Obesity-induced downregulation of miR-192 exacerbates lipopolysaccharide-induced acute lung injury by promoting macrophage activation.

BACKGROUND: Macrophage activation may play a crucial role in the increased susceptibility of obese individuals to acute lung injury (ALI). Dysregulation of miRNA, which is involved in various inflammatory diseases, is often observed in obesity. This study aimed to investigate the role of miR-192 in lipopolysaccharide (LPS)-induced ALI in obese mice and its mechanism of dysregulation in obesity. METHODS: Human lung tissues were obtained from obese patients (BMI ≥ 30.0 kg/m2) and control patients (BMI 18.5-24.9 kg/m2). An obese mouse model was established by feeding a high-fat diet (HFD), followed by intratracheal instillation of LPS to induce ALI. Pulmonary macrophages of obese mice were depleted through intratracheal instillation of clodronate liposomes. The expression of miR-192 was examined in lung tissues, primary alveolar macrophages (AMs), and the mouse alveolar macrophage cell line (MH-S) using RT-qPCR. m6A quantification and RIP assays helped determine the cause of miR-192 dysregulation. miR-192 agomir and antagomir were used to investigate its function in mice and MH-S cells. Bioinformatics and dual-luciferase reporter gene assays were used to explore the downstream targets of miR-192. RESULTS: In obese mice, depletion of macrophages significantly alleviated lung tissue inflammation and injury, regardless of LPS challenge. miR-192 expression in lung tissues and alveolar macrophages was diminished during obesity and further decreased with LPS stimulation. Obesity-induced overexpression of FTO decreased the m6A modification of pri-miR-192, inhibiting the generation of miR-192. In vitro, inhibition of miR-192 enhanced LPS-induced polarization of M1 macrophages and activation of the AKT/ NF-κB inflammatory pathway, while overexpression of miR-192 suppressed these reactions. BIG1 was confirmed as a target gene of miR-192, and its overexpression offset the protective effects of miR-192. In vivo, when miR-192 was overexpressed in obese mice, the activation of pulmonary macrophages and the extent of lung injury were significantly improved upon LPS challenge. CONCLUSIONS: Our study indicates that obesity-induced downregulation of miR-192 expression exacerbates LPS-induced ALI by promoting macrophage activation. Targeting macrophages and miR-192 may provide new therapeutic avenues for obesity-associated ALI.

Interpretation of the coupling mechanism of ecological security and urbanization based on a Computation-Verification-Coupling framework: Quantitative analysis of sustainable development.

In recent decades, China's rapid urbanization has produced numerous economic benefits while simultaneously creating substantial risks to ecological security. China's 14th Five-Year Plan and the United Nations Sustainable Development Goals (SDGs) have recently explicitly called for the coordinated development of ecological security and urbanization. Given this context, it is important to explore the mechanism by which ecological security and urbanization are coupled and coordinated to promote sustainable development. In this study, an index of the relationship between ecological security and urbanization was established via high-resolution data, and a "Computation-Verification-Coupling" (CVC) framework was constructed. The accuracy of the ecological security index was verified using a linear regression model, and the coordination level between ecological security and urbanization was analyzed via a coupled coordination model (CCM). The results revealed a steady increase in the ecological security index from 2010 to 2020; the proportion of the area above the medium level increased from 63.1 % to 74.1 %. The urbanization index in core counties exhibited rapid growth, with level V urbanized areas expanding from 5.5 % to 9.9 %. The ecological security verification model produced a coefficient of determination (R²) of 0.75685, indicating a satisfactory degree of predictive capability. From 2010-2020, the coupled coordination improved, with the high coordination area accounting for 48.8 % and the extreme discoordination area decreasing from 1.8 % to 1.0 %. Coordinated development exhibited a stable progression, characterized by a cyclical evolution from initial coupling to antagonistic coupling and finally to coordinated development. This framework can be used not only to investigate the relationship between ecological security and urbanization but also to provide a quantifiable measure of progress toward achieving the SDGs.

Payer shifting after expansions in access to private care among veterans.

OBJECTIVE: To investigate whether expanded access to Veterans Affairs (VA)-purchased care increased overall utilization or induced a shift from other payers to VA for emergency care among VA enrollees. DATA SOURCES AND STUDY SETTING: This study included all emergency department (ED) encounters in 2019 from hospitals in the state of New York. STUDY DESIGN: We conducted a difference-in-differences analysis comparing VA enrollees to the general population before and after the implementation of the Maintaining Internal Systems and Strengthening Integrated Outside Networks (MISSION) Act in June 2019. DATA COLLECTION/EXTRACTION METHODS: We included all ED visits with individuals aged 30 or older at the time of the encounter. Individuals were considered eligible for the policy change if they were enrolled with VA at the beginning of 2019. PRINCIPAL FINDINGS: Of the 5,577,199 ED visits in the sample, 4.9% (n = 253,799) were made by VA enrollees. Of these, 44.9% of visits were paid by Medicare, 32.8% occurred in VA facilities, and 7% were paid by private health insurance. There was a 6.4% (2.91 percentage points; std. error = 0.18; p < 0.01) decrease in the proportion of ED visits paid by Medicare among VA enrollees relative to the general population after the implementation of the MISSION Act in June 2019. This decrease was larger for ED visits with a subsequent inpatient admission (-8.4%; 4.87 percentage points; std. error = 0.33; p < 0.01). There was no statistically significant change in the total volume of ED visits (0.06%; std. error = 0.08; p = 0.45). CONCLUSIONS: Leveraging a novel dataset, we demonstrate that MISSION Act implementation coincided with a shift in the financing of non-VA ED visits from Medicare to VA without any increase in overall ED utilization. These findings have important implications for VA health care financing and delivery.

Assessment of Retrospective COVID-19 Spatial Clusters with Respect to Demographic Factors: Case Study of Kansas City, Missouri, United States.

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The United States (U.S.) has the highest number of reported COVID-19 infections and related deaths in the world, accounting for 17.8% of total global confirmed cases as of August 2021. As COVID-19 spread throughout communities across the U.S., it became clear that inequities would arise among differing demographics. Several researchers have suggested that certain racial and ethnic minority groups may have been disproportionately impacted by the spread of COVID-19. In the present study, we used the daily data of COVID-19 cases in Kansas City, Missouri, to observe differences in COVID-19 clusters with respect to gender, race, and ethnicity. Specifically, we utilized a retrospective Poisson spatial scan statistic with respect to demographic factors to detect daily clusters of COVID-19 in Kansas City at the zip code level from March to November 2020. Our statistical results indicated that clusters of the male population were more widely scattered than clusters of the female population. Clusters of the Hispanic population had the highest prevalence and were also more widely scattered. This demographic cluster analysis can provide guidance for reducing the social inequalities associated with the COVID-19 pandemic. Moreover, applying stronger preventive and control measures to emerging clusters can reduce the likelihood of another epidemic wave of infection.