Targeted metabolomics analysis identified the role of FOXA1 in the change in glutamate-glutamine metabolic pattern of BaP malignantly transformed 16HBE cells.

The carcinogenic mechanism of benzo[a]pyrene (BaP) is far from being elucidated. FOXA1 has been confirmed to play an oncogenic role in BaP-transformed cell THBEc1. To explore the changes in amino acid metabolic patterns, especially glutamate-glutamine (Glu-Gln) metabolic pattern caused by BaP-induced transformation and the possible role FOXA1 might play in it, we compared amino acid metabolic characteristics between THBEc1 cells and control 16HBE cells using a targeted metabolomics method and determined the effects of FOXA1 knockout on the amino acid metabolic pattern using FOXA1 knockout cell THBEc1-ΔFOXA1-c34. The amino acid metabolic patterns of THBEc1 and 16HBE cells were different, which was manifested by the differential consumption of 18 amino acids and the difference in the intracellular content of 21 amino acids. The consumption and intracellular content of Glu and Gln are different between the two types of cells, accompanied by upregulation of FOXA1, GLUL, SLC1A3, SLC1A4, SLC1A5 and SLC6A14, and downregulation of FOXA2 and GPT2 in THBEc1 cells. FOXA1 knockout changed the consumption of 19 amino acids and the intracellular content of 21 amino acids and reversed the metabolic pattern of Glu and the changes in FOXA2, GLUL, SLC1A3 and SLC6A14 in THBEc1 cells. Additionally, FOXA1 knockout inhibited cell proliferation and further increased the dependence of THBEc1 cells on Glu. In conclusion, FOXA1 knockout partially reversed the change in Glu-Gln metabolism caused by BaP-induced transformation by upregulating the expression of GLUL and SLC1A3. Our findings provide a clue for the possible role of FOXA1 in amino acid metabolism regulation.

Carbon sequestration from refractory dissolved organic carbon produced by biodegradation of Saccharina japonica.

Using macroalgae cultures to sequester carbon has been proposed in recent years. Yet the key mechanism of carbon sequestration-how carbon in degrading biomass is converted into refractory dissolved organic carbon (RDOC) remains poorly understood. The process of producting RDOC via biomass degradation of Saccharina japonica, the most productive algae in China, was thus studied in the laboratory. Most of the carbon in the kelp biomass was converted to dissolved inorganic carbon (DIC) by bacterial respiration. Only 7.8% of the carbon in the kelp biomass was converted into labile DOC, semi-labile or semi-refractory DOC, and refractory DOC in turn. The enrichment of DIC resulted in hypoxic conditions in the water. For the hypoxia in the experiment, the sulfur-degrading bacteria Campylobacteria and Bacteroidia became the dominant bacterial classes, which were the key drivers for the transformation of labile DOC to semi-labile or semi-refractory DOC. Then, semi-labile or semi-refractory DOC was converted to RDOC, driven by the sulfite-reducing bacteria Clostridia and Kapabacteria. Finally, 0.3% of the carbon content in kelp was transformed into RDOC. The resulting RDOC, which was rich in sulfur and nitrogen elements, increased the molecular diversity and average molecular weight in the water. An important finding was that the production of RDOC may be accompanied by the environmental risk of hypoxia.

Health-related quality of life in pilots of a Chinese commercial airline.

Health-related quality of life (HRQOL) is currently an important issue in the medical industry. However, data on HRQOL in commercial airline pilots are lacking. This study aimed to investigate HRQOL and its related factors in a sample of commercial pilots. A purposive sample of 373 participants was recruited from a Chinese Commercial Airline. The median (IQR) score for physical health, psychological health and social relationship were 64.3 (75-53.6), 62.5 (70.8-54.2) and 75 (75-58.3), respectively. The mean (SD) score for Environment was 62.2 (16). After controlling for demographics, the multiple linear regression analyses showed that physical activity, fruit intake and vegetable intake were positively correlated with HRQOL score (p < .05), while time-zone flights, smoking, alcohol drinking and being dyslipidemic showed a negative correlation with HRQOL score (p < .05). Healthcare providers should consider time-zone flights, behavioral factors and dyslipidemia when planning related health promotion and disease prevention programs for commercial pilots in the future.

Source specific PM2.5 associated with heart rate variability in the elderly with coronary heart disease: A community-based panel study.

There is increasingly concern that PM2.5 constituents play a significant role in PM2.5-related cardiovascular outcomes. However, little is known about the associations between specific constituents of PM2.5 and risk for cardiovascular health. To evaluate the exposure to specific chemicals of PM2.5 from various sources and their cardiac effects, a longitudinal investigation was conducted with four repeated measurements of elderly participants' HRV and PM2.5 species in urban Beijing. Multiple chemicals in PM2.5 (metals, ions and PAHs) were characterized for PM2.5 source apportionment and personalized exposure assessment. Five sources were finally identified with specific chemicals as the indicators: oil combustion (1.1%, V & PAHs), secondary particle (11.3%, SO42- & NO3-), vehicle emission (1.2%, Pd), construction dust (28.7%, Mg & Ca), and coal combustion (57.7%, Se & As). As observed, each IQR increase in exposure to oil combustion (V), vehicle emission (Pd), and coal combustion (Se) significantly decreased rMSSD by 13.1% (95% CI: -25.3%, -1.0%), 27.4% (95% CI: -42.9%, -7.6%) and 24.7% (95% CI: -39.2%, -6.9%), respectively, while those of PM2.5 mass with decreases of rMSSD by 11.1% (95% CI: -19.6%, -1.9%) at lag 0. Elevated exposures to specific sources/constituents of PM2.5 disrupt cardiac autonomic function in elderly and have more adverse effects than PM2.5 mass. In the stratified analysis, medication and gender modify the associations of specific chemicals from variable sources with HRV. The findings of this study provide evidence on the roles of influential constituents of ambient air PM2.5 and their sources in terms of their adverse cardiovascular health effects.

Hemispheric Asymmetries of Cortical Thickness in Civil Aviation Pilots.

BACKGROUND: Although several studies have shown that an individual's career influences the brain structure, no study has examined cortical asymmetry in civil aviation pilots. This study focused on hemispheric cortical asymmetries in Chinese civil aviation pilots.METHODS: The MRI structural images of 1065 healthy captains of the Civil Aviation Administration of China were analyzed using a surface-based automated parcellation approach, and hemispheric asymmetries in the global and regional cortical thickness of their brains were examined.RESULTS: The hemispheric asymmetries were relatively significant. In total, 58 regions out of 74 were clearly asymmetrical. Generally, rightward asymmetries (reduction left) were found in slightly more regions than leftward asymmetries. The study also revealed leftward asymmetries mainly throughout the lateral, dorsal, and mesial surfaces of the frontal lobe, extending into the primary sensory, superior parietal, and anterior temporal cortices. In addition, the rightward asymmetries were mainly located in the temporal and occipital cortices.DISCUSSION: Compared with previous studies, in this study, the structural lateralization of the cortical thickness was more significant. Most of the results were in agreement with those of previous studies, although there were different results in some regions. Functional structural lateralization was demonstrated among the regions. Hemispheric differences in the thickness of the cortex might be related to hemisphere-specific functional specializations that may be associated with behavioral asymmetries.Cao Y, Qiu C, Zhao C, Zhang Y, Qi Y, Li S. Hemispheric asymmetries of cortical thickness in civil aviation pilots. Aerosp Med Hum Perform. 2019; 90(5):456-461.

Adherence to a healthy lifestyle and a DASH-style diet and risk of hypertension in Chinese individuals.

Several modifiable risk factors have been shown to lower blood pressure, but little is known about their combined risk in Chinese individuals. In this prospective cohort study, we followed 2751 subjects aged 18-60 years in the China Health and Nutrition Survey who were free of diagnosed hypertension, cardiovascular disease, diabetes or cancer at baseline in 2000. The associations between each of the risk factors and the risk of developing incident hypertension were analyzed by gender. The three low-risk factors for hypertension were a body mass index (BMI) between 18.5 and 24, a moderate or heavy physical activity level ⩾0.5 h per day and a high score on the Dietary Approaches to Stop Hypertension (DASH) diet. Low-risk factors were combined to assess their effects on the risk of hypertension. During the 11-year follow-up, we documented 1147 cases of hypertension. Three risk factors were independently associated with the risk of hypertension even after adjustment for age, alcohol intake and smoking status. Adopting all three low-risk lifestyle factors (normal BMI, DASH-style diet and physical activity) could prevent 38% (95% confidence interval (CI), 19-53%) of new hypertension cases among women and 43% (95% CI, 25-57%) of new hypertension cases among men. Adherence to a healthy lifestyle and a DASH-style diet was associated with a lower risk of hypertension.

Diethyl sulfate induced Cdk2-dependent centrosome amplification in CHL cells.

The function of centrosome that serves as the main microtubule organizing center is essential to ensure the genomic integrity during the cell division cycle. Centrosome abnormalities are frequently observed in many tumors and cells exposed to genotoxic agents. Here, we investigated the centrosome abnormalities induced by diethyl sulfate (DES) in Chinese hamster lung (CHL) fibroblasts and the underlying molecular mechanisms. Our results showed that DES exposure at 0.3, 1 and 3mM for 48 h caused centrosome amplification in a dose dependent manner. This effect was associated with transient S and G2/M phase delay and up-regulating of Cdk2, Cyclin A expressions. Furthermore, inhibition of Cdk2 activities reversed the centrosome amplification induced by DES. These results reveal that centrosome is one of the key subcellular targets of DES. Centrosome abnormalities might be important mechanisms behind the aneuploidy induction and carcinogenicity of DES.

Claspin is involved in S-phase checkpoint induced by benzo(a)pyrene in 16HBE cells.

Environmental carcinogen benzo(a)pyrene (BaP) can damage DNA by forming bulky adducts that are degraded further to DNA strand breaks, thus contributing to induce DNA damage checkpoint response. Claspin is a critical checkpoint protein in response to multiple forms of genotoxic stress including UV, IR and hydroxyurea (HU). In the present study we have investigated the role of human Claspin in the DNA damage checkpoint elicited by BaP in 16HBE cells. We observed that Claspin levels are increased in a time-dependent manner in response to S-phase arrest induced by BaP. In addition, the levels of phosphorylation of Chk1 on S345 were increased, but the levels of Cdc25A were decreased after treatment with BaP. Inhibition of Claspin expression (siRNA) attenuated the effect of BaP on S-phase arrest and abrogated the activation of Chk1 and degradation of Cdc25A in response to BaP. Taken together, these data imply that Claspin plays an important role in S-phase checkpoint induced by BaP, and it participates in the activation of Chk1 and Cdc25A in this checkpoint pathway.

The effects of over-expression and suppression of Cdc25A on the S-phase checkpoint induced by benzo(a)pyrene.

Our previous results have indicated that Cdc25A is involved in benzo(a)pyrene (BaP)-induced S-phase checkpoint in 16HBE cells and A549 cells. In this paper, we reported the changes of the downstream molecular pathway of Cdc25A and the effects of over-expression and suppression of Cdc25A on BaP-induced S-phase checkpoint. In the S-phase checkpoint induced by BaP the reduction of Cdc25A contributes to cyclin A inhibition. Over-expression of Cdc25A abrogated BaP-induced S-phase arrest in 16HBE cells and concomitantly the expression levels of Cdk2 and cyclin A were not obviously changed by BaP when compared with the control. Cdc25A down-regulation by RNA interference (RNAi) prolonged the S-phase arrest induced by BaP and decreased clearly the expression levels of cyclin A and cyclin E. Therefore, our results further demonstrated that Cdc25A was an effector in Chk1-Cdc25A-cyclin A/Cdk2 pathway of S-phase checkpoint elicited by the carcinogen BaP in 16HBE cells.

Manganese-induced single strand breaks of mitochondrial DNA in vitro and in vivo.

The aim of this study was to examine the single strand breaks (SSB) of mitochondrial DNA (mtDNA) induced by MnCl(2) in vitro and in vivo and discuss the possible underlying mechanism. In in vitro study the formation of mtDNA SSB and reactive oxygen species (ROS) in isolated hepatic mitochondria treated with MnCl(2) (0-1.0mmolL(-1)) was observed. In in vivo study the SSB of brain and liver mtDNA was examined, meanwhile the level of glutathione (GSH) and malondialdehyde (MDA) and activity of antioxidant enzymes were examined after 3-month intraperitoneal administration of MnCl(2) daily (0, 5, 10 and 20mg/kg/d) in Sprague-Dawley rats. The in vitro results indicated that MnCl(2) increased the formation of mtDNA SSB and ROS in **a dose-dependent manner in vitro. MnCl(2) exposure in vivo increased in mtDNA SSB in rat brain and liver and decreased in level of GSH in rat hepatic mitochondria and brain homogenates in a dose-dependent manner. The level of MDA and the activities of SOD and GPx were not significantly changed in both hepatic mitochondria and brain homogenates of rats. These results indicated that Mn treatment increased in mtDNA SSB in vitro and in vivo, mediated probably via Mn-induced oxidative stress.

The Cdc25A is involved in S-phase checkpoint induced by benzo(a)pyrene.

Environmental carcinogen benzo(a)pyrene (BaP) generates electrophilic products BaP diolepoxide (BPDE) that react covalently with genomic DNA. Cells that acquire BaP/BPDE-induced DNA damage undergo S-phase arrest in a p53-independent manner. However, the role of Cdc25A in the BaP/BPDE-induced checkpoint is not clear. In the present study, we investigated the change of checkpoint kinase 1 (Chk1) and Cdc25A in S-phase arrest elicited by BaP. The results indicated that BaP (10microM, with S9 mixture) treatment induced S-phase arrest in both human lung carcinoma A549 cells and human bronchial epithelial cells line 16HBE cells, increasing the proportions of cells in S-phase 19.0% and 21.1%, respectively, at 12h after treatment, compared with DMSO control (p<0.01). Then, the S-phase arrest was weakened after 24h. The level of phorsphorylated Chk1 obviously increased and Cdc25A protein level decreased in both two cell lines after treatment with BaP. The results of RT-PCR indicate Cdc25A mRNA in both A549 cells and 16HBE cells was not changed after BaP treatment 12h, and 24h. The treatment of the proteasome inhibitor MG132 greatly increased Cdc25A protein in abundance. Over all, our results indicated Chk1-Cdc25A checkpoint pathway is involved in BaP-induced S-phase arrest. Moreover, transcription of Cdc25A did not change in BaP induced S-phase arrest, the decrease of Cdc25A level was due to increased degradation through the ubiqutin-proteasome pathway.