We aimed to investigate the association of metabolic obesity phenotypes with all-cause mortality risk in a rural Chinese population. This prospective cohort study enrolled 15 704 Chinese adults (38·86 % men) with a median age of 51·00 (interquartile range: 41·00–60·00) at baseline (2007–2008) and followed up during 2013–2014. Obesity was defined by waist circumference (WC: ≥ 90 cm for men and ≥ 80 cm for women) or waist-to-height ratio (WHtR: ≥ 0·5). The hazard ratio (HR) and 95 % CI for the risk of all-cause mortality related to metabolic obesity phenotypes were calculated using the Cox hazards regression model. During a median follow-up of 6·01 years, 864 deaths were identified. When obesity was defined by WC, the prevalence of participants with metabolically healthy non-obesity (MHNO), metabolically healthy obesity (MHO), metabolically unhealthy non-obesity (MUNO) and metabolically unhealthy obesity (MUO) at baseline was 12·12 %, 2·80 %, 41·93 % and 43·15 %, respectively. After adjusting for age, sex, alcohol drinking, smoking, physical activity and education, the risk of all-cause mortality was higher with both MUNO (HR = 1·20, 95 % CI 1·14, 1·26) and MUO (HR = 1·20, 95 % CI 1·13, 1·27) v. MHNO, but the risk was not statistically significant with MHO (HR = 0·99, 95 % CI 0·89, 1·10). This result remained consistent when stratified by sex. Defining obesity by WHtR gave similar results. MHO does not suggest a greater risk of all-cause mortality compared to MHNO, but participants with metabolic abnormality, with or without obesity, have a higher risk of all-cause mortality. These results should be cautiously interpreted as the representation of MHO is small.

Several amino acids can stimulate milk synthesis in mammary epithelial cells (MEC); however, the regulatory role of isoleucine (Ile) and underlying molecular mechanism remain poorly understood. In this study, we aimed to evaluate the regulatory effects of Ile on milk protein and fat synthesis in MEC and reveal the mediation mechanism of Brahma-related gene 1 (BRG1) on this regulation. Ile dose dependently affected milk protein and fat synthesis, mechanistic target of rapamycin (mTOR) phosphorylation, sterol regulatory element binding protein 1c (SREBP-1c) expression and maturation, and BRG1 protein expression in bovine MEC. Phosphatidylinositol 3 kinase (PI3K) inhibition by LY294002 treatment blocked the stimulation of Ile on BRG1 expression. BRG1 knockdown and gene activation experiments showed that it mediated the stimulation of Ile on milk protein and fat synthesis, mTOR phosphorylation, and SREBP-1c expression and maturation in MEC. ChIP-PCR analysis detected that BRG1 bound to the promoters of mTOR and SREBP-1c, and ChIP-qPCR further detected that these bindings were increased by Ile stimulation. In addition, BRG1 positively regulated the binding of H3K27ac to these two promoters, while it negatively affected the binding of H3K27me3 to these promoters. BRG1 knockdown blocked the stimulation of Ile on these two gene expressions. The expression of BRG1 was higher in mouse mammary gland in the lactating period, compared with that in the puberty or dry period. Taken together, these experimental data reveal that Ile stimulates milk protein and fat synthesis in MEC via the PI3K-BRG1-mTOR/SREBP-1c pathway.

To investigate the association between the Metabolic Score for Visceral Fat (METS-VF) and risk of type 2 diabetes mellitus (T2DM) and compare the predictive value of the METS-VF for T2DM incidence with other obesity indices in Chinese people. A total of 12 237 non-T2DM participants aged over 18 years from the Rural Chinese Cohort Study of 2007–2008 were included at baseline and followed up during 2013–2014. The cox proportional hazards regression was used to calculate hazard ratios (HR) and 95 % CI for the association between baseline METS-VF and T2DM risk. Restricted cubic splines were used to model the association between METS-VF and T2DM risk. Area under the receiver operating characteristic curve (AUC) analysis was used to evaluate the ability of METS-VF to predict T2DM incidence. During a median follow-up of 6·01 (95 % CI 5·09, 6·06) years, 837 cases developed T2DM. After adjusting for potential confounding factors, the adjusted HR for the highest v. lowest METS-VF quartile was 5·97 (95 % CI 4·28, 8·32), with a per 1-sd increase in METS-VF positively associated with T2DM risk. Positive associations were also found in the sensitivity and subgroup analyses, respectively. A significant nonlinear dose–response association was observed between METS-VF and T2DM risk for all participants (Pnonlinearity = 0·0347). Finally, the AUC value of METS-VF for predicting T2DM was largest among six indices. The METS-VF may be a reliable and applicable predictor of T2DM incidence in Chinese people regardless of sex, age or BMI.

The present study aimed to investigate the association of the Chinese visceral adiposity index (CVAI) and its 6-year change with hypertension risk and compare the ability of CVAI and other obesity indices to predict hypertension based on the Rural Chinese Cohort Study. Study participants were randomly recruited by a cluster sampling procedure, and 10 304 participants ≥18 years were included. Modified Poisson regression was used to derive adjusted relative risks (RR) and 95 % CI. We identified 2072 hypertension cases during a median of 6·03 years of follow-up. The RR for the highest v. lowest CVAI quartile were 1·29 (95 % CI 1·05, 1·59) for men and 1·53 (95 % CI 1·22, 1·91) for women. Per-sd increase in CVAI was associated with hypertension for both men (RR 1·09, 95 % CI 1·02, 1·16) and women (RR 1·14, 95 % CI 1·06, 1·22). Also, the area under the receiver operating characteristic curve value for hypertension was higher for CVAI than the four other obesity indices for both sexes (all P < 0·05). Finally, per-sd increase in CVAI change was associated with hypertension for both men (RR 1·26, 95 % CI 1·16, 1·36) and women (RR 1·23, 95 % CI 1·15, 1·30). Similar results were observed in sensitivity analyses. CVAI and its 6-year change are positively associated with hypertension risk. CVAI has better performance in predicting hypertension than other visceral obesity indices for both sexes. The current findings suggest CVAI as a reliable and applicable predictor of hypertension in rural Chinese adults.

Graded epistemic logic is a logic for reasoning about uncertainties. Graded epistemic logic is interpreted on graded models. These models are generalizations of Kripke models. We obtain completeness of some graded epistemic logics. We further develop dynamic extensions of graded epistemic logics, along the framework of dynamic epistemic logic. We give an extension with public announcements, i.e., public events, and an extension with graded event models, a generalization also including nonpublic events. We present complete axiomatizations for both logics.