Dankook University

By characterizing the geographic and functional spectrum of human genetic variation, the 1000 Genomes Project aims to build a resource to help to understand the genetic contribution to disease. Here we describe the genomes of 1,092 individuals from 14 populations, constructed using a combination of low-coverage whole-genome and exome sequencing. By developing methods to integrate information across several algorithms and diverse data sources, we provide a validated haplotype map of 38 million single nucleotide polymorphisms, 1.4 million short insertions and deletions, and more than 14,000 larger deletions. We show that individuals from different populations carry different profiles of rare and common variants, and that low-frequency variants show substantial geographic differentiation, which is further increased by the action of purifying selection. We show that evolutionary conservation and coding consequence are key determinants of the strength of purifying selection, that rare-variant load varies substantially across biological pathways, and that each individual contains hundreds of rare non-coding variants at conserved sites, such as motif-disrupting changes in transcription-factor-binding sites. This resource, which captures up to 98% of accessible single nucleotide polymorphisms at a frequency of 1% in related populations, enables analysis of common and low-frequency variants in individuals from diverse, including admixed, populations. This report from the 1000 Genomes Project describes the genomes of 1,092 individuals from 14 human populations, providing a resource for common and low-frequency variant analysis in individuals from diverse populations; hundreds of rare non-coding variants at conserved sites, such as motif-disrupting changes in transcription-factor-binding sites, can be found in each individual. This report by the 1000 Genomes Project describes the genomes of 1,092 individuals from 14 human populations, providing a resource for common and low-frequency variant analysis in individuals from diverse populations. Integrative analyses reveal profiles of rare and common variants in different populations. The frequencies of rare variants vary across biological pathways, and hundreds of rare, non-coding variants at conserved sites — such as changes disrupting transcription-factor motifs — can be established for each individual.

autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.

Phenolic compounds are an important class of plant secondary metabolites which play crucial physiological roles throughout the plant life cycle. Phenolics are produced under optimal and suboptimal conditions in plants and play key roles in developmental processes like cell division, hormonal regulation, photosynthetic activity, nutrient mineralization, and reproduction. Plants exhibit increased synthesis of polyphenols such as phenolic acids and flavonoids under abiotic stress conditions, which help the plant to cope with environmental constraints. Phenylpropanoid biosynthetic pathway is activated under abiotic stress conditions (drought, heavy metal, salinity, high/low temperature, and ultraviolet radiations) resulting in accumulation of various phenolic compounds which, among other roles, have the potential to scavenge harmful reactive oxygen species. Deepening the research focuses on the phenolic responses to abiotic stress is of great interest for the scientific community. In the present article, we discuss the biochemical and molecular mechanisms related to the activation of phenylpropanoid metabolism and we describe phenolic-mediated stress tolerance in plants. An attempt has been made to provide updated and brand-new information about the response of phenolics under a challenging environment.

IMPORTANCE: Body mass index (BMI) and gestational weight gain are increasing globally. In 2009, the Institute of Medicine (IOM) provided specific recommendations regarding the ideal gestational weight gain. However, the association between gestational weight gain consistent with theIOM guidelines and pregnancy outcomes is unclear. OBJECTIVE: To perform a systematic review, meta-analysis, and metaregression to evaluate associations between gestational weight gain above or below the IOM guidelines (gain of 12.5-18 kg for underweight women [BMI <18.5]; 11.5-16 kg for normal-weight women [BMI 18.5-24.9]; 7-11 kg for overweight women [BMI 25-29.9]; and 5-9 kg for obese women [BMI ≥30]) and maternal and infant outcomes. DATA SOURCES AND STUDY SELECTION: Search of EMBASE, Evidence-Based Medicine Reviews, MEDLINE, and MEDLINE In-Process between January 1, 1999, and February 7, 2017, for observational studies stratified by prepregnancy BMI category and total gestational weight gain. DATA EXTRACTION AND SYNTHESIS: Data were extracted by 2 independent reviewers. Odds ratios (ORs) and absolute risk differences (ARDs) per live birth were calculated using a random-effects model based on a subset of studies with available data. MAIN OUTCOMES AND MEASURES: Primary outcomes were small for gestational age (SGA), preterm birth, and large for gestational age (LGA). Secondary outcomes were macrosomia, cesarean delivery, and gestational diabetes mellitus. RESULTS: Of 5354 identified studies, 23 (n = 1 309 136 women) met inclusion criteria. Gestational weight gain was below or above guidelines in 23% and 47% of pregnancies, respectively. Gestational weight gain below the recommendations was associated with higher risk of SGA (OR, 1.53 [95% CI, 1.44-1.64]; ARD, 5% [95% CI, 4%-6%]) and preterm birth (OR, 1.70 [1.32-2.20]; ARD, 5% [3%-8%]) and lower risk of LGA (OR, 0.59 [0.55-0.64]; ARD, -2% [-10% to -6%]) and macrosomia (OR, 0.60 [0.52-0.68]; ARD, -2% [-3% to -1%]); cesarean delivery showed no significant difference (OR, 0.98 [0.96-1.02]; ARD, 0% [-2% to 1%]). Gestational weight gain above the recommendations was associated with lower risk of SGA (OR, 0.66 [0.63-0.69]; ARD, -3%; [-4% to -2%]) and preterm birth (OR, 0.77 [0.69-0.86]; ARD, -2% [-2% to -1%]) and higher risk of LGA (OR, 1.85 [1.76-1.95]; ARD, 4% [2%-5%]), macrosomia (OR, 1.95 [1.79-2.11]; ARD, 6% [4%-9%]), and cesarean delivery (OR, 1.30 [1.25-1.35]; ARD, 4% [3%-6%]). Gestational diabetes mellitus could not be evaluated because of the nature of available data. CONCLUSIONS AND RELEVANCE: In this systematic review and meta-analysis of more than 1 million pregnant women, 47% had gestational weight gain greater than IOM recommendations and 23% had gestational weight gain less than IOM recommendations. Gestational weight gain greater than or less than guideline recommendations, compared with weight gain within recommended levels, was associated with higher risk of adverse maternal and infant outcomes.

Recently, organic thermally activated delayed fluorescence (TADF) emitters have attracted a great deal of attention because they can theoretically realize 100% internal quantum efficiency. Many TADF emitters have been developed since the first demonstration of close to 20% external quantum efficiency in the devices. Recently developed TADF emitters demonstrated close to 37% external quantum efficiency in blue, above 30% external quantum efficiency in green, and close to 18% external quantum efficiency in red devices. Therefore, TADF organic light-emitting diodes could potentially be substituted for high-efficiency phosphorescent organic light-emitting diodes. In this work, we reviewed molecular design strategies of organic-based TADF emitters by classifying them into several categories depending on the material parameters required for the TADF emitters. In addition, we proposed a future development direction of TADF emitters to make them competitive with phosphorescent emitters.

The past decades have been a golden era during which great tasks were accomplished in the field of microbiology, including food microbiology. In the past, culture-dependent methods have been the primary choice to investigate bacterial diversity. However, using cultureindependent high-throughput sequencing of 16S rRNA genes has greatly facilitated studies exploring the microbial compositions and dynamics associated with health and diseases. These culture-independent DNA-based studies generate large-scale data sets that describe the microbial composition of a certain niche. Consequently, understanding microbial diversity becomes of greater importance when investigating the composition, function, and dynamics of the microbiota associated with health and diseases. Even though there is no general agreement on which diversity index is the best to use, diversity indices have been used to compare the diversity among samples and between treatments with controls. Tools such as the Shannon- Weaver index and Simpson index can be used to describe population diversity in samples. The purpose of this review is to explain the principles of diversity indices, such as Shannon- Weaver and Simpson, to aid general microbiologists in better understanding bacterial communities. In this review, important questions concerning microbial diversity are addressed. Information from this review should facilitate evidence-based strategies to explore microbial communities.

Sol-gel chemistry offers a flexible approach to obtaining a diverse range of materials. It allows differing chemistries to be achieved as well as offering the ability to produce a wide range of nano-/micro-structures. The paper commences with a generalized description of the various sol-gel methods available and how these chemistries control the bulk properties of the end products. Following this, a more detailed description of the biomedical areas where sol-gel materials have been explored and found to hold significant potential. One of the interesting fields that has been developed recently relates to hybrid materials that utilize sol-gel chemistry to achieve unusual composite properties. Another intriguing feature of sol-gels is the unusual morphologies that are achievable at the micro- and nano-scale. Subsequently the ability to control pore chemistry at a number of different length scales and geometries has proven to be a fruitful area of exploitation, that provides excellent bioactivity and attracts cellular responses as well as enables the entrapment of biologically active molecules and their controllable release for therapeutic action. The approaches of fine-tuning surface chemistry and the combination with other nanomaterials have also enabled targeting of specific cell and tissue types for drug delivery with imaging capacity.

In order to identify patterns in bacterial community composition in freshwater habitats, we analyzed the available database of 16S rDNA sequences from freshwater plankton, including 24 new sequences from Parker River (Massachusetts, USA), 42 from Lake Soyang (South Korea) and 148 from Lake IJssel (The Netherlands). At this point, combined diversity studies using random cloning have deposited 689 bacterial and 75 plastid 16S rDNA sequences from the water column of rivers and lakes in North America, Europe and Asia. Systematic comparisons with the global database showed that the majority of the bacterial sequences were most closely related to other freshwater clones or isolates, while relatively few were closest to sequences recovered from soils or marine habitats. This habitat-specific clustering suggests that the clustered 16S rDNA sequences represent species or groups of species that are indigenous to freshwater. We have discerned 34 phylogenetic clusters of closely related sequences that are either restricted to freshwater or dominated by freshwater sequences. Of these clusters, 23 contained no cultivated organisms. These putative freshwater clusters were found among the alpha-, beta-and gamma-Proteobacteria, the Cytophaga-Flavobacterium-Bacteroides group, the Cyanobacteria, the Actinobacteria, the Verrucomicrobia, the green non-sulfur bacteria and candidate division OP10. This study shows that rivers and lakes have a specific planktonic bacterial community distinct from bacteria in neighboring environments such as soil and sediments. It also points out that these planktonic bacteria are distributed in diverse freshwater ecosystems around the world.

The gut microbiota has an important role in the gut barrier, inflammation and metabolic functions. Studies have identified a close association between the intestinal barrier and metabolic diseases, including obesity and type 2 diabetes (T2D). Recently, Akkermansia muciniphila has been reported as a beneficial bacterium that reduces gut barrier disruption and insulin resistance. Here we evaluated the role of A. muciniphila-derived extracellular vesicles (AmEVs) in the regulation of gut permeability. We found that there are more AmEVs in the fecal samples of healthy controls compared with those of patients with T2D. In addition, AmEV administration enhanced tight junction function, reduced body weight gain and improved glucose tolerance in high-fat diet (HFD)-induced diabetic mice. To test the direct effect of AmEVs on human epithelial cells, cultured Caco-2 cells were treated with these vesicles. AmEVs decreased the gut permeability of lipopolysaccharide-treated Caco-2 cells, whereas Escherichia coli-derived EVs had no significant effect. Interestingly, the expression of occludin was increased by AmEV treatment. Overall, these results imply that AmEVs may act as a functional moiety for controlling gut permeability and that the regulation of intestinal barrier integrity can improve metabolic functions in HFD-fed mice.

The infection of a novel coronavirus found in Wuhan of China (SARS-CoV-2) is rapidly spreading, and the incidence rate is increasing worldwide. Due to the lack of effective treatment options for SARS-CoV-2, various strategies are being tested in China, including drug repurposing. In this study, we used our pre-trained deep learning-based drug-target interaction model called Molecule Transformer-Drug Target Interaction (MT-DTI) to identify commercially available drugs that could act on viral proteins of SARS-CoV-2. The result showed that atazanavir, an antiretroviral medication used to treat and prevent the human immunodeficiency virus (HIV), is the best chemical compound, showing an inhibitory potency with Kd of 94.94 nM against the SARS-CoV-2 3C-like proteinase, followed by remdesivir (113.13 nM), efavirenz (199.17 nM), ritonavir (204.05 nM), and dolutegravir (336.91 nM). Interestingly, lopinavir, ritonavir, and darunavir are all designed to target viral proteinases. However, in our prediction, they may also bind to the replication complex components of SARS-CoV-2 with an inhibitory potency with Kd < 1000 nM. In addition, we also found that several antiviral agents, such as Kaletra (lopinavir/ritonavir), could be used for the treatment of SARS-CoV-2. Overall, we suggest that the list of antiviral drugs identified by the MT-DTI model should be considered, when establishing effective treatment strategies for SARS-CoV-2.

Fibroblast growth factors (FGFs) that signal through FGF receptors (FGFRs) regulate a broad spectrum of biological functions, including cellular proliferation, survival, migration, and differentiation. The FGF signal pathways are the RAS/MAP kinase pathway, PI3 kinase/AKT pathway, and PLCγ pathway, among which the RAS/MAP kinase pathway is known to be predominant. Several studies have recently implicated the in vitro biological functions of FGFs for tissue regeneration. However, to obtain optimal outcomes in vivo, it is important to enhance the half-life of FGFs and their biological stability. Future applications of FGFs are expected when the biological functions of FGFs are potentiated through the appropriate use of delivery systems and scaffolds. This review will introduce the biology and cellular functions of FGFs and deal with the biomaterials based delivery systems and their current applications for the regeneration of tissues, including skin, blood vessel, muscle, adipose, tendon/ligament, cartilage, bone, tooth, and nerve tissues.

Obesity is a prevalent and complex disease. The prevalence of obesity in Korea increased from 29.7% in 2010 to 35.7% in 2018, with the prevalence of abdominal obesity being 23.8% in 2018. Obesity contributes to medical costs and socioeconomic burden due to associated comorbidities. The treatment and management of obesity is changing based on new clinical evidence. The 2020 Korean Society for the Study of Obesity Guideline for the Management of Obesity in Korea summarizes evidence-based recommendations and treatment guidelines.

Recently, great progress has been made in the device performance of deep blue phosphorescent organic light-emitting diodes (PHOLEDs) by developing high triplet energy charge-transport materials, high triplet energy host and deep blue emitting phosphorescent dopant materials. A high quantum efficiency of over 25% and a high power efficiency of over 15 lm/W have already been achieved at 1000 cd m(-2) in the deep blue PHOLEDs with a y color coordinate less than 0.20. In this work, recent developments in organic materials for high efficiency deep blue PHOLEDs are reviewed and a future strategy for the development of high efficiency deep blue PHOLEDs is proposed.

IMPORTANCE: Use of intravascular ultrasound (IVUS) promotes better clinical outcomes for coronary intervention in complex coronary lesions. However, randomized data demonstrating the clinical usefulness of IVUS are limited for lesions treated with drug-eluting stents. OBJECTIVE: To determine whether the long-term clinical outcomes with IVUS-guided drug-eluting stent implantation are superior to those with angiography-guided implantation in patients with long coronary lesions. DESIGN, SETTING, AND PARTICIPANTS: The Impact of Intravascular Ultrasound Guidance on Outcomes of Xience Prime Stents in Long Lesions (IVUS-XPL) randomized, multicenter trial was conducted in 1400 patients with long coronary lesions (implanted stent ≥28 mm in length) between October 2010 and July 2014 at 20 centers in Korea. INTERVENTIONS: Patients were randomly assigned to receive IVUS-guided (n = 700) or angiography-guided (n = 700) everolimus-eluting stent implantation. MAIN OUTCOMES AND MEASURES: Primary outcome measure was the composite of major adverse cardiac events, including cardiac death, target lesion-related myocardial infarction, or ischemia-driven target lesion revascularization at 1 year, analyzed by intention-to-treat. RESULTS: One-year follow-up was complete in 1323 patients (94.5%). Major adverse cardiac events at 1 year occurred in 19 patients (2.9%) undergoing IVUS-guided and in 39 patients (5.8%) undergoing angiography-guided stent implantation (absolute difference, -2.97% [95% CI, -5.14% to -0.79%]) (hazard ratio [HR], 0.48 [95% CI, 0.28 to 0.83], P = .007). The difference was driven by a lower risk of ischemia-driven target lesion revascularization in patients undergoing IVUS-guided (17 [2.5%]) compared with angiography-guided (33 [5.0%]) stent implantation (HR, 0.51 [95% CI, 0.28 to 0.91], P = .02). Cardiac death and target lesion-related myocardial infarction were not significantly different between the 2 groups. For cardiac death, there were 3 patients (0.4%) in the IVUS-guided group and 5 patients (0.7%) in the angiography-guided group (HR, 0.60 [95% CI, 0.14 to 2.52], P = .48). Target lesion-related myocardial infarction occurred in 1 patient (0.1%) in the angiography-guided stent implantation group (P = .32). CONCLUSIONS AND RELEVANCE: Among patients requiring long coronary stent implantation, the use of IVUS-guided everolimus-eluting stent implantation, compared with angiography-guided stent implantation, resulted in a significantly lower rate of the composite of major adverse cardiac events at 1 year. These differences were primarily due to lower risk of target lesion revascularization. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01308281.

Genome editing offers promising solutions to genetic disorders by editing DNA sequences or modulating gene expression. The clustered regularly interspaced short palindromic repeats (CRISPR)/associated protein 9 (CRISPR/Cas9) technology can be used to edit single or multiple genes in a wide variety of cell types and organisms in vitro and in vivo. Herein, we review the rapidly developing CRISPR/Cas9-based technologies for disease modeling and gene correction and recent progress toward Cas9/guide RNA (gRNA) delivery based on viral and nonviral vectors. We discuss the relative merits of delivering the genome editing elements in the form of DNA, mRNA, or protein, and the opportunities of combining viral delivery of a transgene encoding Cas9 with nonviral delivery of gRNA. We highlight the lessons learned from nonviral gene delivery in the past three decades and consider their applicability for CRISPR/Cas9 delivery. We also include a discussion of bioinformatics tools for gRNA design and chemical modifications of gRNA. Finally, we consider the extracellular and intracellular barriers to nonviral CRISPR/Cas9 delivery and propose strategies that may overcome these barriers to realize the clinical potential of CRISPR/Cas9-based genome editing.

Carbon-based nanomaterials emerge as promising platforms for theranostic applications in disease treatment and tissue repair.

To understand the formation mechanism of magnetic moments at the edges of graphitic fragments, we carry out first-principles density-functional calculations for the electronic and magnetic structures of graphitic fragments with various spin and geometric configurations. We find that interedge and interlayer interactions between the localized moments can be explained in terms of interactions between the magnetic tails of the edge-localized states. In addition, the dihydrogenated edge states as well as Fe ad-atoms at the edge are studied in regard to the magnetic order and proximity effects.

We have developed a simple approach for the large-scale synthesis of water-soluble green carbon nanodots (G-dots) from many kinds of large food waste-derived sources. About 120 g of G-dots per 100 kg of food waste can be synthesized using our simple and environmentally friendly synthesis approach. The G-dots exhibit a high degree of solubility in water because of the abundant oxygen-containing functional groups around their surface. The narrow band of photoluminescence emission (400-470 nm) confirms that the size of the G-dots (∼4 nm) is small because of a similar quantum effects and emission traps on the surfaces. The G-dots have excellent photostability; their photoluminescence intensity decreases slowly (∼8%) under continuous excitation with a Xe lamp for 10 days. We carried out cell viability assay to assess the effect of cytotoxicity by introducing G-dots in cells such as Chinese hamster ovary cells (CHO-K1), mouse muscle cells (C2C12), and African green monkey kidney cells (COS-7), up to a concentration of 2 mg mL(-1) for 24 h. Due to their high photostability and low cytotoxicity, these G-dots are excellent probes for in vitro bioimaging. Moreover, the byproducts (not including G-dots) of G-dot synthesis from large food-waste derived sources promoted the growth and development of seedlings germinated on 3DW-supplemented gauze. Because of the combined advantages of green synthesis, high aqueous stability, high photostability, and low cytotoxicity, the G-dots show considerable promise in various areas, including biomedical imaging, solution state optoelectronics, and plant seed germination and/or growth.

Probiotics, including bacteria and yeast, are live microorganisms that have demonstrated beneficial effects on human health. Recently, probiotic bacteria are constantly being studied and their applications are also being considered in promising adjuvant treatments for various intestinal diseases. Clinical trials and in vivo experiments have extended our current understanding of the important roles that probiotics play in human gut microbiomeassociated diseases. It has been documented through many clinical trials that probiotics could shape the intestinal microbiota leading to potential control of multiple bowel diseases and promotion of overall wellness. In this review, we focused on the relationship between probiotics and the human gut microbiota and its roles in gut microbiome-associated diseases. Here, we also discuss future directions and research areas that need further elucidation in order to better understand the roles of probiotics in the treatment of intestinal diseases.

Silver nanoparticles (AgNPs) have found a variety of uses including biomedical materials; however, studies of the cytotoxicity of AgNPs by size effects are only in the beginning stage. In this study, we examined the size-dependent cellular toxicity of AgNPs using three different characteristic sizes (∼ 10, 50, and 100 nm) against several cell lines including MC3T3-E1 and PC12. The cytotoxic effect determined based on the cell viability, intracellular reactive oxygen species generation, lactate dehydrogenase release, ultrastructural changes in cell morphology, and upregulation of stress-related genes (ho-1 and MMP-3) was fairly size- and dose-dependent. In particular, AgNPs stimulated apoptosis in the MC3T3-E1 cells, but induced necrotic cell death in the PC12 cells. Furthermore, the smallest sized AgNPs (10 nm size) had a greater ability to induce apoptosis in the MC3T3-E1 cells than the other sized AgNPs (50 and 100 nm). These data suggest that the AgNPs-induced cytotoxic effects against tissue cells are particle size-dependent, and thus, the particle size needs careful consideration in the design of the nanoparticles for biomedical uses.