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This paper investigates a Leslie-Gower predator-prey model with advection and double free boundaries. Firstly, we establish the global existence and uniqueness of the solution. Subsequently, we analyze the long-time behaviors of the solution and demonstrate a spreading-vanishing dichotomy. If the initial habitat size or the expanding capacity of the boundaries is large, the invasive predator will spread throughout the entire space; otherwise, both the prey and predator will eventually vanish. When spreading occurs, two subcases arise, depending on the interaction coefficient $ c $ and the environmental support $ \delta $. If $ c\delta < 1 $, the prey and predator coexist, which we refer to as the weakly hunting case; conversely, if $ c\delta \geq 1 $, the predator survives and spreads throughout the space, while the prey vanishes, which we term the strongly hunting case. In the event of spreading, we also provide an estimate of the spreading speed. Finally, we introduce a front-fixing implicit-explicit finite difference method for the free boundary problem. Numerical simulations validate our theoretical findings and uncover some intriguing new phenomena, prompting further investigation into this and general free boundary problems. [ABSTRACT FROM AUTHOR]

Silicosis is a common occupational disease caused by the long-term inhalation of large amounts of silica dust. Lipid metabolism plays an important role in the progression of silicosis, but its contributing mechanism remains unclear. The aim of this study was to investigate the differential lipid metabolites and active metabolic pathways in silicosis rat lung tissue. We first constructed a silicosis rat model, and randomly divided 24 male SD rats into control group (C), silicosis group for 1 week (S1W), silicosis group for 2 weeks (S2W) and silicosis group for 4 weeks (S4W) with 6 rats in each group. 1 mL SiO 2 suspension (50 mg/mL) or normal saline were injected into the trachea, and the rats were killed at 1 week, 2 weeks and 4 weeks, respectively. The lung tissue pathology of the rats was observed by HE staining and VG staining, and the plasma TC and FC levels were detected by the kit. Western blot was used to detect the expression of lipid-related factors CD36, PGC1α and LXR. In addition, lipidomics analysis of lung tissue samples was performed using UPLC-IMS-QTOF mass spectrometer to screen out potential differential metabolites in silicosis models and analyze lipid enrichment, and verified the expression of differential gene CHPT1 in the metabolic pathway. HE and VG staining showed that the number of nodules and fibrosis increased in a time-dependent manner in the silicosis model group, and the levels of TC, FC and CE in silicosis plasma increased. Western blot results showed that PGC1α and LXR decreased in the silicosis model group, while CD36 expression increased. In addition, metabolomics screened out 28 differential metabolites in the S1W group, 32 in the S2W group, and 22 in the S4W group, and found that the differential metabolites were mainly enriched in metabolic pathways such as glycerophospholipid metabolism and ether lipid metabolism, and the expression of differential gene CHPT1 in the metabolic pathway was decreased in the silicosis model group. These results suggest that there are significant changes in lipid metabolites in lung tissue in silicosis rat models, and glycerophospholipid metabolism was significantly enriched, suggesting that glycerophospholipids play an important role in the progression of silicosis. The differential metabolites and pathways reported in this study may provide new ideas for the pathogenesis of silicosis. • SiO 2 caused disordered lipid metabolism in vivo. • Lipid metabolomics screening of differential lipid metabolites in silicosis rat lung tissue. • CHPT1 may regulate lipid metabolism disorders in silicosis by affecting the metabolism of glycerophospholipids. [ABSTRACT FROM AUTHOR]

The safety of oncolytic adenovirus-mediated suicide and interleukin-12 ( IL 12 ) gene therapy was evaluated in metastatic pancreatic cancer patients. In this phase I study, a replication-competent adenovirus (Ad5-yCD/ mut TK SR39 rep -hIL-12) expressing yCD/ mut TK SR39 (yeast cytidine deaminase/mutant S39R HSV-1 thymidine kinase) and human IL-12 ( IL 12 ) was injected into tumors of 12 subjects with metastatic pancreatic cancer (T2N0M1-T4N1M1) at escalating doses (1 × 10 11 , 3 × 10 11 , or 1 × 10 12 viral particles). Subjects received 5-fluorocytosine (5-FC) therapy for 7 days followed by chemotherapy (FOLFIRINOX or gemcitabine/albumin-bound paclitaxel) starting 21 days after adenovirus injection. The study endpoint was toxicity through day 21. Experimental endpoints included measurements of serum IL 12 , interferon gamma (IFNG), and CXCL10 to assess immune system activation. Peripheral blood mononuclear cells and proliferation markers were analyzed by flow cytometry. Twelve patients received Ad5-yCD/ mut TK SR39 rep -hIL-12 and oral 5-FC. Approximately 94% of the 121 adverse events observed were grade 1/2 requiring no medical intervention. Ad5-yCD/ mut TK SR39 rep -hIL-12 DNA was detected in the blood of two patients. Elevated serum IL 12 , IFNG, and CXCL10 levels were detected in 42%, 75%, and 92% of subjects, respectively. Analysis of immune cell populations indicated activation after Ad5-yCD/ mut TK SR39 rep -hIL-12 administration. The median survival of patients in the third cohort is 18.1 (range, 3.5-20.0) months. The study maximum tolerated dose (MTD) was not reached., Competing Interests: K.N.B. and S.O.F. hold a patent “Methods and Composition for Cancer Therapy Using a Novel Adenovirus” (#7,815,902 B2) for an adenovirus similar to the one used in this study., (© 2020 The Authors.)