The evolution of endovascular therapies, particularly in the field of intracranial aneurysm treatment, has been truly remarkable and is characterized by the development of various stents. However, ischemic complications related to thrombosis or downstream emboli pose a challenge for the broader clinical application of such stents. Despite advancements in surface modification technologies, an ideal coating that fulfills all the desired requirements, including anti-thrombogenicity and swift endothelialization, has not been available. To address these issues, we investigated a new coating comprising 3-aminopropyltriethoxysilane (APTES) with both anti-thrombogenic and cell-adhesion properties. We assessed the anti-thrombogenic property of the coating using an in vitro blood loop model by evaluating the platelet count and the level of the thrombin-antithrombin (TAT) complex, and investigating thrombus formation on the surface using scanning electron microscopy (SEM). We then assessed endothelial cell adhesion on the metal surfaces. In vitro blood tests revealed that, compared to a bare stent, the coating significantly inhibited platelet reduction and thrombus formation; more human serum albumin spontaneously adhered to the coated surface to block thrombogenic activation in the blood. Cell adhesion tests also indicated a significant increase in the number of cells adhering to the APTES-coated surfaces compared to the numbers adhering to either the bare stent or the stent coated with an anti-fouling phospholipid polymer. Finally, we performed an in vivo safety test by implanting coated stents into the internal thoracic arteries and ascending pharyngeal arteries of minipigs, and subsequently assessing the health status and vessel patency of the arteries by angiography over the course of 1 week. We found that there were no adverse effects on the pigs and the vascular lumens of their vessels were well maintained in the group with APTES-coated stents. Therefore, our new coating exhibited both high anti-thrombogenicity and cell-adhesion properties, which fulfill the requirements of an implantable stent.

BACKGROUND: Silica nanoparticles (SNPs) have immense potential in biomedical research, particularly in drug delivery and imaging applications, owing to their stability and minimal interactions with biological entities such as tissues or cells.
RESULTS: With synthesized and characterized cyanine-dye-doped fluorescent SNPs (CSNPs) using cyanine 3.5, 5.5, and 7 (Cy3.5, Cy5.5, and Cy7). Through systematic analysis, we discerned variations in the surface charge and fluorescence properties of the nanoparticles contingent on the encapsulated dye-(3-aminopropyl)triethoxysilane conjugate, while their size and shape remained constant. The fluorescence emission spectra exhibited a redshift correlated with increasing dye concentration, which was attributed to cascade energy transfer and self-quenching effects. Additionally, the fluorescence signal intensity showed a linear relationship with the particle concentration, particularly at lower dye equivalents, indicating a robust performance suitable for imaging applications. In vitro assessments revealed negligible cytotoxicity and efficient cellular uptake of the nanoparticles, enabling long-term tracking and imaging. Validation through in vivo imaging in mice underscored the versatility and efficacy of CSNPs, showing single-switching imaging capabilities and linear signal enhancement within subcutaneous tissue environment.
CONCLUSIONS: This study provides valuable insights for designing fluorescence imaging and optimizing nanoparticle-based applications in biomedical research, with potential implications for targeted drug delivery and in vivo imaging of tissue structures and organs.

A versatile family of quaternary propargylamines was synthesized employing the KA2 multicomponent reaction, through the single-step coupling of a number of amines, ketones, and terminal alkynes. Sustainable synthetic procedures using transition metal catalysts were employed in all cases. The inhibitory activity of these molecules was evaluated against human monoaminoxidase (hMAO)-A and hMAO-B enzymes and was found to be significant. The IC50 values for hMAO-B range from 152.1 to 164.7 nM while the IC50 values for hMAO-A range from 765.6 to 861.6 nM. Furthermore, these compounds comply with Lipinski\'s rule of five and exhibit no predicted toxicity. To understand their binding properties with the two target enzymes, key interactions were studied using molecular docking, all-atom molecular dynamics (MD) simulations, and MM/GBSA binding free energy calculations. Overall, herein, the reported family of propargylamines exhibits promise as potential treatments for neurodegenerative disorders, such as Parkinson\'s disease. Interestingly, this is the first time a propargylamine scaffold bearing an internal alkyne has been reported to show activity against monoaminoxidases.

Colonoscopy is the standard procedure for screening, and surveillance of colorectal cancer, including the treatment for colonic lesions. Colonic spasm is an important problem from colonoscopy that affects both surgeons and patients. The spasm also might be the cause of longer cecal intubation time, difficulty of the procedure, and increased pain. Previous reports indicated that antispasmodic agents can decrease such symptoms. Therefore, we conducted this study to investigate the cecal intubation time of antispasmodic agents. A single blinded randomized controlled trial was conducted from 01/11/2020 to 31/08/2021. One hundred four patients were allocated to antispasmodic agent group and control group, in 1:1 ratio. The efficacy of median (range) cecal intubation time showed similar results of 5 (2, 14) and 5 (2, 15) minutes with no statistically significant difference. The mean scores of all domains i.e., pain, spasm, cleanliness, and difficulty were better in the antispasmodic agent group about 2.6 (1.4), 1.8 (0.8), 2.4 (0.9), and 2.0 (0.9), respectively, than control group but there were spasm and cleanliness showed statistically significant difference. Moreover, the satisfaction scores showed better efficacy in decreased spasm, decreased difficulty, and increased cleanliness than control group. Prescribing of antispasmodic drugs before colonoscopy might be the choice of treatment for the patients. The antispasmodic drugs will be beneficial to both of the patient and the doctor.

Bovine serum albumin (BSA) is commonly incorporated in vaccines to improve stability. However, owing to potential allergic reactions in humans, the World Health Organization (WHO) mandates strict adherence to a BSA limit (≤50 ng/vaccine). BSA detection with conventional techniques is time-consuming and requires specialized equipment. Efficient alternatives such as the ion-sensitive field-effect transistor (ISFET), despite rapid detection, affordability, and portability, do not detect BSA at low concentrations because of inherent sensitivity limitations. This study proposes a silicon-on-insulator (SOI) substrate-based dual-gate (DG) ISFET platform to overcome these limitations. The capacitive coupling DG structure significantly enhances sensitivity without requiring external circuits, owing to its inherent amplification effect. The extended-gate (EG) structure separates the transducer unit for electrical signal processing from the sensing unit for biological detection, preventing chemical damage to the transducer, accommodating a variety of biological analytes, and affording easy replaceability. Vapor-phase surface treatment with (3-Aminopropyl) triethoxysilane (APTES) and the incorporation of a SnO2 sensing membrane ensure high BSA detection efficiency and sensitivity (144.19 mV/log [BSA]). This DG-FET-based biosensor possesses a simple structure and detects BSA at low concentrations rapidly. Envisioned as an effective on-site diagnostic tool for various analytes including BSA, this platform addresses prior limitations in biosensing and shows promise for practical applications.

Integrating CYP2D6 genotyping and therapeutic drug monitoring (TDM) is crucial for guiding individualized atomoxetine therapy in children with attention-deficit/hyperactivity disorder (ADHD). The aim of this retrospective study was (1) to investigate the link between the efficacy and tolerability of atomoxetine in children with ADHD and plasma atomoxetine concentrations based on their CYP2D6 genotypes; (2) to offer TDM reference range recommendations for atomoxetine based on the CYP2D6 genotypes of children receiving different dosage regimens. This retrospective study covered children and adolescents with ADHD between the ages of 6 and <18, who visited the psychological and behavioral clinic of Children\'s Hospital of Nanjing Medical University from June 1, 2021, to January 31, 2023. The demographic information and laboratory examination data, including CYP2D6 genotype tests and routine TDM of atomoxetine were obtained from the hospital information system. We used univariate analysis, Mann-Whitney U nonparametric test, Kruskal-Wallis test, and the receiver operating characteristic (ROC) curve to investigate outcomes of interest. 515 plasma atomoxetine concentrations of 385 children (325 boys and 60 girls) with ADHD between 6 and 16 years of age were included for statistical analysis in this study. Based on genotyping results, >60% of enrolled children belonged to the CYP2D6 extensive metabolizer (EM), while <40% fell into the intermediate metabolizer (IM). CYP2D6 IMs exhibited higher dose-corrected plasma atomoxetine concentrations by 1.4-2.2 folds than those CYP2D6 EMs. Moreover, CYP2D6 IMs exhibited a higher response rate compare to EMs (93.55% vs 85.71%, P = 0.0132), with higher peak plasma atomoxetine concentrations by 1.67 times than those of EMs. Further ROC analysis revealed that individuals under once daily in the morning (q.m.) dosing regimen exhibited a more effective response to atomoxetine when their levels were ≥ 268 ng/mL (AUC = 0.710, P < 0.001). In addition, CYP2D6 IMs receiving q.m. dosing of atomoxetine were more likely to experience adverse reactions in the central nervous system and gastrointestinal system when plasma atomoxetine concentrations reach 465 and 509 ng/mL, respectively. The findings in this study provided promising treatment strategy for Chinese children with ADHD based on their CYP2D6 genotypes and plasma atomoxetine concentration monitoring. A peak plasma atomoxetine concentration higher than 268 ng/mL might be requisite for q.m. dosing. Assuredly, to validate and reinforce these initial findings, it is necessary to collect further data in controlled studies with a larger sample size.

Psychosis in Parkinson\'s disease is a common phenomenon associated with poor outcomes. To clarify the pathophysiology of this condition and the mechanisms of antipsychotic treatments, we have here characterized the neurophysiological brain states induced by clozapine, pimavanserin, and the novel prospective antipsychotic mesdopetam in a rodent model of Parkinson\'s disease psychosis, based on chronic dopaminergic denervation by 6-OHDA lesions, levodopa priming, and the acute administration of an NMDA antagonist. Parallel recordings of local field potentials from eleven cortical and sub-cortical regions revealed shared neurophysiological treatment effects for the three compounds, despite their different pharmacological profiles, involving reversal of features associated with the psychotomimetic state, such as a reduction of aberrant high-frequency oscillations in prefrontal structures together with a decrease of abnormal synchronization between different brain regions. Other drug-induced neurophysiological features were more specific to each treatment, affecting network oscillation frequencies and entropy, pointing to discrete differences in mechanisms of action. These findings indicate that neurophysiological characterization of brain states is particularly informative when evaluating therapeutic mechanisms in conditions involving symptoms that are difficult to assess in rodents such as psychosis, and that mesdopetam should be further explored as a potential novel antipsychotic treatment option for Parkinson psychosis.

The cost of physical inactivity is alarming, and calls for whole-of-system approaches to population physical activity promotion (PPAP) are increasing. One innovative approach to PPAP is to use a framework of interdependent attributes and associated dimensions of effective systems for chronic disease prevention. Describing system boundaries can be an elusive task, and this article reports on using an attribute framework as a first step in describing and then assessing and strengthening a provincial system for PPAP in British Columbia, Canada. Interviews were conducted with provincial stakeholders to gather perspectives regarding attributes of the system. Following this, two workshops were facilitated to document important stories about the current system for PPAP and link story themes with attributes. Results from interviews and workshops were summarized into key findings and a set of descriptive statements. One hundred and twenty-one statements provide depth, breadth and scope to descriptions of the system through the lens of an adapted framework including four attributes: (i) implementation of desired actions, (ii) resources, (iii) leadership and (iv) collaborative capacity. The attribute framework was a useful tool to guide a whole-of-system approach and turn elusive boundaries into rich descriptors of a provincial system for PPAP. Immediate implications for our research are to translate descriptive statements into variables, then assess the system through group model building and identify leverage points from a causal loop diagram to strengthen the system. Future application of this approach in other contexts, settings and health promotion and disease prevention topics is recommended.

Wildlife conservation strategies focused on one season or population segment may fail to adequately protect populations, especially when a species\' habitat preferences vary among seasons, age-classes, geographic regions, or other factors. Conservation of golden eagles (Aquila chrysaetos) is an example of such a complex scenario, in which the distribution, habitat use, and migratory strategies of this species of conservation concern vary by age-class, reproductive status, region, and season. Nonetheless, research aimed at mapping priority use areas to inform management of golden eagles in western North America has typically focused on territory-holding adults during the breeding period, largely to the exclusion of other seasons and life-history groups. To support population-wide conservation planning across the full annual cycle for golden eagles, we developed a distribution model for individuals in a season not typically evaluated-winter-and in an area of the interior western U.S. that is a high priority for conservation of the species. We used a large GPS-telemetry dataset and library of environmental variables to develop a machine-learning model to predict spatial variation in the relative intensity of use by golden eagles during winter in Wyoming, USA, and surrounding ecoregions. Based on a rigorous series of evaluations including cross-validation, withheld and independent data, our winter-season model accurately predicted spatial variation in intensity of use by multiple age- and life-history groups of eagles not associated with nesting territories (i.e., all age classes of long-distance migrants, and resident non-adults and adult \"floaters\", and movements of adult territory holders and their offspring outside their breeding territories). Important predictors in the model were wind and uplift (40.2% contribution), vegetation and landcover (27.9%), topography (14%), climate and weather (9.4%), and ecoregion (8.7%). Predicted areas of high-use winter habitat had relatively low spatial overlap with nesting habitat, suggesting a conservation strategy targeting high-use areas for one season would capture as much as half and as little as one quarter of high-use areas for the other season. The majority of predicted high-use habitat (top 10% quantile) occurred on private lands (55%); lands managed by states and the Bureau of Land Management (BLM) had a lower amount (33%), but higher concentration of high-use habitat than expected for their area (1.5-1.6x). These results will enable those involved in conservation and management of golden eagles in our study region to incorporate spatial prioritization of wintering habitat into their existing regulatory processes, land-use planning tasks, and conservation actions.

The K family of vitamins includes a collection of molecules with different pharmacokinetic characteristics. Menaquinone-7 (MK-7) has the finest properties and is the most therapeutically beneficial due to its long plasma half-life and outstanding extrahepatic bioavailability. MK-7 exhibits cis-trans isomerism, and merely the all-trans form is biologically efficacious. Therefore, the remedial value of MK-7 end products is exclusively governed by the quantity of all-trans MK-7. Consumers favour fermentation for the production of MK-7; however, it involves several challenges. The low MK-7 yield and extensive downstream processing requirements increase production costs, resulting in an expensive final product that is not universally available. Bacterial cell immobilisation with iron oxide nanoparticles (IONs) can potentially address the limitations of MK-7 fermentation. Uncoated IONs tend to have low stability and can adversely affect cell viability; thus, amine-functionalised IONs, owing to their increased physicochemical stability and biocompatibility, are a favourable alternative. Nonetheless, employing biocompatible IONs for this purpose is only advantageous if the bioactive MK-7 isomer is obtained in the most significant fraction, exploring which formed the aim of this investigation. Two amine-functionalised IONs, namely 3-aminopropyltriethoxysilane (APTES)-coated IONs (IONs@APTES) and L-Lysine (L-Lys)-coated IONs (L-Lys@IONs), were synthesised and characterised, and their impact on various parameters was evaluated. IONs@APTES were superior, and the optimal concentration (300 μ g/mL) increased all-trans MK-7 production and improved its yield relative to the untreated cells by 2.3- and 3.1-fold, respectively. The outcomes of this study present an opportunity to develop an innovative and effective fermentation method that enhances the production of bioactive MK-7.