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[This retracts the article DOI: 10.1016/j.omtn.2019.07.012.].
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Progress in understanding early human development has been impeded by the scarcity of reference datasets from natural embryos, particularly those with spatial information during crucial stages like gastrulation. We conducted high-resolution spatial transcriptomics profiling on 38,562 spots from 62 transverse sections of an intact Carnegie stage (CS) 8 human embryo. From this spatial transcriptomic dataset, we constructed a 3D model of the CS8 embryo, in which a range of cell subtypes are identified, based on gene expression patterns and positional register, along the anterior-posterior, medial-lateral, and dorsal-ventral axis in the embryo. We further characterized the lineage trajectories of embryonic and extra-embryonic tissues and associated regulons and the regionalization of signaling centers and signaling activities that underpin lineage progression and tissue patterning during gastrulation. Collectively, the findings of this study provide insights into gastrulation and post-gastrulation development of the human embryo.
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Embrión de Mamíferos , Gastrulación , Regulación del Desarrollo de la Expresión Génica , Imagenología Tridimensional , Humanos , Embrión de Mamíferos/metabolismo , Transcriptoma/genética , Gástrula/metabolismo , Gástrula/embriología , Transducción de Señal , Linaje de la Célula , Perfilación de la Expresión Génica , Tipificación del Cuerpo/genéticaRESUMEN
OBJECTIVES: To determine whether the age at menarche (AAM) and the age at menopause (ANM) are causally related to the development of sepsis. METHODS: We performed a two-sample Mendelian randomization (MR) analysis by utilizing summary statistics from genome-wide association study (GWAS) datasets for both the exposure and outcome variables. Single nucleotide polymorphisms (SNPs) that exhibited significant associations with AAM and ANM were chosen as instrumental variables to estimate the causal effects on sepsis. Our study employed a variety of methods, including MR-Egger regression, weighted median estimation, inverse variance weighting, a simple model, and a weighted model. Odds ratios (ORs) along with their corresponding 95% confidence intervals (CIs) were used as the primary indicators for assessing causality. Furthermore, we conducted sensitivity analyses to explore the presence of genetic heterogeneity and validate the robustness of the tools employed. RESULT: Our analysis revealed a significant negative causal relationship between AAM and the risk of sepsis (IVW: OR = 0.870, 95% CI = 0.793-0.955, P = 0.003). However, our Mendelian randomization (MR) analysis did not yield sufficient evidence to support a causal link between ANM and sepsis (IVW: OR = 0.987, 95% CI = 0.971-1.004, P = 0.129). CONCLUSIONS: Our findings suggest that an earlier AAM may be associated with an increased risk of sepsis. However, we did not find sufficient evidence to support a causal relationship between ANM and sepsis.
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Análisis de la Aleatorización Mendeliana , Sepsis , Femenino , Humanos , Estudio de Asociación del Genoma Completo , Menarquia/genética , Menopausia/genética , Sepsis/genéticaRESUMEN
Currently, the development of economical and effective non-noble metal electrocatalysts is vital for advancing hydrogen evolution reaction (HER) and enabling its widespread applications. The customizable pore structure and enormous surface area of metal-organic frameworks (MOFs) have made them to become promising non-noble metal electrocatalysts for HER. However, MOFs have some challenges, including low conductivity and instability, which can result in them having high overpotentials and slow reaction kinetics in electrocatalytic processes. In this work, we present an innovative approach for synthesizing cost-effective and high-efficient Zr-MOF-derived pH-universal electrocatalysts for HER. It entails creating the interfaces of the electrocatalysts with suitable proportions of phosphide nanostructures. Zr-MOF/Ni2P@nickel foam (NF) electrodes with interface regulated by Ni2P nanostructures were successfully developed for high-efficient pH-universal HER electrocatalysts. The presence of Ni2P nanostructures with abundant active sites at the Zr-MOFs@NF interfaces boosted the electronic conductivity and local charge density of the hybrid electrocatalysts. This helped to improve their reaction kinetics and electrocatalytic activity. By optimizing the Ni2P amount, Zr-MOF/Ni2P@NF demonstrated impressive stability and superior HER activities, with a low overpotential of 149 mV (acidic electrolytes) and 143 mV (alkaline electrolytes) at 10 mA cm-2. The proven strategy in this work can be expanded to many types of MOF-based materials for wider practical applications.