In conclusion BmSpry was targeted by three viruses to

In conclusion, BmSpry was targeted by three viruses to regulate the ERK pathway and thus ensure viral reproduction in the silkworm. This is the first report regarding a general mechanism of host regulation by multiple silkworm viruses, and this can pave the way for future virus control in other insects.
Acknowledgments This work was funded by the National Natural Science Foundation of China (No. 31802014), the Natural Science Foundation of Chongqing, China (cstc2018jcyjAX0211, cstc2018jcyjAX0487, cstc2016jcyjA0524), and Chongqing Postdoctoral Science Foundation (XmT2018006).
Introduction Learning disabilities (LDs) often occur in childhood. Also known as children\'s LDs, these children exhibit a variety of learning-related symptoms, such as difficulty in learning and remembering. The 5th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) defines LDs to be neurodevelopmental disorders. These are some of the most important disorders for children globally, and cause widespread concern (Miodovnik et al., 2014). Studies show that on average, one in six children in the United States have LDs, and about 20% to 25% of these children exhibit moderate to severe LDs (Boyle et al., 2011; Landrigan et al., 2012; Iuculano et al., 2015). The global problem of environment-related LDs in children is so severe, that a committee of experts convened by the National Academy of Sciences concluded that 3% of neurodevelopmental disorders are directly caused by exposure to environmental toxins, and that a further 25% of neurodevelopmental disorders are due to the widely understood interaction between environmental factors and genetic susceptibility (Landrigan et al., 2012). Dibutyl phthalate (DBP) is a typical persistent organic neurotoxic pollutant (Kobrosly et al., 2014). It is a widely used plasticizer that results in high exposure levels in normal daily life (Guo et al., 2011). Studies have reported the occurrence of phthalate metabolites in Phosphocreatine disodium salt specimens from the U.S., Germany, Sweden, Mexico, Japan and Korea, indicating the widespread exposure of humans to phthalates. Based on the urinary concentrations of phthalate metabolites, Guo et al. (2011) estimated that the daily intake of DBP in China was 12.2 μg/kg bw/day, exceeded the tolerable daily intake of 10 μg/kg bw/day, proposed for DBP, by the European Food Safety Authority. Infants and children exposed to DBP through diet, inhalation and skin contact show adverse cognitive and behavioral outcomes, with DBP particularly affecting their neurodevelopment (Ejaredar et al., 2015). Epidemiological studies by Cho et al. (2010) suggest that exposure to DBP can significantly reduce student\'s academic achievement and IQ. Other studies confirm that prolonged exposure to DBP during pregnancy can induce LD in children (Lien et al., 2015; Olesen et al., 2017). Lien et al. (2015) found positive associations between maternal DBP exposure and externalizing domain behavior problems in 8-year-old children. Olesen et al. (2017) reported that boys who experienced increased prenatal DBP exposure scored lower in language development assessments. The brain is an important target organ for exogenous stimulation, including DBP (Wójtowicz et al., 2017), while the hippocampus is a key functional region for learning and memory (Whitlock et al., 2006). There is emerging evidence that phthalate including DBP may have deleterious effects on the developing brain in 0–12-year-old children with behavioral problems (Ejaredar et al., 2015). The supporting laboratory studies and proposed mechanisms underlying the adverse impacts of DBP in relation to hippocampal toxicity have also been reported (Holahan and Smith, 2015). Moreover, DBP-induced apoptosis in the hippocampal neurons of DBP-exposed immature rats are also demonstrated (Li et al., 2013; Wójtowicz et al., 2017). Although the observed associations are based on limited studies with a broad range of endpoints, the implications of such outcomes are of concern from a public health standpoint and merit further investigation given the non-negligible influence of the DBP exposure to those LDs (Miodovnik et al., 2014).