Recovery from parenteral nutrition-associated cholestasis takes approximately two months in very low birth weight infants.

AIM: To investigate the clinical characteristics and course of parenteral nutrition-associated cholestasis (PNAC) in very low birth weight (VLBW) infants. METHODS: The charts of VLBW infants were retrospectively reviewed. The clinical characteristics of infants with and without PNAC were compared, trends in liver enzymes were investigated, and the characteristics of infants with PNAC were analysed based on age of onset. RESULTS: PNAC was observed in 53 (13.2%) of 403 infants who survived and completed follow-up and was associated with significantly lower gestational age, birth weight, and adverse neonatal outcomes. PNAC started at a median 32 (interquartile range 23-47) days, PN was applied for 53 (34.5-64.5) days, the maximum direct bilirubin (DB) was observed at 63 (50-76) postnatal days, and PNAC resolved at 94 (79-122) postnatal days postnatal age. PNAC lasted 61 (38-89.5) days. AST and ALT normalised at 111 (100.3-142.0) and 109.5 (97-161.3) postnatal days. Infants with early-onset PNAC had significantly longer PN duration, higher maximum DB, and higher maximum AST than those with late-onset PNAC. CONCLUSION: Elevated DB, AST, and ALT persist for a long period after discontinuing PN. We suggest a cautious approach that involves waiting and reducing the frequency of additional repetitive examinations.

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.

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.

Coronary Artery Calcium Score as a Sensitive Indicator of Cardiovascular Disease in Patients with Type 2 Diabetes Mellitus: A Long-Term Cohort Study.

BACKGRUOUND: Coronary artery calcium score (CACS) has become an important tool for evaluating cardiovascular disease (CVD). This study evaluated the significance of CACS for future CVD through more than 10 years of follow-up in asymptomatic Korean populations with type 2 diabetes mellitus (T2DM) known to have a relatively low CACS burden. METHODS: We enrolled 981 asymptomatic T2DM patients without CVD at baseline who underwent CACS evaluation using multidetector computed tomography between January 2008 and December 2014. They were grouped into five predefined CACS categories based on Agatston scores and followed up by August 2020. The primary endpoint was incident CVD events, including coronary, cerebrovascular, and peripheral arterial disease. RESULTS: The relative risk of CVD was significantly higher in patients with CACS ≥10, and the significance persisted after adjustment for known confounders. A higher CACS category indicated a higher incidence of future CVD: hazard ratio (95% confidence interval) 4.09 (1.79 to 9.36), 12.00 (5.61 to 25.69), and 38.79 (16.43 to 91.59) for 10≤ CACS <100, 100≤ CACS <400, and CACS ≥400, respectively. During the 12-year follow-up period, the difference in event-free survival more than doubled as the category increased. Patients with CACS below 10 had very low CVD incidence throughout the follow-up. The receiver operating characteristic analysis showed better area under curve when the CACS cutoff was 10 than 100. CONCLUSION: CACS can be a sensitive marker of CVD risk. Specifically, CACS above 10 is an indicator of CVD high-risk requiring more intensive medical treatment in Koreans with T2DM.

Increased Risk of NAFLD in Adults with Glomerular Hyperfiltration: An 8-Year Cohort Study Based on 147,162 Koreans.

This study evaluated whether glomerular hyperfiltration (GHF) could predict nonalcoholic fatty liver disease (NAFLD) and fibrosis. A longitudinal cohort study including 147,479 participants aged 20-65 years without NAFLD and kidney disease at baseline was performed. GHF cutoff values were defined as age- and sex-specific estimated glomerular filtration rate (eGFRs) above the 95th percentile, and eGFR values between the 50th and 65th percentiles were used as reference groups. NAFLD was diagnosed via abdominal ultrasonography, and the fibrosis status was evaluated using the NAFLD fibrosis score and Fibrosis-4. During 598,745 person years of follow-up (median, 4.6 years), subjects with GHF at baseline had the highest hazard ratio (HR) for the development of NAFLD (HR 1.21; 95% CI 1.14-1.29) and fibrosis progression (HR 1.42; 95% CI 1.11-1.82) after adjusting for confounding factors. A higher baseline eGFR percentile maintained a higher risk of NAFLD and fibrosis probability. The persistent GHF group during follow-up had the highest HR for NAFLD compared to the persistent non-GHF group (HR 1.31; 95% CI 1.14-1.51). These results were consistent in all subgroups and statistically more prominent in participants without diabetes. GHF was positively associated with increased risk of NAFLD and probability of liver fibrosis in healthy adults.

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.

Genetic diversity analysis of Korean peanut germplasm using 48 K SNPs 'Axiom_Arachis' Array and its application for cultivar differentiation.

Cultivated peanut (Arachis hypogaea) is one of the important legume oilseed crops. Cultivated peanut has a narrow genetic base. Therefore, it is necessary to widen its genetic base and diversity for additional use. The objective of the present study was to assess the genetic diversity and population structure of 96 peanut genotypes with 9478 high-resolution SNPs identified from a 48 K 'Axiom_Arachis' SNP array. Korean set genotypes were also compared with a mini-core of US genotypes. These sets of genotypes were used for genetic diversity analysis. Model-based structure analysis at K = 2 indicated the presence of two subpopulations in both sets of genotypes. Phylogenetic and PCA analysis clustered these genotypes into two major groups. However, clear genotype distribution was not observed for categories of subspecies, botanical variety, or origin. The analysis also revealed that current Korean genetic resources lacked variability compared to US mini-core genotypes. These results suggest that Korean genetic resources need to be expanded by creating new allele combinations and widening the genetic pool to offer new genetic variations for Korean peanut improvement programs. High-quality SNP data generated in this study could be used for identifying varietal contaminant, QTL, and genes associated with desirable traits by performing mapping, genome-wide association studies.

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.

Neonatal Rotavirus-Associated Leukoencephalopathy Is One of the Main Causes of Fifth-Day Fits.

Our province recently experienced an outbreak of neonatal rotavirus-associated leukoencephalopathy. This study aimed to verify whether rotavirus-associated leukoencephalopathy constituted fifth-day fits, which prevailed in Europe and Australia between the 1970s and mid-1980s. Of 118 full-term neonates who were admitted between 2008 and 2017 due to seizures, those who fulfilled the following criteria for fifth-day fits were included: healthy full-term neonates prior to seizures; absence of perinatal asphyxia; seizure onset during 4-6 days of age; and no known cause of neonatal seizures. Overall, 54 patients (45.8%) met the criteria for fifth-day fits. Of them, 44 patients (81.5%) also had rotavirus-associated leukoencephalopathy. The mean annual incidence of fifth-day fits was 5.4 cases, which peaked in 2012-2013 (13 cases) and became zero in 2017. Fifth-day fits with rotavirus-associated leukoencephalopathy accounted for 37.2% of neonatal seizures, which peaked at 70.6% in 2012, and gradually reduced to zero in 2017. Concordance of clinical features between rotavirus-associated leukoencephalopathy and fifth-day fits and their epidemic-like features suggest that rotavirus-associated leukoencephalopathy is one of the main causes of fifth-day fits.

The forehead is a better site than the sternum to check transcutaneous bilirubin during phototherapy in sick infants.

BACKGROUND: To confirm the accuracy of transcutaneous bilirubin (TcB) in the neonatal intensive care unit both with and without phototherapy, and compare forehead and sternum as the TcB assessment site. METHODS: We simultaneously assessed the total serum bilirubin (TSB) and TcB at the forehead and sternum, using a JM-103 bilirubinometer. We analyzed the correlation between the TSB and TcB assessed at the forehead and sternum, with measurements classified as 'without phototherapy' (before phototherapy and > 24 hours after phototherapy discontinuation) and 'with phototherapy' (after 24 hours of phototherapy). RESULTS: There were 1,084 paired forehead and sternum TcB measurements, with the corresponding TSB measurement, from 384 infants. Their mean gestational age of 35.4 ± 3.2 weeks (62% were preterm) and a mean birth weight of 2434 ± 768 grams, and TSB was 6.61 ± 3.56 mg/dL. Without phototherapy, TcB values at the forehead and sternum were correlated well to the TSB value (r = 0.925 and 0.915, respectively). With phototherapy, TcB values at the forehead and sternum were significantly correlated with the TSB value, but TcB at the forehead (r = 0.751) was a better match to the TSB than was TcB at the sternum (r = 0.668). Additionally, Bland-Altman plots showed a greater degree of underestimation of the TSB by TcB at the sternum with phototherapy. CONCLUSIONS: TcB was more accurate in infants not receiving phototherapy. During phototherapy, it is better to assess TcB at the forehead rather than at the sternum.

Serum Transferrin Predicts New-Onset Type 2 Diabetes in Koreans: A 4-Year Retrospective Longitudinal Study.

BACKGROUND: It is well known that high serum ferritin, a marker of iron storage, predicts incident type 2 diabetes. Limited information is available on the association between transferrin, another marker of iron metabolism, and type 2 diabetes. Thus, we investigated the association between transferrin and incident type 2 diabetes. METHODS: Total 31,717 participants (mean age, 40.4±7.2 years) in a health screening program in 2005 were assessed via cross-sectional analysis. We included 30,699 subjects who underwent medical check-up in 2005 and 2009 and did not have type 2 diabetes at baseline in this retrospective longitudinal analysis. RESULTS: The serum transferrin level was higher in the type 2 diabetes group than in the non-type 2 diabetes group (58.32±7.74 µmol/L vs. 56.17±7.96 µmol/L, P<0.001). Transferrin correlated with fasting serum glucose and glycosylated hemoglobin in the correlational analysis (r=0.062, P<0.001 and r=0.077, P<0.001, respectively) after full adjustment for covariates. Transferrin was more closely related to homeostasis model assessment of insulin resistance than to homeostasis model assessment of ß cell function (r=0.042, P<0.001 and r=-0.019, P=0.004, respectively) after full adjustment. Transferrin predicted incident type 2 diabetes in non-type 2 diabetic subjects in a multivariate linear regression analysis; the odds ratio (95% confidence interval [CI]) of the 3rd tertile compared to that in the 1st tertile of transferrin for incident diabetes was 1.319 (95% CI, 1.082 to 1.607) after full adjustment (P=0.006). CONCLUSION: Transferrin is positively associated with incident type 2 diabetes in Koreans.

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.

Routine scrubbing reduced central line associated bloodstream infection in NICU.

BACKGROUND: The main aim of this study was to estimate the effectiveness of routine scrubbing by change of the incidence of central line-associated bloodstream infections (CLABSI). METHODS: We surveyed cultures from the NICU environment in December 2017. We found that areas close to infants harbored more bacteria. We implemented routine scrubbing to control sites with the most bacteria starting from January 2018. We retrospectively reviewed and compared the data between the pre (2017) and post (2018) intervention periods. RESULTS: A total of 916 infants were included; 10 CLABSI episodes were identified, 9 and 1 episodes in the pre- and postintervention periods, respectively. We found that the incidence of CLABSI decreased significantly among all admitted infants (P = .006) and also among very low birth weight infants (P = .085). The number of CLABSI cases per 1,000 central line days decreased from 1.89 in 2017 to 0.23 in 2018 (P = .018). The most common bacterial species found in the cultures established from the NICU environment were identical to the CLABSI-causing coagulase-negative Staphylococcus. CONCLUSIONS: Routine scrubbing significantly reduced CLABSI in the NICU.

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.

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.

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.

Deficiency of Sphingosine-1-Phosphate Reduces the Expression of Prohibitin and Causes ß-Cell Impairment via Mitochondrial Dysregulation.

BACKGROUND: Emerging evidence suggests that sphingolipids may be involved in type 2 diabetes. However, the exact signaling defect through which disordered sphingolipid metabolism induces ß-cell dysfunction remains unknown. The current study demonstrated that sphingosine-1-phosphate (S1P), the product of sphingosine kinase (SphK), is an essential factor for maintaining ß-cell function and survival via regulation of mitochondrial action, as mediated by prohibitin (PHB). METHODS: We examined ß-cell function and viability, as measured by mitochondrial function, in mouse insulinoma 6 (MIN6) cells in response to manipulation of cellular S1P and PHB levels. RESULTS: Lack of S1P induced by sphingosine kinase inhibitor (SphKi) treatment caused ß-cell dysfunction and apoptosis, with repression of mitochondrial function shown by decreases in cellular adenosine triphosphate content, the oxygen consumption rate, the expression of oxidative phosphorylation complexes, the mitochondrial membrane potential, and the expression of key regulators of mitochondrial dynamics (mitochondrial dynamin-like GTPase [OPA1] and mitofusin 1 [MFN1]). Supplementation of S1P led to the recovery of mitochondrial function and greatly improved ß-cell function and viability. Knockdown of SphK2 using small interfering RNA induced mitochondrial dysfunction, decreased glucose-stimulated insulin secretion (GSIS), and reduced the expression of PHB, an essential regulator of mitochondrial metabolism. PHB deficiency significantly reduced GSIS and induced mitochondrial dysfunction, and co-treatment with S1P did not reverse these trends. CONCLUSION: Altogether, these data suggest that S1P is an essential factor in the maintenance of ß-cell function and survival through its regulation of mitochondrial action and PHB expression.

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.