Exploring particle concentrations and inside-to-outside ratios in vehicles: A real-time road test study.

In transportation microenvironments, humans exposed to particulate matter (PM) inside vehicles can experience higher levels of daily exposure. To make inside-vehicle PM exposure measurements more feasible and easy under real driving conditions, and to quantify the relationship between the concentrations and influencing factors, we assessed PM1, PM2.5, and PM10. levels. Additionally, we collected key influencing factors to develop predictive models. The measurements of PM1, PM2.5, and PM10 concentrations showed that the ventilation setting was a significant influencing factor. The concentrations decreased significantly under the recirculation setting (RC) compared to the outside air setting (OA). The inside-to-outside (I/O) ratios of PM were 1.69 to 1.93-fold higher than those of RC under OA conditions. However, a substantial reduction in the I/O ratios was observed when RC was employed. Although both the concentrations and I/O ratios exhibited significant differences, they demonstrated strong potential relationships. PM2.5 I/O ratios accounted for over 85 % of the variation in the PM1 and PM10 I/O ratios. The developed models for the I/O ratios of PM accounted for >40 and 60 % of the variation in the measured I/O ratios for RC and OA, respectively. We used the vehicle age, vehicle interior volume, speed, cabin temperature, cabin humidity, and their higher-order terms as predictive variables. It is important to note that the influential predictive feature importance differed under RC and OA, and considering the vehicle characteristics between vehicles of the same type may be necessary when using RC. Overall, these findings indicate that the inside-vehicle PM exposure can be measured more easily under real driving conditions by considering the key influencing factors and utilizing the developed predictive models.

Mapping the personal PM2.5 exposure of China's population using random forest.

Ambient monitoring may cause estimation errors, and wearable monitoring is expensive and labor-intensive when assessing PM2.5 personal exposure. Estimation errors have limited the development of exposure science and environmental epidemiology. Thus, we developed a scenario-based exposure (SBE) model that covered 8 outdoor exposure scenarios and 1 indoor scenario with corresponding time-activity patterns in Baoding City. The linear regression analysis of the SBE yielded an R2 value of 0.913 with satisfactory accuracy and reliability. To apply the SBE model to large-scale studies, we predicted time-activity patterns with the random forest model and atmosphere-to-scenario ratios with the linear regression model to obtain the essential parameters of the SBE model; their R2 was 0.65-0.93. The developed model would economize the study expenditure of field sampling for personal PM2.5 and deepen the understanding of the influences of indoor and outdoor factors on personal PM2.5. Using this method, we found that the personal PM2.5 exposure of Chinese residents was 10.50-347.02 µg/m3 in 2020, higher than the atmospheric PM2.5 concentration. Residents in North and Central China, especially the Beijing-Tianjin-Hebei region and the Fen-Wei Plains, had higher personal PM2.5 exposure than those in other areas.

Risk SNP-mediated LINC01614 upregulation drives head and neck squamous cell carcinoma progression via PI3K/AKT signaling pathway.

As potential biomarkers and therapeutic targets, long noncoding RNAs (lncRNAs) are involved in the tumorigenesis of various tumors. Genetic variation in long noncoding regions can lead to lncRNA dysfunction and even cancer. Nevertheless, studies on the association between lncRNA-associated single-nucleotide polymorphisms (SNPs) and the risk of head and neck squamous cell carcinoma (HNSCC) remain inadequate. Here, we aimed to explore the association between SNPs in LINC01614 and HNSCC risk, and the potential role of LINC01614 in tumorigenesis. In this study, we found that rs16854802 A > G (odds ratio [OR] = 1.42, 95% confidence interval [CI]: 1.22-1.77, p < 0.001) and rs3113503 G > C (OR = 1.38, 95% CI: 1.15-1.64, p < 0.001) in LINC01614 increased the risk of HNSCC in the Chinese population. Functional bioinformatic analysis and luciferase reporter assay revealed that rs3113503 G > C variant disrupted the binding of miRNA-616-3p to LINC01614, which resulted in the increased expression of LINC01614. Further analysis of the TCGA database demonstrated that the upregulated LINC01614 in HNSCC cancer tissues was associated with poor prognostic in HNSCC patients. In vitro experiments showed that knockdown of LINC01614 inhibited the proliferation, invasion, and migration ability of HNSCC cells. Mechanistically, allele C of rs3113503 in LINC01614 was more effective than allele G in activating the PI3K/AKT signaling pathway. Moreover, the reduced expression of LINC01614 also inhibited the activation of the PI3K/AKT signaling pathway. In summary, our findings revealed that the risk SNP rs3113503 G > C in LINC01614 altered the binding to miR-616-3p, which led to increased LINC01614 expression and promoted HNSCC progression by activating the PI3K/AKT signaling pathway.

Genetic variants of cell cycle pathway genes are associated with head and neck squamous cell carcinoma in the Chinese population.

Genetic alterations in the cell cycle pathway are common in head and neck squamous cell carcinoma (HNSCC). We identified four novel HNSCC susceptibility loci (CDKN1C rs452338, CDK4 rs2072052, E2F2 rs3820028 and E2F2 rs2075993) through a two-stage matched case-control study. There was a combined effect among the four single nucleotide polymorphisms (SNPs), as the number of risk genotypes increased, the risk of HNSCC displayed an increasing trend (Ptrend < 0.001). And there were multiplicative interactions between rs452338 and rs2072052, rs2072052 and rs3820028, rs2072052 and rs2075993. Functional bioinformatics analysis and dual-luciferase reporter assay revealed that E2F2 rs2075993 T>C reduced the stability of E2F2 3'-UTR secondary structure and affected the binding of E2F2 to miR-940, which was up-regulated in HNSCC tumor tissues (P = 2.9e-8) and was correlated with poor overall survival of HNSCC (HR = 1.39, 95% CI = 1.02-1.90). In vitro assays, we discovered that the expression of miR-940 was regulated by METTL3, and miR-940 promoted the proliferation, migration and invasion, and inhibited the senescence and autophagy of tumor cells. In terms of mechanism, compared with rs2075993 allele T, we found that the protective variant rs2075993 allele C interfered with the translational inhibition of E2F2 by miR-940, resulting in increased expression of E2F2 protein, which further reduced the proliferation, migration, invasion, and increased the senescence of tumor cells.

ALKBH5 promotes cadmium-induced transformation of human bronchial epithelial cells by regulating PTEN expression in an m6A-dependent manner.

Cadmium is a carcinogenic heavy metal that poses a severe threat to human beings. The underlying mechanism, however, remains elusive. N6-methyladenosine (m6A) is the most abundant post-transcriptional modification in mRNA that regulates RNA metabolism. Emerging evidence shows that m6A is involved in the pathogenesis of various cancers. In this study, human bronchial epithelial BEAS-2B cells were transformed by exposing to 2 µM of cadmium for 20 weeks to investigate the role of m6A in cadmium carcinogenesis. We found the level of m6A in mRNA was significantly decreased in cadmium-transformed BEAS-2B cells, and this change was regulated by m6A demethylase ALKBH5. ALKBH5 was significantly upregulated in the middle and late stages of cell transformation at week 8, 12, 16 and 20. Knockdown of ALKBH5 in cadmium-transformed cells alleviated cell proliferation, migration, invasion, and anchorage-independent growth, but co-transfection with ALKBH5 siRNA and PTEN siRNA restored the inhibitory effects of ALKBH5 knockdown on those transformation properties. ALKBH5 decreased the m6A level of PTEN mRNA, resulting in its instability and reduction of PTEN protein expression. These results indicate that ALKBH5-mediated demethylation m6A at PTEN mRNA is involved in cadmium-induced cell transformation. Our study provides a new perspective for the involvement of m6A modification in cadmium carcinogenesis.

Circ-SHPRH suppresses cadmium-induced transformation of human bronchial epithelial cells by regulating QKI expression via miR-224-5p.

Circular RNAs (circRNAs) have been demonstrated to play critical roles in the pathogenesis of human cancers and carcinogenesis of several environmental pollutants. Nevertheless, the function of circRNAs in cadmium carcinogenesis is unclear. circ-SHPRH is down-regulated in many cancers including non-small cell lung cancer. In our present study, during cadmium-induced transformation of human bronchial epithelial BEAS-2B cells, epithelial-mesenchymal transition (EMT) was induced. Meanwhile, at the middle and late stages of cell transformation, cadmium down-regulated the expression of circ-SHPRH, as well as QKI, a tumor suppressor protein known to prevent the proliferation and EMT during progression of human cancers, compared with passage-matched control BEAS-2B cells. Overexpression of circ-SHPRH in cadmium-transformed BEAS-2B cells promoted the expression of QKI and significantly inhibited proliferation, EMT, invasion, migration and anchorage-independent growth in soft agar of the cells. Mechanistic studies showed that circ-SHPRH functioned as a sponge of miR-224-5p to regulate QKI expression. Interestingly, QKI and circ-SHPRH could form a positive-feedback loop that perpetuated circ-SHPRH/miR-224-5p/QKI axis. Collectively, our results demonstrated that circ-SHPRH inhibited cadmium-induced transformation of BEAS-2B cells through sponging miR-224-5p to regulate QKI expression under cadmium treatment. Our study uncovered a novel molecular mechanism involved in circRNAs in the development of lung cancer due to cadmium exposure.