Search Results (3,187)

Sodium p-perfluorous nonenoxybenzenesulfonate (OBS) has been proposed as a substitute for perfluorooctanesulfonic acid (PFOS), yet it has garnered increasing attention due to its environmental persistence and potential toxicity. Despite these concerns, the neurotoxic mechanisms of OBS remain unclear. This study investigates and compares the neurotoxic effects and mechanisms of OBS and PFOS in Caenorhabditis elegans. L4-stage worms were exposed to OBS (0.1–100 μM) or PFOS (100 μM) for 24 h. Neurobehavioral analysis showed that OBS exposure induced concentration-dependent neurobehavioral deficits, with 100 μM OBS significantly reducing pharyngeal pumping rate (29.8%), head swing frequency (23.4%), and body bending frequency (46.6%), surpassing the effects of PFOS. Both compounds decreased the fluorescence intensity of dopaminergic, glutamatergic, and γ-aminobutyric acid neurons and downregulated neurotransmitter-associated genes. They also increased ROS generation and inhibited antioxidant gene expression. Molecular docking revealed that OBS had a stronger binding affinity to p38 MAPK key protein (PMK-1) than PFOS. OBS and PFOS upregulated pmk-1 and skn-1, modulating oxidative stress and neuronal function. pmk-1 mutation differentially affected OBS-induced neurobehavioral changes and gene expression alterations. Our findings indicate that OBS exhibits stronger neurotoxicity than PFOS in Caenorhabditis elegans, mediated through the PMK-1 pathway. These results highlight the need for further investigation into the safety of OBS as a PFOS alternative. Full article

Mesenchymal stem cells (MSCs), i.e., adult stem cells with immunomodulatory and secretory properties, contribute to tissue growth and regeneration, including healing processes. Some metal nanoparticles (NPs) are known to exhibit antimicrobial activity and may further potentiate tissue healing. We studied the effect of Ag, CuO, and ZnO NPs after in vitro exposure of mouse MSCs at the transcriptional level in order to reveal the potential toxicity as well as modulation of other processes that may modify the activity of MSCs. mRNA–miRNA interactions were further investigated to explore the epigenetic regulation of gene expression. All the tested NPs mediated immunomodulatory effects on MSCs, generation of extracellular vesicles, inhibition of osteogenesis, and enhancement of adipogenesis. Ag NPs exhibited the most pronounced response; they impacted the expression of the highest number of mRNAs, including those encoding interferon-γ-stimulated genes and genes involved in drug metabolism/cytochrome P450 activity, suggesting a response to the potential toxicity of Ag NPs (oxidative stress). Highly interacting MiR-126 was upregulated by all NPs, while downregulation of MiR-92a was observed after the ZnO NP treatment only, and both effects might be associated with the improvement of MSCs’ healing potency. Overall, our results demonstrate positive effects of NPs on MSCs, although increased oxidative stress caused by Ag NPs may limit the therapeutical potential of the combined MSC+NP treatment. Full article

This study aimed to develop an innovative resin composite with anti-biofouling properties, tailored to prosthesis fabrication in dentistry using a digital light processing (DLP) 3D-printing technique. The resin composite was formulated using a blend of dental monomers, with the integration of 2-methacryloyloxylethyl phosphorylcholine (MPC) with anti-biofouling behavior and γ-MPS-treated silica-zirconia powder for simultaneous mechanical reinforcement. The overall characterization of the resin composite was carried out using various contents of MPC incorporated into the resin (0–7 wt%) for examining the rheological behavior, photopolymerization, flexural strength/modulus, microstructure and anti-biofouling efficiency. The resin composite demonstrated a significant reduction in bacterial adhesion (97.4% for E. coli and 86.5% for S. aureus) and protein adsorption (reduced OD value from 1.3 ± 0.4 to 0.8 ± 0.2) with 7 wt% of MPC incorporation, without interfering with photopolymerization to demonstrate potential suitability for 3D printing without issues (p < 0.01, and p < 0.05, respectively). The incorporation and optimization of γ-MPS-treated silica-zirconia powder (10–40 vol%) enhanced mechanical properties, leading to a reasonable flexural strength (103.4 ± 6.1 MPa) and a flexural modulus (4.3 ± 0.4 GPa) at 30 vol% (n = 6). However, a further increase to 40 vol% resulted in a reduction in flexural strength and modulus; nevertheless, the results were above ISO 10477 standards for dental materials. Full article

Background: Immune checkpoint inhibitor therapy in patients with lung cancer and metastatic melanoma is associated with exacerbation of autoimmune-related diseases. The efficacy of treatment targeting the programmed cell death receptor-1 (PD-1) checkpoint relies upon a feedback loop between interferon gamma (IFN-γ) and the interleukin-12 isoform, IL-12p40. Paradoxically, both cytokines and the anti-PD-1 antibody worsen psoriasis. We previously reported an immunomodulating peptide, designated IK14004, that inhibits progression of Lewis lung cancer in mice yet uncouples IFN-γ from IL-12p40 production in human immune cells. Methods: Immune cells obtained from healthy donors were exposed to IK14004 in vitro to further characterise the signalling pathways affected by this peptide. Using C57BL/6 immunocompetent mice, the effect of IK14004 was tested in models of lung melanoma and psoriatic skin. Results: Differential effects of IK14004 on the expression of IFN-α/β, the interleukin-15 (IL-15) receptor and signal transducers and activators of transcription were consistent with immune responses relevant to both cancer surveillance and immune tolerance. Moreover, both melanoma and psoriasis were inhibited by the peptide. Conclusions: Taken together, these findings suggest mechanisms underlying immune homeostasis that could be exploited in the setting of cancer and autoimmune pathologies. Peptide administered together with checkpoint blockers in relevant models of autoimmunity and cancer may offer an opportunity to gain further insight into how immune tolerance can be retained in patients receiving cancer immunotherapy. Full article

With the global aging population on the rise, identifying environmental factors that modulate immunosenescence is critical for health interventions. While urban green spaces are known to confer health benefits, the long-term effects of forest exposure on immunosenescence remain unclear. This study investigated the differential impacts of urban forest versus urban environments on immunosenescence using a D-galactose-induced murine model. Mice were assigned to urban or forest environments for 8 weeks, with serum cytokines (IL-2, IL-6, TNF-α, IFN-γ), T-cell subsets, and organ indices analyzed. Forest environments exhibited significantly higher humidity and negative air ion concentrations alongside lower noise levels compared to urban settings. Aged forest-exposed mice showed attenuated immunosenescence markers, including significantly lower IL-6 levels (p < 0.01) and improved thymic indices, suggesting urban forest environments may mitigate immune decline. These findings highlight the potential of urban forests in promoting healthy aging, advocating for their integration into urban planning. Further human studies are warranted to translate these findings into public health strategies. Full article

Introduction: Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a very rare subtype of cutaneous T-cell lymphoma. It is characterized by the neoplastic infiltration of subcutaneous adipose tissue. Its clinical presentation, including subcutaneous nodules, fever, and systemic symptoms, often mimics inflammatory panniculitis, making diagnosis difficult. Case Presentation: This case report describes a 14-year-old female presenting with fever, limb pain, swelling, and subcutaneous nodules, who was ultimately diagnosed with SPTCL via punch biopsy and BIOMED-2 clonality assays, confirming positive T-cell receptor-γ chain gene rearrangement. Positron emission tomography–computed tomography revealed diffuse subcutaneous involvement across multiple body regions. Methylprednisolone and cyclosporine A treatment rapidly resolved her symptoms, with laboratory parameters, including ferritin and inflammatory markers, showing significant improvement. Next-generation sequencing identified a heterozygous C9 gene mutation (c.346C>T, p.Arg116Ter), adding a novel genetic dimension to the case. Following a tapered discontinuation of immunosuppressive therapy, the patient achieved sustained remission without relapse for over 1 year. Conclusions: We report a case of adolescent SPTCL treated with immunosuppressive therapy and suggest that immunosuppressive therapy should be considered before chemotherapy in pediatric patients with SPTCL but without HLH. Full article

Under normal conditions, the novel zinc blende beryllium oxide (zb BeO) exhibits in a metastable crystalline phase, which is less stable than its wurtzite counterpart. Ultrathin zb BeO epifilms have recently gained significant interest to create a wide range of advanced high-resolution, high-frequency, flexible, transparent, nano-electronic and nanophotonic modules. BeO-based ultraviolet photodetectors and biosensors are playing important roles in providing safety and efficiency to nuclear reactors for their optimum operations. In thermal management, BeO epifilms have also been used for many high-tech devices including medical equipment. Phonon characteristics of zb BeO at ambient and high-pressure P ≠ 0 GPa are required in the development of electronics that demand enhanced heat dissipation for improving heat sink performance to lower the operating temperature. Here, we have reported methodical simulations to comprehend P-dependent structural, phonon and thermodynamical properties by using a realistic rigid-ion model (RIM). Unlike zb ZnO, the study of the Grüneisen parameter γ(T) and thermal expansion coefficient α(T) in zb BeO has revealed atypical behavior. Possible reasons for such peculiar trends are attributed to the combined effect of the short bond length and strong localization of electron charge close to the small core size Be atom in BeO. Results of RIM calculations are compared/contrasted against the limited experimental and first-principle data. Full article

The strength mobilisation framework was adopted for the first time to describe the stress–strain responses for three different types of sands, including a total of 30 published drained triaxial tests—25 for Karlsruhe Fine Sand, 2 for Ottawa sands and 3 for Fontainebleau sand, under confining pressures ranging from 50 to 400 kPa. The peak shear strength ${\tau }_{peak}$ obtained from drained triaxial shearing of these sands was used to normalise shear stress. Shear strains normalised at peak strength ${\gamma }_{peak}$ and at half peak of shear strength ${\gamma }_{M=2}$ were taken as the normalised reference strains, and the results were compared. Power–law functions were then derived when the mobilised strength was between $0.2{\tau }_{peak}$ and $0.8{\tau }_{peak}$. Exponents of the power–law functions of these sands were found to be lower than in the published undrained shearing data of clays. Using ${\gamma }_{M=2}$ as the reference strain shows a slightly better power–law correlation than using ${\gamma }_{peak}$. Linear relationships between the reference strains and variables, such as relative density, relative dilatancy index, and dilatancy, are identified. Full article

This study aims to clarify the nonlinear pressure loss patterns of the pneumatic system in a pneumatic seeder under varying pipeline structures and airflow parameters, and to develop a rapid prediction equation for the main pipe’s pressure loss. The studied multi-branch pipeline system consists of a main pipe, a header, and ten branch pipes. The main pipe is vertically installed at the center of the header in a straight-line configuration. The ten branch pipes are symmetrically and evenly spaced along the axial direction of the header, distributed on both sides of the main pipe. The outlet directions of the branch pipes are arranged in a 180° orientation opposite to the inlet direction of the main pipe, forming a symmetric multi-branch configuration. Firstly, this study investigated the flow characteristics within the multi-branch pipeline of the pneumatic system and elaborated on the mechanism of flow division in the pipeline. The key geometric factors affecting airflow were identified. Secondly, from a microscopic perspective, CFD simulations were employed to analyze the fundamental causes of pressure loss in the multi-branch pipeline system. Finally, from a macroscopic perspective, a dimensional analysis method was used to establish an empirical equation describing the relationship between the pressure loss (P) and several influencing factors, including the air density (ρ), air’s dynamic viscosity (μ), closed-end length of the header (Δl), branch pipe 1’s flow rate (Q), main pipe’s inner diameter (D), header’s inner diameter (γ), branch pipe’s inner diameter (d), and the spacing of the branch pipe (δ). The results of the bench tests indicate that when 0.0018 m³·s⁻¹ ≤ Q ≤ 0.0045 m³·s⁻¹, 0.0272 m < d ≤ 0.036 m, 0.225 m < δ ≤ 0.26 m, 0.057 m ≤ γ ≤ 0.0814 m, and 0.0426 m ≤ D ≤ 0.0536 m, the prediction accuracy of the empirical equation can be controlled within 10%. Therefore, the equation provides a reference for the structural design and optimization of pneumatic seeders’ multi-branch pipelines. Full article

Background: Disease-modifying drugs (DMDs) for multiple sclerosis (MS) slightly increase the risk of tuberculosis (TB) disease. The QuantiFERON-TB-Plus (QFT-Plus) test is approved for TB infection (TBI) screening. Currently, there are no data available regarding the characterization of QFT-Plus response in patients with MS. Objectives: This study aimed to compare the magnitude of QFT-Plus responses between patients with MS and TBI (MS-TBI) and TBI subjects without MS (NON-MS-TBI). Additionally, discordant responses to TB1/TB2 stimulation were documented. Results were evaluated considering demographic and clinical data, particularly the impact of DMDs and the type of TB exposure. Methods: Patients with MS (N = 810) were screened for TBI (2018–2023). Thirty (3.7%) had an MS-TBI diagnosis, and 20 were recruited for the study. As a control group, we enrolled 106 NON-MS-TBI. Results: MS-TBI showed significantly lower IFN-γ production in response to TB1 (p = 0.01) and TB2 stimulation (p = 0.02) compared to NON-MS-TBI. The 30% of TB2 results of MS-TBI fell into the QFT-Plus grey zone (0.2–0.7 IU/mL). Only 7% of NON-MS-TBI showed this profile (p = 0.002). Conclusions: MS-TBI had a lower QFT-Plus response and more borderline results compared to NON-MS-TBI. Future studies should clarify the significance of the borderline results in this vulnerable population to improve QFT-Plus accuracy regarding sensitivity, specificity, and TB prediction. Full article

Since the monotonicity of the best approximant is crucial to establish partial ordering methods, in this paper, we, respectively, characterize the best approximants in Banach function spaces and Lorentz spaces ${\mathrm{\Gamma }}_{p,w}$, in which we especially focus on the monotonicity characterizations. We first study monotonicity characterizations of the metric projection operator onto sublattices in general Banach function spaces by the property $H_g$. The sufficient and necessary conditions for monotonicity of the metric projection onto cones and sublattices are then, respectively, established in ${\mathrm{\Gamma }}_{p,w}$. The Lorentz spaces ${\mathrm{\Gamma }}_{p,w}$ are also shown to be reflexive under the condition $R{B}_p$, which is the basis for the existence of the best approximant. As applications, by establishing the partial ordering methods based on the obtained monotonicity characterizations, the solvability and approximation theorems for best proximity points are deduced without imposing any contractive and compact conditions in ${\mathrm{\Gamma }}_{p,w}$. Our results extend and improve many previous results in the field of the approximation and partial ordering theory. Full article

Background/Objectives: Anti-p200 pemphigoid is a rare and likely underdiagnosed autoimmune blistering disorder. Laminin γ1 and laminin β4 have been implicated as potential target antigens in its pathogenesis. Recently, a novel indirect immunofluorescence assay targeting anti-laminin β4 antibodies has been developed, demonstrating high sensitivity and specificity, and offering a valuable tool for improved diagnosis. Methods: Of the 451 patients, 21 were selected for further laboratory analysis based on medical records. Sera from 10 patients, which showed a positive direct immunofluorescence (DIF) result and negative results in multiplex enzyme-linked immunosorbent assays (ELISAs) and/or mosaic six-parameter indirect immunofluorescence (IIF) for various autoimmune bullous diseases, were tested for the presence of anti-laminin β4 antibodies. Additionally, sera from 11 patients with positive DIF and positive ELISA for antibodies against BP180 and/or BP230 were analyzed. Results: Among the 10 patients with positive DIF and negative ELISA and/or mosaic six-parameter IIF, 6 sera were positive for anti-laminin β4 antibodies. These patients presented with atypical clinical features. In contrast, all 11 sera from patients with both positive DIF and positive ELISA for BP180 and/or BP230 were negative for anti-laminin β4 antibodies. Conclusions: In patients with a positive DIF result but negative ELISA and/or mosaic six-parameter IIF findings, testing for anti-laminin β4 antibodies should be considered. Furthermore, in cases presenting with atypical clinical features—such as acral distribution of lesions, intense pruritus, or erythematous–edematous plaques—the possibility of anti-p200 pemphigoid should be included in the differential diagnosis. Full article

Fecal microbiota transplantation (FMT) promotes growth performance and intestinal development in yellow-feathered broilers, but whether the virome and metabolites contribute to its growth-promoting effect remains unclear. This study removed the microbiota from FMT filtrate using a 0.45 μm filter membrane, retaining the virome and metabolites to perform fecal virome transplantation (FVT), aiming to investigate its regulatory role in broiler growth. Healthy yellow-feathered broilers with high body weights (top 10% of the population) were used as FVT donors. Ninety-six 8-day-old healthy male yellow-feathered broilers (95.67 ± 3.31 g) served as FVT recipients. Recipient chickens were randomly assigned to a control group and an FVT group. The control group was gavaged with 0.5 mL of normal saline daily, while the FVT group was gavaged with 0.5 mL of FVT solution daily. Growth performance, immune and antioxidant capacity, intestinal development and related gene expression, and microbial diversity were measured. The results showed that FVT improved the feed utilization rate of broilers (the feed conversion ratio decreased by 3%; p < 0.05), significantly increased jejunal length (21%), villus height (69%), and crypt depth (84%) (p < 0.05), and regulated the jejunal barrier: insulin-like growth factor-1 (IGF-1) (2.5 times) and Mucin 2 (MUC2) (63 times) were significantly upregulated (p < 0.05). FVT increased the abundance of beneficial bacteria Lactobacillales. However, negative effects were also observed: Immunoglobulin A (IgA), Immunoglobulin G (IgG), Immunoglobulin M (IgM), Interleukin-1 beta (IL-1β), Interleukin-6 (IL-6), Tumor Necrosis Factor-alpha (TNF-α), and Interferon-gamma (IFN-γ) in broilers were significantly upregulated (p < 0.05), indicating immune system overactivation. Duodenal barrier-related genes Mucin 2 (MUC2), Occludin (OCLN), Claudin (CLDN1), and metabolism-related genes solute carrier family 5 member 1 (SLC5A1) and solute carrier family 7 member 9 (SLC7A9) were significantly downregulated (p < 0.05). The results of this trial demonstrate that, besides the microbiota, the gut virome and metabolites are also functional components contributing to the growth-promoting effect of FMT. The differential responses in the duodenum and jejunum reveal spatial heterogeneity and dual effects of FVT on the intestine. The negative effects limit the application of FMT/FVT. Identifying the primary functional components of FMT/FVT to develop safe and targeted microbial preparations is one potential solution. Full article

Lower respiratory tract infections remain a leading cause of morbidity and mortality among Intensive Care Unit patients, with severe cases often progressing to acute respiratory distress syndrome (ARDS). This life-threatening syndrome results from alveolar–capillary membrane injury, causing refractory hypoxemia and respiratory failure. Early detection and management are critical to treat the underlying cause, provide protective lung ventilation, and, eventually, improve patient outcomes. The 2012 Berlin definition standardized ARDS diagnosis but excluded patients on non-invasive ventilation (NIV) or high-flow nasal cannula (HFNC) modalities, which are increasingly used, especially after the COVID-19 pandemic. By excluding these patients, diagnostic delays can occur, risking the progression of lung injury despite ongoing support. Indeed, sustained, vigorous respiratory efforts under non-invasive modalities carry significant potential for patient self-inflicted lung injury (P-SILI), underscoring the need to broaden diagnostic criteria to encompass these increasingly common therapies. Recent proposals expand ARDS criteria to include NIV and HFNCs, lung ultrasound, and the SpO₂/FiO₂ ratio adaptations designed to improve diagnosis in resource-limited settings lacking arterial blood gases or advanced imaging. However, broader criteria risk overdiagnosis and create challenges in distinguishing ARDS from other causes of acute hypoxemic failure. Furthermore, inter-observer variability in imaging interpretation and inconsistencies in oxygenation assessment, particularly when relying on non-invasive measurements, may compromise diagnostic reliability. To overcome these limitations, a more nuanced diagnostic framework is needed—one that incorporates individualized therapeutic strategies, emphasizes lung-protective ventilation, and integrates advanced physiological or biomarker-based indicators like IL-6, IL-8, and IFN-γ, which are associated with worse outcomes. Such an approach has the potential to improve patient stratification, enable more targeted interventions, and ultimately support the design and conduct of more effective interventional studies. Full article

This study evaluates the performance of tubular solar stills coated with gamma aluminium nanocoatings at concentrations of 5%, 10%, and 15%, compared to a conventional tubular solar still. This is the first experimental study to apply gamma aluminium nanocoatings on tubular solar stills (TSS). The stills were tested for three days, from 9:00 a.m. to 5:00 p.m., under consistent conditions with varying water depths of 1 cm, 2 cm, and 3 cm. The results indicated that the 5% nanocoating achieved the highest water yield, producing 2.571 L/m² with a 1 cm water depth. The 10% coating produced 2.514 L/m², while the conventional solar still generated 2.286 L/m². Thermal efficiency was highest on Day 1 for the 5% concentration, reaching 60.9%, followed by 10% concentration at 59.1%, while the 15% concentration showed the lowest efficiency at 33.8%. In terms of cost-effectiveness, the 5% concentration was the most economical, with the lowest cost per litre (CPL) of USD 0.10 and a payback period of 3.03 months. The 10% concentration had a CPL of USD 0.11 and a payback period of 3.33 months, while the 15% concentration had the highest CPL at USD 0.19 and the longest payback period of 5.63 months. Overall, the 5% concentration offered the best balance of water yield, efficiency, and cost-effectiveness. This research highlights γ-Al₂O₃ as an innovative, cost-effective material for solar distillation, paving the way for sustainable freshwater production. Full article