Efficient identification of QTL for agronomic traits in foxtail millet (Setaria italica) using RTM- and MLM-GWAS.

KEY MESSAGE: Eleven QTLs for agronomic traits were identified by RTM- and MLM-GWAS, putative candidate genes were predicted and two markers for grain weight were developed and validated. Foxtail millet (Setaria italica), the second most cultivated millet crop after pearl millet, is an important grain crop in arid regions. Seven agronomic traits of 408 diverse foxtail millet accessions from 15 provinces in China were evaluated in three environments. They were clustered into two divergent groups based on genotypic data using ADMIXTURE, which was highly consistent with their geographical distribution. Two models for genome-wide association studies (GWAS), namely restricted two-stage multi-locus multi-allele (RTM)-GWAS and mixed linear model (MLM)-GWAS, were used to dissect the genetic architecture of the agronomic traits based on 13,723 SNPs. Eleven quantitative trait loci (QTLs) for seven traits were identified using two models (RTM- and MLM-GWAS). Among them, five were considered stable QTLs that were identified in at least two environments using MLM-GWAS. One putative candidate gene (SETIT_006045mg, Chr4: 744,701-746,852) that can enhance grain weight per panicle was identified based on homologous gene comparison and gene expression analysis and was validated by haplotype analysis of 330 accessions with high-depth (10×) resequencing data (unpublished). In addition, homologous gene comparison and haplotype analysis identified one putative foxtail millet ortholog (SETIT_032906mg, Chr2: 5,020,600-5,029,771) with rice affecting the target traits. Two markers (cGWP6045 and kTGW2906) were developed and validated and can be used for marker-assisted selection of foxtail millet with high grain weight. The results provide a fundamental resource for foxtail millet genetic research and breeding and demonstrate the power of integrating RTM- and MLM-GWAS approaches as a complementary strategy for investigating complex traits in foxtail millet.

The methodological quality of systematic reviews regarding the Core Outcome Set (COS) development.

BACKGROUND: The Core Outcome Measures in Effectiveness Trials (COMET) working group proposed core outcome sets (COS) to address the heterogeneity in outcome measures in clinical studies. According to the recommendations of COMET, performing systematic reviews (SRs) usually was the first step for COS development. However, the SRs that serve as a basis for COS are not specifically appraised by organizations such as COMET regarding their quality. Here, we investigated the status of SRs related to development of COS and evaluated their methodological quality. METHODS: We conducted a search on PubMed to identify SRs related to COS development published from inception to May 2022. We qualitatively summarized the disease included in SR topics, and the studies included in the SRs. We evaluated the methodological quality of the SRs using AMSTAR 2.0 and compared the overall quality of SRs with and without protocols using the Mann-Whitney U test. RESULTS: We included 175 SRs from 23 different countries or regions, and they mainly focused on five diseases: musculoskeletal system or connective tissue disease (n = 19, 10.86%), injury, poisoning, or certain other consequences of external causes (n = 18, 10.29%), digestive system disease (n = 16, 9.14%), nervous system disease (n = 15, 8.57%), and genitourinary system disease (n = 15, 8.57%). Although 88.00% of SRs included randomized controlled trials (RCTs), only a few SRs (23.38%) employed appropriate tools to assess the risk of bias in RCTs. The assessment results on the basis of AMSTAR 2.0 indicated that most SRs (93.71%) were rated as ''critically low'' to ''low'' in terms of overall confidence. The overall confidence of SRs with protocols was significantly higher than that without protocols (P <.001). Compared to the SRs with protocols on Core Outcome Measures in Effectiveness Trials (COMET), SRs with protocols on PROSPERO were of better overall confidence (P = .017). CONCLUSION: The overall quality of published SRs regarding COS development was poor. Our findings emphasize the need for researchers to carefully select the disease topic and strictly adhere to the requirements of optimal methodology when conducting a SR for the establishment of a COS.

Regional policy options for carbon peaking in the Yangtze River Delta under uncertainty.

The Yangtze River Delta (YRD) region plays a crucial role in achieving China's carbon peaking goal. However, due to uncertainties surrounding future economic growth, energy consumption, energy structure, and population, the attainment of carbon peaking in this region remains uncertain. To address this issue, this study utilized the generalized Divisia index method to analyze the driving factors of carbon emissions, including economy, energy, investment, and population. Subsequently, Monte Carlo simulations were combined with scenario analysis to dynamically explore the peak path of regional heterogeneity in the YRD from 2022 to 2035 under uncertain conditions. The findings highlighted that economic uncertainty has the most significant impact on carbon emissions. Furthermore, reducing energy intensity and promoting the transformation of the energy consumption structure contribute to carbon reduction. The study also revealed that the carbon peak in the YRD exhibits regional heterogeneity. According to the baseline scenario, carbon emissions in the YRD will not peak before 2035. However, under the low-carbon development scenario, the carbon emissions of Zhejiang and Shanghai will peak before 2030. Moreover, under the enhanced emission reduction (EE) scenario, carbon emissions in Jiangsu, Zhejiang, and Shanghai will peak before 2025, while Anhui will reach its peak before 2030. Collectively, the entire YRD region is forecasted to attain a carbon emissions peak of 2.29 billion tons by 2025 under the EE scenario. This study provides valuable insights into the carbon emission trajectories of the YRD region under uncertain conditions. The findings can be instrumental in formulating carbon peaking policies that account for regional heterogeneity.

A longevity level-oriented wellness target area identification method: a case study of Yunnan Province, China.

Background: Aging, as a global demographic issue, is characterized by its rapid growth, which drives an increase in people's healthcare awareness. The emergence of wellness bases caters to this market demand. Therefore, the identification of potential areas suitable for wellness activities and the construction of wellness bases, referred to as Wellness Target Areas (WTAs), becomes a crucial first step. Currently, commonly used identification methods are mostly based on traditional statistical approaches, which are often complex, cumbersome, and subject to potential risks of subjective assumptions, affecting the reliability of WTAs identification results. Longevity level serves as a comprehensive indicator reflecting the natural and socio-economic environment of a region, making it the most indicative of the regional wellness environment status. Methods: This study proposes using longevity level as the benchmark for WTAs identification to simplify the identification process and reduce the impact of subjective bias on the results. The study focuses on 129 county-level units in Yunnan Province. Firstly, the Geodetector (GD) is utilized to explore the complex interaction between the longevity level and the geographical environment to determine regional wellness factors. Secondly, using ArcGIS and geographical weighted regression (GWR), the study investigates the role of different wellness factors, ultimately classifying and grading the WTAs. Results: The longevity level in Yunnan Province exhibits a pattern of multi-point clustering, forming three major longevity regions. Factors that significantly influence longevity level include annual average precipitation, sunshine duration, PM2.5 content, per capita disposable income, density of tourist attractions, and distance from residential areas to hospitals. Based on the degree of longevity and the contribution rate of influencing factors, Yunnan Province's WTAs are classified into three levels and two types (natural and comprehensive). Conclusion: Our study aims to establish a connection between longevity level and the selection of wellness bases, exploring regional wellness factors through the relationship between longevity phenomena and geographical environment, identifying potential construction areas for wellness bases (i.e., WTAs), providing new insights for the precise selection of wellness bases, effectively enhancing the scientificity of site selection, promoting population health, and contributing to the global aging process with better health.

Astragalin from Thesium chinense: A Novel Anti-Aging and Antioxidant Agent Targeting IGFR/CD38/Sirtuins.

Astragalin (AG), a typical flavonoid found in Thesium chinense Turcz (T. chinense), is abundant in various edible plants and possesses high nutritional value, as well as antioxidant and antibacterial effects. In this study, we initially predicted the mechanism of action of AG with two anti-aging and antioxidant-related protein targets (CD38 and IGFR) by molecular docking and molecular dynamics simulation techniques. Subsequently, we examined the anti-aging effects of AG in Caenorhabditis elegans (C. elegans), the antioxidant effects in zebrafish, and verified the related molecular mechanisms. In C. elegans, AG synergistically extended the lifespan of C. elegans by up-regulating the expression of daf-16 through inhibiting the expression of daf-2/IGFR and also activating the AMPK and MAPK pathways to up-regulate the expression of sir-2.1, sir-2.4, and skn-1. In oxidatively damaged zebrafish embryos, AG demonstrated a synergistic effect in augmenting the resistance of zebrafish embryos to oxidative stress by up-regulating the expression levels of SIRT1 and SIRT6 within the zebrafish embryos system via the suppression of CD38 enzymatic activity and then inhibiting the expression of IGFR through high levels of SIRT6. These findings highlight the antioxidant and anti-aging properties of AG and indicate its potential application as a supplementary ingredient in aquaculture for enhancing fish health and growth.