Plant biochemistry influences tropospheric ozone formation, destruction, deposition, and response.

Tropospheric ozone (O3) is among the most damaging air pollutant to plants. Plants alter the atmospheric O3 concentration in two distinct ways: (i) by the emission of volatile organic compounds (VOCs) that are precursors of O3; and (ii) by dry deposition, which includes diffusion of O3 into vegetation through stomata and destruction by nonstomatal pathways. Isoprene, monoterpenes, and higher terpenoids are emitted by plants in quantities that alter tropospheric O3. Deposition of O3 into vegetation is related to stomatal conductance, leaf structural traits, and the detoxification capacity of the apoplast. The biochemical fate of O3 once it enters leaves and reacts with aqueous surfaces is largely unknown, but new techniques for the tracking and identification of initial products have the potential to open the black box.

Prenatal exposure to ambient PM2.5 and its chemical constituents and child intelligence quotient at 6 years of age.

There are limited studies on the associations between prenatal exposure to constituents of fine particulate matter (PM2.5) and children's intelligence quotient (IQ). Our study aimed to explore the associations between prenatal PM2.5 and its six constituents and the IQ levels of 6-year-old children. We included 512 mother-child pairs. We used a satellite-based modelling framework to estimate prenatal PM2.5 and its six constituents (ammonium, sulfate, nitrate, organic carbon, soil dust, and black carbon). We assessed the children's IQ using the short form of the Wechsler Intelligence Scale. Perceptual Reasoning Index (PRI), Verbal Comprehension Index (VCI), and Full Scale IQ (FSIQ) scores were computed. The multiple informant model (MIM) was applied to explore the trimester specific effects of PM2.5 and its six constituents' exposure on children's PRI, VCI, and FSIQ. To examine whether the duration of breastfeeding and physical activity (PA) could modify the effects of PM2.5 on children's IQ, we stratified the analyses according to the duration of breastfeeding (≤6 and >6 months) and time of outdoor activities after school (≤2 and >2 h/week). The first trimester PM2.5 and its five constituents' exposures were inversely associated with FSIQ [ß = -1.34, 95 % confidence interval [CI] (-2.71, 0.04) for PM2.5] and PRI [ß = -2.18, 95 %CI (-3.80, -0.57) for PM2.5] in children. The associations were magnified among boys and those with less outdoor activities or shorter breastfeeding duration. Our results indicate that prenatal PM2.5 and several of its main constituents' exposure may disrupt cognitive development in children aged 6 years. More PA and longer breastfeeding duration may alleviate the detrimental effects of prenatal PM2.5 exposure on children's cognitive function.

Cardiac Autonomic Impacts of Bushfire Smoke-A Prospective Panel Study.

BACKGROUND: Air pollution is associated with cardiovascular disease and mortality. Most studies have focussed on urban or traffic-related pollution, and less is known about the impacts from bushfire smoke on cardiovascular autonomic function, although it is associated with increased sudden cardiac death and mortality. We sought to investigate its instantaneous and short-term impacts on heart rate variability (HRV). METHODS: Twenty-four (24)-hour Holter electrocardiography (ECG) was repeated twice (during bushfire [Phase 1] and then clean air [Phase 2]) in 32 participants from two Australian towns (Warburton and Traralgon, Victoria) surrounding planned burning areas. This was compared with 10 control participants in another town (Maffra, Victoria) with two clean air assessments during the same periods. The primary HRV parameters assessed were those assessing overall HRV (Standard Deviation of Normal-to-Normal intervals [SDNN]), long-term HRV (Standard Deviation of the Average of Normal Sinus-to-Normal Sinus intervals for each 5-minutes [SDANN]), low frequency [LF]) and short-term HRV (Root Mean Square of Successive Differences between N-N intervals [RMSSD], High Frequency [HF], LF:HF ratio). Average concentrations of particulate matter <2.5 µm in diameter (PM2.5) were measured at fixed site monitors in each location. RESULTS: Mean PM2.5 levels were significantly elevated during bushfire exposure in Warburton (96.5±57.7 µg/m3 vs 4.0±1.9 µg/m3, p<0.001) and Traralgon (12.6±4.9 µg/m3 vs 3.4±3.1 µg/m3, p<0.001), while it remained low in the control town, Maffra, in each phase (4.3±3.2 µg/m3 and 3.9±3.6 µg/m3, p=0.70). Although SDANN remained stable in controls, the exposed cohort showed significant worsening in SDANN during bushfire smoke exposure by 9.6±25.7ms (p=0.039). In univariable analysis, smoke exposure was significantly associated with higher ΔSDNN and ΔSDANN (p=0.03, p=0.01 exposed vs control). The association remained significant in ΔSDANN after adjusting for age, sex and cigarette smoking (p=0.02) and of borderline significance in ΔSDNN (p=0.06). CONCLUSIONS: Exposure to the bushfire smoke was independently associated with reduced overall and long-term HRV. Our findings suggest that imbalance in cardiac autonomic function is a key mechanism of adverse cardiovascular effects of bushfire smoke.

Metabolic and Lipid Alterations in Mice Brain Cortex after PM2.5 Exposure.

Fine particulate matter (PM2.5) has been reported to be associated with neurological disorders. However, the effects of PM2.5 on changes in metabolic and lipid profile of the brain are unclear. In this study, global metabolomics and lipidomics in mice cortex were investigated from the analyses by ultraperformance liquid chromatography-Orbitrap mass spectrometry. The partial least-squares discriminant analysis showed that the metabolite and lipid profiles were significantly altered by PM2.5 exposure. The changed metabolic pathways including alanine, aspartate, and glutamate metabolism, carnitine metabolism, and glycerophospholipid remodeling pathway were found to be associated with a neurodegenerative process according to their corresponding molecular mechanisms. Our results indicated that PM2.5 exposure could induce neurological damage.

Biomarkers of DNA Oxidation Products: Links to Exposure and Disease in Public Health Studies.

Environmental exposure can increase the production of reactive oxygen species and deplete cellular antioxidants in humans, resulting in oxidatively generated damage to DNA that is both a useful biomarker of oxidative stress and indicator of carcinogenic hazard. Methods of oxidatively damaged DNA analysis have been developed and used in public health research since the 1990s. Advanced techniques detect specific lesions, but they might not be applicable to complex matrixes (e.g., tissues), small sample volume, and large-scale studies. The most reliable methods are characterized by (1) detecting relevant DNA oxidation products (e.g., premutagenic lesions), (2) not harboring technical problems, (3) being applicable to complex biological mixtures, and (4) having the ability to process a large number of samples in a reasonable period of time. Most effort has been devoted to the measurements of 8-oxo-7,8-dihydro-2'-deoxyguanine (8-oxodG), which can be analyzed by chromatographic, enzymic, and antibody-based methods. Results from validation trials have shown that certain chromatographic and enzymic assays (namely the comet assay) are superior techniques. The enzyme-modified comet assay has been popular because it is technically simpler than chromatographic assays. It is widely used in public health studies on environmental exposures such as outdoor air pollution. Validated biomarker assays on oxidatively damaged DNA have been used to fill knowledge gaps between findings in prospective cohort studies and hazards from contemporary sources of air pollution exposures. Results from each of these research fields feed into public health research as approaches to conduct primary prevention of diseases caused by environmental or occupational agents.

In Utero Exposure to Fine Particles Decreases Early Birth Weight of Rat Offspring and TLR4/NF-κB Expression in Lungs.

Particulate matter (PM2.5) exposure is reported to have deleterious effects on health. Maternal PM2.5 exposure has been confirmed to damage the growth of somatic cells and enhance the incidence of chronic respiratory diseases in children. Here we aim to investigate the impact of in utero PM2.5 exposure on early birth weight and postnatal lung development. Pregnant Sprague-Dawley rats were administered PM2.5 (0.1, 0.5, 2.5, or 7.5 mg/kg) intraperitoneally every 3 days until birth. Maternal and birth outcomes and somatic growth were monitored. Lungs were collected on PND1 (where PND = postnatal day) and PND28; the lung wet-to-dry weight ratio (W/D) was analyzed, and reactive oxygen species (ROS) levels were measured. Expression of Toll-like receptor 4 (TLR4) and NF-κB were evaluated by Western blotting and quantitative RT-PCR. There were no significant intergroup differences for maternal outcomes; however, offspring exposed in utero to 2.5 and 7.5 mg/kg PM2.5 were significantly smaller in litter weight than the controls. In utero exposure to 2.5 and 7.5 mg/kg PM2.5 led to lower body weight after birth and disrupted lung development during infancy. ROS levels were significantly increased in the 7.5 mg/kg PM2.5 group. PM2.5-treated rats showed upregulated pulmonary expression of TLR4 and NF-κB. Maternal PM2.5 exposure enhances the risk of low birth weight and affects lung alveolar development. The underlying molecular mechanisms may involve TLR4/NF-κB signaling.

Impact of Hydrogen Sulfide on Mitochondrial and Bacterial Bioenergetics.

This review focuses on the effects of hydrogen sulfide (H2S) on the unique bioenergetic molecular machines in mitochondria and bacteria-the protein complexes of electron transport chains and associated enzymes. H2S, along with nitric oxide and carbon monoxide, belongs to the class of endogenous gaseous signaling molecules. This compound plays critical roles in physiology and pathophysiology. Enzymes implicated in H2S metabolism and physiological actions are promising targets for novel pharmaceutical agents. The biological effects of H2S are biphasic, changing from cytoprotection to cytotoxicity through increasing the compound concentration. In mammals, H2S enhances the activity of FoF1-ATP (adenosine triphosphate) synthase and lactate dehydrogenase via their S-sulfhydration, thereby stimulating mitochondrial electron transport. H2S serves as an electron donor for the mitochondrial respiratory chain via sulfide quinone oxidoreductase and cytochrome c oxidase at low H2S levels. The latter enzyme is inhibited by high H2S concentrations, resulting in the reversible inhibition of electron transport and ATP production in mitochondria. In the branched respiratory chain of Escherichia coli, H2S inhibits the bo3 terminal oxidase but does not affect the alternative bd-type oxidases. Thus, in E. coli and presumably other bacteria, cytochrome bd permits respiration and cell growth in H2S-rich environments. A complete picture of the impact of H2S on bioenergetics is lacking, but this field is fast-moving, and active ongoing research on this topic will likely shed light on additional, yet unknown biological effects.

Ambient sulfur dioxide could have an impact on testicular volume from a observational study on a population of infertile male.

BACKGROUND: The effect of ambient pollutants on the male reproductive system is controversial. This retrospective study investigated the effect of environmental pollutants on male reproductive health. METHODS: Male patients with primary infertility (n = 282) were identified from a single center between January 2016 and December 2017. Patients were physically examined for the presence of varicocele and for the volume of both testicles. Semen quality was measured in terms of the total sperm count, sperm concentration, and the percentage of sperm cells with motility and normal morphology. Data were acquired on the concentration of ambient pollutants, namely particulate matters of diameter < 2.5 µm, sulfur dioxide (SO2), nitrogen oxides (NOx), and ozone (O3), measured on daily and hourly basis, from the Environmental Protection Administration Executive Yuan, Taiwan. Individual exposure to pollutants was estimated based on the reported residential address of each participant. Statistical analysis indicated the effect of each pollutant on the testicular volume, sex hormone profile, and semen parameters. RESULTS: The mean ± standard deviation of age was 36.7 ± 7.3 years. The average sperm count and concentration were 41.9 million/mL and 34.1 million/mL, respectively. The mean levels of serum testosterone, follicle-stimulating hormone, and luteinizing hormone were 3.57 ± 1.68 ng/mL, 7.59 ± 6.3 IU/L, and 4.68 ± 3.49 IU/L, respectively. According to the multivariate linear regression model, NOx exposure was a risk factor for decreased sperm concentration and motility (p = 0.043 and 0.032). Furthermore, SO2 exposure was negatively associated and testicular volume (p < 0.01). CONCLUSIONS: NO2 and SO2 exposure were negatively associated with the seminal parameter and decreased testicular volume, respectively, in a population of men with infertility. However, additional prospective studies are needed to ascertain the cause-effect relation of current results.

Co-expression of Hsp70 Protein and Autophagy Marker Protein LC3 in A549 Cells and THP1 Cells Exposed to Nanoparticles of Air Pollution.

The ability of air particulate matter (PM) to cause reactive oxygen species-driven protein damage is associated with both COPD and lung cancer, but the mechanisms are unsettled. In this study, we investigated the co-expression of Hsp70 and the autophagy marker protein LC3 in A549 cells (alveolar epithelial cell line) and THP-1 cells (monocyte/macrophage cells) grown in media supplemented with 100 µg/mL of four types of PM: carbon black (CB), urban dust (UD), nanoparticulate CB (NPCB), and nanoparticulate CB coated with benzo(a)pyrene (NPCB-BaP). Fluorescent monoclonal antibodies and flow cytometry were used to assess the expression and co-expression of HSP70 and LC3 proteins. Hsp70 expression was significantly increased by all PM, while LC3 was decreased by CB in A549 cells, unchanged by CB and UD in THP-1 cells and increased by NPCB and NPCB-BaP in both cell types. All PMs increased the Hsp70/LC3 ratio in binary scatterplots; the relationship was positive and linear, which may reflect chaperone-dependent autophagy. The UD was the only PM type that affected the slopes of the spatial trend lines and altered binary patterns of Hsp70/LC3 distribution in THP1 cells. These findings provide an insight into the molecular mechanisms regulating proteostasis in PM-exposed cells through the chaperone-autophagy system in the cytoplasm.

Understanding the Functional Impact of VOC-Ozone Mixtures on the Chemistry of RNA in Epithelial Lung Cells.

Introduction: Ambient air pollution is associated with premature death caused by heart disease, stroke, chronic obstructive pulmonary disease (COPD), and lung cancer. Recent studies have suggested that ribonucleic acid (RNA) oxidation is a sensitive environment-related biomarker that is implicated in pathogenesis. Aims and Methods: We used a novel approach that integrated RNA-Seq analysis with detection by immunoprecipitation techniques of the prominent RNA oxidative modification 8-oxo-7,8-dihydroguanine (8-oxoG). Our goal was to uncover specific messenger RNA (mRNA) oxidation induced by mixtures of volatile organic compounds (VOCs) and ozone in healthy human epithelial lung cells. To this end, we exposed the BEAS-2B human epithelial lung cell line to the gas- and particle-phase products formed from reactions of 790 ppb acrolein (ACR) and 670 ppb methacrolein (MACR) with 4 ppm ozone. Results: Using this approach, we identified 222 potential direct targets of oxidation belonging to previously described pathways, as well as uncharacterized pathways, after air pollution exposures. We demonstrated the effect of our VOC-ozone mixtures on the morphology and actin cytoskeleton of lung cells, suggesting the influence of selective mRNA oxidation in members of pathways regulating physical components of the cells. In addition, we observed the influence of the VOC-ozone mixtures on metabolic cholesterol synthesis, likely implicated as a result of the incidence of mRNA oxidation and the deregulation of protein levels of squalene synthase (farnesyl-diphosphate farnesyltransferase 1 [FDFT1]), a key enzyme in endogenous cholesterol biosynthesis. Conclusions: Overall, our findings indicate that air pollution influences the accumulation of 8-oxoG in transcripts of epithelial lung cells that largely belong to stress-induced signaling and metabolic and structural pathways. A strength of the study was that it combined traditional transcriptome analysis with transcriptome-wide 8-oxoG mapping to facilitate the discovery of underlying processes not characterized by earlier approaches. Investigation of the processes mediated by air pollution oxidation of RNA molecules in primary cells and animal models needs to be explored in future studies. Our research has thus opened new avenues to further inform the relationship between atmospheric agents on the one hand and cellular responses on the other that are implicated in diseases.

Multicenter Ozone Study in oldEr Subjects (MOSES): Part 2. Effects of Personal and Ambient Concentrations of Ozone and Other Pollutants on Cardiovascular and Pulmonary Function.

INTRODUCTION: The Multicenter Ozone Study of oldEr Subjects (MOSES) was a multi-center study evaluating whether short-term controlled exposure of older, healthy individuals to low levels of ozone (O3) induced acute changes in cardiovascular biomarkers. In MOSES Part 1 (MOSES 1), controlled O3 exposure caused concentration-related reductions in lung function with evidence of airway inflammation and injury, but without convincing evidence of effects on cardiovascular function. However, subjects' prior exposures to indoor and outdoor air pollution in the few hours and days before each MOSES controlled O3 exposure may have independently affected the study biomarkers and/or modified biomarker responses to the MOSES controlled O3 exposures. METHODS: MOSES 1 was conducted at three clinical centers (University of California San Francisco, University of North Carolina, and University of Rochester Medical Center) and included healthy volunteers 55 to 70 years of age. Consented participants who successfully completed the screening and training sessions were enrolled in the study. All three clinical centers adhered to common standard operating procedures and used common tracking and data forms. Each subject was scheduled to participate in a total of 11 visits: screening visit, training visit, and three sets of exposure visits consisting of the pre-exposure day, the exposure day, and the post-exposure day. After completing the pre-exposure day, subjects spent the night in a nearby hotel. On exposure days, the subjects were exposed for 3 hours in random order to 0 ppb O3 (clean air), 70 ppb O3, and 120 ppm O3. During the exposure period the subjects alternated between 15 minutes of moderate exercise and 15 minutes of rest. A suite of cardiovascular and pulmonary endpoints was measured on the day before, the day of, and up to 22 hours after each exposure.In MOSES Part 2 (MOSES 2), we used a longitudinal panel study design, cardiopulmonary biomarker data from MOSES 1, passive cumulative personal exposure samples (PES) of O3 and nitrogen dioxide (NO2) in the 72 hours before the pre-exposure visit, and hourly ambient air pollution and weather measurements in the 96 hours before the pre-exposure visit. We used mixed-effects linear regression and evaluated whether PES O3 and NO2 and these ambient pollutant concentrations in the 96 hours before the pre-exposure visit confounded the MOSES 1 controlled O3 exposure effects on the pre- to post-exposure biomarker changes (Aim 1), whether they modified these pre- to post-exposure biomarker responses to the controlled O3 exposures (Aim 2), whether they were associated with changes in biomarkers measured at the pre-exposure visit or morning of the exposure session (Aim 3), and whether they were associated with differences in the pre- to post-exposure biomarker changes independently of the controlled O3 exposures (Aim 4). RESULTS: Ambient pollutant concentrations at each site were low and were regularly below the National Ambient Air Quality Standard levels. In Aim 1, the controlled O3 exposure effects on the pre- to post-exposure biomarker differences were little changed when PES or ambient pollutant concentrations in the previous 96 hours were included in the model, suggesting these were not confounders of the controlled O3 exposure/biomarker difference associations. In Aim 2, effects of MOSES controlled O3 exposures on forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) were modified by ambient NO2 and carbon monoxide (CO), and PES NO2, with reductions in FEV1 and FVC observed only when these concentrations were "Medium" or "High" in the 72 hours before the pre-exposure visit. There was no such effect modification of the effect of controlled O3 exposure on any other cardiopulmonary biomarker.As hypothesized for Aim 3, increased ambient O3 concentrations were associated with decreased pre-exposure heart rate variability (HRV). For example, high frequency (HF) HRV decreased in association with increased ambient O3 concentrations in the 96 hours before the pre-exposure visit (-0.460 ln[ms2]; 95% CI, -0.743 to -0.177 for each 10.35-ppb increase in O3; P = 0.002). However, in Aim 4 these increases in ambient O3 were also associated with increases in HF and low frequency (LF) HRV from pre- to post-exposure, likely reflecting a "recovery" of HRV during the MOSES O3 exposure sessions. Similar patterns across Aims 3 and 4 were observed for LF (the other primary HRV marker), and standard deviation of normal-to-normal sinus beat intervals (SDNN) and root mean square of successive differences in normal-to-normal sinus beat intervals (RMSSD) (secondary HRV markers).Similar Aim 3 and Aim 4 patterns were observed for FEV1 and FVC in association with increases in ambient PM with an aerodynamic diameter ≤ 2.5 µm (PM2.5), CO, and NO2 in the 96 hours before the pre-exposure visit. For Aim 3, small decreases in pre-exposure FEV1 were significantly associated with interquartile range (IQR) increases in PM2.5 concentrations in the 1 hour before the pre-exposure visit (-0.022 L; 95% CI, -0.037 to -0.006; P = 0.007), CO in the 3 hours before the pre-exposure visit (-0.046 L; 95% CI, -0.076 to -0.016; P = 0.003), and NO2 in the 72 hours before the pre-exposure visit (-0.030 L; 95% CI, -0.052 to -0.008; P = 0.007). However, FEV1 was not associated with ambient O3 or sulfur dioxide (SO2), or PES O3 or NO2 (Aim 3). For Aim 4, increased FEV1 across the exposure session (post-exposure minus pre-exposure) was marginally significantly associated with each 4.1-ppb increase in PES O3 concentration (0.010 L; 95% CI, 0.004 to 0.026; P = 0.010), as well as ambient PM2.5 and CO at all lag times. FVC showed similar associations, with patterns of decreased pre-exposure FVC associated with increased PM2.5, CO, and NO2 at most lag times, and increased FVC across the exposure session also associated with increased concentrations of the same pollutants, reflecting a similar recovery. However, increased pollutant concentrations were not associated with adverse changes in pre-exposure levels or pre- to post-exposure changes in biomarkers of cardiac repolarization, ST segment, vascular function, nitrotyrosine as a measure of oxidative stress, prothrombotic state, systemic inflammation, lung injury, or sputum polymorphonuclear leukocyte (PMN) percentage as a measure of airway inflammation. CONCLUSIONS: Our previous MOSES 1 findings of controlled O3 exposure effects on pulmonary function, but not on any cardiovascular biomarker, were not confounded by ambient or personal O3 or other pollutant exposures in the 96 and 72 hours before the pre-exposure visit. Further, these MOSES 1 O3 effects were generally not modified, blunted, or lessened by these same ambient and personal pollutant exposures. However, the reductions in markers of pulmonary function by the MOSES 1 controlled O3 exposure were modified by ambient NO2 and CO, and PES NO2, with reductions observed only when these pollutant concentrations were elevated in the few hours and days before the pre-exposure visit. Increased ambient O3 concentrations were associated with reduced HRV, with "recovery" during exposure visits. Increased ambient PM2.5, NO2, and CO were associated with reduced pulmonary function, independent of the MOSES-controlled O3 exposures. Increased pollutant concentrations were not associated with pre-exposure or pre- to post-exposure changes in other cardiopulmonary biomarkers. Future controlled exposure studies should consider the effect of ambient pollutants on pre-exposure biomarker levels and whether ambient pollutants modify any health response to a controlled pollutant exposure.

Combined toxic effects of CBNPs and Pb on rat alveolar macrophage apoptosis and autophagy flux.

Carbon black (CB) and heavy metals are the main components of Particulate Matter (PM). Although the individual toxicities of CB and heavy metals have been extensively studied, the combined toxicity is much less understood. In this study, we choose the nano carbon black (CBNPs) and Pb2+ to simulate fine particles in the atmosphere and study the combined toxic effect on rat alveolar macrophages. The data showed that CBNPs could adsorb Pb2+ to form CBNPs-Pb2+ complex and displayed an altered physical properties by particle characterization. CBNPs-Pb2+ synergistically induced rat alveolar macrophages apoptosis and blocked autophagy flux compared with CBNPs and Pb2+ individually. Consistent with this, CBNPs-Pb2+ could impair the mitochondrial membrane potential (MMP), activate apoptotic signaling pathways, inhibit lysosomal function.

Hydrogen Sulfide Promotes Cell Proliferation and Melanin Synthesis in Primary Human Epidermal Melanocytes.

BACKGROUND/AIM: Hydrogen sulfide (H2S) has been found to act as a physiological intercellular messenger to regulate cell survival. In this study, we evaluated whether H2S could promote cell proliferation and melanin synthesis in human epidermal melanocytes (HEMs). METHODS: Primary HEMs were cocultured with sodium hydrosulfide (NaHS, the most widely used H2S donor) or endogenously overexpressed with cystathionine-γ-lyase (CSE) gene, which is the most predominant H2S-producing enzyme. Then, cell viability, intracellular melanin content, tyrosinase (TYR) activity, and expression of microphthalmia-associated transcription factor (MITF), TYR, together with TYR-related protein 1 (TRP-1) in both transcript and protein levels, were detected. RESULTS: We first confirmed that NaHS (10-100 µm) increased cell viability, intracellular melanin content, and TYR activity in a dose-dependent manner. Then, we found that endogenous H2S production also promoted cell proliferation, intracellular melanin content, and TYR activity. In addition, we observed the mRNA and protein expression of MITF, TYR, and TRP-1 was significantly up-regulated after NaHS treatment and CSE gene transfection. CONCLUSIONS: This study demonstrates that H2S promotes cell proliferation and melanin synthesis in HEMs, which indicates pharmacologic regulation of H2S may be potential treatment for skin disorders caused by loss of melanocytes or dysfunction of melanogenesis.

Crosstalk between Hydrogen Sulfide and Other Signal Molecules Regulates Plant Growth and Development.

Hydrogen sulfide (H2S), once recognized only as a poisonous gas, is now considered the third endogenous gaseous transmitter, along with nitric oxide (NO) and carbon monoxide (CO). Multiple lines of emerging evidence suggest that H2S plays positive roles in plant growth and development when at appropriate concentrations, including seed germination, root development, photosynthesis, stomatal movement, and organ abscission under both normal and stress conditions. H2S influences these processes by altering gene expression and enzyme activities, as well as regulating the contents of some secondary metabolites. In its regulatory roles, H2S always interacts with either plant hormones, other gasotransmitters, or ionic signals, such as abscisic acid (ABA), ethylene, auxin, CO, NO, and Ca2+. Remarkably, H2S also contributes to the post-translational modification of proteins to affect protein activities, structures, and sub-cellular localization. Here, we review the functions of H2S at different stages of plant development, focusing on the S-sulfhydration of proteins mediated by H2S and the crosstalk between H2S and other signaling molecules.

Hydrogen Sulfide Modulates Adult and Reparative Neurogenesis in the Cerebellum of Juvenile Masu Salmon, Oncorhynchus masou.

Fish are a convenient model for the study of reparative and post-traumatic processes of central nervous system (CNS) recovery, because the formation of new cells in their CNS continues throughout life. After a traumatic injury to the cerebellum of juvenile masu salmon, Oncorhynchus masou, the cell composition of the neurogenic zones containing neural stem cells (NSCs)/neural progenitor cells (NPCs) in the acute period (two days post-injury) changes. The presence of neuroepithelial (NE) and radial glial (RG) neuronal precursors located in the dorsal, lateral, and basal zones of the cerebellar body was shown by the immunohistochemical (IHC) labeling of glutamine synthetase (GS). Progenitors of both types are sources of neurons in the cerebellum of juvenile O. masou during constitutive growth, thus, playing an important role in CNS homeostasis and neuronal plasticity during ontogenesis. Precursors with the RG phenotype were found in the same regions of the molecular layer as part of heterogeneous constitutive neurogenic niches. The presence of neuroepithelial and radial glia GS+ cells indicates a certain proportion of embryonic and adult progenitors and, obviously, different contributions of these cells to constitutive and reparative neurogenesis in the acute post-traumatic period. Expression of nestin and vimentin was revealed in neuroepithelial cerebellar progenitors of juvenile O. masou. Patterns of granular expression of these markers were found in neurogenic niches and adjacent areas, which probably indicates the neurotrophic and proneurogenic effects of vimentin and nestin in constitutive and post-traumatic neurogenesis and a high level of constructive metabolism. No expression of vimentin and nestin was detected in the cerebellar RG of juvenile O. masou. Thus, the molecular markers of NSCs/NPCs in the cerebellum of juvenile O. masou are as follows: vimentin, nestin, and glutamine synthetase label NE cells in intact animals and in the post-traumatic period, while GS expression is present in the RG of intact animals and decreases in the acute post-traumatic period. A study of distribution of cystathionine ß-synthase (CBS) in the cerebellum of intact young O. masou showed the expression of the marker mainly in type 1 cells, corresponding to NSCs/NCPs for other molecular markers. In the post-traumatic period, the number of CBS+ cells sharply increased, which indicates the involvement of H2S in the post-traumatic response. Induction of CBS in type 3 cells indicates the involvement of H2S in the metabolism of extracellular glutamate in the cerebellum, a decrease in the production of reactive oxygen species, and also arrest of the oxidative stress development, a weakening of the toxic effects of glutamate, and a reduction in excitotoxicity. The obtained results allow us to consider H2S as a biologically active substance, the numerous known effects of which can be supplemented by participation in the processes of constitutive neurogenesis and neuronal regeneration.

LncRNA MALAT1, an lncRNA acting via the miR-204/ZEB1 pathway, mediates the EMT induced by organic extract of PM2.5 in lung bronchial epithelial cells.

Extensive cohort studies have explored the hazards of particulate matter with aerodynamic diameter 2.5 µm or smaller (PM2.5) to human respiratory health; however, the molecular mechanisms for PM2.5 carcinogenesis are poorly understood. Long non-coding RNAs (lncRNAs) are involved in various pathophysiological processes. In the present study, we investigated the effect of PM2.5 on the epithelial-mesenchymal transition (EMT) in lung bronchial epithelial cells and the underlying mechanisms mediated by an lncRNA. Organic extracts of PM2.5 from Shanghai were used to treat human bronchial epithelial cell lines (HBE and BEAS-2B). The PM2.5 organic extracts induced the EMT and cell transformation. High levels of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), mediated by NF-κB, were involved in the EMT process. For both cell lines, there was a similar response. In addition, MALAT1 interacted with miR-204 and reversed the inhibitory effect of its target gene, ZEB1, thereby contributing to the EMT and malignant transformation. In sum, these findings show that NF-κB transcriptionally regulates MALAT1, which, by binding with miR-204 and releasing ZEB1, promotes the EMT. These results offer an understanding of the regulatory network of the PM2.5-induced EMT that relates to the health risks associated with PM2.5.

Indoor PM2.5 from coal combustion aggravates ovalbumin-induced asthma-like airway inflammation in BALB/c mice.

We hypothesized that indoor PM2.5 exposure from coal combustion exaggerates airway inflammation in the lung tissue of asthmatic mice induced with ovalbumin (OVA). Forty BALB/c mice, randomly divided into four groups (n = 10 per group), were intratracheally instilled with normal saline alone, PM2.5 (2.5 mg/ml PM2.5 alone), OVA (15 µg/ml OVA alone), and PM2.5+OVA (2.5 mg/ml PM2.5 and 15 µg/ml OVA), respectively, four times at 2-wk intervals. Daily mean concentration of PM2.5 from indoor coal combustion was 156.95 µg/m3. The highest metal composition in PM2.5 was Zn (34.81 ± 1.8 µg/m3). Exposure to PM2.5+OVA significantly elevated IL-4 and decreased IFN-γ production in mice compared with the control (P < 0.05). Exposure to PM2.5+OVA showed a significant increase in the protein levels of granulocyte-macrophage colony-stimulating factor and IL-8 and a decrease in the protein level of transforming growth factor-ß1 in bronchoalveolar lavage fluid of mice compared with the control (P < 0.05). The expression of IL-4 mRNA was significantly increased, whereas the expression of IFN-γ mRNA was decreased in lung tissue of the PM2.5+OVA group (P < 0.05). The expression level of Foxp3 mRNA in the PM2.5+OVA group was significantly lower than that in the control group in lung tissue (P < 0.05). Treatment with PM2.5+OVA promoted a prominent neutrophil sequestration into the lung parenchyma, goblet cell proliferation, and severe inflammatory cell infiltration in the airways. Exposure to PM2.5 from indoor coal combustion might induce airway inflammatory immune responses and exacerbate peribronchiolar inflammation due to infiltration of inflammatory cells into the airway submucosa and airway structural pathological changes.

A fluorogenic H2S-triggered prodrug based on thiolysis of the NBD amine.

Based on thiolysis of the NBD amine, a H2S-triggered prodrug has been designed and synthesized for localized production of ciprofloxacin under micromolar H2S. Activation of the prodrug can be monitored through fluorescence in real-time. We envision that thiolysis of the NBD amine could be readily used for development of other H2S-triggered prodrugs in the future.

Role of supplemental UV-B in changing the level of ozone toxicity in two cultivars of sunflower: growth, seed yield and oil quality.

Ultraviolet-B radiation (UV-B) is inherent part of solar spectrum and tropospheric ozone (O3) is a potent secondary air pollutant. Therefore the present study was conducted to evaluate the responses of Helianthus annuus L. cvs DRSF 108 and Sungold (sunflower) to supplemental UV-B (sUV-B; ambient + 7.2 kJ m-2 d-1) and elevated ozone (O3; ambient + 10 ppb), given singly and in combination under field conditions using open-top chambers. The individual and interactive effects of O3 and sUV-B induced varying changes in both the cultivars of sunflower ranging from ultrastructural variations to growth, biomass, yield and oil composition. Reduction in leaf area of Sungold acted as a protective feature which minimized the perception of sUV-B as well as uptake of O3 thus led to lesser carbon loss compared to DRSF 108. Number- and weight of heads plant-1 decreased although more in Sungold with decline of oil content. Both the stresses when given singly and combination induced rancidification of oil and thus made the oil less suitable for human consumption.

Disentangling the effects of acidic air pollution, atmospheric CO2 , and climate change on recent growth of red spruce trees in the Central Appalachian Mountains.

In the 45 years after legislation of the Clean Air Act, there has been tremendous progress in reducing acidic air pollutants in the eastern United States, yet limited evidence exists that cleaner air has improved forest health. Here, we investigate the influence of recent environmental changes on the growth and physiology of red spruce (Picea rubens Sarg.) trees, a key indicator species of forest health, spanning three locations along a 100 km transect in the Central Appalachian Mountains. We incorporated a multiproxy approach using 75-year tree ring chronologies of basal tree growth, carbon isotope discrimination (∆13 C, a proxy for leaf gas exchange), and δ15 N (a proxy for ecosystem N status) to examine tree and ecosystem level responses to environmental change. Results reveal the two most important factors driving increased tree growth since ca. 1989 are reductions in acidic sulfur pollution and increases in atmospheric CO2 , while reductions in pollutant emissions of NOx and warmer springs played smaller, but significant roles. Tree ring ∆13 C signatures increased significantly since 1989, concurrently with significant declines in tree ring δ15 N signatures. These isotope chronologies provide strong evidence that simultaneous changes in C and N cycling, including greater photosynthesis and stomatal conductance of trees and increases in ecosystem N retention, were related to recent increases in red spruce tree growth and are consequential to ecosystem recovery from acidic pollution. Intrinsic water use efficiency (iWUE) of the red spruce trees increased by ~51% across the 75-year chronology, and was driven by changes in atmospheric CO2 and acid pollution, but iWUE was not linked to recent increases in tree growth. This study documents the complex environmental interactions that have contributed to the recovery of red spruce forest ecosystems from pervasive acidic air pollution beginning in 1989, about 15 years after acidic pollutants started to decline in the United States.