Mitochondria-Targetable Near-Infrared Fluorescent Probe for Visualization of Hydrogen Peroxide in Lung Injury, Liver Injury, and Tumor Models.

Hydrogen peroxide (H2O2) overexpressed in mitochondria has been regarded as a key biomarker in the pathological processes of various diseases. However, there is currently a lack of suitable mitochondria-targetable near-infrared (NIR) probes for the visualization of H2O2 in multiple diseases, such as PM2.5 exposure-induced lung injury, hepatic ischemia-reperfusion injury (HIRI), nonalcoholic fatty liver (NAFL), hepatic fibrosis (HF), and malignant tumor tissues containing clinical cancer patient samples. Herein, we conceived a novel NIR fluorescent probe (HCy-H2O2) by introducing pentafluorobenzenesulfonyl as a H2O2 sensing unit into the NIR hemicyanine platform. HCy-H2O2 exhibits good sensitivity and selectivity toward H2O2, accompanied by a remarkable "turn-on" fluorescence signal at 720 nm. Meanwhile, HCy-H2O2 has stable mitochondria-targetable ability and permits monitoring of the up-generated H2O2 level during mitophagy. Furthermore, using HCy-H2O2, we have successfully observed an overproduced mitochondrial H2O2 in ambient PM2.5 exposure-induced lung injury, HIRI, NAFL, and HF models through NIR fluorescence imaging. Significantly, the visualization of H2O2 has been achieved in both tumor-bear mice as well as surgical specimens of cancer patients, making HCy-H2O2 a promising tool for cancer diagnosis and imaging-guided surgery.

The Surface Confinement of FeO Assists in the Generation of Singlet Oxygen and High-Valent Metal-Oxo Species for Enhanced Fenton-Like Catalysis.

Transition metal compounds (TMCs) have long been potential candidate catalysts in persulfate-based advanced oxidation process (PS-AOPs) due to their Fenton-like catalyze ability for radical generation. However, the mechanism involved in TMCs-catalyzed nonradical PS-AOPs remains obscure. Herein, the growth of FeO on the Fe3O4/carbon precursor is regulated by restricted pyrolysis of MIL-88A template to activate peroxymonosulfate (PMS) for tetracycline (TC) removal. The higher FeO incorporation conferred a 2.6 times higher degradation performance than that catalyzed by Fe3O4 and also a higher interference resistance to anions or natural organic matter. Unexpectedly, the quenching experiment, probe method, and electron paramagnetic resonance quantitatively revealed that the FeO reassigned high nonradical species (1O2 and FeIV═O) generation to replace original radical system created by Fe3O4. Density functional theory calculation interpreted that PMS molecular on strongly-adsorbed (200) and (220) facets of FeO enjoyed unique polarized electronic reception for surface confinement effect, thus the retained peroxide bond energetically supported the production of 1O2 and FeIV═O. This work promotes the mechanism understanding of TMCs-induced surface-catalyzed persulfate activation and enables them better perform catalytic properties in wastewater treatment.

PM2.5-induced DNA oxidative stress in A549 cells and regulating mechanisms by GST DNA methylation and Keap1/Nrf2 pathway.

Fine particulate matter (PM2.5) increases the risks of lung cancer. Epigenetics provides a new toxicology mechanism for the adverse health effects of PM2.5. However, the regulating mechanisms of PM2.5 exposure on candidate gene DNA methylation changes in the development of lung cancer remain unclear. Abnormal expression of the glutathione S transferase (GST) gene is associated with cancer. However, the relationship between PM2.5 and DNA methylation-mediated GST gene expression is not well understood. In this study, we performed GST DNA methylation analysis and GST-related gene expression in human A549 cells exposed to PM2.5 (0, 50, 100 µg/mL, from Taiyuan, China) for 24 h (n = 4). We found that PM2.5 may cause DNA oxidative damage to cells and the elevation of GSTP1 promotes cell resistance to reactive oxygen species (ROS). The Kelch-1ike ECH-associated protein l (Keap1)/nuclear factor NF-E2-related factor 2 (Nrf2) pathway activates the GSTP1. The decrease in the DNA methylation level of the GSTP1 gene enhances GSTP1 expression. GST DNA methylation is associated with reduced levels of 5-methylcytosine (5mC), DNA methyltransferase 1 (DNMT1), and histone deacetylases 3 (HDAC3). The GSTM1 was not sensitive to PM2.5 stimulation. Our findings suggest that PM2.5 activates GSTP1 to defend PM2.5-induced ROS and 8-hydroxy-deoxyguanosine (8-OHdG) formation through the Keap1/Nrf2 signaling pathway and GSTP1 DNA methylation.

Regulation of PM2.5 on mitochondrial damage in H9c2 cells through miR-421/SIRT3 pathway and protective effect of miR-421 inhibitor and resveratrol.

Fine particulate matter (PM2.5) exposure is associated with cardiovascular disease (CVD) morbidity and mortality. Mitochondria are sensitive targets of PM2.5, and mitochondrial dysfunction is closely related to the occurrence of CVD. The epigenetic mechanism of PM2.5-triggered mitochondrial injury of cardiomyocytes is unclear. This study focused on the miR-421/SIRT3 signaling pathway to investigate the regulatory mechanism in cardiac mitochondrial dynamics imbalance in rat H9c2 cells induced by PM2.5. Results illustrated that PM2.5 impaired mitochondrial function and caused dynamics homeostasis imbalance. Besides, PM2.5 up-regulated miR-421 and down-regulated SIRT3 gene expression, along with decreasing p-FOXO3a (SIRT3 downstream target gene) and p-Parkin expression and triggering abnormal expression of fusion gene OPA1 and fission gene Drp1. Further, miR-421 inhibitor (miR-421i) and resveratrol significantly elevated the SIRT3 levels in H9c2 cells after PM2.5 exposure and mediated the expression of SOD2, OPA1 and Drp1, restoring the mitochondrial morphology and function. It suggests that miR-421/SIRT3 pathway plays an epigenetic regulatory role in mitochondrial damage induced by PM2.5 and that miR-421i and resveratrol exert protective effects against PM2.5-incurred cardiotoxicity.

Beyond Substituted p-Phenylenediamine Antioxidants: Prevalence of Their Quinone Derivatives in PM2.5.

Substituted para-phenylenediamine (PPD) antioxidants have been extensively used to retard oxidative degradation of tire rubber and were found to pervade multiple environmental compartments. However, there is a paucity of research on the environmental occurrences of their transformation products. In this study, we revealed the co-occurrence of six PPD-derived quinones (PPD-Qs) along with eight PPDs in fine particulate matter (PM2.5) from two Chinese megacities, in which N,N'-bis(1,4-dimethylpentyl)-p-phenylenediamine quinone (77PD-Q) was identified and quantified for the first time. Prevalent occurrences of these emerging PPD-Qs were found in Taiyuan (5.59-8480 pg/m3) and Guangzhou (3.61-4490 pg/m3). Significantly higher levels of PPDs/PPD-Qs were observed at a roadside site, implying the possible contribution of vehicle emissions. Correlation analysis implied potential consistencies in the fate of these PPD-Qs and suggested that most of them were originated from the transformation of their parent PPDs. For different subpopulation groups under different exposure scenarios, the estimated daily intakes of PPD-Qs (0.16-1.25 ng kgbw-1 day-1) were comparable to those of their parent PPDs (0.19-1.41 ng kgbw-1 day-1), suggesting an important but overlooked exposure caused by novel PPD-Qs. Given the prolonged exposure of these antioxidants and their quinone derivatives to traffic-relevant occupations, further investigations on their toxicological and epidemiological effects are necessary.

Study on antibiotics, antibiotic resistance genes, bacterial community characteristics and their correlation in the landfill leachates.

AIM: This study aimed to investigate the contamination levels of antibiotics and antibiotic resistance genes (ARGs) in the landfill leachates and their correlations with the bacteria. METHODS AND RESULTS: Using HPLC-MS, quantitative PCR and high-throughput sequencing, we measured the pollution levels of 14 antibiotics and 10 ARGs in the leachates of the landfill in Taiyuan, China, and analysed changes in the bacterial community and the correlations of bacteria with antibiotics and ARGs. The main results showed high levels of antibiotics (like enrofloxacin, pefloxacin and oxytetracycline) and ARGs (like sulfonamides, tetracycline, macrolides, quinolones and ß-lactam-resistance genes) in the landfill leachates, along with higher diversity and richness of the bacteria. Some types of antibiotics had positive correlations with their corresponding ARGs. The dominant bacteria in the landfill leachates were Pseudomonas, Defluviitoga and Sulfurimonas, which correlated with the antibiotics and ARGs and might have potential effects on degrading them. CONCLUSIONS: Antibiotics and ARG pollution existed in the landfill leachates, while bacteria were closely associated with them. SIGNIFICANCE AND IMPACT OF THE STUDY: It will provide helpful information for the potential application of the bacteria in antibiotics and ARGs pollution control and landfill leachate management.

Influence of COVID-19 lockdown on the variation of organic aerosols: Insight into its molecular composition and oxidative potential.

To prevent the transmission of the novel coronavirus disease 2019 (COVID-19), China adopted nationwide lockdown measures on January 25, 2020, leading to an evident diminution in the observed air pollutants. To investigate the influence of the lockdown on atmospheric chemistry, the specific molecular composition, oxidative potential of organic aerosols (OAs) in PM2.5 were studied using a high-resolution orbitrap mass spectrometry at a typical coal-combustion city, Linfen, in the North China Plain (NCP). The major air pollutants including PM2.5, PM10, SO2, NO2, and CO were observed to be diminished by 28.6-45.4%, while O3 was augmented by 52.5% during the lockdown compared to those before the lockdown. A significant decrease of oxygen-containing (CHO) compounds (24.7%) associated with anthropogenic acids was observed during the lockdown, implying a reduction in fossil fuel combustion. The coal-burning related sulfur-containing organosulfates (CHOS-) and nitrooxy-sulfates (CHONS-) have also shown attenuated in both their relative abundances and anthropogenic/biogenic ratios. Amine/amide-like CHON + components have decreased by 27.6%, while nitro/nitrooxy-containing CHON- compounds have only decreased by 7.1%. Multi-source nitrogen-containing (CHN) compounds have shown a moderate elimination of 24.0%, while the identified high-condensed azaarenes have fallen from 17.7% to 14.7%, implying a potential reduction in the health risk of OAs during quarantine. The measurement of OAs' oxidative potential through dithiothreitol (DTT) assay has confirmed that as it had dropped from 0.88 nmol min-1 m-3 to 0.80 nmol min-1 m-3. High correlations were observed between the abundance of OA subgroups with the concentration of PM2.5 after the execution of the lockdown, suggesting a potential elevation in the contribution of organic components to the total PM2.5 level. Our study provides insightful compositional and health-related information in the variation of OAs during the lockdown period and attests to the validity of joint-control strategy in controlling the level and health risks of numerous atmospheric pollutants.

An integrative analysis of miRNA and mRNA expression in the brains of Alzheimer's disease transgenic mice after real-world PM2.5 exposure.

Fine particulate matter (PM2.5) is associated with increased risks of Alzheimer's disease (AD), yet the toxicological mechanisms of PM2.5 promoting AD remain unclear. In this study, wild-type and APP/PS1 transgenic mice (AD mice) were exposed to either filtered air (FA) or PM2.5 for eight weeks with a real-world exposure system in Taiyuan, China (mean PM2.5 concentration in the cage was 61 µg/m3). We found that PM2.5 exposure could remarkably aggravate AD mice's ethological and brain ultrastructural damage, along with the elevation of the pro-inflammatory cytokines (IL-6 and TNF-α), Aß-42 and AChE levels and the decline of ChAT levels in the brains. Based on high-throughput sequencing results, some differentially expressed (DE) mRNAs and DE miRNAs in the brains of AD mice after PM2.5 exposure were screened. Using RT-qPCR, seven DE miRNAs (mmu-miR-193b-5p, 122b-5p, 466h-3p, 10b-5p, 1895, 384-5p, and 6412) and six genes (Pcdhgb8, Unc13b, Robo3, Prph, Pter, and Tbata) were evidenced the and verified. Two miRNA-target gene pairs (miR-125b-Pcdhgb8 pair and miR-466h-3p-IL-17Rα/TGF-ßR2/Aß-42/AChE pairs) were demonstrated that they were more related to PM2.5-induced brain injury. Results of Gene Ontology (GO) pathways and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways predicted that synaptic and postsynaptic regulation, axon guidance, Wnt, MAPK, and mTOR pathways might be the possible regulatory mechanisms associated with pathological response. These revealed that PM2.5-elevated pro-inflammatory cytokine levels and PM2.5-altered neurotransmitter levels in AD mice could be the important causes of brain damage and proposed the promising miRNA and mRNA biomarkers and potential miRNA-mRNA interaction networks of PM2.5-promoted AD.

High-Precision Automatic Calibration Modeling of Point Light Source Tracking Systems.

To realize high-precision and high-frequency unattended site calibration and detection of satellites, automatic direction adjustment must be implemented in mirror arrays. This paper proposes a high-precision automatic calibration model based on a novel point light source tracking system for mirror arrays. A camera automatically observes the solar vector, and an observation equation coupling the image space and local coordinate systems is established. High-precision calibration of the system is realized through geometric error calculation of multipoint observation data. Moreover, model error analysis and solar tracking verification experiments are conducted. The standard deviations of the pitch angle and azimuth angle errors are 0.0176° and 0.0305°, respectively. The root mean square errors of the image centroid contrast are 2.0995 and 0.8689 pixels along the x- and y-axes, respectively. The corresponding pixel angular resolution errors are 0.0377° and 0.0144°, and the comprehensive angle resolution error is 0.0403°. The calculated model values are consistent with the measured data, validating the model. The proposed point light source tracking system can satisfy the requirements of high-resolution, high-precision, high-frequency on-orbit satellite radiometric calibration and modulation transfer function detection.

Application of a real-ambient fine particulate matter exposure system on different animal models.

Simulation of fine particulate matter (PM2.5) exposure is essential for evaluating adverse health effects. In this work, an ambient exposure system that mimicked real atmospheric conditions was installed in Taiyuan, China to study impacts of chronic PM2.5 exposure on adult and aged mice as well as Sirtuin3 knockout (Sirt3 KO) mice and wild-type (WT) mice. The real-ambient exposure system eliminated the possible artificial effects caused from exposure experiments and maintained the physiochemical characteristics of PM2.5. The case studies indicated that aged mice exhibited apparent heart dysfunction involving increased heart rate and decreased blood pressure after 17-week of real-ambient PM2.5 exposure. Meanwhile, 15-week of real-ambient PM2.5 exposure decreased the heart rate and amounts of associated catecholamines to induce heart failure in Sirt3 KO mice. Additionally, the increased pro-inflammatory cytokines and decreased platelet related indices suggested that inflammation occurred. The changes of biomarkers detected by targeted metabolomics confirmed metabolic disorder in WT and Sirt3 KO mice after exposed to real-ambient PM2.5. These results indicated that the real-ambient PM2.5 exposure system could evaluate the risks of certain diseases associated with air pollution and have great potential for supporting the investigations of PM2.5 effects on other types of rodent models.

Fine particulate matter aggravates intestinal and brain injury and affects bacterial community structure of intestine and feces in Alzheimer's disease transgenic mice.

Fine particulate matter (PM2.5) was a risk factor for neurological disorders when emerging studies revealed that PM2.5 affected the bacterial community structure of gut in Alzheimer's disease (AD) patients. The purpose of this study was to explore the effects of PM2.5 on intestinal and brain injury and on bacterial community structure in the intestine and feces of APP/PS1 transgenic mice exposed to PM2.5 for eight weeks with a real-world whole-body inhalation exposure system in Taiyuan, China. The brain and intestinal tissues were collected to evaluate histopathological changes by HE staining. TNF-α and IL-6 levels in intestines, brains, and serums, and Aß-42 levels in brains were detected. Intestinal and fecal samples were subjected to 16S rRNA gene sequencing. Results showed that PM2.5 significantly aggravated the pathological injury in intestines and brains in AD mice with elevated pro-inflammatory cytokine levels. The estimators of Shannon, Simpson, Chao1, and ACE indexes reflected the diversity and richness of the bacterial community. Compared with the FA-WT group, the FA-AD group had lower diversity and richness when the PM2.5-AD group had the highest ones. PCA and NMDS revealed the specific influence of PM2.5 on the bacterial community of intestine and feces because that the PM2.5-FA and PM2.5-AD group clumped visibly closer than the other groups in both bacterial communities of intestine and feces. The KEGG pathway analysis predicted the vital functional genes and metabolic pathways in the bacterial community of PM2.5-AD mice. This study indicated the histopathological changes and inflammation in the intestine and brain were seriously caused in PM2.5-AD mice when the α-diversity of the bacterial community in intestine and feces was visibly changed.

The cellular effects of PM2.5 collected in Chinese Taiyuan and Guangzhou and their associations with polycyclic aromatic hydrocarbons (PAHs), nitro-PAHs and hydroxy-PAHs.

Numerous studies have demonstrated adverse effects on human health after exposure to fine particulate matter (PM2.5). However, it is still not clear how the toxicological effects and the health risks vary among PM samples of different compositions and concentrations. In this study, we examined effects of region- and season-dependent differences of PM2.5 on cytotoxicity, and the contributions of PAHs, nitro-PAHs (N-PAHs) and hydroxy-PAHs (OH-PAHs) to PM2.5 toxicity by determining different toxicological indicators in three lung cell lines. The results illustrated significant differences in components concentrations and biological responses elicited by PM2.5 collected in different cities and seasons. The concentrations of most PAHs, N-PAHs and OH-PAHs were much higher in Taiyuan than in Guangzhou. PM2.5 from Taiyuan exhibited lower cell viability and higher reactive oxygen species (ROS) and interleukin-6 (IL-6) release on lung cells than those from Guangzhou. Specifically, PM2.5 collected in summer from Taiyuan caused higher levels of pro-inflammatory responses and oxidative potential than those collected in winter. The correlation analysis between 19 PAHs, 17 N-PAHs and 12 OH-PAHs and the measured indicators demonstrated that PAHs were more related to PM2.5-induced CCK-8 cytotoxicity and IL-6 release in Taiyuan while N-PAHs and OH-PAHs were more related to PM2.5-induced CCK-8 cytotoxicity and dithiothreitol (DTT)-based redox activity in Guangzhou, suggesting that the toxicity of PM2.5 from Taiyuan was mostly correlated with PAHs while the toxicity of PM2.5 from Guangzhou was closely associated with N-PAHs and OH-PAHs. These results revealed that composition differences in PM2.5 from different regions and seasons significantly accounted for the differences of their toxicological effects.

GC-MS/MS analysis for source identification of emerging POPs in PM2.5.

Emerging POPs have received increasing attention due to their potential persistence and toxicity, but thus far the report regarding the occurrence and distribution of these POPs in PM2.5 is limited. In this study, an extremely sensitive and reliable method, using ultrasonic solvent extraction and silica gel purification followed by gas chromatography coupled with electron ionization triple quadrupole mass spectrometry, was developed and used for the trace analysis of hexachlorobutadiene (HCBD), pentachloroanisole (PCA) and its analogs chlorobenzenes (CBs) in PM2.5 from Taiyuan within a whole year. The limits of detection and limits of quantitation of analytes were 1.14 × 10-4‒2.74 × 10-4 pg m-3 and 3.80 × 10-4‒9.14 × 10-4 pg m-3. HCBD and PCA were detected at the mean concentrations of 3.69 and 1.84 pg m-3 in PM2.5, which is reported for the first time. Based on the results of statistical analysis, HCBD may come from the unintentional emission of manufacture or incineration of chlorinate-contained products but not coal combustion, while O3-induced photoreaction was the potential source of PCA in PM2.5. The temporal distributions of CBs in PM2.5 were closely related to coal-driven or agricultural activities. Accordingly, our study reveals the contamination profiles of emerging POPs in PM2.5 from Taiyuan.

Water soluble and insoluble components of PM2.5 and their functional cardiotoxicities on neonatal rat cardiomyocytes in vitro.

A growing number of epidemiological surveys show that PM2.5 is an important promoter for the cardiovascular dysfunction induced by atmospheric pollution. PM2.5 is a complex mixture of solid and liquid airborne particles and its components determine the health risk of PM2.5to a great extent. However, the individual cardiotoxicities of different PM2.5 fractions are still unclear, especially in the cellular level. Here we used the neonatal rat cardiomyocytes (NRCMs) to evaluate the cardiac toxicity of PM2.5 exposure. The cytotoxicities of Total-PM2.5, water soluble components of PM2.5 (WS-PM2.5) and water insoluble components of PM2.5 (WIS-PM2.5), which include the cell viability, cell membrane damage, reactive oxygen species (ROS) generation, were examined with NRCMs in vitro. The results indicated that Total-PM2.5 or WIS-PM2.5 exposure significantly decreased the cell viability, induced the cell membrane damage and increased the ROS level in NRCMs at concentrations above 50 µg/mL. However, WS-PM2.5 exposure could induce the cytotoxicity on NRCMs until the concentration of WS-PM2.5 was raised to a higher concentration (75 µg/mL). Furthermore, the DNA damage was detected in NRCMs after 48 h of exposure with Total-PM2.5, WS-PM2.5 or WIS-PM2.5 (75 µg/mL) and the adverse effects on mitochondrial function and action potentials of NRCMs were detected only both in the Total-PM2.5 and WIS-PM2.5 treatment group. In summary, our project not only estimates the risk of PM2.5 on cardiac cells but also reveal that Total-PM2.5 and WIS-PM2.5 exposure were predominantly associated with the functional cardiotoxicities in NRCMs.

Effects of tetrabromobisphenol A on maize (Zea mays L.) physiological indexes, soil enzyme activity, and soil microbial biomass.

TetrabromobisphenolA (TBBPA) is the most widely used brominated flame retardant, and it has the characteristics of persistent organic pollutants (POPs), attracting considerable attention. Many studies mainly focus on TBBPA toxicological effects in aquatic animals and rodents, but the ecotoxicology data of TBBPA on plant-soil system are limited so far. In this study, we assessed the impacts of TBBPA on maize (Zea mays L.) physiological indexes, soil enzyme activity, and soil microbial biomass at different concentrations of TBBPA (0, 0.75, 3.75, 7.5, 15, 37.5 and 75 mg·kg-1) and explored their relationships. Results showed that the maize physiological indexes and chlorophyll contents were significantly decreased by TBBPA, the activities of anti-oxidative enzymes including catalase (CAT), peroxidase (POD) and polyphenol oxidase (PPO) and the contents of malondialdehyde (MDA) were remarkably enhanced. Meanwhile, TBBPA activated the CAT, POD and PPO activities in soil. The low concentrations TBBPA promoted the activities of soil urease (S-UE), neutral phosphatase (S-PE) and increased the soil microbial biomass carbon (SMBC) and nitrogen (SMBN) while the high concentrations TBBPA suppressed them. Notably, the data indicated microbial biomass had respectively a significant correlation with CAT, PPO and S-UE in soil in the presence of TBBPA, and maize chlorophyll contents were associated with SMBN, CAT, and PPO. Taken together, TBBPA caused soil pollution, affected soil enzyme activities and microbial biomass, and hindered maize growth under the current experimental condition, suggesting the interactions among maize growth, soil enzyme, soil microorganism in maize rhizosphere of TBBPA-polluted soils are very important aspects to comprehensively evaluate the ecotoxicological effects of TBBPA.

Fine Particulate Matter and Sulfur Dioxide Coexposures Induce Rat Lung Pathological Injury and Inflammatory Responses Via TLR4/p38/NF-κB Pathway.

Fine particulate matter (PM2.5) and sulfur dioxide (SO2) are 2 common air pollutants, but their toxicological effects of coexposure are still not fully clear. In this study, SO2 exposure (5.6 mg/m3) couldn't cause obvious inflammatory responses in rat lungs. The PM2.5 exposure (1.5 mg/kg body weight) increased inflammatory cell counts in bronchoalveolar lavage fluid (BALF) and some inflammation damage. Importantly, SO2 and PM2.5 (1.5, 6.0, and 24.0 mg/kg) coexposure induced pathological and ultrastructural damage and raised inflammatory cells in BALF compared with the control. Also, they significantly elevated the levels of pro-inflammatory cytokines, adhesion molecule, and nitric oxide (NO) and promoted the gene expression of nuclear factor kappa B (NF-κB), phosphorylated p38 (p-p38), and Toll-like receptor 4 (TLR4) in rat lungs treated with higher dose of PM2.5 (6.0 and 24.0 mg/kg) plus SO2 relative to the control or SO2 group, along with the decreased inhibitor of NF-κBα and increased inhibitor of NF-κB kinase ß expressions. The changes in the inflammatory markers in the presence of PM2.5 plus SO2 were not significant compared with the PM2.5 group. The results indicated that inflammatory injury and pathological and ultrastructural damage in rat lungs exposed to PM2.5 plus SO2 were involved in TLR4/p38/NF-κB pathway activation accompanied by oversecretion of pro-inflammatory cytokine, adhesion molecule, and NO. It provides more useful evidence to understand the possible toxicological mechanism that PM2.5 and SO2 copollution exacerbate lung disease.

The role of pro-/anti-inflammation imbalance in Aß42 accumulation of rat brain co-exposed to fine particle matter and sulfur dioxide.

Taiyuan is a center of coal-based electricity production and many chemicals industries, where mixtures of sulfur dioxide (SO2) and particulate matter may be more prominent. The focus of the present study was to determine if there is a link between adverse effects in the brain and the combined-exposure to SO2 and fine particulate matter (PM2.5). Rats were exposed alternately to PM2.5 with different dosages (1.5, 6.0 and 24.0 mg/kg body weight) and SO2 at the level of 5.6 mg/m3. The results showed that the combined exposure to PM2.5 and SO2 enhanced the mRNA expression and protein level of TNF-α and IL-6 in rat cortex and hippocampus relative to the control, SO2 and PM2.5 alone. Instead, TGF-ß1 mRNA and protein level were down-regulated in the brain. Additionally, PM2.5 at medium and/or high dose caused marked increase in Aß42 level and PM2.5 + SO2 induced further increase of Aß42 level in the cortex and hippocampus. It suggests that SO2 and PM2.5 can synergistically exert inflammation responses and induce Aß42 accumulation in the brain. Also, it is notable that the Aß42 accumulation of rat cortex and hippocampus were closely associated with pro-/anti-inflammatory cytokines ratio. These results clearly demonstrated that the combined exposure to PM2.5 and SO2 can induce the imbalance of pro-/anti-inflammatory cytokine, resulting in Aß42 accumulation of rat brain cortex and hippocampus.

Progression and inflammation of human myeloid leukemia induced by ambient PM2.5 exposure.

PM2.5 (aerodynamic diameter ≤2.5 µm) has been a dominating and ubiquitous air pollutant and has become a global concern. Emerging evidences suggest a positive correlation between PM2.5 and leukemia, but the underlying molecular mechanisms remain unclear and need to be elucidated. Here, we assessed the impacts of PM2.5 on the progression and inflammation of human myeloid leukemia at lower environmental doses and explored the possible pathway. We showed that PM2.5 exposure significantly induced the leukemia cell growth and enhanced the release of inflammatory mediators in both in vitro and in vivo models. Additionally, NF-κB p65 and p-STAT3 were activated in PM2.5-treated leukemia cells, with a concomitant increase in both ROS formation and NADPH oxidase expressions. Strikingly, the supplement of inhibitors, including NAC (ROS), PDTC (NF-κB), or WP1066 (STAT3), contributed to a decline in leukemia cell growth. Furthermore, enhanced expressions of inflammatory cytokines were attenuated by the addition of NAC or PDTC, but not affected by WP1066. This study demonstrates that PM2.5 promotes leukemia progression, identifies a potential intervention target, and provides further understanding of the detrimental effect of PM2.5 exposure on human health.

Effect of ambient PM(2.5) on lung mitochondrial damage and fusion/fission gene expression in rats.

Exposure to ambient fine particulate matter (PM2.5) increases the risk of respiratory disease. Although previous mitochondrial research has provided new information about PM toxicity in the lung, the exact mechanism of PM2.5-mediated structural and functional damage of lung mitochondria remains unclear. In this study, changes in lung mitochondrial morphology, expression of mitochondrial fission/fusion markers, lipid peroxidation, and transport ATPase activity in SD rats exposed to ambient PM2.5 at different dosages were investigated. Also, the release of reactive oxygen species (ROS) via the respiratory burst in rat alveolar macrophages (AMs) exposed to PM2.5 was examined by luminol-dependent chemiluminescence (CL). The results showed that (1) PM2.5 deposited in the lung and induced pathological damage, particularly causing abnormal alterations of mitochondrial structure, including mitochondrial swelling and cristae disorder or even fragmentation in the presence of higher doses of PM2.5; (2) PM2.5 significantly affected the expression of specific mitochondrial fission/fusion markers (OPA1, Mfn1, Mfn2, Fis1, and Drp1) in rat lung; (3) PM2.5 inhibited Mn superoxide dismutase (MnSOD), Na(+)K(+)-ATPase, and Ca(2+)-ATPase activities and elevated malondialdehyde (MDA) content in rat lung mitochondria; and (4) PM2.5 induced rat AMs to produce ROS, which was inhibited by about 84.1% by diphenyleneiodonium chloride (DPI), an important ROS generation inhibitor. It is suggested that the pathological injury observed in rat lung exposed to PM2.5 is associated with mitochondrial fusion-fission dysfunction, ROS generation, mitochondrial lipid peroxidation, and cellular homeostasis imbalance. Damage to lung mitochondria may be one of the important mechanisms by which PM2.5 induces lung injury, contributing to respiratory diseases.

Magnetic graphene composites as both an adsorbent for sample enrichment and a MALDI-TOF MS matrix for the detection of nitropolycyclic aromatic hydrocarbons in PM2.5.

A simple and rapid method that uses synthesized magnetic graphene composites as both an adsorbent for enrichment and as a matrix in MALDI-TOF MS analysis was developed for the detection of nitropolycyclic hydrocarbons (nitro-PAHs) in PM2.5 samples. Three nitro-PAHs were detected down to sub pg µL(-1) levels based on calculations from an instrumental signal-to-noise better than 3, which shows the feasibility of using the new materials in MALDI-TOF MS as a potential powerful analytical approach for the analysis of nitro-PAHs in PM2.5 samples.