NOX4 promotes tumor progression through the MAPK-MEK1/2-ERK1/2 axis in colorectal cancer

BACKGROUND Metabolic reprogramming plays a key role in cancer progression and clinical outcomes;however,the patterns and primary regulators of metabolic reprogramming in colorectal cancer(CRC)are not well understood.AIM To explore the role of nicotinamide adenine dinucleotide phosphate oxidase 4(NOX4)in promoting progression of CRC.METHODS We evaluated the expression and function of dysregulated and survival-related metabolic genes using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes.Consensus clustering was used to cluster CRC based on dysregulated metabolic genes.A prediction model was constructed based on survival-related metabolic genes.Sphere formation,migration,invasion,proliferation,apoptosis and clone formation was used to evaluate the biological function of NOX4 in CRC.mRNA sequencing was utilized to explore the alterations of gene expression NOX4 over-expression tumor cells.In vivo subcutaneous and lung metastasis mouse tumor model was used to explore the effect of NOX4 on tumor growth.RESULTS We comprehensively analyzed 3341 metabolic genes in CRC and identified three clusters based on dysregulated metabolic genes.Among these genes,NOX4 was highly expressed in tumor tissues and correlated with worse survival.In vitro,NOX4 overexpression induced clone formation,migration,invasion,and stemness in CRC cells.Furthermore,RNA-sequencing analysis revealed that NOX4 overexpression activated the mitogen-activated protein kinase-MEK1/2-ERK1/2 signaling pathway.Trametinib,a MEK1/2 inhibitor,abolished the NOX4-mediated tumor progression.In vivo,NOX4 overexpression promoted subcutaneous tumor growth and lung metastasis,whereas trametinib treatment can reversed the metastasis.CONCLUSION Our study comprehensively analyzed metabolic gene expression and highlighted the importance of NOX4 in promoting CRC metastasis,suggesting that trametinib could be a potential therapeutic drugs of CRC clinical therapy targeting NOX4.

Fabrication of Ni Nanoclusters-Modied Brookite TiO2 Quasi Nanocubes and Its Photocatalytic Hydrogen Evolution Performance

The development of low-cost, earth-abundant and highly-ecient cocatalysts is still impor- tant to promote the photocatalytic H2 evolution reaction over semiconductors. Herein, a series of Ni nanoclusters (NCs) modied brookite TiO2 quasi nanocubes (BTN)(marked as Ni/BTN) are fabricated via a chemical reduction process. It is found that the loading content and oxidation state of Ni NCs can signiticantly inuence the optical absorption, photocat-alytic activity, and stability of Ni/BTN composites. Among the resultant Ni NCs-loaded products, 0.1%Ni/BTN composite delivers the best H2 evolution activity (156μmol/h), which is 4.3 times higher than that of the BTN alone (36 mol/h). Furthermore, the Ni NCs with ultrane size (-2 nm) and high dispersity enable shorter charge transfer distance by quickly capturing the photoexcited electrons of BTN, and thus result in the improved activity even though the oxidization of some Ni NCs on BTN is harmful to the activity for H2 evolution due to the much lower electron capturing capability of NiO than metallic Ni. This study not only clari es that brookite TiO2 would be a promising high-ecient photo- catalyst for H2 evolution, but also reveals vital clues for further improving its photocatalytic performance using low-cost Ni-based cocatalyst.

Trigger and noise filtering algorithms for the LHAASO water Cherenkov detector array

Introduction The Large High Altitude Air Shower Observatory(LHAASO)will be constructed at Mt.Haizishan,Sichuan Province,China.Among several detector components of the LHAASO,the Water Cherenkov Detector Array(WCDA)is of great importance for gamma-ray astronomy from 100 GeV to 30 TeV.The single-channel counting rate of a photo-multiplier tube can reach as high as 30-35 kHz,most of them are background noise hits from the low energy cosmic ray showers,bringing a big challenge on data transferring,data storage and event reconstruction.Methods In this paper,a dedicated trigger scheme and a fast noise filtering method aiming to deal with these high rate background noise hits are introduced.These methods are tested with some Monte Carlo simulation data,showing a fair efficiency in filtering background noise hits,while most of the real shower signals are kept.Conclusion This method is proposed to be applied in a stage of the online processing just after the data are acquired in LHAASO-WCDA.