HIF-1α/m6A/NF-κB/CCL3 axis-mediated immunosurveillance participates in low level benzene-related erythrohematopoietic development toxicity.

Defective erythropoiesis is one of the causes of anemia and leukemia. However, the mechanisms underlying defective erythropoiesis under a low-dose environment of benzene are poorly understood. In the present study, multiple omics (transcriptomics and metabolomics) and methods from epidemiology to experimental biology (e.g., benzene-induced (WT and HIF-1α + ) mouse, hiPSC-derived HSPCs) were used. Here, we showed that erythropoiesis is more easily impacted than other blood cells, and the process is reversible, which involves HIF-1 and NF-kB signaling pathways in low-level benzene exposure workers. Decreased HIF-1α expression in benzene-induced mouse bone marrow resulted in DNA damage, senescence, and apoptosis in BMCs and HSCs, causing disturbances in iron homeostasis and erythropoiesis. We further revealed that HIF-1α mediates CCL3/macrophage-related immunosurveillance against benzene-induced senescent and damaged cells and contributes to iron homeostasis. Mechanistically, we showed that m6A modification is essential in this process. Benzene-induced depletion of m6A promotes the mRNA stability of gene NFKBIA and regulates the NF-κB/CCL3 pathway, which is regulated by HIF-1α/METTL3/YTHDF2. Overall, our results identified an unidentified role for HIF-1α, m6A, and the NF-kB signaling machinery in erythroid progenitor cells, suggesting that HIF-1α/METTL3/YTHDF2-m6A/NF-κB/CCL3 axis may be a potential prevention and therapeutic target for chronic exposure of humans to benzene-associated anemia and leukemia.

Metabolic risk factors link unhealthy lifestyles to the risk of colorectal polyps in China.

Colorectal cancer is the second leading cause of global cancer-related deaths, and its precursor lesions are colorectal polyps (CAP). The study aimed to explore the effect of combinations of unhealthy lifestyles on CAP and investigate the mediation role of metabolic disorder in this process. A total of 1299 adults were recruited from a hospital in Jiangsu, China, including 811 cases and 488 adults without diseases. The information on demographic characteristics and lifestyles was collected through questionnaires and the medical record system. Serum biochemical parameters were determined using the automatic biochemical analyzer. Adjusted regression analysis showed that unhealthy lifestyles, including smoking, overnight meals, daily water intake, staying up late, and exercise associated with the risk of CAP. Furthermore, metabolic biomarkers, including BMI, triglycerides, and uric acid, were associated with the risk of CAP. Also, unhealthy lifestyle scores were positively associated with BMI, triglycerides, and CAP. The mediation effect of metabolic biomarkers, such as BMI and triglycerides on the association of unhealthy lifestyle scores with CAP was significant. Available data demonstrate the adverse effect of combinations of unhealthy lifestyle factors on CAP, and metabolic disorders to potentially mediate the association of unhealthy lifestyles with the risk of CAP.

Research development and trends of benzene-induced leukemia from 1990 to 2019-A bibliometric analysis.

Benzene is an occupational and environmental toxicant, causing hematopoietic damage. Our study is aimed to extract the trend of benzene-induced leukemia (BIL) and qualitatively and quantitatively estimate research on it. Publications on BIL were identified from the Web of Science Core Collection (WoSCC). Microsoft Excel 2019 (Redmond, WA) and The CiteSpace 5.6.R5 software (Drexel University, Philadelphia, PA) were used to analyze the publication outcomes, countries, institutions, authors, keywords, and research frontiers. The overall 1152 publications were collected from 1990 to 2019 until November 6, 2020. Environ Health Persp had the highest number of articles published. The USA were the top country in terms of BIL. The Smith MT, Yin SN, Lan Q, and Hayes RB are both listed in the top 10 of co-cited authors, high contribution authors, and the authors of co-cited references. High IF articles account for a considerable proportion, among all the publications. Chinese institutions engaged in BIL and contributed a large part of articles. Exposure population, exposure dose, and exposure risk are the research hotspots in this field. The risk of benzene exposure on childhood leukemia is at issue, and the studies on attributable risk of benzene-induced leukemia are few. More early, sensitive, and specific epigenetic biomarkers of benzolism may be the leading research fields of benzene-induced leukemia in the next few years.

Short-term ambient particulate air pollution exposure, microRNAs, blood pressure and lung function.

Ambient particulate air pollution is a risk factor for cardiovascular and respiratory disease, yet the biological mechanisms underlying this association are not well understood. The current study aimed to investigate the mediation role of microRNAs on the association between personal PM2.5 exposure and blood pressure and lung function. One hundred and twenty adults (60 truck drivers and 60 office workers) aged 18-46 years were assessed on the June 15, 2008 and at follow-up (1- to 2-weeks later). MicroRNAs were extracted from the peripheral blood samples. Compared to truck drivers, there is a significant increase in FEF25-75, FEV1, and FEV1/FVC and a decrease in PM2.5 in office workers (all p < 0.05). According to the Bonferroni corrected threshold p-value < 6.81 × 10-5 (0.05/734) used, personal PM2.5 data showed a significant positive association with miR-644 after the adjustment for age, BMI, smoking status, and habitual alcohol use. The mediation effect of miR-644 on the association between personal PM2.5 exposure and FEF25-75 [B (95%CI) = -1.342 (-2.810, -0.113)], PEF [B (95%CI) = -1.793 (-3.926, -0.195)], and FEV1/FVC [B (95%CI) = -0.119‰ (-0.224‰, -0.026‰)] was significant only for truck drivers after the adjustment for covariates. There were no similar associations with blood pressure. These results demonstrate microRNAs to potentially mediate association of PM2.5 with lung function. Subsequent studies are needed to further elucidate the potential mechanisms of action by which the mediation effect of microRNAs is achieved with this process.

A novel living environment exposure matrix of the common organic air pollutants for exposure assessment.

Although the most accurate estimations of exposure to organic air pollutants are direct personal measurements, it is prohibitive for large-scale epidemiological studies, both in terms of cost-saving and procedure time. Therefore, indirect exposure assessments offer a potentially feasible approach for estimating population exposures to organic air pollution. The purpose of this study was to develop a novel living environment exposure matrix of the common organic air pollutants, which was used in large-scale epidemiological studies. The common organic air pollutants and a range of potential living environment factors were collected and matched according to the statistics of the Centers for Disease Control and Prevention, the United States Environmental Protection Agency, and the World Health Organization. Paints (dyes), paint removing, and furniture are the most common source of living environment exposure (n = 6). Furthermore, most of the common organic air pollutants are associated with exposure to coal, oil and gasoline burning, smoking, and carpet backing (n ≥ 2). Electricity is considered a clean fuel due to they generate less organic air pollutants compared to other living environment factors in this study. However, whether gas burning is considered as a source of indoor organic air pollutants in large-scale epidemiological studies need to be further investigated. The present study summarizes the living environment exposure matrix of the common organic air pollution, which could be used to estimate exposure to organic air pollutants in large-scale epidemiological studies in the future.

Indoor unclean fuel cessation linked with adult cognitive performance in China.

Both indoor unclean fuel use and CVD associates with cognitive function. Indoor fuel has transitioned from the use of unclean fuel to clean fuel in recent years in China. The aim of this study was to evaluate the association between adult cognitive function and such a transition and to investigate the potential role of CVD in this association. 7112 participants (26- to 98-years of age) with 12,676 observations living in twelve provinces of China from 1997 to 2015 were extracted based on having complete data. The associations, combined effects, and further mediation effects between indoor unclean fuel use and its transition, CVD, and cognitive function were tested using regression models, stratified analyses, the relative excess risk due to interaction (RERI), mediation analysis methods, and sensitivity analyses. Between 1997 and 2015, cooking fuel use coal and wood went down a lot in China, from a baseline of 26.9% to 6.1%, from 30.1% to 11.5%, respectively. Such a transition showed a positive association with delayed verbal recall (B = 0.288, p < 0.01), especially in rural area, subjects with age ≥ 65 years old, and women (all P < 0.05). The combined effect of the presence of hypertension during a baseline visit and such a transition on changes in delayed verbal recall was antagonistic (RERI = -0.529, p < 0.05). Moreover, the development of hypertension explained more than 50% of such a fuel transition-related decline of verbal memory. The transition of household energy to clean fuel was associated with a higher adult cognitive function. The presence or the development of CVD appeared to affect the association between indoor air pollution and cognitive function, which suggests a need to further optimize prevention of concurrent CVD and risk factor control in adults at higher risk for cognitive impairment and with indoor unclean cooking fuel, especially in potentially susceptible subgroups.

Oral antimicrobial activity weakened in children with electronic waste lead exposure.

Environmental lead (Pb) exposure can induce dysbacteriosis, impair oral health, and is associated with the development of dental caries. However, the mechanism is unclear. The aim of this study was to explore the effects of Pb toxicity on oral antimicrobial activity in children in an e-waste area. Results showed higher blood Pb levels in e-waste-exposed group children, accompanied by decreased saliva SAG (salivary agglutinin) concentrations, increased peripheral WBC (white blood cell) counts and monocyte counts, and elevated peripheral monocyte percentage. LnPb (natural logarithmic transformation of blood Pb level) was negatively correlated with saliva SAG concentration, while positively correlated with peripheral monocyte percentage. Saliva SAG concentration played a complete mediating role in the correlation of LnPb to peripheral monocyte percentage. To our knowledge, this is the first study on the relationship of environmental Pb exposure and oral antimicrobial activity in children, showing that environmental Pb exposure may weaken oral antimicrobial activity through reducing saliva SAG concentration, which may raise the risk of oral dysbacteriosis and ultimately pathogen infection.

Elevated lead levels from e-waste exposure are linked to sensory integration difficulties in preschool children.

Exposure to lead is associated with adverse effects on neurodevelopment. However, studies of the effects of lead on sensory integration are few. The purpose of this research is to investigate the effect of lead exposure on child sensory integration by correlating the blood lead levels of children with sensory processing measures. A total of 574 children, from 3 to 6 years of age, 358 from an electronic waste (e-waste) recycling town named Guiyu, and 216 from Haojiang, a nearby town with no e-waste recycling activity, were recruited in this study. The median blood lead level in Guiyu children was 4.88 µg/dL, higher than the 3.47 µg/dL blood lead level in Haojiang children (P < 0.001). 47.2% of Guiyu children had blood lead levels exceeding 5 µg/dL. The median concentration of serum cortisol, an HPA-axis biomarker, in Guiyu children was significantly lower than in Haojiang, and was negatively correlated with blood lead levels. All subscale scores and the total score of the Sensory Processing Measure (Hong Kong Chinese version, SPM-HKC) in Guiyu children were higher than Haojiang children, indicating greater difficulties, especially for touch, body awareness, balance and motion, and total sensory systems. Sensory processing scores were positively correlated with blood lead, except for touch, which was negatively correlated with serum cortisol levels. Simultaneously, all subscale scores and the total SPM-HKC scores for children with high blood lead levels (blood lead > 5 µg/dL) were higher than those in the low blood lead level group (blood lead < 5 µg/dL), especially for hearing, touch, body awareness, balance and motion, and total sensory systems. Our findings suggest that lead exposure in e-waste recycling areas may result in a decrease in serum cortisol levels and an increase in child sensory integration difficulties. Cortisol may be involved in touch-related sensory integration difficulties.

Interactions between polycyclic aromatic hydrocarbons and epoxide hydrolase 1 play roles in asthma.

Asthma, as one of the most common chronic diseases in children and adults, is a consequence of complex gene-environment interactions. Polycyclic aromatic hydrocarbons (PAHs), as a group of widespread environmental organic pollutants, are involved in the development, triggering and pathologic changes of asthma. Various previous studies reported the critical roles of PAHs in immune changes, oxidative stress and environment-gene interactions of asthma. EPHX1 (the gene of epoxide hydrolase 1, an enzyme mediating human PAH metabolism) had a possible association with asthma by influencing PAH metabolism. This review summarized that (1) the roles of PAHs in asthma-work as risk factors; (2) the possible mechanisms involved in PAH-related asthma-through immunologic and oxidative stress changes; (3) the interactions between PAHs and EPHX1 involved in asthma-enzymatic activity of epoxide hydrolase 1, which affected by EPHX1 genotypes/SNPs/diplotypes, could influence human PAH metabolism and people's vulnerability to PAH exposure. This review provided a better understanding of the above interactions and underlying mechanisms for asthma which help to raise public's concern on PAH control and develop strategies for individual asthma primary prevention.

Divergent Asymmetric Syntheses of Podophyllotoxin and Related Family Members via Stereoselective Reductive Ni-Catalysis.

A nickel-catalyzed reductive cascade approach to the efficient construction of diastereodivergent cores embedded in podophyllum lignans is developed for the first time. Their gram-scale access paved the way for unified syntheses of naturally occurring podophyllotoxin and other members.

Elevated biomarkers of sympatho-adrenomedullary activity linked to e-waste air pollutant exposure in preschool children.

Air pollution is a risk factor for cardiovascular disease (CVD), and cardiovascular regulatory changes in childhood contribute to the development and progression of cardiovascular events at older ages. The aim of the study was to investigate the effect of air pollutant exposure on the child sympatho-adrenomedullary (SAM) system, which plays a vital role in regulating and controlling the cardiovascular system. Two plasma biomarkers (plasma epinephrine and norepinephrine) of SAM activity and heart rate were measured in preschool children (n = 228) living in Guiyu, and native (n = 104) and non-native children (n = 91) living in a reference area (Haojiang) for >1 year. Air pollution data, over the 4-months before the health examination, was also collected. Environmental PM2.5, PM10, SO2, NO2 and CO, plasma norepinephrine and heart rate of the e-waste recycling area were significantly higher than for the non-e-waste recycling area. However, there was no difference in plasma norepinephrine and heart rate between native children living in the non-e-waste recycling area and non-native children living in the non-e-waste recycling area. PM2.5, PM10, SO2 and NO2 data, over the 30-day and the 4-month average of pollution before the health examination, showed a positive association with plasma norepinephrine level. PM2.5, PM10, SO2, NO2 and CO concentrations, over the 24 h of the day of the health examination, the 3 previous 24-hour periods before the health examination, and the 24 h after the health examination, were related to increase in heart rate. At the same time, plasma norepinephrine and heart rate on children in the high air pollution level group (≤50-m radius of family-run workshops) were higher than those in the low air pollution level group. Our results suggest that air pollution exposure in e-waste recycling areas could result in an increase in heart rate and plasma norepinephrine, implying e-waste air pollutant exposure impairs the SAM system in children.

Air pollution from industrial waste gas emissions is associated with cancer incidences in Shanghai, China.

Outdoor air pollution may be associated with cancer risk at different sites. This study sought to investigate outdoor air pollution from waste gas emission effects on multiple cancer incidences in a retrospective population-based study in Shanghai, China. Trends in cancer incidence for males and females and trends in waste gas emissions for the total waste gas, industrial waste gas, other waste gas, SO2, and soot were investigated between 1983 and 2010 in Shanghai, China. Regression models after adjusting for confounding variables were constructed to estimate associations between waste gas emissions and multiple cancer incidences in the whole group and stratified by sex, Engel coefficient, life expectancy, and number of doctors per 10,000 populations to further explore whether changes of waste gas emissions were associated with multiple cancer incidences. More than 550,000 new cancer patients were enrolled and reviewed. Upward trends in multiple cancer incidences for males and females and in waste gas emissions were observed from 1983 to 2010 in Shanghai, China. Waste gas emissions came mainly from industrial waste gas. Waste gas emissions was significantly positively associated with cancer incidence of salivary gland, small intestine, colorectal, anus, gallbladder, thoracic organs, connective and soft tissue, prostate, kidney, bladder, thyroid, non-Hodgkin's lymphoma, lymphatic leukemia, myeloid leukemia, and other unspecified sites (all p < 0.05). Negative association between waste gas emissions and the esophagus cancer incidence was observed (p < 0.05). The results of the whole group were basically consistent with the results of the stratified analysis. The results from this retrospective population-based study suggest ambient air pollution from waste gas emissions was associated with multiple cancer incidences.

Stereoselective synthesis of a Podophyllum lignan core by intramolecular reductive nickel-catalysis.

A Ni-catalyzed reductive cascade to a diastereocontrolled construction of THN[2,3-c]furan, is developed. The mild reaction conditions led to the tolerance of broad functional groups that can be placed in almost every position of this skeleton with good yields. The conformational control for the observed trans- or cis-fused selectivity during this tandem cyclization-coupling is also proposed.

Temperature drop and the risk of asthma: a systematic review and meta-analysis.

The relationship between asthma and temperature changes remains controversial. The aim of this study was to investigate the association between temperature changes and the risk of asthma. A total of 26 studies (combined total number of subjects N > 26 million), covering 13 countries and Costa Rica, were identified by using a series of keywords in different combinations and searching the papers in PubMed, EMBSEA, Web of Science, MEDLINE, AIM, LILACS, and WPRIM before February 2016. Most of the papers were published in English. Random-effects meta-analyses were performed to evaluate the effect of temperature drop on risk of asthma. Several secondary analyses were also calculated based on stratification for different age, season, latitude, and region on risk of asthma. The odds ratio (OR) estimate between temperature drop and asthma was 1.05 (95% CI 1.02, 1.08) in the meta-analysis. For children, the overall OR was 1.09 (95% CI 1.03, 1.15). Dose-effect analyses showed stronger associations in asthma risk for each 1°1 °C decrement in short-term temperature (OR 1.055, 95% CI 1.00, 1.11). Further stratifications showed that winter (OR 1.03, 95% CI 1.01, 105) and low latitude (OR 1.72, 95% CI 1.23, 2.41) have a statistically significant association with the increased risk of asthma. Exposure of people to short-term temperature drop (per 1 °C decrement) was significantly associated with the risk of lower respiratory tract infections (LRTI) with asthma (OR 1.02, 95% CI 1.00, 1.04). Results suggest an adverse effect of temperature drop on asthma risk, especially in children and low-latitude areas. It may be opportune to consider the preventive actions against temperature drop, including simple face masks, to decrease the risk of asthma.

Elevated lead levels from e-waste exposure are linked to decreased olfactory memory in children.

Lead (Pb) is a developmental neurotoxicant and can cause abnormal development of the nervous system in children. Hence, the aim of this study was to investigate the effect of Pb exposure on child olfactory memory by correlating the blood Pb levels of children in Guiyu with olfactory memory tests. We recruited 61 preschool children, 4- to 7-years of age, from Guiyu and 57 children from Haojiang. The mean blood Pb level of Guiyu children was 9.40 µg/dL, significantly higher than the 5.04 µg/dL mean blood Pb level of Haojiang children. In addition, approximately 23% of Guiyu children had blood Pb levels exceeding 10.00 µg/dL. The correlation analysis showed that blood Pb levels in children highly correlated with e-waste contact (rs = 0.393). Moreover, the mean concentration of serum BDNF in Guiyu children (35.91 ng/ml) was higher than for Haojiang (28.10 ng/ml) and was positively correlated with blood Pb levels. Both item and source olfactory memory tests at 15 min, 5 h and 24 h after odor exposure showed that scores were lower in Guiyu children indicative of reduced olfactory memory in Guiyu children. Olfactory memory tests scores negatively correlated with blood Pb and serum BDNF levels, but were positively associated with parental education levels. At the same time, scores of both tests on children in the high blood Pb level group (blood Pb levels > 5.00 µg/dL) were lower than those in the low blood Pb level group (blood Pb levels ≤ 5.00 µg/dL), implying that Pb exposure decreases olfactory memory in children. Our findings suggest that Pb exposure in e-waste recycling and dismantling areas could result in an increase in serum BDNF level and a decrease in child olfactory memory, in addition, BDNF might be involved in olfactory memory impairment.