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PCIF1 can mediate the methylation of [N.sup.6],2'-O-dimethyladenosine ([m.sup.6]Am) in mRNA. Yet, the detailed interplay between PCIF1 and the potential cofactors and its pathological significance remain elusive. Here, we demonstrated that PCIF1mediated cap mRNA [m.sup.6]Am modification promoted head and neck squamous cell carcinoma progression both in vitro and in vivo. CTBP2 was identified as a cofactor of PCIF1 to catalyze [m.sup.6]Am deposition on mRNA. CLIP-Seq data demonstrated that CTBP2 bound to similar mRNAs as compared with PCIF1. We then used the [m.sup.6]Am-Seq method to profile the mRNA [m.sup.6]Am site at single-base resolution and found that mRNA of TET2, a well-known tumor suppressor, was a major target substrate of the PCIF1-CTBP2 complex. Mechanistically, knockout of CTBP2 reduced PCIF1 occupancy on TET2 mRNA, and the PCIF1-CTBP2 complex negatively regulated the translation of TET2 mRNA. Collectively, our study demonstrates the oncogenic function of the epitranscriptome regulator PCIF1-CTBP2 complex, highlighting the importance of the [m.sup.6]Am modification in tumor progression., Introduction Recently, it has been increasingly evident that dysregulation of mRNA modifications and dysregulation of the modifiers are important factors in the aggressiveness and malignancy of tumors (1-4). Methylated modifications [...]

Objectives: To investigate the inhibitory effects of STM2457, which is a novel METTL3 (m6A writer) inhibitor, both as a monotherapy and in combination with anlotinib, in the treatment of oral squamous cell carcinoma (OSCC) both in vitro and in vivo. Materials and Methods: The efficacy of STM2457 or STM2457 plus anlotinib was evaluated using two OSCC cell lines by CCK8, transwell, colony formation, would‐healing, sphere formation, cell cycle, apoptosis assays, and nude mice tumor xenograft techniques. The molecular mechanism study was carried out by western blotting, qRT‐PCR, MeRIP‐qPCR, immunofluorescence, and immunohistochemistry. Results: STM2457 combined with anlotinib enhanced inhibition of cellular survival/proliferation and promotion of apoptosis in vitro. Moreover, this combinatorial approach exerted a notable reduction in stemness properties and EMT (epithelial‐mesenchymal transition) features of OSCC cells. Remarkably, in vivo studies validated the efficacy of the combination treatment. Mechanistically, our investigations revealed that the combined action of STM2457 and anlotinib exerted downregulatory effects on EGFR (epidermal growth factor receptor) expression in OSCC cells. Conclusions: The combination of STM2457 and anlotinib targeting EGFR exerted a multiple anti‐tumor effect. In near future, anlotinib combined with STM2457 may provide a novel insight for the treatment of OSCC. [ABSTRACT FROM AUTHOR]

Tight gas is the fastest developing unconventional natural gas resource, becoming the principal part for gas reserves and production growth in China. The Sulige gas field is the largest gas field and also the typical low porosity and low permeability tight sandstone gas field discovered in China, with an annual natural gas output exceeding 300 billion and cumulative output exceeding 290 billion, playing an important role in ensuring national energy provision, helping China’s energy transformation, and promoting green, low-carbon, environmental protection and high-quality development. Based on sample collection and laboratory analysis, natural gas compositions including hydrocarbons, non-hydrocarbons, light hydrocarbons, and noble gases of the Sulige gas field are systematically analyzed, their genetic identifications are identified, and finally gas source originations and contribution proportions are comprehensively discussed from the perspectives of noble gases and hydrocarbon gases. The main achievements are as follows: 1) natural gases in the Sulige gas field are mainly alkane gases, with high methane content, high drying coefficient, low heavy hydrocarbon contents, low non-hydrocarbon gas contents of CO2 and N2, and relatively low noble gas contents. The helium content is relative 2 order of magnitude higher than the atmospheric value, while neon, argon, krypton, and xenon are relatively about 1–2 orders of magnitudes lower than the atmospheric values. 2) The carbon and hydrogen isotopes of alkanes are generally positive sequence distributions with some part inversion. The 3He/4He values are mainly distributed in magnitude of 10−8, the 40Ar/36Ar is ranged from 506 to 1940, the 129Xe is relative loss, and the 132Xe is relative surplus. 3) Natural gases in the Sulige gas field are typical coal-formed gases generated from a humic organic mother material with maturity from high mature to over mature according to C7 and C8 light hydrocarbons and alkane carbon isotopes. Noble gases are typical crustal genesis, mainly originating from the radioactive decay of crustal source materials. 4) The gas source correlations of noble gases and alkane gases and their quantitative evaluations on source contributions show that natural gases in the Sulige gas field are originated from Carboniferous-Permian coal measure source rocks in Ordos Basin, mainly contributed by coals and supplemented by mudstones, accounting for 55–60% and 40–45%, respectively.

Natural gases in China are mainly coal-derived gas, with assistance from oil-typed gas. At present, many genetic identification methods, from hydrocarbon composition and isotope to light hydrocarbon and biomarker indexes, have been formed, but combined methods from non-hydrocarbon gases are lacking. Based on compositions and isotopes geochemical characteristics and the differences of non-hydrocarbon nitrogen gas in coal-derived gas and oil-typed gas, and combining the isotopic geochemical characteristics of non-hydrocarbon helium, the comprehensive identification methods of coal-derived gas and oil-typed gas for hydrocarbon gases according to the associated non-hydrocarbon gases of nitrogen and helium are established and the preliminary applications have been engaged. The main recognitions are as follows:1)Coal-derived gas generally has relatively lower nitrogen abundance, mainly distributed from 0 to 31.2% with main frequency from 0 to 2%. Oil-typed gas, on the other hand, usually has relatively higher nitrogen abundance, mainly distributed from 1.1 to 57.1% with main frequency from 2 to 16%. 2) Coal-derived gas generally has relatively heavier nitrogen isotope values, mainly distributed from -8 to 19.3‰ with main frequency from -8 to 8‰.Oil-typed gas usually has relatively lower nitrogen isotope values, mainly distributed from -10.6 to 4.6‰ with main frequency from -8 to 4‰.3)The geochemical characteristic differences of coal-derived gas and oil-typed gas are mainly due to the fact that the sapropel parent material is relatively rich in nitrogen element and rich in light δ14N, while the humic parent material is relatively poor in nitrogen element and rich in heavy δ15N. The differences on thermal maturity of source rocks, the redox conditions of source rock sedimentary environment, and the salinity of water body are also important effective factors.4)Differences on nitrogen abundances and isotopes in coal-derived gas and oil-typed gas have great significance in genetic identification. The genetic identification chart of R/Ra-δ15N for organic and inorganic nitrogen in natural gas and the comprehensive joint identification charts of R/Ra-δ15N-N2 of nitrogen and helium for coal-derived gas and oil-typed gas have been established, and are of great reference in investigating the origins and sources of natural gas and guiding natural gas exploration in China.

It is generally accepted that organic–inorganic interactions involving H-rich fluids (i.e., H2O and H2) contribute significantly to hydrocarbon (HC) generation in sedimentary basins. However, the effects of two hydrogenation processes involving H2O and H2 on the generation and C/H isotope fractionation of HC gases from organic matter (OM) remain unclear. In this study, two groups of hydrothermal experiments involving low-mature kerogen without (Group 1) and with FeS (Group 2) at 330–420 °C and 50 MPa were conducted to simulate the hydrogenation of OM by H2O and H2, respectively. The experimental results show that the redox reactions between H2O and FeS lead to the generation of considerable amounts of H2 in the Group 2 experiments. HC gas yield in the Group 2 experiments reaches 1.8–3.6 times that in the Group 1 experiments at Easy%Ro of 1.05–2.50%. In addition, indirect hydrogenation via H2O-derived H2 generates HC gases with smaller 13C fractionation and more negative δ2H compared with direct hydrogenation via H2O. On this basis, the mechanisms for HC gas generation from two hydrogenations were addressed. Additionally, it is demonstrated that the equilibrium isotope effect (EIE) is responsible for the 13C and 2H isotope fractionation in the hydrogenation of OM by H2. [ABSTRACT FROM AUTHOR]

The complex interplay between tumour cells and the tumour microenvironment (TME) underscores the necessity for gaining comprehensive insights into disease progression. This study centres on elucidating the elusive the elusive role of endothelial cells within the TME of head and neck squamous cell carcinoma (HNSCC). Despite their crucial involvement in angiogenesis and vascular function, the mechanistic diversity of endothelial cells among HNSCC patients remains largely uncharted. Leveraging advanced single‐cell RNA sequencing (scRNA‐Seq) technology and the Scissor algorithm, we aimed to bridge this knowledge gap and illuminate the intricate interplay between endothelial cells and patient prognosis within the context of HNSCC. Here, endothelial cells were categorized into Scissorhigh and Scissorlow subtypes. We identified Scissor+ endothelial cells exhibiting pro‐tumorigenic profiles and constructed a prognostic risk model for HNSCC. Additionally, four biomarkers also were identified by analysing the gene expression profiles of patients with HNSCC and a prognostic risk prediction model was constructed based on these genes. Furthermore, the correlations between endothelial cells and prognosis of patients with HNSCC were analysed by integrating bulk and single‐cell sequencing data, revealing a close association between SHSS and the overall survival (OS) of HNSCC patients with malignant endothelial cells. Finally, we validated the prognostic model by RT‐qPCR and IHC analysis. These findings enhance our comprehension of TME heterogeneity at the single‐cell level and provide a prognostic model for HNSCC. [ABSTRACT FROM AUTHOR]