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OBJECTIVE: Lung adenocarcinoma (LUAD) accounts for the majority of cancer deaths worldwide, with a high incidence rate and mortality. It is highly important to develop biomarker model to accurately predict the prognosis. MATERIALS AND METHODS: RNA-Seq data and clinical follow-up data of LUAD were downloaded from The Cancer Genome Atlas (TCGA) database. Hypoxia-related gene sets were collected from the Gene Set Enrichment Analysis (GSEA) website. A gene signature model was established using the Limma package in the R software, univariate and multivariate survival analyses, and least absolute shrinkage and selection operator (LASSO) algorithms. RESULTS: Two hypoxia subtypes (C1 and C2) were classified according to the expressions of 55 prognostic hypoxic-related genes. Differentially expressed genes (DEGs) between two hypoxia subtypes and immune group were analyzed. Then, 390 DEGs related to hypoxic immune microenvironment were filtered. According to hypoxia type and immune type, the samples were classified into hypoxia- high & immune-low group, hypoxia-low & immune-high group. Based on these differentially expressed genes (DEGs), a 5-genes signature model, which showed a stable prediction performance on datasets of different platforms and immunotherapy datasets, was finally developed. Meanwhile, it demonstrated a better performance compared with other existing models. The AUC of the 5-gene signature was high in both the training dataset and 4 independent validation datasets and was con- firmed as a clinical feature-independent prognostic model. CONCLUSIONS: This study developed a hypoxic immune microenvironment associated gene-based model for prognostic prediction of LUAD, providing clinicians with a reliable prognostic assessment tool and facilitating clinical treatment decision-making. [ABSTRACT FROM AUTHOR]

Summary: Background: Atopic dermatitis (AD) is a common, chronic, severely pruritic, eczematous skin disease that seriously deteriorates the quality of life of patients. Scratching is a cardinal symptom of AD. Although the vicious itch–scratch cycle continues and aggravates skin barrier dysfunction in AD, how scratching induces skin barrier dysfunction through tight junctions remains unclear. Aim: To study the effect of scratching on tight junctions in the itch–scratch cycle. Methods: Scratching behaviour and skin barrier dysfunction on the neck and back in an AD mouse model were assessed. The expression of tight junction proteins was compared between the neck and back mice, and the mechanisms underlying the involvement of Akt/CLDN1 pathways in this process were explored. Results: We used oxazolone to induce AD on the neck or back of mice. There was significantly more scratching behaviour and more pronounced skin barrier dysfunction with the neck than with the back. Downregulation of claudin‐1 (CLDN1) and upregulation of Akt phosphorylation in skin were well correlated with scratching behaviour in this AD model. Furthermore, SC79, an agonist of Akt phosphorylation, could downregulate CLDN1 expression in HaCaT cells. An antagonist of Akt phosphorylation (LY294002) was used to treat the AD mice; this treatment rescued CLDN1 expression through inhibiting Akt phosphorylation in skin, and importantly, also inhibited the scratching behaviour induced by AD. Conclusion: The results reveal the underlying mechanism of tight junction damage promoted by scratching in the itch–scratch cycle of AD, and opens a new avenue to pruritus management in AD, through Akt antagonists. [ABSTRACT FROM AUTHOR]

Urban public transportation has several advantages, including intensiveness, high-efficiency, energy-saving and environmental-friendliness. Giving development priority to public transportation is a necessary requirement in reducing trafficjams, transforming development mode of urban transportation and improving the life quality of people. And improving the coverage rate of bus stop is an important mean to prioritize public transportation development. The coverage rate of bus stop is an important index to evaluate the level of bus services. Under the consideration of deficiencies of calculating the coverage rate with traditional methods, including the great difficulty to acquire the information of bus stops, the low efficiency in deducting repeated area and the inaccuracy of calculation results, an idea of calculating the coverage rate of bus stop with GIS buffer tool and isochrones tool is put forward in this paper. In addition, case study is done in this paper to prove the powerful operability of the two tools, which provides good technical supports for urban public service. [ABSTRACT FROM AUTHOR]