ABSTRACT
BACKGROUND & AIMS: As the most abundant memory T cells and major source of tumor necrosis factor α in the intestinal mucosa of Crohn's disease (CD) patients, CD4+ tissue-resident memory T (TRM) cells play a critical role in CD pathogenesis. We investigated the role of metabolic reprogramming in the regulation of proinflammatory and apoptosis-resistant phenotype for CD4+ TRM cells. METHODS: CD4+ TRM cells were collected from intestinal resection tissues from control and CD patients. Transcriptomic and metabolomic analysis were performed to identify metabolic characteristics of CD4+ TRM cells. Enzyme-linked immunosorbent assay and quantitative polymerase chain reaction experiments were used to assess cytokines level in CD4+ TRM cells; activation-induced cell apoptosis rate was evaluated by flow cytometry. Transwell assay and wound healing assay were performed to detect the effect of CD4+ TRM cells on the migration of normal intestinal epithelial cells. RESULTS: Transcriptomic data combined with unbiased metabolomic analysis revealed an increased fatty acid oxidation (FAO) phenotype existed in CD4+ TRM cells from CD patients. The lipidomic data and stable isotope tracer experiments demonstrated that CD4+ TRM cells up-regulated their lipid lipolysis and fatty acid uptake to fuel FAO in CD patients. Mechanistically, the activated nuclear factor kappa B signaling increased transcription of genes involved in lipid lipolysis, fatty acid uptake, and oxidation in CD4+ TRM cells from CD patients. Targeting FAO of CD4+ TRM cells reversed their apoptosis-resistant and proinflammatory phenotype in CD patients. CONCLUSIONS: CD4+ TRM cells process an accelerated FAO mediated by activated nuclear factor kappa B signaling in CD patients; targeting FAO could reverse their apoptosis-resistant and proinflammatory phenotype. These findings shed a new light on the pathogenic mechanism investigation and novel therapy development in CD patients.
Subject(s)
Apoptosis , CD4-Positive T-Lymphocytes , Crohn Disease , Fatty Acids , Memory T Cells , Oxidation-Reduction , Phenotype , Humans , Crohn Disease/immunology , Crohn Disease/pathology , Crohn Disease/metabolism , Fatty Acids/metabolism , CD4-Positive T-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/metabolism , Memory T Cells/immunology , Memory T Cells/metabolism , Adult , Male , Female , Intestinal Mucosa/immunology , Intestinal Mucosa/pathology , Intestinal Mucosa/metabolism , NF-kappa B/metabolism , Case-Control Studies , Immunologic Memory , Inflammation/pathology , Inflammation/immunology , Inflammation/metabolism , Signal TransductionABSTRACT
PDAC is one of the most common malignant tumors worldwide. The difficulty of early diagnosis and lack of effective treatment are the main reasons for its poor prognosis. Therefore, it is urgent to identify novel diagnostic and therapeutic targets for PDAC patients. The m7G methylation is a common type of RNA modification that plays a pivotal role in regulating tumor development. However, the correlation between m7G regulatory genes and PDAC progression remains unclear. By integrating gene expression and related clinical information of PDAC patients from TCGA and GEO cohorts, m7G binding protein NCBP2 was found to be highly expressed in PDAC patients. More importantly, PDAC patients with high NCBP2 expression had a worse prognosis. Stable NCBP2-knockdown and overexpression PDAC cell lines were constructed to further perform in-vitro and in-vivo experiments. NCBP2-knockdown significantly inhibited PDAC cell proliferation, while overexpression of NCBP2 dramatically promoted PDAC cell growth. Mechanistically, NCBP2 enhanced the translation of c-JUN, which in turn activated MEK/ERK signaling to promote PDAC progression. In conclusion, our study reveals that m7G reader NCBP2 promotes PDAC progression by activating MEK/ERK pathway, which could serve as a novel therapeutic target for PDAC patients.
ABSTRACT
Solar-driven water vaporization is considered one of the most sustainable ways to solve water scarcity. The design of highly efficient solar absorber systems has received extensive attention. Here, we report a novel light absorption material for water evaporation using laser-treated wood. The obtained laser-treated wood possesses interconnected 3D porous networks formed by the random construction of carbon arrays and a hydrophilic surface due to the oxygen implantation by laser treatment. When under 1 sun solar-simulated light irradiation (1 kW m-2), the surface temperatures of dry and water-saturated wood reach 59.5 °C and 40.4 °C, respectively, indicating good heat localization. As a result, the laser-treated wood under 1 sun illumination shows high solar to vapor efficiencies of 93.1% and 92.6% for pure water and seawater, respectively, which are higher than that of most wood-based reported photo-thermal conversion materials. Therefore, the fabricated laser-treated wood may pave the way for harvesting solar energy to produce clean water at low cost.
