Identification of immune-associated biomarker for predicting lung adenocarcinoma: bioinformatics analysis and experiment verification of PTK6.

BACKGROUND: Abnormal expression of protein tyrosine kinase 6 (PTK6) has been proven to be involved in the development of gynecological tumors. However, its immune-related carcinogenic mechanism in other tumors remains unclear. OBJECTIVE: The aim of this study was to identify PTK6 as a novel prognostic biomarker in pan-cancer, especially in lung adenocarcinoma (LUAD), which is correlated with immune infiltration, and to clarify its clinicopathological and prognostic significance. METHODS: The prognostic value and immune relevance of PTK6 were investigated by using bio-informatics in this study. PTK6 expression was validated in vitro experiments (lung cancer cell lines PC9, NCI-H1975, and HCC827; human normal lung epithelial cells BEAS-2B). Western blot (WB) revealed the PTK6 protein expression in lung cancer cell lines. PTK6 expression was inhibited by Tilfrinib. Colony formation and the Cell Counting Kit-8 (CCK-8) assay were used to detect cell proliferation. The wound healing and trans-well were performed to analyze the cell migration capacity. Then flow cytometry was conducted to evaluate the cell apoptosis. Eventually, the relationship between PTK6 and immune checkpoints was examined. WB was used to estimate the PD-L1 expression at different Tilfrinib doses. RESULTS: PTK6 was an independent predictive factor for LUAD and was substantially expressed in LUAD. Pathological stage was significantly correlated with increased PTK6 expression. In accordance with survival analysis, poor survival rate in LUAD was associated with a high expression level of PTK6. Functional enrichment of the cell cycle and TGF-ß signaling pathway was demonstrated by KEGG and GSEA analysis. Moreover, PTK6 expression considerably associated with immune infiltration in LUAD, as determined by immune analysis. Thus, the result of vitro experiments indicated that cell proliferation and migration were inhibited by the elimination of PTK6. Additionally, PTK6 suppression induced cell apoptosis. Obviously, PD-L1 protein expression level up-regulated while PTK6 was suppressed. CONCLUSION: PTK6 has predictive value for LUAD prognosis, and could up regulated PD-L1.

Event-Triggered Mechanism-Based Discrete-Time Nash Equilibrium Seeking for Graphic Game With Outlier-Resistant ESO.

In this article, we consider a discrete-time Nash equilibrium (NE) seeking problem for graphic game subject to disturbances. For the first-order dynamics, the discrete-time outlier-resistant extended state observer (ESO)-based game strategy is proposed to enable the players to estimate the disturbances under effect of anomaly measurements and then compensate them. An event-triggered mechanism is applied between adjacent players to reduce the frequency of communication. The convergence of the outlier-resistant ESO and control strategy is presented. Moreover, the upper bound of ϵ -NE solution deviating from the unique point of nominal system is given analytically. Then, the addressed issues are extended to high-order game systems. The NE seeking-based control strategy for each player is designed such that the equilibrium point converges to the ϵ -NE which is also analytically calculated. Finally, in order to verify the effectiveness of the proposed game strategy, an example of satellite system is given.

HPV16 infection promotes the malignant transformation of the esophagus and progression of esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) may be correlated with HPV infection, and the mechanism underlying the ESCC formation induced by HPV16 infection remains elusive. Here, we overexpressed HPV16 E6 and E7 and coordinated the overexpression of these two genes in EPC2 and ESCC cells. We found that E7 and coordinated expression of E6 and E7 promoted the proliferation of EPC2 cells, and upregulation of shh was responsible for cell proliferation since the use of vismodegib led to the failure of organoid formation. Meanwhile, overexpression of E6 and E7 in ESCC cells promoted cell proliferation, migration, and invasion in vitro. Importantly, E6 and E7 coordinately increased the capability of tumor growth in nude mice, while vismodegib slowed the growth of tumors in NCG mice. Moreover, a series of genes and proteins changed in cell lines after overexpression of the E6 and E7 genes, the potential biological processes and pathways were systematically analyzed using a bioinformatics assay. Together, these findings suggest that the activation of the hedgehog pathway induced by HPV16 infection may initially transform basal cells in the esophagus and promote following malignant processes in ESCC cells. The application of hedgehog inhibitors may represent a therapeutic avenue for ESCC treatment.

GABA Metabolism, Transport and Their Roles and Mechanisms in the Regulation of Abiotic Stress (Hypoxia, Salt, Drought) Resistance in Plants.

γ- Aminobutyric acid (GABA) is a ubiquitous four-carbon non-protein amino acid. In plants, GABA is found in different cell compartments and performs different metabolic functions. As a signalling molecule, GABA participates in the regulation of tolerance to various abiotic stresses. Many research studies have found that GABA accumulates in large amounts when plants are subjected to abiotic stress, which have been demonstrated through the Web of Science, PubMed, Elsevier and other databases. GABA enhances the tolerance of plants to abiotic stress by regulating intracellular pH, ion transport, activating antioxidant systems and scavenging active oxygen species. In the process of GABA playing its role, transport is very important for the accumulation and metabolism pathway of GABA in cells. Therefore, the research on the transport of GABA across the cell membrane and the organelle membrane by transport proteins is a direction worthy of attention. This paper describes the distribution, biosynthesis and catabolism of GABA in plants. In addition, we focus on the latest progress in research on the transport of exogenous GABA and on the function and mechanism in the regulation of the abiotic stress response. Based on this summary of the role of GABA in the resistance to various abiotic stresses, we conclude that GABA has become an effective compound for improving plant abiotic tolerance.

Silica nanoparticle-based dual-responsive nanoprodrug system for liver cancer therapy.

A thiol-terminated polyethyleneglycol (PEG)-paclitaxel (PTX) conjugate was synthesized and utilized to construct a novel drug delivery system with thiol-functionalized silica nanoparticles (SLNs) to improve the overall performance of PTX in liver cancer therapy. Drug loading was performed by coating the PTX conjugate on the surface of SLNs. The PTX-PEG/SLNs showed a binary responsive drug release behavior to esterase as well as high concentrations of glutathione. The synergic effects of these cancer cell-specific factors on the release characteristics of PTX-PEG/SLNs resulted in a significantly (P<0.01) elevated anti-cancer efficiency. This included prolonged circulation and passive tumor-targeting properties in vivo due to surface modification of PEG and targeted release of PTX inside tumor cells, which resulted in increased anti-cancer efficiency. Improving the in vitro properties of PTX-PEG/SLNs not only significantly (P<0.01) enhanced its therapeutic efficacy in a murine liver cancer model, but rendered these drug-conjugated SLNs a promising nanoprodrug system for potential use as clinical cancer therapeutics.