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Ingestion of food toxins such as aflatoxin B1 (AFB1) during pregnancy may impair fetal neurodevelopment. However, animal model results may not be accurate due to the species' differences, and testing on humans is ethically impermissible. Here, we developed an in vitro human maternal–fetal multicellular model composed of a human hepatic compartment, a bilayer placental barrier, and a human fetal central nervous system compartment using neural stem cells (NSCs) to investigate the effect of AFB1 on fetal-side NSCs. AFB1 passed through the HepG2 hepatocellular carcinoma cells to mimic the maternal metabolic effects. Importantly, even at the limited concentration (0.0641 ± 0.0046 μM) of AFB1, close to the national safety level standard of China (GB-2761-2011), the mixture of AFB1 crossing the placental barrier induced NSC apoptosis. The level of reactive oxygen species in NSCs was significantly elevated and the cell membrane was damaged, causing the release of intracellular lactate dehydrogenase (p < 0.05). The comet experiment and γ-H2AX immunofluorescence assay showed that AFB1 caused significant DNA damage to NSCs (p < 0.05). This study provided a new model for the toxicological evaluation of the effect of food mycotoxin exposure during pregnancy on fetal neurodevelopment. [ABSTRACT FROM AUTHOR]

Avian influenza (AI) is an important zoonotic disease, which can be transmitted across species barriers to other hosts, especially humans, posing a serious threat to the poultry industry and public health. In recent years, human cases infected with the H10N8, H9N2, and H7N9 of avian influenza viruses (AIVs) have been identified frequently as have the internal genes of H7N9 and H10N8, which are derived from H9N2 viruses. The adaptive mutation of the PB2 gene is an important way for the H10N8, H9N2, and H7N9 AIVs to spread across species to adapt to new hosts. Several well‐known adaptive mutations in the PB2 gene, such as E627K, D701N, and A588V, significantly enhanced the virulence of the AIVs in mammals. However, the co‐adaptation of AIVs to avian and mammalian hosts is rarely studied. In this study, we found that the mutations of PB2‐I292V, PB2‐R389K, PB2‐A588V, PB2‐T598M/V, PB2‐L648V, and PB2‐T676M substitutions significantly increased after 2012. In addition, in our previous studies, we found that the human‐origin and avian‐origin of H10N8 AIVs with very high homology also have these six mutation differences in PB2 gene, and the avian‐origin H10N8 strain known as JX102 with all the key amino acids on the PB2 protein in the pre‐evolutionary stage, so JX102 was chosen as a model strain. Among them, PB2‐A588V significantly enhanced the activity of polymerase in avian and mammalian cells. Notably, animal experiments showed that PB2‐A588V substitution increased the pathogenicity and transmissibility in chickens and the virulence of mice. The combined mutations of PB2‐F6 (including PB2‐I292V, PB2‐R389K, PB2‐A588V, PB2‐T598M, PB2‐L648V, and PB2‐T676M) obtained higher adaptability of AIVs in avians and mammals than that of the single mutation of PB2‐A588V, which suggested that the PB2 588 site is a key co‐adaptation site and that synergies with other mutation sites can further enhance this co‐adaptability. The results of this study show that the emergence of co‐adaptation not only increases the threat to avians and mammals but may also contribute to a pandemic among avians and cross the interspecies barrier to mammals. [ABSTRACT FROM AUTHOR]