Search Results (1,294)

Leishmaniasis is an infectious disease common in tropical and subtropical regions worldwide. This study aimed to develop a topical meglumine antimoniate gel (MA-gel) for the treatment of cutaneous leishmaniasis. The MA-gel was characterized in terms of morphology, pH, swelling, porosity, rheology, and thermal properties by differential scanning calorimetry (DSC). Biopharmaceutical evaluation included in vitro drug release and ex vivo skin permeation. Safety was evaluated through biomechanical skin property measurements and cytotoxicity in HaCaT and RAW 267 cells. Leishmanicidal activity was tested against promastigotes and amastigotes of Leishmania infantum, and in silico studies were conducted to explore possible mechanisms of action. The composition of the MA-gel included 30% MA, 20% Pluronic^® F127 (P407), and 50% water. Scanning electron microscopy revealed a sponge-like and porous internal structure of the MA-gel. This formula exhibited a pH of 5.45, swelling at approximately 12 min, and a porosity of 85.07%. The DSC showed that there was no incompatibility between MA and P407. Drug release followed a first-order kinetic profile, with 22.11 µg/g/cm² of the drug retained in the skin and no permeation into the receptor compartment. The MA-gel showed no microbial growth, no cytotoxicity in keratinocytes, and no skin damage. The IC₅₀ for promastigotes and amastigotes of L. infantum were 3.56 and 23.11 µg/mL, respectively. In silico studies suggested that MA could act on three potential therapeutic targets according to its binding mode. The MA-gel demonstrated promising physicochemical, safety, and antiparasitic properties, supporting its potential as a topical treatment for cutaneous leishmaniasis. Full article

Ceramic pastes used in additive manufacturing offer several advantages, including low production costs due to the availability of raw materials and efficient processing methods, as well as a reduced environmental footprint through minimized material waste, optimized resource use, and the inclusion of recyclable or sustainably sourced components. This study evaluates the effect of diatomite content in a ceramic paste composed of carboxymethyl cellulose, kaolinite, and feldspar on its extrusion behavior and thermal conductivity, with additional analysis of its implications for microstructure, mechanical properties, and thermal performance. Four ceramic pastes were prepared with diatomite additions of 0, 10, 30, and 60% by weight. Thermal conductivity, extrusion behavior, morphology, and distribution were examined using scanning electron microscopy (SEM), while thermal degradation was assessed through thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). The results show that increasing diatomite content leads to a reduction in thermal conductivity, which ranged from 0.719 W/(m·°C) for the control sample to 0.515 W/(m·°C) for the 60% diatomite sample, as well as an improvement in extrusion behavior. The ceramic paste demonstrated adequate extrusion performance for 3D printing at diatomite contents above 30%. These findings lay the groundwork for future research and optimization in the development of functional ceramic pastes for advanced manufacturing applications. Full article

Accurate segmentation of cardiac MR images using deep neural networks is crucial for cardiac disease diagnosis and treatment planning, as it provides quantitative insights into heart anatomy and function. However, achieving high segmentation accuracy relies heavily on extensive, precisely annotated datasets, which are costly and time-consuming to obtain. This study addresses this challenge by proposing a novel data augmentation framework based on a condition-guided diffusion generative model, controlled by multiple cardiac labels. The framework aims to expand annotated cardiac MR datasets and significantly improve the performance of downstream cardiac segmentation tasks. The proposed generative data augmentation framework operates in two stages. First, a Label Diffusion Module is trained to unconditionally generate realistic multi-category spatial masks (encompassing regions such as the left ventricle, interventricular septum, and right ventricle) conforming to anatomical prior probabilities derived from noise. Second, cardiac MR images are generated conditioned on these semantic masks, ensuring a precise one-to-one mapping between synthetic labels and images through the integration of a spatially-adaptive normalization (SPADE) module for structural constraint during conditional model training. The effectiveness of this augmentation strategy is demonstrated using the U-Net model for segmentation on the enhanced 2D cardiac image dataset derived from the M&M Challenge. Results indicate that the proposed method effectively increases dataset sample numbers and significantly improves cardiac segmentation accuracy, achieving a 5% to 10% higher Dice Similarity Coefficient (DSC) compared to traditional data augmentation methods. Experiments further reveal a strong correlation between image generation quality and augmentation effectiveness. This framework offers a robust solution for data scarcity in cardiac image analysis, directly benefiting clinical applications. Full article

An anion exchange-assisted technique was used for the synthesis of platinum-decorated SnO₂ supports, providing nanocatalysts with enhanced activity for the reduction of 4-nitrophenol (4-NP) to 4-aminophenol (4-AP). In this study, a series of SnO₂ supports, namely SnA (synthesized almost at room temperature), SnB (hydrothermally treated at 180 °C), and SnC (annealed at 600 °C), are systematically investigated, all loaded with 1 mol% Pt from H₂PtCl₆ under identical mild conditions. The chloride ions from the SnCl₄ precursors were efficiently removed via a strong-base anion exchange reaction, resulting in highly dispersed, crystalline ~5 nm cassiterite SnO₂ particles. All Pt/SnO₂ composites displayed mesoporous structures with type IVa isotherms and H₂-type hysteresis, with SP1a (Pt on SnA) exhibiting the largest surface area (122.6 m²/g) and the smallest pores (~3.5 nm). STEM-HAADF imaging revealed well-dispersed PtOx domains (~0.85 nm), while XPS confirmed the dominant Pt⁴⁺ and Pt²⁺ species, with ~25% Pt⁰ likely resulting from photoreduction and/or interactions with Sn–OH surface groups. Raman spectroscopy revealed three new bands (260–360 cm⁻¹) that were clearly visible in the sample with 10 mol% Pt and were due to the vibrational modes of the PtOx species and Pt-Cl bonds introduced due the addition and hydrolysis of H₂PtCl₆ precursor. TGA/DSC analysis revealed the highest mass loss for SP1a (~7.3%), confirming the strong hydration of the PtOx domains. Despite the predominance of oxidized PtOx species, SP1a exhibited the highest catalytic activity (k_app = 1.27 × 10⁻² s⁻¹) and retained 84.5% activity for the reduction of 4-NP to 4-AP after 10 cycles. This chloride-free low-temperature synthesis route offers a promising and generalizable strategy for the preparation of noble metal-based nanocatalysts on oxide supports with high catalytic activity and reusability. Full article

Background: Lysosomal-associated membrane protein 1 (LAMP1), typically localized to the lysosomal membrane, is increasingly implicated as a marker of cancer aggressiveness and metastasis when expressed on the cell surface. This study aimed to develop a LAMP1-targeted antibody-based PET tracer and assess its efficacy in mouse models of human breast and colon adenocarcinoma. Methods: To determine the source of LAMP1 expression, we utilized human single-cell RNA sequencing and spatial transcriptomics, complemented by in-house flow cytometry on xenografted mouse models. Tissue microarrays of multiple epithelial cancers and normal tissue were stained for LAMP-1, and staining was quantified. An anti-LAMP1 monoclonal antibody was conjugated with desferrioxamine (DFO) and labeled with zirconium-89 (⁸⁹Zr). Human triple-negative breast cancer (MDA-MB-231) and colon cancer (Caco-2) cell lines were implanted in nude mice. PET/CT imaging was conducted at 24, 72, and 168 h post-intravenous injection of ⁸⁹Zr-DFO-anti-LAMP1 and ⁸⁹Zr-DFO-IgG (negative control), followed by organ-specific biodistribution analyses at the final imaging time point. Results: Integrated single-cell and spatial RNA sequencing demonstrated that LAMP1 expression was localized to myeloid-derived suppressor cells (MDSCs) and cancer-associated fibroblasts (CAFs) in addition to the cancer cells. Tissue microarray showed significantly higher staining for LAMP-1 in tumor tissue compared to normal tissue (3986 ± 2635 vs. 1299 ± 1291, p < 0.001). Additionally, xenograft models showed a significantly higher contribution of cancer cells than the immune cells to cell surface LAMP1 expression. In vivo, PET imaging with ⁸⁹Zr-DFO-anti-LAMP1 PET/CT revealed detectable tumor uptake as early as 24 h post-injection. The ⁸⁹Zr-DFO-anti-LAMP1 tracer demonstrated significantly higher uptake than the control ⁸⁹Zr-DFO-IgG in both models across all time points (MDA-MB-231 SUV_max at 168 h: 12.9 ± 5.7 vs. 4.4 ± 2.4, p = 0.003; Caco-2 SUV_max at 168 h: 8.53 ± 3.03 vs. 3.38 ± 1.25, p < 0.01). Conclusions: Imaging of cell surface LAMP-1 in breast and colon adenocarcinoma is feasible by immuno-PET. LAMP-1 imaging can be expanded to adenocarcinomas of other origins, such as prostate and pancreas. Full article

Segmentation of skin lesions in dermoscopic images is critical for the accurate diagnosis of skin cancers, particularly malignant melanoma, yet it is hindered by irregular lesion shapes, blurred boundaries, low contrast, and artifacts, such as hair interference. Conventional deep learning methods, typically based on UNet or Transformer architectures, often face limitations in regard to fully exploiting lesion features and incur high computational costs, compromising precise lesion delineation. To overcome these challenges, we propose SGNet, a structure-guided network, integrating a hybrid CNN–Mamba framework for robust skin lesion segmentation. The SGNet employs the Visual Mamba (VMamba) encoder to efficiently extract multi-scale features, followed by the Dual-Domain Boundary Enhancer (DDBE), which refines boundary representations and suppresses noise through spatial and frequency-domain processing. The Semantic-Texture Fusion Unit (STFU) adaptively integrates low-level texture with high-level semantic features, while the Structure-Aware Guidance Module (SAGM) generates coarse segmentation maps to provide global structural guidance. The Guided Multi-Scale Refiner (GMSR) further optimizes boundary details through a multi-scale semantic attention mechanism. Comprehensive experiments based on the ISIC2017, ISIC2018, and PH2 datasets demonstrate SGNet’s superior performance, with average improvements of 3.30% in terms of the mean Intersection over Union (mIoU) value and 1.77% in regard to the Dice Similarity Coefficient (DSC) compared to state-of-the-art methods. Ablation studies confirm the effectiveness of each component, highlighting SGNet’s exceptional accuracy and robust generalization for computer-aided dermatological diagnosis. Full article

A recently proposed method called “controlled swelling of monolithic films” was implemented to prepare ultra-high-molecular-weight polyethylene (UHMWPE) ultrafiltration membranes. For the first time, the effect of UHMWPE molecular weight (MW) on the structure and properties of the membranes prepared via this special case of thermally induced phase separation was studied in detail. The morphology and properties of the membranes were studied using SEM, DSC, liquid–liquid displacement porometry, and standard methods for the evaluation of mechanical properties, permeance, rejection, and abrasion resistance. High-quality membranes with a tensile strength of 5.0–17.8 MPa, a mean pore size of 25–50 nm, permeance of 17–107 L m⁻² h⁻¹ bar⁻¹, rejection of model contaminant (blue dextran) of 72–98%, and great abrasion resistance can be prepared only if the MW of the polymer in the initial monolithic film is sufficiently high. The properties of the membranes can effectively be controlled by changing the MW of the polymer and the mass fraction of the latter in the swollen film. Shrinkage is responsible for the variation in the membrane properties. The membranes prepared from a higher-MW polymer are more prone to shrinking after the removal of the solvent. Shrinkage decreases before rising again and minimizes with an increase in the polymer content in the swollen film. Full article

Dark sweet cherries (DSC) phytochemicals have emerged as a promising dietary strategy to combat triple-negative breast cancer (TNBC). This study explored the effects of DSC extract rich in anthocyanins (ACN) as a chemopreventive agent and as a complement to doxorubicin (DOX) in treating TNBC tumors and metastasis using a 4T1 syngeneic animal model. Initiating ACN intake as a chemopreventive one week before 4T1 cell implantation significantly delayed tumor growth without any signs of toxicity. Both DOX treatment and the combination of DOX-ACN effectively delayed tumor growth rate, but DOX-ACN allowed for body weight gain, which was hindered by DOX alone. As a chemopreventive, ACN downregulated metastasis- and immune-suppression-related genes, including STAT3, Snail1, mTOR, SIRT1, TGFβ1, IKKβ, and those unaffected by DOX alone, such as HIF, Cd44, and Rgcc32. Correlations between mRNA levels seen in control and DOX groups were absent in ACN and/or DOX-ACN groups, indicating that Cd44, mTOR, Rgcc32, SIRT1, Snail1, and TGFβ1 may be ACN targets. The DOX-ACN treatment showed a trend toward enhanced efficacy involving CREB, PI3K, Akt-1, and Vim compared to DOX alone. Particularly, ACN significantly suppressed lung metastasis compared to the other groups. ACN also decreased the frequency and incidence of metastasis in the liver, heart, kidneys, and spleen, while their metastatic area (%) and number of breast cancer (BC) metastatic tumor nodules were lowered without reaching significance. Further research is needed to explore the efficacy of combining ACN with drug therapy in the context of drug resistance. Full article

Background/Objectives: This review discusses the resistance mechanisms in the tumor microenvironment (TME) of malignant melanoma that disrupt the efficacy of immune checkpoint inhibitors (ICIs). In this review, we focus on the roles of immune cells, including tumor-infiltrating lymphocytes (TILs), macrophages, dendritic cells, and other signaling pathways. We explore the interplay between innate and adaptive immunity in the TME and tumor intrinsic resistance mechanisms, such as β-catenin, which has future implications for the usage of ICIs in patients with therapy-resistant tumors. Methods: A total of 1052 studies were extracted from the PubMed database searching for keywords and phrases that included [melanoma AND immune checkpoint inhibitor resistance]. After a title/abstract and full-text review, 101 studies were identified that fit the inclusion/exclusion criteria. Results: Cancer-associated fibroblasts (CAFs), M2 macrophages, and myeloid-derived suppressor cells (MDSCs) are significant in remodeling the TME to promote melanoma growth. Melanoma resistance to ICIs is complex and involves TME alterations, tumor intrinsic factors, and immune evasion. Key components of resistance include reduced CD8+ T cell infiltration, decreased host immune response, and immunosuppressive cytokines. Conclusions: Predictive biomarkers and specific models are the future of individualized melanoma management and show great promise in their approach to targeted therapy production. Tumor profiling can be utilized to help predict the efficacy of ICIs, and specific biomarkers predicting therapy responses are instrumental in moving towards personalized and more efficacious medicine. As more melanoma resistance emerges, alternative and combinatorial therapy based on knowledge of existing resistance mechanisms will be needed. Full article

Moroccan oil shale ash (MOSA) represents an underutilized industrial by-product, particularly in the Rif region, where its high mineral content has often led to its neglect in value-added applications. This study highlights the successful conversion of MOSA into amorphous mesoporous silica (AS-Si) using a sol–gel process assisted by polyethylene glycol (PEG-6000) as a soft template. The resulting AS-Si material was extensively characterized to confirm its potential for environmental remediation. FTIR analysis revealed characteristic vibrational bands corresponding to Si–OH and Si–O–Si bonds, while XRD confirmed its amorphous nature with a broad diffraction peak at 2θ ≈ 22.5°. SEM imaging revealed a highly porous, sponge-like morphology composed of aggregated nanoscale particles, consistent with the nitrogen adsorption–desorption isotherm. The material exhibited a specific surface area of 68 m²/g, a maximum in the pore size distribution at a pore diameter of 2.4 nm, and a cumulative pore volume of 0.11 cm³/g for pores up to 78 nm. DLS analysis indicated an average hydrodynamic diameter of 779 nm with moderate polydispersity (PDI = 0.48), while a zeta potential of –34.10 mV confirmed good colloidal stability. Furthermore, thermogravimetric analysis (TGA) and DSC suggested the thermal stability of our amorphous silica. The adsorption performance of AS-Si was evaluated using methylene blue (MB) and ciprofloxacin (Cipro) as model pollutants. Kinetic data were best fitted by the pseudo-second-order model, while isotherm studies favored the Langmuir model, suggesting monolayer adsorption. AS-Si could be used four times for the removal of MB and Cipro. These results collectively demonstrate that AS-Si is a promising, low-cost, and sustainable adsorbent derived from Moroccan oil shale ash for the effective removal of organic contaminants from aqueous media. Full article

Inflammation is a self-defense mechanism that controls the homeostasis of an organism, and its alteration by persistent noxious stimuli could lead to an imbalance in the regulation of inflammatory responses mediated by innate and adaptive immunity. During chronic inflammation, sustained exposure of myeloid cells to the various inflammatory signals derived from inflamed tissue could lead to the generation of myeloid cells with an immunosuppressive state, called myeloid-derived suppressor cells (MDSCs), which can exert protective or deleterious functions depending on the nature of signals and the specific inflammatory conditions created by different pathophysiological contexts. Initially identified in various tumor models and cancer patient samples, these cells have long been recognized as negative regulators of anti-tumor immunity. Consequently, researchers have focused on elucidating the molecular mechanisms underlying their potent immunosuppressive activity. As a key component of the signal transducing processes, protein kinases play a central role in regulating the signal transduction mechanisms of many cellular activities, including differentiation and immunosuppression. Over the past decade, at least a dozen kinases, including mechanistic target of rapamycin (mTOR), phosphoinositide 3-kinases (PI3Ks), TAM (Tyro3, Axl, Mer) family of receptor tyrosine kinases (TAM RTKs), mitogen-activated protein kinases (MAPKs), and others, have emerged as key contributors to the generation and differentiation of MDSCs. Here, we discuss the recent findings on these kinases that directly contribute to the immunosuppressive functions of MDSCs. Full article

Background/Objectives: The work presented herein focused on the development and characterization of a transdermal caffeine platform fabricated from ultrathin micro- and submicron fibers produced via electrospinning. Methods: The formulations incorporated caffeine encapsulated in a polyethylene oxide (PEO) matrix, combined with various permeation enhancers. A backing layer made of annealed electrospun polycaprolactone (PCL) facilitated the lamination of the two layers to form the final multilayer patch. Comprehensive characterization was conducted, utilizing scanning electron microscopy (SEM) to assess the fiber morphology, attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) for chemical detection and to assess the stability of the caffeine, and differential scanning calorimetry (DSC) along with wide-angle X-ray scattering (WAXS) to analyze the physical state of the caffeine within the fibers of the active layer. Additionally, Franz cell permeation studies were performed using both synthetic membranes (Strat-M) and ex vivo human stratum corneum (SC) to evaluate and model the permeation kinetics. Results: These experiments demonstrated the significant role of enhancers in modulating the caffeine permeation rates provided by the patch, achieving permeation rates of up to 0.73 mg/cm² within 24 h. Conclusions: This work highlights the potential of using electro-hydrodynamic processing technology to develop innovative transdermal delivery systems for drugs, offering a promising strategy for enhancing efficacy and innovative therapeutic direct plasma administration. Full article

Electrospun nanofiber membranes based on cellulose acetate (CA) have gained increasing attention for wastewater treatment due to their high surface area, tuneable structure, and ease of functionalization. In this study, the performance of CA membranes was enhanced by incorporating aluminum oxide (Al₂O₃) nanoparticles (NPs) at varying concentrations (0–2 wt.%). The structural, morphological, and thermal properties of the resulting CA/Al₂O₃ nanocomposite membranes were investigated through FTIR, XRD, SEM, water contact angle (WCA), pore size measurements, and DSC analyses. FTIR and XRD confirmed strong interactions and the uniform dispersion of the Al₂O₃ NPs within the CA matrix. The incorporation of Al₂O₃ improved membrane hydrophilicity, reducing the WCA from 107° to 35°, and increased the average pore size from 0.62 µm to 0.86 µm. These modifications led to enhanced filtration performance, with the membrane containing 2 wt.% Al₂O₃ achieving a 99% removal efficiency for Indigo Carmine (IC) dye, a maximum adsorption capacity of 45.59 mg/g, and a high permeate flux of 175.47 L·m⁻² h⁻¹ bar⁻¹. Additionally, phytotoxicity tests using Lactuca sativa seeds showed a significant increase in germination index from 20% (untreated) to 88% (treated), confirming the safety of the permeate for potential reuse in agricultural irrigation. These results highlight the effectiveness of Al₂O₃-modified CA electrospun membranes for sustainable wastewater treatment and water reuse. Full article

The effect of severe plastic deformation during milling and conventional and Spark Plasma Sintering (SPS) on the wt. % microstructural, structural, thermal, magnetic, and mechanical properties of the Al–16 wt. % Mn–7 wt. % Cu alloy was studied. A milling process for up to 24 h (A24) leads to microstructure refinement and the presence of Al, Mn, and Cu solid solutions. The energy dispersive spectroscopy (EDS) analysis reveals the existence of Cu–Al, Mn–Al, and Al–Mn enriched particles. The powders exhibit weak ferromagnetism and an exchange bias (EB) behaviour that decreases with increasing milling time. The Ms values fitted using the law of approach to saturation (LAS) are comparable to the experimental values. The exothermic and endothermic peaks that appear in the differential scanning calorimetry (DSC) scans in the 500–900 °C range on heating/cooling are related to different phase transformations. The crystal structure of the A24 powders heated up to 900 °C (A24_900 °C) consists of a dual-phase microstructure of Al₂₀Cu₂Mn₃ nanoprecipitates (~28%) and Al matrix (~72%). The sintering of the A24 powders at 500 °C for one hour (A24S) leads to the precipitation of Al₆Mn, Al₂Cu, and the Al₂₀Cu₂Mn₃ T-phase into the Al-enriched matrix. In contrast, the consolidation by SPS (A24SPS) leads to a mixture of an Al solid solution, Al₆Mn, T-phase, and α-Mn with an increased weight fraction of the T-phase and Al₆Mn. The sintered samples exhibit the coexistence of a significant PM/AFM contribution to the M-H curves, with increasing Hc and decreasing EB. A higher microhardness value of about 581 HV is achieved for the A24SPS sample compared to those of the A24 (68 HV) and A24S (80 HV) samples. Full article

This study investigates the effects of repeated mechanical recycling on the structural, thermal, mechanical, and aesthetic properties of poly(butylene succinate) (PBS), a commercially available bio-based and biodegradable aliphatic polyester. PBS production scraps were subjected to five consecutive recycling cycles through semi-industrial extrusion compounding followed by injection molding to simulate realistic mechanical reprocessing conditions. Melt mass-flow rate (MFR) analysis revealed a progressive increase in melt fluidity. Initially, the trend of viscosity followed the melt flow rate; however, increasing the reprocessing number (up to 5) resulted in a partial recovery of viscosity, which was caused by chain branching mechanisms. The phenomenon was also confirmed by data of molecular weight evaluation. Differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) confirmed the thermal stability of the polymer, with minimal shifts in glass transition, crystallization, and degradation temperatures during the reprocessing cycles. Tensile tests revealed a slight reduction in strength and stiffness, but an increase in elongation at break, indicating improved ductility. Impact resistance declined moderately from 8.7 to 7.3 kJ/m² upon reprocessing; however, it exhibited a pronounced reduction to 1.8 kJ/m² at −50 °C, reflecting brittle behavior under sub-ambient conditions. Despite these variations, PBS maintained excellent color stability (ΔE < 1), ensuring aesthetic consistency while retaining good mechanical and thermal properties. Full article