Comparative Developmental Toxicity of New Aromatic Halogenated DBPs in a Chlorinated Saline Sewage Effluent to the Marine Polychaete <i>Platynereis dumerilii</i>

Using seawater for toilet flushing may introduce high levels of bromide and iodide into a city’s sewage treatment works, and result in the formation of brominated and iodinated disinfection byproducts (DBPs) during chlorination to disinfect sewage effluents. In a previous study, the authors’ group has detected the presence of many brominated DBPs and identified five new aromatic brominated DBPs in chlorinated saline sewage effluents. The presence of brominated DBPs in chlorinated saline effluents may pose adverse implications for marine ecology. In this study, besides the detection and identification of another seven new aromatic halogenated DBPs in a chlorinated saline sewage effluent, their developmental toxicity was evaluated using the marine polychaete <i>Platynereis dumerilii</i>. For comparison, the developmental toxicity of some commonly known halogenated DBPs was also examined. The rank order of the developmental toxicity of 20 halogenated DBPs was 2,5-dibromohydroquinone > 2,6-diiodo-4-nitrophenol ≥ 2,4,6-triiodophenol > 4-bromo-2-chlorophenol ≥ 4-bromophenol > 2,4-dibromophenol ≥ 2,6-dibromo-4-nitrophenol > 2-bromo-4-chlorophenol > 2,6-dichloro-4-nitrophenol > 2,4-dichlorophenol > 2,4,6-tribromophenol > 3,5-dibromo-4-hydroxybenzaldehyde > bromoform ≥ 2,4,6-trichlorophenol > 2,6-dibromophenol > 2,6-dichlorophenol > iodoacetic acid ≥ tribromoacetic acid > bromoacetic acid > chloroacetic acid. On the basis of developmental toxicity data, a quantitative structure–activity relationship (QSAR) was established. The QSAR involved two physical–chemical property descriptors (log <i>P</i> and p<i>K</i>_a) and two electronic descriptors (the lowest unoccupied molecular orbital energy and the highest occupied molecular orbital energy) to indicate the transport, biouptake, and biointeraction of these DBPs. It can well predict the developmental toxicity of most of the DBPs tested

Halopyrroles: A New Group of Highly Toxic Disinfection Byproducts Formed in Chlorinated Saline Wastewater

Utilizing seawater for toilet flushing is an effective way to conserve freshwater in coastal cities. During chlorination for disinfecting saline wastewater effluents, the high levels of bromide from seawater are oxidized to hypobromous acid which may then react with effluent organics to form brominated disinfection byproducts (DBPs). In this research, by applying a new precursor ion scan method, we detected and identified a group of halopyrroles in a chlorinated saline wastewater effluent, including tetrabromopyrrole, tribromochloropyrrole, tribromoiodopyrrole, and tribromopyrrole, with tetrabromopyrrole as the predominant species. It is the first time that this group of halopyrroles were identified as wastewater DBPs (though 2,3,5-tribromopyrrole has been found to be a DBP in drinking water before). Detection of halopyrroles was problematic as these compounds in the pretreated samples were found to convert to halonitropyrroles; the problem was successfully solved by diluting the pretreated samples. The formation, occurrence, precursor, and toxicity of tetrabromopyrrole were investigated. This DBP showed significantly higher developmental toxicity than any of the haloaliphatic and haloaromatic DBPs previously tested

Comparative Toxicity of Chlorinated Saline and Freshwater Wastewater Effluents to Marine Organisms

Toilet flushing with seawater results in saline wastewater, which may contain approximately 33–50% seawater. Halogenated disinfection byproducts (DBPs), especially brominated and iodinated DBPs, have recently been found in chlorinated saline wastewater effluents. With the occurrence of brominated and iodinated DBPs, the adverse effects of chlorinated saline wastewater effluents to marine ecology have been uncertain. By evaluating the developmental effects in the marine polychaete <i>Platynereis dumerilii</i> directly exposed to chlorinated saline/freshwater wastewater effluents, we found surprisingly that chlorinated saline wastewater effluents were less toxic than a chlorinated freshwater wastewater effluent. This was also witnessed by the marine alga <i>Tetraselmis marina</i>. The toxicity of a chlorinated wastewater effluent to the marine species was dominated by its relatively low salinity compared to the salinity in seawater. The organic matter content in a chlorinated wastewater effluent might be partially responsible for the toxicity. The adverse effects of halogenated DBPs on the marine species were observed pronouncedly only in the “concentrated” chlorinated wastewater effluents. pH and ammonia content in a wastewater effluent caused no adverse effects on the marine species. The results suggest that using seawater to replace freshwater for toilet flushing might mitigate the “direct” acute detrimental effect of wastewater to the marine organisms

Data_Sheet_1_Sex-specific association between elective cesarean section and growth trajectories in preschool children: A prospective birth cohort study.pdf

BackgroundElective cesarean section (ECS) primarily contributes to the rising cesarean section (CS) rate, and much attention has been attracted to its health consequences. The association between ECS and overweight and obesity in children has been controversial, and few studies distinguished ECS with medical indications from those without indications. Based on a large sample birth cohort, we aim to examine the association of ECS with or without medical indications on children's physical development by using repeated anthropometric data from birth to 6 years of age.MethodsA total of 2304 mother-child pairs with complete data on delivery mode and children's anthropometric measurements were recruited from the Ma'anshan-Anhui Birth Cohort (MABC) in China. ECS was the main exposure in this study, and the primary outcomes were children's growth trajectories and early adiposity rebound (AR). Children's BMI trajectories were fitted by using group-based trajectory models and fractional polynomial mixed-effects models. The association between ECS and children's growth trajectories and early AR was performed using multiple logistic regression models.ResultsAmong 2,304 mother-child pairs (1199 boys and 1105 girls), 1088 (47.2%) children were born by CS, including 61 (5.6%) emergency CS, 441 (40.5%) ECS with medical indications, and 586 (53.9%) ECS without medical indications. After adjusting for potential confounders, it was found that ECS with medical indications was associated with a “high level” of BMI trajectory (OR = 1.776; 95% CI: 1.010–3.123), and ECS without medical indications was associated with early AR (OR = 1.517; 95% CI: 1.123–2.050) in girls. In boys, we found that ECS without medical indications was unlikely to experience an accelerated growth trajectory (OR = 0.484; 95%CI: 0.244–0.959).ConclusionsECS may be related to girls' “high level” BMI trajectories and early AR. If causal, the findings will provide an evidence-based reference for early life interventions for childhood obesity.</p

Table_1_Association of maternal thyroid peroxidase antibody during pregnancy with placental morphology and inflammatory and oxidative stress responses.docx

BackgroundStudies suggest that thyroid peroxidase antibody (TPOAb) positivity exposure during pregnancy may contribute to changes in placental morphology and pathophysiology. However, little is known about the association of maternal TPOAb during pregnancy with placental morphology and cytokines. This study focuses on the effect of repeated measurements of maternal TPOAb during pregnancy on the placental morphology and cytokines.MethodsBased on Ma’anshan Birth Cohort (MABC) in China, maternal TPOAb levels were retrospectively detected in the first, second and third trimesters. Placental tissues were collected 30 minutes after childbirth, placental morphological indicators were obtained by immediate measurement and formula calculation, and cytokine mRNA expression was detected by real-time quantitative polymerase chain reaction (RT-qPCR) afterward. Generalized linear models and linear mixed models were analyzed for the relationships of maternal TPOAb in the first, second and third trimesters with placental indicators.ResultsTotally 2274 maternal-fetal pairs were included in the analysis of maternal TPOAb levels and placental morphology, and 2122 pairs were included in that of maternal TPOAb levels and placental cytokines. Maternal TPOAb levels in early pregnancy were negatively associated with placental length, thickness, volume, weight and disc eccentricity, while positively correlated with placental IL-6, TNF-α, CRP, CD68, MCP-1, IL-10, HO-1, HIF-1α and GRP78. In mid-pregnancy, maternal TPOAb levels were negatively correlated with placental length, width and area. In late pregnancy, maternal TPOAb levels were negatively correlated with placental length, area, volume and weight. Repeated measures analysis showed that maternal TPOAb positivity tended to increase placental TNF-α, CD68 and MCP-1 while decreasing placental length, width and area than TPOAb negativity. Repeated measures analysis showed that maternal TPOAb levels were positively correlated with placental IL-6, TNF-α, CD68, MCP-1, IL-10, HO-1, HIF-1α and GRP78, while negatively correlated with placental length, area, volume, weight, and disc eccentricity.ConclusionThere may be trimester-specific associations between maternal TPOAb levels and placental morphology and inflammatory and oxidative stress responses. The effect of maternal TPOAb levels on placental morphology is present throughout pregnancy. Early pregnancy may be the critical period for the association between maternal TPOAb levels and placental inflammatory and oxidative stress responses.</p

Image_1_Association of maternal thyroid peroxidase antibody during pregnancy with placental morphology and inflammatory and oxidative stress responses.jpeg

BackgroundStudies suggest that thyroid peroxidase antibody (TPOAb) positivity exposure during pregnancy may contribute to changes in placental morphology and pathophysiology. However, little is known about the association of maternal TPOAb during pregnancy with placental morphology and cytokines. This study focuses on the effect of repeated measurements of maternal TPOAb during pregnancy on the placental morphology and cytokines.MethodsBased on Ma’anshan Birth Cohort (MABC) in China, maternal TPOAb levels were retrospectively detected in the first, second and third trimesters. Placental tissues were collected 30 minutes after childbirth, placental morphological indicators were obtained by immediate measurement and formula calculation, and cytokine mRNA expression was detected by real-time quantitative polymerase chain reaction (RT-qPCR) afterward. Generalized linear models and linear mixed models were analyzed for the relationships of maternal TPOAb in the first, second and third trimesters with placental indicators.ResultsTotally 2274 maternal-fetal pairs were included in the analysis of maternal TPOAb levels and placental morphology, and 2122 pairs were included in that of maternal TPOAb levels and placental cytokines. Maternal TPOAb levels in early pregnancy were negatively associated with placental length, thickness, volume, weight and disc eccentricity, while positively correlated with placental IL-6, TNF-α, CRP, CD68, MCP-1, IL-10, HO-1, HIF-1α and GRP78. In mid-pregnancy, maternal TPOAb levels were negatively correlated with placental length, width and area. In late pregnancy, maternal TPOAb levels were negatively correlated with placental length, area, volume and weight. Repeated measures analysis showed that maternal TPOAb positivity tended to increase placental TNF-α, CD68 and MCP-1 while decreasing placental length, width and area than TPOAb negativity. Repeated measures analysis showed that maternal TPOAb levels were positively correlated with placental IL-6, TNF-α, CD68, MCP-1, IL-10, HO-1, HIF-1α and GRP78, while negatively correlated with placental length, area, volume, weight, and disc eccentricity.ConclusionThere may be trimester-specific associations between maternal TPOAb levels and placental morphology and inflammatory and oxidative stress responses. The effect of maternal TPOAb levels on placental morphology is present throughout pregnancy. Early pregnancy may be the critical period for the association between maternal TPOAb levels and placental inflammatory and oxidative stress responses.</p

Gel Phase Membrane Retards Amyloid β‑Peptide (1–42) Fibrillation by Restricting Slaved Diffusion of Peptides on Lipid Bilayers

Plasma membranes in the human brain can interact with amyloid β-peptide (1–42; Aβ₄₂) and induce Aβ₄₂ fibrillation, which is considered to be a crucial process underlying the neurotoxicity of Aβ₄₂ and the pathogenesis of Alzheimer’s disease (AD). However, the mechanism of membrane-mediated Aβ₄₂ fibrillation at the molecular level remains elusive. Here we study the role of adsorbed Aβ₄₂ peptides on membrane-mediated fibrillation using supported lipid bilayers of varying phase structures (gel and fluid). Using total internal reflection fluorescence microscopy and interfacial specific second-order nonlinear optical spectroscopy, we show that the dynamics of 2D-mobile Aβ₄₂ molecules, facilitated by the highly mobile lipids underneath the peptides, are critical to Aβ₄₂ fibrillation on liquid phase membranes. This growth mechanism is retarded on gel phase membranes where the dynamics of 2D-mobile peptides are restricted by the “frozen” lipids with less mobility