Identification of the Expression of TIE1 and Its Mediated Immunosuppression in Gastric Cancer.

Background: Recently, various evidence has confirmed that Tyrosine Kinase with Immunoglobulin-like and EGF-like domains 1 (TIE1) promotes tumor growth in many cancers. However, the precise mechanism underlying TIE1's involvement in Gastric Cancer (GC) remains elusive. This research aimed to investigate the biological function of TIE1 in regulating GC progression. Methods: The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), GEPIA2.0, Sangerbox3.0 and TIMER databases were used to analyze the TIE1 expression. Immunohistochemistry (IHC) was used to demonstrate the expression of TIE1. TCGA, GEPIA2.0 and Kaplan-Meier were utilized for survival analysis and to explore the association of TIE1 with clinicopathological features. Protein-Protein Interaction (PPI) networks were constructed using Cytoscape. The potential molecular mechanism of TIE1 was investigated by Gene Ontology (GO), Kyoto Encyclopedia of Gene Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA). We studied the relationships between TIE1 and mutations, immune checkpoints (ICs), tumor mutational burden (TMB), as well as microsatellite instability (MSI) to explore the underlying mechanism of immunity in GC. Results: Compared with normal tissue, TIE1 was significantly overexpressed in GC tissues (p = 0.0072) and was associated with poor survival (P < 0.05). According to GO and KEGG enrichment analyses, TIE1 was enriched in signal pathways related to the occurrence, invasion, and migration of malignant tumors (i.e., PI3K-Akt signaling pathway, Calcium signaling pathway, etc.). Immune infiltration analysis suggested that TIE1 is positively correlated with macrophages M2 and negatively correlated with Mast cells, naive B cells and Follicular helper T cells (TFH), which may be a contributing factor to tumor progression. Furthermore, the research on the tumor microenvironment (TME) and tumor purity also proved that TIE1 may be an oncogene. Mutation analysis showed that the high expression group of TIE1 had a higher frequency of mutations in TP53 and ARID1, while the TMB score was lower. Conclusion: TIE1 might be an oncogene via regulating dysregulated immune infiltration to cause immunosuppression in GC and could be identified as a biomarker for prognosis and a therapeutic target for GC.

Integrated analysis of a competing endogenous RNA network reveals a ferroptosis-related 6-lncRNA prognostic signature in clear cell renal cell carcinoma.

BACKGROUND: Establishing a robust signature for prognostic prediction and precision treatment is necessary due to the heterogeneous prognosis and treatment response of clear cell renal cell carcinoma (ccRCC). OBJECTIVES: This study set out to elucidate the biological functions and prognostic role of ferroptosis-related long non-coding RNAs (lncRNAs) based on a synthetic analysis of competing endogenous RNA networks in ccRCC. MATERIAL AND METHODS: Ferroptosis-related genes were obtained from the FerrDb database. The expression data and matched clinical information of lncRNAs, miRNAs and mRNAs from The Cancer Genome Atlas (TCGA) database were obtained to identify differentially expressed RNAs. The lncRNA-miRNA-mRNA ceRNA network was established utilizing the common miRNAs that were predicted in the RNAHybrid, StarBase and TargetScan databases. Then, using progressive univariate Cox regression, least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression analysis of gene expression data and clinical information, a ferroptosis-related lncRNA prognosis signature was constructed based on the lncRNAs in ceRNA. Finally, the influence of independent lncRNAs on ccRCC was explored. RESULTS: A total of 35 ferroptosis-related mRNAs, 356 lncRNAs and 132 miRNAs were sorted out after differential expression analysis in the TCGA-KIRC. Subsequently, overlapping lncRNA-miRNA and miRNA-mRNA interactions among the RNAHybrid, StarBase and TargetScan databases were constructed and identified; then a ceRNA network with 77 axes related to ferroptosis was established utilizing mutual miRNAs in 2 interaction networks as nodes. Next, a 6-ferroptosis-lncRNA signature including PVT1, CYTOR, MIAT, SNHG17, LINC00265, and LINC00894 was identified in the training set. Kaplan-Meier analysis, PCA, t-SNE analysis, risk score curve, and receiver operating characteristic (ROC) curve were performed to confirm the validity of the signature in the training set and verified in the validation set. Finally, single-sample gene set enrichment analysis (ssGSEA) and ESTIMATE (Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data) analysis showed that the signature was related to immune cell infiltration. CONCLUSIONS: Our research underlines the role of the 6-ferroptosis-lncRNA signature as a predictor of prognosis and a therapeutic alternative for ccRCC.

Identification and characterization of CLEC11A and its derived immune signature in gastric cancer.

Introduction: C-type lectin domain family 11 member A (CLEC11A) was characterized as a growth factor that mainly regulates hematopoietic function and differentiation of bone cells. However, the involvement of CLEC11A in gastric cancer (GC) is not well understood. Methods: Transcriptomic data and clinical information pertaining to GC were obtained and analyzed from publicly available databases. The relationships between CLEC11A and prognoses, genetic alterations, tumor microenvironment (TME), and therapeutic responses in GC patients were analyzed by bioinformatics methods. A CLEC11A-derived immune signature was developed and validated, and its mutational landscapes, immunological characteristics as well as drug sensitivities were explored. A nomogram was established by combining CLEC11A-derived immune signature and clinical factors. The expression and carcinogenic effects of CLEC11A in GC were verified by qRT-PCR, cell migration, invasion, cell cycle analysis, and in vivo model analysis. Myeloid-derived suppressor cells (MDSCs), regulatory T cells (Tregs), M2 macrophages, and T cells in tumor samples extracted from mice were analyzed utilizing flow cytometry analysis. Results: CLEC11A was over-expressed in GC, and the elevated CLEC11A expression indicated an unfavorable prognosis in GC patients. CLEC11A was involved in genomic alterations and associated with the TME in GC. Moreover, elevated CLEC11A was found to reduce the benefit of immunotherapy according to immunophenoscore (IPS) and the tumor immune dysfunction, exclusion (TIDE). After validation, the CLEC11A-derived immune signature demonstrated a consistent ability to predict the survival outcomes in GC patients. A nomogram that quantifies survival probability was constructed to improve the accuracy of prognosis prediction in GC patients. Using shRNA to suppress the expression of CLEC11A led to significant inhibitions of cell cycle progression, migration, and invasion, as well as a marked reduction of in vivo tumor growth. Moreover, the flow cytometry assay showed that the knock-down of CLEC11A increased the infiltration of cytotoxic CD8+ T cells and helper CD4+ T into tumors while decreasing the percentage of M2 macrophages, MDSCs, and Tregs. Conclusion: Collectively, our findings revealed that CLEC11A could be a prognostic and immunological biomarker in GC, and CLEC11A-derived immune signature might serve as a new option for clinicians to predict outcomes and formulate personalized treatment plans for GC patients.

Ambient-Stable 2D Dion-Jacobson Phase Tin Halide Perovskite Field-Effect Transistors with Mobility over 1.6 Cm2 V-1 s-1.

Solution-processed metal halide perovskites hold immense potential for the advancement of next-generation field-effect transistors (FETs). However, the instability of perovskite-based transistors has impeded their progress and practical applications. Here, ambient-stable high-performance FETs based on 2D Dion-Jacobson phase tin halide perovskite BDASnI4 , which has high film quality and excellent electrical properties, are reported. The perovskite channels are established by engineering the film crystallization process via the employment of ammonium salt interlayers and the incorporation of NH4 SCN additives within the precursor solution. The refined FETs demonstrate field-effect hole mobilities up to 1.61 cm2 V-1 s-1 and an on/off ratio surpassing 106 . Moreover, the devices show impressive operational and environmental stability and retain their functional performance even after being exposed to ambient conditions with a temperature of 45 °C and humidity of 45% for over 150 h.

High-Density Vertical Transistors with Pitch Size Down to 20 nm.

Vertical field effect transistors (VFETs) have attracted considerable interest for developing ultra-scaled devices. In particular, individual VFET can be stacked on top of another and does not consume additional chip footprint beyond what is needed for a single device at the bottom, representing another dimension for high-density transistors. However, high-density VFETs with small pitch size are difficult to fabricate and is largely limited by the trade-offs between drain thickness and its conductivity. Here, a simple approach is reported to scale the drain to sub-10 nm. By combining 7 nm thick Au with monolayer graphene, the hybrid drain demonstrates metallic behavior with low sheet resistance of ≈100 Ω sq-1 . By van der Waals laminating the hybrid drain on top of 3 nm thick channel and scaling gate stack, the total VFET pitch size down to 20 nm and demonstrates a higher on-state current of 730 A cm-2 . Furthermore, three individual VFETs together are vertically stacked within a vertical distance of 59 nm, representing the record low pitch size for vertical transistors. The method pushes the scaling limit and pitch size limit of VFET, opening up a new pathway for high-density vertical transistors and integrated circuits.

A Methodology of Fabricating Novel Electrodes for Semiconductor Devices: Doping and Van der Waals Integrating Organic Semiconductor Films.

Electrodes are indispensable components in semiconductor devices, and now are mainly made from metals, which are convenient for use but not ideal for emerging technologies such as bioelectronics, flexible electronics, or transparent electronics. Here the methodology of fabricating novel electrodes for semiconductor devices using organic semiconductors (OSCs) is proposed and demonstrated. It is shown that polymer semiconductors can be heavily p- or n-doped to achieve sufficiently high conductivity for electrodes. In contrast with metals, the doped OSC films (DOSCFs) are solution-processable, mechanically flexible, and have interesting optoelectronic properties. By integrating the DOSCFs with semiconductors through van der Waals contacts different kinds of semiconductor devices can be constructed. Importantly, these devices exhibit higher performance than their counterparts with metal electrodes, and/or excellent mechanical or optical properties that are unavailable in metal-electrode devices, suggesting the superiority of DOSCF electrodes. Given the existing large amount of OSCs, the established methodology can provide abundant electrode choices to meet the demand of various emerging devices.

3-Phenyl-1-(pyrrol-2-yl)prop-2-en-1-one.

The title mol-ecule, C(13)H(11)NO, is almost flat, the angle between the pyrrole and the phenyl rings being 10.9 (1)°. The atoms of the central C(3)O unit are coplanar, with a mean deviation from the plane of 0.001 (1) Å. The angles between this plane and the pyrrole and phenyl rings are 3.3 (1) and 8.0 (1)°, respectively. The mol-ecules form centrosymmetric dimers through a pair of N-H⋯O hydrogen bonds with an R(2) (2)(10) motif.