Aberrant DNA methylation patterns, including global hypomethylation, gene-specific hypermethylation/hypomethylation, and loss of imprinting (LOI), are common in acute myelogenous leukemia (AML) and other cancer tissues. We investigated for the first time whether such epigenetic changes are induced in healthy subjects by low-level exposure to benzene, a widespread pollutant associated with AML risk. Blood DNA samples and exposure data were obtained from subjects with different levels of benzene exposure, including 78 gas station attendants, 77 traffic police officers, and 58 unexposed referents in Milan, Italy (personal airborne benzene range, <6-478 Mg/m 3 ). Bisulfite-PCR pyrosequencing was used to quantitate DNA methylation in long interspersed nuclear element-1 (LINE-1) and AluI repetitive elements as a surrogate of genome-wide methylation and examine genespecific methylation of MAGE-1 and p15. Allele-specific pyrosequencing of the H19 gene was used to detect LOI in 96 subjects heterozygous for the H19 imprinting center G/A single-nucleotide polymorphism. Airborne benzene was associated with a significant reduction in LINE-1 (À2.33% for a 10-fold increase in airborne benzene levels; P = 0.009) and AluI (À1.00%; P = 0.027) methylation. Hypermethylation in p15 (+0.35%; P = 0.018) and hypomethylation in MAGE-1 (À0.49%; P = 0.049) were associated with increasing airborne benzene levels. LOI was found only in exposed subjects (4 of 73, 5.5%) and not in referents (0 of 23, 0.0%). However, LOI was not significantly associated with airborne benzene (P > 0.20). This is the first human study to link altered DNA methylation, reproducing the aberrant epigenetic patterns found in malignant cells, to low-level carcinogen exposure. [Cancer Res 2007;67(3):876-80]

Autophagy protects hematopoietic cells from radiation damage in part by promoting DNA damage repair. However, the molecular mechanisms by which autophagy regulates DNA damage repair remain largely elusive. Here, we report that this radioprotective effect of autophagy depends on STAT3 signaling in murine bone marrow mononuclear cells (BM-MNCs). Specifically, we found that STAT3 activation and nuclear translocation in BM-MNCs were increased by activation of autophagy with an mTOR inhibitor and decreased by knockout of the autophagy gene Atg7. The autophagic regulation of STAT3 activation is likely mediated by induction of KAP1 degradation, because we showed that KAP1 directly interacted with STAT3 in the cytoplasm and knockdown of KAP1 increased the phosphorylation and nuclear translocation of STAT3. Subsequently, activated STAT3 transcriptionally upregulated the expression of BRCA1, which increased the ability of BM-MNCs to repair radiation-induced DNA damage. This novel finding that activation of autophagy can promote DNA damage repair in BM-MNCs via the ATG-KAP1-STAT3-BRCA1 pathway suggests that autophagy plays an important role in maintaining genomic integrity of BM-MNCs and its activation may confer protection of BM-MNCs against radiation-induced genotoxic stress.

Establishing an age-friendly environment at the community level is essential for promoting healthy aging. This study focused on the relationship between older adults and the community environment through their levels of satisfaction within it. We measured their physical activity (PA) in the community environment and three variables of community-level satisfaction: community environment (SCE), community social infrastructure (SSI), and community street networks (SSN). We analyzed 108 older adult participants in Suzhou using mediation analysis and multiple linear regression to investigate the relationship between physical activity and the community environment. The results of the mediation effect model showed that SCE, SSI, and SSN all affected the physical functions of older adults via the total amount of physical activity (TPA); SSI and SSN affected older adults’ physical functions by affecting the total duration of moderate-intensity physical activity (MPA) and vigorous-intensity physical activity (VPA). In addition, SSI and SSN are related to the types of community facilities, street space quality, and accessibility. Our study provides valuable insights into optimizing aging-friendly neighborhoods through moderate-to-vigorous-intensity PAs at both the facility and street space levels.

To date, most studies on building environments and walking behavior have utilized top-down approaches (e.g., big data or social media data) yet lack bottom-up approaches to verify their findings. Therefore, this study divided urban streets into three main settings (community streets, waterfront paths, and urban greenways) and collected data from a sample of 411 urban residents in Chengdu via an online questionnaire to examine the impact of street environmental factors on their choice of walking path. It was found that: (1) people with higher levels of education preferred streets with water bodies as walking paths; (2) the environmental quality of the physical and aesthetic aspects both had an impact on residents’ choices, and the aesthetic environmental quality had a stronger impact; (3) the impact of most infrastructures on community streets was stronger than on other streets; (4) residents were more concerned about the environmental quality of waterfront paths and urban greenways. Based on these findings, three design patterns for residents’ preferred street environments are proposed.