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Summary: Background: ALKBH5 belongs to the ALKB family consists of a Fe (II) and a-ketoglutarate-dependent dioxygenase. ALKBH5 directly catalyzes the oxidative demethylation of m6A-methylated adenosine. ALKBH5 involves in tumorigenesis and tumor progression, and is often dysregulated in a wide range of cancers, including colorectal cancer. Emerging evidence indicates that the expression of ALKBH5 is associated with the abundance of infiltrating immune cells in the microenvironment. However, how ALKBH5 affects immune cell infiltration in the microenvironment in colorectal cancer (CRC) has not been reported. The aim of this study was to identify how the expression of ALKBH5 affects the biological behaviors of CRC cell lines and regulates the effects on infiltrating CD8+ T cells in CRC microenvironment with its specific mechanism. Methods: Firstly, the transcriptional expression profiles of CRC were downloaded from TCGA database and integrated via R software (4.1.2). Between CRC and normal colorectal tissues, ALKBH5 mRNA expressions were compared (Wilcoxon rank-sum). We further identified the expression levels of ALKBH5 in CRC tissues and cell lines through quantitative PCR, western blot, and immunohistochemistry. Then, how ALKBH5 affects the biological behaviors of CRC cells were confirmed by gain- and loss-of-function analysis. Furthermore, the relationship between ALKBH5 level and 22 tumor-infiltrating immune cells was examined through CIBERSORT in R software. Furthermore, we explored the correlation between ALKBH5 expression and tumor-infiltrated CD8+, CD4+ and regulatory T cells by utilizing the TIMER database. Finally, the association between chemokines and CD8+ T cells infiltration in CRC was analyzed using GEPIA online database. qRT-PCR, WB and IHC were used to further determine the effect of ALKBH5 on NF-κB-CCL5 signaling axis and CD8+ T cells infiltration. Results: Clinically, ALKBH5 expression was downregulated in CRC and low levels of ALKBH5 expression were correlated with poor overall survival (OS). Functionally, overexpression of ALKBH5 reduced the proliferation, migration and invasion of CRC cells, and vice versa. Overexpression of ALKBH5 suppresses NF-κB pathway, thus reduces CCL5 expression and promotes CD8+ T cells infiltration in CRC microenvironment. Conclusions: ALKBH5 is poorly expressed in CRC, and overexpression of ALKBH5 attenuates CRC malignant progression by inhibiting CRC cell proliferation, migration, invasion and promoting CD8+ T cells infiltration in the tumor microenvironment through NF-κB-CCL5 axis.

A series of significant breakthroughs in exploration for conventional and unconventional resource have been acquired. But the quality of increased reserves decreased with unconventional resource into the reserve sequence, which means that there is a need for clarifying the conventional and unconventional resource potential as well as the important explorative regions in residue resource and the favorable directions.For this and based on the results in exploration for oil and gas, the recognitions in petroleum geology and the accumulations about explorative data in more than recent decade acquired by PetroChina, an entire system in resource assessment for conventional and unconventional resource is established. The 4th round of resource assessment is accordingly and systematically executed.The result acquired in the assessment indicates that the total amount of domestic conventional resource is 78×1012m3 with an increase of 8×1012m3 compared to the result from the 3rd round of assessment. Unconventional resource includes four types such as tight gas, shale gas, coalbed methane and natural gas hydrate.A mong them, there is 21.86×1012m3 for tight gas (Jiyang, Dongpu, Nanxiang, Subei, etc. are excluded for the region being assessed), 80.12×1012m3 for shale gas, 29.82×1012m3 for coalbed methane and 153.06×1012m3 for natural gas hydrate. The residue resource for onshore conventional natural gas mainly distributed in 4 significant respects such as lithology-strata (clastic rock), carbonatites of marine facies, foreland thrust belts and complex tectonic belts, which is predominated by carbonatites of marine facies and foreland thrust belts. The resource for off shore natural gas mainly concentrates in the reserves of three respects such as offshore structures, organic reef and lithology in deep water. The total amount of residue resource contained in reserves as carbonatites of marine facies, foreland, lithology-strata, complex tectonic belts and South China Sea are 59.83 ×1012m3, which occupies 94% of residue resource in China.Based on the assessment, favorable targets are selected optimally, which include 10 targets for conventional resource, 4 targets for tight gas, 4 targets for coalbed methane and 6 targets for shale gas. [ABSTRACT FROM AUTHOR]

Natural gas contained in deep formation is a respect with strategic importance for hydrocarbon exploration in China, which presents a low exploration degree(18.46%). It indicates that there is confirmative necessity and research value for clarifying the resource potential and ascertaining the favorable explorative direction. From elaborating the present condition in exploration for natural gas resource, methodologies including hydrocarbon generation, analogy and statistics are applied based on the result of the 4th round of resource assessment of PetroChina, which indicates there is a huge total amount of resource potential.lt occupies a predominant position as 55% (20.31 ×1012m3)of the totalamount of resource potential for natural gas.The anisotropic characteristic is presented in the respect of resource distribution.Sichuan, Tarim and Songliao Basins are recognized as the relatively more concentrated (76.70%) in resource potential.Similar feature in anisotropy also exists in the respect of lithology,carbonates occupies 57.27% of the proved reservoir of natural gas contained in deep formations, which mainly correlates to the marine strata of Paleozoic cratons in the center and west basins. In the respect of remaining resource, it is quite abundant (16.56×1012m3). 76.07% of the remaining resource is contained in three main basins such as Sichuan, Songliao and Tarim Basins.In these basins, the favorable directions to further exploration for natural gas in deep formations are acquired as the clastic and volcanic reservoir from Jurassic to Cretaceous formed in the fault depression of Songliao Basin.Favorable exploration direction includes the dolomite reservoir of the lithological facie as mound and shoal in the center of paleo-uplift in Sichuan Basin, bioclaslic limestone and dolomite reservoir in the facies of reef flat contained in Changxing and Feixianguan Formations in the north and northwest of Sichuan Basin,the dolomite reservoir from Devonian to Lower Permian in the west of Sichuan Basin, the Ordovician dolomite reservoir in the facies of mound and shoal in the center of Tarim Basin, and the Cretaceous clastic reservoir in Kuche Depression of Tarim Basin, etc., which consequently reveals the prominent prospect for natural gas contained in deep formations. [ABSTRACT FROM AUTHOR]