OBJECTIVEFibroblast growth factor 19 (FGF19), a hormone secreted from the small intestine, has recently been shown to stimulate glycogen synthesis and inhibit gluconeogenesis through insulin-independent pathways. This study investigated the change of FGF19 in prediabetes and newly diagnosed type 2 diabetes mellitus (T2DM) and explored the association of serum FGF19 levels with parameters of glucose metabolism in Chinese subjects.RESEARCH DESIGN AND METHODSFasting serum FGF19 levels were determined by ELISA in 81 normal glucose tolerance (NGT), 91 impaired fasting glucose (IFG), 93 impaired glucose tolerance (IGT), and 104 newly diagnosed T2DM subjects, and their association with parameters of glucose metabolism was studied. An ordinal logistic regression analysis was performed in subjects with NGT, IFG, and T2DM. Serum FGF19 levels at 2 h after a 75-g oral glucose tolerance test in the different glucose tolerance categories were studied in a subgroup.RESULTSFasting serum FGF19 levels in subjects with IFG (210 pg/mL [142–327]) (median [interquartile range]) and T2DM (196 pg/mL [137–280]) were significantly lower than those in NGT subjects (289 pg/mL [224–393]) (both P < 0.001). However, no significant difference in fasting FGF19 levels was observed between IGT (246 pg/mL [138–379]) and NGT subjects. Fasting serum FGF19 levels were negatively associated with fasting plasma glucose and independently associated with the deterioration of glucometabolic status from NGT to IFG and T2DM.CONCLUSIONSFasting serum FGF19 levels were decreased in Chinese subjects with IFG and inversely associated with fasting glucose levels.
Objectives To investigate the associations of thyroid-stimulating hormone (TSH), free triiodothyronine (FT3) and free thyroxine (FT4) with body mass index (BMI) and the effect of age and gender on these relationships in a large Chinese population. Methods A total of 97,997 individuals from a health examination center were selected. The medians (25th and 75th) of TSH, FT3 and FT4 were used to explore the trends based on gender, 10-year age groups and BMI. The relationships of TSH, FT3 and FT4 with BMI were assessed by generalized additive models (GAM) along with adjusting the effect of age and gender. Results After applying our exclusion criteria, 77,991 euthyroid participants (45,428 males and 32,563 females) were analyzed. The medians of TSH level based on BMI groups were significantly higher in female participants than those in males in all age groups (P < 0.05), and the median FT3 level was lower in female subjects; however, there was no significant difference between male and female subjects in median FT4 level. The GAM analysis showed the non-linear positive association of TSH and FT3 with BMI, and these relationships were markedly influenced by age and gender. However, FT4 had a negative relationship with BMI, with neglectable effect of age and gender. Conclusions TSH, FT3 and BMI have a non-linear and positive quadratic relationship after age and gender adjustment. FT4, however, has a negative non-linear relationship with BMI with neglectable influence of age and gender.
Introduction The HbA1c has been considered as the ‘gold standard’ in diabetes diagnosis and management, however, age, gender and body mass index (BMI) might have certain effects on HbA1c. We are aiming to further investigate the correlation between age and HbA1c, and whether it was affected by gender and BMI. Methods A cross-sectional survey including 135,893 nondiabetic individuals who took the physical examination between 2013 and 2017 was conducted. The subjects were grouped by gender, age and BMI, and the interactive and independent effects of the 3 factors on the HbA1c were detected. The median and 95% confidence interval (CI) of HbA1c levels were calculated. Results The HbA1c levels gradually increased along with age, both in female and male, and there is a positive association between BMI and the HbA1c. The difference on HbA1c in gender was associated with both age and BMI, the age-related increase in HbAlc was accentuated in the subgroup with higher BMI, and there was a marked accentuation of the positive association between BMI and HbA1c as age increased. In almost all the young and middle-aged (aged 20–59) subgroups, the 97.5th percentiles of HbA1c levels were lower than 6.5%, suggesting that the single HbA1c cutoff value is probably not applicable to the young and middle-aged population. Conclusions We recommend that the effects of age, gender and BMI should be taken into consideration when using HbA1c for the diagnosis and management of diabetes, especially in the young and middle-aged population.
A novel bacterial strain (MSC19T) was isolated from a deep-sea sponge Cacospongia mycofijiensis collected in the Mariana Trench at a depth of 2681 m. The cells of the new isolate were Gram-stain-positive, non-motile, oxidase- and catalase-positive, rod-shaped and yellow-coloured. They could grow at 4–32 °C (optimum, 28 °C), pH 5.5–12 (optimum, pH 7.0) and with 0–12 % (w/v) NaCl (optimum, 4 %). The strain’s 16S rRNA gene sequence showed 98.41 % similarity to that of Mycetocola saprophilus CM-01T. Phylogenetic analysis further suggested that strain MSC19T represents a new species within the genus Mycetocola . The total genome of MSC19T was approximately 3 196 754 bp in size with a G+C content of 66.43 mol%. The average nucleotide identity (ANI) and digital DNA–DNA hybridization (dDDH) values among MSC19T and other Mycetocola type strains were 70.35–75.37 % (ANIb), 83.79–84.73 % (ANIm) and 20.3–21.7 % (dDDH). The major fatty acids of MSC19T were composed of anteiso-C15 : 0, iso-C16 : 0 and anteiso-C17 : 0, and its predominant menaquinones were MK-10 and MK-9. The polar lipids of MSC19T mainly consisted of diphosphatidylglycerol, phosphatidylglycerol and glycolipid. The diagnostic cell-wall diamino acid was lysine. Combined molecular, physiological, biochemical and chemotaxonomic analyses suggest that strain MSC19T represents a novel species of the genus Mycetocola , for which the name Mycetocola spongiae sp. nov. is proposed. The type strain is MSC19T (=MCCC 1K06265T=KCTC 49701T).
The gut-derived hormone Fibroblast growth factor 19 (FGF19) could regulate glucose metabolism and is induced by bile acids (BAs) through activating Farnesoid X Receptor (FXR). FGF19 was found to decrease in subjects with isolated-impaired fasting glucose (I-IFG) and type 2 diabetes mellitus (T2DM). However, the reason for the change of FGF19 in subjects with different glucometabolic status remained unclear. Here we measured six BAs including chenodeoxycholic acid (CDCA), cholic acid, deoxycholic acid, their glycine conjugates and FGF19 levels during oral glucose tolerance test (OGTT) in normal glucose tolerance (NGT), isolated-impaired glucose tolerance, I-IFG, combined glucose intolerance (CGI) and T2DM subjects. After OGTT, serum FGF19 peaked at 120 min in all subjects. Glycine conjugated BAs peaked at 30 min, while free BAs did not elevated significantly. Consistent with the decrease trend in FGF19 levels, fasting serum CDCA levels in subjects with I-IFG, CGI and T2DM were significantly lower than NGT subjects (P < 0.05). Fasting serum CDCA was independently associated with FGF19. CDCA strongly upregulated FGF19 mRNA levels in LS174T cells in a dose- and time-dependent manner. These results suggest that the decrease of FGF19 in subjects with I-IFG was at least partially due to their decrease of CDCA acting via FXR.
Although diverse fungi have been found in the deep-sea habitats, the space distribution of fungi has not been well characterized. In this study, the fungal horizontal and vertical distribution of the deep-sea sediments, four locations, three depths each, in the South China Sea, were compared using ITS2 high-throughput sequencing. It was revealed that the South China Sea deep-sea sediments harbor diverse marine fungi, including 82.39% Ascomycota, 8.10% Basidiomycota, 0.55% Zygomycota and 8.96% unknown fungi. The results indicate that fungal community structure is not uniform among the different sediment habitats. Though surface sediments have similar fungal diversity across the 4 locations, the fungal abundance and diversity increase with the depth of the sediments from 0 to 2 m, and 1 and 2 m deep sediments show obvious location-dependent fungal community structure. This is the first time to compare the horizontal and vertical distribution of fungal community among different deep-sea sediments in the South China Sea by high-throughput sequencing, providing novel insights into the space distribution characteristics of deep-sea sediments fungi.
Driver mutations can contribute to the initial processes of cancer, and their identification is crucial for understanding tumorigenesis as well as for molecular drug discovery and development. Allostery regulates protein function away from the functional regions at an allosteric site. In addition to the known effects of mutations around functional sites, mutations at allosteric sites have been associated with protein structure, dynamics, and energy communication. As a result, identifying driver mutations at allosteric sites will be beneficial for deciphering the mechanisms of cancer and developing allosteric drugs. In this study, we provided a platform called DeepAlloDriver to predict driver mutations using a deep learning method that exhibited >93% accuracy and precision. Using this server, we found that a missense mutation in RRAS2 (Gln72 to Leu) might serve as an allosteric driver of tumorigenesis, revealing the mechanism of the mutation in knock-in mice and cancer patients. Overall, DeepAlloDriver would facilitate the elucidation of the mechanisms underlying cancer progression and help prioritize cancer therapeutic targets. The web server is freely available at: https://mdl.shsmu.edu.cn/DeepAlloDriver.
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