Spatial Heterogeneity and Attribution Analysis of Urban Thermal Comfort in China from 2000 to 2020.

Research on urban thermal environments based on thermal comfort can help formulate effective measures to improve urban thermal and human settlement environments, which is of great significance for improving urban quality, urban climate change adaptation, and sustainable development. Taking 344 municipal administrative districts in China as study areas, the Universal Thermal Climate Index (UTCI) of each city in the last 20 years was calculated to evaluate thermal comfort. We then analyzed the thermal comfort and spatiotemporal heterogeneity of each city during a typical heat wave. Finally, the driving forces of the potential socioeconomic, natural, and landscape factors influencing thermal comfort were analyzed using geographic detectors. The results show that the thermal comfort index had similar spatial patterns and differentiation characteristics in different years, and the interannual variation was not obvious. Cities in the typical heat wave period were mainly distributed in East and Northwest China. The driving factor in the contribution rate of the same index in different years was basically the same and was not affected by the change in years, and the highest contribution rate was the natural factor.

Identifying Spatial Matching between the Supply and Demand of Medical Resource and Accessing Carrying Capacity: A Case Study of Shenzhen, China.

Previous Studies, such as the evaluation of the supply of and demand for regional medical resources and carrying capacity assessments, require further development. This paper aims to evaluate the carrying capacity and spatial distribution of medical resources in Shenzhen from the perspective of supply and demand, and to conduct a time-series variation of the coupling coordination degree from 1986 to 2019. The two-step floating catchment area method was employed to quantify the carrying capacity and coupling coordination degree method and spatial autocorrelation analysis were applied to analyze spatial distribution between supply and demand. The results were as follows. (1) The carrying capacity index in more than 50% of the districts was classified as low-grade. The percentage of regions with good grades was 8.27%. The regions with a high carrying capacity were distributed in the central and southeastern areas. (2) The coupling coordination continued to rise, increasing from 0.03397 in 1986 to 0.33627 in 2019. (3) The level of supply and demand for medical resources in Shenzhen increased from 1986 to 2019, and the highest degree of compatibility between the supply and the population size was largely concentrated in the western and eastern regions. This research can provide a theoretical reference for Shenzhen to rationally plan medical resources and improve the carrying capacity of medical resources.

HDAC4 mediates IFN-γ induced disruption of energy expenditure-related gene expression by repressing SIRT1 transcription in skeletal muscle cells.

Metabolic homeostasis is achieved through balanced energy storage and output. Impairment of energy expenditure is a hallmark event in patients with obesity and type 2 diabetes. Previously we have shown that the pro-inflammatory cytokine interferon gamma (IFN-γ) disrupts energy expenditure in skeletal muscle cells via hypermethylated in cancer 1 (HIC1)-class II transactivator (CIITA) dependent repression of SIRT1 transcription. Here we report that repression of SIRT1 transcription by IFN-γ paralleled loss of histone acetylation on the SIRT1 promoter region with simultaneous recruitment of histone deacetylase 4 (HDAC4). IFN-γ activated HDAC4 in vitro and in vivo by up-regulating its expression and stimulating its nuclear accumulation. HIC1 and CIITA recruited HDAC4 to the SIRT1 promoter and cooperated with HDAC4 to repress SIRT1 transcription. HDAC4 depletion by small interfering RNA or pharmaceutical inhibition normalized histone acetylation on the SIRT1 promoter and restored SIRT1 expression in the presence of IFN-γ. Over-expression of HDAC4 suppressed the transcription of genes involved in energy expenditure in a SIRT1-dependent manner. In contrast, HDAC4 knockdown/inhibition neutralized the effect of IFN-γ on cellular metabolism by normalizing SIRT1 expression. Therefore, our data reveal a role for HDAC4 in regulating cellular energy output and as such provide insights into rationalized design of novel anti-diabetic therapeutics.

Interferon gamma (IFN-γ) disrupts energy expenditure and metabolic homeostasis by suppressing SIRT1 transcription.

Chronic inflammation impairs metabolic homeostasis and is intimately correlated with the pathogenesis of type 2 diabetes. The pro-inflammatory cytokine IFN-γ is an integral part of the metabolic inflammation circuit and contributes significantly to metabolic dysfunction. The underlying mechanism, however, remains largely unknown. In the present study, we report that IFN-γ disrupts the expression of genes key to cellular metabolism and energy expenditure by repressing the expression and activity of SIRT1 at the transcription level. Further analysis reveals that IFN-γ requires class II transactivator (CIITA) to repress SIRT1 transcription. CIITA, once induced by IFN-γ, is recruited to the SIRT1 promoter by hypermethylated in cancer 1 (HIC1) and promotes down-regulation of SIRT1 transcription via active deacetylation of core histones surrounding the SIRT1 proximal promoter. Silencing CIITA or HIC1 restores SIRT1 activity and expression of metabolic genes in skeletal muscle cells challenged with IFN-γ. Therefore, our data delineate an IFN-γ/HIC1/CIITA axis that contributes to metabolic dysfunction by suppressing SIRT1 transcription in skeletal muscle cells and as such shed new light on the development of novel therapeutic strategies against type 2 diabetes.