Pyroptosis is a novel proinflammatory programmed cell death process. This study was designed to investigate the functional mechanisms of long noncoding RNA growth arrest‐specific transcript 5 (lncRNA ...GAS5) on lipopolysaccharide (LPS)‐induced human bronchial epithelial cell (HBEC) pyroptosis. LPS was used to induce pyroptosis in HBECs, followed by the detection of the expression of GAS5, forkhead box O3 (FOXO3), and nuclear factor E2‐related factor 2/heme oxygenase 1 (Nrf2/HO‐1) signaling pathway‐related factors. Cell viability was evaluated using CCK‐8 assay, lactate dehydrogenase (LDH) release was assessed by LDH assay kit and caspase‐1 activity by flow cytometry. Furthermore, expression of NOD‐like receptor family pyrin domain containing 3 and pyroptosis‐related proteins was evaluated using Western blot analysis, while enzyme‐linked immunosorbent assay was used to determine the levels of inflammatory factors. The interaction between GAS5 and FOXO3 was confirmed using bioinformatic prediction, RNA immunoprecipitation assay, RNA pull‐down, and dual‐luciferase reporter gene assay. Treatment of HBECs with LPS upregulated the expression of GAS5 and FOXO3, resulting in the inactivation of the Nrf2/HO‐1 signaling pathway. On the other hand, inhibition of both GAS5 and FOXO3 promoted cell viability, reduced LDH release, pyroptosis, and inflammatory response in LPS‐induced HBECs. Furthermore, FOXO3 could interact with GAS5, while FOXO3 overexpression reversed the inhibitory effect of GAS5 knockdown on cell pyroptosis. Thus, mechanistically, inhibition of FOXO3 activates the Nrf2/HO‐1 pathway to suppress LPS‐induced pyroptosis in HBECs. This study revealed that GAS5 knockdown attenuates FOXO3 expression thereby activating the Nrf2/HO‐1 pathway to inhibit LPS‐induced pyroptosis in HBECs. These findings may contribute to identifying novel targets that inhibit pyroptosis in HBECs.
Sponge cities provide broad hydrological functions to alleviate urban flooding and other water-related problems in China. Conventional impervious paving cannot meet contemporary sustainable city ...goals. The permeable paving technology offers primary benefits such as increasing stormwater infiltration, drainage, purification, groundwater recharge, and microclimatic amelioration. Few studies have evaluated the embracive range of benefits and the social functions holistically. This study aimed to develop a comprehensive benefit evaluation system to cover a broad range of indicators. Nineteen indicators were selected based on the literature review, field studies, and research experience. Organized in a three-tiered hierarchical structure, they were divided into environmental, economic, and social benefits. A grey intuitionistic fuzzy comprehensive evaluation model was built by combining intuitionistic fuzzy analysis with a grey comprehensive evaluation. The computational tools could determine the differential weights of indicators and benefit scores. Taking an example of a permeable pavement project in Quanzhou City, the comprehensive benefits were assessed and validated using our evaluation model. The results show that (1) the comprehensive benefits of the project met the economic feasibility criteria with advantages over conventional paving; (2) the environmental benefits were prominently expressed; (3) the social benefits were assessed and confirmed. The results verified the feasibility and applicability of the quantitative-qualitative model. The method could permit the integrated and systematic benefit assessment of permeable paving designs. It also provides guidance and reference to evaluate the performance of permeable pavements and their comprehensive range of benefits. The findings could reference choosing and refining designs, optimizing the benefits, and promoting a science-oriented development of permeable paving.
AIM:To develop models to predict hepatitis B e antigen(HBe Ag)seroconversion in response to interferon(IFN)-αtreatment in chronic hepatitis B patients.METHODS:We enrolled 147 treatment-nave HBe ...Agpositive chronic hepatitis B patients in China and analyzed variables after initiating IFN-α1b treatment.Patients were tested for serum alanine aminotransferase(ALT),hepatitis B virus-DNA,hepatitis B surface antigen(HBs Ag),antibody to hepatitis B surface antigen,HBe Ag,antibody to hepatitis B e antigen(anti-HBe),and antibody to hepatitis B core antigen(anti-HBc)at baseline and 12 wk,24 wk,and 52 wk after initiating treatment.We performed univariate analysis to identify response predictors among the variables.Multivariate models to predict treatment response were constructed at baseline,12 wk,and 24 wk.RESULTS:At baseline,the 3 factors correlating most with HBe Ag seroconversion were serum ALT level>4×the upper limit of normal(ULN),HBe Ag≤500 S/CO,and anti-HBc>11.4 S/CO.At 12 wk,the 3 factors most associated with HBe Ag seroconversion were HBe Ag level≤250 S/CO,decline in HBe Ag>1 log10 S/CO,and anti-HBc>11.8 S/CO.At 24 wk,the 3 factors most associated with HBe Ag seroconversion were HBe Ag level≤5 S/CO,anti-HBc>11.4 S/CO,and decline in HBe Ag>2 log10 S/CO.Each variable was assigned a score of1,a score of 0 was given if patients did not have any of the 3 variables.The 3 factors most strongly correlating with HBe Ag seroconversion at each time point were used to build models to predict the outcome after IFN-αtreatment.When the score was 3,the response rates at the 3 time points were 57.7%,83.3%,and 84.0%,respectively.When the score was 0,the response rates were 2.9%,0.0%,and 2.1%,respectively.CONCLUSION:Models with good negative and positive predictive values were developed to calculate the probability of response to IFN-αtherapy.
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