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Our MR approach further identified new metabolites potentially playing a causal role on T2D, including betaine, lysine and mannose. ARS853 Interestingly, for valine and leucine a strong reverse causal effect was detected, indicating that the genetic predisposition to T2DM may trigger early changes of these metabolites, which appear well-before any clinical symptoms. In addition, our study revealed a reverse causal effect of metabolites such as glutamic acid and alanine. Collectively, these findings indicate that molecular traits linked to the genetic basis of T2DM may be particularly promising early biomarkers.Myopia (near-sightedness) is an important public health issue. Spending more time outdoors can prevent myopia but the long-term association between this exposure and myopia has not been well characterised. We investigated the relationship between time spent outdoors in childhood, adolescence and young adulthood and risk of myopia in young adulthood. The Kidskin Young Adult Myopia Study (KYAMS) was a follow-up of the Kidskin Study, a sun exposure-intervention study of 1776 children aged 6-12 years. Myopia status was assessed in 303 (17.6%) KYAMS participants (aged 25-30 years) and several subjective and objective measures of time spent outdoors were collected in childhood (8-12 years) and adulthood. Index measures of total, childhood and recent time spent outdoors were developed using confirmatory factor analysis. Logistic regression was used to assess the association between a 0.1-unit change in the time outdoor indices and risk of myopia after adjusting for sex, education, outdoor occupation, parental myopia, parental education, ancestry and Kidskin Study intervention group. Spending more time outdoors during childhood was associated with reduced risk of myopia in young adulthood (multivariable odds ratio [OR] 0.82, 95% confidence interval [CI] 0.69, 0.98). Spending more time outdoors in later adolescence and young adulthood was associated with reduced risk of late-onset myopia (≥ 15 years of age, multivariable OR 0.79, 95% CI 0.64, 0.98). Spending more time outdoors in both childhood and adolescence was associated with less myopia in young adulthood.A brain atlas is necessary for analyzing structure and function in neuroimaging research. Although various annotation volumes (AVs) for the mouse brain have been proposed, it is common in magnetic resonance imaging (MRI) of the mouse brain that regions-of-interest (ROIs) for brain structures (nodes) are created arbitrarily according to each researcher's necessity, leading to inconsistent ROIs among studies. One reason for such a situation is the fact that earlier AVs were fixed, i.e. combination and division of nodes were not implemented. This report presents a pipeline for constructing a flexible annotation atlas (FAA) of the mouse brain by leveraging public resources of the Allen Institute for Brain Science on brain structure, gene expression, and axonal projection. A mere two-step procedure with user-specified, text-based information and Python codes constructs FAA with nodes which can be combined or divided objectively while maintaining anatomical hierarchy of brain structures. Four FAAs with total node count of 4, 101, 866, and 1381 were demonstrated. Unique characteristics of FAA realized analysis of resting-state functional connectivity (FC) across the anatomical hierarchy and among cortical layers, which were thin but large brain structures. FAA can improve the consistency of whole brain ROI definition among laboratories by fulfilling various requests from researchers with its flexibility and reproducibility.It has been demonstrated that a staggered window achieves better noise reduction performance than a traditional single glazing one at middle to high frequencies while maintaining a degree of natural ventilation. There is, however, little improvement in the low frequency range. In contrast, this work proposes to apply coiled-up silencers consisting of coupled tubes on the side walls of staggered windows to obtain noise attenuation in a broad band, especially in the low frequency range. Each element in the silencer consists of two coupled tubes with different cross sections so that noise at more frequencies can be attenuated than that with a uniform cross section. The simulation results show that 8.8 dB overall insertion loss can be obtained between 100 and 500 Hz after applying a combination of silencers designed at 7 different frequencies, and the insertion loss of the staggered window is increased from 6.7 to 15.6 dBA between 100 and 2000 Hz for normal incident traffic noise with the proposed silencers installed. The design is validated by the experiments with a 14 scale down model.Fertilizer-induced changes in soil nutrients regulate nitrogen (N) fixation in the terrestrial biosphere, but the influences of N and phosphorus (P) fertilization on the diazotroph communities in successive crop seasons were unclear. In this study, we assessed the effects of N and P (high vs. low doses) on the abundance and structure of N2-fixation communities after wheat and soybean harvest in a long-term (34 and 35 years) fertilization experiment. In both seasons, long-term N addition significantly decreased the abundance of nifH genes and 16S rDNA; in addition, high doses of N and P fertilizer decreased the richness of diazotrophs, whereas low doses did not. The proportion of the dominant genus, Bradyrhizobium, in the soybean season (86.0%) was higher than that in the wheat season (47.9%). Fertilization decreased diazotroph diversity and the relative abundance of Bradyrhizobium in the wheat season, but had insignificant effects in the soybean season. The addition of N, but not P, significantly changed the communities of both diazotrophs (at the genus level) and rhizobia (at the species level) in the two seasons. Soil pH was positively associated with nifH abundance and diazotrophic richness; soil NO3- content was negatively correlated with diazotrophic richness and positively correlated with diversity. Soil pH and NO3- content were the two main drivers shaping the soil diazotrophic community. Overall, long-term inorganic N had a greater influence than P on both diazotrophic abundance and community composition, and diazotrophic diversity was more clearly affected by fertilization in the wheat season than in the soybean season.

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