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Genetic profiles of the bladder Depending on the environment of the individual, the human bladder can be exposed to carcinogens as they are flushed through the body. Lawson et al. and Li et al. examined the genetic composition of laser-dissected microbiopsies from normal and cancer cells collected from the urothelium, a specialized epithelium lining the lower urinary tract (see the Perspective by Rozen). These complementary studies identified the mutational landscape of bladder urothelium through various sequencing strategies and identified high mutational heterogeneity within and between individuals and tumors. Both studies identified mutational profiles related to specific carcinogens such as aristolochic acid and the molecules found in tobacco. These studies present a comprehensive description of the diverse mutational landscape of the human bladder in health and disease, unraveling positive selection for cancer-causing mutations, a diversity of mutational processes, and large differences across individuals. Science , this issue p. 75 , p. 82 ; see also p. 34

Polycyclic aromatic hydrocarbons (PAHs) are one of the most prevalent classes of environmental pollutants resulting from the incomplete combustion of hydrocarbons. Exposure to PAHs is implicated in the pathogenesis of the cardiovascular disease, pulmonary disease, and even cancer. However, little is known about organ- and tissue-specific distribution patterns of PAHs in animals at macro-tissue and microscopic levels. Here, by combining GC-MS and single-molecule fluorescence microscopy (SMFM), we revealed the distribution characteristics of four different PAHs (phenanthrene (Phe), pyrene (Pyr), perylene (Per), and benzo[a]pyrene (BaP)) in atherosclerosis model mice (ApoE-KO mice) at macro-tissue and micro-region level after long-term oral exposure. Average PAH concentrations detected by GC-MS in seven tissues ranged from 6.44 to 441 ng/g. The gastrointestinal tract, epididymal fat pat, and lung accumulated higher levels of PAHs, whereas relatively lower PAH residuals were found in the liver, brain, and kidney. Correlation analysis showed that PAHs with higher molecular weight (r: −0.972 to −0.746), Log Kow (r: −0.984 to −0.746) and lower water solubility (r: 0.720 to 0.994) were less prone to bioaccumulate. For the first time, SMFM demonstrated a distinct heterogeneous distribution of Per in the tissue slices. More interestingly, we observed many micro-cluster regions, namely hotspots, showed much higher Per fluorescent intensity than the other common regions. In the area of atherosclerotic plaque, the Per hotspots were colocalized with the micro-regions with the most severe inflammatory response. The hotspots with very high enrichment in PAHs were likely to stimulate the local inflammation and cause excessive damage of the aorta, which resulted in a significant increase of the relative area of atherosclerosis lesion and aggravated atherosclerosis, as observed in PAH exposed mice.

Bioaccumulation of perylene in Escherichia coli and Staphylococcus aureus was visualized and quantified in real time with high sensitivity at high temporal resolution. For the first time, single-molecule fluorescence microscopy (SMFM) with a microfluidic flow chamber and temperature control has enabled us to record the dynamic process of perylene bioaccumulation in single bacterial cells and examine the cell-to-cell heterogeneity. Although with identical genomes, individual E. coli cells exhibited a high degree of heterogeneity in perylene accumulation dynamics, as shown by the high coefficient of variation (C.V = 1.40). This remarkable heterogeneity was exhibited only in live E. coli cells. However, the bioaccumulation of perylene in live and dead S. aureus cells showed similar patterns with a low degree of heterogeneity (C.V = 0.36). We found that the efflux systems associated with Tol C played an essential role in perylene bioaccumulation in E. coli, which caused a significantly lower accumulation and a high cell-to-cell heterogeneity. In comparison with E. coli, the Gram-positive bacteria S. aureus lacked an efficient efflux system against perylene. Therefore, perylene bioaccumulation in S. aureus was simply a passive diffusion process across the cell membrane.