Genomic Analyses Reveal Mutational Signatures and Frequently Altered Genes in Esophageal Squamous Cell Carcinoma

Esophageal squamous cell carcinoma (ESCC) is one of the most common cancers worldwide and the fourth most lethal cancer in China. However, although genomic studies have identified some mutations associated with ESCC, we know little of the mutational processes responsible. To identify genome-wide mutational signatures, we performed either whole-genome sequencing (WGS) or whole-exome sequencing (WES) on 104 ESCC individuals and combined our data with those of 88 previously reported samples. An APOBEC-mediated mutational signature in 47% of 192 tumors suggests that APOBEC-catalyzed deamination provides a source of DNA damage in ESCC. Moreover, PIK3CA hotspot mutations (c.1624G>A [p.Glu542Lys] and c.1633G>A [p.Glu545Lys]) were enriched in APOBEC-signature tumors, and no smoking-associated signature was observed in ESCC. In the samples analyzed by WGS, we identified focal (<100 kb) amplifications of CBX4 and CBX8. In our combined cohort, we identified frequent inactivating mutations in AJUBA, ZNF750, and PTCH1 and the chromatin-remodeling genes CREBBP and BAP1, in addition to known mutations. Functional analyses suggest roles for several genes (CBX4, CBX8, AJUBA, and ZNF750) in ESCC. Notably, high activity of hedgehog signaling and the PI3K pathway in approximately 60% of 104 ESCC tumors indicates that therapies targeting these pathways might be particularly promising strategies for ESCC. Collectively, our data provide comprehensive insights into the mutational signatures of ESCC and identify markers for early diagnosis and potential therapeutic targets

Microbial fuel cells: From fundamentals to applications. A review

© 2017 The Author(s) In the past 10–15 years, the microbial fuel cell (MFC) technology has captured the attention of the scientific community for the possibility of transforming organic waste directly into electricity through microbially catalyzed anodic, and microbial/enzymatic/abiotic cathodic electrochemical reactions. In this review, several aspects of the technology are considered. Firstly, a brief history of abiotic to biological fuel cells and subsequently, microbial fuel cells is presented. Secondly, the development of the concept of microbial fuel cell into a wider range of derivative technologies, called bioelectrochemical systems, is described introducing briefly microbial electrolysis cells, microbial desalination cells and microbial electrosynthesis cells. The focus is then shifted to electroactive biofilms and electron transfer mechanisms involved with solid electrodes. Carbonaceous and metallic anode materials are then introduced, followed by an explanation of the electro catalysis of the oxygen reduction reaction and its behavior in neutral media, from recent studies. Cathode catalysts based on carbonaceous, platinum-group metal and platinum-group-metal-free materials are presented, along with membrane materials with a view to future directions. Finally, microbial fuel cell practical implementation, through the utilization of energy output for practical applications, is described

Role of Epidermal Growth Factor Receptor-Specific CAR-T Cells in the Suppression of Esophageal Squamous Cell Carcinoma

ESCC is a highly malignant tumor, and its morbidity and mortality in China account for more than 50% of the world&rsquo;s total rates. As effective treatments are lacking, the 5-year survival rate of patients does not exceed 30%. CAR-T-cell-based immunotherapy has emerged as one of the most promising cancer treatments; however, there are relatively fewer reports regarding its application for ESCC. In this study, we conducted large-sample whole-genome sequencing (WGS) and RNA-seq analysis of patients with ESCC from China to examine the feasibility of EGFR-targeting CAR-T cells in the treatment of ESCC. We found much higher levels of EGFR gene amplification and overexpression in tumors than in the normal tissues, indicating that EGFR could be a promising target of CAR-T-cell-based immunotherapy in ESCC. Therefore, we tested EGFR-targeting CAR-T cells for lytic activity against ESCC cells as a model to establish cellular immunotherapy for ESCC. Five types of CAR-T cells targeting EGFR were constructed, two of which, CAR1-T and CAR2-T, showed a strong cytotoxicity against ESCC in in vitro and in vivo experiments. The results of this study suggest that CAR1-T and CAR2-T have the potential to be used for anti-ESCC immunotherapy in clinics

Effects of Different Injection Strategies on Combustion and Emission Characteristics of Diesel Engine Fueled with Dual Fuel

In this work, an effective numerical simulation method was developed and used to analyze the effects of natural gas mixing ratio and pilot-main injection, main-post injection, and pilot-main-post injection strategies on the combustion and emission characteristics of diesel engine fueled with dual fuel. Firstly, the one-dimensional calculation model and three-dimensional CFD model of the engine were established by AVL-BOOST and AVL-Fire, respectively. In addition, the simplified chemical kinetics mechanism was adopted, which could accurately calculate the combustion and emission characteristics of the engine. The results show that the cylinder pressure and heat release rate decrease with the increase of the natural gas mixing ratio and the NOx emission is reduced. When the NG mixing ratio is 50%, the NOx and CO emission are reduced by 47% and 45%, respectively. When the SODI3 is 24 °CA ATDC, the NOx emission is reduced by 29.6%. In addition, with suitable pilot-main injection and pilot-main-post injection strategies, the combustion in the cylinder can be improved and the trade-off relationship between NOx and soot can be relaxed. Thus, the proper main-post injection strategy can improve the combustion and emission characteristics, especially the reduction in the NOx and CO emissions

RPS15 interacted with IGF2BP1 to promote esophageal squamous cell carcinoma development via recognizing m6A modification

Abstract Increased rates of ribosome biogenesis have been recognized as hallmarks of many cancers and are associated with poor prognosis. Using a CRISPR synergistic activation mediator (SAM) system library targeting 89 ribosomal proteins (RPs) to screen for the most oncogenic functional RPs in human esophageal squamous cell carcinoma (ESCC), we found that high expression of RPS15 correlates with malignant phenotype and poor prognosis of ESCC. Gain and loss of function models revealed that RPS15 promotes ESCC cell metastasis and proliferation, both in vitro and in vivo. Mechanistic investigations demonstrated that RPS15 interacts with the K homology domain of insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1), which recognizes and directly binds the 3′-UTR of MKK6 and MAPK14 mRNA in an m6A-dependent manner, and promotes translation of core p38 MAPK pathway proteins. By combining targeted drug virtual screening and functional assays, we found that folic acid showed a therapeutic effect on ESCC by targeting RPS15, which was augmented by the combination with cisplatin. Inhibition of RPS15 by folic acid, IGF2BP1 ablation, or SB203580 treatment were able to suppress ESCC metastasis and proliferation via the p38 MAPK signaling pathway. Thus, RPS15 promotes ESCC progression via the p38 MAPK pathway and RPS15 inhibitors may serve as potential anti-ESCC drugs

Genomic analyses reveal mutational signatures and frequently altered genes in esophageal squamous cell carcinoma

Esophageal squamous cell carcinoma (ESCC) is one of the most common cancers world wide and the fourth most lethal cancer in China. However, although genomic studies have identified some mutations associated with ESCC, we know little of the mutational processes responsible. To identify genome-wide mutational signatures, we performed either whole-genome sequencing (WGS) or whole-exome sequencing (WES) on 104 ESCC individuals and combined our data with those of 88 previously reported samples. An APOBEC-mediated mutational signature in 47% of 192 tumors suggests that APOBEC-catalyzed deamination provides a source of DNA damage in ESCC. Moreover, PIK3CA hotspot mutations (c.1624G> A [p.Glu542Lys] and c.1633G>A [p.Glu545Lys]) were enriched in APOBEC-signature tumors, and no smoking associated signature was observed in ESCC. In the samples analyzed by WGS, we identified focal

Supplemental Material, Table_S1_Information_of_104_ESCC_patients - High TSTA3 Expression as a Candidate Biomarker for Poor Prognosis of Patients With ESCC

<p>Supplemental Material, Table_S1_Information_of_104_ESCC_patients for High TSTA3 Expression as a Candidate Biomarker for Poor Prognosis of Patients With ESCC by Jie Yang, Pengzhou Kong, Jian Yang, Zhiwu Jia, Xiaoling Hu, Zianyi Wang, Heyang Cui, Yanghui Bi, Yu Qian, Hongyi Li, Fang Wang, Bin Yang, Ting Yan, Yanchun Ma, Ling Zhang, Caixia Cheng, Bin Song, Yaoping Li, Enwei Xu, Haiyan Liu, Wei Gao, Juan Wang, Yiqian Liu, Yuanfang Zhai, Lu Chang, Yi Wang, Yingchun Zhang, Ruyi Shi, Jing Liu, Qi Wang, Xiaolong Cheng, and Yongping Cui in Technology in Cancer Research & Treatment</p