Polydopamine Nanoparticles as Mimicking RPE Melanin for the Protection of Retinal Cells Against Blue Light-Induced Phototoxicity.

Exposure of the eyes to blue light can induce the overproduction of reactive oxygen species (ROS) in the retina and retinal pigment epithelium (RPE) cells, potentially leading to pathological damage of age-related macular degeneration (AMD). While the melanin in RPE cells absorbs blue light and prevents ROS accumulation, the loss and dysfunction of RPE melanin due to age-related changes may contribute to photooxidation toxicity. Herein, a novel approach utilizing a polydopamine-replenishing strategy via a single-dose intravitreal (IVT) injection is presented to protect retinal cells against blue light-induced phototoxicity. To investigate the effects of overexposure to blue light on retinal cells, a blue light exposure Nrf2-deficient mouse model is created, which is susceptible to light-induced retinal lesions. After blue light irradiation, retina degeneration and an overproduction of ROS are observed. The polydopamine-replenishing strategy demonstrated effectiveness in maintaining retinal structural integrity and preventing retina degeneration by reducing ROS production in retinal cells and limiting the phototoxicity of blue light exposure. These findings highlight the potential of polydopamine as a simple and effective replenishment for providing photoprotection against high-energy blue light exposure.

Long-term follow-up of inpatients with traumatic fractures who received integrative Korean Medicine treatment: A retrospective analysis and questionnaire survey study.

Previous studies have reported pain reduction after Korean medicine (KM) treatment in patients with fractures. However, these studies were limited by small sample sizes and short observation periods. To address these limitations, we aimed to analyze the outcomes of patients with traumatic fractures who received integrative KM treatment and investigate their long-term progress through follow-up observations. This study was a retrospective analysis and questionnaire survey conducted at a multi-center inpatient care setting in Korea. A total of 1150 patients who had traumatic fractures and received at least 5-day inpatient care at one of 5 KM hospitals. Finally, 339 patients completed the follow-up survey. The questionnaire survey was administered 3 months post discharge. The primary outcome was the difference in numeric rating scale (NRS) scores at admission and discharge for fracture-related pain. The secondary outcomes were EuroQol 5-Dimension 5-Level (EQ-5D-5L) score, Oswestry Disability Index, Neck Disability Index, Western Ontario and McMaster Universities Arthritis Index, Shoulder Pain and Disability Index, and Patient Global Impression of Change (PGIC) score. The follow-up questionnaire survey included questions on surgery and imaging before admission and after discharge and treatment within the past 3 months. The mean NRS score at follow-up showed a significant decrease of 4.41 points compared with that at admission (P < .001). The mean EQ-5D-5L score at follow-up showed a significant increase of 0.18 points compared with that at admission (P < .05). In the follow-up survey on PGIC, 307 participants (90.56%) were "minimally improved" or better. Integrative KM treatment can help improve pain, functional impairment, and long-term quality of life in patients with traumatic fractures.

Development and application of novel peptide-formulated nanoparticles for treatment of atopic dermatitis.

Atopic dermatitis is a chronic inflammatory skin condition that is characterized by skin inflammation, itching, and redness. Although various treatments can alleviate symptoms, they often come with side effects, highlighting the need for new treatments. Here, we discovered a new peptide-based therapy using the intra-dermal delivery technology (IDDT) platform developed by Remedi Co., Ltd (REMEDI). The platform screens and identifies peptides derived from proteins in the human body that possess cell-penetrating peptide (CPP) properties. We screened over 1000-peptides and identified several derived from the Speckled protein (SP) family that have excellent CPP properties and have anti-inflammatory effects. We assessed these peptides for their potential as a treatment for atopic dermatitis. Among them, the RMSP1 peptide showed the most potent anti-inflammatory effects by inhibiting the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and signal transducer and activator of transcription 3 (STAT3) signaling pathways while possessing CPP properties. To further improve efficacy and stability, we developed a palmitoylated version called Pal-RMSP1. Formulation studies using liposomes (Pal-RMSP1 LP) and micelles (Pal-RMSP1 DP) demonstrated improved anti-inflammatory effects in vitro and enhanced therapeutic effects in vivo. Our study indicates that nano-formulated Pal-RMSP1 could have the potential to become a new treatment option for atopic dermatitis.

Gene augmentation for autosomal dominant retinitis pigmentosa using rhodopsin genomic loci nanoparticles in the P23H+/- knock-in murine model.

Gene therapy for autosomal dominant retinitis pigmentosa (adRP) is challenged by the dominant inheritance of the mutant genes, which would seemingly require a combination of mutant suppression and wild-type replacement of the appropriate gene. We explore the possibility that delivery of a nanoparticle (NP)-mediated full-length mouse genomic rhodopsin (gRho) or human genomic rhodopsin (gRHO) locus can overcome the dominant negative effects of the mutant rhodopsin in the clinically relevant P23H+/--knock-in heterozygous mouse model. Our results demonstrate that mice in both gRho and gRHO NP-treated groups exhibit significant structural and functional recovery of the rod photoreceptors, which lasted for 3 months post-injection, indicating a promising reduction in photoreceptor degeneration. We performed miRNA transcriptome analysis using next generation sequencing and detected differentially expressed miRNAs as a first step towards identifying miRNAs that could potentially be used as rhodopsin gene expression enhancers or suppressors for sustained photoreceptor rescue. Our results indicate that delivering an intact genomic locus as a transgene has a greater chance of success compared to the use of the cDNA for treatment of this model of adRP, emphasizing the importance of gene augmentation using a gDNA that includes regulatory elements.

Melanin-like Nanoparticles as an Alternative to Natural Melanin in Retinal Pigment Epithelium Cells and Their Therapeutic Effects against Age-Related Macular Degeneration.

Melanin is a natural pigment that is widely distributed in many parts of the human body, such as the skin and retinal pigment epithelium (RPE) in eyes. In contrast to skin melanin, which is being constantly synthesized by the epidermal melanocytes, melanin in the RPE does not regenerate. Melanin is known to function as a potential radical scavenger and photoprotective agent. However, the protective effects of melanin against oxidative stress decline with increasing age. This phenomenon has been correlated with the pathogenesis of age-related macular degeneration (AMD). To increase the potential antioxidant and photoprotective characteristics of melanin, we designed a therapeutic strategy for replenishment of melanin using PEGylated synthetic melanin-like nanoparticles (MNPs) in the RPE for the treatment of AMD. We performed experiments using AMD-like cellular and mouse models and demonstrated that MNPs are biocompatible and selectively target reactive oxygen species (ROS) with powerful antioxidant properties. MNPs can traffic and accumulate in the RPE and are exclusively located in cytosol, but not the nucleus and mitochondria of the cells, for at least 3 months after a single-dose intravitreal injection. Our findings demonstrate that MNPs are able to substitute for natural melanin in the RPE and suggest the potential efficacy of MNPs as a natural radical scavenger against oxidative stress in ROS-related diseases, such as AMD.

Differences of Gut Microbiota in the Freshwater Blackworm (Lumbriculus variegatus: Oligochaeta) in Two Different Habitat Conditions.

The distribution of organisms is governed by their habitat condition. We analyzed bacterial communities in the gut of the blackworm Lumbriculus variegatus by pyrosequencing of the extracted intestinal metagenomic DNA. Blackworms were collected from two sampling sites with differences in irradiance and riparian vegetation, where site GP7 was covered by riparian vegetation and site GP8 was exposed to sunlight. We obtained the filtered 6414 reads from three samples of each site. At GP7, 271 OTUs were identified, including 32 OTUs unique to the site, whereas at GP8, 238 OTUs were identified, including 22 unique OTUs. Among them, 18 OTUs were shared between both sites. The phylum Proteobacteria was a major component contributing 67.84% and 64.05% of sequences at sites GP7 and GP8, respectively, while each remaining phylum contributed less than 10% at both sites. The two sites differed in microbial community composition and KEGG-indicated biochemical pathways. Community indices such as species richness and Shannon diversity were higher at site GP7 than at GP8. Meanwhile, the abundance of Cyanobacteria was significantly higher at site GP8, while site GP7 showed a greater proportion of genes for membrane transport and carbohydrate metabolism, reflecting differences in food resources.

Prediction of Geosmin at Different Depths of Lake Using Machine Learning Techniques.

Geosmin is a major concern in the management of water sources worldwide. Thus, we predicted concentration categories of geosmin at three different depths of lakes (i.e., surface, middle, and bottom), and analyzed relationships between geosmin concentration and factors such as phytoplankton abundance and environmental variables. Data were collected monthly from three major lakes (Uiam, Cheongpyeong, and Paldang lakes) in Korea from May 2014 to December 2015. Before predicting geosmin concentration, we categorized it into four groups based on the boxplot method, and multivariate adaptive regression splines, classification and regression trees, and random forest (RF) were applied to identify the most appropriate modelling to predict geosmin concentration. Overall, using environmental variables was more accurate than using phytoplankton abundance to predict the four categories of geosmin concentration based on AUC and accuracy in all three models as well as each layer. The RF model had the highest predictive power among the three SDMs. When predicting geosmin in the three water layers, the relative importance of environmental variables and phytoplankton abundance in the sensitivity analysis was different for each layer. Water temperature and abundance of Cyanophyceae were the most important factors for predicting geosmin concentration categories in the surface layer, whereas total abundance of phytoplankton exhibited relatively higher importance in the bottom layer.

Characteristics of Microbial Communities of Pachygrontha antennata (Hemiptera: Pachygronthidae) in Relation to Habitat Variables.

The microbial community interacts with the environment and the health and immune function of its host both directly and indirectly. However, very few studies about microbial communities have considered habitat and external environmental variables. This study examined environmental influences on the microbial community of Pachygrontha antennata, which is found in various habitats (e.g., urban, forested, and agricultural areas). The results demonstrated that the composition of the microbial community differed according to land use, while the bacterial diversity did not. In urban areas with high environmental heterogeneity, microbial community diversity tended to be high. Furthermore, bacteria in forests and agricultural areas (e.g., Paraburkholderia, Burkholderia) have been found to be highly correlated with habitat variables. Therefore, we suggest that habitat variables should be considered in future symbiotic studies.

Improvement of bio-crude oil properties via co-pyrolysis of pine sawdust and waste polystyrene foam.

Conversion technology of solid biomass to liquid fuel, named bio-crude oil, has been researched widely for the production of renewable energy to replace fossil fuel oil. As the result of many admirable researches, fast pyrolysis technology for bio-crude oil production is close to commercialization. However, bio-crude oil has unsatisfactory properties compared to general petroleum oil, for instance, low heating value, high water content, and high viscosity. In this study, pine sawdust (SD) biomass was co-pyrolyzed with waste polystyrene foam (WPSF), which was expected to improve the bio-crude oil quality due to high heating value and non-oxygen composition of polystyrene. The co-pyrolysis experiment was conducted in a bubbling fluidized bed reactor under the following conditions: temperature of 500 °C which was chosen based on the results from thermogravimetric analysis of SD and WPSF, nitrogen flow rate of 20-25 L/min., and feeding rate of 200 g/hr. Various mixing ratios of SD/WPSF by weight percentage were tested as follows: 100/0, 95/5, 90/10, 85/15, 80/20, 75/25, 70/30, 60/40, 50/50, 25/75, 0/100. Experimental results showed that in case of only SD feeding the bio-crude oil yield and higher heating value (HHV) were 48.83 wt% and 17.81 MJ/kg respectively. By contrast, oil yield and HHV in case of 25% SD with 75% WPSF mixture were 63.31 wt% and 39.65 MJ/kg respectively. Additional analysis showed that water content, and acetic acid concentration of bio-crude oil from co-pyrolysis of SD/WPSF mixture were decreased almost proportionally with the increasing WPSF ratio. Furthermore, measured values of water content, and acetic acid concentration were lower than the calculated values by linear interpolation, which means that the synergistic effect between SD and WPSF was achieved during the co-pyrolysis. In conclusion, co-pyrolysis of SD and WPSF was found as a promising solution to improve bio-crude oil quality. With this technology, the industrial growth of bio-crude oil area is expected as well as waste plastic.

Osteogenic differentiation of mesenchymal stem cells modulated by a chemically modified super-hydrophilic titanium implant surface.

This study investigated the osteogenic functionality of multipotent mesenchymal stem cells (MSCs) modulated by a chemically modified super-hydrophilic titanium (Ti) bone implant surface to elucidate the biological mechanism underlying the bone healing capacity of this modified Ti surface. A microstructured Ti surface incorporating bioactive ions (in this study, phosphate (P) ions) was prepared by wet chemical treatment. The results showed that the hydrothermally obtained crystalline P-incorporated Ti surface (P surface) displayed long-term super-hydrophilicity (water contact angles <5°) during a 36-week observation period. The hydrophilic P surface enhanced early cellular functions and osteogenic differentiation of multipotent MSCs derived from mouse bone marrow and human adipose tissue. The expression of critical integrins affecting subsequent osteoblast function and osteoblast phenotype genes was notably upregulated in multipotent MSCs grown on the P surface compared with the commercially available grit-blasted microrough clinical oral implant surface. The P surface supported better cell spreading, focal adhesion and ALP activity of MSCs. These results indicate that a super-hydrophilic P-incorporated Ti surface accelerates implant bone healing by enhancing the early osteogenesis functions of multipotent MSCs.

Modeling Occurrence of Urban Mosquitos Based on Land Use Types and Meteorological Factors in Korea.

Mosquitoes are a public health concern because they are vectors of pathogen, which cause human-related diseases. It is well known that the occurrence of mosquitoes is highly influenced by meteorological conditions (e.g., temperature and precipitation) and land use, but there are insufficient studies quantifying their impacts. Therefore, three analytical methods were applied to determine the relationships between urban mosquito occurrence, land use type, and meteorological factors: cluster analysis based on land use types; principal component analysis (PCA) based on mosquito occurrence; and three prediction models, support vector machine (SVM), classification and regression tree (CART), and random forest (RF). We used mosquito data collected at 12 sites from 2011 to 2012. Mosquito abundance was highest from August to September in both years. The monitoring sites were differentiated into three clusters based on differences in land use type such as culture and sport areas, inland water, artificial grasslands, and traffic areas. These clusters were well reflected in PCA ordinations, indicating that mosquito occurrence was highly influenced by land use types. Lastly, the RF represented the highest predictive power for mosquito occurrence and temperature-related factors were the most influential. Our study will contribute to effective control and management of mosquito occurrences.

Ultrasound-mediated gene and drug delivery using a microbubble-liposome particle system.

Theranostic agents present a promising clinical approach for cancer detection and treatment. We herein introduce a microbubble and liposome complex (MB-Lipo) developed for ultrasound (US) imaging and activation. The MB-Lipo particles have a hybrid structure consisting of a MB complexed with multiple Lipos. The MB components are used to generate high echo signals in US imaging, while the Lipos serve as a versatile carrier of therapeutic materials. MB-Lipo allows high contrast US imaging of tumor sites. More importantly, the application of high acoustic pressure bursts MBs, which releases therapeutic Lipos and further enhances their intracellular delivery through sonoporation effect. Both imaging and drug release could thus be achieved by a single US modality, enabling in situ treatment guided by real-time imaging. The MB-Lipo system was applied to specifically deliver anti-cancer drug and genes to tumor cells, which showed enhanced therapeutic effect. We also demonstrate the clinical potential of MB-Lipo by imaging and treating tumor in vivo.

Changes of heavy metals in Pollutant Release and Transfer Registers (PRTRs) in Korea.

Industrial effluent containing heavy metals discharged into streams may pose high toxicity risks to aquatic organisms and to human health. Therefore, it is important to understand how to change the amount of effluent with heavy metals discharged from industries into open aquatic ecosystems both for effective management of heavy metals and to foster sustainable ecosystems. This study was conducted to characterize the release of heavy metals from industries based on the Pollutant Release and Transfer Registers database in Korea from 1999 to 2010. From the database, we selected nine heavy metals (Pb, Cd, Mn, Sb, Cu, Zn, Cr, Sn, and Ni) and compared the differences in their effluent for different types of industries. The heavy metal effluents released into freshwater ecosystems were classified into four clusters through the learning process of the self-organizing map. Cluster 1 was characterized by the relatively higher effluent volumes of heavy metals, whereas cluster 4 had lower effluent volumes. The different patterns of the effluent volumes in heavy metals were closely associated with the differences of industrial types, and the changes of effluents of heavy metals reflected the changes in regulations and laws for aquatic ecosystem management.

Potential impacts of global warming on the diversity and distribution of stream insects in South Korea.

Globally, the East Asian monsoon region is one of the richest environments in terms of biodiversity. The region is undergoing rapid human development, yet its river ecosystems have not been well studied. Global warming represents a major challenge to the survival of species in this region and makes it necessary to assess and reduce the potential consequences of warming on species of conservation concern. We projected the effects of global warming on stream insect (Ephemeroptera, Odonata, Plecoptera, and Trichoptera [EOPT]) diversity and predicted the changes of geographical ranges for 121 species throughout South Korea. Plecoptera was the most sensitive (decrease of 71.4% in number of species from the 2000s through the 2080s) order, whereas Odonata benefited (increase of 66.7% in number of species from the 2000s through the 2080s) from the effects of global warming. The impact of global warming on stream insects was predicted to be minimal prior to the 2060s; however, by the 2080s, species extirpation of up to 20% in the highland areas and 2% in the lowland areas were predicted. The projected responses of stream insects under global warming indicated that species occupying specific habitats could undergo major reductions in habitat. Nevertheless, habitat of 33% of EOPT (including two-thirds of Odonata and one-third of Ephemeroptera, Plecoptera, and Trichoptera) was predicted to increase due to global warming. The community compositions predicted by generalized additive models varied over this century, and a large difference in community structure in the highland areas was predicted between the 2000s and the 2080s. However, stream insect communities, especially Odonata, Plecoptera, and Trichoptera, were predicted to become more homogenous under global warming.

Relaxivity control of magnetic nanoclusters for efficient magnetic relaxation switching assay.

50 nm Magnetic nanocluster (MNC) was deliberately selected as an efficient probe for the magnetic relaxation switching (MRSw) assay. After surface modification of MNCs with poly(acrylic acid) to give PAA-MNCs, and employing streptavidin-biotin interactions for the MRSw assay model, a few tenths pM concentration of strepavidin could be determined.

Response of fish communities to various environmental variables across multiple spatial scales.

A better understanding of the relative importance of different spatial scale determinants on fish communities will eventually increase the accuracy and precision of their bioassessments. Many studies have described the influence of environmental variables on fish communities on multiple spatial scales. However, there is very limited information available on this topic for the East Asian monsoon region, including Korea. In this study, we evaluated the relationship between fish communities and environmental variables at multiple spatial scales using self-organizing map (SOM), random forest, and theoretical path models. The SOM explored differences among fish communities, reflecting environmental gradients, such as a longitudinal gradient from upstream to downstream, and differences in land cover types and water quality. The random forest model for predicting fish community patterns that used all 14 environmental variables was more powerful than a model using any single variable or other combination of environmental variables, and the random forest model was effective at predicting the occurrence of species and evaluating the contribution of environmental variables to that prediction. The theoretical path model described the responses of different species to their environment at multiple spatial scales, showing the importance of altitude, forest, and water quality factors to fish assemblages.