FGF2 is overexpressed in asthma and promotes airway in airway epithelial cells

Background: Airway inflammation is the core pathological process of asthma, with the key inflammatory regulators incompletely defined. Recently, fibroblast growth factor 2(FGF2) has been reported to be an inflammatory regulator;however, its role in asthma remains elusive. This study aimed to investigate the immunomodulatory role of FGF2 in asthma.Methods: First, FGF2 expression was characterised in clinical asthma samples and the house dust mite(HDM)-induced mouse chronic asthma model. Second, recombinant mouse FGF2(rm-FGF2) protein was intranasally delivered to determine the effect of FGF2 on airway inflammatory cell infiltration. Third, human airway epithelium-derived A549 cells were stimulated with either HDM or recombinant human interleukin-1β(IL-1β) protein combined with or without recombinant human FGF2. IL-1β-induced IL-6 or IL-8 release levels were determined using enzyme-linked immunosorbent assay, and the involved signalling transduction was explored via Western blotting.Results: Compared with the control groups, the FGF2 protein levels were significantly upregulated in the bronchial epithelium and alveolar areas of clinical asthma samples [(6.70±1.79) vs.(16.32±2.40), P=0.0184;(11.20±2.11) vs.(21.00±3.00), P=0.033, respectively] and HDM-induced asthmatic mouse lung lysates [(1.00±0.15) vs.(5.14±0.42),P<0.001]. Moreover, FGF2 protein abundance was positively correlated with serum total and anti-HDM IgE levels in the HDM-induced chronic asthma model(R^(2)=0.857 and 0.783, P=0.0008 and 0.0043, respectively). Elevated FGF2protein was mainly expressed in asthmatic bronchial epithelium and alveolar areas and partly co-localised with infiltrated inflammatory cell populations in HDM-induced asthmatic mice. More importantly, intranasal instillation of rm-FGF2 aggravated airway inflammatory cell infiltration [(2.45±0.09) vs.(2.88±0.14), P=0.0288] and recruited more subepithelial neutrophils after HDM challenge [(110.20±29.43) cells/mm^(2) vs.(238.10±42.77) cells/mm^(2), P=0.0392]without affecting serum IgE levels and Th2 cytokine transcription. In A549 cells, FGF2 was upregulated through HDM stimulation and promoted IL-1β-induced IL-6 or IL-8 release levels [up to(1.41±0.12)-or(1.44±0.14)-fold change vs.IL-1β alone groups, P=0.001 or 0.0344, respectively]. The pro-inflammatory effect of FGF2 is likely mediated through the fibroblast growth factor receptor(FGFR)/mitogen-activated protein kinase(MAPK)/nuclear factor kappa B(NF-κB)pathway.Conclusions: Our findings suggest that FGF2 is a potential inflammatory modulator in asthma, which can be induced by HDM and acts through the FGFR/MAPK/NF-κB pathway in the airway epithelial cells.

Influential factors of spatial performance in metro-led urban underground public space:A case study in Shanghai

Spatial performance measures the space usage of each underground segment in metro-led urban underground public space(UUPS).It usually varies in different UUPS segments and at different periods.Many environmental factors and space attractors can influence spatial performance in UUPS including spatial configurations,transportation facilities,space design characteristics,and commercial and work-ing facilities.This study intends to figure out the temporal and spatial distribution patterns of spatial performance in UUPS and then reveal the main influential factors and their impact mechanisms.The UUPS in Jiangwan–Wujiaochang Sub-center was selected as the study case.Cordon counting methods and multiple regression models were employed to collect the pedestrian data and quantitatively analyze the correlations between pedestrian flows and candidate influential factors.The study verified that spatial configurations were the most important factors instead of underground or surface attractors.There existed an interactive effect among pedestrian move-ments,spatial configurations,and commerce distribution in metro-led UUPS.Walkway width and the distribution of metro stations could partly affect spatial performance.The influential mechanisms of metro stations were different on weekdays and at weekends.Underground segments belonging to shopping malls in UUPS had a negative impact on spatial performance only on weekdays.Results of this study can provide insights for more efficient layout planning and design of metro-led UUPS in Chinese metropolitan cities.

A collaborative approach for urban underground space development toward sustainable development goals:Critical dimensions and future directions

The utilization of urban underground space(UUS)offers an effective solution to urban problems but may also negatively affect urban development.Therefore,UUS development needs better concerted guidelines to coordinate various urban systems and the multiple components of the underground world.Sustainable Development Goals(SDGs),which should be viewed as important yardsticks for UUS development,do not explicitly mention urban underground space,although many of them are affected by both the positive and negative consequences of its development.To fill this gap,this review lays the foundations of relevant UUS concepts and uses exemplary cases to reveal that 11 out of 17 SDGs can be linked with UUS uses.These linkages also manifest that land administration,integrated planning,architectural design,and construction technology are critical dimensions for increasing the contributions of UUS to the realization of SDGs.To achieve multi-disciplinary synergies among these four critical dimensions,a collaborative approach framework based on spatial data infrastructure is required.Thus,this work provides academics and practitioners with a holistic view of sustainable UUS development.