A case study on occupational exposure assessment and characterization of particles in a printing shop in China.

Printers can release numerous particles to contaminate indoor environments and pose health risks. Clarifying the exposure level and physicochemical properties of printer-emitted particles (PEPs) will help to evaluate the health risks of printer operator. In our study, the particles concentration in the printing shop was monitored in real time for a long time (12 h/day, total 6 days), and the PEPs were collected to characterize their physicochemical properties including shape, size and compositions. The result showed that the concentration of PEPs is closely related to the printing workload and the highest particle mass concentration of PM10 and PM2.5 was 212.73 µg m-3 and 91.48 µg m-3, respectively. The concentration of PM1 in the printing shop was in the range of 11.88-80.59 µg m-3 for mass value, and 174.83-1348.84 P cm-3 for count value which changed with the printing volume. The particle sizes of PEPs were less than 900 nm, 47.99% of PEPs was less than 200 nm, and 14.21% of the particles were at the nanoscale. PEPs contained 68.92% organic carbon (OC), 5.31% elemental carbon (EC), 3.17% metal elements, and 22.60% other inorganic additives, which contained more OC and metal elements than toners. Total polycyclic aromatic hydrocarbons (PAHs) levels were 18.95 ng/mg in toner and 120.70 ng/mg in PEPs. The carcinogenic risk of PAHs in PEPs was 1.40 × 10-7. These findings suggested future studies should pay more attention to the health effects of printing workers exposed to nanoparticles.

Protein phosphatase 2A-B56γ-Drp1-Rab7 signaling axis regulates mitochondria-lysosome crosstalk to sensitize the anti-cancer therapy of hepatocellular carcinoma.

Mitochondria-lysosome crosstalk is an intercellular communication platform regulating mitochondrial quality control (MQC). Activated dynamin-related protein 1 (Drp1) with phosphorylation at serine 616 (p-Drp1Ser616) plays a critical role in mitophagy-dependent cell survival and anti-cancer therapy for hepatocellular carcinoma (HCC). However, the underlying mechanisms that p-Drp1Ser616 involved in regulating mitochondria-lysosome crosstalk and mediating anti-HCC therapy remain unknown. HCC cells and mouse xenograft models were conducted to evaluate the relationship between p-Drp1Ser616 and Ras-associated protein 7 (Rab7) and the underlying mechanism by protein phosphatase 2A (PP2A)-B56γ regulating mitophagy via dephosphorylation of p-Drp1Ser616 in HCC. Herein, we found that Drp1 was frequently upregulated and was associated with poor prognosis in HCC. Mitochondrial p-Drp1Ser616 was a novel inter-organelle tethering protein localized to mitochondrion and lysosome membrane contact sites (MCSs) via interaction with Rab7 to trigger an increase in the mitochondria-lysosome crosstalk, resulting in PINK1-Parkin-dependent mitophagy and anti-apoptosis in HCC cells under the treatment of chemotherapy drugs. Moreover, we demonstrate that B56γ-mediated direct dephosphorylation of p-Drp1Ser616 inhibited mitophagy and thus increased mitochondria-dependent apoptosis. Overall, our findings demonstrated that activation of B56γ sensitizes the anti-cancer effect of HCC chemoprevention via dephosphorylated regulation of p-Drp1Ser616 in inhibiting the interaction between p-Drp1Ser616 and Rab7, which may provide a novel mechanism underlying the theranostics for targeting intervention in HCC.

The modifying effect of trait anxiety on the association of fine particulate matter with heart rate variability variables.

BACKGROUND: Previous studies have shown that exposures to ambient particulate matter with aerodynamic diameter <2.5 µm (PM2.5) and stress are associated with adverse cardiovascular health effects. OBJECTIVES: To investigate the potential modifying effect of trait anxiety on the association between short-term exposures to PM2.5 and HRV variables. METHODS: A panel of 92 middle-aged and elderly adults in Tianjin and Shanghai were recruited for repeated follow-ups with measurements of 24-h personal exposures to air pollutants and Holter ECG monitoring. Heart rate variability (HRV) variables calculated over 5-minute segments during the 24 h, including low frequency power (LF), high frequency power (HF), standard deviation of normal-to-normal intervals (SDNN) and root mean square of successive differences (rMSSD), were included in the analysis. The Trait Anxiety Inventory was used to investigate the long-term general anxiety level of the participants. Generalized linear mixed-effects model was used to analyze the association between exposure factors and HRV variables, and potential effect modification by trait anxiety. RESULTS: Data on 87 participants were included in final analysis after exclusions. Higher exposure to PM2.5 was associated with lower levels of LF, HF, SDNN and rMSSD, and the largest decreases in LF, HF, SDNN and rMSSD were found at 3-h moving average. Trait anxiety significantly modified the associations of PM2.5 with LF, HF, SDNN and rMSSD, with stronger inverse associations found in high trait anxiety group than in low trait anxiety group. For an IQR (27.3 µg/m³) increase in PM2.5 at 3-h moving average, there were decreases of 3.50% (95% CI: -4.46%, -2.54%) and 3.50% (95% CI: -4.49%, -2.50%) in the high trait anxiety group, and decreases of 0.81% (95% CI: -1.22%, -0.40%) and 0.65% (95% CI: -1.07%, -0.23%) in the low trait anxiety group in HF and rMSSD, respectively (both p for interaction<0.01). CONCLUSION: Our study suggests that trait anxiety could modify the association of short-term exposure to PM2.5 with HRV variables, indicating that higher trait anxiety may increase the cardiac susceptibility to air pollution in the study participants.

Ambient particulate air pollution, blood cell parameters, and effect modification by psychosocial stress: Findings from two studies in three major Chinese cities.

The associations between particulate matter (PM) exposure, psychosocial stress and blood cell parameters are bringing novel insights to characterize the early damage of multiple diseases. Based on two studies conducted in three Chinses cities using cross-sectional (Beijing, 425 participants) and panel study (Tianjin and Shanghai, 92 participants with 361 repeated measurements) designs, this study explored the associations between short-term exposure to ambient PM and blood cell parameters, and the effect modification by psychosocial stress. Increasing PM2.5 exposure was significantly associated with decreases in red blood cell (RBC) count and mean corpuscular hemoglobin concentration (MCHC), and increases in mean corpuscular volume (MCV), platelets count (PLT) and platelet hematocrit (PCT) in both studies. For instance, a 10 µg/m3 increment in PM2.5 concentration was associated with a 1.04% (95%CI: 0.16%, 1.92%) increase in PLT (4-d) and a 1.09% (95%CI: 0.31%, 1.87%) increase in PCT (4-d) in the cross-sectional study, and a 0.64% (95%CI: 0.06%, 1.22%) increase in PLT (1-d) and a 0.72% (95%CI: 0.33%, 1.11%) increase in PCT (1-d) in the panel study, respectively. In addition, stronger increases in MCV, PLT, and PCT associated with PM2.5 exposure were found in higher psychosocial stress group compared to lower psychosocial stress group (p for interaction <0.10), indicating that blood cell parameters of individuals with higher psychosocial stress might be more susceptible to the early damages of PM2.5 exposure.

Cardiorespiratory responses in healthy young adults with exposure to indoor airborne PAEs: A randomized, crossover trial of air purification.

BACKGROUND: Phthalic acid esters (PAEs) are widely used as plasticizers in industrial process and consumer products. Nowadays, PAEs are ubiquitous in the environment and are reported to be associated with cardiorespiratory diseases. However, studies about the association between indoor airborne PAEs exposure and cardiorespiratory health were limited, and the potential biological mechanism remains under-recognized. METHODS: A randomized crossover trial was conducted on 57 healthy young adults in Beijing. Repeated health measurements were performed under real and sham indoor air purification with a washout interval of at least 2 weeks. The concentration of indoor airborne PAEs were determined by gas chromatography-orbit ion trap mass spectrometry. Health indicators including blood pressure, lung function, airway inflammation, and circulating biomarkers reflecting blood coagulation and systematic oxidative stress were measured. Linear mixed-effect model was used to examine the between-treatment differences in health indicators, and three models including single-constituent, constituent-fine particulate matter (PM2.5) joint, and single-constituent residual model were used to estimate the association between indoor airborne PAEs and health indicators. RESULTS: The indoor airborne PAEs were reduced effectively under real air purification. The total indoor airborne di-2-ethylhexyl phthalate (DEHP), bis (4-Methyl-2-pentyl) phthalate (DMPP), diphenyl phthalate (DPP), and diethyl phthalate (DEP) were identified to be most significantly associated with the increase of blood pressure and airway inflammation, and decrease of lung function. A doubling increase in DEHP, DMPP, DPP, DEP was associated with the increase of 17.2% (95% CI: 3.9%, 32.2%), 11.7% (95% CI: 3.5%, 20.6%), 7.0% (95% CI: 2.4%, 11.8%), 6.0% (95% CI: 1.8%, 10.4%) in FeNO, respectively, in single-constituent residual model. Significant associations between specific total indoor airborne PAEs and increased levels of health biomarkers including oxidized low-density lipoprotein (ox-LDL), 8-isoprostane (8-isoPGF2α), and soluble P-selectin (sP-selectin) were observed. CONCLUSION: Indoor airborne PAEs may cause adverse cardiorespiratory health effects in young healthy adults, and indoor air purification could ameliorate the adverse cardiorespiratory effects.

Urinary metabolites of polycyclic aromatic hydrocarbons after short-term fine particulate matter exposure: A randomized crossover trial of air filtration.

Research on the relationship between short-term exposure to fine particulate matter (PM2.5) and urinary metabolites of polycyclic aromatic hydrocarbons (PAHs) is sparse in the nonoccupationally exposed populations. A quasi-experimental observation of haze events nested within a randomized crossover trial of alternative 1-week real or sham indoor air filtration was conducted to evaluate the associations of urinary monohydroxy-PAHs (OH-PAHs) with short-term exposure to PM2.5 and PM2.5-bound PAHs. The study was conducted among 57 healthy college students in Beijing, China. PM2.5-bound PAHs and urinary OH-PAHs were quantified using gas chromatography coupled with a triple-quadrupole tandem mass spectrometer. Linear mixed-effect models were applied to evaluate the association of urinary OH-PAHs with time-weighted personal PM2.5 and PM2.5-bound PAHs, controlling for potentially confounding variables. The results demonstrated that air filtration could markedly reduce external exposure to PM2.5 and PM2.5-bound parent, nitrated, and oxygenated PAHs. In the intervention trial, the urinary concentrations of 2-hydroxyfluorene (2-OH-FLU) and 9-hydroxyphenanthrene (9-OH-PHE) were elevated significantly by 16.5% (95% CI, 2.1%, 33.1%) and 37.9% (95% CI, 8.4%, 75.4%), respectively, in association with a doubling increase in personal PM2.5 exposure. Urinary 9-OH-PHE was also significantly positively associated with the increase in the sum of PM2.5-bound parent PAHs. Furthermore, the levels of urinary OH-PAHs such as 2-OH-FLU and 9-OH-PHE in the haze events were elevated by 31.1% (95% CI, 8.7%, 53.4%) and 73.5% (95% CI, 16.0%, 131.0%), respectively, in association with a doubling increase in personal PM2.5 exposure. The findings indicated that urinary 2-OH-FLU and 9-OH-PHE could serve as potential internal exposure biomarkers for assessing short-term PM2.5 exposure in nonoccupational populations.

Simultaneous analysis of typical halogenated endocrine disrupting chemicals and metal(loid)s in human hair.

Hair analysis has been an important approach in evaluating population exposure to various environmental factors. To meet the requirements of human environmental epidemiology studies, we aimed to develop an efficient method for simultaneous analysis of various metal(loid)s and some typical environmental halogenated endocrine disrupting chemicals (hEDCs) (i.e., polychlorinated biphenyls, polybrominated diphenyl ethers, and organochlorine pesticides, as well as some of their hydroxyl substituted metabolites) in a single hair sample. The hair was washed successively with surfactant solutions, methanol solvent, and deionized water to remove impurities attached to the hair surface. Efficiency was comprehensively compared among various washing strategies. The hair sample was further pulverized into fine powder with a median diameter (25th-75th percentile) of 8.6 (5.9-13.5) µm. The hair organic components were extracted by acetonitrile solvent and compared with the microwave-assisted extraction method. The hEDCs in the supernatant acetonitrile phase were quantified by gas chromatography-mass spectrometry, and the metal(loid)s in the precipitate hair were further analyzed by inductively coupled plasma mass spectrometry. Our developed method was further applied to analyze the hair samples of 165 pregnant women. The results showed that particles attached to the surface of the hair could not be washed off completely. However, we proposed a protocol framework to wash hair with relatively high efficience, which includes warm water incubation, and use of surfactant and organic solvent. The recoveries of the concerned hEDCs and metal(loid)s were overall in the range of 80% to 120%. For the women population, the method can efficiently recognize the typical exposure characteristics of the concerned hEDCs and metal(loid)s. Our study significantly ameliorated the deficiencies of the traditional hair washing strategy and developed an efficient method for simultaneous analysis of various metal(loid)s and hEDCs in a single hair sample. This method will provide important support for population complex exposure analysis and facilitate environmental exposome studies.

Drp1 and RB interaction to mediate mitochondria-dependent necroptosis induced by cadmium in hepatocytes.

Mitochondrial quality control (MQC) is implicated in cell death induced by heavy metal pollutants. Dynamin-related protein 1 (Drp1) regulates mitochondrial fission, which is an important part of MQC. Retinoblastoma (RB) protein can regulate MQC in a transcription-independent manner. Necroptosis plays a critical role in hepatic pathologies such as inflammatory, infectious, and xenobiotics-induced injury and diseases. We aimed to explore the role and mechanism of Drp1 interaction with RB in hepatocyte's necroptosis caused by cadmium (Cd). CdCl2 was employed to expose to Institute of Cancer Research (ICR) mice and human hepatic L02 cells. CdCl2 exposure induced necroptosis and hepatic injury both in vivo and in vitro. Moreover, Drp1 and RB protein were up-regulated and translocated to mitochondria in CdCl2-exposed hepatocytes. Inhibition of Drp1 with siRNA (siDNM1L) or inhibitors not only suppressed the RB expression and its mitochondrial translocation, but also alleviated MQC disorder, necroptosis, and hepatotoxicity caused by CdCl2. Moreover, blocking Drp1 with metformin rescued necroptosis and hepatic injury triggered by CdCl2. RB was proved to directly interact with Drp1 at mitochondria to form a complex which then bound to receptor interaction protein kinase (RIPK3) and enhanced the formation of necrosome after CdCl2 exposure. In summary, we found a new molecular mechanism of regulated cell death that Drp1 interacted with RB and promoted them mitochondrial translocation to mediate necroptosis and hepatic injury in hepatocytes induced by Cd-exposure. The mitochondrial Drp1-RB axis would be a novel target for the protection cells from xenobiotics triggering hepatic injury and diseases involved in necroptosis.