Our data suggest that monitoring nuclear abnormalities in umbilical cord blood samples could be a useful tool to identify transplacental mutagens perfusion that is being discharged into the local environment.Polycystic Ovary Syndrome (PCOS) is a kind of endocrine disorder which is prevalent in adult women, so exploring more biomarkers for PCOS is imperative. Recently, circular RNA and microRNA are confirmed to be related with PCOS development. Whether circular RNA ASPH (circASPH) is involved in PCOS need to be studied further. We utilized RT-qPCR to measure the expression levels of circASPH, miR-375 and MAP2K6 in PCOS patients and normal group. The effects of circASPH and miR-375 on KGN cells proliferation and apoptosis were observed by CCK-8 assay, EdU incorporation assay and apoptosis assay, separately. Then Dual-luciferase reporter assay was carried out to verify the circASPH/miR375 axis and miR375/MAP2K6 axis. The interaction between circASPH and MAP2K6 were detected with the support of RT-qPCR and Western blot. We found circASPH and MAP2K6 were both over-expressed in PCOS patients, while miR-375 was in the opposite direction. IMT1B Moreover, miR-375 was negatively regulated by circASPH, while MAP2K6 was positively regulated by circASPH. In addition, circASPH directly targeted miR-375, which targeted MAP2K6. More than that, the knockdown of circASPH repressed KGN cells proliferation and enhanced apoptosis, while the silence of miR-375 reversed the above effects. In conclusion, circASPH promotes KGN cells proliferation through miR-375/MAP2K6 axis in PCOS, and they are thought-provoking biomarkers for PCOS diagnosis and therapy.Ocean global warming affects the distribution, life history and physiology of marine life. Extreme events, like marine heatwaves, are increasing in frequency and intensity. During sensitive stages of early fish development, the consequences may be long-lasting and mediated by epigenetic mechanisms. Here, we used European sea bass as a model to study the possible long-lasting effects of a marine heatwave during early development. We measured DNA methylation and gene expression in four tissues (brain, muscle, liver and testis) and detected differentially methylated regions (DMRs). Six genes were differentially expressed and contained DMRs three years after exposure to increased temperature, indicating direct phenotypic consequences and representing persistent changes. Interestingly, nine genes contained DMRs around the same genomic regions across tissues, therefore consisting of common footprints of developmental temperature in environmentally responsive loci. These loci are, to our knowledge, the first metastable epialleles (MEs) described in fish. MEs may serve as biomarkers to infer past life history events linked with persistent consequences. These results highlight the importance of subtle phenotypic changes mediated by epigenetics to extreme weather events during sensitive life stages. Also, to our knowledge, it is the first time the molecular effects of a marine heatwave during the lifetime of individuals are assessed. MEs could be used in surveillance programs aimed at determining the footprints of climate change on marine life. Our study paves the way for the identification of conserved MEs that respond equally to environmental perturbations across species. Conserved MEs would constitute a tool of assessment of global change effects in marine life at a large scale.The biota of European rivers are affected by a wide range of stressors impairing water quality and hydro-morphology. Only about 40% of Europe's rivers reach 'good ecological status', a target set by the European Water Framework Directive (WFD) and indicated by the biota. It is yet unknown how the different stressors in concert impact ecological status and how the relationship between stressors and status differs between river types. We linked the intensity of seven stressors to recently measured ecological status data for more than 50,000 sub-catchment units (covering almost 80% of Europe's surface area), which were distributed among 12 broad river types. Stressor data were either derived from remote sensing data (extent of urban and agricultural land use in the riparian zone) or modelled (alteration of mean annual flow and of base flow, total phosphorous load, total nitrogen load and mixture toxic pressure, a composite metric for toxic substances), while data on ecological status were taken from national statutory reporting of the second WFD River Basin Management Plans for the years 2010-2015. We used Boosted Regression Trees to link ecological status to stressor intensities. The stressors explained on average 61% of deviance in ecological status for the 12 individual river types, with all seven stressors contributing considerably to this explanation. On average, 39.4% of the deviance was explained by altered hydro-morphology (morphology 23.2%; hydrology 16.2%), 34.4% by nutrient enrichment and 26.2% by toxic substances. More than half of the total deviance was explained by stressor interaction, with nutrient enrichment and toxic substances interacting most frequently and strongly. Our results underline that the biota of all European river types are determined by co-occurring and interacting multiple stressors, lending support to the conclusion that fundamental management strategies at the catchment scale are required to reach the ambitious objective of good ecological status of surface waters. Andrographis paniculata is one of the commonly used herbal medicines worldwide. Nevertheless, evidences on adverse events (AEs) associated with Andrographis paniculata are very limited. This systematic review and meta-analysis was conducted to estimate and to compare the AE incidence of oral monotherapy Andrographis paniculata with others among patients with upper respiratory tract infection, noninfective diarrhea, and autoimmune disease. Systematic search was performed through six databases from inception until August 2018. Randomized controlled trial (RCT), cohort, or intensive monitoring of AEs was eligible for review if AE incidence was examined. The incidence of AEs was, then, pooled across studies using meta-analysis. Ten RCTs and 3 intensive monitoring studies were included. Incidence of serious AEs was very rare with the pooled incidence (95% CI) from RCTs of 0.02 per 1000 patients (0.0-0.5). However, the incidence of nonserious AEs was considered very common with the pooled incidence (95% CI) from RCTs of 102.