Screening Organic Components and Toxicogenic Structures from Regional Fine Particulate Matters Responsible for Myocardial Fibrosis in Male Mice.

Numerous studies indicate that fine particulate matters (PM2.5) and its organic components are urgent risk factors for cardiovascular diseases (CVDs). Combining toxicological experiments, effect-directed analyses, and nontarget identification, this study aims to explore whether PM2.5 exposure in coal-combustion areas induces myocardial fibrosis and how to identify the effective organic components and their toxic structures to support regional risk control. First, we constructed an animal model of real-world PM2.5 exposure during the heating season and found that the exposure impaired cardiac systolic function and caused myocardial fibrosis, with chemokine Ccl2-mediated inflammatory response being the key cause of collagen deposition. Then, using the molecular event as target coupled with two-stage chromatographic isolation and mass spectrometry analyses, we identified a total of 171 suspect organic compounds in the PM2.5 samples. Finally, using hierarchical characteristic fragment analysis, we predicted that 40 of them belonged to active compounds with 6 alert structures, including neopentane, butyldimethylamine, 4-ethylphenol, hexanal, decane, and dimethylaniline. These findings provide evidence for risk management and prevention of CVDs in polluted areas.

Research on Miniaturized UHF Sensing Technology for PD Detection in Power Equipment Based on Symmetric Cut Theory.

In answer to the demand for high sensitivity and miniaturization of ultra-high frequency (UHF) sensors for partial discharge (PD) detection in power equipment, this paper proposes research on miniaturized UHF-sensing technology for PD detection in power equipment based on symmetric cut theory. The symmetric cut theory is applied for the first time to the miniaturization of PD UHF sensors for power equipment. A planar monopole UHF sensor with a size of only 70 mm × 70 mm × 1.6 mm is developed using an exponential asymptotic feed line approach, which is a 50% size reduction. The frequency-response characteristics of the sensor are simulated, optimized and tested; the results show that the standing wave ratio of the sensor developed in this paper is less than 2 in the frequency band from 427 MHz to 1.54 GHz, and less than 5 in the frequency band from 300 MHz to 1.95 GHz; in the 300 MHz~1.5 GHz band; the maximum and average gains of the sensor E-plane are 4.76 dB and 1.02 dB, respectively. Finally, the PD simulation experiment platform for power equipment is built to test the sensor's sensing performance; the results show that the sensor can effectively detect the PD signals; the sensing sensitivity is improved by about 95% relative to an elliptical monopole UHF sensor.

Prenatal PM2.5 exposure impairs spatial learning and memory in male mice offspring: from transcriptional regulation to neuronal morphogenesis.

BACKGROUND: As one of the environmental risk factors for human health, atmospheric fine particulate matter (PM2.5) contributes to cognitive deterioration in addition to respiratory and cardiovascular injuries. Recently, increasing evidence implicates that PM2.5 inhalation can affect neurological functions in offspring, but the sex-specific outcomes and the underlying biological processes are largely unknown. OBJECTIVES: To observe the influence of prenatal PM2.5 exposure on cognitive performance in offspring, to elucidate the neuronal morphological alterations and possible transcriptional regulation based on mRNA-sequencing (mRNA-Seq) data after birth, and to determine the key components of PM2.5 contributing to the adverse effects. METHODS: Pregnant C57BL/6J mice were exposed to sterile saline or PM2.5 suspension. Morris water maze test was used to assess the cognitive function in weanling offspring. Microscopic observation was applied to detect neuronal morphogenesis in vivo and in vitro. The cortex tissues from male offspring were collected on postnatal days (PNDs) 1, 7, and 21 for mRNA-Seq analysis. The organic and inorganic components of PM2.5 were separated to assess their contributions using primary cultured neurons. RESULTS: Prenatal PM2.5 exposure impaired spatial learning and memory in weanling male mice, but not female mice. The sex-specific outcomes were associated with mRNA expression profiles of the cortex during postnatal critical windows, and the annotations in Gene Ontology (GO) of differentially expressed genes (DEGs) revealed that the exposure persistently disrupted the expression of genes involved in neuronal features in male offspring. Consistently, axonal growth impairment and dendritic complexity reduction were observed. Importantly, Homeobox A5 (Hoxa5), a critical transcription factor regulating all of the neuronal morphogenesis-associated hub genes on PNDs 1, 7, and 21, significantly decreased in the cortex of male offspring following PM2.5 exposure. In addition, both inorganic and organic components were harmful to axonal and dendritic growth, with organic components exhibiting stronger inhibition than inorganic ones. CONCLUSION: Prenatal PM2.5 exposure affected spatial learning and memory in male mice by disrupting Hoxa5-mediated neuronal morphogenesis, and the organic components, including polycyclic aromatic hydrocarbons (PAHs), posed more adverse effects than the inorganic components.

Bisphenol A Analogs Induce Cellular Dysfunction in Human Trophoblast Cells in a Thyroid Hormone Receptor-Dependent Manner: In Silico and In Vitro Analyses.

Bisphenol A (BPA) and its analogs are frequently detected in human daily necessities and environmental media. Placental thyroid hormone plays an important role in fetal development. Herein, we followed the adverse outcome pathway (AOP) to explore the toxic mechanisms of BPA and its analogs toward placental thyroid hormone receptor (TR). First, the TOX21 database was used, and the interactions between BPA analogs and the ligand-binding domains (LBDs) of two subtypes of TR (TRα and TRß) were subjected to in silico screening using molecular docking (MD) and molecular dynamics simulation (MDS). Fluorescence spectra and circular dichroism (CD) showed that BPA and its analogs interfere with TRs as a molecular initiation event (MIE), including static fluorescence quenching and secondary structural content changes in TR-LBDs. Key events (KEs) of the AOP, including the toxicity induced in placental chorionic trophoblast cells (HTR-8/SVneo) by an inverted U-shaped dose effect and changes in ROS levels, were tested in vitro. BPA, BPB, and BPAF significantly changed the expression level of TRß, and only BPAF significantly downregulated the expression level of TRα. In conclusion, our study contributes to the health risk assessment of BPA and its analogs regarding placental adverse outcomes (AOs).

Gestational exposure to NO2 aggravates placental senescence.

Placental senescence is a normal physiological process of placenta, while premature placental senescence has been confirmed to be associated with some adverse pregnancy complications. Epidemiological studies indicate that NO2 exposure can aggravate placental senescence which is represented by fibrosis and abnormal telomere homeostasis, etc. In this study, pregnant C57BL/6 mice were exposed to NO2 (2.5 ppm, 5 h/day) daily in a dynamic exposure chamber throughout the gestation period, and were sacrificed at embryonic day 13.5 (E13.5), E15.5 and E18.5. Placenta were harvested and conducted for histopathological examination and telomere evaluation. Our results showed that gestational NO2 exposure significantly aggravated placental fibrosis and calcification, and up-regulated the related bio-markers (connective tissue growth factor (Ctgf) and transforming growth factor-ß1 (Tgf-ß1)) at E18.5. In addition, gestational exposure to NO2 also activated senescence related pathway (p53/p21) at E18.5. Furthermore, gestational NO2 exposure significantly shortened telomere length at E18.5, and the expression of telomere homeostasis regulation genes telomeric repeat binding factor 1 (Trf1), protection of telomeres 1a (Pot1a) and Pot1b were significantly increased while telomerase reverse transcriptase (Tert) was suppressed after NO2 exposure at E13.5 or E18.5, respectively. Importantly, DNA methylation status of the 22nd at E13.5 and 32nd at E18.5 site in sub-telomeric region of chromosome 1 was significantly altered. Based on the above results, our present study indicated that gestational NO2 exposure could lead to premature placental senescence during the late trimester of pregnancy via aggravation of fibrosis and telomere length shortening regulated by telomere regulatory enzyme and DNA methylation.

Prenatal PM2.5 exposure contributes to neuronal tau lesion in male offspring mice through mitochondrial dysfunction-mediated insulin resistance.

The epidemiological evidence has linked prenatal exposure to fine particulate matter (PM2.5) pollution with neurological diseases in offspring. However, the biological process and toxicological mechanisms remain unclear. Tau protein is a neuronal microtubule-associated protein expressed in fetal brain and plays a critical role in mediating neuronal development. Aberrant expression of tau is associated with adverse neurodevelopmental outcomes. To study whether prenatal exposure to PM2.5 pollution induce tau lesion in mice offspring and elucidate the underlying pathogenic mechanism, we exposed pregnant mice to PM2.5 (3 mg/kg b.w.) by oropharyngeal aspiration every other day. The results indicate that prenatal PM2.5 exposure induced hyperphosphorylation of tau in the cortex of postnatal male offspring, which was accompanied by insulin resistance through the IRS-1/PI3K/AKT signaling pathway. Importantly, we further found that prenatal PM2.5 exposure induced mitochondrial dysfunction by disrupting mitochondrial ultrastructure and decreasing the expression of rate-limiting enzymes (CS, IDH2 and FH) in the Krebs cycle and the subunits of mitochondrial complex IV and V (CO1, CO4, ATP6, and ATP8) during postnatal neurodevelopment. The findings suggest that prenatal PM2.5 exposure could induce tauopathy-like changes in male offspring, in which mitochondrial dysfunction-induced insulin resistance might play an important role.

Maternal NO2 exposure disturbs the long noncoding RNA expression profile in the lungs of offspring in time-series patterns.

Gestation is a sensitive window to nitrogen dioxide (NO2) exposure, which may disturb fetal lung development and lung function later in life. Animal and epidemiological studies indicated that long noncoding RNAs (lncRNAs) participate in abnormal lung development induced by environmental pollutant exposure. In the present study, pregnant C57BL/6J mice were exposed to 2.5 ppm NO2 (mimicking indoor occupational exposure) or clean air, and lncRNAs expression profiles in the lungs of offspring mice were determined by lncRNA-seq on embryonic day 13.5 (E13.5), E18.5, postnatal day 1 (P1), and P14. The lung histopathology examination of offspring was performed, followed by weighted gene coexpression network analysis (WGCNA), prediction of lncRNAs-target genes, and the biological processes enrichment analysis of lncRNAs. Our results indicated that maternal NO2 exposure induced hypoalveolarization on P14 and differentially expressed lncRNAs showed a time-series pattern. Following WGCNA and enrichment analysis, 2 modules participated in development-related pathways. Importantly, the expressions of related genes were altered, some of which were confirmed to be related to abnormal vascular development and even lung diseases. The research points out that the maternal NO2 exposure leads to abnormal lung development in offspring that might be related to altered lncRNAs expression profiles with time-series-pattern.

Tebuconazole induces liver injury coupled with ROS-mediated hepatic metabolism disorder.

Tebuconazole, the most widely used fungicide, is reported to cause various environmental problems and have serious health risks in humans. Despite numerous advances in toxicity studies, its internal metabolic process and the underlying mechanisms have not been systemically studied. The present study administered low doses (0.02 g/kg bw and 0.06 g/kg bw) of tebuconazole to C57BL/6 mice in vivo. The high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was developed and validated to analyze the tebuconazole in different organs, and our data revealed that tebuconazole mainly accumulated in the liver and that histopathological damage were exhibited in this organ. Tebuconazole significantly dysregulated phase Ⅰ- and phase II-metabolizing enzymes, ATP-binding cassette (ABC) efflux transporters (Abcc2 and Abcc3) and fatty acid metabolism-related genes (Cdkn1a and Fasn), thereby directly causing liver hypertrophy and steatosis. Importantly, the excessive induction of reactive oxygen species (ROS) and oxidative stress partially accounted for the metabolic abnormalities mediated by tebuconazole. Moreover, these alterations were related to the abnormal transcriptional levels of peroxisome proliferator-activated receptor α (PPAR-α) and liver x receptor α (LXR-α), which were predicted to bind to tebuconazole via hydrogen bonding interactions. The current findings provide new insight into the molecular mechanisms of metabolic abnormalities induced by tebuconazole at low concentration, and are conducive to a better understanding of the environmental risk posed by this fungicide.

Maternal PM2.5 exposure and abnormal placental nutrient transport.

Epidemiological studies of human and animal experiments indicated that gestational exposure to atmospheric pollutants could be followed by the abnormal placental development. However, the effects of this exposure on the placental transportation for nutrients have not been systematically investigated. In this study, fine particulate matters (PM2.5) samples were collected in Taiyuan and pregnant rodent models were administered with 3 mg/kg b.w. PM2.5 by oropharyngeal aspiration every other day starting on embryonic day 0.5 (E0.5). Then the pregnant mice were sacrificed and their placentas were collected at different time points. The results showed that maternal PM2.5 exposure (MPE) disrupted the expression of proliferating cell nuclear antigen (PCNA) at all time points and inhibited the cell proliferation in placenta. Following that, the capacity for placental nutrient transport was impaired. The changes at E18.5 were observed most significantly, showing the altered mRNA expression of amino acid, long-chain polyunsaturated fatty acid (LCPUFA), glucose and folate transporters. In addition, the glycogen content was elevated at E18.5, and the triglyceride content was increased at E13.5 and E15.5 and decreased at E18.5 in the placenta after MPE. In a word, the adverse effect induced by MPE revealed that MPE led tothe disruption on the nutrient supply to the developing fetus via modulating the abundance of placental nutrient transporters (PNT).

The Role of Cyclooxygenases-2 in Benzo(a)pyrene-Induced Neurotoxicity of Cortical Neurons.

With the help of particulate matter, benzo(a)pyrene (BaP) has become a widely distributed environmental contaminant. In addition to the well-known carcinogenicity, a growing number of studies have focused on the neurotoxicity of BaP, especially on adverse neurobehavioral effects. However, the molecular modulating mechanisms remain unclear. In this paper, we confirmed that BaP exposure produced a neuronal insult via its metabolite benzo(a)pyrene diol epoxide (BPDE) on the primary cultured cortical neuron in vitro and mice in vivo models, and the effects were largely achieved by activating cyclooxygenases-2 (COX-2) enhancement. Also, the action of BaP on elevating COX-2 was initiated by BPDE firmly binding to the active pockets of COX-2, then followed by the production of prostaglandin E2 (PGE2) and upregulation of its EP2 and EP4 receptors, finally stimulating the cyclic adenosine monophosphate/protein kinase A (cAMP/PKA) signaling pathway. Our results reveal a mechanistic association underlying BaP exposure and increased risk for neurological dysfunction and clarify the ways to prevent and treat brain injuries in polluted environments.

Maternal Exposure to PM2.5 Affects Fetal Lung Development at Sensitive Windows.

Lung development continues from the embryonic period to adulthood. Previous epidemiological studies have noted that maternal exposure of atmospheric pollutants during the sensitive windows disturbed the lung development and increased the risk of lung diseases after birth, but the experimental evidence was insufficient. In the present study, we exposed plug-positive mice to PM2.5 (3 mg/kg b.w.) by oropharyngeal aspiration every other day, and intended to test whether maternal PM2.5 exposure affected prenatal lung development in the offspring. First, maternal PM2.5 exposure decreased embryo weight and crown-rump length at E18.5 but not in earlier developmental stages (E0-E16.5). Second, maternal PM2.5 exposure did not prevent lung-bud and tracheal specification, and did not cause abnormalities in branching morphogenesis, distal lung epithelium, and mesenchyme differentiation in earlier stages of lung development (E0-E16.5). However, the exposure significantly disturbed the distal lung epithelium and mesenchyme differentiation of lung, led to reduced intact rings of trachea, and suppressed the expression of lung development-related genes (Nkx2.1, Tbx4, Tbx5, and Sox9) at E18.5. Finally, we found that the exposure not only increased PM2.5-bound metal content (Pb and Cu) but also caused inflammatory response in the placenta, which transmitted from the mother to the fetus and contributed to the developmental abnormalities.

PM2.5 exposure induces age-dependent hepatic lipid metabolism disorder in female mice.

Particulate matter exposure has been described to elevate the risk of lung and cardiovascular diseases. An increasing number of recent studies have indicated positive correlations between PM2.5 (the fraction of airborne particles with an aerodynamic diameter less than 2.5 µm) exposure and the risk of liver diseases. However, research on the effects of PM2.5 exposure on liver fat synthesis, secretion, and clearance mechanisms under normal diet conditions is limited, and whether these effects are age-dependent is largely unknown. Female C57BL/6 mice at different ages (4 weeks (4 w), 4 months (4 m), and 10 months (10 m)) were treated with 3 mg/kg body weight of PM2.5 every other day for 4 weeks. Subsequently, the ultrastructural changes of liver, the expression of genes involved in oxidative damage and lipid metabolism in the liver were examined. Observation of hepatic ultrastructure showed more and larger lipid droplets in the livers of 4-week-old and 10-month-old mice exposed to PM2.5. Further analysis showed that PM2.5 exposure increased the expression of genes related to lipid synthesis, but decreased the expression of genes involved in lipid transport and catabolism in the livers of 10-month-old mice. Our findings suggest that exposure to PM2.5 disrupts the normal metabolism of liver lipids and induces lipid accumulation in the liver of female mice in an age-dependent manner, with older mice being more susceptible to PM2.5.

Ambient PM2.5 causes lung injuries and coupled energy metabolic disorder.

Ambient fine particulate matter (PM2.5) is a challenge to public health worldwide. Although increasing numbers of recent epidemiological studies have emphasized the critical role of PM2.5 in promoting respiratory diseases, the precise mechanism behind PM2.5-mediated lung obstruction remains obscure. In the present study, we analyzed lung structure and function and further investigated mitochondrial morphology and transcription-modulated energy metabolism in mice following PM2.5 aspiration. The results showed that PM2.5 exposure reduced pulmonary function and induced severe pathological alterations, including alveolar endothelial disruption and airway obstruction. Based on ultrastructural observations, we also found mitochondrial vacuolation and mitochondrial membrane rupture in alveolar type II epithelial cells. Importantly, the abnormality of mitochondrial structure was coupled with energy metabolism disorders, as evidenced by the decrease in ATP levels, the accumulation of pyruvate and lactate content, and the altered transcription of related genes. Moreover, the reduction in mitochondrial markers, including PGC-1α, NRF-1, and TFAM, were involved in mitochondrial dysfunction. These findings suggest that energy metabolic disorders and mitochondrial dysfunction may be the important contributors to pulmonary injuries in response to PM2.5 exposure, indicating possible targets for protection and therapy in polluted areas.

Atmospheric PM2.5 aspiration causes tauopathy by disturbing the insulin signaling pathway.

Epidemiological and toxicological studies have shown that ambient fine particulate matter (PM2.5) is a healthy risk factor for neurodegenerative diseases. Hyperphosphorylated tau is the common feature of numerous neurodegenerative diseases known as tauopathy, which could be inhibited by insulin stimulation. However, the effects of PM2.5 on tau protein injury by disturbing the insulin signaling pathway still need to be illuminated. In present study, male C57BL/6 J mice were administered with PM2.5 to determine whether PM2.5 inhalation can induce tauopathy via the insulin resistance (IR) related pathway (IRS-1/AKT/GSK-3ß signaling pathway). The results showed that PM2.5 treatment induced the generation of phosphorylated tau (P-tau) and contributed to the development of tauopathy because of the insulin signaling disorders in insulin targeting organs. As expected, the occurrence of central and peripheral IR and accompanying hyperinsulinemia aggravated the disturbance of the IRS-1/AKT/GSK-3ß signaling pathway. These observations indicated that PM2.5 exposure led to neurodegenerative tau lesion, and insulin signaling pathway might be a potential therapeutic target for tauopathy.

Exposure to Nitro-PAHs interfere with germination and early growth of Hordeum vulgare via oxidative stress.

Nitrated polycyclic aromatic hydrocarbons (Nitro-PAHs) as important organic pollutants are ubiquitous in the atmospheric environment, agricultural soils and aquatic environments to pose a severe polluting risk. However, little is known about the mechanism of Nitro-PAHs genotoxicity in plants. We analyzed seeds germination, seedlings growth, and toxicity mechanism following 1-Nitropyrene treatment in Hordeum vulgare. Our results reveal that 1-NP treatment could be an inhibited agent on seeds germination and growth of roots and shoots. Additionally, the reduction of mitotic index and the increasing frequency of micronucleus suggest that 1-NP may pose a potential risk of genotoxicity in the plant. We further clarify that O2- and H2O2 radicals contribute to 1-NP stimulation induced oxidative damage. Our study provides insights into the role of Nitro-PAHs exposure on growth processing toxicity and genotoxicity in plant and provided a useful reference for the surveillance and risk management of Nitro-PAHs in environments.

Maternal NO2 exposure induces cardiac hypertrophy in male offspring via ROS-HIF-1α transcriptional regulation and aberrant DNA methylation modification of Csx/Nkx2.5.

Maternal exposure to nitrogen dioxide (NO2) poses a risk for morbidity and mortality in infantile congenital heart diseases and even adult cardiovascular diseases. However, the experimental evidence supporting these effects is insufficient, and the related regulatory mechanisms are unknown. In the present study, we aimed to determine whether maternal NO2 exposure causes cardiac hypertrophy-related consequences in offspring, and if so, how these adverse effects occur in the postnatal heart. The results indicate that in mice, maternal NO2 exposure causes cardiac hypertrophy in male offspring. This altered phenotype was accompanied by increased expression of atrial natriuretic peptide, B-type natriuretic peptide, bone morphogenetic protein 10 and ß-myosin heavy chain and elevated activities of cardiomyocyte injury markers, including serum glutamate-oxaloacetate transaminase, lactate dehydrogenase and kinases creatine phosphokinase (CK-MB) in serum. The cardiac-specific transcription factor Csx/Nkx2.5 played an important role in the induction of cardiac hypertrophy and cardiomyocyte injury, and the action was associated with ROS-HIF-1α transcriptional regulation and DNA hypomethylation modification.

Comprehensive hippocampal metabolite responses to PM2.5 in young mice.

Fine particulate matter (PM2.5) exposure alters brain development, clinical cognition and behavior in childhood. Previous studies of this subject have mainly been epidemiological investigations or analyses of gene and protein levels; however, gas chromatography-mass spectrometry (GC-MS)-based metabolic profiling, which will help clarify the molecular mechanisms of susceptibility in PM2.5-induced neurotoxicity, is lacking. In the present study, C57BL/6 mice at different ages (4 weeks, 4 months and 10 months) received oropharyngeal aspiration of PM2.5 (3 mg/kg) every other day for 4 weeks. The Morris water maze showed that PM2.5 exposure caused deterioration of spatial learning and memory in young (4 week old) mice. In addition, the levels of several metabolites belonging to different metabolite classes were significantly changed by PM2.5 exposure in 4-week-old mice. Based on metabolic pathway analysis, we speculated that the decline in spatial learning and memory due to PM2.5 exposure may be directly or indirectly associated with hippocampal region-specific metabolic alterations involving energy metabolism (citric acid, succinic acid, malic acid, maltose and creatinine); cholesterol metabolism (desmosterol, lanosterol and campesterol); arachidonic acid metabolism (methyl arachidonic acid, nonanoic acid and linoleic acid); inositol phosphate metabolism (myo-inositol, myo-inositol-1-phosphate and methyl-phosphate) and aspartic acid metabolism (aspartic acid, asparagine and homoserine).

Sulfate Aerosols Promote Lung Cancer Metastasis by Epigenetically Regulating the Epithelial-to-Mesenchymal Transition (EMT).

Secondary inorganic aerosols (SIA), particularly sulfate aerosols, are central particulate matter (PM) constituents of severe haze formation in China and exert profound impacts on human health; however, our understanding of the mechanisms by which sulfate aerosols cause malignancy in lung carcinogenesis remains incomplete. Here, we show that exposure to secondary inorganic aerosols induced the invasion and migration of lung epithelial cells, and that (NH4)2SO4 exerted the most serious effects in vitro and promoted lung tumor metastasis in vivo. This action was associated with alterations of phenotype markers in the epithelial-to-mesenchymal transition (EMT), such as the up-regulation of fibronectin (Fn1) and the down-regulation of E-cadherin (E-cad). Hypoxia-inducible factor 1α (HIF-1α)-Snail signaling, regulated by the generation of reactive oxygen species (ROS), was involved in the (NH4)2SO4-induced EMT, and the potent antioxidant N-acetylcysteine (NAC) inhibited the activation of HIF-1α-Snail and blocked the EMT, cell invasion, and migration in response to (NH4)2SO4. Additionally, CpG hypermethylation in the E-cad promoter regions partly contributed to the (NH4)2SO4-regulated E-cad repression, and the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine (5-Aza) restored the (NH4)2SO4-induced down-regulation of E-cad. Our findings reveal a potential mechanistic basis for exploring the association between sulfate aerosol exposure and increased malignancy during lung carcinogenesis, and suggest new approaches for the treatment, improvement, and prevention of lung cancer resulting from sulfate aerosol exposure in severe haze-fog.

NF-κB-regulated microRNA-574-5p underlies synaptic and cognitive impairment in response to atmospheric PM2.5 aspiration.

BACKGROUND: PM2.5 (particulate matter ≤ 2.5 µm) is one of the leading environmental risk factors for the global burden of disease. Whereas increasing evidence has linked the adverse roles of PM2.5 with cardiovascular and respiratory diseases, limited but growing emerging evidence suggests that PM2.5 exposure can affect the nervous system, causing neuroinflammation, synaptic dysfunction and cognitive deterioration. However, the molecular mechanisms underlying the synaptic and cognitive deficits elicited by PM2.5 exposure are largely unknown. METHODS: C57BL/6 mice received oropharyngeal aspiration of PM2.5 (1 and 5 mg/kg bw) every other day for 4 weeks. The mice were also stereotaxically injected with ß-site amyloid precursor protein cleaving enzyme 1 (ß-secretase, BACE1) shRNA or LV-miR-574-5p lentiviral constructs in the absence or presence of PM2.5 aspiration at 5 mg/kg bw every other day for 4 weeks. Spatial learning and memory were assessed with the Morris water maze test, and synaptic function integrity was evaluated with electrophysiological recordings of long-term potentiation (LTP) and immunoblot analyses of glutamate receptor subunit expression. The expression of α-secretase (ADAM10), BACE1, and γ-secretase (nicastrin) and the synthesis and accumulation of amyloid ß (Aß) were measured by immunoblot and enzyme-linked immunosorbent assay (ELISA). MicroRNA (miRNA) expression was screened with a microRNA microarray analysis and confirmed by real-time quantitative reverse transcription PCR (qRT-PCR) analysis. Dual-luciferase reporter gene and chromatin immunoprecipitation (ChIP) analyses were used to detect the binding of miR-574-5p in the 3'UTR of BACE1 and NF-κB p65 in the promoter of miR-574-5p, respectively. RESULTS: PM2.5 aspiration caused neuroinflammation and deteriorated synaptic function integrity and spatial learning and memory, and the effects were associated with the induction of BACE1. The action was mediated by NF-κB p65-regulated downregulation of miR-574-5p, which targets BACE1. Overexpression of miR-574-5p in the hippocampal region decreased BACE1 expression, restored synaptic function, and improved spatial memory and learning following PM2.5 exposure. CONCLUSIONS: Taken together, our findings reveal a novel molecular mechanism underlying impaired synaptic and cognitive function following exposure to PM2.5, suggesting that miR-574-5p is a potential intervention target for the prevention and treatment of PM2.5-induced neurological disorders.

A comparison of the toxicity of landfill leachate exposure at the seed soaking and germination stages on Zea mays L. (maize).

To compare the toxicity of landfill leachate exposure at the early stages of seed soaking and germination on maize, a field experiment was conducted to evaluate the physiological aspects of growth, yield and potential clastogenicity of root-tip cells. The maizes were treated with leachate at levels of 2%, 10%, 20%, 30% or 50% (V/V). First, the change of physiological indexes, including chlorophyll (Chl), Malondialdehyde (MDA) and Reactive oxygen species (ROS) levels, combined with yield all showed that soaking with leachate, but not germination, generated a greater ecological risk on maize. After a soaking treatment of maize with 50% leachate, the Chl, MDA and ROS levels during a vigorous growth period were 47.3%, 149.8% and 309.7%, respectively, of the control, whereas the yield decreased to 68.6% of the control. In addition, our results demonstrated that the leachate at lower levels could promote growth. This is mainly embodied in that the yield of maize treated with 10% leachate at the soaking stage increased to 116.0% of the control. Moreover, the cytological analysis experiment also demonstrated that the ecological risk of leachate still exists in both cases. Furthermore, the gray relational analysis showed that the ear row number and tassel branch number were the major factors affecting the yield of maize treated with 50% leachate at the stages of soaking and germination, respectively. In general, these results are helpful in understanding the phytotoxicity of leachate, which provides additional reference data for risk assessment and management of leachate.