Tenovin 3 induces apoptosis and ferroptosis in EGFR 19del non small cell lung cancer cells.

Epidermal growth factor receptor (EGFR) exon 19 deletion is a major driver for the drug resistance of non-small cell lung cancer (NSCLC). Identification small inhibitor capable of selectively inhibiting EGFR-19del NSCLC is a desirable strategy to overcome drug resistance in NSCLC. This study aims to screen an inhibitor for EGFR exon 19 deletion cells and explore its underlying mechanism. High through-put screen was conducted to identify an inhibitor for EGFR-19del NSCLC cells. And tenovin-3 was identified as a selective inhibitor of PC9 cells, an EGFR-19del NSCLC cells. Tenovin-3 showed particular inhibition effect on PC9 cells proliferation through inducing apoptosis and ferroptosis. Mechanistically, tenovin-3 might induce the apoptosis and ferroptosis of PC9 cells through mitochondrial pathway, as indicated by the change of VDAC1 and cytochrome c (cyt c). And bioinformatics analyses showed that the expression levels of SLC7A11 and CPX4 were correlated with NSCLC patient's survival. Our findings provide evidences for tenovin-3 to be developed into a novel candidate agent for NSCLC with EGFR exon 19 deletion. Our study also suggests that inducing ferroptosis may be a therapeutic strategy for NSCLC with EGFR exon 19 deletion.

Wintertime fine aerosol particles composition and its evolution in two megacities of southern and northern China.

Study on fine aerosols composition can help understand the particles formation and is crucial for improving the accuracy of model simulations. Based on field data measured by a Q-ACSM (Quadrupole-Aerosol Chemical Speciation Monitor), we have comprehensively compared the characteristics, evolution, and potential formation mechanisms of the components in NR-PM2.5 during wintertime at two megacities (Beijing and Guangzhou) of southern and northern China. We show that as PM pollution intensifies, the mass fraction of the primary aerosols (e.g., COA, HOA) in PM2.5 in Guangzhou increased, along with a slight decline in proportion of both the secondary organic (SOA) and inorganic (SIA) aerosols; In contrast, in Beijing, the proportion of the SIA ramped up from 28 % to 53 % with the pollution evolution; and the fraction of SOA in total OA also increased due to a substantial increment in the proportion of MO-OOA (from 29 % to 48 %), suggesting a significance of the secondary processes in worsening aerosols pollution in Beijing. Our further analysis demonstrates a leading role of aqueous pathway in the secondary formation of aerosols at the Beijing site, presenting an exponential rising of SIA and SOA with the relative humidity (RH) increase. Compared to Beijing, however, we find that the photochemical oxidation other than aqueous process in Guangzhou plays a more critical role in those secondary aerosols formation. Combined with the Hysplit trajectory model, we identify the high humid conditions in Guangzhou are typically affected by clean marine air masses, explaining the slower response of secondary components to the RH changes. Moreover, the particles in Guangzhou were observed less hygroscopic that is adverse to the aerosol aqueous chemistry. The results provide basis for the precise control of PM pollution in different regions across China and would be helpful in improving model simulations.

Contrasting the characteristics, sources, and evolution of organic aerosols between summer and winter in a megacity of China.

Organic aerosol (OA) accounts for the largest fraction of fine particles in the ambient atmosphere, however, its formation process remains highly uncertain. Here, with an aim of obtaining insights to OA formation mechanism, we have focused on contrasting the characteristics, sources and evolution of OA of PM2.5 (particulate matter with an aerodynamic diameter < 2.5 µm) between summer and winter based on two field campaigns of urban Beijing. The results show that secondary OA (SOA) dominates OA mass in PM2.5 both in summer and winter, accounting for 87 % and 74 %, respectively. This is much higher compared to the mass fraction of ~56 % that observed in PM1, indicating an important role of SOA in larger size particles. We also show that, the SOA is becoming more dominant in total OA and our observed high SOA proportion is reconciled with its overall upward trends in recent years. The observed mass concentrations of SOA (less oxidized oxygenated OA, LO-OOA; more oxidized OOA, MO-OOA) in winter are about twice higher than those in summer. The Van-Krevelen diagram implies that the addition of carboxylic acid may be a primary oxidation process of OA in summer, while the addition of alcohol/peroxide may play a dominant role in OA evolution in winter. Our observation and analysis illustrate a more efficient conversion from LO-OOA to MO-OOA through aqueous-phase processes in winter of Beijing. While, in summer, cooking OA may be easier to convert to MO-OOA through photochemical process than other OA factors. We further show that the POA is mainly locally emitted, while the origin of SOA is from both regional transport and locally formed. The results of this study may provide policy basis for the precise control of OA pollution and would also help to improve the accuracy of assessing the environmental and climate effects of OA.

The effect of black carbon aging from NO2 oxidation of SO2 on its morphology, optical and hygroscopic properties.

Atmospheric aging of black carbon (BC) leads to changes in its physiochemical properties, exerting complex effects on environment and climate. In this study, we have conducted laboratory chamber experiments to investigate the effects of BC aging on its morphology, hygroscopicity and optical properties by exposing monodisperse fresh BC particles to ambient ubiquitous species of nitrogen dioxide (NO2), sulfur dioxide (SO2) and ammonia (NH3) in absence of UV light. We show a rapid aging from highly fractal to compacted aggregates for the monodisperse BC particles with an initial diameter of 150 nm, with decline in the dynamic shape factor (χ) from about 1.8 to nearly 1. The effective density of the monodisperse BC particles increases from ∼0.54 to 1.50 g cm-3 accordingly. The aging process leads to that the light scattering, absorption, and single scattering albedo of the monodisperse BC particles are strongly enhanced by factors of 7.0, 1.8 and 3.0 respectively. By comparing with the BC aging from other mechanisms, we reveal a critical role of the composition of the coating materials on BC in determining its light absorption enhancement. Moreover, due to strong water uptake capacity of the aged BC particles, the light absorption enhancement (Eabs) could be 40-60% higher at humid atmosphere compared with dry conditions. This BC aging process from NO2 oxidation of SO2 may occur commonly in polluted regions and thus considerably alter its effects on regional air quality and climate.

Rapid narrowing of the urban-suburban gap in air pollutant concentrations in Beijing from 2014 to 2019.

Understanding the spatial patterns of atmospheric pollutants in urban and suburban areas is important for evaluating their effects on regional air quality, climate, and human health. The analyses of pollutant monitoring data of the China National Environmental Monitoring Center revealed that the differences in the concentrations of ambient O3, PM2.5, NO2, SO2, and CO between urban and suburban areas rapidly decreased from 2014 to 2019 in Beijing. Considering the negligible urbanization and interannual meteorological changes during the study period, the results reveal a quick response of the urban-to-suburban difference (ΔUrban-Suburban) in the ambient pollutants concentrations to emission reduction measures implemented in China in 2013. However, owing to the efficient O3 formation in summer in urban areas in recent years, we observed a more rapid decrease in the ΔUrban-Suburban in O3 concentration in summer (64.8%) than in winter (16.1%). In addition, the ΔUrban-Suburban in daytime summer O3 changed from negative in 2014-2018 to positive in 2019, indicating that the daytime O3 concentration in urban areas exceeded that in suburban areas. Furthermore, instantaneous changes in ΔUrban-Suburban in air pollutants were more sensitive to meteorological variations in 2014 than in 2019. The results indicate a less significant role of regional air mass transport in the spatial variability of pollutants under a future scenario of strong emission reduction in China.