Background Airborne fine particulate matter with aerodynamic diameter ≤ 2.5 μm (PM2.5) pollution is associated with the prevalence of respiratory diseases, including asthma, bronchitis and chronic obstructive pulmonary disease. In patients with those diseases, circulating asymmetric dimethylarginine (ADMA) levels are increased, which contributes to airway nitric oxide deficiency, oxidative stress and inflammation. Overexpression of dimethylarginine dimethylaminohydrolase 1 (DDAH1), an enzyme degrading ADMA, exerts protective effects in animal models. However, the impact of DDAH1/ADMA on PM2.5-induced lung injury has not been investigated. Methods Ddah1−/− and DDAH1-transgenic mice, as well as their respective wild-type (WT) littermates, were exposed to either filtered air or airborne PM2.5 (mean daily concentration ~ 50 µg/m3) for 6 months through a whole-body exposure system. Mice were also acutely exposed to 10 mg/kg PM2.5 and/or exogenous ADMA (2 mg/kg) via intratracheal instillation every other day for 2 weeks. Inflammatory response, oxidative stress and related gene expressions in the lungs were examined. In addition, RAW264.7 cells were exposed to PM2.5 and/or ADMA and the changes in intracellular oxidative stress and inflammatory response were determined. Results Ddah1−/− mice developed more severe lung injury than WT mice after long-term PM2.5 exposure, which was associated with greater induction of pulmonary oxidative stress and inflammation. In the lungs of PM2.5-exposed mice, Ddah1 deficiency increased protein expression of p-p65, iNOS and Bax, and decreased protein expression of Bcl-2, SOD1 and peroxiredoxin 4. Conversely, DDAH1 overexpression significantly alleviated lung injury, attenuated pulmonary oxidative stress and inflammation, and exerted opposite effects on those proteins in PM2.5-exposed mice. In addition, exogenous ADMA administration could mimic the effect of Ddah1 deficiency on PM2.5-induced lung injury, oxidative stress and inflammation. In PM2.5-exposed macrophages, ADMA aggravated the inflammatory response and oxidative stress in an iNOS-dependent manner. Conclusion Our data revealed that DDAH1 has a marked protective effect on long-term PM2.5 exposure-induced lung injury.

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Reasonable equipment layout is essential for creating a healthy and safe environment, especially in a three-level biosafety laboratory with high potential risk factors of infection. Since 2019, COVID-19, an emerging infection has swept the world and caused severe losses. Biosafety laboratories are mandatory sites for detecting high-risk viruses, so related research is urgently needed to prevent further laboratory-acquired infections of operators. This study investigated the effects of obstacles on exposure infection of staff in a biosafety laboratory with related experimental equipment. The numerical simulation results are highly verified by the measured results. The results indicate that although the equipment layout does not affect the bioaerosol removal time, nearly 17% of the pollutant particles in the actual laboratory cannot be discharged effectively compared with the ideal situation. These particles lingered in the lower space under the influence of vortex, which would increase the respiratory risk of operators. In addition, after the experiment a large part of bioaerosol particles would be captured by equipment and floor, and the deposition rate per unit area is 0.45%/m 2 and 0.8%/m 2 , respectively. Although the results show that the equipment layout could reduce the pollution on the floor, the disinfection is still an important link, especially on the surfaces of equipment. Meanwhile, the result also indicates that the action should be light and slow when operating in BSL-3 laboratory, so as to avoid the secondary suspension pollution of bioaerosol particles on the equipment surface and floor.

Numerous epidemiological and experimental studies have demonstrated that the exposure to fine particulate matter (aerodynamic diameter <2.5 μm, PM2.5) was closely associated with cardiovascular morbidity and mortality. Our previous studies revealed that PM2.5 exposure induced cardiac dysfunction and fibrosis. However, the corresponding underlying mechanism remains largely unaddressed. Here, PM2.5-induced cardiotoxicity is presented to directly promote collagen deposition in cardiomyocytes through the transforming growth factor-β (TGF-β)-containing small extracellular vesicles (sEV). The sEV transition may play an important role in PM2.5-induced cardiac fibrosis. Firstly, long-term PM2.5 exposure can directly induce cardiac fibrosis and increase the level of serum sEV. Secondly, PM2.5 can directly activate macrophages and increase the release of tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), and TGF-β-containing sEV. Thirdly, TGF-β-containing sEV increases the expression of α-smooth muscle actin (α-SMA), collagen I, and collagen III in mouse cardiac muscle HL-1 cells. Finally, TGF-β-containing sEV released from PM2.5-treated macrophages can increase collagen through the activation of the TGF-β-Smad2/3 signaling pathway in HL-1 cells from which some fibroblasts involved in cardiac fibrosis are thought to originate. These findings suggest that TGF-β-containing sEV from PM2.5-activated macrophages play a critical role in the process of increasing cardiac collagen content via activating the TGF-β-Smad2/3 signaling pathway.