Extracellular vesicles derived from M2-like macrophages alleviate acute lung injury in a miR-709-mediated manner.

Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is characterised by an uncontrolled inflammatory response, and current treatment strategies have limited efficacy. Although the protective effect of M2-like macrophages (M2φ) and their extracellular vesicles (EVs) has been well-documented in other inflammatory diseases, the role of M2φ-derived EVs (M2φ-EVs) in the pathogenesis of ALI/ARDS remains poorly understood. The present study utilised a mouse model of lipopolysaccharide-induced ALI to first demonstrate a decrease in endogenous M2-like alveolar macrophage-derived EVs. And then, intratracheal instillation of exogenous M2φ-EVs from the mouse alveolar macrophage cell line (MH-S) primarily led to a take up by alveolar macrophages, resulting in reduced lung inflammation and injury. Mechanistically, the M2φ-EVs effectively suppressed the pyroptosis of alveolar macrophages and inhibited the release of excessive cytokines such as IL-6, TNF-α and IL-1ß both in vivo and in vitro, which were closely related to NF-κB/NLRP3 signalling pathway inhibition. Of note, the protective effect of M2φ-EVs was partly mediated by miR-709, as evidenced by the inhibition of miR-709 expression in M2φ-EVs mitigated their protective effect against lipopolysaccharide-induced ALI in mice. In addition, we found that the expression of miR-709 in EVs derived from bronchoalveolar lavage fluid was correlated negatively with disease severity in ARDS patients, indicating its potential as a marker for ARDS severity. Altogether, our study revealed that M2φ-EVs played a protective role in the pathogenesis of ALI/ARDS, partly mediated by miR-709, offering a potential strategy for assessing disease severity and treating ALI/ARDS.

Temporal patterns of organ dysfunction in COVID-19 patients hospitalized in the intensive care unit: A group-based multitrajectory modelling analysis.

BACKGROUND: The course of organ dysfunction (OD) in Corona Virus Disease 2019 (COVID-19) patients is unknown. Herein, we analyse the temporal patterns of OD in intensive care unit-admitted COVID-19 patients. METHODS: Sequential organ failure assessment scores were evaluated daily within 2 weeks of admission to determine the temporal trajectory of OD using group-based multitrajectory modelling (GBMTM). RESULTS: 392 patients were enrolled with a 28-day mortality rate of 53.6%. GBMTM identified four distinct trajectories. Group 1 (mild OD, n=64), with a median APACHE II score of 13 (IQR 9-21), had an early resolution of OD and a low mortality rate. Group 2 (moderate OD, n=140), with a median APACHE II score of 18 (IQR 13-22), had a 28-day mortality rate of 30.0%. Group 3 (severe OD, n=117), with a median APACHR II score of 20 (IQR 13-27), had a deterioration trend of respiratory dysfunction and a 28-day mortality rate of 69.2%. Group 4 (extremely severe OD, n=71), with a median APACHE II score of 20 (IQR 17-27), had a significant and sustained OD affecting all organ systems and a 28-day mortality rate of 97.2%. CONCLUSIONS: Four distinct trajectories of OD were identified, and respiratory dysfunction trajectory could predict nonpulmonary OD trajectories and patient prognosis.

Regulatory mechanisms and therapeutic implications of insulin-like growth factor 2 mRNA-binding proteins, the emerging crucial m6A regulators of tumors.

Insulin-like growth factor 2 mRNA-binding proteins (IGF2BPs) serve essential biological functions as post-transcriptional performers, participating in the acquisition or maintenance of tumor hallmarks due to their distinct protein structures. Emerging evidence indicates that IGF2BPs belong to the class III type of RNA N6-methyladenosine (m6A) modification readers, controlling RNA stability, storage, localization, metabolism, and translation in multiple vital bioprocesses, particularly tumorigenesis and tumor progression. Here, we discuss the underlying regulatory mechanisms and pathological functions of IGF2BPs which act as m6A readers in the context of tumor pathogenesis and multidrug resistance. Furthermore, we highlight the potential of IGF2BPs as drug targets in clinical tumor treatment. Hence, precise and novel tumor therapeutic approaches could be uncovered by targeting epigenetic heterogeneity.

The effect of renin-angiotensin-aldosterone system inhibitors in patients with hypertension and COVID-19: A meta-analysis of randomized controlled trials and propensity score-matched studies.

Background: High-quality evidence for whether the use of renin-angiotensin-aldosterone system (RAAS) inhibitors worsens clinical outcomes for patients with coronavirus disease 2019 (COVID-19) is lacking. The present study aimed to evaluate the effect of RAAS inhibitors on disease severity and mortality in patients with hypertension and COVID-19 using randomized controlled trials (RCTs) and propensity score-matched (PSM) studies. Methods: A literature search was conducted with PubMed, Embase, and Scopus databases from 31 December 2019 to 10 January 2022. We included RCTs and PSM studies comparing the risk of severe illness or mortality in patients with hypertension and COVID-19 treated or not treated with RAAS inhibitors. Individual trial data were combined to estimate the pooled odds ratio (OR) with a random-effects model. Results: A total of 17 studies (4 RCTs and 13 PSM studies) were included in the meta-analysis. The use of RAAS inhibitors was not associated with an increased risk of severe illness (OR=1.00, 95% confidence interval [CI]: 0.88-1.14, I2=28%) or mortality (OR=0.96, 95% CI: 0.83-1.11, I2=16%) for patients with hypertension and COVID-19. Furthermore, there was no significant difference in the severity of COVID-19 when patients continued or discontinued treatment with RAAS inhibitors (OR=1.01, 95% CI: 0.78-1.29, I2=0%). Conclusions: This study suggests that there was no association between treatment with RAAS inhibitors and worsened COVID-19 disease outcomes. Our findings support the current guidelines that RAAS inhibitors should be continued in the setting of the COVID-19 pandemic. However, the benefit of RAAS inhibitor medications for COVID-19 patients should be further validated with more RCTs.

Health damage to housewives by contaminants emitted from coal combustion in the Chinese countryside: focusing on day-to-day cooking.

PURPOSE: The study aimed to estimate the health damage and find out the main exposure pathways of housewives posed by polycyclic aromatic hydrocarbons (PAHs) and heavy metals (HMs) from coal combustion in rural areas of China. METHODS: We obtained the concentrations of 16 PAHs and 8 HMs from published literatures and the Monte Carlo simulation was used to process and analysis the data. Sensitivity analysis was also applied to clear parameter uncertainty and the health damage of housewives was quantitatively evaluated by loss of life expectancy. RESULTS: Housewives' carcinogenic risks from PAHs exposure were in descending order of inhalation > ingestion > dermal contact, while exposed to HMs were ingestion > dermal contact > inhalation. The carcinogenic risks from PAHs primarily originated from benzo[a]pyrene (BaP), dibenz[ah]anthracene (DahA) and benzo[b]fluorathene (BbF). For HMs, arsenic posed the highest carcinogenic risk to housewives, with a contribution of 92.98%. In addition, the life expectancy loss of housewives exposed to PAHs was 469.04 min from inhalation and 51.82 min for HMs from ingestion. CONCLUSION: Through a comprehensive assessment of the health risks in housewives exposed to emissions from coal combustion, we can gain insight into the hazards from PAHs and HMs in housewives, and take measures to reduce their exposure risks.

Exploring the Relationships between Safety Compliance, Safety Participation and Safety Outcomes: Considering the Moderating Role of Job Burnout.

Safety compliance (SC) and safety participation (SP), which are key factors predicting safety outcomes (e.g., accidents, injuries and near misses), are related but distinct. However, which component is more significant remains controversial. Job burnout is a typical occupational psychological syndrome of employees that impacts safety outcomes, but the role that it plays in the relationship between SC, SP and safety outcomes is ambiguous. To clarify these relationships, Chinese coal mine workers were sampled. Then, hypotheses on the influencing mechanisms were initially proposed and later tested empirically. To conduct this testing, SC and SP scales were revised, and a job burnout scale was developed. The results showed that there were significant relationships between workers' SC and SP and safety outcomes; meanwhile, exhaustion, cynicism and low professional efficacy had significant effects on these relationships. Job burnout acted as a significant and indispensable moderator. Moreover, workers' occupational psychological health condition should be considered when improving safety outcomes.

Effectiveness of road dust suppressants: insights from particulate matter-related health damage.

Although dust suppressants are widely applied to control road dust pollution, a consensus on their effectiveness has not been reached. To evaluate the effectiveness of dust suppressants (a calcium-magnesium complex) from health risks and health damage, spraying and sampling activities were conducted at four sites in Beijing. Using inhalation risk model and health damage assessment, health risks of PMx for three sensitive occupational groups were calculated and converted to life and economic loss. Results revealed that dust suppressants can indeed mitigate PM pollution and its accompanying health risks and health damage in road dust, but at a limited efficiency. By spraying dust suppressants, the total PM-related life loss reduced by 1.60E-02 years and 2.50E-04 years in urban and suburban areas on average, and the total willingness to pay (WTP) values decreased by 120 and 50 US$ for PM2.5 and PM10, indicating a more considerable environmental gain if dust suppressants were sprayed in additional regions when necessary. Overall, our study demonstrated that the effectiveness of dust suppressants cannot be pictured only by the variations of pollutant concentrations, and indicators with practice and economic value should be more useful for traffic-related pollution management.