Introduction Recent studies demonstrated that living in areas with high ambient air pollution may have adverse effects on pregnancy outcomes, but few studies have investigated its association with spontaneous abortion. Further investigation is needed to explore the acute effect and lag effect of air pollutants exposure on spontaneous abortion. Objective To investigate the acute effect and lag effect between exposure to ambient air pollutants and spontaneous abortion. Methods Research data of spontaneous abortion were collected from the Chongqing Health Center for Women and Children (CQHCWC) in China. The daily ambient air pollution exposure measurements were estimated for each woman using inverse distance weighting from monitoring stations. A time-stratified, case-crossover design combined with distributed lag linear models was applied to assess the associations between spontaneous pregnancy loss and exposure to each of the air pollutants over lags 0–7 days, adjusted for temperature and relative humidity. Results A total of 1399 women who experienced spontaneous pregnancy loss events from November 1, 2016, to September 30, 2019, were selected for this study. Maternal exposure to particulate matter 2.5 (PM2.5), particle matter 10 (PM10) nitrogen dioxide (NO2), and sulfur dioxide (SO2) exhibited a significant association with spontaneous abortion. For every 20 μg/m3 increase in PM2.5, PM10, NO2, and SO2, the RRs were 1.18 (95% CI: 1.06, 1.34), 1.12 (95% CI, 1.04–1.20), 1.15 (95% CI: 1.02, 1.30), and 1.92 (95% CI: 1.18, 3.11) on lag day 3, lag day 3, lag day 0, and lag day 3, respectively. In two-pollutant model combined with PM2.5 and PM10, a statistically significant increase in spontaneous abortion incidence of 18.0% (RR = 1.18, 95% CI: 1.06, 1.32) was found for a 20 μg/m3 increase in PM2.5 exposure, and 11.2% (RR = 1.11, 95% CI: 1.03, 1.20) for a 20 μg/m3 increase in PM10 exposure on lag day 3, similar to single-pollutant model analysis. Conclusion Maternal exposure to high levels of PM2.5, PM10, NO2, and SO2 during pregnancy may increase the risk of spontaneous abortion for acute effects and lag effects. Further research to explore sensitive exposure time windows is needed.

Recent study results on the association between maternal exposure to ambient air pollution with preterm birth have been inconsistent. The sensitive window of exposure and influence level of air pollutants varied greatly. We aimed to explore the association between maternal exposure to ambient air pollutants and the risk of preterm birth, and to estimate the sensitive exposure time window. A total of 572,116 mother–newborn pairs, daily concentrations of air pollutants from nearest monitoring stations were used to estimate exposures for each participant during 2015–2020 in Chongqing, China. We applied a generalized additive model and estimated RRs and 95% CIs for preterm birth in each trimester and the entire pregnancy period. In the single-pollutant model, we observed that each 10 μg/m3 increase in PM2.5 had a statistically significant effect on the third trimester and entire pregnancy, with RR = 1.036 (95% CI: 1.021, 1.051) and RR = 1.101 (95% CI: 1.075, 1.128), respectively. Similarly, for each 10 μg/m3 increase in PM10, there were 2.7% (RR = 1.027, 95% CI: 1.016, 1.038) increase for PTB on the third trimester, and 3.8% (RR = 1.038, 95% CI: 1.020, 1.057) increase during the whole pregnancy. We found that for each 10 mg/m3 CO increases, the relative risk of PTB increased on the first trimester (RR = 1.081, 95% CI: 1.007, 1.162), second trimester (RR = 1.116, 95% CI: 1.035, 1.204), third trimester (RR = 1.167, 95% CI: 1.090, 1.250) and whole pregnancy (RR = 1.098, 95% CI: 1.011, 1.192). No statistically significant RR was found for SO2 and NO2 on each trimester of pregnancy. Our study indicates that maternal exposure to high levels of PM2.5 and PM10 during pregnancy may increase the risk for preterm birth, especially for women at the late stage of pregnancy. Statistically increased risks of preterm birth were associated with CO exposure during each trimester and entire pregnancy. Reducing exposure to ambient air pollutants for pregnant women is clearly necessary to improve the health of infants.

Cisplatin (DDP)-based chemotherapy remains one of the standard treatment options for patients with advanced lung adenocarcinoma (LUAD), and cisplatin resistance is the biggest challenge to this therapy. Autophagy is also closely associated with chemoresistance in LUAD. Desperately need to find a way to improve the treatment efficiency of cisplatin-resistant LUAD in clinical practice. Previous studies reported that methylseleninic acid (MSA) has good anti-proliferation and pro-apoptotic activities in tumor cells. However, the effectiveness of MSA on cisplatin-resistant LUAD and its effect on the induction of autophagy is still unclear. In the current study, we found that MSA effectively inhibited the proliferation of LUAD cell lines and triggered mitochondrial pathway-mediated apoptosis. This effect was more pronounced in cisplatin-resistant LUAD cells with high MDR1 expression. In contrast, the mitochondrial damage caused by MSA treatment can be degraded by inducing selective autophagy in LUAD cells, thereby exerting a self-protective effect on tumor cells. Mechanistically, MSA inhibits proliferation, promotes apoptosis, and induces autophagy in LUAD cells by inhibiting of the Akt/mTOR pathway. Combination with autophagy inhibitors reduces the effect of this selective autophagy-induced resistance, and thus enhancing even more the anti-tumor effect of MSA on cisplatin-resistant LUAD cells. Finally, We speculate that MSA in combination with autophagy inhibitors may be a promising new therapeutic strategy for the treatment of cisplatin-resistant LUAD.

For patients with platinum-resistant lung adenocarcinoma (LUAD), the exploration of new effective drug candidates is urgently needed. Fibroblast growth factor receptors (FGFRs) have been identified as promising targets for LUAD therapy. The purpose of this study was to determine the exact role of the irreversible FGFR1-4 inhibitor FIIN-2 in LUAD and to clarify its underlying molecular mechanisms. Our results demonstrated that FIIN-2 significantly inhibited the proliferation, colony formation, and migration of A549 and A549/DDP cells but induced the mitochondria-mediated apoptosis of these cells. Meanwhile, FIIN-2 increased the autophagy flux of A549 and A549/DDP cells by inhibiting the mammalian target of rapamycin (mTOR) and further activating the class III PI3K complex pathway. More importantly, in vivo and in vitro experiments showed that autophagy inhibitors could enhance the cytotoxicity of FIIN-2 on A549 and A549/DDP cells, confirming that FIIN-2 induced protective autophagy. These findings indicated that FIIN-2 is a potential drug candidate for LUAD treatment, and its use in combination with autophagy inhibitors might be an efficient treatment strategy, especially for patients with cisplatin resistance.

IntroductionThere have been many researches done on the association between maternal exposure to ambient air pollution and adverse pregnancy outcomes, but few studies related to very low birth weight (VLBW). This study thus explores the association between maternal exposure to ambient air pollutants and the risk of VLBW, and estimates the sensitive exposure time window.MethodsA retrospective cohort study analyzed in Chongqing, China, during 2015–2020. The Generalized Additive Model were applied to estimate exposures for each participant during each trimester and the entire pregnancy period.ResultsFor each 10 μg/m3 increase in PM2.5 during pregnancy, the relative risk of VLBW increased on the first trimester, with RR = 1.100 (95% CI: 1.012, 1.195) in the single-pollutant model. Similarly, for each 10 μg/m3 increase in PM10, there was a 12.9% (RR = 1.129, 95% CI: 1.055, 1.209) increase for VLBW on the first trimester in the single-pollutant model, and an 11.5% (RR = 1.115, 95% CI: 1.024, 1.213) increase in the multi-pollutant model, respectively. The first and second trimester exposures of NO2 were found to have statistically significant RR values for VLBW. The RR values on the first trimester were 1.131 (95% CI: 1.037, 1.233) and 1.112 (95% CI: 1.015, 1.218) in the single-pollutant model and multi-pollutant model, respectively; The RR values on the second trimester were 1.129 (95% CI: 1.027, 1.241) and 1.146 (95% CI: 1.038, 1.265) in the single-pollutant model and multi-pollutant model, respectively. The RR of O3 exposure for VLBW on the entire trimester was 1.076 (95% CI: 1.010–1.146), and on the second trimester was 1.078 (95% CI: 1:016, 1.144) in the single-pollutant model.ConclusionThis study indicates that maternal exposure to high levels of PM2.5, PM10, NO2, and O3 during pregnancy may increase the risk of very low birth weight, especially for exposure on the first and second trimester. Reducing the risk of early maternal exposure to ambient air pollution is thus necessary for pregnant women.