Search Results (35,673)

This study examined the effects of selenium (Se) fertilization, applied via foliar and rhizosphere methods, on the physiological and biochemical characteristics of ‘Muscat Hamburg’ grapes. Sodium selenite (Na₂SeO₃) treatments were administered at three concentrations (50, 100, and 150 ppm) during critical phenological stages. The results showed that Se at 50 ppm effectively increased the chlorophyll content and enhanced chlorophyll fluorescence parameters. Se significantly elevated total soluble solid content and reduced titratable acidity, thereby increasing the TSS/TA ratio. Foliar fertilization with 50 ppm Se enhanced cluster size without affecting berry dimensions, whereas rhizosphere fertilization increased both with increasing Se concentrations, albeit with negative impacts on berry size at higher concentrations. Se increased flavonoid content in grape peels, with rhizosphere fertilization exerting more pronounced effects. Se—via rhizosphere fertilization at 100 and 150 ppm—significantly influenced VOCs derived from fatty acid and isoprene metabolic pathways. Mantel’s test confirmed that foliar fertilization significantly increased chlorophyll content and fluorescence indices, while rhizosphere fertilization had more marked effects on flavonoid content, berry and cluster size, and VOCs, particularly through fatty acid metabolism. These findings suggest that Se can enhance grape quality, but optimal concentrations and fertilization methods must be carefully determined to avoid adverse effects. Full article

Background/Objective: Hot-melt extrusion has been established as a formulation strategy for various pharmaceutical applications. However, tailoring the screw configuration is a major challenge where 1D modeling is utilized. This usually requires specific screw parameters, which are rarely noted in the literature, especially when dealing with shear-thinning formulations. Methods: Therefore, a custom-made test rig was used to assess the behavior of various conveying and kneading elements using Newtonian silicon oil and shear-thinning silicon rubber. The pressure and the power were measured as a function of volume flow. A model was proposed characterizing the screw element behavior by six individual parameters . Results: The experimental results regarding the behavior with respect to Newtonian fluids were in good agreement with the literature and were modeled in accordance with the Pawlowski approach. In terms of shear-thinning fluids, the influence of screw speed on pressure and power was quantified. An evaluation framework was proposed to assess this effect using two additional parameters. Based on a high number of repetitive measurements, a confidence interval for the individual screw parameters was determined that is suitable to highlight the differences between element types. Conclusions: Finally, geometrical screw parameters for Newtonian and shear-thinning flow were assessed and modeled, with three conveying and three kneading elements characterized. Full article

Background: Activated hepatic stellate cells (aHSCs) play a significant role during the onset of hepatic fibrosis, ultimately leading to excessive deposition of extracellular matrix (ECM) and other typical pathological features, and thus have become a popular target for the treatment of hepatic fibrosis. However, current aHSC-centric therapy strategies achieve unsatisfactory results, mainly due to the lack of approved anti-fibrosis drugs and sufficiently efficient aHSC-targeted delivery systems. In this study, our aim was to develop an Imatinib-loaded nanoparticle delivery system based on a chondroitin sulfate derivative to enhance aHSC targeting efficiency, improve the therapeutic effect for hepatic fibrosis, and investigate the underlying mechanism. Methods: The carboxyl group of chondroitin sulfate and the amino group of 1-hexadecylamine were linked by an amide bond in this study to produce the amphiphilic carrier CS-HDA. Then, the Imatinib-loaded nanoparticles (IM-CS NPs) were designed to efficiently target aHSCs through CD44-mediated endocytosis and effectively inhibit HSC overactivation via PDGF and TGF-β signaling pathways. Results: Both in vitro cellular uptake experiments and in vivo distribution experiments demonstrated that CS-HDA-modified nanoparticles (IM-CS NPs) exhibited a better targeting ability for aHSCs, which were subsequently utilized to treat carbon tetrachloride-induced hepatic fibrosis mouse models. Finally, significant fibrosis resolution was observed in the carbon tetrachloride-induced hepatic fibrosis mouse models after tail vein injection of the IM-CS NPs, along with their outstanding biocompatibility and biological safety. Conclusions: IM-loaded NPs based on an amphiphilic CS derivative have remarkable antifibrotic effects, providing a promising avenue for the clinical treatment of advanced hepatic fibrosis. Full article

Pharmaceutical 3D printing, combined with nanomaterials and nanodevices, presents a transformative approach to precision medicine for treating neurological diseases. This technology enables the creation of tailored dosage forms with controlled release profiles, enhancing drug delivery across the blood−brain barrier (BBB). The integration of nanoparticles, such as poly lactic-co-glycolic acid (PLGA), chitosan, and metallic nanomaterials, into 3D-printed scaffolds improves treatment efficacy by providing targeted and prolonged drug release. Recent advances have demonstrated the potential of these systems in treating conditions like Parkinson’s disease, epilepsy, and brain tumors. Moreover, 3D printing allows for multi-drug combinations and personalized formulations that adapt to individual patient needs. Novel drug delivery approaches, including stimuli-responsive systems, on-demand dosing, and theragnostics, provide new possibilities for the real-time monitoring and treatment of neurological disorders. Despite these innovations, challenges remain in terms of scalability, regulatory approval, and long-term safety. The future perspectives of this technology suggest its potential to revolutionize neurological treatments by offering patient-specific therapies, improved drug penetration, and enhanced treatment outcomes. This review discusses the current state, applications, and transformative potential of 3D printing and nanotechnology in neurological treatment, highlighting the need for further research to overcome the existing challenges. Full article

The increasing complexity of healthcare delivery and the advancements in medical technology have highlighted the necessity for improved training in nursing education. While traditional training methods have their merits, they often encounter challenges such as limited access to clinical placements, static physical simulations, and performance anxiety during hands-on practice. Virtual reality (VR) has been increasingly adopted for immersive and interactive training environments, allowing nursing students to practice essential skills repeatedly in realistic, risk-free settings. This study presents NursingXR, a VR-based platform designed to help nursing students master essential clinical skills. With a scalable and flexible architecture, NursingXR is tailored to support a variety of nursing lessons and adapt to evolving curricula. The platform has a modular design and offers two interactive modes: Training Mode, which provides step-by-step guided instruction, and Evaluation Mode, which allows for independent performance assessment. This article details the development process of the platform, including key design principles, system architecture, and implementation strategies, while emphasizing its utility and scalability. A mixed-methods evaluation involving 78 participants—both novices and experts—was conducted to evaluate the platform’s usability and user satisfaction. The results underscore NursingXR’s effectiveness in fostering an effective and engaging learning environment as well as its potential as a supplementary resource for nursing training. Full article

This study develops an MTSP model for multi-UAV delivery optimization from a central hub, proposing a hybrid algorithm that integrates genetic simulated annealing-enhanced clustering with an improved Hopfield neural network to minimize the total flight distance. The proposed methodology initially employs an enhanced fuzzy C-means clustering technique integrated with genetic simulated annealing (GSA) to effectively partition the MTSP formulation into multiple discrete traveling salesman problem (TSP) instances. The subsequent phase implements an enhanced Hopfield neural network (HNN) architecture incorporating three key modifications: data normalization procedures, adaptive step-size control mechanisms, and simulated annealing integration, collectively improving the TSP solution quality and computational efficiency. The proposed algorithm’s effectiveness is validated through comprehensive case studies, demonstrating significant performance improvements in the computational efficiency and solution quality compared to conventional methods. The results show that during clustering, the improved clustering algorithm is more stable in its clustering effect. With regard to path optimization, the improved neural network algorithm has a higher computational efficiency and makes it easier to obtain the global optimal solution. Compared with the genetic algorithm and ant colony algorithm, its iteration times, path length, and delivery time are reduced to varying degrees. To sum up, the hybrid optimization algorithm has obvious advantages for solving a multi-UAV collaborative distribution path optimization problem. Full article

Background/Objectives: Hyperlipidemia is a silent threat lurking in the bloodstream of millions worldwide. The nano-based platform has emerged as a promising drug delivery technology. Repaglinide, an anti-diabetic drug, was investigated recently as an antihyperlipidemic candidate that could supersede the available antihyperlipidemic drugs. Our goal was to optimize albumin-based nanoparticles loaded with Repaglinide for parenteral delivery and conduct in silico and in vivo studies to explore the efficacy of Repaglinide for the management of hyperlipidemia along with its anti-diabetic effect. Methods: The impact of three independent factors, the albumin%, acetone volume, and glutaraldehyde/albumin, on the particle size, zeta potential, and entrapment efficiency was investigated. Results: The optimized formulation was spherical, homogenous of an average diameter (~181.86 nm) with a narrow size distribution, a zeta potential of −24.26 mV, and 76.37% as the EE%. The in vitro release of Repaglinide from nanoparticles showed a sustained release pattern for 168 h, with an initial burst release after 24 h, and was fitted to the Fickian diffusion mechanism. A molecular docking simulation showed a strong affinity to several protein targets, and the results were very promising, where Repaglinide gave a score of −7.70 Kcal/mol compared to Mevastatin (−6.71 Kcal/mol) and Atorvastatin (−8.36 Kcal/mol). On conducting in vivo studies on animal models, the optimized formula recorded a statistically significant decrease in the serum levels of total cholesterol, triglyceride, and low-density lipoproteins, with an increased high-density lipoprotein. Conclusions: This study suggested albumin nanoparticles as potential nanocarriers for the parenteral delivery of Repaglinide to ameliorate its antihyperlipidemic benefits, especially in diabetic patients. Full article

The blood–brain barrier (BBB) is essential for maintaining brain homeostasis by regulating molecular exchange between the systemic circulation and the central nervous system. However, its dysfunction, often driven by peripheral inflammatory processes, has been increasingly linked to the development and progression of neurodegenerative diseases such as Alzheimer’s and Parkinson’s. Emerging evidence suggests that the gut–brain axis plays a key role in BBB integrity, with intestinal dysbiosis and chronic inflammation contributing to barrier disruption through immune and metabolic pathways. Furthermore, the selective vulnerability of specific brain regions to BBB dysfunction appears to be influenced by regional differences in vascularization, metabolic activity, and permeability, making certain areas more susceptible to neurodegenerative processes. This review explored the molecular mechanisms linking peripheral inflammation, gut microbiota, and BBB dysfunction, emphasizing their role in neurodegeneration. A comprehensive literature review was conducted using Web of Science, PubMed, Scopus, Wiley, ScienceDirect, and Medline, covering publications from 2015 to 2025. The findings highlight a complex interplay between gut microbiota-derived metabolites, immune signaling, and BBB permeability, underscoring the need for targeted interventions such as microbiome modulation, anti-inflammatory therapies, and advanced drug delivery systems. The heterogeneity of the BBB across different brain regions necessitates the development of region-specific therapeutic strategies. Despite advancements, critical knowledge gaps persist regarding the precise mechanisms underlying BBB dysfunction. Future research should leverage cutting-edge methodologies such as single-cell transcriptomics and organ-on-chip models to translate preclinical findings into effective clinical applications. Addressing these challenges will be crucial for developing personalized therapeutic approaches to mitigate the impact of BBB dysfunction in neurodegenerative diseases. Full article

In recent years, hydrogels have emerged as promising candidates for bone defect repair due to their excellent biocompatibility, high porosity, and water-retentive properties. However, conventional hydrogels face significant challenges in clinical translation, including brittleness, low mechanical strength, and poorly controlled drug degradation rates. To address these limitations, as a multifunctional polymer, polydopamine (PDA) has shown great potential in both bone regeneration and drug delivery systems. Its robust adhesive properties, biocompatibility, and responsiveness to photothermal stimulation make it an ideal candidate for enhancing hydrogel performance. Integrating PDA into conventional hydrogels not only improves their mechanical properties but also creates an environment conducive to cell adhesion, proliferation, and differentiation, thereby promoting bone defect repair. Moreover, PDA facilitates controlled drug release, offering a promising approach to optimizing treatment outcomes. This paper first explores the mechanisms through which PDA promotes bone regeneration, laying the foundation for its clinical translation. Additionally, it discusses the application of PDA-based nanocomposite hydrogels as advanced drug delivery systems for bone defect repair, providing valuable insights for both research and clinical translation. Full article

Organodichalcogenides have been explored due to their therapeutic properties. They have been demonstrated to be active against several diseases such as cancer, bacteria, viruses, parasites, or neurological diseases. Among the different classes of dichalcogenides, disulfide derivatives have been widely studied, and many studies cover their therapeutical use. For this reason, this review includes the latest studies of diselenides and ditellurides derivatives with biological applications. With this aim, several bioactive small molecules containing the diselenide or ditelluride bond in their structure have been discussed. Furthermore, it should be highlighted that, in recent years, there has been an increasing interest in the development of nanomaterials for drug delivery due to their therapeutic advantages. In this context, diselenide and ditelluride-containing nanocarriers have emerged as novel approaches. The information compiled in this review includes small molecules and more complex materials containing diselenide or ditelluride bonds in their structure for different therapeutical applications, which could be helpful for the further development of novel drugs for the treatment of different diseases. Full article

This study investigates the fabrication and characterization of polymeric nanoparticles based on polyhydroxyalkanoates (PHAs) loaded with curcumin for biomedical applications. PHAs, biodegradable and biocompatible polymers, were synthesized via bacterial fermentation and used to encapsulate curcumin using the nanoprecipitation method. The resulting nanoparticles were characterized for their particle size, polydispersity index, and encapsulation efficiency, achieving high entrapment rates (above 80%) and nanometric size distribution. Stability assessments demonstrated prolonged structural integrity under storage conditions. In vitro release studies conducted in phosphate-buffered saline at pH 5 and 7.4 revealed sustained drug release profiles. Biocompatibility and cytotoxicity assays using human astrocytes and fibroblasts confirmed the nanoparticles’ safety, while antiproliferative tests on glioblastoma and colon cancer cell lines indicated potential therapeutic efficacy. Additionally, skin irritation and corrosion tests using the EpiDerm™ model classified the formulations as non-irritant and non-corrosive. These findings suggest that PHA-based nanoparticles offer a promising nanocarrier system for curcumin delivery, with potential applications in cancer treatment and regenerative medicine. Future research should focus on optimizing the formulation and evaluating in vivo therapeutic effects. Full article

Abstract: Objective: Intrahepatic cholestasis of pregnancy (ICP) is associated with an elevated risk of adverse perinatal outcomes, including perinatal morbidity and mortality. The objectives of this study were to evaluate the bile acid (BA) metabolism profiles in the urine of patients with ICP and to investigate the association between specific BAs and maternal and neonatal outcomes in patients with ICP. Methods: A total of 127 Chinese women with ICP and 55 healthy pregnant women were enrolled in our retrospective study. Spot urine samples and clinical data were collected from pregnant women from January 2019 to December 2022 at the First Affiliated Hospital of Chongqing Medical University, Chongqing. Based on total bile acid (TBA) levels, the ICP group was subdivided into mild (10–40 μmol/L) and severe (≥40 μmol/L) ICP groups. Patients in the ICP group were further divided into two categories according to neonatal outcomes: an ICP with adverse pregnancy outcomes group and an ICP with non-adverse pregnancy outcomes group. Metabolites from maternal urine were collected and analyzed using ultra-high-performance liquid chromatography–triple quadrupole time-of-flight mass spectroscopy (UPLC-triple TOF-MS). Results: Significant differences were observed between the mild and severe ICP groups in the onset time of symptoms, gestational weeks at time of ICP diagnosis, the duration of using ursodeoxycholic acid (UDCA) drugs during pregnancy, gestational age at delivery, premature delivery, and cesarean delivery. The expression levels of the composition of different urinary bile acids including THCA, TCA, T-ω-MCA, TCA-3-S, TCDCA-3-S, TDCA-3-S, GCDCA-3-S, DCA-3-G and GDCA-3-G were remarkably higher in the ICP with adverse pregnancy outcomes group than those in the ICP with non-adverse pregnancy outcomes group and the control group. The single-parameter model used to predict adverse pregnancy outcomes in ICP had similar areas under the curve (AUCs) of the receiver operating characteristic (ROC), ranging from 0.755 to 0.869. However, an AUC of 0.886 and 95% CI were obtained by the index of combined urinary bile acids in multiple prediction models (95% CI 0.790 to 0.983, p < 0.05). TCA-3-S in the urinary bile acids had a strong positive correlation with the aspartate aminotransferase (AST) level (r = 0.617, p < 0.05). Furthermore, TCDCA-3-S and GCDCA-3-S in the urinary bile acids had a strong positive correlation with the alanine aminotransferase (ALT) level (r = 0.607, p < 0.05; r = 0.611, p < 0.05) and AST level (r = 0.629, p < 0.05; r = 0.619, p < 0.05). Conclusions: Maternal urinary bile acid profiles were prominent for the prognosis of maternal and neonatal outcomes of ICP. Elevated levels of TCA-3-S, TCDCA-3-S, and GCDCA-3-S in urine might be important predictors for indicating adverse pregnancy outcomes in ICP. Full article

Over the past years, numerous novel dosage forms, including gels, have been investigated for paediatric treatment due to the need to provide flexible dose adjustment possibilities, as well as a patient-friendly approach to drug delivery. Simultaneously, 3D printing technology is continuously advancing and gaining interest as a tool for personalised formulation development. Multiple additive manufacturing methods, including the semi-solid extrusion, especially used in gel printing, provide flexibility regarding the dose of active ingredients and the adjustment of the design of soft dosage forms. 3D printing techniques can be considered as a possible answer to the demand for medicines tailored to small patients’ needs. This review intends to present an overview of the current possibilities, comparing gel-like and non-gel-formulated dosage forms and crucial aspects of developing those cutting-edge dosage forms by 3D printing. This paper discusses soft formulations such as chewing gums, which still require extensive evaluation, and explores the question of the three-dimensional printing process. Furthermore, it highlights soft dosage forms, such as gel-based gummies and hydrogels, for which 3D fabrication has been intensively studied in previous years. However, the research still needs to advance. Full article

Transfection is a fundamental method in biomedical research to study intracellular molecular mechanisms by manipulating target protein expression. Various methods have been developed to deliver nucleic acids into the cells of interest in vitro, with chemical transfection by cationic lipids being the most widely used for RNA interference (RNAi). However, translating these in vitro results into in vivo remains a significant challenge. In this study, we established an ex vivo transfection model using cationic lipids in human whole blood. Three different lipid-based reagents were evaluated regarding toxicity, transfection efficiency, and immunogenicity across leukocyte populations using spectral flow cytometry. CD14⁺ monocytes were identified as the primary population to be transfected by cationic lipids in whole blood. To assess immunogenicity, the monocyte-specific activation markers CD80 and human leukocyte antigen DR isotype (HLA-DR) were analyzed upon transfection. Our results demonstrated that Lipofectamine RNAiMAX outperforms the other two reagents, showing low toxicity and high transfection efficiency in combination with a minimal potential for monocyte activation. Functional knockdown experiments using siRNA targeting CIITA and the microRNA mir-3972 targeting HLA-DRA showed dose-dependent suppression in HLA-DR expression. This study provides the framework for preliminary testing of RNAi in a physiologically relevant ex vivo model, enabling assessment of key endpoints such as toxicity, transfection efficiency, and immune activation potential of gene delivery systems. Full article

To develop an efficient drug delivery system, we co-entrapped superparamagnetic Fe₃O₄ and the chemotherapeutic drug doxorubicin (DOX) in oleoyl-chitosan (OC) to prepare DOX-entrapped magnetic OC (DOX-MOC) nanoparticles (NPs) through ionic gelation of OC with sodium tripolyphosphate (TPP). The NPs provide magnetically targeted delivery of DOX in cancer therapy. Using folic acid (FA)-grafted OC, FA-conjugated DOX-entrapped magnetic OC (FA-DOX-MOC) NPs were prepared similarly for FA-mediated active targeting of cancer cells with overexpressed folate receptors. Considering DOX loading and release, the best conditions for preparing DOX-MOC NPs were an OC:TPP mass ratio = 1:4 and OC concentration = 0.2%. These spherical NPs had a particle size of ~250 nm, 87.9% Fe₃O₄ content, 53.1 emu/g saturation magnetization, 83.1% drug encapsulation efficacy, and 2.81% drug loading efficiency. FA did not significantly change the physico-chemical characteristics of FA-DOX-MOC compared to DOX-MOC, and both NPs showed pH-dependent drug release behaviors, with much faster release of DOX at acidic pH values found in endosomes. However, FA could enhance the intracellular uptake of the NPs and DOX accumulation in the nucleus. This active targeting effect led to significantly higher cytotoxicity towards U87 cancer cells. These results suggest that FA-DOX-MOC NPs can efficiently deliver DOX for controlled drug release in cancer therapy. Full article