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Long non-coding RNAs (lncRNAs) play a critical role in a variety of human diseases such as cancer. Here, to elucidate a novel function of a lncRNA called LINC00173, we investigated its binding partner, target gene, and its regulatory mechanism in lung adenocarcinoma, including the A549 cell line and patients. In the A549 cell line, RNA immunoprecipitation (RIP) assays revealed that LINC00173 efficiently binds to SNAIL. RNA-seq and RT-qPCR analyses revealed that the expression of FHIT was decreased upon LINC00173 depletion, indicating that FHIT is a target gene of LINC00173. Overexpression of SNAIL suppressed and depletion of SNAIL increased the expression of FHIT, indicating that SNAIL negatively regulates FHIT. The downregulation of FHIT expression upon LINC00173 depletion was restored by additional SNAIL depletion, revealing a LINC00173-SNAIL-FHIT axis for FHIT regulation. Data from 501 patients with lung adenocarcinoma also support the existence of a LINC00173-SNAIL-FHIT axis, as FHIT expression correlated positively with LINC00173 (p = 1.75 × 10−6) and negatively with SNAIL (p = 7.00 × 10−5). Taken together, we propose that LINC00173 positively regulates FHIT gene expression by binding to SNAIL and inhibiting its function in human lung adenocarcinoma. Thus, this study sheds light on the LINC00173-SNAIL-FHIT axis, which may be a key mechanism for carcinogenesis and progression in human lung adenocarcinoma. [ABSTRACT FROM AUTHOR]

We investigated the effects of by 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase inhibitors, cerivastatin and fluvastatin, on the induction of nitric oxide (NO) production in vascular smooth muscle cells ( VSMC) stimulated by interleukin-1β (1L-1) or in combination with interferon-γ (IFN). IL-1 activated VSMC to synthesize and release NO, which was significantly potentiated by IFN. NO production induced by IL-1 or IL-1/lFN was dosedependently enhanced by both HMG-CoA reductase inhibitors. Incubating VSMC with IL-1/IFN stimulated inducible NO synthase (iNOS) mRNA expression. Both HMG-CoA reductase inhibitors significantly upreguiated IL/IFN-stimulated iNOS mRNA expression, and enhanced iNOS gene transcription as shown by nuclear run-on assays. Both IIMG-CoA reductase inhibitors slightly modulated IL-1/IFN-induced NF-kB activation, which was not associated with their effect on NO production. Cytokines induce the de novo synthesis of tetrahydrobiopterin (BH4) in VSMC. This event is essential for the induction of NO synthesis, which requires transcriptional induction of the genes that encode not only iNOS but also guanosine triphosphate cyclohydrolase I (GTPCH), the first and rate-limiting enzyme in de novo BH4 synthesis. The synthesis of BH4 and GFPCH mRNA induced by IL-1/IFΝ were enhanced by both HMG-CoA reductase inhibitors. Exogenous mevalonate significantly prevented and geranylgeranylpyrophosphate reversed the stimulatory effect of HMG-CoA reductase inhibitors. Thus, the effect of HMG-CoA reductase inhibitors on NO production is due at least partly through blocking the biosynthesis of mevalonate, which prevents isoprenoid biosynthesis. Our data demonstrated that HMG-CoA reductase inhibitors enhance immunostimulants-induced NO production by increasing iNOS gene expression at the transcriptional level via an NF-kB-independent pathway. In addition to augmenting iNOS expression, HMG-CoA reductase inhibitors potentiate GTPCH gene expression and BH4 synthesis, thereby prevents a relative shortage of BH4 which may shift in the balance between NOS-catalyzed generation of protective NO and deletorious reactive oxygen species.

Managing uncertainty is the way to secure stability of the supply chain. Uncertainty within chipping operation and chip transportation causes production loss. In the wood chip supply chain for bioenergy, operational uncertainty mainly appears in the moisture content of the material, chipping productivity, and the interval of truck arrival. This study theoretically quantified the loss in wood chip production by applying queuing theory and stochastic modelling. As well as the loss in production, the inefficiency was identified as the idling time of chipper and the queuing time of trucks. The aim of this study is to quantify the influence of three uncertainties on wood chip production. This study simulated the daily chip production using a mobile chipper by applying queuing theory and stochastic modelling of three uncertainties. The result was compared with the result of deterministic simulation which did not consider uncertainty. Uncertainty reduced the production by 14% to 27% compared to the production of deterministic simulation. There were trucks scheduled but not used. The cases using small trucks show the largest daily production amount, but their lead time was the longest. The large truck was sensitive to the moisture content of material because of the balance between payload and volumetric capacity. This simulation method can present a possible loss in production amount and enables to evaluate some ways for the loss compensation quantitatively such as outsourcing or storing buffer. For further development, the data about the interval of truck arrival should be collected from fields and analyzed. We must include the other uncertainties causing technical and operator delays. [ABSTRACT FROM AUTHOR]