Aster glehni Extract, Including Caffeoylquinic Acids as the Main Constituents, Induces PPAR ß/δ-Dependent Muscle-Type Change and Myogenesis in Apolipoprotein E Knockout Mice.

To probe the functions of Aster glehni (AG) extract containing various caffeoylquinic acids on dyslipidemia, obesity, and skeletal muscle-related diseases focused on the roles of skeletal muscle, we measured the levels of biomarkers involved in oxidative phosphorylation and type change of skeletal muscle in C2C12 cells and skeletal muscle tissues from apolipoprotein E knockout (ApoE KO) mice. After AG extract treatment in cell and animal experiments, western blotting, immunohistochemistry, and enzyme-linked immunosorbent assay (ELISA) were used to estimate the levels of proteins that participated in skeletal muscle type change and oxidative phosphorylation. AG extract elevated protein expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), phosphorylated 5'-AMP-activated protein kinase (p-AMPK), peroxisome proliferator-activated receptor beta/delta (PPARß/δ), myoblast determination protein 1 (MyoD), and myoglobin in skeletal muscle tissues. Furthermore, it elevated the ATP concentration. However, protein expression of myostatin was decreased by AG treatment. In C2C12 cells, increments of MyoD, myoglobin, myosin, ATP-producing pathway, and differentiation degree by AG were dependent on PPARß/δ and caffeoylquinic acids. AG extract can contribute to the amelioration of skeletal muscle inactivity and sarcopenia through myogenesis in skeletal muscle tissues from ApoE KO mice, and function of AG extract may be dependent on PPARß/δ, and the main functional constituents of AG are trans-5-O-caffeoylquinic acid and 3,5-O-dicaffeoylquinic acid. In addition, in skeletal muscle, AG has potent efficacies against dyslipidemia and obesity through the increase of the type 1 muscle fiber content to produce more ATP by oxidative phosphorylation in skeletal muscle tissues from ApoE KO mice.

Depression and Subclinical Coronary Atherosclerosis in Adults Without Clinical Coronary Artery Disease.

BACKGROUND: The relationship between depression and subclinical coronary atherosclerosis in asymptomatic individuals is not clear. We evaluated this relationship in a Korean population. METHODS AND RESULTS: We analyzed 3920 individuals (mean age 54.7±7.9 years and 2603 men [66.4%]) with no history of coronary artery disease who voluntarily underwent coronary computed tomographic angiography and screening for depression using the Beck Depression Inventory as part of a general health examination. The degree and extent of subclinical coronary atherosclerosis were evaluated by coronary computed tomographic angiography, and ≥50% diameter stenosis was defined as significant. Participants were categorized into groups of those with or without depression using the Beck Depression Inventory scores ≥16 as a cutoff value. Of the study participants, 272 (6.9%) had a Beck Depression Inventory score of 16 or higher. After adjustment for cardiovascular risk factors, depression was not significantly associated with any coronary plaque (adjusted odds ratio [OR], 1.05 [95% CI, 0.78-1.41]; P=0.746), calcified plaque (OR, 0.95 [95% CI, 0.71-1.29]; P=0.758), noncalcified plaque (OR, 1.31 [95% CI, 0.79-2.17]; P=0.305), mixed plaque (OR, 1.16 [95% CI, 0.60-2.23]; P=0.659), or significant coronary artery stenosis (OR, 1.22 [95% CI, 0.73-2.03]; P=0.450). In the propensity score-matched population (n=1318) as well, none of the coronary artery disease measures of subclinical coronary atherosclerosis were statistically significantly associated with depression (all P>0.05). CONCLUSIONS: In this large cross-sectional study with asymptomatic individuals undergoing coronary computed tomographic angiography and Beck Depression Inventory evaluation, depression was not associated with an increased risk of subclinical coronary atherosclerosis.

Exploring horticultural traits and disease resistance in Capsicum baccatum through segmental introgression lines.

KEY MESSAGE: Segmental introgression and advanced backcross lines were developed and validated as important tools for improving agronomically important traits in pepper, offering improved sensitivity in detecting quantitative trait loci for breeding. Segmental introgression lines (SILs) and advanced backcross lines (ABs) can accelerate genetics and genomics research and breeding in crop plants. This study presents the development of a complete collection of SILs and ABs in pepper using Capsicum annuum cv. 'CM334' as the recipient parent and Capsicum baccatum 'PBC81', which displays various agronomically important traits including powdery mildew and anthracnose resistance, as donor parent. Using embryo rescue to overcome abortion in interspecific crosses, and marker-assisted selection with genotyping-in-thousands by sequencing (GT-seq) to develop SILs and ABs containing different segments of the C. baccatum genome, we obtained 63 SILs and 44 ABs, covering 94.8% of the C. baccatum genome. We characterized them for traits including powdery mildew resistance, anthracnose resistance, anthocyanin accumulation, trichome density, plant architecture, and fruit morphology. We validated previously known loci for these traits and discovered new sources of variation and quantitative trait loci (QTLs). A total of 15 QTLs were identified, including four for anthracnose resistance with three novel loci, seven for plant architecture, and four for fruit morphology. This is the first complete collection of pepper SILs and ABs validated for agronomic traits and will enhance QTL detection and serve as valuable breeding resources. Further, these SILs and ABs will be useful for comparative genomics and to better understand the genetic mechanisms underlying important agronomic traits in pepper, ultimately leading to improved crop productivity and sustainability.

Genome-wide association study of resistance to anthracnose in pepper (Capsicum chinense) germplasm.

BACKGROUND: Anthracnose is a fungal disease caused by Colletotrichum spp. that has a significant impact on worldwide pepper production. Colletotrichum scovillei is the most common pathogenic anthracnose-causing species in the Republic of Korea. RESULTS: The resistances of 197 pepper (Capsicum chinense) accessions deposited in Korea's National Agrobiodiversity Center were evaluated for their response against the virulent pathogens Colletotrichum acutatum isolate 'KSCa-1' and C. scovillei isolate 'Hana') in the field and in vitro methods for three consecutive years (2018 to 2020). The severity of the disease was recorded and compared between inoculation methods. Six phenotypically resistant pepper accessions were selected based on three years of disease data. All of the selected resistant pepper accessions outperformed the control resistant pepper in terms of resistance (PI 594,137). A genome-wide association study (GWAS) was carried out to identify single nucleotide polymorphisms (SNPs) associated with anthracnose resistance. An association analysis was performed using 53,518 SNPs and the disease score of the 2020 field and in vitro experiment results. Both field and in vitro experiments revealed 25 and 32 significantly associated SNPs, respectively. These SNPs were found on all chromosomes except Ch06 and Ch07 in the field experiment, whereas in the in vitro experiment they were found on all chromosomes except Ch04 and Ch11. CONCLUSION: In this study, six resistant C. chinense accessions were selected. Additionally, in this study, significantly associated SNPs were found in a gene that codes for a protein kinase receptor, such as serine/threonine-protein kinase, and other genes that are known to be involved in disease resistance. This may strengthen the role of these genes in the development of anthracnose resistance in Capsicum spp. As a result, the SNPs discovered to be strongly linked in this study can be used to identify a potential marker for selecting pepper material resistant to anthracnose, which will assist in the development of resistant varieties.

Description of Salinimicrobium tongyeongense sp. nov., isolated from seawater.

A Gram-stain-negative, non-motile by gliding and moderately halophilic rod-shaped bacterium HN-2-9-2T was isolated from seawater in Tongyeong, Republic of Korea. The strain grew at concentrations of 0.5‒7 % (w/v) NaCl, at pH 5.5‒8.5 and in a temperature range of 18‒45 °C. HN-2-9-2T shared the highest 16S rRNA gene sequence percentage with Salinimicrobium xinjiangense BH206T (98.2 %). The average nucleotide identity (ANI), average amino acid identity (AAI) and digital DNA-DNA hybridisation (dDDH) values between HN-2-9-2T and the S. xinjiangense BH206T were 76.0 %, 81.9 % and 19.7 %, respectively. The genome comprised 3 509 958 bp with a DNA G+C content of 43.0%. HN-2-9-2T contained MK-6 as the sole menaquinone. The predominant fatty acids were iso-C15 : 0, anteiso-C15 : 0, iso-C17 : 0 3-OH, iso-C16 : 0, iso-C15 : 1G and summed feature 9, comprising iso-C17 : 1ω6c/C16 : 1 10-methyl. The polar lipids contained phosphatidylethanolamine, one unidentified phospholipid, two unidentified aminolipids, an unidentified glycolipid and six unidentified lipids. The polyphasic taxonomic properties indicate that the strain represents a novel species within the genus Salinimicrobium, for which the name Salinimicrobium tongyeongense sp. nov. is proposed. The type strain is HN-2-9-2T (=KCTC 82934T=NBRC 115920T).

Buspirone Induces Weight Loss and Normalization of Blood Pressure via the Stimulation of PPARδ Dependent Energy Producing Pathway in Spontaneously Hypertensive Rats.

Introduction: Buspirone, as a partial agonist for a 5-hydroxytryptamine (serotonin) receptor 1A (5-HT1A), has been prescribed as an anxiolytic drug for patients. In addition, the lowering effect of serotonin on blood pressure was reported in hypertensive animal model. We investigated the therapeutic mechanism of buspirone against lipid metabolism disturbed by hypertension of early stage via hypertensive and obese animal model. Methods: The levels of various biomarkers related to lipid metabolism and hypertension were estimated through the measurement of body weight and fat weight, blood analysis, western blotting, immunohistochemistry, and staining methods. Results: The lipid accumulation was lowered in differentiated 3T3-L1 cells by buspirone treatments of 50 and 100 µM compared with untreated differentiated control. Body weight and abdominal fat weight were lowered in spontaneously hypertensive rats (SHRs) administered with buspirone of 10 mg/kg/day for 4 weeks than 8-week untreated group. Triglyceride (TG) level was decreased in SHRs administered with buspirone of 5 and 10 mg/kg/day compared to 8-week untreated group. High-density lipoprotein (HDL)-cholesterol concentration was elevated by buspirone 10 mg/kg/day treatment compared to 8-week untreated group. Blood pressures in SHRs were lowered by buspirone treatments of 5 and 10 mg/kg/day compared with 8-week untreated group. Protein levels for peroxisome proliferator-activated receptor δ (PPARδ), 5' adenosine monophosphate-activated protein kinase (AMPK), and PPARγ coactivator-1 alpha (PGC-1α) were increased both in C2C12 cells treated by buspirone of 100 µM and in SHRs administered by buspirone of 1, 5, and 10 mg/kg/day compared to untreated control cells and 8-week untreated group. Fat cell numbers decreased in 8-week untreated group were increased in SHRs administered by buspirone treats of 1, 5, and 10 mg/kg/day. Protein expression levels for angiotensin II type 1 receptor (AT1R) and vascular cell adhesion molecule 1 (VCAM1) were increased in 8-week untreated group compared to 4-week group, however, they were decreased by buspirone treatments of 1, 5, and 10 mg/kg/day. Conclusion: Buspirone may induce the losses of body weight and abdominal fat weight through the activation of PPARδ dependent catabolic metabolism producing energy, and eventually, the ameliorated lipid metabolism could normalize high blood pressure.

Comprehensive Prediction of Subclinical Coronary Atherosclerosis in Subjects Without Traditional Cardiovascular Risk Factors.

It is not uncommon for asymptomatic individuals without identified cardiovascular risk factors to present with atherosclerosis-related adverse events. We aimed to evaluate the predictors of subclinical coronary atherosclerosis in individuals without traditional cardiovascular risk factors. We analyzed 2,061 individuals without identified cardiovascular risk factors who voluntarily underwent coronary computed tomography angiography as part of a general health examination. Subclinical atherosclerosis was defined as the presence of any coronary plaque. Of 2,061 individuals, subclinical atherosclerosis was observed in 337 individuals (16.4%). Clinical variables, such as age, gender, body mass index (BMI), systolic blood pressure (SBP), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C), were significantly associated with subclinical coronary atherosclerosis. The participants were randomly split into train and validation data sets. In the train set, a prediction model using 6 variables with optimal cutoffs (age >53 years for men and >55 years for women, gender, BMI >22 kg/m2, SBP >120 mm Hg, HDL-C <55 mg/100 ml, and LDL-C >130 mg/100 ml) was derived (area under the curve 0.780, 95% confidence interval 0.751 to 0.809, goodness-of-fit p = 0.693). In the validation set, this model performed well (area under the curve 0.792, 95% confidence interval 0.726 to 0.858, goodness-of-fit p = 0.073). In conclusion, together with nonmodifiable risk factors, such as age and gender, modifiable variables, such as BMI, SBP, LDL-C, and HDL-C, were shown to be associated with subclinical coronary atherosclerosis, even at currently acceptable levels. These results suggest that stricter control of BMI, blood pressure, and cholesterol might be helpful in the primary prevention of future coronary events.

Description of Brachybacterium sillae sp. nov., a thermophilic bacterium isolated from a hot spring.

The taxonomic position of strain EF45031T, isolated from the Neungam Carbonate hot spring, was examined using the polyphasic taxonomic approach. Strain EF45031T shared the highest percentage of 16S rRNA gene sequence with Brachybacterium nesterenkovii CIP 104813 T (97.7%). The average nucleotide identity (ANI), average amino acid identity (AAI), and digital DNA-DNA hybridization (dDDH) values between strain EF45031T and the type strains B. nesterenkovii CIP 104813 T and B. phenoliresistens Phenol-AT were 77.0%, 69.15%, 21.9% and 75.73%, 68.81%, 20.5%, respectively. Phylogenomic analysis using an up-to-date bacterial core gene (UBCG) set revealed that strain EF45031T belonged to the genus Brachybacterium. Growth occurred between 25 and 50 ℃ at pH 6.0-9.0 and could tolerate salinity up to 5% (w/v). Strain had anteiso-C15:0 and anteiso-C17:0 as major fatty acids. Menaquinone-7 (MK-7) was the predominant respiratory menaquinone. The polar lipids were diphosphatidylglycerol, phosphatidylglycerol, three aminolipids, and two unidentified glycolipids. The cell-wall peptidoglycan contained meso-diaminopimelic acid as a diagnostic diamino acid. The genome comprised 2,663,796 bp, with a G + C content of 70.9%. Stress-responsive periplasmic chaperone/protease coding genes were identified in the genome of EF45031T and were not detected in other Brachybacterium species. The polyphasic taxonomic properties indicate that the strain represents a novel species within the genus Brachybacterium, for which the name Brachybacterium sillae sp. nov. is proposed. The type strain is EF45031T (= KCTC 49702 T = NBRC 115869 T).

Fermentation of Abelmoschus manihot Extract with Halophilic Bacillus licheniformis CP6 Results in Enhanced Anti-Inflammatory Activities.

Microbial fermentation provides a valorization strategy, through biotransformation, to convert plant-derived raw materials into health-promoting agents. In this study, we have investigated the antioxidative activity of Abelmoschus manihot fermented with various Bacillaceae strains from specific environments and demonstrated the anti-inflammatory effects of Bacillus licheniformis CP6 fermented A. manihot extract (FAME) in lipopolysaccharide (LPS)-stimulated Raw264.7 macrophages. Of 1500 bacteria isolated from various specific environments, 47 extracellular protease- and amylase-producing strains with qualified presumption safety status, belonging to the family Bacillaceae, were selected for A. manihot fermentation. Among them, strain CP6, a halophilic bacterium isolated from Tongyeong seawater in Korea and identified as B. licheniformis, showed the highest antioxidant activity. In particular, FAME exerted anti-inflammatory effects on LPS-stimulated Raw264.7 macrophages. Consequently, FAME had a potent inhibitory effect on nitric oxide (NO) production in LPS-stimulated macrophages, without cytotoxicity. Moreover, FAME downregulated LPS-induced pro-inflammatory mediator and enzyme levels in LPS-induced Raw264.7 cells, including IL-1ß, IL-6, TNF-α, iNOS, and COX-2, compared to levels when cells were incubated in A. manihot extract (IAME). Further detailed characterization indicated that FAME suppresses inflammation by blocking NF-κB via IKK phosphorylation inhibition and IκB-α degradation and by downregulating NO production, and inflammatory mediators also decreased NF-κB translocation. Furthermore, FAME inhibited LPS-stimulated activation of MAPKs, including ERK1/2, JNK, and p38, compared to that with either IAME. Therefore, we suggest that FAME could be used for inflammation-related disorders.

Isolation and Characterization of Thermophilic Bacteria from Hot Springs in Republic of Korea.

Thermophiles that produce extracellular hydrolases are of great importance due to their applications in various industries. Thermophilic enzymes are of interest for industrial applications due to their compatibility with industrial processes, and the availability of the organisms is essential to develop their full potential. In this study, a culture-dependent approach was used to identify thermophilic bacteria from five hot springs in Republic of Korea. Characterization, taxonomic identification, and extracellular hydrolase (amylase, lipase, and protease) activity of 29 thermophilic bacterial isolates from the Neungam carbonate, Mungang sulfur, Deokgu, Baegam, and Dongnae hot springs were investigated. Identification based on the full-length 16S rRNA gene sequence revealed that strains belonged to the phylum Bacillota and were classified as Aeribacillus, Bacillus, Caldibacillus, Geobacillus, and Thermoactinomyces genera. It was found that 22 isolates could produce at least one extracellular enzyme. Geobacillus, representing 41.4% of the isolates, was the most abundant. The highest amount of proteolytic and lipolytic enzymes was secreted by strains of the genus Geobacillus, whereas Caldibacillus species produced the highest amount of amylolytic enzyme. The Geobacillus species producing hydrolytic extracellular enzymes appeared to be the most promising.

Description of Microbacterium neungamense sp. nov. isolated from a hot spring.

The Gram-positive, nonmotile, rod-shaped bacterium EF45044T was isolated from a hot spring in Chungju, South Korea. The strain was able to grow at concentrations of 0‒5% (w/v) NaCl, at pH 6.0‒10.0 and in the temperature range of 18‒50 °C. Strain EF45044T showed the highest 16S rRNA gene sequence similarity (98.2%) with Microbacterium ketosireducens DSM 12510T, and the digital DNA‒DNA hybridization (dDDH), average amino acid identity (AAI), and average nucleotide identity (ANI) values were all lower than the accepted species threshold. Strain EF45044T contained MK‒12 and MK‒13 as the predominant respiratory quinones and anteiso‒C17:0, anteiso‒C15:0, and iso‒C16:0 as the major fatty acids. Diphosphatidylglycerol, phosphatidylglycerol, and glycolipid were detected as the major polar lipids. The cell-wall peptidoglycan contained ornithine. The DNA G + C content was 71.4 mol%. Based on the polyphasic data, strain EF45044T (= KCTC 49703T) presents a novel species of the genus Microbacterium, for which the name Microbacterium neungamense sp. nov. is proposed.

Marital Status and Subclinical Coronary Atherosclerosis in Asymptomatic Individuals.

Background Data are limited on the association between marital status and subclinical coronary atherosclerosis. This study investigated the influence of marital status on subclinical coronary atherosclerosis detected by coronary computed tomographic angiography in an asymptomatic population. Methods and Results This retrospective study analyzed 9288 asymptomatic individuals (mean age, 53.7±8.0 years; 6041 [65%] men) with no history of coronary artery disease who voluntarily underwent coronary computed tomographic angiography during a general health examination. Marital categories were married (n=8481) versus unmarried (n=807), comprising never married (n=195), divorced (n=183), separated (n=119), and widowed (n=310) individuals. The degree and extent of subclinical coronary atherosclerosis were evaluated by coronary computed tomographic angiography; ≥50% diameter stenosis was defined as significant. Logistic regression and propensity score matching analyses were used to determine the association between marital status and subclinical coronary atherosclerosis. After adjustment for cardiovascular risk factors, no significant differences were observed in the adjusted odds ratio (OR) of unmarried status for any coronary plaque (OR, 1.077; 95% CI, 0.899-1.291), calcified plaque (OR, 1.058; 95% CI, 0.881-1.271), noncalcified plaque (OR, 0.966; 95% CI, 0.691-1.351), mixed plaque (OR, 1.301; 95% CI, 0.884-1.917), and significant coronary artery stenosis (OR, 1.066; 95% CI, 0.771-1.474). Similarly, in the 2:1 propensity-score matched population (n=2398), no statistically significant differences were observed for the OR of marital status for any subclinical coronary atherosclerosis (P>0.05 for all). Conclusions In this large cross-sectional study, marital status was not associated with an increased risk of subclinical coronary atherosclerosis.

Serum phosphorus and subclinical coronary atherosclerosis in asymptomatic subjects without kidney dysfunction.

BACKGROUND AND AIMS: There is limited data on the association between serum phosphorus concentration (SPC) and subclinical coronary atherosclerosis in low-risk asymptomatic subjects without kidney dysfunction. MATERIALS AND METHODS: We retrospectively analyzed 1,636 Korean individuals (mean age 52.6 ± 7.6 years; males: 712 (43.5%)) without traditional cardiovascular risk factors (CVRFs) and kidney dysfunction who voluntarily underwent coronary computed tomography angiography (CCTA) as part of a general health examination. Traditional CVRFs were defined as follows: systolic/diastolic blood pressure ≥ 140/90 mmHg, fasting blood glucose ≥ 126 mg/dL, hemoglobin A1c ≥ 6.5%, total cholesterol ≥ 240 mg/dL, low-density lipoprotein cholesterol ≥ 160 mg/dL, high-density lipoprotein cholesterol < 40 mg/dL, body mass index ≥ 25.0 kg/m2, currently smoking, and medical history of hypertension, diabetes, and hyperlipidemia. Study participants were stratified into tertiles according to their SPC levels (≤ 3.2, 3.3 - 3.6, and ≥ 3.7 mg/dL). RESULTS: 297 (18.2%) study participants had subclinical coronary atherosclerosis, characterized by any coronary plaque on CCTA. In multivariable regression analysis, the risk of subclinical coronary atherosclerosis increased in the second (odds ratio (OR): 1.629; 95% confidence interval (CI): 1.149 - 2.308; p = 0.006) and third (OR: 1.645; 95% CI: 1.093 - 2.476; p = 0.017) SPC tertiles compared to the first SPC tertile. In addition, the risk of calcified plaque increased in the second (OR: 1.605; 95% CI: 1.124 - 2.292; p = 0.009) and third (OR 1.790; 95% CI 1.179 - 2.716; p = 0.006) SPC tertiles. CONCLUSION: In low-risk asymptomatic Korean individuals without kidney dysfunction, a higher SPC level was an independent predictor of subclinical coronary atherosclerosis.

Stimulation of Alpha-1-Adrenergic Receptor Ameliorates Obesity-Induced Cataracts by Activating Glycolysis and Inhibiting Cataract-Inducing Factors.

BACKGROUND: Obesity, the prevalence of which is increasing due to the lack of exercise and increased consumption of Westernized diets, induces various complications, including ophthalmic diseases. For example, obesity is involved in the onset of cataracts. METHODS: To clarify the effects and mechanisms of midodrine, an α1-adrenergic receptor agonist, in cataracts induced by obesity, we conducted various analytic experiments in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a rat model of obesity. RESULTS: Midodrine prevented cataract occurrence and improved lens clearance in OLETF rats. In the lenses of OLETF rats treated with midodrine, we observed lower levels of aldose reductase, tumor necrosis factor-α, and sorbitol, but higher levels of hexokinase, 5'-adenosine monophosphate-activated protein kinase-alpha, adenosine 5´-triphosphate, peroxisome proliferator-activated receptordelta, peroxisome proliferator-activated receptor gamma coactivator 1-alpha, superoxide dismutase, and catalase. CONCLUSION: The ameliorating effects of midodrine on cataracts in the OLETF obesity rat model are exerted via the following three mechanisms: direct inhibition of the biosynthesis of sorbitol, which causes cataracts; reduction of reactive oxygen species and inflammation; and (3) stimulation of normal aerobic glycolysis.

Lipoprotein(a) and subclinical coronary atherosclerosis in asymptomatic individuals.

BACKGROUND AND AIMS: There are limited data regarding the association between lipoprotein(a) (Lp[a]) and subclinical coronary atherosclerosis. This study investigated the association between Lp(a) and subclinical coronary atherosclerosis detected by coronary computed tomographic angiography (CCTA) in an asymptomatic population. METHODS: We retrospectively analyzed 7201 asymptomatic individuals (mean age 54.4 ± 7.9 years; 65.3% men with no prior history of coronary artery disease who voluntarily underwent CCTA as part of a general health examination). The degree and extent of subclinical coronary atherosclerosis were evaluated by CCTA. Study participants were stratified into quartiles according to their Lp(a) levels (<4.3, 4.3-8.9, 9.0-20.1, and ≥20.2 mg/dL). RESULTS: Of the study participants, any coronary plaque on CCTA was observed in 2557 (35.5%). Specifically, calcified, non-calcified, and mixed plaques were observed in 2411 (33.5%), 363 (5.0%) and 249 (3.5%) participants, respectively. After adjustment for the presence of cardiovascular risk factors, the fourth Lp(a) quartile was significantly associated with any coronary (odds ratio [OR] 1.212; 95% confidence interval [CI] 1.038-1.416), calcified (1.205, 95% CI 1.030-1.410), non-calcified (1.588, 95% CI 1.152-2.189), or mixed (1.674, 95% CI 1.172-2.391) plaque compared with the first Lp(a) quartile. In addition, 442 (6.1%) had significant coronary artery stenosis (≥50% diameter stenosis). The odds ratio for significant stenosis (1.537, 95% CI 1.153-2.048) was higher in the fourth quartile compared with the first quartile. CONCLUSIONS: In this large cross-sectional study with asymptomatic individuals undergoing CCTA, higher Lp(a) level was associated with subclinical coronary atherosclerosis.

Frequency and Significance of Right Bundle Branch Block and Subclinical Coronary Atherosclerosis in Asymptomatic Individuals.

Limited data exist regarding the association between right bundle branch block (RBBB) and subclinical coronary atherosclerosis. This study investigated the influence of RBBB on subclinical coronary atherosclerosis detected by coronary computed tomographic angiography (CCTA) in an asymptomatic population. We retrospectively analyzed 7,205 asymptomatic individuals (mean age 54.4 ± 7.9 years and 4,695 men [65.2%]) with no prior history of coronary artery disease who voluntarily underwent CCTA and 12-lead electrocardiographic evaluation as part of a general health examination. The degree and extent of subclinical coronary atherosclerosis were evaluated by CCTA, and ≥50% diameter stenosis was defined as significant. The association between RBBB and subclinical coronary atherosclerosis was determined by logistic regression and propensity score matching analyses. Of study participants, 116 (1.6%) had RBBB. After adjustment for cardiovascular risk factors, there were no statistically significant differences in the adjusted odds ratios of RBBB for any atherosclerotic plaque (0.87, 95% confidence interval [CI] 0.57 to 1.32), calcified plaque (0.78, 95% CI 0.51 to 1.19), noncalcified plaque (1.44, 95% CI 0.77 to 2.69), mixed plaque (1.12, 95% CI 0.52 to 2.39), and significant coronary artery stenosis (0.92, 95% CI 0.48 to 1.74). Similarly, in the 5: 1 propensity score-matched population (n = 696), there were no statistically significant differences in the odds ratios for any subclinical coronary atherosclerosis between participants with and without RBBB (p for all >0.05). In conclusion, through this large cross-sectional study of asymptomatic individuals who underwent CCTA and electrocardiography evaluation, individuals with RBBB were not associated with an increased risk of subclinical coronary atherosclerosis compared with those without RBBB.

A large-scale metagenomic study for enzyme profiles using the focused identification of the NGS-based definitive enzyme research (FINDER) strategy.

Excavating the molecular details of many diverse enzymes from metagenomes remains challenging in agriculture, food, health, and environmental fields. We present a versatile method that accelerates metabolic enzyme discovery for highly selective gene capture in metagenomes using next-generation sequencing. Culture-independent enzyme mining of environmental DNA is based on a set of short identifying degenerate sequences specific for a wide range of enzyme superfamilies, followed by multiplexed DNA barcode sequencing. A strategy of 'focused identification of next-generation sequencing-based definitive enzyme research' enabled us to generate targeted enzyme datasets from metagenomes, resulting in minimal hands-on obtention of high-throughput biological diversity and potential function profiles, without being time-consuming. This method also provided a targeted inventory of predicted proteins and molecular features of metabolic activities from several metagenomic samples. We suggest that the efficiency and sensitivity of this method will accelerate the decryption of microbial diversity and the signature of proteins and their metabolism from environmental samples.

Cholesterol Control for Subclinical Coronary Atherosclerosis in Subjects Without Indication for Statin Therapy.

Low-risk individuals still experience adverse cardiac events. We sought to evaluate long-term cardiac events and predictors for subclinical coronary atherosclerosis in subjects without indication for statin therapy. We analyzed 3,272 individuals without indication for statin therapy who voluntarily underwent coronary computed tomography angiography as part of a general health examination. A cardiac event was defined as a composite of cardiac death, nonfatal myocardial infarction, unstable angina requiring hospitalization, or late coronary revascularization. The prevalence of normal coronary arteries, nonobstructive coronary artery disease (CAD) (diameter stenosis < 50%), and obstructive CAD (diameter stenosis ≥50%) was 2,338 (71.5%), 809 (24.7%), and 125 (3.8%), respectively. During the follow-up period (median 5.3 [interquartile range, 4.3-6.3] years), the 6-year event-free survival rates were 99.2%±0.2% in subjects with normal coronary arteries, 98.2%±0.6% in those with nonobstructive CAD, and 90.2%±2.7% in those with obstructive CAD (log-rank p < 0.001). Multivariable regression analysis showed that low-density lipoprotein cholesterol (LDL-C, odds ratio [OR]: 1.012; 95% confidence interval (CI): 1.005-1.019) and high-density lipoprotein cholesterol (HDL-C, OR: 0.968; 95% CI: 0.952-0.984) levels were associated with subclinical obstructive CAD, together with age (OR: 1.080; 95% CI: 1.040-1.121) and male sex (OR: 3.102; 95% CI: 1.866-5.155) (all p < 0.05). In conclusion, LDL-C and HDL-C are significantly associated with the presence of subclinical obstructive CAD with a worse prognosis in subjects without indication for statin therapy. These findings suggest that stricter control of LDL-C and HDL-C levels may be necessary for primary prevention even in a relatively low-risk population.

Rapid Establishment of Tracheal Stenosis in Pigs Using Endotracheal Tube Cuff Overpressure and Electrocautery.

To apply a new airway treatment to humans, preclinical studies in an appropriate animal model is needed. Canine, porcine and leporine tracheas have been employed as animal airway stenosis models using various methods such as chemical caustic agents, laser, and electrocautery. However, existing models take a long time to develop (3-8 weeks) and the mechanism of stenosis is different from that in humans. The aim of the present study was to establish a new and fast tracheal stenosis model in pigs using a combination of cuff overpressure intubation (COI) and electrocautery. Fourteen pigs were divided into three groups: tracheal cautery (TC) group (n=3), COI group (n=3), and COI-TC combination group (n=8). Cuff overpressure (200/400/500 mmHg) was applied using a 9-mm endotracheal tube. Tracheal cautery (40/60 watts) was performed using a rigid bronchoscopic electrocoagulator. After intervention, the pigs were observed for 3 weeks and bronchoscopy was performed every 7 days. When the cross-sectional area decreased by > 50%, it was confirmed that tracheal stenosis was established. The time for tracheal stenosis was 14 days in the TC group and 7 days in the COI-TC combination group. In the COI group, no stenosis occurred. In the COI-TC group, electrocautery (40 watts) immediately after intubation for >1 h with a cuff pressure of 200 mmHg or more resulted in sufficient tracheal stenosis within 7 days. Moreover, the degree of tracheal stenosis increased in proportion to the cuff pressure and tracheal intubation time. The combined use of cuff overpressure and electrocautery helped to establish tracheal stenosis in pigs rapidly.

The mechanical characteristics and performance evaluation of a newly developed silicone airway stent (GINA stent).

Central airway obstruction (CAO) can be attributed to several benign or malignant conditions. Although surgery is the preferred therapeutic option for the management of CAO, bronchoscopic treatment can be performed in scenarios where the surgical procedure is not possible. Recent years have witnessed several improvements in the field of bronchoscopic treatment, especially with regard to airway stents. Current research involves new attempts to overcome the existing shortcomings pertaining to the stents (migration, mucostasis, and granulation tissue formation). The authors have recently developed a new silicone airway stent (GINA stent) with an anti-migration design, dynamic structure that enables the reduction of stent cross-sectional area, and radio-opacity. The present study aimed to evaluate the mechanical characteristics and performance of the novel GINA stent using a porcine tracheal stenosis model. In the current study, all the tests involved the comparison of the GINA stent [outer diameter (OD, mm): 14; length (L, mm): 55] with the Dumon stent (OD: 14; L: 50). The mechanical tests were performed using a digital force gauge, in order to determine the anti-migration force, expansion force, and flexibility. The present study evaluated the short-term (3 weeks) performance of the two stents after implantation [GINA (n = 4) vs. Dumon (n = 3)] in the porcine tracheal stenosis model. The results pertaining to the comparison of the mechanical properties of the GINA and Dumon stents are stated as follows: anti-migration force (18.4 vs. 12.8 N, P = 0.008); expansion force (11.9 vs. 14.5 N, P = 0.008); and flexibility (3.1 vs. 4.5 N, P = 0.008). The results pertaining to the comparison of the short-term performance of the GINA and Dumon stents are stated as follows: mucus retention (0/4 vs. 0/3); granulation tissue formation (0/4 vs. 0/3); and migration (1/4 vs. 2/3). The GINA stent displayed better mechanical properties and comparable short-term performance, compared to the Dumon stent.