H2O2 negatively regulates aluminum resistance via oxidation and degradation of the transcription factor STOP1.

Aluminum (Al) stress triggers the accumulation of hydrogen peroxide (H2O2) in roots. However, whether H2O2 plays a regulatory role in aluminum resistance remains unclear. In this study, we show that H2O2 plays a crucial role in regulation of Al resistance, which is modulated by the mitochondrion-localized pentatricopeptide repeat protein REGULATION OF ALMT1 EXPRESSION 6 (RAE6). Mutation in RAE6 impairs the activity of complex I of the mitochondrial electron transport chain, resulting in the accumulation of H2O2 and increased sensitivity to Al. Our results suggest that higher H2O2 concentrations promote the oxidation of SENSITIVE TO PROTON RHIZOTOXICITY 1 (STOP1), an essential transcription factor that promotes Al resistance, thereby promoting its degradation by enhancing the interaction between STOP1 and the F-box protein RAE1. Conversely, decreasing H2O2 levels or blocking the oxidation of STOP1 leads to greater STOP1 stability and increased Al resistance. Moreover, we show that the thioredoxin TRX1 interacts with STOP1 to catalyze its chemical reduction. Thus, our results highlight the importance of H2O2 in Al resistance and regulation of STOP1 stability in Arabidopsis (Arabidopsis thaliana).

Association between ambient exposure to PM2.5 and upper aerodigestive tract cancer in Los Angeles.

Fine particulate matter (PM2.5 ) contains carcinogens similar to those generated by tobacco smoking, which may increase the risks of developing smoking-related cancers, such as upper aerodigestive track (UADT) cancers, for both smokers and never-smokers. Therefore, it is imperative to understand the relation between ambient PM2.5 exposure and risk of UADT cancers. A population-based case-control study involving 565 incident UADT cancer cases and 983 controls was conducted in Los Angeles County from 1999 to 2004. The average residential PM2.5 concentration 1 year before the diagnosis date for cases and the reference date for controls was assessed using a chemical transport model. The association between ambient PM2.5 and the UADT cancers was estimated by unconditional logistic regression, adjusting for confounders at the individual and block-group level. Stratified analyses were conducted by sex, tobacco smoking status and UADT subsites. We also assessed the interaction between PM2.5 and tobacco smoking on UADT cancers. PM2.5 concentrations were associated with an elevated odds of UADT cancers (adjusted odds ratio = 1.21 per interquartile range [4.5 µg/m3 ] increase; 95% confidence interval: 1.02, 1.44). The association between PM2.5 and UADT cancers was similar across UADT subsites, sex and tobacco smoking status. The interaction between PM2.5 and tobacco smoking on UADT cancers was approximately additive on the odds scale. The effect estimate for PM2.5 and UADT cancers was similar among never smokers. Our findings support the hypothesis that exposure to PM2.5 increases the risk of UADT cancers. Improvements in air quality may reduce the risk of UADT cancers.

Ambient exposure to fine particulate matter with oxidative potential affects oxidative stress biomarkers in pregnancy.

Prenatal exposures to ambient particulate matter (PM2.5) from traffic may generate oxidative stress, and thus contribute to adverse birth outcomes. We investigated whether PM2.5 constituents from brake and tire wear affect levels of oxidative stress biomarkers (malondialdehyde (MDA), 8-hydroxy-2'-deoxyguanosine (8-OHdG)) using urine samples collected up to three times during pregnancy in 156 women recruited from antenatal clinics at the University of California Los Angeles. Land use regression models with co-kriging were employed to estimate average residential outdoor concentrations of black carbon (BC), PM2.5 mass, PM2.5 metal components, and three PM2.5 oxidative potential metrics during the 4-weeks prior to urine sample collection. 8-OHdG concentrations in mid-pregnancy increased by 24.8% (95% CI: 9.0, 42.8) and 14.3% (95% CI: 0.4%, 30.0%) per interquartile range (IQR) increase in PM2.5 mass and BC, respectively. The brake wear marker (barium) and the oxidative potential metrics were associated with increased MDA concentration in the 1st sample collected (10-17 gestational week), but 95% CIs included the null. Traffic-related air pollution contributed in early to mid-pregnancy to oxidative stress generation previously linked to adverse birth outcomes.

Persistent Environmental Injustice due to Brake and Tire Wear Emissions and Heavy-Duty Trucks in Future California Zero-Emission Fleets.

The adoption of zero-emission vehicles (ZEVs) offers multiple benefits for the climate, air quality, and public health by reducing tailpipe emissions. However, the environmental justice implications of the nonexhaust emissions from future ZEV fleets for near-roadway communities remain unclear. Here, we model the on-road fine particulate matter (PM2.5) emissions across all California counties and assess the near-roadway exposure disparities at the census block group level in the Los Angeles County in 2050, when almost all passenger vehicles are projected to be ZEVs. We found that promoting zero-emission heavy-duty trucks generates more air quality benefits for disadvantaged communities than light-duty passenger vehicles. Persistent disparities in near-roadway PM2.5 levels, however, exist due to the remaining brake and tire wear emissions and increased truck traffic in disadvantaged communities. We recommend implementing fleet-specific ZEV policies to address brake and tire wear emissions and optimizing freight structures to address these persistent environmental justice issues in California.

Electronic and Tobacco Cigarettes Alter Polyunsaturated Fatty Acids and Oxidative Biomarkers.

[Figure: see text].

Association between gestational weight gain and preterm birth and post-term birth: a longitudinal study from the National Vital Statistics System database.

BACKGROUND: To evaluate the association between gestational weight gain (GWG) and preterm birth and post-term birth. METHODS: This longitudinal-based research studied singleton pregnant women from the National Vital Statistics System (NVSS) (2019). Total GWG (kg) was converted to gestational age-standardized z scores. The z-scores of GWG were divided into four categories according to the quartile of GWG, and the quantile 2 interval was used as the reference for the analysis. Univariate and multivariate logistic regression analyses were performed to investigate the association between GWG and preterm birth, post-term birth, and total adverse outcome (preterm birth + post-term birth). Subgroup analysis stratified by pre-pregnancy body mass index (BMI) was used to estimate associations between z-scores and outcomes. RESULTS: Of the 3,100,122 women, preterm birth occurred in 9.45% (292,857) population, with post-term birth accounting for 4.54% (140,851). The results demonstrated that low GWG z-score [odds ratio (OR): 1.04, 95% confidence interval (CI): 1.03 to 1.05, P < 0.001], and higher GWG z-scores (quantile 3: OR: 1.42, 95% CI: 1.41 to 1.44, P < 0.001; quantile 4: OR: 2.79, 95% CI: 2.76 to 2.82, P < 0.001) were positively associated with preterm birth. Low GWG z-score (OR: 1.18, 95% CI: 1.16 to 1.19, P < 0.001) was positively associated with an increased risk of post-term birth. However, higher GWG z-scores (quantile 3: OR: 0.84, 95% CI: 0.83 to 0.85, P < 0.001; quantile 4: 0.59, 95% CI: 0.58 to 0.60, P < 0.001) was associated with a decreased risk of post-term birth. In addition, low GWG z-score and higher GWG z-scores were related to total adverse outcome. A subgroup analysis demonstrated that pre-pregnancy BMI, low GWG z-score was associated with a decreased risk of preterm birth among BMI-obesity women (OR: 0.96, 95% CI: 0.94 to 0.98, P < 0.001). CONCLUSION: Our result suggests that the management of GWG may be an important strategy to reduce the number of preterm birth and post-term birth.

Aerosol Oxidative Potential in the Greater Los Angeles Area: Source Apportionment and Associations with Socioeconomic Position.

Oxidative potential (OP) has been proposed as a possible integrated metric for particles smaller than 2.5 µm in diameter (PM2.5) to evaluate adverse health outcomes associated with particulate air pollution exposure. Here, we investigate how OP depends on sources and chemical composition and how OP varies by land use type and neighborhood socioeconomic position in the Los Angeles area. We measured OH formation (OPOH), dithiothreitol loss (OPDTT), black carbon, and 52 metals and elements for 54 total PM2.5 samples collected in September 2019 and February 2020. The Positive Matrix Factorization source apportionment model identified four sources contributing to volume-normalized OPOH: vehicular exhaust, brake and tire wear, soil and road dust, and mixed secondary and marine. Exhaust emissions contributed 42% of OPOH, followed by 21% from brake and tire wear. Similar results were observed for the OPDTT source apportionment. Furthermore, by linking measured PM2.5 and OP with census tract level socioeconomic and health outcome data provided by CalEnviroScreen, we found that the most disadvantaged neighborhoods were exposed to both the most toxic particles and the highest particle concentrations. OPOH exhibited the largest inverse social gradients, followed by OPDTT and PM2.5 mass. Finally, OPOH was the metric most strongly correlated with adverse health outcome indicators.

A Review of Road Traffic-Derived Non-Exhaust Particles: Emissions, Physicochemical Characteristics, Health Risks, and Mitigation Measures.

Implementation of regulatory standards has reduced exhaust emissions of particulate matter from road traffic substantially in the developed world. However, nonexhaust particle emissions arising from the wear of brakes, tires, and the road surface, together with the resuspension of road dust, are unregulated and exceed exhaust emissions in many jurisdictions. While knowledge of the sources of nonexhaust particles is fairly good, source-specific measurements of airborne concentrations are few, and studies of the toxicology and epidemiology do not give a clear picture of the health risk posed. This paper reviews the current state of knowledge, with a strong focus on health-related research, highlighting areas where further research is an essential prerequisite for developing focused policy responses to nonexhaust particles.

Arachidonic acid metabolism and inflammatory biomarkers associated with exposure to polycyclic aromatic hydrocarbons.

Exposure to polycyclic aromatic hydrocarbons (PAHs) has been associated with systemic inflammation, yet what mechanisms regulate PAHs' inflammatory effects are less understood. This study evaluated the change of arachidonic acid (ARA) metabolites and inflammatory biomarkers in response to increased exposure to PAHs among 26 non-smoking healthy travelers from Los Angeles to Beijing. Traveling from Los Angeles to Beijing significantly increased urinary metabolites of dibenzofuran (800%), fluorene (568%), phenanthrene (277%), and pyrene (176%), accompanied with increased C-reactive protein, fibrinogen, IL-8, and IL-10, and decreased MCP-1, sCD40L, and sCD62P levels in the blood. Meanwhile, the travel increased the levels of ARA lipoxygenase metabolites that were positively associated with a panel of pro-inflammatory biomarkers. Concentrations of cytochrome P450 metabolite were also increased in Beijing and were negatively associated with sCD62P levels. In contrast, concentrations of ARA cyclooxygenase metabolites were decreased in Beijing and were negatively associated with anti-inflammatory IL-10 levels. Changes in both inflammatory biomarkers and ARA metabolites were reversed 4-7 weeks after participants returned to Los Angeles and were associated with urinary PAH metabolites, but not with other exposures such as secondhand smoke, stress, or diet. These results suggested possible roles of ARA metabolic alteration in PAHs-associated inflammatory effects.

Up-Regulation of SLC26A6 in Hepatocellular Carcinoma and Its Diagnostic and Prognostic Significance.

Hepatocellular carcinoma (HCC), is one of the most common malignancies worldwide, which is globally the third most common cause of cancer-related mortality. This study aims to identify new potential early-stage diagnostic and prognostic biomarker for HCC. The candidate gene SLC26A6 expression was analyzed based on the Oncomine and Tumor Immune Estimation Resource (TIMER) databases and verified forwards with Gene Expression Omnibus (GEO) datasets. The protein expression was retrieved from Human Protein Atlas (HPA) database. We also validated the diagnostic and prognostic value in HCC, and the relationship between SLC26A6 and clinicopathologic parameters were also accessed. The Gene Set Enrichment Analysis (GSEA) and Protein-Protein Interaction (PPI) network were constructed to analyze the SLC26A6-related pathway. These results reveal that SLC26A6 expression was elevated in HCC, and the diagnostic sensitivity of SLC26A6 was higher than α-fetoprotein (AFP). SLC26A6 expression was independent prognostic factor for HCC. SLC26A6 up-regulation was mainly associated with excision repair, DNA replication, etc. SLC26A6-related mR-NAs was enriched in PI3K-AKT signaling pathway, axon guidance, pathways in cancer, and so on. PPI network indicated that SLC26A6 was interacted with solute carrier members, ABC transporters and other ion transport molecule. We further analyzed three positively correlated microRNAs and 10 negatively correlated microRNAs, all of these were reported participating or inhibiting in cancer progression. This is the first study demonstrated that SLC26A6 is up-regulated in HCC and correlated with poor prognosis, which might be served as a diagnostic marker or prognostic biomarker for HCC.

Metabolomic Changes after Subacute Exposure to Polycyclic Aromatic Hydrocarbons: A Natural Experiment among Healthy Travelers from Los Angeles to Beijing.

Emerging epidemiological evidence has associated exposure to polycyclic aromatic hydrocarbons (PAHs) with chronic diseases including cardiometabolic diseases and neurodegeneration. However, little information is available about their subacute effects, which may accumulate over years and contribute to chronic disease development. To fill this knowledge gap, we designed a natural experiment among 26 healthy young adults who were exposed to elevated PAHs for 10 weeks after traveling from Los Angeles to Beijing in 2014 and 2015. Serum was collected before, during, and after the trip for metabolomics analysis. We identified 50 metabolites that significantly changed 6-8 weeks after the travel to Beijing (FDR < 5%). The network analysis revealed two main independent modules. Module 1 was allocated to oxidative homeostasis-related response and module 2 to delayed enzymatic deinduction response. Remarkably, the module 1 metabolites were recovered 4-7 weeks after participants' return, while the module 2 metabolites were not. Urinary hydroxylated PAHs were significantly associated with metabolites from both modules, while PAH carboxylic acids, likely metabolites of alkylated PAHs, were only associated with antioxidation-related metabolites. These results suggested differential subacute effects of unsubstituted and alkylated PAHs. Further studies are warranted to elucidate the role of the reversibility of metabolite changes in adverse health effects of PAHs.

Electronic cigarette aerosols induce oxidative stress-dependent cell death and NF-κB mediated acute lung inflammation in mice.

Electronic cigarette (e-cigarette) use has been linked to recent acute lung injury case clusters in over 2000 patients and dozens of deaths in the United States, however, the mechanism leading to lung injury is not certain although ultrafine particles, heavy metals, volatile organic compounds, and other harmful ingredients have been implicated. To systematically evaluate e-cigarette toxicity, we generated e-cigarette aerosols by varying the puff numbers (20-480), nicotine contents (0-24 mg/mL), and collected e-cigarette samples through an impinger system for biological assays. The calculated samples' concentration ranged from 1.96 to 47.06 mg/mL. THP-1 monocyte-differentiated macrophages, BEAS-2B bronchial epithelial cells, wild-type C57BL/6 mice, and NF-κB-luc transgenic mice were used to test the effects of these samples. E-cigarette samples showed cytotoxicity to THP-1 cells and BEAS-2B in vitro, leading to increased oxidative stress, inflammatory cytokine production with or without nicotine, and cell death. Furthermore, aerosol generated from PG is more toxic than VG. The toxicity of e-cigarette samples is at least partially due to the reactive oxygen species and aldehydes, which are generated during the aerosolization processes by the e-cigarette device. After NF-κB-luc mice exposed with e-cigarette samples by oropharyngeal aspiration, NF-κB expressions were observed in a dose-response fashion with or without nicotine. In addition, the e-cigarette samples induced neutrophil infiltration, IL-1ß production, oxidative stress marker heme oxygenase-1 expression in wild-type C57BL/6 mice. These results suggested that oxidative stress, pro-inflammatory NF-κB pathway activation, and cell death are involved in e-cigarette aerosol-induced acute lung inflammation.

Pro-Oxidative and Proinflammatory Effects After Traveling From Los Angeles to Beijing: A Biomarker-Based Natural Experiment.

BACKGROUND: Exposure to air pollution increases cardiovascular morbidity and mortality. Preventing chronic cardiovascular diseases caused by air pollution relies on detecting the early effects of pollutants on the risk of cardiovascular disease development, which is limited by the lack of sensitive biomarkers. We have previously identified promising biomarkers in experimental animals but comparable evidence in humans is lacking. METHODS: Air pollution is substantially worse in Beijing than in Los Angeles. We collected urine and blood samples from 26 nonsmoking, healthy adult residents of Los Angeles (mean age, 23.8 years; 14 women) before, during, and after spending 10 weeks in Beijing during the summers of 2014 and 2015. We assessed a panel of circulating biomarkers indicative of lipid peroxidation and inflammation. Personal exposure to polycyclic aromatic hydrocarbons (PAHs), a group of combustion-originated air pollutants, was assessed by urinary PAH metabolite levels. RESULTS: Urinary concentrations of 4 PAH metabolites were 176% (95% CI, 103% to 276%) to 800% (95% CI, 509% to 1780%) greater in Beijing than in Los Angeles. Concentrations of 6 lipid peroxidation biomarkers were also increased in Beijing, among which 5-, 12-, and 15-hydroxyeicosatetraenoic acid and 9- and 13-hydroxyoctadecadienoic acid levels reached statistical significance (false discovery rate <5%), but not 8-isoprostane (20.8%; 95% CI, -5.0% to 53.6%). The antioxidative activities of paraoxonase (-9.8%; 95% CI, -14.0% to -5.3%) and arylesterase (-14.5%; 95% CI, -22.3% to -5.8%) were lower and proinflammatory C-reactive protein (101%; 95% CI, 3.3% to 291%) and fibrinogen (48.3%; 95% CI, 4.9% to 110%) concentrations were higher in Beijing. Changes in all these biomarkers were reversed, at least partially, after study participants returned to Los Angeles. Changes in most outcomes were associated with urinary PAH metabolites (P<0.05). CONCLUSIONS: Traveling from a less-polluted to a more-polluted city induces systemic pro-oxidative and proinflammatory effects. Changes in the levels of 5-, 12-, and 15-hydroxyeicosatetraenoic acid and 9- and 13-hydroxyoctadecadienoic acid as well as paraoxonase and arylesterase activities in the blood, in association with exposures to PAH metabolites, might have important implications in preventive medicine as indicators of increased cardiovascular risk caused by air pollution exposure.

Ambient air pollution and cause-specific risk of hospital admission in China: A nationwide time-series study.

BACKGROUND: The impacts of air pollution on circulatory and respiratory systems have been extensively studied. However, the associations between air pollution exposure and the risk of noncommunicable diseases of other organ systems, including diseases of the digestive, musculoskeletal, and genitourinary systems, remain unclear or inconclusive. We aimed to systematically assess the associations between short-term exposure to main air pollutants (fine particulate matter [PM2.5] and ozone) and cause-specific risk of hospital admission in China over a wide spectrum of human diseases. METHODS AND FINDINGS: Daily data on hospital admissions for primary diagnosis of 14 major and 188 minor disease categories in 252 Chinese cities (107 cities in North China and 145 cities in South China) from January 1, 2013, to December 31, 2017, were obtained from the Hospital Quality Monitoring System of China (covering 387 hospitals in North China and 614 hospitals in South China). We applied a 2-stage analytic approach to assess the associations between air pollution and daily hospital admissions. City-specific associations were estimated with quasi-Poisson regression models and then pooled by random-effects meta-analyses. Each disease category was analyzed separately, and the P values were adjusted for multiple comparisons. A total of 117,338,867 hospital admissions were recorded in the study period. Overall, 51.7% of the hospitalized cases were male, and 71.3% were aged <65 years. Robust positive associations were found between short-term PM2.5 exposure and hospital admissions for 7 major disease categories: (1) endocrine, nutritional, and metabolic diseases; (2) nervous diseases; (3) circulatory diseases; (4) respiratory diseases; (5) digestive diseases; (6) musculoskeletal and connective tissue diseases; and (7) genitourinary diseases. For example, a 10-µg/m3 increase in PM2.5 was associated with a 0.21% (95% CI 0.15% to 0.27%; adjusted P < 0.001) increase in hospital admissions for diseases of the digestive system on the same day in 2-pollutant models (adjusting for ozone). There were 35 minor disease categories significantly positively associated with same-day PM2.5 in both single- and 2-pollutant models, including diabetes mellitus, anemia, intestinal infection, liver diseases, gastrointestinal hemorrhage, renal failure, urinary tract calculus, chronic ulcer of skin, and back problems. The association between short-term ozone exposure and respiratory diseases was robust. No safety threshold in the exposure-response relationships between PM2.5 and hospital admissions was observed. The main limitations of the present study included the unavailability of data on personal air pollution exposures. CONCLUSIONS: In the Chinese population during 2013-2017, short-term exposure to air pollution, especially PM2.5, was associated with increased risk of hospitalization for diseases of multiple organ systems, including certain diseases of the digestive, musculoskeletal, and genitourinary systems; many of these associations are important but still not fully recognized. The effect estimates and exposure-response relationships can inform policy making aimed at protecting public health from air pollution in China.

Plastin 1 drives metastasis of colorectal cancer through the IQGAP1/Rac1/ERK pathway.

Tumor metastasis is the dominant cause of death in colorectal cancer (CRC) patients, and it often involves dysregulation of various cytoskeletal proteins. Plastin 1 (PLS1) is an actin-bundling protein that has been implicated in the structure of intestinal epithelial microvilli; however, its role in CRC metastasis has not yet been determined. In this study, we demonstrated that PLS1 is highly expressed in 33.3% (45/135) of CRC patients and is correlated with lymph node metastasis and poor survival. In in vitro and in vivo experiments, PLS1 induced the migration and invasion of CRC cells and the metastases to the liver and lung in mice. Moreover, the expressions of key factors for CRC metastases, matrix metalloproteinase (MMP) 9 and 2, were enhanced by PLS1, which was dependent on phosphorylating ERK1/2 activated by IQGAP1/Rac1 signaling. The connection between these signals and PLS1 was further confirmed in CRC tissues of patients and the metastatic nodules from a mouse model. These findings suggest that PLS1 promotes CRC metastasis through the IQGAP1/Rac1/ERK pathway. Targeting PLS1 may provide a potential approach to inhibit the metastasis of CRC cells.

Effects of Electronic Cigarettes on Indoor Air Quality and Health.

With the rapid increase in electronic cigarette (e-cig) users worldwide, secondhand exposure to e-cig aerosols has become a serious public health concern. We summarize the evidence on the effects of e-cigs on indoor air quality, chemical compositions of mainstream and secondhand e-cig aerosols, and associated respiratory and cardiovascular effects. The use of e-cigs in indoor environments leads to high levels of fine and ultrafine particles similar to tobacco cigarettes (t-cigs). Concentrations of chemical compounds in e-cig aerosols are generally lower than those in t-cig smoke, but a substantial amount of vaporized propylene glycol, vegetable glycerin, nicotine, and toxic substances, such as aldehydes and heavy metals, has been reported. Exposures to mainstream e-cig aerosols have biologic effects but only limited evidence shows adverse respiratory and cardiovascular effects in humans. Long-term studies are needed to better understand the dosimetry and health effects of exposures to secondhand e-cig aerosols.

Promotion of esophageal adenocarcinoma metastasis via Wnt/ß-catenin signal pathway by sorting nexins 3.

BACKGROUND: Esophageal adenocarcinoma is often associated with late diagnoses, poor prognoses, significant morbidities, and high mortality rates. Aberrant expression of Wnt/ß-catenin signal pathways were observed in the tumorigenesis and metastasis of esophageal adenocarcinoma. Sorting nexins 3 has been shown to participate in Wnt protein sorting and regulate Wnt/ß-catenin signal transduction. Thus, we studied the role and molecular mechanism of sorting nexins 3 in esophageal adenocarcinoma. METHODS: Tissue microassay were used to analyze the expression of sorting nexins 3 in esophageal adenocarcinoma tissue and its relationship with survival rate. Using in vivo and in vitro models, we further investigated the effect of sorting nexins 3 on tumor growth and metastasis and underling mechanism. RESULTS: Immunohistochemical staining of human esophageal adenocarcinoma tissue microassay revealed an increased sorting nexins 3 level in esophageal adenocarcinoma tissue and high expression of sorting nexins 3 correlated with the poor prognosis. In vitro study showed that sorting nexins 3 knockdown suppressed esophageal adenocarcinoma cell invasion, metastasis, and epithelial-mesenchymal translation (EMT) process, and this result was confirmed by in vivo tumor metastasis assays. Moreover, we further proved that sorting nexins 3 affected cell invasion and EMT through Wnt/ß-catenin signal pathway. CONCLUSION: Our data provided strong evidence that sorting nexins 3 played a critical role in esophageal adenocarcinoma metastasis through Wnt/ß-catenin signal pathway.

Histone deacetylase 9 downregulation decreases tumor growth and promotes apoptosis in non-small cell lung cancer after melatonin treatment.

Histone deacetylase 9 functions as an oncogene in a variety of cancers, but its role on non-small cell lung cancer (NSCLC) has not been reported. Melatonin was proven to possess anticancer actions, whereas its effect on NSCLC and underlying mechanisms remains poorly understood. In this study, 337 patients with complete clinicopathologic characteristics who underwent NSCLC surgery were recruited for the study. We found that NSCLC patients with high HDAC9 expression were correlated with worse overall survival and poor prognosis. HDAC9 knockdown significantly reduced NSCLC cell growth and induced apoptosis both in vivo and in vitro. Melatonin application also markedly inhibited cell proliferation, metastasis, and invasion and promoted apoptosis in NSCLC cells. Moreover, RNA-seq, real-time quantitative polymerase chain reaction, and western blot analyses showed that melatonin treatment decreased the HDAC9 level in NSCLC cells. A mechanistic study revealed that HDAC9 knockdown further enhanced the anticancer activities of melatonin treatment, whereas HDAC9 overexpression partially reversed the melatonin's anticancer effects. Additionally, the in vivo study found melatonin exerted anti-proliferative and pro-apoptotic effects on xenograft tumors which were also strengthened by HDAC9 knockdown. These results indicated that HDAC9 downregulation mediated the anti-NSCLC actions of melatonin, and targeting HDAC9 may be the novel therapeutic strategy for NSCLC.

Air Quality and Health Cobenefits of Different Deep Decarbonization Pathways in California.

As the world's fifth-largest economy, California has committed to reduce its greenhouse gas (GHG) emissions by 80% below 1990 levels by 2050. While previous studies have shown that GHG reductions could synergistically decrease air pollutant emissions and protect public health, limited research has been conducted to compare the health cobenefits of different technology pathways toward deep decarbonization. Using an integrated approach that combines energy and emission technology modeling, high-resolution chemical transport simulation, and health impact assessment, we find that achievement of the 80% GHG reduction target would bring substantial air quality and health cobenefits. The cobenefits, however, highly depend on the selected technology pathway largely because of California's relatively clean energy structure. Compared with the business-as-usual levels, a decarbonization pathway that focuses on electrification and clean renewable energy is estimated to reduce concentrations of fine particulate matter (PM2.5) by 18-37% in major metropolitan areas of California and subsequently avoid about 12 100 (9600-14 600) premature deaths. In contrast, only a quarter of such health cobenefits, i.e., 2800 (2300-3400) avoided deaths, can be achieved through a pathway focusing more on combustible renewable fuels. After subtracting the cost, the net monetized benefit of the electrification-focused pathway still exceeds that of the renewable fuel-focused pathway, indicating that a cleaner but more expensive decarbonization pathway may be more preferable in California.

Identification and quantification of electronic cigarette exhaled aerosol residue chemicals in field sites.

BACKGROUND: Electronic cigarette (EC) users may exhale large clouds of aerosol that can settle on indoor surfaces forming ECEAR (EC exhaled aerosol residue). Little is known about the chemical composition or buildup of this residue. OBJECTIVE: Our objective was to identify and quantify ECEAR chemicals in two field sites: an EC user's living room and a multi-user EC vape shop. METHODS: We examined the buildup of ECEAR in commonly used materials (cotton, polyester, or terrycloth towel) placed inside the field sites. Materials were subjected to different lengths of exposure. Nicotine, nicotine alkaloids, and tobacco-specific nitrosamines (TSNAs) were identified and quantified in unexposed controls and field site samples using analytical chemical techniques. RESULTS: Nicotine and nicotine alkaloids were detected in materials inside the EC user's living room. Concentrations of ECEAR chemicals remained relatively constant over the first 5 months, suggesting some removal of the chemicals by air flow in the room approximating a steady state. ECEAR chemicals were detected in materials inside the vape shop after 6 h of exposure and levels continually increased over a month. By 1 month, the nicotine in the vape shop was 60 times higher than in the EC user's living room. ECEAR chemical concentrations varied in different locations in the vape shop. Control fabrics had either no detectable or very low concentrations of chemicals. CONCLUSIONS: In both field sites, chemicals from exhaled EC aerosols were deposited on indoor surfaces and accumulated over time forming ECEAR. Non-smokers, EC users, and employees of vape shops should be aware of this potential environmental hazard.