capacity (FRAP: 2909.3 ± 37.6; ORAC-FL: 1864.3 ± 157.8 µmol TE/g dw) and was selected for microencapsulation via spray drying using maltodextrin. This scalable technique protects thermosensitive compounds and enhances their applicability. The optimized 1:50 extract-to-carrier ratio achieved high encapsulation efficiency (85.7 ± 0.7%). In Caco-2 cells, the microencapsulated extract (5–250 µg/mL) showed no alteration in metabolic activity and significantly reduced intracellular ROS levels (65% inhibition at 250 µg/mL). Solvent polarity selectively influenced polyphenol recovery—50% ethanol favored catechin (581.1 µg/g) and epicatechin (1788.3 µg/g), while 80% ethanol enhanced malvidin-3-O-glucoside (118.0 µg/g). These findings support the valorization of Carménère grape pomace as a sustainable source of antioxidants and highlight the role of microencapsulation in improving extract stability and functionality. Full article

Background: Experimental studies suggest that some insecticides, fungicides, and herbicides can result in liver cell death, but population-based evidence is lacking. We investigated associations between urinary pesticide metabolites and liver biomarkers among adolescents and adults in an Ecuadorian agricultural area. Methods: We examined participants in 2016 (N = 528, 11–17 years) and 2022 (N = 505, 17–24 years). Plasma alanine aminotransferase (ALT), aspartate aminotransferase, soluble cytokeratin-18, and erythrocytic acetylcholinesterase were measured. Urinary biomarkers included four organophosphates, six neonicotinoids, three pyrethroids, two herbicides, and two fungicides. Generalized estimating equation (GEE) models examined associations and introduced sex and age interaction terms and quadratic terms. Quantile g-computation evaluated the effects of pesticide mixtures. Results: No significant associations were observed between pesticide biomarkers and liver biomarkers in longitudinal or cross-sectional analyses. A curvilinear association was found between 3-phenoxybenzoic acid (3-PBA; pyrethroid) and ALT (β_quadratic = −0.35, 95% CI: [−0.67, −0.04]) in 2016, but not in 2022. Sex modified the associations of 3-PBA with AST, ALT, and CK18-M65 in adolescents (2016), with non-significant positive associations observed in males and non-significant negative associations observed in females. No pesticide mixture effects were observed. Conclusions: Urinary biomarkers of various insecticides, herbicides, fungicides, and their mixtures were not associated with liver biomarkers among adolescents and young adults in agricultural settings. These largely null findings, consistent across time points, suggest background-level exposures in these settings possibly do not harm liver health in this population, though effects at higher exposures cannot be ruled out. Full article

Cardiovascular diseases (CVDs) remain the leading cause of morbidity and mortality in industrialized countries. Coronary artery disease (CAD) represents the most prevalent form of cardiovascular disease and remains a leading cause of morbidity, mortality, and long-term disability worldwide. Therefore, the identification of early biomarkers and clarification of the mechanism of action of pharmacological adjuvants is urgently needed. Nutraceuticals such as Arthrospira platensis (commonly known as spirulina) have emerged as promising modulators for their notable vascular anti-inflammatory properties. In this study, we provide novel evidence of the anti-inflammatory and anti-atherosclerotic potential of Arthrospira platensis toward endothelial cells and immune interactions, combining in vitro assays with bioinformatic profiling. Spirulina treatment significantly attenuated endothelial and angiogenic activation, reducing pro-inflammatory cytokine and VEGFA/VEGFR2 expression. Additionally, it also decreased the activation and adhesion capabilities of THP-1 monocytic cell lines. Through computational analysis of the complex molecular mixture present in Arthrospira platensis, we have identified a subset of compounds exhibiting high structural similarity to CHEMBL3559503, a well-characterized synthetic molecule with dual activity as a TLR9 agonist and anti-angiogenic agent. This represents a novel insight, suggesting that spirulina may serve as a natural source of analogues capable of modulating both immune and angiogenic pathways. These results highlight Arthrospira platensis as a promising candidate nutraceutical for targeting endothelial/immune crosstalk in the context of atherosclerosis prevention, offering both mechanistic insights and translational potential. Full article

Bacterial infection is a cause of life-threatening diseases. The emergence of antimicrobial-resistant bacteria exacerbates this situation, highlighting the need for the discovery of new antimicrobial agents. Our previous study identified a novel antimicrobial peptide, BrSPR20-P1 (P1), which showed potential activity against MRSA. Additionally, silver nanoparticles (AgNPs) exhibit broad-spectrum antibacterial activity, capable of killing multidrug-resistant bacteria. The combination of antimicrobial agents presents a novel strategy for combating these pathogens. This study aimed to evaluate the antibacterial activity of the combination of P1 and AgNPs. It revealed that the combinations showed synergy. The P1 and AgNP mixture at a concentration of 1 and 8 µg/mL (1:8) doubled the activity against S. aureus and MRSA, while that combination of 64 and 64 µg/mL (64:64) exhibited broad-spectrum activity, expanding to E. coli with a 32-fold increase. These combinations exhibited a bactericidal effect, showing the rapid killing of tested bacteria at 10× MIC, with killing rates during the first 3 h ranging from 4.04 ± 0.01 to 4.31 ± 0.03 h⁻¹. The P1 and AgNP mixtures caused a low risk of antibacterial resistance up to 30 passages. It was demonstrated that the synergistic activity of P1 and AgNPs occurred through the disruption of cell walls and membranes, leakage of intracellular materials, and cell lysis. Additionally, the mixtures appeared to interact with bacterial genomic DNA, as indicated by a gel retardation assay. These activities of the combinations were concentration-dependent. The 1:8 µg/mL mixture caused low hemolysis and cytotoxicity and did not impede the wound healing process. In contrast, although the 64:64 µg/mL mixture showed excellent antibacterial efficacy, it was toxic to erythrocytes and mammalian cells. It implies that dose optimization is required to balance its efficacy and toxicity. Therefore, the P1 and AgNP combinations exhibit synergistic antimicrobial activity and have the potential to resolve bacterial infections. Full article

Background/Objectives: Lung squamous cell carcinoma (SCC), a major subtype of non-small cell lung cancer, remains a significant clinical challenge due to a scarcity of actionable molecular targets and the limited effectiveness of current targeted therapies. Emerging treatment strategies inhibit the gene expression of lineage survival oncogenes such as ΔNp63 and SOX2. CRISPR interference (CRISPRi) is a promising method to downregulate these genes; however, the efficacy depends on effective delivery. Here, we focused on the delivery system using nanobubbles (NBs) and ultrasound (US) for site-specific CRISPRi delivery to SCC. We evaluated the therapeutic efficacy of plasmid-based CRISPRi (pCRISPRi) targeting SOX2 or ΔNp63 using intratumoral pCRISPRi/NBs injections followed by US. Methods: A mixture of NBs and pCRISPRi was injected directly into the tumors and exposed to US-induced cavitation to facilitate pCRISPRi uptake. Tumor volume was measured every other day, and apoptosis was assessed by TUNEL assay. Results: In a lung SCC xenograft model, NBs/US-mediated pCRISPRi delivery induced apoptosis and significantly suppressed tumor growth. Conclusions: These findings suggest that US-guided, NB-facilitated delivery of pCRISPRi can locally suppress lineage survival oncogenes and trigger tumor cell death, representing a promising targeted therapy for lung SCC. Additionally, this platform could be adapted to other cancers by targeting alternative factors. Full article

Impervious surfaces reduce natural infiltration, leading to increased runoff, erosion, and pollutant transport. The Alabama Department of Transportation (ALDOT) relies on implementing infiltration swales, a linear bioretention-based practice, along roadside drainage channels to reduce surface runoff. This study developed and constructed modified permeameters and infiltrometers to evaluate and optimize media used to construct infiltration swales. The average measured falling head infiltration rate of sandy topsoil used in the media matrix was 0.63 ft/day (0.19 m/day). A series of amended topsoil mixtures were tested to improve the infiltration rate of the media. In particular, the mixture of 80% topsoil and 20% pine bark fines (by weight) significantly improved the infiltration rates of the swale media. Through iterative testing, the F3 design with 6 in. (15.2 cm) mixture and 10 in. (25.4 cm) sand achieved up to 13.73 ft/day (4.18 m/day) of infiltration rate under constant head, far surpassing the infiltration rate of the current ALDOT design. SWMM bioretention cell models were developed to understand the swale infiltration process and revealed that the infiltration rates obtained from column tests were the saturated hydraulic conductivities of the soil layer when there was no other restriction on vertical flow. The simulated swale hydrological performance depends not only on variations in soil conductivity but also on other swale characteristics under field conditions. Findings from this research can be used to enhance the performance of infiltration-based stormwater practices. Full article

This study used NMR-based metabolomics to investigate the mode of action (MoA) of 6-hydroxydopamine (6-OHDA) toxicity in the SH-SY5Y neuroblastoma cell model. 6-OHDA, a structural analogue of dopamine, has been used to create a Parkinson’s disease model since 1968. Its selective uptake via catecholaminergic transporters leads to intracellular oxidative stress and mitochondrial dysfunction. SH-SY5Y cells were treated with 6-OHDA at its IC₅₀ concentration of 60 μM, and samples of treated and untreated groups were collected after 24 h. The endo metabolome was extracted using a methanol–water mixture, while the exo metabolome was represented by the culture media. Further, endo- and exo metabolomes of treated and untreated cells were analysed for metabolic changes. Our results demonstrated significantly high levels of glutathione, acetate, propionate, and NAD⁺, which are oxidative stress markers, enhanced due to ROS production in the system. In addition, alteration of myoinositol, taurine, and o-phosphocholine could be due to oxidative stress-induced membrane potential disturbance. Mitochondrial complex I inhibition causes electron transport chain (ETC) dysfunction. Changes in key metabolites of glycolysis and energy metabolism, such as glucose, pyruvate, lactate, creatine, creatine phosphate, glycine, and methionine, respectively, demonstrated ETC dysfunction. We also identified changes in amino acids such as glutamine, glutamate, and proline, followed by nucleotide metabolism such as uridine and uridine monophosphate levels, which were decreased in the treated group. Full article

Developments of new research tools in flotation studies, including bubble–particle attachment time efficiency and dynamic froth analysis, can help improve our understanding of particle–bubble interactions in flotation processes. In particular, the selection of new collectors and frothers, and their mixtures can provide a wide distribution of bubble sizes at their respective concentrations. In the literature, several studies have reported the effect of different frothers and collector mixtures on bubble characteristics like bubble size and critical coalescence concentration (CCC). The general trend obtained from these studies showed that the addition of frothers, along with collectors, which also act as frothers during flotation, resulted in finer bubbles and required lower concentrations of frothers, which in turn positively affected the flotation recoveries. In this study, an attempt was made to study fine-sized magnesite in the presence of sodium oleate (NaOL) and five different types of frothers (PPG600, PPG400, BTPG, BDPG, and MIBC). Bubble–particle attachment time with different sized capillary tubes and dynamic froth analysis values in a liquid–air system, along with flotation recoveries in a micro-flotation cell, were interpreted to show possible correlations and provide an optimum bubble/particle size ratio in the presence of different frothers. Full article

Lignin used in this work was isolated from sapele (Entandrophragma cylindricum) wood through a hybrid pulping process using soda/ethanol as pulping liquor and denoted soda-oxyethylated lignin (SOL). SOL was mixed with a polyethylene glycol (PEG)–glycerol mixture (80/20 v/v) as liquefying solvent with 98% wt. sulfur acid as catalyst, and the mixture was taken to boil at 140 °C for 2, 2.5, and 3 h. Three bio-polyols LBP1, LBP2, and LBP3 were obtained, and each of them exhibited a high proportion of -OH groups. Lignin-based polyurethane foams (LBPUFs) were prepared using the bio-polyols obtained with a toluene diisocyanate (TDI) prepolymer by the one-shot method. Gel permeation chromatography (GPC), Fourier transform infrared spectroscopy (FTIR), and carbon-13 nuclear magnetic resonance spectroscopy (¹³C NMR) were used characterize lignin in order to determine viscosity, yield, and composition and to characterize their structure. The PEG-400–glycerol mixture was found to react with the lignin bio-polyols’ phenolic -OHs. The bio-polyols’ viscosity was found to increase as the liquefaction temperature increased, while simultaneously their molecular weights decreased. All the NCO groups were eliminated from the samples, which had high thermal stability as the liquefaction temperature increased, leading to a decrease in cell size, density, and crystallinity and an improvement in mechanical performance. Based on these properties, especially the presence of some aromatic rings in the bio-polyols, the foams produced can be useful in automotive applications and for floor carpets. Full article