Accumulating evidence suggests that ketogenic diets (KDs) mediate the rise of circulating ketone bodies and exert a potential anti-inflammatory effect; however, the consequences of this unique diet on colitis remain unknown. We performed a series of systematic studies using a dextran sulfate sodium (DSS) animal model of inflammatory colitis. Animals were fed with a KD, low-carbohydrate diet (LCD), or normal diet (ND). Germ-free mice were utilized in validation experiments. Colon tissues were analyzed by transcriptome sequencing, RT2 profiler PCR array, histopathology, and immunofluorescence. Serum samples were analyzed by metabolic assay kit. Fecal samples were analyzed by 16S rRNA gene sequencing, liquid chromatography–mass spectrometry and gas chromatography–mass spectrometry. We observed that KD alleviated colitis by altering the gut microbiota and metabolites in a manner distinct from LCD. Quantitative diet experiments confirmed the unique impact of KD relative to LCD with a reproducible increase in Akkermansia, whereas the opposite was observed for Escherichia/Shigella. After colitis induction, the KD protected intestinal barrier function, and reduced the production of RORγt+CD3− group 3 innate lymphoid cells (ILC3s) and related inflammatory cytokines (IL-17α, IL-18, IL-22, Ccl4). Finally, fecal microbiota transplantation into germ-free mice revealed that the KD- mediated colitis inhibition and ILC3 regulation were dependent on the modification of gut microbiota. Taken together, our study presents a global view of microbiome-metabolomics changes that occur during KD colitis treatment, and identifies the regulation of gut microbiome and ILC3s as novel targets involving in IBD dietary therapy.
Invasion and metastasis are the main causes of treatment failure and death in breast cancer. Thus, novel invasion-based therapies such as those involving natural agents are urgently required. In this study, we examined the effects of magnolol (Mag), a compound extracted from medicinal herbs, on breast cancer cells in vitro and in vivo. Highly invasive cancer cells were found to be highly sensitive to treatment. Mag markedly inhibited the activity of highly invasive MDA-MB-231 cells. Furthermore, Mag significantly downregulated matrix metalloproteinase-9 (MMP-9) expression, an enzyme critical to tumor invasion. Mag also inhibited nuclear factor-κB (NF-κB) transcriptional activity and the DNA binding of NF-κB to MMP-9 promoter. These results indicate that Mag suppresses tumor invasion by inhibiting MMP-9 through the NF-κB pathway. Moreover, Mag overcame the promoting effects of phorbol 12-myristate 13-acetate (PMA) on the invasion of MDA-MB-231 cells. Our findings reveal the therapeutic potential and mechanism of Mag against cancer.
Conversion of agricultural lands to urban uses affects regional and global climate not only through the release of greenhouse gases but also through altering land surface physical processes such as energy and water balances. Most existing studies on the meteorological impacts of urbanization focus on urban heat island effects with little attention on its impacts of atmospheric humidity, a key variable in hydrometeorology and climate science. We define the influences of urbanization on reducing atmospheric humidity and elevating vapor pressure deficit as urban dry island (UDI) effects. We conduct a case study in the Yangtze River Delta, a typical humid area in southern China that is under rapid urbanization. We examine spatiotemporal characteristics of UDI and identify potential drivers during 2001–2014. Relationships and interactions between variations of air temperature, atmospheric humidity, evapotranspiration, and leaf area index of different land cover were determined using correlation and attribution analyses at both station and regional levels. We show that atmospheric humidity decreased dramatically and vapor pressure deficit increased sharply in the urban core, resulting in enhanced UDI. In addition to global warming and localized urban heat island, UDI is closely related to the loss of vegetation cover (i.e., natural wetlands and paddies). Reduction of evapotranspiration or latent heat is another important factor contributing to UDI effects. We conclude that the role of vegetated land cover and associated ecohydrological processes in moderating UDI and maintaining a stable climate and environment should be considered in massive urban planning and global change impact assessment in southern China.
Highlights d A subset of high-grade glioma-associated microglia (HGG-AM) is identified by scRNA-seq d TGF-b1 activated from SETD2-mut/IDH-WT GBM cells promotes activation of HGG-AM d HGG-AM exhibits pro-inflammation and proliferation features, promoting tumor progression
Fires play a critical role in modulating regional and global climate through disturbances on meteorological, biogeochemical, and hydrological processes, while fires are strongly affected by climate, terrestrial ecosystems, and human activities. The complex climate-fire-ecosystem interactions with anthropogenic disturbance are not well understood. We developed a REgion-Specific ecosystem feedback Fire (RESFire) model in the Community Earth System Model (CESM) that provides modeling capability to reproduce the observed burning patterns and trends and to understand fire related climatic processes. Comparing with the default Community Land Model version 4.5 fire model in CESM, the RESFire model includes heterogeneous natural and anthropogenic constraints on fire ignition and spread, improved fire impact parameterization including online fire emissions and fire induced land cover changes, and modeling bias corrections for online fire weather simulation. Evaluation results based on the International Land Model Benchmarking package show significant improvements in fire simulation performance. The overall modeling score of burned area simulation increases from 0.50 with Community Land Model version 4.5 to 0.62 (RESFire driven by the observation-reanalysis data) and 0.60 (RESFire driven by the bias-corrected Community Atmosphere Model version 5 simulation). The attribution analysis of decadal burned area trends suggests distinct contributions of natural and anthropogenic forcing in different regions, which are consistent with previous observations. The model also includes a fire impact module for estimating atmospheric responses to fire emissions as well as fire disturbances on ecosystems, land cover, and surface radiation budget. These results demonstrate the latest progress of global fire model development that enables fully interactive climate-fire-ecosystem studies using CESM.Plain Language Summary We improved the fire simulation capability in the Earth system model to better understand the complex interactions among climate, fire, and ecosystems with anthropogenic disturbance.
a b s t r a c tWith the rural-to-urban migration under China's rapid urbanization, the Bohai Rim of China experienced dramatic rural housing land transition (RHLT) in the last decade, especially in terms of per capita rural housing land (PRHL). The objectives of this study are to (i) analyze the spatio-temporal patterns of RHLT, and (ii) detect the underlying driving forces and mechanism of RHLT in Bohai Rim during 2000e2010. To achieve these goals, we collected and rasterized high resolution Landsat TM data, socio-economic and physical environmental data for the Bohai Rim. Spatial econometric regression models at both grid scale and county scale were developed to examine the driving forces of RHLT in Bohai Rim. The results indicated that the distribution of rural housing land was characterized by vertical zonality, i.e., the proportion of rural housing land decreased gradually with the increase of elevation, and was more sensitive to slope than to elevation. The results of hot spots analysis showed that the spatial mismatch of rural housing land change and rural population migration made the regional differences of RHLT more remarkable, based on which four rural housing land consolidation regional types were differentiated. The authors argue that towns are effective hubs for linking the urban system and rural system, and it is better to get the farmers to migrate to towns instead of big cities in the process of pushing forward China's newtype urbanization in the future. For this, it is necessary to further improve related system and institution. Only by this way can the relationship between out-migrated farmers and rural housing land be orderly and completely removed, so as to smoothly pushing forward rural housing land consolidation.
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