Abstract Carbon black (CB) is a material produced by the combustion of hydrocarbon gases or liquids and widely used in various industrial settings. The International Agency for Research on Cancer has classified CB as possibly carcinogenic to humans. Previous studies suggest that CB might induce lung inflammation and injury and it is well known that inflammation can play an important role in tumor development. However, the relationship between CB exposure and peripheral white blood cell counts is still not clear. To address this issue, we conducted a cross-sectional molecular epidemiology study of 106 CB-exposed male workers responsible for packing CB in a CB manufacturing facility that produced very high purity CB and 112 unexposed male control workers from the same geographic region who were frequency-matched to the exposed workers by age. The average number of years worked in the factory for the exposed workers was 12.5 years. Peripheral blood samples were collected and a complete blood cell count (CBC) and lymphocyte subset analysis were conducted. There was a borderline significant increase in eosinophil count, and a significant decrease in total lymphocyte and NK cell counts, among the exposed vs. control workers. Among non-smokers (35 exposed and 29 controls), CB exposure was associated with a borderline significant increase in total white blood cell and neutrophil counts, a significant increase in eosinophil counts, and a significant decrease in total lymphocyte, CD3+ T cell, CD8+ T cell and NK cell counts. There were no significant differences between exposed and control workers for any white blood cell measure among smokers. Also, there was some evidence of an interaction between carbon black exposure and smoking status for neutrophil, total lymphocyte, CD3+ T cell, and CD8+ T cell counts. Our results suggest that CB exposure may be associated with altered levels of cells that play an important role in the inflammatory process among non-smokers. Also, there was evidence for an interaction between CB exposure and tobacco use. These findings may provide new insights into particulate-associated disease. Citation Format: Yufei Dai, Rong Zhang, Yong Niu, Huawei Duan, Tao Meng, Meng Ye, Meili Shen, Ping Bin, Shanfa Yu, Roel Vermeulen, Nathaniel Rothman, Qing Lan, Yuxin Zheng. Effects of occupational exposure to carbon black on peripheral white blood cell counts. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 839. doi:10.1158/1538-7445.AM2015-839
Left-sided colon cancer (LCC) and right-sided colon cancer (RCC) have distinct characteristics in tumor immune microenvironment (TIME). Although existing studies have shown a strong association between gene mutations and TIME, whether the regulatory mechanisms between gene mutations and TIME are different between RCC and LCC is still unclear. In this study, we showed the fractions of CD8+ T cells were higher while those of regulatory T cells were lower in RCC. Besides, a stronger association between gene mutations and TIME was observed in RCC. Specifically, using multi-omics data, we demonstrated the mutations of most top mutated genes (TMGs) including BRAF, PCLO, MUC16, LRP2, ANK3, KMT2D, RYR2 made great contributions to elevated fraction of immune cells by up-regulating immune-related genes directly or indirectly through miRNA and DNA methylation, whereas the effects of APC, TP53 and KRAS mutations on TIME were reversed in RCC. Remarkably, we found the expression levels of several immune checkpoint molecules such as PD-1 and LAG3 were correlated with corresponding DNA methylation levels, which were associated with the mutations of TMGs in RCC. In contrast, the associations between gene mutations and TIME were less significant in LCC. Besides, survival analyses showed APC mutation had adverse impact on immunotherapy while patients with BRAF mutation were more suitable for immunotherapy in colon cancer. We hope that our results will provide a deeper insight into the sophisticated mechanism underlying the regulation between mutations and TIME, and thus boost the discovery of differential immunotherapeutic strategies for RCC and LCC.
To compare the effect of 7 antipsychotic drugs on the life quality of schizophrenia patients including chlorpromazine, sulpiride, clozapine, risperidone, olanzapine, quetiapine, and aripiprazole.A total of 1,227 stable schizophrenic patients within 5 years onset who took 1 of the 7 study medications as maintenance treatment were followed up for 1 year at 10 China sites. Patients were evaluated by the short form-36 health survey (SF-36) at the baseline and at the end of 1 year.The life quality was improved obviously at the end of the follow-up. There was significant difference in body pain, vitality, and mental health (P<0.05) among these antipsychotic drugs.All 7 antipsychotic drugs can improve the life quality of schizophrenia patients. Atypical antipsychotic drugs, especially olazapine and quetiapine, are superior to typical antipsychotic drugs in improving life quality.
Despite of their high carrier mobilities, pristine Dirac materials (such as graphene, silicene, and germanene) are unsuitable for effective field effect transistors due to their zero band gaps. In a vertical heterostructure composed by two Dirac materials, the Dirac cones of the two materials survive the weak interlayer Van der Waals interaction based on density functional theory method, and electron transport from the Dirac cone of one material to the one of the other material is therefore forbidden without assistance of phonon because of momentum mismatch. First-principles quantum transport simulations of the vertical Dirac material heterostructure devices confirm the existence of a transport gap of over 0.4 eV, accompanied by a switching ratio of over 104. Such a striking behavior is robust against the relative rotation between the two Dirac materials and can be extended to twisted bilayer graphene. Therefore, novel avenue is opened up for Dirac material vertical structures in high-performance devices without opening their band gaps.
Background: Silicosis is a respiratory disease caused by long-term silica dust exposure. Our previous study has demonstrated that silica mediates the activation of phosphatidylinositol 3-kinase (PI3K)/phosphatase and tensin homolog deleted on chromosome 10 (PTEN)/serine or threonine kinase (AKT)/mitogen-activated protein kinases (MAPK)/AP-1 pathway in human embryo lung fibroblasts (HELFs). The purpose of this study is to identify genome-wide aberrant DNA methylation profiling in lung tissues from silicosis patients. Methods: We performed Illumina Human Methylation 450K Beadchip arrays to investigate the methylation alteration in formalin-fixed, paraffin-embedded (FFPE) lung specimens, immunohistochemistry to detect the level of c-Jun and PTEN proteins; methylation specific PCR (MS-PCR) to identify PTEN and c-Jun promoter methylation in HELFs. Results: We found 86,770 CpG sites and 79,660 CpG sites significantly differed in methylation status in early-stage and advanced-stage compared with GEO normal lung methylation data. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed the methylated status of MAPK signaling pathway was considered changed. The number of PTEN and c-Jun CpG promoter methylated-sites were increased in advanced-stage. Early-stage showed the positive expression of c-Jun and PTEN protein and negative or mild expression in advanced-stage. PTEN promoter was no differentially methylated and c-Jun promoter differed at 12 and 24 h in HELFs. Conclusions: Abnormal DNA methylation on genome-scale was implicated in silicosis, and PTEN promoter hypermethylation might be associated with decrease of PTEN protein.
It is an ongoing pursuit to use metal as a channel material in a field effect transistor. All metallic transistor can be fabricated from pristine semimetallic Dirac materials (such as graphene, silicene, and germanene), but the on/off current ratio is very low. In a vertical heterostructure composed by two Dirac materials, the Dirac cones of the two materials survive the weak interlayer van der Waals interaction based on density functional theory method, and electron transport from the Dirac cone of one material to the one of the other material is therefore forbidden without assistance of phonon because of momentum mismatch. First-principles quantum transport simulations of the all-metallic vertical Dirac material heterostructure devices confirm the existence of a transport gap of over 0.4 eV, accompanied by a switching ratio of over 104. Such a striking behavior is robust against the relative rotation between the two Dirac materials and can be extended to twisted bilayer graphene. Therefore, all-metallic junction can be a semiconductor and novel avenue is opened up for Dirac material vertical structures in high-performance devices without opening their band gaps.
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