Prognostic value of fatty acid metabolism-related genes in colorectal cancer and their potential implications for immunotherapy

IntroductionColorectal cancer is one of the most common gastrointestinal cancers and the second leading cause of cancer-related death. Although colonoscopy screening has greatly improved the early diagnosis of colorectal cancer, its recurrence and metastasis are still significant problems. Tumour cells usually have the hallmark of metabolic reprogramming, while fatty acids play important roles in energy storage, cell membrane synthesis, and signal transduction. Many pathways of fatty acid metabolism (FAM) are involved in the occurrence and development of colon cancer, and the complex molecular interaction network contains a variety of genes encoding key enzymes and related products.MethodsClinical information and RNA sequencing data were collected from TCGA and GEO databases. The prognosis model of colon cancer was constructed by LASSO-Cox regression analysis among the selected fatty acid metabolism genes with differential expression. Nomogram for the prognosis model was also constructed in order to analyze its value in evaluating the survival and clinical stage of the colon cancer patients. The differential expression of the selected genes was verified by qPCR and immunohistochemistry. GSEA and GSVA were used to analyze the enrichment pathways for high- and low-risk groups. CIBERSORT was used to analyze the immune microenvironment of colon cancer and to compare the infiltration of immune cells in the high- and low-risk groups. The “circlize” package was used to explore the correlation between the risk score signature and immunotherapy for colon cancer.ResultsWe analysed the differential expression of 704 FAM-related genes between colon tumour and normal tissue and screened 10 genes with prognostic value. Subsequently, we constructed a prognostic model for colon cancer based on eight optimal FAM genes through LASSO Cox regression analysis in the TCGA-COAD dataset, and its practicality was validated in the GSE39582 dataset. Moreover, the risk score calculated based on the prognostic model was validated as an independent prognostic factor for colon cancer patients. We further constructed a nomogram composed of the risk score signature, age and American Joint Committee on Cancer (AJCC) stage for clinical application. The colon cancer cohort was divided into high- and low-risk groups according to the optimal cut-off value, and different enrichment pathways and immune microenvironments were depicted in the groups.DiscussionSince the risk score signature was significantly correlated with the expression of immune checkpoint molecules, the prognostic model might be able to predict the immunotherapy response of colon cancer patients. In summary, our findings expand the prognostic value of FAM-related genes in colon cancer and provide evidence for their application in guiding immunotherapy

Covalently grafting conjugated porous polymers to MXene offers a two-dimensional sandwich-structured electrocatalytic sulfur host for lithium–sulfur batteries

© 2022 Elsevier B.V.Lithium–sulfur (Li–S) batteries have received increasing attention due to their high energy density (2600 W h kg−1) as well as the low cost and nontoxicity of sulfur. However, sluggish conversion kinetics and the notorious shuttle effect of the polysulfides present in sulfur cathodes hinder the practical use of Li–S batteries. Herein, an electrocatalytic sulfur host with a two-dimensional (2D) sandwich structure is synthesized and found to display excellent properties for overcoming the noted challenges. The electrocatalytic sulfur host is prepared by covalently grafting a conjugated microporous polymer (CMP) to MXene nanosheets and denoted as CMP-M. The CMP component features triazine and benzothiophene units and thus the constituent heteroatoms endow CMP-M with a plethora of chemisorption sites to capture various polysulfides. The MXene component provides an electrocatalytic template to construct the 2D sandwich composite and can facilitate charge transfer while accelerating polysulfide conversion. Li–S cells prepared using CMP-M as sulfur hosts are found to exhibit a number of outstanding performance metrics including a high specific capacity (i.e., 1402 mA h g−1 at 0.1C), an outstanding rate capability (i.e., 610 mA h g−1 at 4C), and a low capacity decay (from an initial value of 730 to 550 after 1000 cycles at 2C, corresponding to 0.025% per cycle). The methodology presented herein offers a universal approach for constructing electrocatalytic 2D composites that are useful not only in Li–S batteries but also in other contemporary energy technologies.11Nsciescopu

Coaxially grafting conjugated microporous polymers containing single-atom cobalt catalysts to carbon nanotubes enhances sulfur cathode reaction kinetics

© 2022 Elsevier B.V.Conjugated microporous polymers (CMPs) hold great potential for use in energy related applications due to their extended π-conjugated structures, tunable pore sizes, and modular molecular functionalities. Herein, we report a novel composite material (labeled as Co-CMP-MWNTs) that consists of a CMP containing Co single-atom catalysts (Co SACs) and being coaxially grafted to multi-walled carbon nanotubes (MWNTs), and show that the material synergistically promotes the cathode reaction kinetics in lithium−sulfur (Li−S) batteries. The Co-CMP-MWNTs are synthesized by coupling 2,4,6-tris(4-ethynylphenyl)-1,3,5-triazine to a dibromobipyridine-Co complex in the presence of bromopyrimidinyl-functionalized MWNTs. The composite features a conductive MWNT-based core and a CMP-based shell that contains nitrogen as well as Co. Cs-corrected high-resolution transmission electron microscopy and X-ray absorption near-edge structure (XANES) spectroscopy reveal that the Co species exist as single atoms. Additional XANES data coupled with density functional theory calculations elucidate the adsorption interactions formed between the Co SACs and various sulfur species as well as their electrocatalytic effects. Li−S cells prepared using Co-CMP-MWNTs as a cathode host material exhibit excellent performance in terms of specific capacity (1485 mA h g−1 at 0.1 C), rate capability (602 mA h g−1 at 3 C), and cycling stability (510 mA h g−1 at 0.5 C after 1000 cycles, which corresponds to a capacity decay of 0.050% per cycle). Collectively, the results demonstrate that SACs can be prepared under benign conditions and used to enhance sulfur cathode reaction kinetics. The methodology described may be extended to enable the use of SACs in other contemporary energy conversion technologies.11Nsciescopu