Search

With the operation of the first route in Xi'an City, the matching relationship between the metro networks and the urban population is a root factor affecting the utilization of rail transit facilities. The mismatch between the metro networks and the urban population has led to an imbalance between the supply and demand for rail transport, resulting in wasted urban infrastructure. Based on this issue, the research objective is to focus on the spatiotemporal variations of the matching relationship. Firstly, the topological network model abstractly extracted metro spatial distribution features, and the spatial autocorrelation model was adopted to identify the evolution characteristics of the metro networks and urban population. Secondly, this paper adopted a time-lagged regression model to demonstrate the action relationship from 2011 to 2021. Then, the compositive coordination index was utilized to assess the variation of the global matching relationship. Finally, the paper explored spatial heterogeneity through the coupling coherence degree attached to grid cells. The research results indicate that the Moran's I value of metro elements decreased from 0.782 to 0.510 with the further complexity of topological networks, while the population was consistently high in spatial dependence with a Moran's I value of around 0.75 during the decade. Based on the regression coefficients and significance, this paper verified the hypothesis that the metro networks and urban population had a positive time-lagged feedback effect in urban development. From 2011 to 2021, the compositive coordination index symbolizing the global matching relationship increased from 0.29 to 0.90, but the coupling coherence degree shows significant spatial heterogeneity in different grid units. Differentiated spatial planning strategies were proposed for varied areas to efficiently utilize rail transit, which may provide a reference for other cities with the same reality problem. [ABSTRACT FROM AUTHOR]

N6‐methyladenosine (m6A) modification, installed by METTL3‐METTL14 complex, is abundant and critical in eukaryotic mRNA. However, its role in oral mucosal immunity remains ambiguous. Periodontitis is a special but prevalent infectious disease characterized as hyperinflammation of oral mucosa and bone resorption. Here, it is reported that genetic deletion of Mettl3 alleviates periodontal destruction via suppressing NLRP3 inflammasome activation. Mechanistically, the stability of TNFAIP3 (also known as A20) transcript is significantly attenuated upon m6A modification. When silencing METTL3, accumulated TNFAIP3 functioning as a ubiquitin‐editing enzyme facilitates the ubiquitination of NEK7 [NIMA (never in mitosis gene a)‐related kinase 7], and subsequently impairs NLRP3 inflammasome assembly. Furtherly, Coptisine chloride, a natural small‐molecule, is discovered as a novel METTL3 inhibitor and performs therapeutic effect on periodontitis. The study unveils a previously unknown pathogenic mechanism of METTL3‐mediated m6A modifications in periodontitis and indicates METTL3 as a potential therapeutic target. [ABSTRACT FROM AUTHOR]

Exploring the correlation of the built environment with metro ridership is vital for fostering sustainable urban growth. Although the research conducted in the past has explored how ridership is nonlinearly influenced by the built environment, less research has focused on the spatiotemporal ramifications of these nonlinear effects. In this study, density, diversity, distance, destination, and design parameters are utilized to depict the "5D" traits of the built environment, while Shapley Additive Explanations with eXtreme Gradient Boosting (XGBoost-SHAP) are adopted to uncover the spatial and temporal features concerning the nonlinear relationship of the built environment with ridership for metro stations located in Xi'an. We conducted a K-means clustering analysis to detect different site clusters by utilizing local SHAP coefficients. The results show that (1) built environment variables significantly influence metro ridership in a nonlinear manner at different periods and thresholds, with the POI facility density being the most critical variable and the other variables demonstrating time-driven effects; (2) the variables of population density and parking lot density exhibit spatial impact heterogeneity, while the number of parks and squares do not present a clear pattern; and (3) based on the clustering results, the metro stations are divided into four categories, and differentiated guidance strategies and planning objectives are proposed. Moreover, the current work offers a more developed insight into the spatiotemporal influence of built environments on metro travel in Xi'an, China, using nonlinear modeling, which has vital implications for coordinated urban–metro development. [ABSTRACT FROM AUTHOR]

Crown simulation based on basis spline (b-spline) interpolation is a compatible method to simulate tree polymorphism at present. However, there are two problems when it simulates the crown: the first problem is that the derivative value at the top point needs to be given manually, and the second is that the type of value point needs to be collected equidistantly. To solve the above problems and realize convenient and accurate tree polymorphism simulation, this study took Chinese fir as the study object, set the crown morphological feature as the model value point, and constructed a coupling model of generalized B-spline curve and crown (CMGBCC) as the constraint condition of the crown shape to simulate the polymorphism in the process of a tree three-dimensional (3D) model. The position and size of the distribution on the 3D model of the branches were constrained by the curve, and the 3D modeling of a Chinese fir polymorphism was constructed. According to the collection of Chinese fir-type value points in the sample plot, the study realized the detailed types of value points' precise simulation for three polymorphisms of the Chinese fir crown, including natural pruning, crown displacement, and crown shape difference. At the same time, the different withered existence states of the branches were considered preliminarily. Compared to the 3D model with the field survey data, indicating that constructed models could simulate the difference in tree crown morphology precisely, the branch models were separated by convenience to simulate the process of Chinese fir growth. In the process of construction, CMGBCC did not need to add the derivative value in a manual way and could collect the type of value points according to the characteristics of the crown morphological changes completely. Compared to the results of the crown curve constructed, which were based on generalized B-spline (GB-spline) interpolation and b-spline interpolation, it showed that the number of crown value points collected by the GB-spline interpolation method decreased by 18% on average. The precision of the crown shape constraint was improved by 7.63% compared to b-spline interpolation. The 3D modeling of tree polymorphism was combined with the relationship between tree morphology and environment. At the same time, it was convenient to simulate the behavior of forest management measures, such as pruning. [ABSTRACT FROM AUTHOR]

Translation of mRNA to protein is tightly regulated by tRNAs, which are subject to various chemical modifications that maintain the structure, stability and function. Deficiency of tRNA N7-methylguanosine (m7G) modification in patients causes a type of primordial dwarfism, but the underlying mechanism remains unknown. Here we report the loss of m7G rewires cellular metabolism, leading to the pathogenesis of primordial dwarfism. Conditional deletion of the catalytic enzyme Mettl1 or missense mutation of the scaffold protein Wdr4 severely impaired endochondral bone formation and bone mass accrual. Mechanistically, Mettl1 knockout decreased abundance of m7G-modified tRNAs and inhibited translation of mRNAs relating to cytoskeleton and Rho GTPase signaling. Meanwhile, Mettl1 knockout enhanced cellular energy metabolism despite of incompetent proliferation and osteogenic commitment. Further exploration revealed that impaired Rho GTPase signaling upregulated branched-chain amino acid transaminase 1 (BCAT1) level that rewired cell metabolism and restricted intracellular α-ketoglutarate (αKG). Supplementation of αKG ameliorated the skeletal defect of Mettl1-deficient mice. In addition to the selective translation of metabolism-related mRNAs, we further revealed that Mettl1 knockout globally regulated translation via integrated stress response (ISR) and mammalian target of rapamycin complex 1 (mTORC1) signaling. Restoring translation either by targeting ISR or mTORC1 aggravated bone defects of Mettl1-deficient mice. Overall, our study unveils a critical role of m7G tRNA modification in bone development by regulating cellular metabolism, and indicates that suspension of translation initiation as quality control mechanism in response to tRNA dysregulation.

AlphaMissense identifies 23 million human missense variants as likely pathogenic, but only 0.1% have been clinically classified. To experimentally validate these predictions, chemical mutagenesis presents a rapid, cost-effective method to produce billions of mutations in model organisms. However, the prohibitive costs and limitations in the throughput of whole-genome sequencing (WGS) technologies, crucial for variant identification, constrain its widespread application. Here, we introduce a Tn5 transposase-assisted tagmentation technique for conducting WGS in Caenorhabditis elegans, Escherichia coli, Saccharomyces cerevisiae, and Chlamydomonas reinhardtii. This method, demands merely 20 min of hands-on time for a single-worm or single-cell clones and incurs a cost below 10 US dollars. It effectively pinpoints causal mutations in mutants defective in cilia or neurotransmitter secretion and in mutants synthetically sterile with a variant analogous to the B-Raf Proto-oncogene, Serine/Threonine Kinase (BRAF) V600E mutation. Integrated with chemical mutagenesis, our approach can generate and identify missense variants economically and efficiently, facilitating experimental investigations of missense variants in diverse species., Competing Interests: Conflicts of interest The author(s) declare no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Genetics Society of America.)

METTL5 is a methyltransferase that mediates eukaryotic 18S ribosomal RNA m 6 A modification, and its mutations lead to intellectual disability, microcephaly, and facial dysmorphism in patients. However, the role of METTL5 in craniofacial development remains poorly understood. This study demonstrates that Mettl5 knockout mice exhibit poor ossification, widened cranial sutures, and a cleidocranial dysplasia-like phenotype. Deletion of Mettl5 leads to increased proliferation and decreased osteogenic differentiation of suture mesenchymal stem cells. Mechanistically, we find that Wnt signaling is significantly downregulated after Mettl5 knockout. Overall, we reveal an essential role of METTL5 in craniofacial development and osteogenic differentiation of suture mesenchymal stem cells, making METTL5 a potential diagnostic and therapeutic target for craniofacial developmental diseases., (© 2022 The Authors. Publishing Services by Elsevier B.V. on behalf of KeAi Communications Co. Ltd.)