Dysregulated maternal nutrition, such as vitamin deficiencies and excessive levels of glucose and fatty acids, increases the risk for congenital heart disease (CHD) in the offspring. However, the association between maternal amino-acid levels and CHD is unclear. Here, it is shown that increased leucine levels in maternal plasma during the first trimester are associated with elevated CHD risk in the offspring. High levels of maternal leucine increase embryonic lysine-leucylation (K-Leu), which is catalyzed by leucyl-tRNA synthetase (LARS). LARS preferentially binds to and catalyzes K-Leu modification of lysine 339 within T-box transcription factor TBX5, whereas SIRT3 removes K-Leu from TBX5. Reversible leucylation retains TBX5 in the cytoplasm and inhibits its transcriptional activity. Increasing embryonic K-Leu levels in high-leucine-diet fed or Sirt3 knockout mice causes CHD in the offspring. Targeting K-Leu using the leucine analogue leucinol can inhibit LARS activity, reverse TBX5 K-Leu modification, and decrease the occurrence of CHD in high-leucine-diet fed mice. This study reveals that increased maternal leucine levels increases CHD risk in the offspring through inhibition of embryonic TBX5 signaling, indicating that leucylation exerts teratogenic effects during heart development and may be an intervening target of CHD.

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In this study, a monofunctionalized bio‐based benzoxazine monomer (VAnBZ‐CN) is synthesized by condensation of vanillin, formaldehyde, and aniline, and a bifunctional epoxy‐functionalized poly(dimethylsiloxane) (PDMS‐epoxy) is also prepared through hydrosilylation reactions with allyl glycidyl ether. By blending the inorganic PDMS‐epoxy with the VAnBZ‐CN benzoxazine monomer, an organic/inorganic hybrid material is formed, which exhibited enhanced thermal stability after thermal curing polymerization. The improved thermal stability observed in the hybrid material can be attributed to a combination of the formation of the triazine structure by VAnBZ‐CN and the presence of the inorganic part of PDMS‐epoxy on the surface. For example, the PDMS‐epoxy/VAnBZ‐CN = 1/1 hybrid showed the thermal decomposition temperature (Td10) of 309 °C, the glass transition temperature (Tg) of 165 °C, and the char yield of 54 wt.% after the thermal curing polymerization process conducted at 240 °C based on thermogravimetric (TGA) and dynamic mechanical analyses (DMA). Furthermore, the char yield of the hybrid material with PDMS‐epoxy/VAnBZ‐CN = 1/3 is higher than that both of pure VAnBZ‐CN and PDMS‐epoxy after the thermal curing polymerization process. This result indicates that the addition of PDMS‐epoxy resin can improve the formation of a char residue and then enhance the resistance to thermal decomposition for their overall thermal stabilities.