Effects of exposure to polycyclic aromatic hydrocarbons and heavy metals on placental trophoblasts and childhood inflammation

Environmental pollution, the introduction of harmful substances into the environment, is one of our most serious public health issues. The pollutants introduced into the natural environment by human activities not only destroy the natural environment but also have adverse effects on human health. Pregnant women and children are more vulnerable than the general population to the health impacts of environmental pollutant exposure. Polycyclic aromatic hydrocarbons (PAHs), and heavy metals, i.e., lead (Pb) and cadmium (Cd), have been found in the human placenta, which also can cross the placenta into the fetus. In addition, exposure to these environmental pollutants can profoundly affect the immune system, especially in children with immature immune systems. To expand our knowledge about the effects of PAHs and heavy metals on the placental trophoblast, in the present thesis, we separately revealed the impacts of environmental pollutants, such as PAHs, Pb, and Cd, on human placental trophoblast cells in vitro and childhood inflammation. In vitro studies have shown that different placental trophoblast cell lines had cell type-dependent responses to benzo[a]pyrene (BaP) and heavy metals Pb/Cd exposure under normoxic, hypoxic, or pro-inflammatory conditions. This implies that BaP and heavy metals exposure may affect trophoblast cells of different origins differently. Additionally, our cross-sectional population studies provided new insights into the relationship between PAH exposure and inflammation in children: platelets and CYP-derived oxylipins play essential regulatory roles in PAH exposure-induced inflammation. Future studies, including animal models, are necessary to verify our findings

An Integrative Paradigm for Enhanced Stroke Prediction: Synergizing XGBoost and xDeepFM Algorithms

Stroke prediction plays a crucial role in preventing and managing this debilitating condition. In this study, we address the challenge of stroke prediction using a comprehensive dataset, and propose an ensemble model that combines the power of XGBoost and xDeepFM algorithms. Our work aims to improve upon existing stroke prediction models by achieving higher accuracy and robustness. Through rigorous experimentation, we validate the effectiveness of our ensemble model using the AUC metric. Through comparing our findings with those of other models in the field, we gain valuable insights into the merits and drawbacks of various approaches. This, in turn, contributes significantly to the progress of machine learning and deep learning techniques specifically in the domain of stroke prediction

A Fast Algorithm to Compute Maximum k-Plexes in Social Network Analysis

A clique model is one of the most important techniques on the cohesive subgraph detection; however, its applications are rather limited due to restrictive conditions of the model. Hence much research resorts to k-plex — a graph in which any vertex is adjacent to all but at most k vertices — which is a relaxation model of the clique. In this paper, we study the maximum k-plex problem and propose a fast algorithm to compute maximum k-plexes by exploiting structural properties of the problem. In an n-vertex graph, the algorithm computes optimal solutions in cnnO(1) time for a constant c < 2 depending only on k. To the best of our knowledge, this is the first algorithm that breaks the trivial theoretical bound of 2n for each k ≥ 3. We also provide experimental results over multiple real-world social network instances in support

Early-life exposure to widespread environmental toxicants and maternal-fetal health risk:A focus on metabolomic biomarkers

Prenatal exposure to widespread environmental toxicants is detrimental to maternal health and fetal development. The effects of environmental toxicants on maternal and fetal metabolic profile changes have not yet been summarized. This systematic review aims to summarize the current studies exploring the association between prenatal exposure to environmental toxicants and metabolic profile alterations in mother and fetus. We searched the MEDLINE (PubMed) electronic database for relevant literature conducted up to September 18, 2019 with some key terms. From the initial 155 articles, 15 articles met the inclusion and exclusion criteria, and consist of highly heterogeneous research methods. Seven studies assessed the effects of multiple environmental pollutants (metals, organic pollutants, nicotine, air pollutants) on the maternal urine and blood metabolomic profile; five studies evaluated the effects of arsenic, polychlorinated biphenyls (PCBs), nicotine, and ambient fine particulate matter (PM2.5) on the cord blood metabolomic profile; and one study assessed the effects of smoking exposure on the amniotic fluid metabolomic profile. The alteration of metabolic pathways in these studies mainly involve energy metabolism, hormone metabolism, oxidative stress and inflammation. No population study investigated the association between environmental toxicants and placental metabolomics. This systematic review provides evidence that prenatal exposure to a variety of environmental pollutants can affect maternal and fetal metabolomic characteristics. Integration of environmental toxicant exposure and metabolomics data in maternal-fetal samples is helpful to understand the interaction between toxicants and metabolites, so as to reveal the pathogenesis of fetal disease or diseases of fetal origin

On Information Coverage for Location Category Based Point-of-Interest Recommendation

Point-of-interest(POI) recommendation becomes a valuable service in location-based social networks. Based on the norm that similar users are likely to have similar preference of POIs, the current recommendation techniques mainly focus on users' preference to provide accurate recommendation results. This tends to generate a list of homogeneous POIs that are clustered into a narrow band of location categories(like food, museum, etc.) in a city. However, users are more interested to taste a wide range of flavors that are exposed in a global set of location categories in the city.In this paper, we formulate a new POI recommendation problem, namely top-K location category based POI recommendation, by introducing information coverage to encode the location categories of POIs in a city.The problem is NP-hard. We develop a greedy algorithm and further optimization to solve this challenging problem. The experimental results on two real-world datasets demonstrate the utility of new POI recommendations and the superior performance of the proposed algorithms

Alterations in platelet indices link polycyclic aromatic hydrocarbons toxicity to low-grade inflammation in preschool children

Background: Environmental exposure to carcinogenic polycyclic aromatic hydrocarbons (PAHs) can disturb the immune response. However, the effect of PAHs on low-grade inflammation related to platelets in humans is unknown. Objectives: We investigated the association of PAH exposure with low-grade inflammation and platelet parameters in healthy preschoolers. Methods: The present study recruited 239 participants, aged 2-7 years, from an electronic-waste (e-waste)-exposed (n = 118) and a reference (n = 121) area. We measured ten urinary PAH metabolites, four types of immune cells and cytokines, and seven platelet parameters, and compared their differences between children from the two groups. Spearman correlation analysis was performed to explore the potential risk factors for PAH exposure and the associations between urinary monohydroxylated PAHs (OH-PAHs) and biological parameters. Associations between urinary PAH metabolites and platelet indices were analyzed using quantile regression models. Mediation analysis was used to understand the relationship between urinary total hydroxynaphthalene (Sigma OHNa) and interleukin (IL)-1 beta through seven platelet indices, as mediator variables. Results: We found higher urinary monohydroxylated PAH (OH-PAH) concentrations, especially 1-hydroxynaphthalene (1-OHNa) and 2-hydroxynaphthalene (2-OHNa), in children from the e-waste-exposed group than in the reference group. These were closely associated with child personal habits and family environment. A decreased lymphocyte ratio and increased pro-inflammatory cytokines, such as gamma interferon-inducible protein (IP)-10 and IL-1 beta, were found in the e-waste-exposed children. After adjustment for confounding factors, significantly negative correlations were found between levels of mean platelet volume (MPV), platelet distribution width (PDW), platelet-large cell ratio (P-LCR) and ratio of mean platelet volume to platelet count (MPVP) and OH-PAHs. In addition, Sigma OHNa was positively associated with IL-1 beta mediated through MPV, PDW, P-LCR, and ratio of platelet count to lymphocyte count (PLR). Conclusions: Platelet indices were significantly associated with the changes in urinary OH-PAH levels, which may can be regarded as effective biomarkers of low-grade inflammation resulting from low PAH exposure in healthy children

Elevated expression of AhR and NLRP3 link polycyclic aromatic hydrocarbon exposure to cytokine storm in preschool children

BACKGROUND: Polycyclic aromatic hydrocarbons (PAHs), as a group of persistent organic pollutants, are linked to impaired immune function and low-grade inflammation in adults and children. However, the potential of PAHs to lead to a cytokine storm associated with AhR (aryl hydrocarbon receptor) and NLRP3 (NLR family pyrin domain containing 3) in humans has been poorly studied. OBJECTIVES: We aimed to investigate the associations between PAH exposure, AhR and NLRP3 expression, and cytokines associated with a cytokine storm in healthy preschoolers. METHODS: Basic demographic surveys and physical examinations were conducted on 248 preschoolers from an electronic waste (e-waste) recycling area (Guiyu, n = 121) and a reference area (Haojiang, n = 127). Ten urinary PAH metabolite (OH-PAH) concentrations were measured. We also measured the expression levels of AhR and NLRP3 and seventeen serum cytokine levels. RESULTS: The concentrations of multiple OH-PAHs were significantly higher in the exposed group than those in the reference group, especially 1-hydroxynaphthalene (1-OH-Nap) and 2-hydroxynaphthalene (2-OH-Nap). PAH exposure was closely related to a child's living environment and hygiene habits. Expression levels of AhR and NLRP3 were significantly higher in the exposed group than in the reference group. Similarly, serum IL-1β, IL-4, IL-5, IL-10, IL-12p70, IL-13, IL-17A, IL-18, IL-22, IL-23, and IFN-γ levels were notably higher in the e-waste-exposed children than in the reference children. After adjusting for age, gender, BMI, family income, parental education level, and second-hand smoke exposure, we found that increased PAH exposure was associated with higher AhR and NLRP3 expression and elevated IL-4, IL-10, IL-12p70, IL-18, IL-22, IL-23, TNF-α, and IFN-γ levels. The associations between PAH exposure and IL-1β, IL-18, IFN-γ, and TNF-β were mediated by NLRP3 expression, and the relationships between PAH exposure and IL-4, IL-10, IL-12p70, IL-22, IL-23, and TNF-α were mediated by AhR expression. CONCLUSIONS: Our findings suggest that the association between PAH exposure and a cytokine storm may be mediated by AhR and NLRP3 expression among preschoolers

A Targeted Lipidomic Reveals CYP450-Derived Oxylipin Linked to the Inflammatory Response by Polycyclic Aromatic Hydrocarbon Exposure in Children

Polycyclic aromatic hydrocarbon (PAH) exposure is a cause of chronic inflammation. The effect of PAHs on bioactive lipid mediators involved in the inflammatory process remains largely unknown. This study measured ten urinary monohydroxy-PAHs (OH-PAHs), 54 plasma oxylipins, and inflammation-related markers. Children with high PAH exposure had higher levels of ten OH-PAHs, (±)18-HETE, 19(S)-HETE, 5,6-DiHETrE, 9,10-DiHOME, more monocytes, interleukin (IL)-10, tumor necrosis factor (TNF)-α and IL-6 than those with low PAH exposure (all p &lt; 0.05). The ƩOH-PAHs were inversely correlated to the levels of anti-inflammatory oxylipins, including 5,6-EET (p for trend = 0.007), 11,12-EET (p for trend = 0.035), 14,15-EET (p for trend = 0.022), and 16(17)-EpDPE (p for trend = 0.043), but positively associated with pro-inflammatory 9,10-DiHOME (p for trend &lt; 0.001). Mediation analyses indicated that cytochrome P450 (CYP)-derived 9,10-DiHOME mediated a separate 42.7%, 31.1%, 57.8%, and 38.5% of the associations between OH-PAHs and monocytes, IL-6, IL-10, TNF-α (p = 0.017, 0.014, 0.005 and 0.012, respectively). Our study suggests that CYP-derived oxylipins can be considered sensitive lipid mediators to signal the early inflammation response to PAH exposure.</p