Search Results (9,656)

Glyphosate, a widely used herbicide, is under scrutiny for its potential neurotoxic effects. This study investigated whether oral exposure to glyphosate, even at doses currently considered safe in Europe, alters the neurochemical profile of enteric nervous system (ENS) neurons in the porcine jejunum. Fifteen immature female pigs were allocated to three groups: control (C), low-dose (G50; 50 µg/kg b.w./day), and higher-dose (G500; 500 µg/kg b.w./day). Following 28 days of exposure, jejunal samples were subjected to double-labelling immunofluorescence staining for neuronal markers, including Hu C/D and PACAP, CGRP, CART, nNOS, or VAChT. Results revealed dose-dependent neurochemical alterations across all enteric plexuses, with glyphosate increasing the number of neurons expressing PACAP, CGRP, CART, and nNOS, while reducing VAChT-positive neurons. The effect of glyphosate on enteric neurons appeared largely uniform across different plexus types, with more pronounced changes at the higher dose and only minor regional variation. Overall, the findings suggest that glyphosate exposure, even within regulatory limits, may alter the neurochemical profile of enteric neurons in a broadly uniform manner, potentially reflecting responses to oxidative stress or early neurotoxic effects, as reported in previous studies. This study challenges current safety thresholds and emphasises the need to reassess regulatory guidelines, particularly in the context of chronic exposure and potential risks to vulnerable populations. Full article

Background: Continuous insulin infusion protocols are essential for managing decompensated diabetic dogs, but comparative data between variable and fixed infusion rates are limited. Methods: This prospective observational study evaluated the glycemic response of 21 diabetic dogs treated with a fixed-dose continuous-rate infusion (CRI) of regular insulin at 0.05 IU/kg/h for 12 h. Capillary blood glucose was measured hourly. Statistical analyses included Wilcoxon signed-rank tests, Friedman test, Mann–Whitney U, and Kruskal–Wallis tests. Results: A significant reduction in glucose concentration occurred during the first five hours of infusion (p < 0.0001), followed by a stabilization phase with no further significant changes. No differences in glycemic response were found by sex or breed. The protocol was well tolerated, with no hypoglycemic events observed. Conclusions: A fixed-dose CRI of 0.05 IU/kg/h offers a safe and effective option for acute glycemic control in diabetic dogs, including those with early ketoacidosis. The standardized approach simplifies management without compromising efficacy and supports its inclusion in emergency treatment protocols. Full article

FVPB1, a novel heteropolysaccharide, was extracted from the Flammulina velutipes fruiting body, and its structure was determined by methylation analysis, nuclear magnetic resonance (NMR) spectroscopy. FVPB1 demonstrated efficacy in inhibiting lipid accumulation in Raw264.7 cells and zebrafish, as well as in reducing weight gain and ameliorating liver injury in high-fat diet-induced mice. High concentration of FVPB1 significantly increased serum ApoA1 levels, while all tested doses (low, medium, and high) reduced serum ApoB levels in mice. Intervention with FVPB1 significantly increased the mRNA expression of Lcat and Cyp7a1 enzymes while markedly reducing the transcriptional level of Hmgcr reductase. Additionally, low concentration of FVPB1 enhanced CYP7A1 protein expression, whereas medium and high concentrations of FVPB1 promoted LCAT protein expression. Medium and high concentrations of FVPB1 significantly enhanced bile acid excretion in mice, with the high dose additionally promoting fecal sterol output. Alpha and beta diversity analyses demonstrated that a high-fat diet induced substantial dysbiosis in the gut microbiota of mice, characterized by reduced microbial diversity and richness. Intervention with FVPB1 significantly modulated the structural composition of the intestinal microbiota in high-fat diet-fed mice. Therefore, FVPB1 exerts lipid-lowering effect in high-fat diet-fed mice by modulating cholesterol metabolism and ameliorating gut microbiota dysbiosis. Full article

Introduction: Despite global improvements in immunization, major gaps persist. By 2024, an estimated 14.3 million infants, predominantly in low- and middle-income countries (LMICs), remained zero-dose (ZD), never having received even the first DTP vaccine. In 2022, 33 million children missed their measles vaccination (22 million missed the first dose, 11 million missed the second dose), highlighting entrenched structural, behavioral, and systemic barriers that continue to exclude marginalized populations. Addressing these inequities requires innovative, context-adapted approaches that strengthen primary health care (PHC) and extend services to the hardest-to-reach populations. Objectives: This study aims to document and synthesize implementation research (IR) projects on immunization programs in LMICs, identifying key enablers and effective strategies that reduce inequities, improve outcomes, and support efforts to reach ZD children. Methods: We conducted a retrospective multiple-case study of 36 IR projects across 13 LMICs, embedded within an evidence review framework and complemented by policy analysis. Data were drawn from systematic document reviews and validation discussions with project leads. A total of 326 strategies were extracted, coded using a structured codebook, and mapped to the WHO–UNICEF PHC Levers for Action. Descriptive analysis synthesized patterns across service delivery and policy outcomes, including coverage gains, improved microplanning, community engagement, and system integration. Results: Of the 326 immunization strategies identified, most (76.1%) aligned with operational PHC levers, particularly monitoring and evaluation (19.3%), workforce development (18.7%), and models of care (12%). Digital technologies (11.7%) were increasingly deployed for real-time tracking and oversight. Core strategic levers comprised 23.9% of strategies, with community engagement (8.9%) and governance frameworks (7.7%) emerging as critical enablers, though sustainable financing (4%) and private-sector engagement (0.9%) were rarely addressed. While the majority of projects focused on routine immunization (n = 32), only a few directly targeted ZD children (n = 3). Interventions yielded improvements in both service delivery and policy outcomes. Improvements in microplanning and data systems (23.5%) reflected the increased uptake of digital dashboards, GIS-enabled tools, and electronic registries. Community engagement (16.2%) emphasized the influence of local leaders and volunteers in building trust, while health system strengthening (15.7%) invested in cold chain, supervision, and workforce capacity. Coverage gains (10.6%) were achieved through delivery innovations, though sustainable financing remained a critical problem (3.4%). Conclusions: Reaching ZD children requires equity-driven strategies that combine digital innovations, community engagement, and resilient system planning. Sustained progress depends on strengthening governance, financing, and research. Embedding IR in immunization programs generates actionable evidence, supports context-specific strategies, and reduces equity gaps, offering practical insights that complement health system research and advance the Immunization Agenda 2030. Full article

Fluoride is a widespread environmental toxin that disrupts metabolic and endocrine functions, but its impact on pancreatic inflammation and hormone secretion remains unclear. This study examined how chronic fluoride exposure affects pancreatic inflammation and secretory function in rats. Pregnant Wistar rats received sodium fluoride (NaF) at 50 mg/L in drinking water during gestation and lactation. Male offspring continued exposure until 3 months old. Controls received fluoride-free water. Pancreatic tissue and serum were collected. Fluoride levels were measured potentiometrically. Eicosanoids were quantified by SPE and HPLC. Serum insulin, glucagon, and somatostatin were measured by ELISA. Histological and biochemical markers of inflammation and oxidative stress were assessed. Fluoride exposure did not lead to significant accumulation in the pancreas or serum. However, fluoride-exposed rats exhibited a significant decrease in serum insulin and somatostatin concentrations, while glucagon levels remained unchanged. Additionally, the pancreas of fluoride-treated animals showed markedly elevated levels of pro-inflammatory eicosanoids, including prostaglandin E2, leukotrienes A4 and B4, and HETE/HODE derivatives, indicating activation of cyclooxygenase and lipoxygenase pathways. Sustained low-dose fluoride exposure induced pancreatic inflammation and disrupted endocrine homeostasis in rats. These findings suggest that chronic fluoride intake may impair insulin secretion and promote pre-diabetic alterations, warranting further research. Full article

Background and Objectives: In the context of hip fracture surgeries, episodes of hypotension are common, and have been associated in various studies with increased complications and mortality. The latest clinical guidelines recommend close hemodynamic management. Our research team hypothesized that the use of peripheral nerve blocks in this surgery could help adjust the doses of subarachnoid anesthesia for these procedures, thereby limiting the hypotensive episodes, without compromising an adequate depth and duration of intraoperative anesthesia. Materials and Methods: A retrospective study of 184 elderly patients undergoing hip fracture surgery is proposed. In total, 76 patients were operated under subarachnoid anesthesia using 9.5 mg of hyperbaric bupivacaine 0.5% and 10 mcg of fentanyl (Group S), while 108 received a reduced dose of 5 mg hyperbaric bupivacaine 0.5% and 10 mcg of fentanyl, supplemented by preoperative PENG and FLCN blocks (Group B). The main outcome of this study is to compare the number and duration of hypotensive episodes, and its secondary outcome is to compare the use of vasoactive drugs between the groups. Results: The number of hypotensive episodes and their duration were lower in Group B: −12.94 min (−8.57 to −18.03, p = 0.000). The consumption of vasoactive drugs did not reach statistical significance. None of the patients in Group B required supplementary intraoperative anesthesia. Conclusions: Reducing the dose in subarachnoid anesthesia is associated with better hemodynamic control in hip fracture surgeries, and PENG + NFCL blocks are proposed as an appropriate adjunct to ensure adequate anesthetic depth and duration despite a substantial subarachnoid anesthesia dose adjustment. Full article

The utilization of carbon dioxide (CO₂) offers an effective approach for alleviating the carbon-reduction pressures associated with fossil energy consumption. However, studies on the use of CO₂ as an auxiliary agent in water treatment to enhance the removal of emerging contaminants are limited. In this study, the photodegradation of ciprofloxacin (CIP) was investigated using ultraviolet (UV) irradiation combined with CO₂ dosing (UV/CO₂). The results demonstrated that the UV/CO₂ system effectively degraded CIP, with CO₂ concentration and solution pH exerting a critical influence. Inorganic anions and metal cations had negligible effects on CIP degradation efficiency, whereas natural organic matter (NOM) had a pronounced inhibitory effect. Mechanistic analysis revealed that superoxide radicals ($·{\mathrm{O}}_2^{-}$) and carbonate radicals (${\mathrm{CO}}_3^{•-}$) were the primary oxidizing species, whereas the excited triplet state of CIP (³CIP*) and singlet oxygen played crucial roles in initiating radical generation. LC–MS analysis and density functional theory calculations indicated that the main degradation routes involved defluorination, decarboxylation, and epoxidation of the piperazine ring. Toxicity assessment indicated that the transformation products generated by UV/CO₂ were less toxic than the parent compound. Furthermore, the UV/CO₂ process demonstrated high energy efficiency, with a low electrical energy per order (EEO) value of 0.4193 kWh·m⁻³·order⁻¹. These findings suggest that the UV/CO₂ system is a promising alternative for the treatment of photosensitive organic pollutants and provides a beneficial pathway for CO₂ utilization. Full article

Introduction/Background: Rift Valley fever virus (RVFV) and peste des petits ruminants virus (PPRV) are significant pathogens affecting small ruminants, causing substantial economic losses in the affected regions. The development of effective vaccines against both viruses is crucial for disease control. Recombinant viruses expressing heterologous antigens have shown promise as multivalent vaccine candidates. Unlike conventional PPRV vaccines, our recombinant RVFV-vectored vaccines offer a novel dual-protection strategy against RVF and PPR, combining safety, immunogenicity, and a DIVA strategy. Methods: Recombinant RVFVs (ZH548 strain) were generated to express either the hemagglutinin (H) or fusion (F) proteins from the PPRV strain Nigeria 75/1. The stability of these recombinant viruses was assessed through consecutive passages in cell culture. Immunogenicity studies were carried out in both mice and sheep to assess the induction of cellular and humoral immune responses capable of providing protection against RVFV and PPRV. These studies included intracellular cytokine staining (ICS), IFN-γ ELISAs, standard ELISAs for antibody detection, and virus neutralization assays. Results: The recombinant RVFVs expressing PPRV H or F proteins demonstrated stability in cell culture, maintaining high viral titers and consistent transgene expression over four passages. Immunization of mice resulted in the production of serum antibodies capable of neutralizing both RVFV and PPRV in vitro as well as cell-mediated immune responses specific to PPRV and RVFV antigens. In mice vaccinated with a high dose (10⁵ pfu), RVFV neutralizing titers reached ≥1:160 and PPRV neutralizing titers ranged from 1:40 to 1:80 by day 30 post-immunization. In sheep, neutralizing antibody titers against RVFV exceeded 1:160 as early as 2 days post-inoculation, while PPRV-specific neutralization titers reached up to 1:80 by day 21 in responsive individuals. In mice, administration of rZH548ΔNSs:F_PPRV elicited a detectable CD8+ IFNγ+ T-cell response against PPRV, with levels ranging from 1.29% to 1.56% for the low and high doses, respectively. In sheep, rZH548ΔNSs:F_PPRV also induced a robust IFNγ production against PPRV at 14 and 21 days post-infection (dpi). Conclusions: The successful generation and characterization of recombinant RVFVs expressing PPRV antigens demonstrate the potential of using rationally attenuated RVFV as a vector for multivalent vaccine development. Notably, the strategy proved more effective for the recombinant virus expressing the F protein, as it consistently induced more robust cellular and humoral immune responses. These results suggest that this approach could be a viable strategy for simultaneous immunization against Rift Valley fever and other prevalent ruminant diseases, such as peste des petits ruminants. Even though challenge studies were not performed in target species, the strong immune response observed supports including them in future studies. Full article

This study presents the results of an experimental evaluation of ride comfort for children transported in child restraint systems (CRS) during passages over speed bumps, with particular emphasis on the energy contained in vibrations. The tests were carried out under real operating conditions using two vehicles with different suspension characteristics and three loading levels corresponding to different stages of child development. Vertical accelerations were recorded at key points of the vehicle–seat system and subsequently analyzed in accordance with ISO 2631-1. Based on the vibration signals, root mean square acceleration (RMS), vibration dose value (VDV), seat effective amplitude transmissibility (SEAT), and root mean quad (RMQ) indices were calculated, enabling not only the assessment of discomfort levels but also the estimation of mechanical energy transmitted through the seat structure. The results showed that, depending on the type of vehicle, bump geometry, and load mass, the vibration energy can be significant and, in many cases, corresponds to levels classified as “severe” or “extreme discomfort.” At the same time, this energy constitutes a potential power source for low-power sensors in “smart seat” systems, such as those monitoring the child’s posture or environmental conditions. The findings highlight the need to consider vibration comfort criteria and the potential for vibration energy harvesting in the design and homologation of CRS, which aligns with the concept of sustainable transport and the development of energy self-sufficient technologies. Full article

TiO₂ is the most used material for the photocatalytic removal of organic pollutants in aqueous media. TiO₂, specifically its anatase phase, is well-known for its great performance under UV irradiation, high chemical stability, low cost and non-toxicity. Nevertheless, TiO₂ presents two main drawbacks: its limited absorption of the visible spectrum; and its relatively low specific surface area and pore volume. Regarding the latter, several works in the literature have addressed the issue by developing new synthesis approaches in which anatase is dispersed and supported on the surface of porous materials. In the present work, two series of materials have been prepared where anatase has been supported on mesoporous silica (MSTiR%) in situ through a hydrothermal synthesis approach, where, in addition to using tetraethoxysilane (TEOS) as a silicon precursor, three organotriethoxysilanes [RTEOS, where R = methyl (M), propyl (P) or phenyl (Ph)] were used at a RTEOS:TEOS molar percentage of 10 and 30%. The materials were thoroughly characterized by several techniques to determine their morphological, textural, chemical, and UV-vis light absorption properties and then the most promising materials were used as photocatalysts in the photodegradation of the emerging contaminant and antiepileptic carbamazepine (CBZ) under UV irradiation. The materials synthesized using 10% molar percentage of RTEOS (MSTiR10) were able to almost completely degrade (~95%), 1 mg L⁻¹ of CBZ after 1 h of irradiation using a 275 nm LED and 0.5 g L⁻¹ of catalyst dose. Therefore, this new synthesis approach has proven useful to develop photoactive TiO₂ composites with enhanced textural properties. Full article

Use of dicamba, an auxin-mimic herbicide, has increased in recent years. Both the effects of dicamba on non-target plants and the determination of a biological model to determine the dicamba ecotoxicity dynamics are important to monitor the correct and safe use of this herbicide. The objectives of this study were to determine the effects of low doses (simulating herbicide drift) and to determine the acute toxicity of dicamba to aquatic bioindicator species (Lemna minor, Pomacea canaliculate, Hyphessobrycon eques, and Danio rerio) and terrestrial non-target plants (Cucumis sativus, Solanum lycopersicum, and Lactuca sativa) in tropical conditions. Measurements of acute toxicity of dicamba at the concentrations that cause 50% of symptoms of injury (LC50) and other biometric variables were performed. Dicamba was virtually non-toxic to all aquatic bioindicator species (LC50 > 118.0 mg L⁻¹), while it was highly toxic to all terrestrial non-target plants (LC50 < 0.5 mg L⁻¹). Severe injury symptoms (70% to 100%) caused by application of low doses of dicamba were found for all non-target terrestrial plants. Severe injury symptoms (70% to 100%) caused by volatilization of dicamba were found only for S. lycopersicum. Since S. lycopersicum was found as the most sensitive non-target plant, showing high injury symptoms caused by dicamba and significant injury from volatilized dicamba, this species is suitable for environmental monitoring of dicamba applications. Full article

Consumption of meat singed with non-standard fuels is a common practice in many low- and middle-income settings, yet it may introduce combustion-derived toxicants with serious health consequences. While the toxicological effects of pollutants such as polycyclic aromatic hydrocarbons and heavy metals are well documented, the specific impact of singed meat consumption on endocrine regulation remains poorly understood. Of particular concern is the reproductive hormonal network, which not only serves as a sensitive biomarker of systemic disruption but also represents an evolutionary safeguard of fertility and generational continuity. Our study addresses this knowledge gap using male Wistar rats fed for 90 days (week 0 to week 12) on diets containing increasing proportions (25%, 50%, 75%) of meat singed with firewood, liquefied petroleum gas (LPG), or tyres. Firewood- and tyre-singed meat induced dose- and source-dependent toxicity, including hepatocellular injury, impaired protein metabolism, elevated blood urea nitrogen and creatinine, organ hypertrophy, and pronounced oxidative stress. Hormonal analysis revealed reduced testosterone alongside increased FSH, LH, and prolactin, indicating hypothalamic–pituitary–gonadal axis disruption and reproductive risk. In contrast, LPG-singed meat caused only minor alterations. These findings highlight reproductive hormones as sensitive biomarkers, underscoring the health risks of singeing practices and their evolutionary implications for fertility and population fitness. Full article

This study explores the anticancer, antioxidant, and phytochemical activities of Laurus nobilis L. ethanolic leaf extract. The extract demonstrated selective cytotoxicity against four human cancer cell lines, showing strong cytotoxic effect against ovarian (ES2), head and neck (SAS), and colorectal (HT-29) cancer cells, with IC₅₀ values ranging from 3.8 ± 0.3 to 4.4 ± 0.6 µg/mL. Notably, it exhibited only moderate inhibition of the MDA-MB-231 breast cancer cell line (IC₅₀ = 18.5 ± 0.8 µg/mL), possibly reflecting intrinsic differences in cell line sensitivity. Importantly, the extract showed low toxicity toward normal human fibroblasts (HDF), with an IC₅₀ value exceeding 100 µg/mL, indicating a favorable selectivity profile. The flow cytometry analysis showed that the extract caused cell death and stopped the cell cycle in both SAS and ES2 cancer cell lines. In SAS cells, extract treatment significantly increased apoptotic cells (21.1% ± 0.3%) compared to the control (6.3% ± 0.4%), along with G2 phase accumulation, indicating G2 arrest. Similarly, in ES2 cells, apoptosis increased (16.2% ± 1.3% vs. control 8.1% ± 1.0%), and a significant cell accumulation in the S phase was observed, suggesting disruption of cell cycle progression. Antioxidant screenings showed impressive dose-dependent DPPH radical scavenging activity (25–2000 µg/mL), although less potent than ascorbic acid (2.6 µg/mL). UPLC-QTOF/MS phytochemical analysis revealed various phenolic constituents, such as flavonoids and phenolic acids, and an inferred association with the recorded bioactivities. This preliminary work indicates that L. nobilis extracts may act as natural anticancer and antioxidant agents; however, it was limited to in vitro testing with non-standardized samples, underscoring the need for further research to validate and extend these findings for future applications. Full article

Quasi-two-dimensional (Q2D) perovskite films have garnered significant attention as novel gain media for lasers due to their tunable bandgap, narrow linewidth, and solution processability. Q2D perovskites endowed with intrinsic quantum well structures demonstrate remarkable potential as gain media for cost-effective miniaturized lasers, owing to their superior ambient stability and enhanced photon confinement capabilities. However, the mixed-phase distribution within Q2D films constitutes a critical determinant of their optical properties, exhibiting pronounced sensitivity to specific fabrication protocols and processing parameters, including annealing temperature, duration, antisolvent volume, injection timing, and dosing rate. These factors frequently lead to broad phase distribution in Q2D perovskite films, thereby inducing incomplete exciton energy transfer and multiple emission peaks, while simultaneously making the fabrication processes intricate and reducing reproducibility. Here, we report a novel annealing-free and antisolvent-free method for the preparation of Q2D perovskite films fabricated in ambient atmosphere. By constructing a tailored mixed-solvent vapor atmosphere and systematically investigating its regulatory effects on the nucleation and growth processes of film via in situ photoluminescence spectra, we successfully achieved the fabrication of Q2D perovskite films with large n narrow phase distribution characteristics. Due to the reduced content of small n domains, the incomplete energy transfer from small n to large n phases and the carriers’ accumulation in small n can be greatly suppressed, thereby suppressing the trap-assistant nonradiative recombination and Auger recombination. Ultimately, the Q2D perovskite film showed a single emission peak at 519 nm with the narrow full width at half maximum (FWHM) of 21.5 nm and high photoluminescence quantum yield (PLQY) of 83%. And based on the optimized Q2D film, we achieved an amplified spontaneous emission (ASE) with a low threshold of 29 μJ·cm⁻², which was approximately 60% lower than the 69 μJ·cm⁻² of the control film. Full article

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease affecting the joints, with neurogenic inflammation involving the nervous system being a hallmark of the condition. Treatments include medications such as disease-modifying antirheumatic drugs (DMARDs), corticosteroids, and biologics targeting inflammatory pathways. Yet, these treatments are not curative for RA. Heat Shock Proteins (HSPs) are molecular chaperones with immunoregulatory properties; however, their role is not yet fully understood, as these molecules may play a dual, pro- and anti-inflammatory role. In this study, we evaluated the protein expression levels of HSPs 27, 60, 70, and 90 in the synovial membrane and spinal cord of the RA rats’ model to determine their roles during the disease course, both on the neurological and immunological levels. Furthermore, HSP levels have been evaluated in the spinal cord of control and RA rats’ model after high and low doses of ketamine injection. Significant changes in Hsp60, 70, and 90 expression levels were observed only in the spinal cord of RA rats. We demonstrated that blocking N-methyl-D-aspartate receptors with ketamine can modulate spinal cord HSPs expression in RA rats and subsequently impact neurogenic inflammation and adult neurogenesis. This suggests that HSPs may be a promising target for RA treatment due to their complex immunomodulatory effects and potential interactions with the nervous system. Further research is needed to explore their therapeutic potential and develop effective interventions for RA. Full article