Determination of progressive stages of type 2 diabetes in a 45% high-fat diet-fed C57BL/6J mouse model is achieved by utilizing both fasting blood glucose levels and a 2-hour oral glucose tolerance test.

Type 2 diabetes is considered one of the top ten life-threatening diseases worldwide. Following economic growth, obesity and metabolic syndrome became the most common risk factor for type 2 diabetes. In this regard, high-fat diet-fed C57BL/6J mouse model is widely used for type 2 diabetes pathogenesis and novel therapeutics development. However, criteria for classifying type 2 diabetes progressive stages in this mouse model are yet to be determined, led to the difficulty in experimental end-point decision. In this study, we fed C57BL/6J male mice with 45% high-fat diet, which is physiologically close to human high-fat consumption, and evaluated the progression of type 2 diabetes. After consuming high-fat diet for 4 weeks, mice developed metabolic syndrome, including obesity, significant increase of fasting plasma cholesterol level, elevation of both C-peptide and fasting blood glucose levels. By combining both fasting blood glucose test and 2-hour-oral glucose tolerance test, our results illustrated clear progressive stages from metabolic syndrome into pre-diabetes before onset of type 2 diabetes in C57BL/6J mice given a 45% high-fat diet. Besides, among metabolic measurements, accumulating body weight gain > 16.23 g for 12 weeks could be utilized as a potential parameter to predict type 2 diabetes development in C57BL/6J mice. Thus, these results might support future investigations in term of selecting appropriate disease stage in high-fat diet-fed C57BL/6J mouse model for studying early prevention and treatment of type 2 diabetes.

PTK7, a Catalytically Inactive Receptor Tyrosine Kinase, Increases Oncogenic Phenotypes in Xenograft Tumors of Esophageal Squamous Cell Carcinoma KYSE-30 Cells.

Protein tyrosine kinase 7 (PTK7), a catalytically defective receptor protein tyrosine kinase, is upregulated in tumor tissues and cell lines of esophageal squamous cell carcinoma (ESCC). We showed that PTK7 plays an oncogenic role in various ESCC cell lines. However, its role as an oncogene has not been demonstrated in vivo. Here, we examined the influence of PTK7 on the tumorigenic potential of ESCC KYSE-30 cells, which are known to establish xenograft tumors. Overexpression of PTK7 enhanced the proliferation, adhesion, wound healing, and migration of KYSE-30 cells, and these effects were reversed by the knockdown of PTK7. PTK7 overexpression and knockdown, respectively, increased and decreased the tyrosine phosphorylation of cellular proteins and the phosphorylation of ERK, AKT, and FAK, which are important for cell proliferation, survival, adhesion, and migration. Additionally, PTK7 overexpression and silencing, respectively, increased and decreased the weight, volume, and number of Ki-67-positive proliferating cells in xenograft tumors of KYSE-30 cells. Therefore, we propose that PTK7 plays an important role in the tumorigenesis of ESCC cells in vivo and is a potential therapeutic target for ESCC.

Acetyl-CoA carboxylase-1/2 blockade locks dendritic cells in the semimature state associated with FA deprivation by favoring FAO.

Immunometabolism is rising as an intriguing topic that reveals the connection between immune cell function and metabolic processes. Especially, fatty acid metabolism plays an essential role in the dendritic cells (DCs) during the differentiation and maturation period. We questioned whether regulation of acetyl-CoA carboxylases 1 and 2-(ACC1/2), the core enzymes of fatty acid synthesis (FAS), would control DC function. Here, we report that blocking ACC1/2 to prevent FAS during DC maturation switched their cellular metabolism into fatty acid oxidation to fuel oxidative phosphorylation. This action turned DCs to utilize exogenous fatty acids to sustain their basal energy demand and maintain a stable cellular respiration rate. Coincidentally, under the ACC1/2 inhibitor treatment, LPS-treated DCs exhibited a semimaturation phenotype with a maturation-resistance feature, with decreased expression of costimulatory molecules including CD86 and CD40, along with the reduction of IL-12 and IL-6. The migratory capability of DCs has been known to relate to the glycolysis pathway, and here we showed that the ACC1/2 blockade did not affect the expression of CCR7 and DC migration. Furthermore, we found that under the ACC1/2 blocking condition, DCs pulsed with OVA failed to activate OVA-specific CD4+ T cell proliferation even though their antigen uptake capacity was intact. Together, our data suggest ACC1/2 as a promising target to control DC fate.

Inference of a causal relation between low-density lipoprotein cholesterol and hypertension using mendelian randomization analysis.

BACKGROUND: It is known in some studies that higher the LDL-C, the greater the risk of developing cardiovascular disease. However, studies of the causal effects between LDL-C and hypertension are limited by their observational study design, and genetic epidemiology studies of associations between LDL-C and hypertension are lacking, as are studies using data for Koreans. In this study, we confirmed the causal effect of LDL-C on hypertension using Korean chip data. METHOD: The epidemiology and genotype data were collected from the Korean Genome and Epidemiology Study conducted by the Korea National Institute of Health and covered 20,701 subjects. Single-nucleotide polymorphisms associated with LDL-C were selected (p-value < 5 × 10- 8) from the Global Lipids Genetics Consortium database, and Mendelian randomization analysis (MRA) was performed with counted genetic risk scores and weighted genetic risk scores (WGRSs) for 24 single-nucleotide polymorphisms. RESULT: The assumptions for MRA were statistically confirmed, and WGRSs showed a strong association with LDL-C. Interestingly, while the relationship between LDL-C and hypertension was not statistically significant in the observational study, MRA study demonstrated that the risk of hypertension increased as LDL-C increased in both men and women. CONCLUSIONS: The results of this study confirmed that the relationship between LDL-C and hypertension is greatly influenced by genetic information.

The blockade of cytoplasmic HMGB1 modulates the autophagy/apoptosis checkpoint in stressed islet beta cells.

High mobility group (HMGB1) is an alarmin known to be harmful to pancreatic beta cells and associated with diabetes mellitus pathogenesis and pancreatic islet graft failure. It has been long thought that the suppression of HMGB1 molecule is beneficial to the beta cells. However, recent studies have indicated that cytoplasmic HMGB1 (cHMGB1) could function as a modulator to relieve cells from apoptotic stress by autophagy induction. Particularly, pancreatic beta cells have been known to utilize the autophagy-to-apoptosis switch when exposed to hypoxia or lipotoxicity. This study aimed to investigate the beta cells under hypoxic and lipotoxic stress while utilizing a small molecule inhibitor of HMGB1, inflachromene (ICM) which can suppress cHMGB1 accumulation. It was revealed that under cellular stress, blockade of cHMGB1 accumulation decreased the viability of islet grafts, primary islets and MIN6 cells. MIN6 cells under cHMGB1 blockade along with lipotoxic stress showed decreased autophagic flux and increased apoptosis. Moreover, cHMGB1 blockade in HFD-fed mice produced unfavorable outcomes on their glucose tolerance. In sum, these results suggested the role of cHMGB1 within beta cell autophagy/apoptosis checkpoint. Given the importance of autophagy in beta cells under apoptotic stresses, this study might provide further insights regarding HMGB1 and diabetes.

Burden of male hardcore smokers and its characteristics among those eligible for lung cancer screening.

BACKGROUND: There are few data available about hardcore smokers and their behavioral characteristics among the lung cancer screening (LCS) population. The study investigated the burden of hardcore smokers within the LCS population, and determine the characteristics of hardcore smokers using nationally representative data in South Korea. METHODS: We used data from 2007 to 2012 from the Korean National Health and Nutrition Examination Survey. This study enrolled current male smokers aged 55-74 years. Among them, subjects eligible for LCS were defined as these populations with smoking histories of at least 30 PY. Hardcore smoking was defined as smoking >15 cigarettes per day, with no plan to quit, and having made no attempt to quit. Multivariate logistic regression analyses were used to estimate associations between hardcore smokers and various sociodemographic and other variables. RESULTS: The proportion of hardcore smokers among those who met LCS eligibility criteria decreased from 2007 to 2012 (from 39.07 to 29.47% of the population) but did not change significantly thereafter (P = 0.2770), and that proportion was consistently 10-15% higher than that of hardcore smokers among all male current smokers. The proportion without any plan to quit smoking decreased significantly from 54.35% in 2007 to 38.31% in 2012. However, the smokers who had made no intentional quit attempt in the prior year accounted for more than half of those eligible for LCS, and the proportion of such smokers did not change significantly during the study period (50.83% in 2007 and 51.03% in 2012). Multivariate logistic regression analyses showed that hardcore smokers were older (OR = 1.05, 95% confidence interval [CI] 1.01-1.09) than non-hardcore smokers. Hardcore smokers exhibited higher proportion of depression (OR = 6.55, 95% CI 1.75-24.61) and experienced extreme stress more frequently (OR = 1.93, 95% CI 1.13-3.29). Smokers who did not receive smoking cessation education within the past year were significantly more likely to be hardcore smokers (OR = 4.15, 95% CI 1.30-13.22). CONCLUSIONS: It is important to identify a subset of smokers unwilling or minimally motivated to quit within the context of lung cancer screening. Anti-smoking education should be enhanced to influence hardcore smokers' behavior.

Applicability of Aerosol Deposition Process for flexible electronic device and determining the Film Formation Mechanism with Cushioning Effects.

In this paper, we demonstrated the feasibility of the Aerosol Deposition (AD) method which can be adapted as a future fabrication process for flexible electronic devices. On the basis of this method's noticeable advantages such as room-temperature processing, suitability for mass production, wide material selectivity, and direct fabrication on a flexible substrate, we fabricated and evaluated a flexible conductive bridge random access memory (CBRAM) to confirm the feasibility of this method. The CBRAM was fabricated by the AD-method, and a novel film formation mechanism was observed and analyzed. Considering that the analyzed film formation mechanism is notably different with previously reported for film formation mechanisms of the AD method, these results of study will provide strong guidance for the fabrication of flexible electronic device on ductile substrate.

Metabolic syndrome epidemic among Korean adults: Korean survey of Cardiometabolic Syndrome (2018).

BACKGROUND AND AIMS: Little information exists on the prevalence of metabolic syndrome (MetS) in Korea since 2007. We aimed to provide up-to-date estimates of the prevalence of MetS and its trend in the general adult population in Korea. METHODS: We compared the prevalence and pattern of MetS among participants in the Korean National Health and Nutrition Examination Surveys (KNHANES) IV (2007-2009), V (2010-2012), and VI (2013-2015), aged ≥19 years. Data from the 2005 census of the Korean population were presented according to age standardization. RESULTS: The overall age-standardized prevalence of MetS in 2013-2015 was 20.3% (95% confidence interval [CI], 19.6%-21%). Since 2007, the overall prevalence of MetS has remained stable, whereas the prevalences among men and women, respectively, have increased and decreased slightly. By contrast, the prevalence of MetS among men aged 19-49 years has shown an increasing tendency since 2007. Moreover, nearly 40% of women aged ≥60 years had MetS in 2013-2015. Among the five components of MetS, only elevated fasting glucose level has shown an increasing trend since 2007 in both men and women. As the family income and educational level decreased, the prevalence of MetS increased. CONCLUSIONS: The overall prevalence of MetS has remained stable since 2007. However, the prevalence of MetS was higher in middle-aged men and women aged ≥60 years. Considering the close association between MetS and socioeconomic status, age- and sex-specific strategies should be developed at the national level for the treatment and prevention of MetS in Korea.

Incident-angle-controlled semitransparent colored perovskite solar cells with improved efficiency exploiting a multilayer dielectric mirror.

See-through perovskite solar cells with high efficiency and iridescent colors are demonstrated by employing a multilayer dielectric mirror. A certain amount of visible light is used for wide color gamut semitransparent color generation, which can be easily tuned by changing an angle of incidence, and a wide range of visible light is efficiently reflected back toward a photoactive layer of the perovskite solar cells by the dielectric mirror for highly efficient light-harvesting performance, thus achieving 10.12% power conversion efficiency. We also rigorously examine how the number of pairs in the multilayer dielectric mirror affects optical properties of the colored semitransparent perovskite solar cells. The described approach can open the door to a large number of applications such as building-integrated photovoltaics, self-powered wearable electronics and power-generating color filters for energy-efficient display systems.

Highly Efficient Colored Perovskite Solar Cells Integrated with Ultrathin Subwavelength Plasmonic Nanoresonators.

Highly efficient colored perovskite solar cells that exploit localized surface plasmon resonances in ultrathin subwavelength plasmonic nanoresonators are demonstrated. Localized resonances in ultrathin metal nano-strip optical resonators consisting of an array of metallic subwavelength nanowires on a transparent substrate, fabricated by using low-cost nanoimprint lithography over a large area, lead to a sharp peak in a reflection spectrum for distinctive color generation with angle-insensitive property up to 60°, and simultaneously transmit the complementary spectrum of visible light that can be efficiently harvested by the perovskite solar cells for electric power generation. The plasmonic color filter-integrated perovskite solar cells provide 10.12%, 8.17% and 7.72% of power conversion efficiencies with capabilities of creating vivid reflective red, green and blue colors. The scheme described in this work could be applied to a variety of applications such as power-generating decorations, tandem cells, power-saving wearable devices and energy-efficient reflective display technologies.