Relation of Dietary Carbohydrates Intake to Circulating Sex Hormone-binding Globulin Levels in Postmenopausal Women

Background Low circulating levels of sex hormone‐binding globulin (SHBG) have been shown to be a direct and strong risk factor for type 2 diabetes, cardiovascular diseases, and hormone‐dependent cancers, although the relationship between various aspects of dietary carbohydrates and SHBG levels remains unexplored in population studies. Methods Among postmenopausal women with available SHBG measurements at baseline (n = 11 159) in the Women's Health Initiative, a comprehensive assessment was conducted of total dietary carbohydrates, glycemic load (GL), glycemic index (GI), fiber, sugar, and various carbohydrate‐abundant foods in relation to circulating SHBG levels using multiple linear regressions adjusting for potential covariates. Linear trend was tested across quartiles of dietary variables. Benjamini and Hochberg's procedure was used to calculate the false discovery rate for multiple comparisons. Results Higher dietary GL and GI (both based on total and available carbohydrates) and a higher intake of sugar and sugar‐sweetened beverages were associated with lower circulating SHBG concentrations (all P trend < 0.05; Q ‐values = 0.04,0.01, 0.07, 0.10, 0.01, and <0.0001, respectively). In contrast, women with a greater intake of dietary fiber tended to have elevated SHBG levels (P trend = 0.01, Q ‐value = 0.04). There was no significant association between total carbohydrates or other carbohydrate‐abundant foods and SHBG concentrations. Conclusions The findings suggest that low GL or GI diets with low sugar and high fiber content may be associated with higher serum SHBG concentrations among postmenopausal women. Future studies investigating whether lower GL or GI diets increase SHBG concentrations are warranted

Genetic Drivers of Heterogeneity in Type 2 Diabetes Pathophysiology

Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes1,2 and molecular mechanisms that are often specific to cell type3,4. Here, to characterize the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study data from 2,535,601 individuals (39.7% not of European ancestry), including 428,452 cases of T2D. We identify 1,289 independent association signals at genome-wide significance (P \u3c 5 × 10-8) that map to 611 loci, of which 145 loci are, to our knowledge, previously unreported. We define eight non-overlapping clusters of T2D signals that are characterized by distinct profiles of cardiometabolic trait associations. These clusters are differentially enriched for cell-type-specific regions of open chromatin, including pancreatic islets, adipocytes, endothelial cells and enteroendocrine cells. We build cluster-specific partitioned polygenic scores5 in a further 279,552 individuals of diverse ancestry, including 30,288 cases of T2D, and test their association with T2D-related vascular outcomes. Cluster-specific partitioned polygenic scores are associated with coronary artery disease, peripheral artery disease and end-stage diabetic nephropathy across ancestry groups, highlighting the importance of obesity-related processes in the development of vascular outcomes. Our findings show the value of integrating multi-ancestry genome-wide association study data with single-cell epigenomics to disentangle the aetiological heterogeneity that drives the development and progression of T2D. This might offer a route to optimize global access to genetically informed diabetes care

Genetic drivers of heterogeneity in type 2 diabetes pathophysiology

Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes1,2 and molecular mechanisms that are often specific to cell type3,4. Here, to characterize the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study data from 2,535,601 individuals (39.7% not of European ancestry), including 428,452 cases of T2D. We identify 1,289 independent association signals at genome-wide significance (P &lt; 5 × 10-8) that map to 611 loci, of which 145 loci are, to our knowledge, previously unreported. We define eight non-overlapping clusters of T2D signals that are characterized by distinct profiles of cardiometabolic trait associations. These clusters are differentially enriched for cell-type-specific regions of open chromatin, including pancreatic islets, adipocytes, endothelial cells and enteroendocrine cells. We build cluster-specific partitioned polygenic scores5 in a further 279,552 individuals of diverse ancestry, including 30,288 cases of T2D, and test their association with T2D-related vascular outcomes. Cluster-specific partitioned polygenic scores are associated with coronary artery disease, peripheral artery disease and end-stage diabetic nephropathy across ancestry groups, highlighting the importance of obesity-related processes in the development of vascular outcomes. Our findings show the value of integrating multi-ancestry genome-wide association study data with single-cell epigenomics to disentangle the aetiological heterogeneity that drives the development and progression of T2D. This might offer a route to optimize global access to genetically informed diabetes care.</p

Does aluminum exposure affect cognitive function? a comparative cross-sectional study.

ObjectivesThis study assessed the cognitive function of aluminum-exposed participants from an alum mining zone, compared them with unexposed subjects, and aimed to elucidate the effect of aluminum exposure on cognition.DesignThis was a comparative cross-sectional study. Univariate analyses were used to assess the differences between the aluminum-exposed and unexposed groups. Binary logistic regression models were applied to analyze the effect of aluminum exposure.SettingThe aluminum-exposed participants were included from an alum mining zone and the unexposed subjects were residents from another district without alum-mine-related factories.ParticipantsWe included 539 aluminum-exposed participants (254 men, 285 women) and 1720 unexposed participants (692 men, 1028 women).ResultsThe mean cognition score on Mini-Mental State Examination was 21.34 (± 6.81) for aluminum-exposed participants. The exposed group had 6.77 times (95% confidence interval, 5.09-9.00) more risk of cognitive impairment than the unexposed group, after adjusting for age, sex, and educational level. No statistically significant association was found between exposure duration and cognition.ConclusionsThis study demonstrated a significant association between aluminum exposure and lower cognitive function

Identification of miRNAs Mediating Seed Storability of Maize during Germination Stage by High-Throughput Sequencing, Transcriptome and Degradome Sequencing

Seed storability is an important trait for improving grain quality and germplasm conservation, but little is known about the regulatory mechanisms and gene networks involved. MicroRNAs (miRNAs) are small non-coding RNAs regulating the translation and accumulation of their target mRNAs by means of sequence complementarity and have recently emerged as critical regulators of seed germination. Here, we used the germinating embryos of two maize inbred lines with significant differences in seed storability to identify the miRNAs and target genes involved. We identified a total of 218 previously known and 448 novel miRNAs by miRNA sequencing and degradome analysis, of which 27 known and 11 newly predicted miRNAs are differentially expressed in two maize inbred lines, as measured by Gene Ontology (GO) enrichment analysis. We then combined transcriptome sequencing and real-time quantitative polymerase chain reaction (RT-PCR) to screen and confirm six pairs of differentially expressed miRNAs associated with seed storability, along with their negative regulatory target genes. The enrichment analysis suggested that the miRNAs/target gene mediation of seed storability occurs via the ethylene activation signaling pathway, hormone synthesis and signal transduction, as well as plant organ morphogenesis. Our results should help elucidate the mechanisms through which miRNAs are involved in seed storability in maize

Slow energy transfer in self-doped beta-conformation film of steric polydiarylfluorenes toward stable dual deep-blue amplified spontaneous emission

Exciton behavior is crucial for improving the optoelectronic property of a light-emitting conjugated polymer. Herein, the photoexcitation dynamics of exciton migration and energy transfer in a self-doped β-conformation film of the polydiarylfluorenes (poly[4-(octyloxy)-9,9-diphenylfluoren-2,7-diyl]-co-[5-(octyloxy)-9,9- diphenylfluoren-2,7-diyl], PODPF) are demonstrated. Compared to the first generation of the β-conformation polyfluorene, poly(9,9-dioctylfluorene) (PFO), energy transfer occurs in PODPF β-conformation films in a time period of ≈150 ps, much longer than those of the PFO ones (<5 ps), associated with the effective intrachain energy transfer (few hundred picoseconds), rather than interchain Förster energy transfer (a few picoseconds). Similar to PFO, the PODPF β-conformation also displays well-resolved vibronic emission peaks at 20 K, attributed to the planar and rigid conformation. Interestingly, a residual 0-0 band emission of nonplanar conformation chain segments (435 nm, 2.85 eV) at 20 K also further confirms the exciton migration from the amorphous state to the β-conformation domain in PODPF films. Therefore, the stable dual amplified spontaneous emission (ASE) behavior of the PODPF self-doped films at 461 nm (2.69 eV) and 483 nm (2.57 eV), originates from the individual amorphous and β-conformation domains