Human molybdenum exposure risk in industrial regions of China: New critical effect indicators and reference dose.

Evidence increasingly suggests molybdenum exposure at environmental levels is still associated with adverse human health, emphasizing the necessity to establish a more protective reference dose (RfD). Herein, we conducted a study measuring 15 urinary metals and 30 clinical health indicators in 2267 participants residing near chemical enterprises across 11 Chinese provinces to investigate their relationships. The kidney and cystatin-C emerged as the most sensitive organ and critical effect indicator of molybdenum exposure, respectively. Odds of cystatin-C-defined chronic kidney disease (CKD) in the highest quantile of molybdenum exposure significantly increased by 133.5% (odds ratio [OR]: 2.34, 95% CI: 1.78, 3.11) and 75.8% (OR: 1.76, 95% CI: 1.24, 2.49) before and after adjusting for urinary 14 metals, respectively. Intriguingly, cystatin-C significantly mediated 15.9-89.5% of molybdenum's impacts on liver and lung function, suggesting nephrotoxicity from molybdenum exposure may trigger hepatotoxicity and pulmonary toxicity. We derived a new RfD for molybdenum exposure (0.87 µg/kg-day) based on cystatin-C-defined estimated glomerular filtration rate by employing Bayesian Benchmark Dose modeling analysis. This RfD is significantly lower than current exposure guidance values (5-30 µg/kg-day). Remarkably, >90% of participants exceeded the new RfD, underscoring the significant health impacts of environmental molybdenum exposure on populations in industrial regions of China.

The role of lifestyle in the association between long-term ambient air pollution exposure and cardiovascular disease: a national cohort study in China.

BACKGROUND: Cardiovascular disease (CVD) caused by air pollution poses a considerable burden on public health. We aim to examine whether lifestyle factors mediate the associations of air pollutant exposure with the risk of CVD and the extent of the interaction between lifestyles and air pollutant exposure regarding CVD outcomes. METHODS: We included 7000 participants in 2011-2012 and followed up until 2018. The lifestyle evaluation consists of six factors as proxies, including blood pressure, blood glucose, blood lipids, body mass index, tobacco exposure, and physical activity, and the participants were categorized into three lifestyle groups according to the number of ideal factors (unfavorable, 0-1; intermediate, 2-4; and favorable, 5-6). Satellite-based spatiotemporal models were used to estimate exposure to ambient air pollutants (including particles with diameters ≤ 1.0 µm [PM1], ≤ 2.5 µm [PM2.5], ≤ 10 µm [PM10], nitrogen dioxide [NO2], and ozone [O3]). Cox regression models were used to examine the associations between air pollutant exposure, lifestyles and the risk of CVD. The mediation and modification effects of lifestyle categories on the association between air pollutant exposure and CVD were analyzed. RESULTS: After adjusting for covariates, per 10 µg/m3 increase in exposure to PM1 (HR: 1.09, 95% CI: 1.05-1.14), PM2.5 (HR: 1.04, 95% CI: 1.00-1.08), PM10 (HR: 1.05, 95% CI: 1.03-1.08), and NO2 (HR: 1.11, 95% CI: 1.05-1.18) was associated with an increased risk of CVD. Adherence to a healthy lifestyle was associated with a reduced risk of CVD compared to an unfavorable lifestyle (HR: 0.65, 95% CI: 0.56-0.76 for intermediate lifestyle and HR: 0.41, 95% CI: 0.32-0.53 for favorable lifestyle). Lifestyle played a significant partial mediating role in the contribution of air pollutant exposure to CVD, with the mediation proportion ranging from 7.4% for PM10 to 14.3% for PM2.5. Compared to an unfavorable lifestyle, the relative excess risk due to interaction for a healthier lifestyle to reduce the effect on CVD risk was - 0.98 (- 1.52 to - 0.44) for PM1, - 0.60 (- 1.05 to - 0.14) for PM2.5, - 1.84 (- 2.59 to - 1.09) for PM10, - 1.44 (- 2.10 to - 0.79) for NO2, and - 0.60 (- 1.08, - 0.12) for O3. CONCLUSIONS: Lifestyle partially mediated the association of air pollution with CVD, and adherence to a healthy lifestyle could protect middle-aged and elderly people from the adverse effects of air pollution regarding CVD.

Computational identification of DNA damage-relevant lncRNAs for predicting therapeutic efficacy and clinical outcomes in cancer.

OBJECTIVES: The role of long non-coding RNAs (lncRNAs) in cancer treatment, particularly in modulating DNA repair programs, is an emerging field that warrants systematic exploration. This study aimed to systematically identify the lncRNA regulators that potentially regulate DNA damage response (DDR). METHODS: Using genome-wide mRNA and lncRNA expression profiles of the same tumor patients, we proposed a novel computational framework. This framework performed Gene Set Variation Analysis to calculate DDR pathway enrichment score, which relies on weighting by tumor purity to obtain DDR activity score for each patient. Then, an in-depth differential expression profiling was conducted to identify pathway activity lncRNAs between high- and low-activity groups, utilizing a bootstrap-based randomization method. RESULTS: We comprehensively charted the landscape of DDR-relevant lncRNAs across 23 epithelial-based cancer types. Its effectiveness was validated by assessing the consistency of these lncRNAs within various datasets of the same cancer type (hypergeometric test P < 0.001), examining the expression perturbation of these lncRNAs in response to treatment and demonstrating its application in prioritizing clinically-related lncRNAs. Furthermore, leveraging 820 epithelial ovarian cancer patients from four public datasets, we applied these lncRNAs identified by DDRLnc to establish and validate a risk stratification model to evaluate the benefits of platinum-based adjuvant chemotherapy for the improvement of clinical treatment outcomes. CONCLUSIONS: Comprehensive pan-cancer analysis illustrates the utility of computational framework in identifying potentially lncRNAs involved in DDR, thereby offering novel insights into the complex realm of cancer research, and it will become a valuable tool for identifying potential therapeutic targets for cancer.

ACP-ML: A sequence-based method for anticancer peptide prediction.

Cancer is a serious malignant tumor and is difficult to cure. Chemotherapy, as a primary treatment for cancer, causes significant harm to normal cells in the body and is often accompanied by serious side effects. Recently, anti-cancer peptides (ACPs) as a type of protein for treating cancers dominated research into the development of new anti-tumor drugs because of their ability to specifically target and destroy cancer cells. The screening of proteins with cancer-inhibiting properties from a large pool of proteins is key to the development of anti-tumor drugs. However, it is expensive and inefficient to accurately identify protein functions only through biological experiments due to their complex structure. Therefore, we propose a new prediction model ACP-ML to effectively predict ACPs. In terms of feature extraction, DPC, PseAAC, CTDC, CTDT and CS-Pse-PSSM features were used and the most optimal feature set was selected by comparing combinations of these features. Then, a two-step feature selection process using MRMD and RFE algorithms was performed to determine the most crucial features from the most optimal feature set for identifying ACPs. Furthermore, we assessed the classification accuracy of single learning models and different strategies-based ensemble models through ten-fold cross-validation. Ultimately, a voting-based ensemble learning method is developed to predict ACPs. To validate its effectiveness, two independent test sets were used to perform tests, achieving accuracy of 90.891 % and 92.578 % respectively. Compared with existing anticancer peptide prediction algorithms, the proposed feature processing method is more effective, and the proposed ensemble model ACP-ML exhibits stronger generalization capability and higher accuracy.

Reprogramming of DNA methylation patterns mediates perfluorooctane sulfonate-induced fetal cardiac dysplasia.

Prenatal exposure to perfluorooctane sulfonate (PFOS) is associated with adverse health effects, including congenital heart disease, yet the underlying mechanisms remain elusive. Herein, we aimed to evaluate the embryotoxicity of PFOS using C57BL/6 J mice to characterize fetal heart defects after PFOS exposure, with the induction of human embryonic stem cells (hESC) into cardiomyocytes (CMs) as a model of early-stage heart development. We also performed DNA methylation analysis to clarify potential underlying mechanisms and identify targets of PFOS. Our results revealed that PFOS caused septal defects and excessive ventricular trabeculation cardiomyopathy at 5 mg/kg/day in embryonic mice and inhibited the proliferation and pluripotency of ESCs at concentrations >20 µM. Moreover, it decreased the beating rate and the population of CMs during cardiac differentiation. Decreases were observed in the abundances of NPPA+ trabecular and HEY2+ compact CMs. Additionally, DNA methyl transferases and ten-eleven translocation (TET) dioxygenases were regulated dynamically by PFOS, with TETs inhibitor treatment inducing significant decreases similar as PFOS. 850 K DNA methylation analysis combined with expression analysis revealed several potential targets of PFOS, including SORBS2, FHOD1, SLIT2, SLIT3, ADCY9, and HDAC9. In conclusion, PFOS may reprogram DNA methylation, especially demethylation, to induce cardiac toxicity, causing ventricular defects in vivo and abnormal cardiac differentiation in vitro.

The associations of secondhand smoke exposure with neurodevelopmental disorders and critical time window identification: A systematic review and meta-analysis.

BACKGROUND: Secondhand smoke (SHS) exposure was harmful for brain development. However, the association between SHS exposure and NDDs diagnosis were unclear. OBJECTIVES: To evaluate associations between SHS exposure and NDDs diagnosis, identify critical time windows, and summarize the strength of evidence. METHODS: To investigate the associations of SHS exposure and the development of NDDs, we searched Ovid, EMBASE, Web of Science, Cochrane Library, and PubMed for all the relevant studies up to 31 March 2023. The risk estimates and standardized mean differences (SMD) for the individuals with any NDDs who were exposed to SHS exposure compared with those unexposed or low-exposed. RESULTS: The results showed that a total of 31,098 citations were identified, of which 54 studies were included. We identified significant associations between SHS exposure and the risks of NDDs including specific types of NDDs like attention deficit hyperactivity disorder (ADHD) and learning disabilities (LD) despite the observed heterogeneity for NDDs and ADHD. We also observed a significant association between cotinine exposure and ADHD. However, inconsistent ratings between the two quality-of-evidence methods for all the meta-analyses indicated the current evidence of the associations and the potential exposure window remained inconclusive. DISCUSSION: Our findings suggested that SHS exposure was associated with a higher risk of developing ADHD and LD, with inconclusive quality-of-evidence. In addition, period-specific associations remained unclear based on current evidence.

Prenatal Exposure to PFAS, Associations with Preterm Birth and Modification by Maternal Estrogen Levels: The Maoming Birth Study.

BACKGROUND: Estrogens play a critical role in parturition, and poly- and perfluoroalkyl substances (PFAS), which have estrogenic effects, have been associated with preterm birth. However, the impact of estrogens on the association between PFAS and preterm birth is unknown. OBJECTIVE: The objective of this study is to investigate if estrogens modified the association between PFAS and preterm birth, using a nested case-control study design. METHODS: A total of 371 preterm births and 508 controls were selected from a birth cohort study in China between 2016 and 2018. Perfluorobutanoic acid (PFBA), perfluorohexanesulfonic acid (PFHxS) and its branched isomer, perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS) and its branched isomer, and perfluorononanoic acid (PFNA) were quantified in maternal serum (mean gestational age of 32 wk). Estradiol and estriol were quantified in cord serum. Preterm birth was defined as live delivery at <37 gestational weeks. Causal mediation analysis was used to estimate the mediation and interaction effects of estrogen on the association between PFAS and preterm birth. Latent profile analysis was used to identify important estrogen profiles. Multiple linear regression was used to estimate associations between PFAS and preterm birth and interactions between PFAS and estrogens on preterm birth. RESULTS: Overall, higher odds ratios (ORs) of preterm birth were associated with each 1 ln-unit PFAS increase: PFBA [1.20, 95% confidence interval (CI): 1.14, 1.26], PFNA (1.30, 95% CI: 1.21, 1.39), PFOA (1.98, 95% CI: 1.54, 2.55), and PFOS (1.91, 95% CI: 1.76, 2.07) and its branched isomer (1.91, 95% CI: 1.90, 1.92). We detected statistically significant interactions between cord estradiol and PFAS on preterm birth, while no mediation effects of cord estrogen were observed. The ORs of PFOS (4.29, 95% CI: 1.31, 8.25), its branched isomer (6.71, 95% CI: 1.06, 11.91), and preterm birth were greater for participants with high cord estrogen levels than for participants with low cord estrogen levels. DISCUSSION: Our findings suggest that estrogen modified the association between maternal PFAS exposure and preterm birth. Further studies on maternal PFAS exposure and preterm birth, taking interaction effects of cord estrogens into account, are warranted. https://doi.org/10.1289/EHP11377.

Carotid-cavernous fistula following mechanical thrombectomy of the tortuous internal carotid artery: A case report.

BACKGROUND: A carotid-cavernous fistula (CCF) is an abnormal connection between the internal carotid artery (ICA) and the cavernous sinus. Although direct CCFs typically result from trauma or as an iatrogenic complication of neuroendovascular procedures, they can occur as surgery-related complications after mechanical thrombectomy (MT). With the widespread use of MT in patients with acute ischemic stroke complicated with large vessel occlusion, it is important to document CCF following MT and how to avoid them. In this study, we present a case of a patient who developed a CCF following MT and describe in detail the characteristics of ICA tortuosity in this case. CASE SUMMARY: A 60-year-old woman experienced weakness in the left upper and lower limbs as well as difficulty speaking for 4 h. The neurological examination revealed left central facial paralysis and left hemiplegia, with a National Institutes of Health Stroke Scale score of 9. Head magnetic resonance imaging revealed an acute cerebral infarction in the right basal ganglia and radial crown. Magnetic resonance angiography demonstrated an occlusion of the right ICA and middle cerebral artery. Digital subtraction angiography demonstrated distal occlusion of the cervical segment of the right ICA. We performed suction combined with stent thrombectomy. Then, postoperative angiography was performed, which showed a right CCF. One month later, CCF embolization was performed, and the patient's clinical symptoms have significantly improved 5 mo after the operation. CONCLUSION: Although a CCF is a rare complication after MT, it should be considered. Understanding the tortuosity of the internal carotid-cavernous sinus may help predict the complexity of MT and avoid this complication.

The association between childhood adiposity in northeast China and anthropogenic heat flux: A new insight into the comprehensive impact of human activities.

Anthropogenic heat has been reported to have significant health impacts, but research on its association with childhood adiposity is still lacking. In this study, we matched the 2008-2012 average anthropogenic heat flux, as simulated by a grid estimation model using inventory methods, with questionnaire and measurement data of 49,938 children randomly recruited from seven cities in Northeast China in 2012. After adjusting for social demographic and behavioral factors, we used generalized linear mixed-effect models to assess the association between anthropogenic heat flux and adiposity among children. We also examined the effect modification of various social demographic and behavioral confounders. We found that each 10 W/m2 increase in total anthropogenic heat flux and that from the industry source was associated with an increase of 5.82% (95% CI = 0.84%-11.05%) and 6.62% (95% CI = 0.87%-12.70%) in the odds of childhood adiposity. Similarly, the excess rate of adiposity among children were 5.26% (95% CI = -1.33%-12.29%) and 8.51% (95% CI = 2.24%-15.17%) per 1 W/m2 increase in the anthropogenic heat flux from transportation and buildings, and was 7.94% (95% CI = 2.28%-13.91%) per 0.001 W/m2 increase in the anthropogenic heat flux from human metabolism. We also found generally greater effect estimates among female children and children who were exposed to passive smoking during pregnancy, born by caesarean section, non-breastfed/mixed-fed, or lived within 20 m adjacent to the main road. The potential deleterious effect of anthropogenic heat exposure on adiposity among children may make it a new but major threat to be targeted by future mitigation strategies.

Individual and joint associations of long-term exposure to air pollutants and cardiopulmonary mortality: a 22-year cohort study in Northern China.

Background: Evidence on the associations between long-term exposure to multiple air pollutants and cardiopulmonary mortality is limited, especially for developing regions with higher pollutant levels. We aimed to characterise the individual and joint (multi-pollutant) associations of long-term exposure to air pollutants with cardiopulmonary mortality, and to identify air pollutant that primarily contributes to the mortality risk. Methods: We followed 37,442 participants with a mean age of 43.5 years in four cities in northern China (Tianjin, Shenyang, Taiyuan, and Rizhao) from January 1998 to December 2019. Annual particulate matter (PM) with diameters ≤2.5 µm (PM2.5), ≤10 µm (PM10), sulfur dioxide (SO2) and nitrogen dioxide (NO2) were estimated using daily average values from satellite-derived machine learning models and monitoring stations. Time-varying Cox proportional hazards model was used to evaluate the individual association between air pollutants and mortality from non-accidental causes, cardiovascular diseases (CVDs), non-malignant respiratory diseases (RDs) and lung cancer, accounting for demographic and socioeconomic factors. Effect modifications by age, sex, income and education level were also examined. Quantile-based g-Computation integrated with time-to-event data was additionally applied to evaluate the co-effects and the relative weight of contributions for air pollutants. Findings: During 785,807 person-years of follow-up, 5812 (15.5%) died from non-accidental causes, among which 2932 (7.8%) were from all CVDs, 479 (1.3%) from non-malignant RDs, and 552 (1.4%) from lung cancer. Long-term exposure to PM10 (mean [baseline]: 136.5 µg/m3), PM2.5 (mean [baseline]: 70.2 µg/m3), SO2 (mean [baseline]: 113.0 µg/m3) and NO2 (mean [baseline]: 39.2 µg/m3) were adversely and consistently associated with all mortality outcomes. A 10 µg/m3 increase in PM2.5 was associated with higher mortality from non-accidental causes (hazard ratio 1.20; 95% confidence interval 1.17-1.23), CVDs (1.23; 1.19-1.28), non-malignant RDs (1.37; 1.25-1.49) and lung cancer (1.14; 1.05-1.23). A monotonically increasing curve with linear or supra-linear shape with no evidence of a threshold was observed for the exposure-response relationship of mortality with individual or joint exposure to air pollutants. PM2.5 consistently contributed most to the elevated mortality risks related to air pollutant mixture, followed by SO2 or PM10. Interpretation: There was a strong and positive association of long-term individual and joint exposure to PM10, PM2.5, SO2, and NO2 with mortalities from non-accidental causes, CVDs, non-malignant RDs and lung cancer in high-exposure settings, with PM2.5 potentially being the main contributor. The shapes of associations were consistent with a linear or supra-linear exposure-response relationship, with no lower threshold observed within the range of concentrations in this study. Funding: National Key Research and Development Program of China, the China Scholarship Council, the National Natural Science Foundation of China, Natural Science Foundation of Guangdong Province.

Moderate body lipid accumulation in mice attenuated benzene-induced hematotoxicity via acceleration of benzene metabolism and clearance.

Recent population and animal studies have revealed a correlation between fat content and the severity of benzene-induced hematologic toxicity. However, the precise impact of lipid deposition on benzene-induced hematotoxicity and the underlying mechanisms remain unclear. In this study, we established a mouse model with moderate lipid accumulation by subjecting the mice to an 8-week high-fat diet (45% kcal from fat, HFD), followed by 28-day inhalation of benzene at doses of 0, 1, 10, and 100 ppm. The results showed that benzene exposure caused a dose-dependent reduction of peripheral white blood cell (WBC) counts in both diet groups. Notably, this reduction was less pronounced in the HFD-fed mice, suggesting that moderate lipid accumulation mitigates benzene-related hematotoxicity. To investigate the molecular basis for this effect, we performed bioinformatics analysis of high-throughput transcriptome sequencing data, which revealed that moderate lipid deposition alters mouse metabolism and stress tolerance towards xenobiotics. Consistently, the expression of key metabolic enzymes, such as Cyp2e1 and Gsta1, were upregulated in the HFD-fed mice upon benzene exposure. Furthermore, we utilized a real-time exhaled breath detection technique to monitor exhaled benzene metabolites, and the results indicated that moderate lipid deposition enhanced metabolic activation and increased the elimination of benzene metabolites. Collectively, these findings demonstrate that moderate lipid deposition confers reduced susceptibility to benzene-induced hematotoxicity in mice, at least in part, by accelerating benzene metabolism and clearance.

Maternal transfer of F-53B inhibited neurobehavior in zebrafish offspring larvae and potential mechanisms: Dopaminergic dysfunction, eye development defects and disrupted calcium homeostasis.

Maternal exposure to environment toxicants is an important risk factor for neurobehavioral health in their offspring. In our study, we investigated the impact of maternal exposure to chlorinated polyfluoroalkyl ether sulfonic acids (Cl-PFESAs, commercial name: F-53B) on behavioral changes and the potential mechanism in the offspring larvae of zebrafish. Adult zebrafish exposed to Cl-PFESAs (0, 0.2, 2, 20 and 200 µg/L) for 21 days were subsequently mated their embryos were cultured for 5 days. Higher concentrations of Cl-PFESAs in zebrafish embryos were observed, along with, reduced swimming speed and distance travelled in the offspring larvae. Molecular docking analysis revealed that Cl-PFESAs can form hydrogen bonds with brain-derived neurotropic factor (BDNF), protein kinase C, alpha, (PKCα), Ca2+-ATPase and Na, K - ATPase. Molecular and biochemical studies evidenced Cl-PFESAs induce dopaminergic dysfunction, eye developmental defects and disrupted Ca2+ homeostasis. Together, our results showed that maternal exposure to Cl-PFESAs lead to behavioral alteration in offspring mediated by disruption in Ca2+ homeostasis, dopaminergic dysfunction and eye developmental defects.

Findings of indoor air pollution and childhood obesity in a cross-sectional study of Chinese schoolchildren.

BACKGROUND: Air pollution exposures are increasingly suspected to influence the development of childhood adiposity, especially focusing on outdoor exposure, but few studies investigated indoor exposure and childhood obesity. OBJECTIVES: We aimed to examine the association between exposure to multiple indoor air pollutants and childhood obesity in Chinese schoolchildren. METHODS: In 2019, we recruited 6499 children aged 6-12 years from five Chinese elementary schools in Guangzhou, China. We measured age-sex-specific body mass index z score (z-BMI), waist circumference (WC), waist-to-hip ratio (WHR), and waist-to-height ratio (WHtR) on standard procedures. Four different indoor air pollution (IAP) exposures, including cooking oil fumes (COFs), home decoration, secondhand smoke (SHS), and incense burning, were collected by questionnaire and then converted into an IAP exposure index with four categories. Association between indoor air pollutants and childhood overweight/obesity as well as four obese anthropometric indices were assessed by logistic regression models and multivariable linear regression models, respectively. RESULTS: Children exposed to ≥3 types of indoor air pollutants had higher z-BMI (coefficient [ß]:0.142, 95% confidence interval [CI]:0.011-0.274) and higher risk of overweight/obesity (odd ratio [OR]:1.27, 95%CI:1.01-1.60). And a dose-response relationship was discovered between the IAP exposure index and z-BMI as well as overweight/obesity (pfor trend<0.05). We also found that exposure to SHS and COFs was positively associated with z-BMI and overweight/obesity (p < 0.05). Moreover, there was a significant interaction between SHS exposure and COFs on the higher risk of overweight/obesity among schoolchildren. Boys appear more susceptible to multiple indoor air pollutants than girls. CONCLUSIONS: Indoor air pollution exposures were positively associated with higher obese anthropometric indices and increased odds of overweight/obesity in Chinese schoolchildren. More well-designed cohort studies are needed to verify our results.

Pre-conceptional and prenatal exposure to secondhand smoke and autism spectrum disorder: a national multi-center study in China.

BACKGROUND: Despite extensive research evaluating the association between prenatal exposure to secondhand smoke (SHS) and the development of autism spectrum disorders (ASD), no study has investigated the association by considering the pre-conceptional period. This study aimed to investigate the associations of pre-conceptional and prenatal SHS exposure and the development of ASD among toddlers. METHODS: In this cross-sectional study, parents of 6049 toddlers aged 16-30 months were recruited from 7 tertiary hospitals, 21 communities, and 7 kindergartens located in seven cities in six provinces from five geographical regions of China. We analyzed the associations of SHS exposure and the odds of ASD among toddlers in different exposure windows (pre-conceptional and/or prenatal periods). Data were analyzed from November 2021 to January 2022. RESULTS: Among the 6049 toddlers included in the analysis [22.7 (4.1) months; 44.8% girls], 71 were identified and diagnosed with ASD. Compared with the unexposed toddlers, toddlers with pre-conceptional SHS exposure had higher odds of ASD (OR 2.30, 95% CI 1.36-3.84), while we observed a non-significantly positive association regarding prenatal SHS exposure. When considering both pre-conceptional and prenatal periods, toddlers who were continuously exposed to SHS during these two periods had higher odds than those without SHS exposure (OR 2.32, 95% CI 1.24-4.14). CONCLUSION: We reported positive SHS-ASD associations when exposed during the pre-conceptional period and continuously exposed during pre-conceptional and prenatal periods, emphasizing the critical window of pre-conception for targeted intervention on smoking.

Environmentally relevant concentrations of F-53B induce eye development disorders-mediated locomotor behavior in zebrafish larvae.

The perfluorooctane sulfonate alternative, F-53B, induces multiple physiological defects but whether it can disrupt eye development is unknown. We exposed zebrafish to F-53B at four different concentrations (0, 0.15, 1.5, and 15 µg/L) for 120 h post-fertilization (hpf). Locomotor behavior, neurotransmitters content, histopathological alterations, morphological changes, cell apoptosis, and retinoic acid signaling were studied. Histology and morphological analyses showed that F-53B induced pathological changes in lens and retina of larvae and eye size were significantly reduced as compared to control. Acridine orange (AO) staining revealed a dose-dependent increase in early apoptosis, accompanied by upregulation of p53, casp-9 and casp-3 genes. Genes related to retinoic acid signaling (aldh1a2), lens developmental (cryaa, crybb, crygn, and mipa) and retinal development (pax6, rx1, gant1, rho, opn1sw and opn1lw) were significantly downregulated. In addition, behavioral responses (swimming speed) were significantly increased, while no significant changes in the neurotransmitters (dopamine and acetylcholine) level were observed. Therefore, in this study we observed that exposure to F-53B inflicted histological and morphological changes in zebrafish larvae eye, induced visual motor dysfunctions, perturbed retinoid signaling and retinal development and ultimately triggering apoptosis.

Benzene Exposure Leads to Lipodystrophy and Alters Endocrine Activity In Vivo and In Vitro.

Benzene is a ubiquitous pollutant and mainly accumulates in adipose tissue which has important roles in metabolic diseases. The latest studies reported that benzene exposure was associated with many metabolic disorders, while the effect of benzene exposure on adipose tissue remains unclear. We sought to investigate the effect using in vivo and in vitro experiments. Male adult C57BL/6J mice were exposed to benzene at 0, 1, 10 and 100 mg/kg body weight by intragastric gavage for 4 weeks. Mature adipocytes from 3T3-L1 cells were exposed to hydroquinone (HQ) at 0, 1, 5 and 25 µM for 24 hours. Besides the routine hematotoxicity, animal experiments also displayed significant body fat content decrease from 1 mg/kg. Interestingly, the circulating non-esterified fatty acid (NEFA) level increased from the lowest dose (ptrend < 0.05). Subsequent analysis indicated that body fat content decrease may be due to atrophy of white adipose tissue (WAT) upon benzene exposure. The average adipocyte area of WAT decreased significantly even from 1 mg/kg with no significant changes in total number of adipocytes. The percentages of small and large adipocytes in WAT began to significantly increase or decrease from 1 mg/kg (all p < 0.05), respectively. Critical genes involved in lipogenesis and lipolysis were dysregulated, which may account for the disruption of lipid homeostasis. The endocrine function of WAT was also disordered, manifested as significant decrease in adipokine levels, especially the leptin. In vitro cell experiments displayed similar findings in decreased fat content, dysregulated critical lipid metabolism genes, and disturbed endocrine function of adipocytes after HQ treatment. Pearson correlation analysis showed positive correlations between white blood cell (WBC) count with WAT fat content and plasma leptin level (r = 0.330, 0.344, both p < 0.05). This study shed light on the novel aspect that benzene exposure could induce lipodystrophy and disturb endocrine function of WAT, and the altered physiology of WAT might in turn affect benzene-induced hematotoxicity and metabolic disorders. The study provided new insight into understanding benzene-induced toxicity and the relationship between benzene and adipose tissue.

Fine and ultrafine airborne PM influence inflammation response of young adults and toxicological responses in vitro.

Little evidence is available regarding the impact of different sizes of inhaled particulate matter (PM) on inflammatory responses in healthy young adults in connection with toxicological responses. We conducted a five-time repeated measurement panel study on 88 healthy young college students in Guangzhou, China from December 2017 to January 2018. Blood samples were collected from each participant and tested for tumor necrosis factor alpha (TNF-α) levels every week for 5 consecutive weeks. Mass concentrations of ambient PM2.5, PM1, PM0.5 and number concentrations of ambient PM0.1 were measured. RAW 264.7 macrophages were exposed to PM (PM10-2.5, PM2.5-1, PM1-0.2, PM0.2) collected at the same time as the panel study. Cytotoxicity, oxidation and inflammatory parameters, cell cycle and genotoxicity were tested. Particles were characterized for their chemical composition. The trends of associations between PM2.5, PM1, PM0.5 and TNF-α level were consistent in lag 0 and 3 days, and the relative risk decreased as the particle size decreased. All the ambient air pollutants had the similar change trends in lag 1, 4 and 5 days. Similar results in RAW 264.7 macrophages were found; PM10-2.5 induced the greatest TNF-α and macrophage inflammatory protein 2 (MIP-2) productions and oxidative damage. PM1-0.2 and PM0.2 induced more significant dose-dependent increases of cell cycle and genotoxic response. In the component concentrations of PM samples, metal elements were PM10-2.5 > PM2.5-1 > PM0.2 ≥ PM1-0.2; ions and polycyclic aromatic hydrocarbons (PAHs) were PM0.2 > PM1-0.2 > PM2.5-1 > PM10-2.5. Our results suggested that exposure to all particle sizes was significantly associated with inflammation among healthy young adults and toxicological responses in RAW 264.7 macrophages. Different human and toxicological reactions caused by PM samples indicated the importance of investigating various particle sizes.

Chlorinated Polyfluorinated Ether Sulfonates and Thyroid Hormone Levels in Adults: Isomers of C8 Health Project in China.

Chlorinated polyfluorinated ether sulfonates (Cl-PFESAs) are one kind of replacement chemistry for perfluorooctanesulfonate (PFOS). Recent studies have shown that Cl-PFESAs could interfere with thyroid function in animal models. However, epidemiological evidence on the link between Cl-PFESAs and thyroid function remains scarce. In this study, we focused on two representative legacy perfluoroalkyl substances (PFAS), including PFOS and perfluorooctanoic acid (PFOA), and two PFOS alternatives (6:2 and 8:2 Cl-PFESAs) in the general adult population from a cross-sectional study, the "Isomers of C8 Health Project in China". Three serum thyroid hormones (THs), thyroid stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4), were measured. We fitted generalized linear regression, restricted cubic spline regression, and Bayesian kernel machine regression models to assess associations of individual Cl-PFESAs, legacy PFAS, and PFAS mixtures with THs, respectively. We found individual PFAS and their mixtures were nonlinearly associated with THs. The estimated changes of the TSH level (µIU/mL) at the 95th percentile of 6:2 Cl-PFESA and PFOS against the 5th percentile were -0.74 (95% CI: -0.94, -0.54) and -1.18 (95% CI: -1.37, -0.98), respectively. The present study provided epidemiological evidence for the association of 6:2 Cl-PFESA with thyroid hormone levels in the general adult population.

A novel approach for assessing the spatiotemporal trend of health risk from ambient particulate matter components: Case of Hong Kong.

The spatiotemporal assessment of health risk due to exposure to particulate matter (PM) components should be well studied because of the different toxicity among PM components. However, this research topic has long been overlooked. This study aimed to examine the spatiotemporal variability in ambient respirable PM (PM10) components associated inhalation carcinogenic and non-carcinogenic risk (ICR and INCR) in Hong Kong over 2015-2019. The land-use regression (LUR) approach was adopted to predict the spatial distribution of PM10 component concentrations for the period of 2015-2019, whereas the ICR and INCR values of PM10 components were also estimated using the classic health risk assessment method. Both concentration of PM10 and INCR of PM10 components showed a general decreasing trend, while ICR of PM10 components increased slightly over the study period. LUR-model-based spatial maps at 500 m × 500 m resolution revealed the important spatial variability in PM10 and its eleven components, and their associated ICR and INCR values. High pollution levels and high ICR and INCR of studied PM10 components were generally found in developed urban areas and along the road network. Despite the fact that the PM10 concentrations met the Hong Kong annual PM10 air quality objective of 50 µg/m3, there was still significant potential health risk from the studied PM10 components. This study highlights the importance of taking PM component concentrations and associated inhalation health risk as well as PM mass concentrations into account for the perspective of air quality management and protecting public health.