Natural Coevolution of Tumor and Immunoenvironment in Glioblastoma.

Isocitrate dehydrogenase (IDH) wild-type glioblastoma (GBM) has a dismal prognosis. A better understanding of tumor evolution holds the key to developing more effective treatment. Here we study GBM\u27s natural evolutionary trajectory by using rare multifocal samples. We sequenced 61,062 single cells from eight multifocal IDH wild-type primary GBMs and defined a natural evolution signature (NES) of the tumor. We show that the NES significantly associates with the activation of transcription factors that regulate brain development, including MYBL2 and FOSL2. Hypoxia is involved in inducing NES transition potentially via activation of the HIF1A-FOSL2 axis. High-NES tumor cells could recruit and polarize bone marrow-derived macrophages through activation of the FOSL2-ANXA1-FPR1/3 axis. These polarized macrophages can efficiently suppress T-cell activity and accelerate NES transition in tumor cells. Moreover, the polarized macrophages could upregulate CCL2 to induce tumor cell migration. SIGNIFICANCE: GBM progression could be induced by hypoxia via the HIF1A-FOSL2 axis. Tumor-derived ANXA1 is associated with recruitment and polarization of bone marrow-derived macrophages to suppress the immunoenvironment. The polarized macrophages promote tumor cell NES transition and migration. This article is highlighted in the In This Issue feature, p. 2711

Oral administration of bovine milk-derived extracellular vesicles induces senescence in the primary tumor but accelerates cancer metastasis

The concept that extracellular vesicles (EVs) from the diet can be absorbed by the intestinal tract of the consuming organism, be bioavailable in various organs, and in-turn exert phenotypic changes is highly debatable. Here, we isolate EVs from both raw and commercial bovine milk and characterize them by electron microscopy, nanoparticle tracking analysis, western blotting, quantitative proteomics and small RNA sequencing analysis. Orally administered bovine milk-derived EVs survive the harsh degrading conditions of the gut, in mice, and is subsequently detected in multiple organs. Milk-derived EVs orally administered to mice implanted with colorectal and breast cancer cells reduce the primary tumor burden. Intriguingly, despite the reduction in primary tumor growth, milk-derived EVs accelerate metastasis in breast and pancreatic cancer mouse models. Proteomic and biochemical analysis reveal the induction of senescence and epithelial-to-mesenchymal transition in cancer cells upon treatment with milk-derived EVs. Timing of EV administration is critical as oral administration after resection of the primary tumor reverses the pro-metastatic effects of milk-derived EVs in breast cancer models. Taken together, our study provides context-based and opposing roles of milk-derived EVs as metastasis inducers and suppressors

A novel community driven software for functional enrichment analysis of extracellular vesicles data.

Bioinformatics tools are imperative for the in depth analysis of heterogeneous high-throughput data. Most of the software tools are developed by specific laboratories or groups or companies wherein they are designed to perform the required analysis for the group. However, such software tools may fail to capture "what the community needs in a tool". Here, we describe a novel community-driven approach to build a comprehensive functional enrichment analysis tool. Using the existing FunRich tool as a template, we invited researchers to request additional features and/or changes. Remarkably, with the enthusiastic participation of the community, we were able to implement 90% of the requested features. FunRich enables plugin for extracellular vesicles wherein users can download and analyse data from Vesiclepedia database. By involving researchers early through community needs software development, we believe that comprehensive analysis tools can be developed in various scientific disciplines

Progress in Researches on Evaluation of Quality of Cultivated Land Consolidated from Coal Mining Subsided Land

The evaluation of consolidated cultivated land quality can provide basic information for how to perfect the program of land consolidation,as well as a reference for the dynamic monitoring of farmland quality in mining area.Based on the consultation and analysis of related literature,we can conclude that:firstly,most scholars focus on soil consolidation, while consider little about land use and economic condition. Secondly, foreign scholars usually use crop yields to judge the success of land consolidation, while domestic scholars have been evaluated the quality of consolidated cultivated land synthetically from several aspects,such as soil fertility,soil environmental quality,and farmland infrastruture conditions.Specifically,most of the evaluations are static,and indicators are different.Besides,the quality of consolidated cultivated land is generally low,and it lacks systematic research on technologies for improving quality of cultivated land consolidated from coal mining subsided land.It is concluded that future researches should focus on establishing scientific and feasible evaluation system to realize comparison of quality change in the dynamic course of “undisturbed — subsided — consolidated” cultivated land in coal mining areas, as well as technologies for improving quality of cultivated land consolidated from coal mining subsided land

Soil Health Evaluation of Farmland Based on Functional Soil Management—A Case Study of Yixing City, Jiangsu Province, China

Given that farmland serves as a strategic resource to ensure national food security, blind emphasis on the improvement of food production capacity can lead to soil overutilization and impair other soil functions. Hence, the evaluation of soil health (SH) should comprehensively take soil productivity and ecological environmental effects into account. In this study, five functions from the perspective of functional soil management were summarized, including primary productivity, provision and cycling of nutrients, the provision of functional and intrinsic biodiversity, water purification and regulation, and carbon sequestration and regulation. For each soil function, in view of the natural and ameliorable conditions affecting SH, basic indicators were selected from the two aspects of inherent and dynamic properties, and restrictive indicators were chosen considering the external properties or environmental elements, with the minimum limiting factor method coupled with weighted linear model. The new evaluation system was tested and verified in Yixing City, China. The healthy and optimally functional soils were concentrated in the northeast and mid-west of Yixing City, whereas unhealthy soils were predominant in the south and around Taihu Lake. The main limitations to SH improvement included cation exchange capacity, nutrient elements, and soluble carbon. The SH evaluation method was verified using the crop performance validation method, and a positive correlation was noted between food production stability index and soil health index, indicating that the evaluation system is reasonable

Poincaré-friedrichs inequalities for piecewise H\u3csup\u3e2\u3c/sup\u3e functions

Poincaré-Friedrichs inequalities are derived for piecewise H functions on two dimensional domains. These inequalities can be applied to classical nonconforming finite element methods, mortar methods and discontinuous Galerkin methods.

The Spatial Distribution and Prediction of Soil Heavy Metals Based on Measured Samples and Multi-Spectral Images in Tai Lake of China

Soil is an important natural resource. The excessive amount of heavy metals in soil can harm and threaten human health. Therefore, monitoring of soil heavy metal content is urgent. Monitoring soil heavy metals by traditional methods requires many human and material resources. Remote sensing has shown advantages in the field of monitoring heavy metals. Based on 971 heavy metal samples and Sentinel-2 multi-spectral images in Tai Lake, China, we analyzed the correlation between six heavy metals (Cd, Hg, As, Pb, Cu, Zn) and spectral factors, and selected As and Hg as the input factors of inversion model. The correlation coefficient of the best model of As was 0.53 (p p < 0.01). We used the methods of partial least squares regression (PLSR) and back propagation neural network (BPNN) to establish inversion models with different combinations of spectral factors by using 649 measured samples. In addition, 322 measured samples were used for accuracy evaluation. Compared with the PLSR model, the BP neural network builds the model with higher accuracy, and B1-B4 combined with LnB1-LnB4 builds the model with the highest accuracy. The accuracy of the best model was verified, with an average error of 19% for As and 45% for Hg. Analyzing the spatial distribution of heavy metals by using the interpolation method of Kriging and IDW. The overall distribution trend of the two interpolations is similar. The concentration of As elements tends to increase from north to south, and the relatively high value of Hg elements is distributed in the east and west of the study area. The factories in the study area are distributed along rivers and lakes, which is consistent with the spatial distribution of heavy metal enrichment areas. The relatively high-value areas of heavy metal elements are related to the distribution of metal products factories, refractory porcelain factories, tile factories, factories and mining enterprises, etc., indicating that factory pollution is the main reason for the enrichment of heavy metals

Cultivated Land Use Zoning Based on Soil Function Evaluation from the Perspective of Black Soil Protection

Given that cultivated land serves as a strategic resource to ensure national food security, blind emphasis on improvement of food production capacity can lead to soil overutilization and impair other soil functions. Therefore, we took Heilongjiang province as an example to conduct a multi-functional evaluation of soil at the provincial scale. A combination of soil, climate, topography, land use, and remote sensing data were used to evaluate the functions of primary productivity, provision and cycling of nutrients, provision of functional and intrinsic biodiversity, water purification and regulation, and carbon sequestration and regulation of cultivated land in 2018. We designed a soil function discriminant matrix, constructed the supply-demand ratio, and evaluated the current status of supply and demand of soil functions. Soil functions demonstrated a distribution pattern of high grade in the northeast and low grade in the southwest, mostly in second-level areas. The actual supply of primary productivity functions in 71.32% of the region cannot meet the current needs of the population. The dominant function of soil in 34.89% of the area is water purification and regulation, and most of the cultivated land belongs to the functional balance region. The results presented herein provide a theoretical basis for optimization of land patterns and improvement of cultivated land use management on a large scale, and is of great significance to the sustainable use of black soil resources and improvement of comprehensive benefits

Enhanced durability of Li-O₂ batteries employing vertically standing Ti nanowire array supported cathodes

Enhanced durability of Li–O2 batteries (more than 500 cycles) based on Ti nanowire array supported cathodes.</p