Preparation and Properties of Composite Graphene/Carbon Fiber Pouring Conductive Asphalt Concrete.

To solve the problem of snow on steel bridge areas endangering traffic safety and low road traffic efficiency in winter, conductive gussasphait concrete (CGA) was prepared by mixing conductive phase materials (graphene and carbon fiber) into Gussasphalt (GA). First, through high-temperature rutting test, low-temperature bending test, immersion Marshall test, freeze-thaw splitting test and fatigue test, the high-temperature stability, low-temperature crack resistance, water stability and fatigue performance of CGA with different conductive phase materials were systematically studied. Second, the influence of different content of conductive phase materials on the conductivity of CGA was studied through the electrical resistance test, and the microstructure characteristics were analyzed via SEM. Finally, the electrothermal properties of CGA with different conductive phase materials were studied via heating test and simulated ice-snow melting test. The results showed that the addition of graphene/carbon fiber can significantly improve the high-temperature stability, low-temperature crack resistance, water stability and fatigue performance of CGA. The contact resistance between electrode and specimen can be effectively reduced when the graphite distribution is 600 g/m2. The resistivity of 0.3% carbon fiber + 0.5% graphene rutting plate specimen can reach 4.70 Ω·m. Graphene and carbon fiber in asphalt mortar construct a complete conductive network. The heating efficiency of 0.3% carbon fiber + 0.5% graphene rutting plate specimen is 71.4%, and the ice-snow melting efficiency is 28.73%, demonstrating good electrothermal performance and ice-snow melting effect.

PSMD2 contributes to the progression of esophageal squamous cell carcinoma by repressing autophagy.

BACKGROUND: The ubiquitin-proteasome and autophagy-lysosomal systems collaborate in regulating the levels of intracellular proteins. Dysregulation of protein homeostasis is a central feature of malignancy. The gene encoding 26S proteasome non-ATPase regulatory subunit 2 (PSMD2) of the ubiquitin-proteasome system is an oncogene in various types of cancer. However, the detailed role of PSMD2 in autophagy and its relationship to tumorigenesis in esophageal squamous cell carcinoma (ESCC) remain unknown. In the present study, we have investigated the tumor-promoting roles of PSMD2 in the context of autophagy in ESCC. METHODS: Molecular approaches including DAPgreen staining, 5-Ethynyl-2'-deoxyuridine (EdU), cell counting kit 8 (CCK8), colony formation, transwell assays, and cell transfection, xenograft model, immunoblotting and Immunohistochemical analysis were used to investigate the roles of PSMD2 in ESCC cells. Data-independent acquisition (DIA) quantification proteomics analysis and rescue experiments were used to study the roles of PSMD2 in ESCC cells. RESULTS: We demonstrate that the overexpression of PSMD2 promotes ESCC cell growth by inhibiting autophagy and is correlated with tumor progression and poor prognosis of ESCC patients. DIA quantification proteomics analysis shows a significant positive correlation between argininosuccinate synthase 1 (ASS1) and PSMD2 levels in ESCC tumors. Further studies indicate that PSMD2 activates the mTOR pathway by upregulating ASS1 to inhibit autophagy. CONCLUSIONS: PSMD2 plays an important role in repressing autophagy in ESCC, and represents a promising biomarker to predict prognosis and a therapeutic target of ESCC patients.

Study on the Properties of Multi-Walled Carbon Nanotubes (MWCNTs)/Polypropylene Fiber (PP Fiber) Cement-Based Materials.

In order to improve the mechanical properties and durability of cement-based materials, a certain amount of multi-walled carbon nanotubes (MWCNTs) and polypropylene fiber (PP fiber) were incorporated into cement-based materials. The mechanical properties of the multi-walled carbon nanotubes/polypropylene fiber cement-based materials were evaluated using flexural strength tests, compressive strength tests, and splitting tensile tests. The effects of multi-walled carbon nanotubes and polypropylene fiber on the durability of cement-based materials were studied using drying shrinkage tests and freeze-thaw cycle tests. The effects of the multi-walled carbon nanotubes and polypropylene fibers on the microstructure and pore structure of the cement-based materials were compared and analyzed using scanning electron microscopy and mercury intrusion tests. The results showed that the mechanical properties and durability of cement-based materials can be significantly improved when the content of multi-walled carbon nanotubes is 0.1-0.15%. The compressive strength can be increased by 9.5% and the mass loss rate is reduced by 27.9%. Polypropylene fiber has little effect on the compressive strength of the cement-based materials, but it significantly enhances the toughness of the cement-based materials. When its content is 0.2-0.3%, it has the best effect on improving the mechanical properties and durability of the cement-based materials. The flexural strength is increased by 19.1%, and the dry shrinkage rate and water loss rate are reduced by 14.3% and 16.1%, respectively. The three-dimensional network structure formed by the polypropylene fiber in the composite material plays a role in toughening and cracking resistance, but it has a certain negative impact on the pore structure of the composite material. The incorporation of multi-walled carbon nanotubes can improve the bonding performance of the polypropylene fiber and cement matrix, make up for the internal defects caused by the polypropylene fiber, and reduce the number of harmful holes and multiple harmful holes so that the cement-based composite material not only has a significant increase in toughness but also has a denser internal structure.

Characterization of genomic alterations and neoantigens and analysis of immune infiltration identified therapeutic and prognostic biomarkers in adenocarcinoma at the gastroesophageal junction.

Objectives: Adenocarcinoma at the gastroesophageal junction (ACGEJ) refers to a malignant tumor that occurs at the esophagogastric junction. Despite some progress in targeted therapies for HER2, FGFR2, EGFR, MET, Claudin 18.2 and immune checkpoints in ACGEJ tumors, the 5-year survival rate of patients remains poor. Thus, it is urgent to explore genomic alterations and neoantigen characteristics of tumors and identify CD8+ T-cell infiltration-associated genes to find potential therapeutic targets and develop a risk model to predict ACGEJ patients' overall survival (OS). Methods: Whole-exome sequencing (WES) was performed on 55 paired samples from Chinese ACGEJ patients. Somatic mutations and copy number variations were detected by Strelka2 and FACETS, respectively. SigProfiler and SciClone were employed to decipher the mutation signature and clonal structure of each sample, respectively. Neoantigens were predicted using the MuPeXI pipeline. RNA sequencing (RNA-seq) data of ACGEJ samples from our previous studies and The Cancer Genome Atlas (TCGA) were used to identify genes significantly associated with CD8+ T-cell infiltration by weighted gene coexpression network analysis (WGCNA). To construct a risk model, we conducted LASSO and univariate and multivariate Cox regression analyses. Results: Recurrent MAP2K7, RNF43 and RHOA mutations were found in ACGEJ tumors. The COSMIC signature SBS17 was associated with ACGEJ progression. CCNE1 and VEGFA were identified as putative CNV driver genes. PI3KCA and TP53 mutations conferred selective advantages to cancer cells. The Chinese ACGEJ patient neoantigen landscape was revealed for the first time, and 58 potential neoantigens common to TSNAdb and IEDB were identified. Compared with Siewert type II samples, Siewert type III samples had significant enrichment of the SBS17 signature, a lower TNFRSF14 copy number, a higher proportion of samples with complex clonal architecture and a higher neoantigen load. We identified 10 important CD8+ T-cell infiltration-related Hub genes (CCL5, CD2, CST7, GVINP1, GZMK, IL2RB, IKZF3, PLA2G2D, P2RY10 and ZAP70) as potential therapeutic targets from the RNA-seq data. Seven CD8+ T-cell infiltration-related genes (ADAM28, ASPH, CAMK2N1, F2R, STAP1, TP53INP2, ZC3H3) were selected to construct a prognostic model. Patients classified as high risk based on this model had significantly worse OS than low-risk patients, which was replicated in the TCGA-ACGEJ cohort. Conclusions: This study provides new neoantigen-based immunotherapeutic targets for ACGEJ treatment and effective disease prognosis biomarkers.

Multi-omic characterization of genome-wide abnormal DNA methylation reveals diagnostic and prognostic markers for esophageal squamous-cell carcinoma.

This study investigates aberrant DNA methylations as potential diagnosis and prognosis markers for esophageal squamous-cell carcinoma (ESCC), which if diagnosed at advanced stages has <30% five-year survival rate. Comparing genome-wide methylation sites of 91 ESCC and matched adjacent normal tissues, we identified 35,577 differentially methylated CpG sites (DMCs) and characterized their distribution patterns. Integrating whole-genome DNA and RNA-sequencing data of the same samples, we found multiple dysregulated transcription factors and ESCC-specific genomic correlates of identified DMCs. Using featured DMCs, we developed a 12-marker diagnostic panel with high accuracy in our dataset and the TCGA ESCC dataset, and a 4-marker prognostic panel distinguishing high-risk patients. In-vitro experiments validated the functions of 4 marker host genes. Together these results provide additional evidence for the important roles of aberrant DNA methylations in ESCC development and progression. Our DMC-based diagnostic and prognostic panels have potential values for clinical care of ESCC, laying foundations for developing targeted methylation assays for future non-invasive cancer detection methods.

CstF64-Induced Shortening of the BID 3'UTR Promotes Esophageal Squamous Cell Carcinoma Progression by Disrupting ceRNA Cross-talk with ZFP36L2.

The majority of human genes have multiple polyadenylation sites, which are differentially used through the process of alternative polyadenylation (APA). Dysregulation of APA contributes to numerous diseases, including cancer. However, specific genes subject to APA that impact oncogenesis have not been well characterized, and many cancer APA landscapes remain underexplored. Here, we used dynamic analyses of APA from RNA-seq (DaPars) to define both the 3'UTR APA profile in esophageal squamous cell carcinoma (ESCC) and to identify 3'UTR shortening events that may drive tumor progression. In four distinct squamous cell carcinoma datasets, BID 3'UTRs were recurrently shortened and BID mRNA levels were significantly upregulated. Moreover, system correlation analysis revealed that CstF64 is a candidate upstream regulator of BID 3'UTR length. Mechanistically, a shortened BID 3'UTR promoted proliferation of ESCC cells by disrupting competing endogenous RNA (ceRNA) cross-talk, resulting in downregulation of the tumor suppressor gene ZFP36L2. These in vitro and in vivo results were supported by human patient data whereby 3'UTR shortening of BID and low expression of ZFP36L2 are prognostic factors of survival in ESCC. Collectively, these findings demonstrate that a key ceRNA network is disrupted through APA and promotes ESCC tumor progression.Significance: High-throughput analysis of alternative polyadenylation in esophageal squamous cell carcinoma identifies recurrent shortening of the BID 3'UTR as a driver of disease progression.

Dissecting esophageal squamous-cell carcinoma ecosystem by single-cell transcriptomic analysis.

Esophageal squamous-cell carcinoma (ESCC), one of the most prevalent and lethal malignant disease, has a complex but unknown tumor ecosystem. Here, we investigate the composition of ESCC tumors based on 208,659 single-cell transcriptomes derived from 60 individuals. We identify 8 common expression programs from malignant epithelial cells and discover 42 cell types, including 26 immune cell and 16 nonimmune stromal cell subtypes in the tumor microenvironment (TME), and analyse the interactions between cancer cells and other cells and the interactions among different cell types in the TME. Moreover, we link the cancer cell transcriptomes to the somatic mutations and identify several markers significantly associated with patients' survival, which may be relevant to precision care of ESCC patients. These results reveal the immunosuppressive status in the ESCC TME and further our understanding of ESCC.

VAV2 is required for DNA repair and implicated in cancer radiotherapy resistance.

Radiotherapy remains the mainstay for treatment of various types of human cancer; however, the clinical efficacy is often limited by radioresistance, in which the underlying mechanism is largely unknown. Here, using esophageal squamous cell carcinoma (ESCC) as a model, we demonstrate that guanine nucleotide exchange factor 2 (VAV2), which is overexpressed in most human cancers, plays an important role in primary and secondary radioresistance. We have discovered for the first time that VAV2 is required for the Ku70/Ku80 complex formation and participates in non-homologous end joining repair of DNA damages caused by ionizing radiation. We show that VAV2 overexpression substantially upregulates signal transducer and activator of transcription 1 (STAT1) and the STAT1 inhibitor Fludarabine can significantly promote the sensitivity of radioresistant patient-derived ESCC xenografts in vivo in mice to radiotherapy. These results shed new light on the mechanism of cancer radioresistance, which may be important for improving clinical radiotherapy.

Metabolic remodeling by TIGAR overexpression is a therapeutic target in esophageal squamous-cell carcinoma.

Rationale: Whole-genome sequencing has identified many amplified genes in esophageal squamous-cell carcinoma (ESCC). This study investigated the role and clinical relevance of these genes in ESCC. Methods: We collected ESCC and non-tumor esophageal tissues from 225 individuals who underwent surgery. Clinical data were collected and survival time was measured from the date of diagnosis to the date of last follow-up or death. Patient survival was compared with immunohistochemical staining score using Kaplan-Meier methods and hazard ratios were calculated by Cox models. Cells with gene overexpression and knockout were analyzed in proliferation, migration and invasion assays. Cells were also analyzed for levels of intracellular lactate, NADPH, ATP and mRNA and protein expression patterns. Protein levels in cell line and tissue samples were measured by immunoblotting or immunohistochemistry. ESCC cell were grown as xenograft tumors in nude mice. Primary ESCC in genetically engineered mice and patient-derived xenograft mouse models were established for test of therapeutic effects. Results: We show that TP53-induced glycolysis and apoptosis regulator (TIGAR) is a major player in ESCC progression and chemoresistance. TIGAR reprograms glucose metabolism from glycolysis to the glutamine pathway through AMP-activated kinase, and its overexpression is correlated with poor disease outcomes. Tigar knockout mice have reduced ESCC tumor burden and growth rates. Treatment of TIGAR-overexpressing ESCC cell xenografts and patient-derived tumor xenografts in mice with combination of glutaminase inhibitor and chemotherapeutic agents achieves significant more efficacy than chemotherapy alone. Conclusion: These findings shed light on an important role of TIGAR in ESCC and might provide evidence for targeted treatment of TIGAR-overexpressing ESCC.