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It is generally known that although a connection between abdominal obesity and chronic kidney disease (CKD) is well-established, there is a lack of systematic research investigating the specific roles of serum metabolites, including lipid metabolites, amino acid metabolites, carbohydrate metabolites and inflammatory substances in explaining this associations. We included 118,020 general patients with data of serum metabolites from UK Biobank. We defined abdominal obesity and CKD based on waist circumference and ICD-10 criteria. The serum metabolites were assessed by a high-throughput nuclear magnetic resonance (NMR) based metabolic biomarker profiling platform. We conducted mediation analysis by R software and used the proportion of mediation to quantify the mediation effect. This study demonstrated that lipid metabolites played a more important role in mediating the relationship between abdominal obesity and CKD than amino acid metabolites and carbohydrate metabolites. And Glycoprotein Acetyls (GlycA) was the strongest mediator for the correlation between abdominal obesity and CKD, accounting for 26.4 %. And In the mediation analysis stratified by sex, we found that the mediating effects of lipid metabolites were mostly higher in men than in women, while GlycA accounted for the largest proportion of the mediation association in both two groups (31.0 % for women and 19.8 % for men). Among lipid metabolites, amino acid metabolites, carbohydrate metabolites and inflammatory substances, our study showed that infammation marker GlycA was the novel and key mediator for the correlation between abdominal obesity and CKD. [ABSTRACT FROM AUTHOR]

Obesity has become a global problem that poses a serious threat to human health. Laparoscopic sleeve gastrectomy (LSG) is an effective long-term treatment. However, the weight loss of some patients after LSG is still insufficient. It is necessary to investigate the factors associated with inadequate weight loss after LSG. The objective of this study was to explore whether preoperative insulin secretion could be associated with weight loss after LSG in patients with obesity. This is a single-center prospective cohort study conducted in a university hospital. Patients from a prospective database who underwent LSG were analyzed. All 178 participants underwent a 75-g oral glucose tolerance test (OGTT) to assess preoperative insulin and c-peptide secretion before LSG. The areas under the curve (AUCs) for glucose, insulin, and c-peptide were determined in the OGTT. The percentage of excess weight loss (%EWL) and the percentage of total weight loss (%TWL) were used to estimate the effect of weight loss after LSG. Regression models were used to assess the correlation between preoperative insulin and c-peptide secretion with %EWL ≥75% and TWL ≥35% at 12 months after LSG. The AUCs of insulin and c-peptide were significantly lower in the %EWL ≥75% and %TWL ≥35% groups at 0–30 minutes, 0–60 minutes, and 0–120 minutes during the OGTT. At 30, 60, and 120 minutes during the OGTT, c-peptide levels were significantly lower in the %EWL ≥75% group and %TWL ≥35% group. The preoperative c-peptide level at 30 minutes during the OGTT (C 30) was significantly negatively correlated with %EWL (β = −.37, P <.001) and %TWL (β = −.28, P =.011). Univariate logistic regression analysis showed that preoperative C 30 was associated with %EWL ≥75% and %TWL ≥35% after LSG. According to multiple logistic regression analysis, patients with a low preoperative C 30 had an 8-fold higher %TWL ≥35% after LSG than those with a high C 30 (odds ratio: 8.41 [95% confidence interval: 1.46–48.58], P =.017). Similarly, patients with a low preoperative C 30 had a 7-fold higher EWL% ≥75% after LSG than patients with a high C 30 (odds ratio: 7.25 [95% confidence interval: 1.11–47.50], P =.039). The rate of weight loss after LSG is low among patients with preoperative hyperinsulinemia. The preoperative c-peptide level at 30 minutes during the OGTT is associated with weight loss after LSG. • Early-phase insulin levels are associated with unrelieved obesity. • Hyperinsulinemia might predict inadequate weight loss after laparoscopic sleeve gastrectomy (LSG). • Preoperative C-peptide at 30 minutes after OGTT could be used as an independent predictor of weight loss outcome after LSG. [ABSTRACT FROM AUTHOR]

The relationship between cereals intake and diabetes is unclear. We aimed to explore associations between individual cereals intake and risks of incident and progression of diabetes. We included 502,490 participants from UK Biobank at baseline. A single touchscreen food frequency questionnaire was used to estimate the intake of individual cereals (bran, biscuit, oat, muesli, and other cereals). Main outcomes included incident diabetes and diabetic complications of cardiovascular disease (CVD), chronic kidney disease (CKD) and diabetic retinopathy (DR). Polygenic risk score (PRS) of glycosylated hemoglobin (HbA1c) was calculated for mediating effects analysis. Among participants without diabetes, when compared to subjects who never had cereals, hazard ratios (95%CI) of developing diabetes in those who had ≥6 bowls/week were 0.72 (0.67–0.78) for bran, 0.86 (0.81–0.92) for biscuit, 0.75(0.66–0.84) for oat, and 0.57(0.53,0.61) for muesli. Among people with diabetes without CVD, a higher intake of aforementioned four individual cereals was associated with a 13%–32 % lower risk of developing CVD. Among people with diabetes without CKD, a higher intake of aforementioned four individual cereals was associated with a 9%–28 % lower risk of developing CKD. We observed a significant mediating effect of the PRS of HbA1c for the association between aforementioned four individual cereals and developing diabetes. A higher consumption of cereals was significantly associated with lower risks of diabetes and diabetic complications. Polygenic of HbA1c mediates the effect of cereals on incident diabetes. • Cereals intake is associated with lower risks of diabetes and its complications. HbA1c related genes mediate the effect of cereals on diabetes. [ABSTRACT FROM AUTHOR]

Renin-independent aldosteronism (RIA) describes the spectrum of autonomous aldosterone secretion from mild to overt. We aimed to explore whether RIA is causally associated with chronic kidney disease (CKD) in patients with diabetes. We cross-sectionally included 1027, 402 and 39,709 patients with any type of diabetes from cohorts of EIMDS, CONPASS and UK Biobank, respectively. In EIMDS, we defined RIA and renin-dependent aldosteronism based on plasma aldosterone and renin concentrations. We performed captopril challenge test to confirm renin-dependent or independent aldosteronism in CONPASS. In UK Biobank, we generated genetic instruments for RIA based on the genome-wide association studies (GWAS). We extracted the corresponding single nucleotide polymorphisms (SNPs) information from the GWAS data of CKD in diabetes. We harmonized the SNP-RIA and SNP-CKD data to conduct the two-sample Mendelian randomization analyses. In EIMDS and CONPASS, when compared to subjects with normal aldosterone concentration or renin-dependent aldosteronism, participants with RIA had a lower estimated glomerular filtration rate, a higher prevalence of CKD, and a higher multivariate-adjusted odds ratio (OR) of CKD (OR 2.62 [95%CI 1.09–6.32] in EIMDS, and 4.31 [1.39–13.35] in CONPASS). The two-sample Mendelian randomization analysis indicated that RIA was significantly associated with a higher risk of CKD (inverse variance weighted OR 1.10 [95 % CI 1.05–1.14]), with no evidence of significant heterogeneity or substantial directional pleiotropy. Among patients with diabetes, renin-independent aldosteronism is causally associated with a higher risk of CKD. Targeted treatment of autonomous aldosterone secretion may benefit renal function in diabetes. • Diabetic patients with RIA had a higher risk of CKD compared to normal aldosterone or renin-dependent aldosteronism. • Two-sample Mendelian randomization analysis indicated that RIA was causally associated with CKD in diabetic patients. • Targeted treatment of autonomous aldosterone secretion may benefit renal function in diabetic patients. [ABSTRACT FROM AUTHOR]

The ability to use infrared imaging systems with multicolor capabilities, high photoresponsivity and polarization sensitivity, is central to practical photodetectors and has been demonstrated with conventional devices based on Ⅲ-Ⅴ or Ⅱ-Ⅵ semiconductors. However, the photodetectors working at room temperature with high responsivity for polarized infrared light detection remains elusive. Here, we first demonstrate a broadband photodetector using a vertical photogate heterostructure of BP-on-WSe 2 (black phosphorus-on-tungsten diselenide) in which BP serves as the photogate and WSe 2 as the conductive channel. Ultrahigh visible and infrared photoresponsivity at room temperature can reach up to ~10 3 A/W and ~5×10 −1 A/W, respectively, and ultrasensitive visible and infrared specific detectivity is obtained up to ~10 14 and ~10 10 Jones respectively at room temperature. Moreover, the high sensitivity to infrared polarization is about 40 mA/W with incident light polarized along the horizontal axis (defined as 0° polarization). This performance is due to the strong intrinsic linear dichroism of BP and the device design which can sufficiently collect the photoinduced carriers isotropically, as well as the influence from the orientation of the edge of the BP-on-WSe 2 overlapped area which is the same for all polarizations. The high responsivity, good sensitive detectivity and highly polarization-sensitive infrared photoresponse suggest that the photodetectors based on photogate structure afford new opportunities for infrared detecting or imaging at room temperature by using two-dimensional materials. [ABSTRACT FROM AUTHOR]

The association between fat mass and mortality has been equivocally shown to be linear, J-shaped, and U-shaped. We aimed to clarify this relationship based on Mendelian randomization (MR) analysis and lifestyle modification. This prospective analysis included 449,831 participants from UK Biobank. Linear MR analysis was used to estimate the linear relationship between fat mass and mortality. We assessed whole body fat mass by bioimpedance analysis at baseline and categorized subjects into five equal groups based on fat mass index (FMI). The association between FMI and mortality were investigated among whole population and in subgroups stratified by individual lifestyle factors, including diet, physical activity, smoking, alcohol, sleep and psychological health. Linear MR analyses indicated a positive association between genetically predicted fat mass and all-cause mortality (HR 1.10, 95 % CI 1.08–1.12, P < 0.001). The association between FMI and all-cause mortality was manifested as J-shaped (HRs across FMI categories: 1.04, 1.00, 1.07, 1.21, 1.54), which was significantly modified by the number of low-risk lifestyle factors (P for interaction<0.001). When evaluating individual lifestyle factors, we observed a nonlinear relationship between FMI and all-cause mortality among participants who had high-risk lifestyle factors, while a linear relationship was observed among participants who had low-risk lifestyle factors, especially for those with adequate physical activity (HRs across FMI categories: 0.95, 1.00, 1.05, 1.17, 1.44) and who never smoked (0.96, 1.00, 1.03, 1.14, 1.51). Genetically determined fat mass is causally and linearly associated with mortality. The J-shape association between anthropometric FMI and mortality is caused by high-risk lifestyle factors. [Display omitted] • Mendelian randomization analyses indicated a causal association between genetically determined fat mass and mortality. • The association between anthropometric fat mass and all-cause mortality was manifested as J-shaped. • The elevated risk of mortality observed in people with low fat mass was modified by a high-risk lifestyle. [ABSTRACT FROM AUTHOR]

Epidemiologic studies have provided solid evidence for the neurotoxic effect of lead for decades of years. In view of the fact that children are more vulnerable to the neurotoxicity of lead, lead exposure has been an urgent public health concern. The modes of action of lead neurotoxic effects include disturbance of neurotransmitter storage and release, damage of mitochondria, as well as induction of apoptosis in neurons, cerebrovascular endothelial cells, astroglia and oligodendroglia. Our studies here, from a novel point of view, demonstrates that lead specifically caused induction of COX-2, a well known inflammatory mediator in neurons and glia cells. Furthermore, we revealed that COX-2 was induced by lead in a transcription-dependent manner, which relayed on transcription factor NFAT, rather than AP-1 and NFκB, in glial cells. Considering the important functions of COX-2 in mediation of inflammation reaction and oxidative stress, our studies here provide a mechanistic insight into the understanding of lead-associated inflammatory neurotoxicity effect via activation of pro-inflammatory NFAT3/COX-2 axis. [ABSTRACT FROM AUTHOR]