Nanohybrid liposomes coated with amphiphilic hyaluronic acid–ceramide (HACE) was fabricated for targeted delivery of anticancer drug and in vivo cancer imaging. Nanohybrid liposomes including ...doxorubicin (DOX) and Magnevist, a contrast agent for magnetic resonance (MR) imaging, with 120–130nm mean diameter and a narrow size distribution were developed. DOX release from the developed formulation was improved at acidic pH (pH5.5 and 6.8) versus physiological pH (pH7.4). Cytotoxicity induced by the blank plain liposome was reduced by coating the outer surface of the nanohybrid liposome with HACE. Cellular uptake of DOX from the nanohybrid liposome was enhanced by HA and CD44 receptor interaction, versus the plain liposome. In vivo contrast-enhancing effects revealed that the nanohybrid liposome can be used as a tumor targeting MR imaging probe for cancer diagnosis. In a pharmacokinetic study in rats, in vivo clearance of DOX was decreased in the order DOX solution, plain liposome (F2), and nanohybrid liposome (F3), indicating prolonged circulation of the drug in the blood stream and improved therapeutic efficacy of the nanohybrid liposome (F3). Based on these findings, the nanohybrid liposomal system may be a useful candidate for real-time cancer diagnosis and therapy.
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Particle focusing in planar geometries is essentially required in order to develop cost-effective lab-on-a-chips, such as cell counting and point-of-care (POC) devices. In this study, a novel method ...for sheathless particle focusing, called "Elasto-Inertial Particle Focusing", was demonstrated in a straight microchannel. The particles were notably aligned along the centerline of the straight channel under a pressure-driven flow without any additional external force or apparatus after the addition of an elasticity enhancer: PEO (poly(ethylene oxide)) (∼O(100) ppm). As theoretically predicted (elasticity number: El≈O(100)), multiple equilibrium positions (centerline and corners) were observed for the viscoelastic flow without inertia, whereas three-dimensional particle focusing only occurred when neither the elasticity nor the inertia was negligible. Therefore, the three-dimensional particle focusing mechanism was attributed to the synergetic combination of the elasticity and the inertia (elasticity number: El≈O(1-10)). Furthermore, from the size dependence of the elastic force upon particles, we demonstrated that a mixture of 5.9 and 2.4 µm particles was separated at the exit of the channel in viscoelastic flows. We expect that this method can contribute to develop the miniaturized flow cytometry and microdevices for cell and particle manipulation.
The study aimed to assess the risk of reoperations for strabismus in the pediatric population and to identify high-risk groups. This was a nationwide population-based study that used data from the ...Korean National Health Claims Database from 2008 to 2020. Two major cohorts were established based on initial strabismus: age-, sex-, and recruitment year-matched controls were randomly selected. Patients aged ≤ 9 years who underwent initial strabismus surgery for exotropia and esotropia were included, resulting in a total of 24,816 patients included to this study. The cumulative incidence of reoperations was 843 per 10,000 persons for exotropia, 1559 per 10,000 persons for esotropia. To assess the significant exposure factors, conditional logistic regression was performed to obtain odds ratio (OR) in each cohort. In patients with exotropia, the OR of reoperations was 4.26 times higher when the initial surgery is performed at younger age (earlier than 3-year-old) and 6.49 times higher when only one eye underwent than two eye. Similarly, in patients with esotropia, younger age (6.57 times) and unilateral surgery (7.20 times) were identified as common factors that increase the risk of reoperations. Based on the findings, special attention is recommended for patients younger than 3 years, especially those performed unilateral surgery as initial intervention in practical settings.
•South Korea will expand the solar power generation using domestic facilities.•Price premium for electricity generated from the domestic facilities was estimated.•Contingent valuation (CV) was ...applied to obtaining the price premium.•To this end, a CV survey was conducted on 1,000 interviewees.•Price premium was KRW 26 per kWh and amounted to 24.8% of the electricity price.
South Korea seeks to increase the capacity of solar power generation from 10.5GW in 2019 to 68.8GW in 2034. In the process of promoting the increase, the government is trying to increase the use of domestic solar power generation facilities by enhancing their technological competitiveness and price competitiveness. This study attempts to estimate price premium or additional willingness to pay (WTP) for electricity generated using domestic solar power facilities over that from imported ones. As a method to do so, contingent valuation (CV) is adopted. A nationwide CV survey was conducted on 1,000 people during October 2020. A closed-ended question was used to elicit the WTP responses. Furthermore, a spike model was applied to analyzing the WTP data with many zeros. The price premium was estimated to be KRW 26.0 (USD 0.023) per kWh, with statistical significance, which comes to 24.8% of the price of electricity for 2019 (KRW 105 or USD 0.089 per kWh). Some factors related to the interviewees’ characteristics or recognition were found to affect the price premium significantly.
Dual CD44 and folate receptor targetable nanoparticles (NPs) based on hyaluronic acid-ceramide-folic acid (HACE-FA) were fabricated for improving tumor targetability. HACE-FA was synthesized via ...esterification between the carboxylic group of FA and hydroxyl group of HA. Doxorubicin (DOX)-loaded HACE-FA NPs, with a mean diameter of 120–130nm, narrow size distribution, and negative zeta potential, were prepared. The drug release from HACE-FA NPs were significantly increased in acidic pH (pH5.5) compared with physiological pH (7.4) (p<0.05). The cellular accumulation of the drug in HACE-FA NPs group was higher than that of HACE NPs group in SKOV-3 cells (human ovarian cancer cells; CD44 and folate receptor (FR)-positive cells). Dual targetability of HACE-FA NPs, compared to HACE NPs, was also verified in the SKOV-3 tumor-xenografted mouse model by near-infrared fluorescence (NIRF) imaging. Twenty-four hours after injection, HACE-FA NPs were accumulated mainly in tumor regions and their fluorescence intensity was 4.82-fold higher than that of HACE NPs (p<0.05). These findings suggest successful application of HACE-FA NPs for the accurate delivery of anticancer drugs to ovarian cancer.
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Plastic pollution of the oceans is increasing, and toxic interactions between microplastics (MPs) and organic pollutants have become a major environmental concern. However, the combined effects of ...organic pollutants and MPs on microbiomes and metabolomes have not been studied extensively. In the present study, to evaluate whether MPs and phenanthrene (Phe) act synergistically in the guts of marine medaka (Oryzias melastigma), we performed toxicity assessments, 16 S rRNA gene sequencing, and liquid chromatography-tandem mass spectrometry (LC-MS/MS) analyses. Our investigations revealed increased toxicity induced by Phe, as well as disturbances in gut microbiota (known as dysbiosis) when MPs were present. Furthermore, combined exposure to Phe and MPs resulted in greater alterations to microbiota composition and metabolite profiles. Notably, MP exposure was distinctly associated with the abundance of Shewanella and Spongiibacteraceae, while Phe exposure was associated with the abundance of Marimicrobium. Among key microbiota, Marimicrobium and Roseibacillus were significantly correlated with metabolites responsible for coenzyme A and glycerophospholipid metabolism in medaka. These results suggest that interactions between Phe and MPs may have significant effects on the gut microbiota and metabolism of aquatic organisms and underscore the importance of acknowledging the interplay between MPs and contaminants in aquatic environments.
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•Co-exposure of phenanthrene (Phe) and microplastic (MP) induced synergistic toxicity.•Exposure to Phe and/or MP led to dysbiosis of the gut microbiota.•Synergistic effects of Phe and MP were revealed by microbiome and metabolome analysis.•Correlations between microbiota and metabolites were identified upon combined exposure.
In this study, green coffee beans were fermented using three yeast and three lactic acid bacteria (LAB) starters. The effects of each starter on the metabolite profiles of green coffee beans were ...comparatively analyzed. The principal component analysis (PCA) biplot showed a clear separation between the groups fermented with LAB (Leuconostoc mesenteroides, Lactobacillus plantarum, and Pediococcus pentosaceus) and the groups fermented with yeast (Saccharomyces cerevisiae, Candida parapsilosis, and Pichia guilliermondii). Various metabolites, including palmitic acid, stearic acid, and piperidine, were associated with the LAB strains. 2-Palmitoylglycerol, ribonic acid, and arabitol were related to C. parapsilosis and P. guilliermondii. Phenylethyl alcohol, succinic acid, shikimic acid, and methylamine contributed greatly to the separation of S. cerevisiae from the other strains in the PCA biplot. In addition, chlorogenic acid levels were higher in the LAB strains than in the yeast strains after fermentation. In particular, C. parapsilosis and P. guilliermondii showed much lower levels. The level of caffeine was highest in P. pentosaceus and lowest in C. parapsilosis after fermentation. This study provides comprehensive information on the metabolic changes after green coffee bean fermentation according to the type of microbes used.
•Green coffee bean fermentation with three LAB and three yeast strains was investigated.•Metabolites of green coffee beans were constantly changed for 5 days of fermentation.•LAB and yeast showed different fermentation pattern during fermentation.•The contents of metabolite can be changed by controlling the starter strain.
Abstract Hyaluronic acid-ceramide (HA-CE)-based self-assembled nanoparticles were developed for intravenous docetaxel (DCT) delivery. In this study, physicochemical properties, cellular uptake ...efficiency, and in vivo targeting capability of the nanoparticles developed were investigated. DCT-loaded nanoparticles composed of HA-CE and Pluronic 85 (P85) with a mean diameter of 110–140 nm were prepared and their morphological shapes were assessed using transmission electron microscopy (TEM). DCT release from nanoparticle was enhanced with increasing P85 concentrations in our in vitro model. Blank nanoparticles exhibited low cytotoxicity in U87-MG, MCF-7 and MCF-7/ADR cell lines. From cellular uptake studies, the nanoparticles developed enhanced the intracellular DCT uptake in the CD44-overexpressing cell line (MCF-7). The nanoparticles were shown to be taken up by the HA–CD44 interaction according to DCT and coumarin 6 (C6) cellular uptake studies. The multidrug resistance (MDR)-overcoming effects of DCT-loaded HA-CE/P85-based nanoparticles were also observed in cytotoxicity tests in MCF-7/ADR cells. Following the intravenous injection of DCT-loaded cyanine 5.5 (Cy5.5)-conjugated nanoparticles in MCF-7/ADR tumor-bearing mice, its in vivo targeting for CD44-overexpressing tumors was identified by non-invasive near-infrared (NIR) fluorescence imaging. These results indicate that the HA-CE-based nanoparticles prepared may be a promising anti-cancer drug delivery system through passive and active tumor targeting.
Human skin is an organ located in the outermost part of the body; thus, it frequently exhibits visible signs of physiological health. Ethical concerns and genetic differences in conventional animal ...studies have increased the need for alternative in vitro platforms that mimic the structural and functional hallmarks of natural skin. Despite significant advances in in vitro skin modeling over the past few decades, different reproducible biofabrication strategies are required to reproduce the pathological features of diseased human skin compared to those used for healthy-skin models. To explain human skin modeling with pathological hallmarks, we first summarize the structural and functional characteristics of healthy human skin. We then provide an extensive overview of how to recreate diseased human skin models in vitro, including models for wounded, diabetic, skin-cancer, atopic, and other pathological skin types. We conclude with an outlook on diseased-skin modeling and its technical perspective for the further development of skin engineering.
Gelatin methacrylate (GelMA) bioink has been widely used in bioprinting because it is a printable and biocompatible biomaterial. However, it is difficult to print GelMA bioink without any temperature ...control because it has a thermally-sensitive rheological property. Therefore, in this study, we developed a temperature-controlled printing system in real time without affecting the viability of the cells encapsulated in the bioink. In addition, a skin-derived decellularized extracellular matrix (SdECM) was printed with GelMA to better mimic the native tissue environment compared with solely using GelMA bioink with the enhancement of structural stability. The temperature setting accuracy was calculated to be 98.58 ± 1.8 % for the module and 99.48 ± 1.33 % for the plate from 5 °C to 37 °C. The group of the temperature of the module at 10 °C and the plate at 20 °C have 93.84 % cell viability with the printable range in the printability window. In particular, the cell viability and proliferation were increased in the encapsulated fibroblasts in the GelMA/SdECM bioink, relative to the GelMA bioink, with a morphology that significantly spread for seven days. The gene expression and growth factors related to skin tissue regeneration were relatively upregulated with SdECM components. In the bioprinting process, the rheological properties of the GelMA/SdECM bioink were successfully adjusted in real time to increase printability, and the native skin tissue mimicked components providing tissue-specific biofunctions to the encapsulated cells. The developed bioprinting strategies and bioinks could support future studies related to the skin tissue reconstruction, regeneration, and other medical applications using the bioprinting process.
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