Identification of quantitative trait loci associated with flowering time in perilla using genotyping-by-sequencing.

Understanding the transition to the reproductive period is important for crop breeding. This information can facilitate the production of novel varieties that are better adapted to local environments or changing climatic conditions. Here, we report the development of a high-density linkage map based on genotyping-by-sequencing (GBS) for the genus perilla. Through GBS library construction and Illumina sequencing of an F2 population, a total of 9607 single-nucleotide polymorphism (SNP) markers were developed. The ten-group linkage map of 1309.39 cM contained 2518 markers, with an average marker density of 0.56 cM per linkage group (LG). Using this map, a total of six QTLs were identified. These quantitative trait loci (QTLs) are associated with three traits related to flowering time: days to visible flower bud, days to flowering, and days to maturity. Ortholog analysis conducted with known genes involved in the regulation of flowering time among different crop species identified GI, CO and ELF4 as putative perilla orthologs that are closely linked to the QTL regions associated with flowering time. These results provide a foundation that will be useful for future studies of flowering time in perilla using fine mapping, and marker-assisted selection for the development of new varieties of perilla.

Association between thyroid hormone levels, body composition and insulin resistance in euthyroid subjects with normal thyroid ultrasound: The Kangbuk Samsung Health Study.

OBJECTIVE: Thyroid hormones play crucial roles in the control of energy homoeostasis and can influence body composition. In contrast, the changes in body composition might influence thyroid hormone levels. We evaluated associations between thyroid hormone levels, body composition and insulin resistance in euthyroid subjects with normal thyroid ultrasound (US) findings. DESIGN AND PATIENTS: This retrospective cross-sectional study included 36 655 euthyroid subjects who joined the medical health check-up programme at our institution. Serum thyroid hormone levels were analysed in association with body fat percentage (BFP), skeletal muscle mass index (SMI) and homoeostatic model assessment of insulin resistance (HOMA-IR). Linear regression analyses were performed to evaluate relationships between thyroid hormone levels and anthropometric parameters. RESULTS: Mean age was 36.4 years, and 49% of subjects were female. In multiple linear regression analysis, serum-free triiodothyronine (FT3) levels exhibited positive associations with waist circumference (WC) and HOMA-IR and a negative association with body weight, body mass index (BMI) and SMI among both men and women. The association between serum-free thyroxine (FT4) levels and anthropometric markers showed inconsistent results in men and women. Serum thyroid-stimulating hormone (TSH) levels showed a positive association with HOMA-IR in both men and women. CONCLUSIONS: Lower SMI was significantly associated with higher serum FT3 levels, the active form of thyroid hormone, in both men and women. Higher insulin resistance was positively associated with serum FT3 levels and inversely associated with serum TSH levels in euthyroid subjects with normal thyroid US findings.

Association of low baseline free thyroxin levels with progression of coronary artery calcification over 4 years in euthyroid subjects: the Kangbuk Samsung Health Study.

OBJECTIVE: Overt and subclinical hypothyroidism are risk factors for atherosclerosis and cardiovascular diseases. It is unclear whether thyroid hormone levels within the normal range are also associated with atherosclerosis measured by coronary artery calcium (CAC). CONTEXT: This study aimed to examine the relationship between normal variations in thyroid function and changes in CAC. MEASUREMENTS: We conducted a 4-year retrospective study of 2173 apparently healthy men and women with normal thyroid hormone levels. Their free thyroxin (FT4), free triiodothyronin (FT3) and thyroid-stimulating hormone (TSH) levels were measured by electrochemiluminescent immunoassay. The CAC score (CACS) of each subject was measured by multidetector computed tomography in both 2010 and 2014. Progression of CAC was defined as a CACS change over 4 years > 0. RESULTS: The mean CACS changes over 4 years by quartiles of baseline FT4 level (lowest to highest) were 12·9, 8·43, 7·82 and 7·81 (P = 0·028). CAC progression was not significantly associated with either the baseline FT3 or TSH levels. The odds ratios (OR) for CAC progression over 4 years (highest vs lowest quartile for baseline FT4) were 0·647 (95% confidence interval (CI) 0·472-0·886) after adjustment for confounding factor, which were attenuated with further adjustment for lipid profiles, homoeostasis model assessment of insulin resistance, high-sensitivity C-reactive protein and hypertension [0·747 (95% CI 0·537-1·038)]. Quartiles of baseline FT3 or TSH level did not show any increased OR for CAC progression after adjustment for confounding factors. CONCLUSIONS: In this cohort of euthyroid men and women, a low baseline FT4 level was associated with a high risk of CACS progression over 4 years.

The relationship between serum fatty-acid binding protein 4 level and lung function in Korean subjects with normal ventilatory function.

BACKGROUND: The aim of this study was to assess the association of lung function with serum fatty-acid binding protein 4 (FABP4) in apparently healthy Korean adults. METHODS: In 495 participants in a health screening program, Force Exploratory Volume (FEV) 1 and Forced Vital Capacity (FVC) were assessed with standard spirometry. Subjects with obstructive (n = 19) and restrictive (n = 45) lung function were excluded from the analysis. Serum FABP4 level was measured by enzyme-linked immunosorbent assay and transformed into Ln(FABP4). 431 subjects with normal ventilator function (72.4% men, mean age 41 years) were included in the final analysis. RESULTS: Mean Ln(FABP4) significantly decreased in subjects from 1(st) quartile to 4(th) quartile of FVC (p = 0.008). Ln(FABP4) did not show significant differences across the quartile groups of FEV1. The odds ratio (OR) of being in the lowest quartile of FVC was 2.704 in subject with 3(rd) tertile of Ln(FABP4) after full adjustment for confounding variables {95% confidence interval (CI) 1.397 ~ 5.357}. OR of being in the lowest quartile of FEV1 was 1.822 (95% CI 1.021 ~ 3.298) in subjects with 3(rd) tertile of Ln(FABP4) after adjustment of age and sex, which was attenuated after full adjustment for confounding variables. CONCLUSION: Increased FABP4 level showed increased risk for reduced lung function in subjects with normal ventilatory function.

Higher association of coronary artery calcification with non-alcoholic fatty liver disease than with abdominal obesity in middle-aged Korean men: the Kangbuk Samsung Health Study.

BACKGROUND: It is uncertain whether non-alcoholic fatty liver disease (NAFLD) or abdominal obesity is more associated with atherosclerosis. The aim of this study was to determine whether NAFLD or abdominal obesity is more strongly associated with subclinical atherosclerosis represented by coronary artery calcification (CAC). METHODS: A total of 21,335 male participants in a health screening program (mean age 41 years) were enrolled. Ultrasonographic measurements of fatty liver and multi-detector computed tomography were performed to determine the coronary artery calcium score (CACS). The presence of CAC was defined as CACS > 0. Subjects were divided into four groups according to the presence or absence of NAFLD and/or abdominal obesity as assessed by waist-hip ratio (WHR) > 0.9. RESULTS: The presence of CAC was detected in 2,385 subjects (11.2%). The proportion of subjects with CAC was highest in the abdominal obesity only group (23.2%). After adjustment for age, diabetes history, hypertension, cigarette smoking, and physical inactivity, the odds ratio (OR) for CAC was the highest in the group with both abnormalities [1.465 (1.324-1.623)]. The NAFLD only group showed significantly increased OR for CAC compared to that in the abdominal obesity only group [1.286 (1.151-1.436) vs. 1.076 (0.939-1.233)]. CONCLUSION: Non-alcoholic fatty liver disease is more closely associated with CAC than abdominal obesity as assessed by the WHR. NAFLD could be considered an independent determinant of subclinical atherosclerosis as assessed by CAC.

Electroless chemical grafting of nitrophenyl groups on n-doped hydrogenated amorphous silicon surfaces.

The direct spontaneous grafting of 4-nitrophenyl molecules onto n-doped hydrogenated amorphous silicon (a-Si:H) surfaces without external ultraviolet, thermal, or electrochemical energy was invegtigated. Clean n-doped a-Si:H thin films were dipped in a solution of 4-nitrobenzenediazonium salts (PNBD) in acetonitrile. After the modified surfaces were rinsed, they were analyzed qualitatively and quantitatively by X-ray photoelectron spectroscopy (XPS) and atomic force microscopy (AFM). XPS and AFM results show that the reaction of an n-doped a-Si:H thin film with PNBD self-terminates without polymerization, after 5 h, and the surface number density of 4-nitrophenyl molecules is 4.2 x 10(15)/cm2. These results demonstrate that the spontaneous grafting of nitrophenyl layers onto n-doped a-Si:H thin films is an attractive pathway toward forming interfaces between a-Si:H and organic layers under ambient conditions.

Analysis of yield of eleutherosides B and E in Acanthopanax divaricatus and A. koreanum grown with varying cultivation methods.

An analysis of the yield of eleutherosides B and E in Acanthopanax divaricatus and A. koreanum was performed using high performance liquid chromatography to evaluate production by different cultivation methods. In A. divaricatus and A. koreanum, the total content of eleutherosides B and E was 2.466-7.360 mg/g varying by plant section, 3.886-11.506 mg/g by pinching site, 3.655-10.083 mg/g by planting time, and 3.652-10.108 mg/g by fertilizer ratio. Thus the total content of eleutherosides B and E in A. divaricatus and A. koreanum differed depending on cultivation methods. These results present useful information for high eleutheroside content applications in A. divaricatus and A. koreanum. This information can affect selection of plant section and cultivation methods for nutraceutical, pharmaceutical, and cosmeceutical material development.

Genome-wide association study (GWAS) with high-throughput SNP chip DNA markers identified novel genetic factors for mesocotyl elongation and seedling emergence in rice (Oryza sativa L.) using multiple GAPIT models.

This study employed a joint strategy high-density SNP Chip DNA markers and multiple Genome Association and Prediction Integrated Tool (GAPIT) models [(Bayesian-information and Linkage-disequilibrium Iteratively Nested Keyway (BLINK), Fixed and random model Circulating Probability Uniform (FarmCPU), General Linear Model (GLM), and Settlement of Mixed Linear Model (MLM) Under Progressively Exclusive Relationship (SUPER)], to investigate novel genetic factors controlling mesocotyl elongation and seedling emergence for direct-seeded rice. Genotype data (230,526 SNP Chip DNA makers) of 117 doubled haploid lines (derived from a cross between 93-11 (Oryza sativa L. ssp. indica) and Milyang352 (O. sativa L. ssp. japonica) were used to perform a Genome-Wide Association Study (GWAS). Results revealed the association between five (5) topmost significant SNP markers, of which number two [AX-155741269, Chr2: 15422406 bp, and AX-155200917, Chr7: 23814085 bp, explaining 37.5% and 13.8% of the phenotypic variance explained (PVE)] are linked to the mesocotyl elongation loci, while three (AX-282097034 and AX-283652873, Chr9: 9882817 bp and 1023383 bp, PVE 64.5%, and 20.2%, respectively, and AX-154356231, Chr1: 17413989 bp, PVE 21.1%) are tightly linked to the loci controlling seedling emergence. The qMEL2-1 and qSEM9-1 are identified as major QTLs explaining 37.5% and 64.5% of the PVE for mesocotyl elongation and seedling emergence, respectively. The AX-282097034 (Chr9: 9882817 bp) was co-detected by four GAPIT models (BLINK, FarmCPU, SUPER, and GLM), while AX-155741269 was co-detected by BLINK and SUPER. Furthermore, a high estimated heritability (Mesocotyl elongation: h2 = 0.955; seedling emergence: h2 = 0.863; shoot length: h2 = 0.707) was observed. Genes harbored by qMEL2-1 and qSEM9-1 have interesting annotated molecular functions that could be investigated through functional studies to uncover their roles during mesocotyl elongation and seedling emergence events in rice. Furthermore, the presence of genes encoding transcription factors, growth- and stress response, or signaling-related genes would suggest that mesocotyl elongation and seedling emergence from deep direct-seeded rice might involve an active signaling cascade and transport of molecules, which could be elucidated through functional analysis. Likewise, genomic selection analysis suggested markers useful for downstream marker-assisted selection (MAS).

Acceleration of wheat breeding: enhancing efficiency and practical application of the speed breeding system.

BACKGROUND: Crop breeding should be accelerated to address global warming and climate change. Wheat (Triticum aestivum L.) is a major food crop. Speed breeding (SB) and speed vernalization (SV) techniques for spring and winter wheat have recently been established. However, there are few practical examples of these strategies being used economically and efficiently in breeding programs. We aimed to establish and evaluate the performance of a breeder-friendly and energy-saving generation acceleration system by modifying the SV + SB system. RESULTS: In this study, a four-generation advancement system for wheat (regardless of its growth habits) was established and evaluated using an energy-efficient extended photoperiod treatment. A glasshouse with a 22-hour photoperiod that used 10 h of natural sunlight and 12 h of LED lights, and minimized temperature control during the winter season, was successful in accelerating generation. Even with one or two field tests, modified speed breeding (mSB) combined with a speed vernalization system (SV + mSB) reduced breeding time by more than half compared to traditional field-based methods. When compared to the existing SV + SB system, the SV + mSB system reduced energy use by 80% to maintain a 22-hour photoperiod. Significant correlations were found between the SV + mSB and field conditions in the number of days to heading (DTH) and culm length (CL). Genetic resources, recombinant inbred lines, and breeding materials that exhibited shorter DTH and CL values under SV + mSB conditions showed the same pattern in the field. CONCLUSIONS: The results of our SV + mSB model, as well as its practical application in wheat breeding programs, are expected to help breeders worldwide incorporate generation acceleration systems into their conventional breeding programs.

Rice (Oryza sativa L.) Grain Size, Shape, and Weight-Related QTLs Identified Using GWAS with Multiple GAPIT Models and High-Density SNP Chip DNA Markers.

This study investigated novel quantitative traits loci (QTLs) associated with the control of grain shape and size as well as grain weight in rice. We employed a joint-strategy multiple GAPIT (Genome Association and Prediction Integrated Tool) models [(Bayesian-information and Linkage-disequilibrium Iteratively Nested Keyway (BLINK)), Fixed and random model Circulating Probability Uniform (FarmCPU), Settlement of MLM Under Progressive Exclusive Relationship (SUPER), and General Linear Model (GLM)]-High-Density SNP Chip DNA Markers (60,461) to conduct a Genome-Wide Association Study (GWAS). GWAS was performed using genotype and grain-related phenotypes of 143 recombinant inbred lines (RILs). Data show that parental lines (Ilpum and Tung Tin Wan Hein 1, TTWH1, Oryza sativa L., ssp. japonica and indica, respectively) exhibited divergent phenotypes for all analyzed grain traits), which was reflected in their derived population. GWAS results revealed the association between seven SNP Chip makers and QTLs for grain length, co-detected by all GAPIT models on chromosomes (Chr) 1-3, 5, 7, and 11, were qGL1-1BFSG (AX-95918134, Chr1: 3,820,526 bp) explains 65.2-72.5% of the phenotypic variance explained (PVE). In addition, qGW1-1BFSG (AX-273945773, Chr1: 5,623,288 bp) for grain width explains 15.5-18.9% of PVE. Furthermore, BLINK or FarmCPU identified three QTLs for grain thickness independently, and explain 74.9% (qGT1Blink, AX-279261704, Chr1: 18,023,142 bp) and 54.9% (qGT2-1Farm, AX-154787777, Chr2: 2,118,477 bp) of the observed PVE. For the grain length-to-width ratio (LWR), the qLWR2BFSG (AX-274833045, Chr2: 10,000,097 bp) explains nearly 15.2-32% of the observed PVE. Likewise, the major QTL for thousand-grain weight (TGW) was detected on Chr6 (qTGW6BFSG, AX-115737727, 28,484,619 bp) and explains 32.8-54% of PVE. The qTGW6BFSG QTL coincides with qGW6-1Blink for grain width and explained 32.8-54% of PVE. Putative candidate genes pooled from major QTLs for each grain trait have interesting annotated functions that require functional studies to elucidate their function in the control of grain size, shape, or weight in rice. Genome selection analysis proposed makers useful for downstream marker-assisted selection based on genetic merit of RILs.

Inhibitory effect of ethanol extract of Magnolia officinalis on memory impairment and amyloidogenesis in a transgenic mouse model of Alzheimer's disease via regulating ß-secretase activity.

Alzheimer's disease (AD) is the most common form of dementia and is characterized by deposition of amyloid beta (Aß) in the brain. The components of the herb Magnolia officinalis are known to have antiinflammatory, antioxidative and neuroprotective activities. In this study we investigated the effects of ethanol extract of M. officinalis on memory dysfunction and amyloidogenesis in a transgenic mouse model of AD. Oral pretreatment of ethanol extract of M. officinalis (10 mg/kg in 0.05% ethanol) into drinking water for 3 months inhibited memory impairment and Aß deposition in the brain of Tg2576 mice. Ethanol extract of M. officinalis also decreased activity of ß-secretase, cleaving Aß from amyloid precursor protein (APP), and expression of ß-site APP cleaving enzyme 1 (BACE1), APP and its product, C99. Our results showed that ethanol extract of M. officinalis effectively prevented memory impairment via down-regulating ß-secretase activity.

Structural parts based on Municipal-Solid-Waste incineration ashes.

We investigated a novel processing technique of municipal solid waste incineration (MSWI) ashes. By using two thermodynamic driving forces - a strong alkaline activator and a compaction pressure, the otherwise relatively nonreactive MSWI ashes could form strong solids, with relatively high flexural and compressive strengths. The produced material was dense, with a low defect density. The effects of the compaction pressure range, the alkaline activator amount, and the MSWI fly ash to bottom ash ratio were examined. We also used 5 wt% class-C fly ash, 5 wt% class-F fly ash, and/or 1 wt% epoxy as additives. This study may open a door to advanced MSWI ash upcycling approaches, useful to environmental preservation and sustainability.

Autonomic Imbalance Increases the Risk for Non-alcoholic Fatty Liver Disease.

Background: Although autonomic imbalance is associated with an increased risk for metabolic disease, its effects on nonalcoholic fatty liver disease (NAFLD) remains unclear. We aimed to evaluate whether autonomic dysfunction predicts the risk for nonalcoholic fatty liver disease (NAFLD). Methods: A total of 33,899 participants without NAFLD who underwent health screening programs between 2011 and 2018 were enrolled. NAFLD was identified by ultrasonography. Autonomic activity was estimated using heart rate variability (HRV). Time domain [standard deviation of the normal-to-normal interval (SDNN) and root mean square difference (RMSSD)]; frequency domain [total power (TP), low frequency (LF), and high frequency (HF), and LF/HF ratio were analyzed. Findings: A total 6,466 participants developed NAFLD within a median of 5.7 years. Subjects with incident NAFLD showed decreased overall autonomic modulation and vagal activity with lowered SDNN, RMSSD, HF, normalized HF, compared to those without NAFLD. As the SDNN, RMSSD, TP, LF, and HF tertiles increased, the risk of NAFLD decreased with tertile 1 being the reference group [the hazard ratios (95% confidence intervals) of tertile 3 were 0.90 (0.85-0.96), 0.83 (0.78-0.88), 0.91 (0.86-0.97), 0.93 (0.87-0.99) and 0.89 (0.83-0.94), respectively] after adjusting for potential confounders. The risk for NAFLD was significantly higher in subjects in whom sustained elevated heart rate, normalized LF, and LF/HF ratio values than in those with sustained decrease in these parameters during follow-up. Conclusions: Overall autonomic imbalance, decreased parasympathetic activity, and recently increased sympathetic activity might increase the risk of NAFLD.

An Integrated Approach of QTL Mapping and Genome-Wide Association Analysis Identifies Candidate Genes for Phytophthora Blight Resistance in Sesame (Sesamum indicum L.).

Phytophthora blight (PB) caused by Phytophthora nicotianae is a highly destructive disease in sesame (Sesamum indicum L.). In this study, we used linkage mapping and genome-wide association study (GWAS) to identify quantitative trait loci (QTL) and candidate genes associated with PB resistance. The QTL mapping in 90 RILs of the Goenbaek × Osan cross using genotyping-by-sequencing detected significant QTLs for PB resistance on chromosome 10, explaining 12.79%-13.34% of phenotypic variation. Association of this locus to PB resistance was also revealed through bulked segregant analysis in second RIL population (Goenbaek × Milsung cross) comprising 188 RILs. The GWAS of 87 sesame accessions evaluated against three P. nicotianae isolates identified 29 SNPs on chromosome 10 significantly associated with PB resistance. These SNPs were located within a 0.79 Mb region, which co-located with the QTL intervals identified in RIL populations, and hence scanned for identifying candidate genes. This region contained several defense-related candidate R genes, five of which were selected for quantitative expression analysis. One of these genes, SIN_1019016 was found to show significantly higher expression in the resistant parent compared to that in the susceptible parents and selected RILs. Paired-end sequencing of the gene SIN_1019016 in parental cultivars revealed two synonymous SNPs between Goenbaek and Osan in exon 2 of coding DNA sequence. These results suggested SIN_1019016 as one of the candidate gene conferring PB resistance in sesame. The findings from this study will be useful in the marker-assisted selection as well as the functional analysis of PB resistance candidate gene(s) in sesame.

The relationship between Receptor Activator of Nuclear Factor-kappaB Ligand (RANKL) gene polymorphism and aortic calcification in Korean women.

The aim of this study was to investigate the relationship between RANKL gene polymorphisms and aortic calcification in Korean women. In 237 healthy Korean women, aortic calcification in thoracic and abdominal aorta was examined in simple radiologic method and lumbar spine and femoral neck BMD were examined by dual energy X-ray absorptiometry. Serum OPG levels, bone turnover markers, such as ALP levels and urine deoxypyridinoline levels, and urine calcium excretion were measured. Genotyping of two RANKL gene polymorphisms, rs2277438 and rs9594782, was performed by allelic discrimination using the 5' nuclease polymerase chain reaction assay. The subjects with CT/CC genotypes of the rs9594782 polymorphism had a 3.9 times higher risk of aortic calcification compared with TT genotype. This significance was significant even after adjustment for age, BMI, blood pressure, fasting plasma glucose, serum high and low-density lipoprotein cholesterol levels. Mean levels of urine deoxypyridinoline were significantly higher in the subjects with AG/GG genotypes of the rs2277438 polymorphism compared with AA genotype, and this significance was persistent even after adjustment for age and BMI. There were no associations of mean values for age, BMI, serum OPG and ALP levels, urine calcium excretion, and BMD with RANKL gene polymorphisms. The RANKL gene rs9594782 polymorphism was associated with aortic calcification in Korean women. Rs2277438 polymorphism showed significant association with urine deoxypyridinoline levels, a bone resorption marker. These results suggest its role on vascular calcification and bone metabolism in humans.

Serum lipoprotein(a) levels and insulin resistance have opposite effects on fatty liver disease.

BACKGROUND AND AIMS: High lipoprotein(a) [Lp(a)] levels are associated with increased risk of cardiovascular disease. However, the association between Lp(a) and fatty liver disease (FLD) remains controversial. Therefore, we analyzed the relationship between FLD and serum Lp(a) levels in Korean adults. METHODS: A total of 22,534 participants who underwent a routine health screening program at Kangbuk Samsung Hospital in 2010 and 2014 were enrolled. Anthropometric and biochemical parameters, including Lp(a), were measured. The presence of FLD was assessed using abdominal ultrasonography. Odds ratios (ORs) for the presence of FLD were analyzed in quartile groups of serum Lp(a) levels using logistic regression. We divided the participants into four groups according to the median values of Lp(a) and homeostasis model assessment for insulin resistance (HOMA-IR). RESULTS: Among the total study population, 3030 (13.4%) participants had fatty liver disease. The mean Lp(a) level was lower in subjects with FLD than in those without (70.0 vs 73.8 nmol/L, p < 0.001). The OR for FLD was the lowest in the fourth Lp(a) quartile group, using the first quartile group as the reference group after adjusting for confounding factors [0.815; 95% confidence interval (CI) 0.725-0.916]. When the OR for FLD was analyzed in four groups divided by the median values of Lp(a) and HOMA-IR, the low Lp(a)-high HOMA-IR group had the greatest OR for FLD, using the high Lp(a)-low HOMA-IR group as the reference (1.903; 95% CI 1.679-2.158). CONCLUSIONS: Serum Lp(a) levels were inversely associated with the presence of FLD. Subjects with low Lp(a) and high insulin resistance (IR) showed higher risk of FLD than those with high Lp(a) and low IR, suggesting the opposite associations of Lp(a) and IR with FLD.

Decreased Vagal Activity and Deviation in Sympathetic Activity Precedes Development of Diabetes.

OBJECTIVE: The objective of this study was to examine whether altered heart rate variability (HRV) could predict the risk of diabetes in Asians. RESEARCH DESIGN AND METHODS: A cohort study was conducted in 54,075 adults without diabetes who underwent 3-min HRV measurement during health checkups between 2011 and 2014 at Kangbuk Samsung Hospital. We analyzed the time domain (SD of the normal-to-normal interval [SDNN] and root mean square differences of successive normal-to-normal intervals [RMSSD]) and the frequency domain (total power, normalized low-frequency power [LF], and normalized high-frequency power [HF] and LF/HF ratio). We compared the risk of diabetes until 2017 according to tertiles of heart rate and HRV variables, with tertile 1 serving as the reference group. RESULTS: During 243,758.2 person-years, 1,369 subjects were diagnosed with diabetes. Both time and frequency domain variables were lower in the group with diabetes, with the exception of those with normalized LF and LF/HF ratio. In Cox analysis, as SDNN, RMSSD, and normalized HF tertiles increased, the risk of diabetes decreased (hazard ratios [95% CIs] of tertile 3: 0.81 [0.70-0.95], 0.76 [0.65-0.90], and 0.78 [0.67-0.91], respectively), whereas the risk of diabetes increased in the case of heart rate, normalized LF, and LF/HF ratio (hazard ratios [95% CIs] of tertile 3: 1.41 [1.21-1.65], 1.32 [1.13-1.53], and 1.31 [1.13-1.53), respectively) after adjusting for age, sex, BMI, smoking, drinking, systolic blood pressure, lipid level, CRP, and HOMA of insulin resistance. CONCLUSIONS: Abnormal HRV, especially decreased vagal activity and deviation in sympathovagal imbalance to sympathetic activity, might precede incident diabetes.

Inhibitory effect of proanthocyanidin on ultraviolet B irradiation-induced melanogenesis.

Repetitive exposure of the skin to ultraviolet (UV) radiation induces various adverse effects, including skin thickening, wrinkle formation, inflammation, and pigmentation. Various natural and synthetic compounds were studied to determine whether they might prevent UV induction of these adverse effects. In particular, naturally occurring antioxidants were used for regulating skin damage induced by UV radiation since several antioxidants were found to inhibit photoaging through prevention of collagen synthesis via inhibition of matrix metalloproteinases (MMP) and/or decrease of melanin synthesis. The L values in pigmented skin were lower at 4 wk (52.97 +/- 2.09) than at the start of this study (0 wk, 62.89 +/- 0.56) in the control. In the proanthocyanidin mixture group, the L value was increased (56.83 +/- 1.71) similar to the control (52.97 +/- 2.09). Proanthocyanidin also suppressed the expression levels of tyrosinase by 20-40%, and blocked the expression of MITF, TRP-1, and TRP-2, which are factors implicated in the control of melanogenesis. Taken together, these data indicate that proanthocyanidin may be useful to attenuate UVB-induced melanogenesis.

Metabolic Obesity Phenotypes and Thyroid Cancer Risk: A Cohort Study.

BACKGROUND: No cohort studies have evaluated the effect of obesity on the incidence of thyroid cancer according to metabolic health status. Therefore, this study examined the association of body mass index (BMI) and metabolic health status with thyroid cancer risk. METHODS: A cohort study was performed involving 255,051 metabolically healthy (MH) and metabolically unhealthy (MUH) adults free of thyroid cancer at baseline who were followed for a median of 5.3 years. A parametric proportional hazard model was used to estimate the adjusted hazard ratio (aHR) and confidence interval (CI). RESULTS: During 1,402,426.3 person-years of follow-up, 2927 incident thyroid cancers were identified. Among men, the multivariable aHR for thyroid cancer comparing obesity, defined as a BMI ≥25 kg/m2, with a BMI of 18.5-22.9 kg/m2 was 1.47 [CI 1.12-1.93] in MH individuals, whereas the corresponding HR in MUH individuals was 1.26 [CI 1.03-1.53]. Among women, the corresponding HR in MH individuals was 1.05 [CI 0.80-1.36], whereas the corresponding HR in MUH individuals was 1.43 [CI 1.22-1.69]. Increasing quartiles of waist circumference were positively associated with risk of thyroid cancer in MUH men and women (p for trend <0.005) but not in MH individuals. CONCLUSIONS: In both MH and MUH men, obesity was associated with an increased risk of incident thyroid cancer, indicating excessive adiposity per se as an independent risk factor for thyroid cancer. Conversely, women with MUH obesity but not MH obesity were found to have an increased risk of thyroid cancer, indicating that obesity with accompanying metabolic abnormalities may affect thyroid cancer risk in women.

Resveratrol, an activator of SIRT1, improves ER stress by increasing clusterin expression in HepG2 cells.

Endoplasmic reticulum stress (ER stress) is involved in lipid metabolism and lipotoxicity and can lead to apoptosis. Resveratrol, a sirtuin 1 (SIRT1) agonist, prevents ER stress and improves ER stress-induced hepatic steatosis and cell death. Clusterin is a secreted chaperone and has roles in various physiological processes. However, changes in the expression of clusterin upon ER stress and the connection between SIRT1 and clusterin in protection against ER stress are not well known. In cells treated with tunicamycin, resveratrol increased the expression of clusterin mRNA and protein and the secreted clusterin protein level in conditioned medium. Resveratrol decreased protein expression of the ER stress markers, p-PERK, p-IRE1α, and CHOP, and increased the expression of the ER-associated degradation (ERAD) factors, SEL1L and HRD1, in tunicamycin-treated cells. However, no changes in the expression of these genes were observed in clusterin siRNA-transfected cells. Moreover, increased LAMP2 and LC3 expression and decreased Rubicon expression were observed in cells treated with resveratrol or secreted clusterin. These data suggest that SIRT1 activation by resveratrol attenuates ER stress by promoting protective processes such as ERAD and autophagy pathways and that these protective effects are mediated by clusterin.