Hippo pathway in intestinal diseases: focusing on ferroptosis

The incidence of intestinal diseases, such as inflammatory bowel disease, gastric cancer, and colorectal cancer, has steadily increased over the past decades. The Hippo pathway is involved in cell proliferation, tissue and organ damage, energy metabolism, tumor formation, and other physiologic processes. Ferroptosis is a form of programmed cell death characterized by the accumulation of iron and lipid peroxides. The Hippo pathway and ferroptosis are associated with various intestinal diseases; however, the crosstalk between them is unclear. This review elaborates on the current research on the Hippo pathway and ferroptosis in the context of intestinal diseases. We summarized the connection between the Hippo pathway and ferroptosis to elucidate the underlying mechanism by which these pathways influence intestinal diseases. We speculate that a mutual regulatory mechanism exists between the Hippo pathway and ferroptosis and these two pathways interact in several ways to regulate intestinal diseases

Spatial accessibility of emergency medical services in Chongqing, Southwest China

BackgroundTimely access to emergency medical services (EMS) can significantly reduce mortality. In China, the evidence of the accessibility of complete EMS which considers two related trips and involves large rural areas is insufficient. This study aimed to explore the accessibility of ambulance services and complete EMS in Chongqing and its regional differences, and to provide a reference for improving spatial accessibility of EMS in Chongqing and optimizing allocation of EMS resources.MethodsThe nearest neighbor method was used to measure spatial accessibility of ambulance services and complete EMS. Spatial aggregation patterns and influencing factors of spatial accessibility of complete EMS were analyzed using Moran's I index, Pearson correlation and multiple linear regression.ResultsThe medians of shortest travel time for ambulance, monitoring ambulance, primary EMS and advanced EMS in Chongqing were 7.0, 18.6, 36.2, and 47.8 min. The shortest travel time for complete EMS showed significant spatial aggregation characteristics. The Low-Low types that referred to cluster of short EMS travel time mainly distributed in city proper. The High-High types that referred to cluster of long EMS travel time mainly distributed in northeast and southeast of Chongqing. Urbanization rate was a negative influencing factor on shortest travel time for primary EMS, while average elevation and the number of settlements were positive influencing factors. GDP per capita and urbanization rate were negative influencing factors on shortest travel time for advanced EMS, while the number of settlements was a positive influencing factor.ConclusionThis study evaluated the accessibility of EMS which considers two related trips in Chongqing. Although the accessibility of ambulances in Chongqing was relatively high, the accessibility of monitoring ambulance was relatively low. Regional and urban-rural differences in the accessibility of complete EMS integrating two related trips were obvious. It was recommended to increase financial investment in economic backward areas, increase high-quality EMS resources, enhance EMS capacity of central township health centers, strengthen road construction in mountainous areas, and provide reasonable planning of rural settlements for improving the spatial accessibility of EMS, narrowing the urban-rural gap and improving equity in getting EMS for all the people

Single-cell chromatin accessibility profiling of cell-state-specific gene regulatory programs during mouse organogenesis

In mammals, early organogenesis begins soon after gastrulation, accompanied by specification of various type of progenitor/precusor cells. In order to reveal dynamic chromatin landscape of precursor cells and decipher the underlying molecular mechanism driving early mouse organogenesis, we performed single-cell ATAC-seq of E8.5-E10.5 mouse embryos. We profiled a total of 101,599 single cells and identified 41 specific cell types at these stages. Besides, by performing integrated analysis of scATAC-seq and public scRNA-seq data, we identified the critical cis-regulatory elements and key transcription factors which drving development of spinal cord and somitogenesis. Furthermore, we intersected accessible peaks with human diseases/traits-related loci and found potential clinical associated single nucleotide variants (SNPs). Overall, our work provides a fundamental source for understanding cell fate determination and revealing the underlying mechanism during postimplantation embryonic development, and expand our knowledge of pathology for human developmental malformations

Global diversity and biogeography of bacterial communities in wastewater treatment plants

Microorganisms in wastewater treatment plants (WWTPs) are essential for water purification to protect public and environmental health. However, the diversity of microorganisms and the factors that control it are poorly understood. Using a systematic global-sampling effort, we analysed the 16S ribosomal RNA gene sequences from ~1,200 activated sludge samples taken from 269 WWTPs in 23 countries on 6 continents. Our analyses revealed that the global activated sludge bacterial communities contain ~1 billion bacterial phylotypes with a Poisson lognormal diversity distribution. Despite this high diversity, activated sludge has a small, global core bacterial community (n = 28 operational taxonomic units) that is strongly linked to activated sludge performance. Meta-analyses with global datasets associate the activated sludge microbiomes most closely to freshwater populations. In contrast to macroorganism diversity, activated sludge bacterial communities show no latitudinal gradient. Furthermore, their spatial turnover is scale-dependent and appears to be largely driven by stochastic processes (dispersal and drift), although deterministic factors (temperature and organic input) are also important. Our findings enhance our mechanistic understanding of the global diversity and biogeography of activated sludge bacterial communities within a theoretical ecology framework and have important implications for microbial ecology and wastewater treatment processes

Cell transcriptomic atlas of the non-human primate Macaca fascicularis.

Studying tissue composition and function in non-human primates (NHPs) is crucial to understand the nature of our own species. Here we present a large-scale cell transcriptomic atlas that encompasses over 1 million cells from 45 tissues of the adult NHP Macaca fascicularis. This dataset provides a vast annotated resource to study a species phylogenetically close to humans. To demonstrate the utility of the atlas, we have reconstructed the cell-cell interaction networks that drive Wnt signalling across the body, mapped the distribution of receptors and co-receptors for viruses causing human infectious diseases, and intersected our data with human genetic disease orthologues to establish potential clinical associations. Our M. fascicularis cell atlas constitutes an essential reference for future studies in humans and NHPs.We thank W. Liu and L. Xu from the Huazhen Laboratory Animal Breeding Centre for helping in the collection of monkey tissues, D. Zhu and H. Li from the Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory) for technical help, G. Guo and H. Sun from Zhejiang University for providing HCL and MCA gene expression data matrices, G. Dong and C. Liu from BGI Research, and X. Zhang, P. Li and C. Qi from the Guangzhou Institutes of Biomedicine and Health for experimental advice or providing reagents. This work was supported by the Shenzhen Basic Research Project for Excellent Young Scholars (RCYX20200714114644191), Shenzhen Key Laboratory of Single-Cell Omics (ZDSYS20190902093613831), Shenzhen Bay Laboratory (SZBL2019062801012) and Guangdong Provincial Key Laboratory of Genome Read and Write (2017B030301011). In addition, L.L. was supported by the National Natural Science Foundation of China (31900466), Y. Hou was supported by the Natural Science Foundation of Guangdong Province (2018A030313379) and M.A.E. was supported by a Changbai Mountain Scholar award (419020201252), the Strategic Priority Research Program of the Chinese Academy of Sciences (XDA16030502), a Chinese Academy of Sciences–Japan Society for the Promotion of Science joint research project (GJHZ2093), the National Natural Science Foundation of China (92068106, U20A2015) and the Guangdong Basic and Applied Basic Research Foundation (2021B1515120075). M.L. was supported by the National Key Research and Development Program of China (2021YFC2600200).S

The effect of daily mean temperature on hand, foot and mouth disease and the source of regional heterogeneity in Chongqing, China, 2010–2019

Background: Hand, foot and mouth disease (HFMD) is a serious infectious disease which has become a public health problem. A multi-regional study was conducted in this study to explore the relationship between temperature and HFMD in different regions and the source of heterogeneity, and further detect the effect modifiers such as socio-economic factors, medical and health factors and meteorological factors. Methods: The data on daily reported HFMD cases and meteorological data from 2010 to 2019 in Chongqing were collected. Thirty-eight districts and counties of Chongqing were divided into 6 regions. The distributed lag nonlinear model (DLNM) was applied to assess the effect of daily mean temperature on HFMD at region level with the pooled effect estimates from multivariate meta-regression model analysis. Stratified analyses by gender, age and children’s type were also conducted. Potential modifiers were considered in meta regression to explore the source of heterogeneity. Results: There were nonlinear relationships with an inverted V-shape between temperature and HFMD. A maximum cumulative relative risk (CRR) of 1.22 (95% confidence interval (CI): 1.12–1.34) peaked at 23.8 °C, and the risk appeared immediately and lasted for the whole 14 days. Compared with other groups, warm temperature had a stronger effect on children aged 0–1 and scattered children, while cold temperature had a stronger effect on female, children aged 3–6 and childcare children with an M-shape. We found that socio-economic factors, medical health factors and meteorological factors were significantly associated with heterogeneity. Density of medical technical personnel, urbanization rate and density of health care institutions were the main modifiers for explaining heterogeneity of 26.10%, 24.90% and 24.86% respectively which were revealed by meta-analysis. Conclusions: There was a significant nonlinear correlation between temperature and HFMD. Compared with other groups, children aged 0–1 and scattered children were more susceptible to warm temperature, while female, children aged 3–6 and childcare children were more susceptible to cold temperature. Socio-economic factors, medical health factors and meteorological factors may be the source of the heterogeneity. Therefore, local governments should consider different temperature–HFMD relationships between different regions and populations when formulating appropriate preventive measures

Microstructural design for mechanical–optical multifunctionality in the exoskeleton of the flower beetle Torynorrhina flammea

Biological systems have a remarkable capability of synthesizing multifunctional materials that are adapted for specific physiological and ecological needs. When exploring structure–function relationships related to multifunctionality in nature, it can be a challenging task to address performance synergies, trade-offs, and the relative importance of different functions in biological materials, which, in turn, can hinder our ability to successfully develop their synthetic bioinspired counterparts. Here, we investigate such relationships between the mechanical and optical properties in a multifunctional biological material found in the highly protective yet conspicuously colored exoskeleton of the flower beetle, Torynorrhina flammea. Combining experimental, computational, and theoretical approaches, we demonstrate that a micropillar-reinforced photonic multilayer in the beetle’s exoskeleton simultaneously enhances mechanical robustness and optical appearance, giving rise to optical damage tolerance. Compared with plain multilayer structures, stiffer vertical micropillars increase stiffness and elastic recovery, restrain the formation of shear bands, and enhance delamination resistance. The micropillars also scatter the reflected light at larger polar angles, enhancing the first optical diffraction order, which makes the reflected color visible from a wider range of viewing angles. The synergistic effect of the improved angular reflectivity and damage localization capability contributes to the optical damage tolerance. Our systematic structural analysis of T. flammea’s different color polymorphs and parametric optical and mechanical modeling further suggest that the beetle’s microarchitecture is optimized toward maximizing the first-order optical diffraction rather than its mechanical stiffness. These findings shed light on material-level design strategies utilized in biological systems for achieving multifunctionality and could thus inform bioinspired material innovations.</jats:p

A scATAC-seq atlas of chromatin accessibility in axolotl brain regions

Abstract Axolotl (Ambystoma mexicanum) is an excellent model for investigating regeneration, the interaction between regenerative and developmental processes, comparative genomics, and evolution. The brain, which serves as the material basis of consciousness, learning, memory, and behavior, is the most complex and advanced organ in axolotl. The modulation of transcription factors is a crucial aspect in determining the function of diverse regions within the brain. There is, however, no comprehensive understanding of the gene regulatory network of axolotl brain regions. Here, we utilized single-cell ATAC sequencing to generate the chromatin accessibility landscapes of 81,199 cells from the olfactory bulb, telencephalon, diencephalon and mesencephalon, hypothalamus and pituitary, and the rhombencephalon. Based on these data, we identified key transcription factors specific to distinct cell types and compared cell type functions across brain regions. Our results provide a foundation for comprehensive analysis of gene regulatory programs, which are valuable for future studies of axolotl brain development, regeneration, and evolution, as well as on the mechanisms underlying cell-type diversity in vertebrate brains

Single-cell RNA-seq reveals dynamic transcriptome profiling in human early neural differentiation

Background: Investigating cell fate decision and subpopulation specification in the context of the neural lineage is fundamental to understanding neurogenesis and neurodegenerative diseases. The differentiation process of neural-tube-like rosettes in vitro is representative of neural tube structures, which are composed of radially organized, columnar epithelial cells and give rise to functional neural cells. However, the underlying regulatory network of cell fate commitment during early neural differentiation remains elusive. Results: In this study, we investigated the genome-wide transcriptome profile of single cells from six consecutive reprogramming and neural differentiation time points and identified cellular subpopulations present at each differentiation stage. Based on the inferred reconstructed trajectory and the characteristics of subpopulations contributing the most toward commitment to the central nervous system lineage at each stage during differentiation, we identified putative novel transcription factors in regulating neural differentiation. In addition, we dissected the dynamics of chromatin accessibility at the neural differentiation stages and revealed active cis-regulatory elements for transcription factors known to have a key role in neural differentiation as well as for those that we suggest are also involved. Further, communication network analysis demonstrated that cellular interactions most frequently occurred in the embryoid body stage and that each cell subpopulation possessed a distinctive spectrum of ligands and receptors associated with neural differentiation that could reflect the identity of each subpopulation. Conclusions: Our study provides a comprehensive and integrative study of the transcriptomics and epigenetics of human early neural differentiation, which paves the way for a deeper understanding of the regulatory mechanisms driving the differentiation of the neural lineage