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Abstract Background Motivated by the need for precise epidemic control and epidemic-resilient urban design, this study aims to reveal the joint and interactive associations between urban socioeconomic, density, connectivity, and functionality characteristics and the COVID-19 spread within a high-density city. Many studies have been made on the associations between urban characteristics and the COVID-19 spread, but there is a scarcity of such studies in the intra-city scale and as regards complex joint and interactive associations by using advanced machine learning approaches. Methods Differential-evolution-based association rule mining was used to investigate the joint and interactive associations between the urban characteristics and the spatiotemporal distribution of COVID-19 confirmed cases, at the neighborhood scale in Hong Kong. The associations were comparatively studied for the distribution of the cases in four waves of COVID-19 transmission: before Jun 2020 (wave 1 and 2), Jul–Oct 2020 (wave 3), and Nov 2020–Feb 2021 (wave 4), and for local and imported confirmed cases. Results The first two waves of COVID-19 were found mainly characterized by higher-socioeconomic-status (SES) imported cases. The third-wave outbreak concentrated in densely populated and usually lower-SES neighborhoods, showing a high risk of within-neighborhood virus transmissions jointly contributed by high density and unfavorable SES. Starting with a super-spread which considerably involved high-SES population, the fourth-wave outbreak showed a stronger link to cross-neighborhood transmissions driven by urban functionality. Then the outbreak diffused to lower-SES neighborhoods and interactively aggravated the within-neighborhood pandemic transmissions. Association was also found between a higher SES and a slightly longer waiting period (i.e., the period from symptom onset to diagnosis of symptomatic cases), which further indicated the potential contribution of higher-SES population to the pandemic transmission. Conclusions The results of this study may provide references to developing precise anti-pandemic measures for specific neighborhoods and virus transmission routes. The study also highlights the essentiality of reliving co-locating overcrowdedness and unfavorable SES for developing epidemic-resilient compact cities, and the higher obligation of higher-SES population to conform anti-pandemic policies.

Abstract Background The urban built environment (BE) has been globally acknowledged as one of the main factors that affects the spread of infectious disease. However, the effect of the street network on coronavirus disease 2019 (COVID-19) incidence has been insufficiently studied. Severe acute respiratory syndrome coronavirus 2, which causes COVID-19, is far more transmissible than previous respiratory viruses, such as severe acute respiratory syndrome coronavirus, which highlights the role of the spatial configuration of street network in COVID-19 spread, as it is where humans have contact with each other, especially in high-density areas. To fill this research gap, this study utilized space syntax theory and investigated the effect of the urban BE on the spatial diffusion of COVID-19 cases in Hong Kong. Method This study collected a comprehensive dataset including a total of 3815 confirmed cases and corresponding locations from January 18 to October 5, 2020. Based on the space syntax theory, six space syntax measures were selected as quantitative indicators for the urban BE. A linear regression model and Geographically Weighted Regression model were then applied to explore the underlying relationships between COVID-19 cases and the urban BE. In addition, we have further improved the performance of GWR model considering the spatial heterogeneity and scale effects by adopting an adaptive bandwidth. Result Our results indicated a strong correlation between the geographical distribution of COVID-19 cases and the urban BE. Areas with higher integration (a measure of the cognitive complexity required for a pedestrians to reach a street) and betweenness centrality values (a measure of spatial network accessibility) tend to have more confirmed cases. Further, the Geographically Weighted Regression model with adaptive bandwidth achieved the best performance in predicting the spread of COVID-19 cases. Conclusion In this study, we revealed a strong positive relationship between the spatial configuration of street network and the spread of COVID-19 cases. The topology, network accessibility, and centrality of an urban area were proven to be effective for use in predicting the spread of COVID-19. The findings of this study also shed light on the underlying mechanism of the spread of COVID-19, which shows significant spatial variation and scale effects. This study contributed to current literature investigating the spread of COVID-19 cases in a local scale from the space syntax perspective, which may be beneficial for epidemic and pandemic prevention.

Abstract Background The P38 mitogen-activated protein kinase (MAPK) pathway plays an essential role in CVB3-induced diseases. We previously demonstrated microRNA-21 has potential inhibitory effect on the MAP2K3 which locates upstream of P38 MAPK and was upregulated in mouse hearts upon CVB3 infection. However, the effect and underlying mechanism of miRNA-21 on CVB3 infection remain unclear. Methods We detected continuous changes of cellular miRNA-21 and P38 MAPK proteins expression profiling post CVB3 infection in vitro within 12 h. P38 MAPK signaling was inhibited by the specific inhibitor, small interfering RNA and miRNA-21 mimic in vitro, CVB3 replication, cell apoptosis rate and proliferation were detected. Viral load in the mice heart, cardiomyocyte apoptosis rate and histological of the heart were also detected in the mice model of viral myocarditis pretreated with miRNA-21-lentivirus. Results We observed significant upregulation of miRNA-21 expression followed by suppression of the MAP2K3/P38 MAPK signaling in CVB3-infected Hela cells. The inactivation of the MAP2K3/P38 MAPK signaling by P38 MAPK specific inhibitor, small interfering RNA against MAP2K3, or miRNA-21 overexpression significantly inhibited viral progeny release from CVB3-infected cells. Mechanistically, when compared with control miRNA, miRNA-21 showed no effect on capsid protein VP1 expression and viral load within host cells, while significantly reversing CVB3-induced caspase-3 activation and cell apoptosis rate, further promoting proliferation of infected cells, which indicates the inhibitory effect of miRNA-21 on CVB3 progeny release. In the in vivo study, when compared with control miRNA, miRNA-21 pretreatment remarkably inactivated the MAP2K3/P38 MAPK signaling in mice and protected them against CVB3 infection as evidenced by significantly alleviated cell apoptosis rate, reduced viral titers, necrosis in the heart as well as by remarkably prolonged survival time. Conclusions miRNA-21 were reverse correlated with P38 MAPK activation post CVB3 infection, miRNA-21 overexpression significantly inhibited viral progeny release and decreased myocytes apoptosis rate in vitro and in vivo, suggesting that miRNA-21 may serve as a potential therapeutic agent against CVB3 infection through targeting the MAP2K3/P38 MAPK signaling.

Abstract Background Interleukin (IL)-37 has emerged as a novel anti-inflammatory cytokine that play an immunosuppressive role in regulating inflammatory response. This study aimed to measure IL-37 levels in the plasma and peripheral blood mononuclear cells (PBMCs) of patients with systemic juvenile idiopathic arthritis (sJIA), and to establish the correlation between IL-37 levels and disease activity, laboratory parameters and inflammatory cytokines. Methods The mRNA levels of IL-37 in PBMCs and plasma IL-37 concentrations in 46 sJIA patients and 30 age- and sex-matched healthy controls were measured by real-time polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. The correlations between plasma IL-37 levels and disease activity, laboratory parameters and inflammatory cytokines in sJIA were analyzed by Spearman correlation test. PBMCs from the sJIA patients were stimulated with recombinant human IL-37 (rhIL-37) protein, expressions of IL-1β, IL-6, TNF-α and IL-17 were detected by RT-PCR and ELISA. Results Plasma levels of IL-37 and relative IL-37 mRNA expression were significantly elevated in sJIA patients, especially in active sJIA patients, when compared with the healthy controls (P