Targeted inhibition of the HNF1A/SHH axis by triptolide overcomes paclitaxel resistance in non-small cell lung cancer.

Paclitaxel resistance is associated with a poor prognosis in non-small cell lung cancer (NSCLC) patients, and currently, there is no promising drug for paclitaxel resistance. In this study, we investigated the molecular mechanisms underlying the chemoresistance in human NSCLC-derived cell lines. We constructed paclitaxel-resistant NSCLC cell lines (A549/PR and H460/PR) by long-term exposure to paclitaxel. We found that triptolide, a diterpenoid epoxide isolated from the Chinese medicinal herb Tripterygium wilfordii Hook F, effectively enhanced the sensitivity of paclitaxel-resistant cells to paclitaxel by reducing ABCB1 expression in vivo and in vitro. Through high-throughput sequencing, we identified the SHH-initiated Hedgehog signaling pathway playing an important role in this process. We demonstrated that triptolide directly bound to HNF1A, one of the transcription factors of SHH, and inhibited HNF1A/SHH expression, ensuing in attenuation of Hedgehog signaling. In NSCLC tumor tissue microarrays and cancer network databases, we found a positive correlation between HNF1A and SHH expression. Our results illuminate a novel molecular mechanism through which triptolide targets and inhibits HNF1A, thereby impeding the activation of the Hedgehog signaling pathway and reducing the expression of ABCB1. This study suggests the potential clinical application of triptolide and provides promising prospects in targeting the HNF1A/SHH pathway as a therapeutic strategy for NSCLC patients with paclitaxel resistance. Schematic diagram showing that triptolide overcomes paclitaxel resistance by mediating inhibition of the HNF1A/SHH/ABCB1 axis.

[Pollution Characteristics and Source Analysis of Atmospheric PM2.5-bound Polycyclic Aromatic Hydrocarbons in a Port Area].

In order to explore the pollution characteristics and potential sources of polycyclic aromatic hydrocarbons (PAHs) in the polluted air of a port area, PM2.5 samples (n=59) were collected from Qingdao Port for four seasons from August 2018 to May 2019. The seasonal variation and composition characteristics of PM2.5-bound PAHs were analyzed, the influence of meteorological factors on PAH concentrations was explored using correlation analysis, and the potential sources were analyzed using positive definite matrix factorization and potential source contribution function models. The results showed that the total mean concentration of PAHs was (8.11±12.31) ng·m-3, which was higher in autumn and winter than that in spring and summer. The seasonal molecular compositions of PAHs were similar, dominated by 4-5 ring PAHs (75.43%). Fluoranthene, benzo[e]pyrene, benzo[a]anthracene, phenanthrene, pyrene, and chrysene were the dominant species of PAHs in the study area, which are similar to the major compounds in ship exhaust. Correlation analysis showed that PAH concentrations were significantly negatively correlated with temperature and relative humidity and significantly positively correlated with atmospheric pressure and wind direction and had a poor correlation with wind speed. PMF analysis extracted six contribution factors, and the results indicated that Qingdao Port was mainly influenced by shipping emissions (28.83%), followed by vehicle emissions (20.49%), as well as crude oil volatilization (13.47%). Summer had the greatest impact on shipping emissions. The PSCF results suggested that Beijing-Tianjin-Hebei, Bohai Rim, and northern Shandong were the main source regions for long-range transport.

[Long-term Trends and Sources of Atmospheric Halocarbons at Mount Taishan, Northern China].

Halocarbons are hot topics in atmospheric environment and climate change research. Combining observational data from six field campaigns at the summit of Mount Taishan (36.25°N, 117.10°E, 1534 m above sea level) with backward trajectory and receptor source analyses, this study analyzed the long-term trends and major emission sources of halocarbons in the regional background atmosphere of the North China Plain (NCP) from 2003 to 2018. The results showed that the volume fraction of species eliminated by the Montreal Protocol (MP) showed a significant downward trend; however, the MP-controlled and unregulated species showed an overall upward trend. Meanwhile, the median volume fraction of the MP-controlled and unregulated species at Mount Taishan were significantly higher than the mid-latitude median background values in the northern hemisphere. Mount Taishan air was mainly affected by four types of air masses, of which the air mass originating from NCP accounted for the highest proportion (41%). The major sources of halocarbons were biomass/biofuel burning (38.1%), refrigeration (26.2%), industrial and domestic solvent use (21.7%), solvent use in the electronic industry (8.7%), and leakage of chlorofluorocarbon (CFCs) banks (5.3%). This study fully demonstrates that MP has been effectively implemented in China and provides evidence and recommendations to further reduce and control the volume fraction of halocarbons.

[Characteristics of Atmospheric PM2.5 Pollution and Its Influence on Visibility in Background Areas of Ji'nan].

In order to study the seasonal variations in the chemical composition of atmospheric particulate matter with diameters less than 2.5 µm (PM2.5) and its influence on visibility in background areas, atmospheric PM2.5 samples were collected in spring, summer, autumn, and winter 2016 at Qixingtai in Ji'nan. The pollution characteristics of water-soluble ions components, organic carbon (OC), and elemental carbon (EC) were analyzed, and their regional transmission contributions were studied. The results show that NH4+, SO42-, and NO3- were the main components of water-soluble ions, accounting for 90.24% of the annual total ion concentration. The secondary water soluble inorganic ions were polluted severely. NO3-/SO42- presented obvious seasonal variations of high (low) levels in winter (summer). In each season, SO42- and NH4+ existed mainly in the form of (NH4)2SO4. The value of secondary OC (SOC)/OC ranged from 21.17% to 54.21%, indicating the presence of relatively severe secondary organic pollution in this area. The sulfur oxidation ratio (SOR) value in all seasons was greater than 0.1, indicating that the secondary generation of SO42- occurs in all seasons in this region, and the value of nitrogen oxidation ratio (NOR) in all seasons was higher than the SOR value. The secondary transformation of NO2 in the Qixingtai region was stronger than that of SO2. The range of atmospheric extinction coefficient (Bext) was 172.68-320.61 Mm-1, with an annual mean of 256.48 Mm-1. The atmospheric extinction coefficient showed an obvious seasonal trend of the lowest (highest) in summer (winter). The backward airflow trajectory shows that the Qixingtai was affected mainly by the long-distance transmission from Northwest China and the ocean in spring and summer and by local sources in autumn and winter. A comparison of the characteristics of atmospheric PM2.5 pollution in Ji'nan in 2008 revealed that the influence of motor vehicles on the atmospheric environment has been significantly improved.

[Organic Distribution Characteristics and Influence on Drinking Water Quality in the Typical Water Sources for Towns in the Southwest Hilly Area of China].

This study analyzed the organic distribution characteristics of original and treated water and their impacts on drinking water quality using a conventional water treatment process in the typical water supply sources for towns in the southwest hilly area of China. The results showed that the water supply source in this area is micro-polluted water. Dissolved organics of low molecular weight accounted for the great majority of the organics, with the proportion ranging from 50% to 80%. There were 53 kinds and 14 classes of organics, including alkanes, esters, phenolic compounds, and benzenes, with the proportion from 80% to 90%. The amounts of organic acid, alkene, alcohols, and aldehyde were small, while the amounts of dichloromethane, phenol, and dibutyl-phthalate were relatively high. Herbicides, food additives, and antibiotics were detected, such as terbuthylazine, 2,6-di-tert-butyl-p-cresol, and nalidixic acid. The conventional water treatment process could efficiently remove the compounds with molecular weights higher than 10×103 and organic acid; however, it was limited greatly in its removal of alkanes, esters, phenolic compounds, and benzenes.

Influence of meteorological conditions and particulate matter on visual range impairment in Jinan, China.

To understand the influence of aerosol particles and meteorological conditions on visual range in Jinan, the capital of Shandong Province, China, PM(2.5) and PM(10) samples were collected from November 2004 to September 2005. The mass concentrations of PM(2.5) and PM(10), concentrations of water-soluble ions in PM(2.5) and concentrations of black carbon (BC) in the atmosphere were analyzed. The decrease of visual range in Jinan results from the combined influence of PM(2.5), PM(10) and meteorological conditions. For the period studied, the average light extinction coefficient, b(ext), which was estimated from an equation developed by the IMPROVE network was 292 Mm(-1). Ammonium sulfate was the major contributor to visual range impairment, accounting for 41%, while ammonium nitrate, particulate organic matter (POM) and BC made comparable contributions accounting for 20%, 22% and 18%, respectively. This highlights the significance of secondary particles ((NH(4))(2)SO(4), NH(4)NO(3), POM) in visual range impairment in Jinan. The data from this study are also compared with the long-term variations of visual range in Jinan from 1961 to 2005.