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.

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).

California's zero-emission vehicle adoption brings air quality benefits yet equity gaps persist.

Zero-emission vehicle (ZEV) adoption is a key climate mitigation tool, but its environmental justice implications remain unclear. Here, we quantify ZEV adoption at the census tract level in California from 2015 to 2020 and project it to 2035 when all new passenger vehicles sold are expected to be ZEVs. We then apply an integrated traffic model together with a dispersion model to simulate air quality changes near roads in the Greater Los Angeles. We found that per capita ZEV ownership in non-disadvantaged communities (non-DACs) as defined by the state of California is 3.8 times of that in DACs. Racial and ethnic minorities owned fewer ZEVs regardless of DAC designation. While DAC residents receive 40% more pollutant reduction than non-DACs due to intercommunity ZEV trips in 2020, they remain disproportionately exposed to higher levels of traffic-related air pollution. With more ZEVs in 2035, the exposure disparity narrows. However, to further reduce disparities, the focus must include trucks, emphasizing the need for targeted ZEV policies that address persistent pollution burdens among DAC and racial and ethnic minority residents.

Differential Toxicity of Electronic Cigarette Aerosols Generated from Different Generations of Devices In Vitro and In Vivo.

Electronic cigarettes (e-cigs) have become increasingly popular, especially among youth, raising concerns about their potential health risks. JUUL and Tank devices are two common types of e-cigs that deliver aerosols with varying nicotine levels and flavors. However, the differences in the aerosols generated from different devices and their corresponding cytotoxicity and pulmonary injury effects remain poorly understood. This study addresses these knowledge gaps by characterizing the aerosols of JUUL and Tank e-cig devices and testing their toxic effects on THP-1 and BEAS-2B human cell lines as well as the C57BL/6J mouse model. In our study, the lower-voltage device, the 3.7 V JUUL generates 2.72 mg/puff aerosols by using e-liquid containing 3% nicotine salt (i.e., nicotine benzoate), which is less than the 11.06 mg/puff aerosols generated by the 7.5 V Tank using e-liquid containing 2.4% freebase nicotine. Yet, the cytotoxicity results reveal that JUUL aerosols induced higher toxicity and increased production of pro-inflammation cytokines compared to Tank aerosols per puff. Additionally, we observed that JUUL induced more severe pulmonary inflammation and DNA damage compared to Tank after normalizing for cotinine, a nicotine metabolite, in vivo. Our findings suggest that the device design plays a more important role in e-cig aerosol-induced toxicity than the composition of the e-liquid or voltage. These results provide valuable insights into the health risks associated with various electronic-cig devices and offer an approach for evaluating them.

Fine Particulate Matter Metal Composition, Oxidative Potential, and Adverse Birth Outcomes in Los Angeles.

BACKGROUND: Although many studies have linked prenatal exposure to PM2.5 to adverse birth outcomes, little is known about the effects of exposure to specific constituents of PM2.5 or mechanisms that contribute to these outcomes. OBJECTIVES: Our objective was to investigate effects of oxidative potential and PM2.5 metal components from non-exhaust traffic emissions, such as brake and tire wear, on the risk of preterm birth (PTB) and term low birth weight (TLBW). METHODS: For a birth cohort of 285,614 singletons born in Los Angeles County, California, in the period 2017-2019, we estimated speciated PM2.5 exposures modeled from land use regression with cokriging, including brake and tire wear related metals (barium and zinc), black carbon, and three markers of oxidative potential (OP), including modeled reactive oxygen species based on measured iron and copper (ROS), OH formation (OPOH), and dithiothreitol (DTT) loss (OPDTT). Using logistic regression, we estimated odds ratios (OR) and 95% confidence intervals (CI) for PTB and TLBW with speciated PM2.5 exposures and PM2.5 mass as continuous variables scaled by their interquartile range (IQR). RESULTS: For both metals and oxidative potential metrics, we estimated increased risks for PTB (ORs ranging from 1.01 to 1.03) and TLBW (ORs ranging from 1.02 to 1.05) per IQR exposure increment that were robust to adjustment for PM2.5 mass. Associations for PM2.5 mass, black carbon, metal components, and oxidative potential (especially ROS and OPOH) with adverse birth outcomes were stronger in Hispanic, Black, and mixed-race or Native American women. DISCUSSION: Our results indicate that exposure to PM2.5 metals from brake and tire wear and particle components that contribute to oxidative potential were associated with an increased risk of PTB and TLBW in Los Angeles County, particularly among Hispanic, Black, and mixed-race or Native American women. Thus, reduction of PM2.5 mass only may not be sufficient to protect the most vulnerable pregnant women and children from adverse effects due to traffic source exposures. https://doi.org/10.1289/EHP12196.

Development and validation of a MUC16 mutation-associated immune prognostic model for lung adenocarcinoma.

Mucin 16 (MUC16) mutation ranks third among all common mutations in lung adenocarcinoma (LUAD), and it has a certain effect on LUAD development and prognostic outcome. This research aimed to analyze the effects of MUC16 mutation on LUAD immunophenotype regulation and determine the prognostic outcome using an immune prognostic model (IPM) built with immune-related genes. The MUC16 mutation status and mRNA expression profiles were analyzed using diverse platforms and among several LUAD patients (n = 691). An IPM was then constructed using differentially expressed immune-related genes (DEIRGs) in MUC16MUT LUAD cases, and the data were compared with those of MUC16WT LUAD cases. The IPM's performance in distinguishing high-risk cases from low-risk ones among 691 LUAD cases was verified. Additionally, a nomogram was built and applied in the clinical setting. Furthermore, a comprehensive IPM-based analysis of how MUC16 mutation affected the tumor immune microenvironment (TIME) of LUAD was performed. MUC16 mutation decreased the immune response in LUAD. As revealed by functional annotation, the DEIRGs in the IPM were most significantly enriched in the humoral immune response function and the immune system disease pathway. Moreover, high-risk cases were associated with increased proportions of immature dendritic cells, neutrophils, and B-cells; enhanced type I interferon T-cell response; and increased expression of PD-1, CTLA-4, TIM-3, and LAG3 when compared with low-risk cases. MUC16 mutation shows potent association with TIME of LUAD. The as-constructed IPM displays high sensitivity to MUC16 mutation status and can be applied to discriminate high-risk LUAD cases from low-risk ones.

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.

Environmental justice analysis of wildfire-related PM2.5 exposure using low-cost sensors in California.

The increasing number and severity of wildfires is negatively impacting air quality for millions of California residents each year. Community exposure to PM2.5 in two main population centers (San Francisco Bay area and Los Angeles County area) was assessed using the low-cost PurpleAir sensor network for the record-setting 2020 California wildfire season. Estimated PM2.5 concentrations in each study area were compared to census tract-level environmental justice vulnerability indicators, including environmental, health, and demographic data. Higher PM2.5 concentrations were positively correlated with poverty, cardiovascular emergency department visits, and housing inequities. Sensors within 30 km of actively burning wildfires showed statistically significant increases in indoor (~800 %) and outdoor (~540 %) PM2.5 during the fires. Results indicate that wildfire emissions may exacerbate existing health disparities as well as the burden of pollution in disadvantaged communities, suggesting a need to improve monitoring and adaptive capacity among vulnerable populations.

A new method of hotspot analysis on the management of CO2 and air pollutants, a case study in Guangzhou city, China.

Emission inventory plays an important role in designing effective emission control strategies. Currently, there is unbalanced development of CO2 and air pollutant emission inventories in China and the spatial information of both cannot be obtained simultaneously, which prevents a collaborative control strategy. In this study, we developed a unified emission inventory including both CO2 and air pollutants, then utilized spatial mapping methods to identify the co-hotspots of both CO2 and air pollutants at a high spatial resolution (1 × 1 km2). We applied Guangzhou city as a case study to illustrate the method. The results showed that CO2 and air pollutants were mainly emitted from the stationary combustion sector and the transportation sector. These two sectors contributed 95 %, 67 %, and 93 % to total CO2, SO2, and NOx emissions, respectively. Up to 86 %, 86 %, 66 %, and 72 % of total CO2, SO2, NOx, and PM2.5 emissions were attributed to the top 10 % emission grids with 1 × 1 km2 resolution. However, our results showed high emission grids were not surrounded by other high emissions grids for all types of emissions analyzed in this study. The co-hotspot analysis enables accurate identification of high-emission grids, which helps environment managers to prioritize resource allocation when designing control strategies. Our study underscores the importance of managing CO2 and air pollutants simultaneously at the city level.

A novel negative pressure isolation device reduces aerosol exposure: A randomized controlled trial.

Background and aim: The COVID-19 pandemic has led to a proliferation of intubation barriers designed to protect healthcare workers from infection. We developed the Suction-Assisted Local Aerosol Containment Chamber (SLACC) and tested it in the operating room. The primary objectives were to determine the ease and safety of airway management with SLACC, and to measure its efficacy of aerosol containment to determine if it significantly reduces exposure to health care workers. Methods: In this randomized clinical trial, adult patients scheduled to undergo elective surgery with general endotracheal anesthesia were screened and informed consent obtained from those willing to participate. Patients were randomized to airway management either with or without the SLACC device. Patients inhaled nebulized saline before and during anesthesia induction to simulate the size and concentration of particles seen with severe symptomatic SARS-CoV-2 infection. Results: 79 patients were enrolled and randomized. Particle number concentration (PNC) at the patients' and healthcare workers' locations were measured and compared between the SLACC vs. control groups during airway management. Ease and success of tracheal intubation were recorded for each patient. All intubations were successful and time to intubation was similar between the two groups. Healthcare workers were exposed to significantly lower particle number concentrations (#/cm3) during airway management when SLACC was utilized vs. control. The particle count outside SLACC was reduced by 97% compared to that inside the device. Conclusions: The SLACC device does not interfere with airway management and significantly reduces healthcare worker exposure to aerosolized particles during airway management.

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.

Impaired sustained attention in groups at high risk for antisocial personality disorder: A contingent negative variation and standardized low-resolution tomographic analysis study.

Objective: This study aimed to explore the characteristics of contingent negative variation (CNV) in groups at high risk for antisocial personality disorder. Materials and methods: A classic CNV paradigm was used to compare the characteristics of attention maintenance among a group of individuals with conduct disorder (CD group; n = 27), a group of individuals with antisocial personality traits (AP; n = 29), a group of individuals with conduct disorder and antisocial personality traits (CD + AP group; n = 25), and a group of healthy controls (CG group; n = 30), to examine the characteristics of the amplitude and latency of CNV in different processing stages. Results: Results of the event-related potential analysis were as follows: The mean amplitude analysis between 500 and 1,000 ms revealed that the mean CNV amplitudes in the CD + AP group (-1.388 ± 0.449 µV, P < 0.001) were significantly lower than that in the CG group (-4.937 ± 0.409 µV). The mean amplitude analysis between 1,000 and 1,500 ms revealed that the mean CNV amplitude in the CD + AP group (-0.931 ± 0.646 µV) was significantly lower than that in the CG group (4.809 ± 0.589 µV, P < 0.001). The mean amplitude analysis between 1,500 and 2,000 ms revealed that the mean CNV amplitude in the CG group (3.121 ± 0.725 µV) was significantly higher than that in the CD + AP group (-0.277 ± 0.795 µV, P = 0.012), whereas the mean CNV amplitude in the CD + AP group was not significantly different in the AP group (P = 0.168) and CD group (P > 0.05). Source localization results indicated altered activity in frontal-temporal regions. Conclusion: The CNV amplitude characteristics in the CD + AP group and AP group were more consistent and fluctuated around the baseline, indicating the absence of attention maintenance resulted in impairments in attention allocation and motor preparation in the CD + AP group and AP group.

The Profile and Clinical Significance of ITGB2 Expression in Non-Small-Cell Lung Cancer.

Integrins are involved in extracellular and intracellular signaling and are often aberrantly expressed in tumors. Integrin beta 2 (ITGB2) has previously been demonstrated to be correlated with the host defense. However, the expression profile and role of ITGB2 in non-small-cell lung cancer (NSCLC) remain unclear. Here, we found that the genetic alterations in ITGB2 was predominated by gene mutation and copy number deletion using cBioPortal analysis, and its expression was downregulated in the NSCLC tissues, as validated by the UALCAN, TCGA, and GEO databases and our tissue samples. Kaplan-Meier (KM) plotter analysis revealed that patients with a lower ITGB2 expression had a shorter overall survival (OS) time (p = 0.01). Moreover, 1089 differentially expressed genes (DEGs) in the NSCLC tissues were screened using the TCGA database. The GO and KEGG enrichment analysis showed that the DEGs were closely associated with immune processes and cell adhesion. The protein-protein interaction (PPI) network revealed that 10 of 15 EMT-related genes among the DEGs might lead to the metastasis of NSCLC. Concomitantly, the expression of ITGB2 was positively correlated with the infiltration of Treg cells and Myeloid-derived suppressor cells (MDSC). Biologically, the ectopic expression of ITGB2 significantly inhibited the proliferation and metastasis of NSCLC cells. Mechanistically, we demonstrated that ITGB2 suppressed the expression of N-cadherin, Vimentin, Slug, Snail, and Twist, while it promoted E-cadherin expression, according to gain-of-function studies. In conclusion, ITGB2 can inhibit the proliferation and migration of NSCLC cells, leading to a poor prognosis, via epithelial-mesenchymal transition (EMT) signaling.

Passive smoking and urinary oxidative biomarkers: A pilot study of healthy travelers from Los Angeles to Beijing.

There is a great heterogeneity in smoking prevalence and tobacco control policy across different countries. However, it is unknown whether this heterogeneity could cause increased passive smoking and adverse health effects among international travelers. In this pilot study, we collected 190 urine samples from 26 Los Angeles residents before (LA-before), during (Beijing), and after (LA-after) a 10-week visit to Beijing to measure biomarkers of passive smoking (cotinine), exposure to polycyclic aromatic hydrocarbons (OH-PAHs), and oxidative stress (malondialdehyde, 8-isoprostane, and uric acid). The geometric mean concentrations of urinary cotinine were 0.14, 1.52, and 0.22 µg/g creatinine in LA-before, Beijing, and LA-after, respectively. Likewise, OH-PAH levels were significantly higher in Beijing as compared to LA-before or LA-after, in association with the urinary cotinine levels. One-fold increase in urinary cotinine levels was associated with 10.1% (95% CI: 5.53-14.8%), 8.75% (95% CI: 2.33-15.6%), and 25.4% (95%CI: 13.1-39.1%) increases in urinary levels of malondialdehyde, 8-isoprotane, and uric acid, respectively. OH-PAHs mediated 9.1-23.3% of the pro-oxidative effects associated with passive smoking. Taken together, our findings indicate that traveling to a city with higher smoking prevalence may increase passive smoking exposure, in association with pro-oxidative effects partially mediated by PAHs.

Adulthood Psychosocial Disadvantages and Risk of Hypertension in U.S. Workers: Effect Modification by Adverse Childhood Experiences.

Hypertension is a key driver of cardiovascular diseases. However, how stressors contribute to the development of hypertension remains unclear. The objective of this study was to examine prospective associations of adverse childhood experiences (ACEs) and adulthood psychosocial disadvantages (APDs) with incident hypertension. Data were from the Mid-life in the United States (MIDUS) study, a national, population-based, prospective cohort study. ACEs were examined via retrospective reports, and APDs including work stress and social isolation were assessed using survey measures. Incident hypertension was defined based on self-reported physician diagnosis. Baseline data were collected in 1995, with follow-up in 2004-2006 and 2013-2014. Cox proportional hazards regression was applied to assess prospective associations of ACEs and APDs with incident hypertension in 2568 workers free from hypertension at baseline. After adjustment for covariates, baseline APDs were associated with increased incident hypertension (aHR and 95% CI = 1.48 [1.09, 2.01]) during a 20-year follow-up, whereas ACEs showed null associations. Moreover, a moderating effect by ACEs was observed-the effect of APDs on risk of hypertension was stronger when ACEs were present (aHR and 95% CI = 1.83 [1.17, 2.86]). These findings underscore the importance of psychosocial stressors as nontraditional risk factors of cardiometabolic disorders.

Construction of Pulmonary Embolism Prediction, Early Warning, and Precontrol MDT Collaborative Nursing Model Based on the Smith Model.

The purpose of this study was to construct a multidisciplinary collaborative nursing model for pulmonary embolism risk prediction, early warning, and precontrol based on the Smith model and evaluate the application effect and hospitalization satisfaction. 2,037 patients hospitalized in the thoracic surgery department from June 1, 2019, to May 31, 2021, were selected as the research subjects. The control group received routine pulmonary embolism prevention management, while the experimental group received safe, case-based, and programmatic multidisciplinary intervention management based on the Smith policy management model. The data were analyzed statistically. The experimental group's extubation and hospitalization time, D-dimer value, incidence of deep vein thrombosis, and pulmonary embolism on the seventh day after surgery were lower than those in the control group, and the satisfaction of hospitalization in the experimental group was higher than that in the control group. The implementation of the multidisciplinary collaborative nursing model of pulmonary embolism risk prediction, early warning, and precontrol based on the Smith model can promote the preventive effect of pulmonary embolism risk of surgical patients in our department and effectively improve the satisfaction of hospitalization, which is worthy for further promotion.

Co-kriging with a low-cost sensor network to estimate spatial variation of brake and tire-wear metals and oxidative stress potential in Southern California.

Due to regulations and technological advancements reducing tailpipe emissions, an increasing proportion of emissions arise from brake and tire wear particulate matter (PM). PM from these non-tailpipe sources contains heavy metals capable of generating oxidative stress in the lung. Although important, these particles remain understudied because the high cost of actively collecting filter samples. Improvements in electrical engineering, internet connectivity, and an increased public concern over air pollution have led to a proliferation of dense low-cost air sensor networks such as the PurpleAir monitors, which primarily measure unspeciated fine particulate matter (PM2.5). In this study, we model the concentrations of Ba, Zn, black carbon, reactive oxygen species concentration in the epithelial lining fluid, dithiothreitol (DTT) loss, and OH formation. We use a co-kriging approach, incorporating data from the PurpleAir network as a secondary predictor variable and a land-use regression (LUR) as an external drift. For most pollutant species, co-kriging models produced more accurate predictions than an LUR model, which did not incorporate data from the PurpleAir monitors. This finding suggests that low-cost sensors can enhance predictions of pollutants that are costly to measure extensively in the field.

Pharmacokinetics, Bioequivalence, and Safety Studies of a Generic Selective Tyrosine Kinase Inhibitor Nilotinib Capsule Versus a Branded Product in Healthy Chinese Volunteers.

Nilotinib, a second-generation tyrosine kinase inhibitor (TKI), has been approved in the United States and Europe as a treatment for patients with newly diagnosed chronic myeloid leukemia (CML)-chronic phase (CP) and patients with CML-CP or chronic myeloid leukemia-accelerated phase (CML-AP) who are resistant or intolerant to imatinib (a first-generation TKI). This study compared the bioequivalence and safety of the test nilotinib capsule and reference nilotinib capsule (Tasigna, Novartis) in healthy Chinese volunteers under fasting conditions for marketing authorization in China. The results of the study are reported for the first time. This was a single-dose, randomized, open-label, two-period, and cross-over study. Thirty healthy volunteers were randomly assigned to receive a single dose of a 200-mg test or reference capsule under fasting conditions in each period with a 10-day washout. Plasma samples were analyzed with liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters were calculated with WinNonlin software. The geometric mean ratio and the corresponding 90% confidence intervals of Cmax , AUC0-t , and AUC0-∞ for nilotinib between the two fixed-dose combination formulations were within the bioequivalence acceptance range of 80%-125%, therefore the generic and branded formulations were bioequivalent in healthy Chinese volunteers.

A systematic assessment of city-level climate change mitigation and air quality improvement in China.

China is facing dual challenges of air pollution and climate change. By using city-level data, we comprehensively assessed air quality and CO2 emission changes from 2015 to 2019 for 335 Chinese cities. We selected important regions for air pollution control and categorized all cities into different classes according to their development levels. Our novel approach revealed new insights on different patterns of changes of PM2.5, O3, and CO2 by region and city class. We found that PM2.5 concentrations decreased remarkably due to mandatory city-level reduction targets, especially in the Beijing-Tianjin-Hebei (-27%) region. Nonetheless, O3 concentrations and CO2 emissions increased in 91% and 69% of Chinese cities, respectively. Observed CO2 emission reductions in more developed cities were mainly due to prominent energy intensity reduction and energy structure improvement. Our study indicates a lack of synergy in air pollution control and CO2 mitigation under current policies in China. To address both challenges holistically, we suggest setting mandatory city-level CO2 emission reduction targets and reinforcing clean energy and energy efficiency measures.

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.