Discovery of Novel 5,6-Dihydro-4-pyrido[2,3,4-]quinazoline Irreversible Inhibitors Targeting Both Wild-Type and A775_G776insYVMA Mutated HER2 Kinases.

HER2 mutations were seen in 4% of non-small-cell lung cancer (NSCLC) patients. Most of these mutations (90%) occur as an insertion mutation within the exon 20 frame, leading to the downstream activation of the PI3K-AKT and RAS/MAPK pathways. However, no targeted therapies have yet been approved worldwide.

Identification of amino acid response element of SLC38A9 as an ATF4-binding site in porcine skeletal muscle cells.

Amino acids can affect protein synthesis by activating mammalian target of rapamycin complex 1 (mTORC1) signaling pathway. Amino acid transporters SLC38A9 on the lysosomal membrane not only transport amino acids, but also can sense amino acids and activate mTORC1 signaling pathway. Activating transcription factor 4 (ATF4) can promote the expression of amino acid transporters by binding with amino acid response element (AARE).

Identification of novel regulatory GRE-binding elements in the porcine IP3R1 gene promoter and their transcriptional activation under glucocorticoid stimulation.

Inositol 1,4,5-trisphosphate receptor 1 (IP3R1) is a type of ligand-gated calcium channel that is expressed predominantly in mammalian skeletal muscle, where it acts as a key regulator of calcium homeostasis. In meat, calcium disequilibrium is accompanied by the deterioration of meat quality. Here we show that serum cortisol concentration was higher and the IP3R1 gene expression level increased markedly in pigs exposed to high stress.

The effects of reduced dietary protein level on amino acid transporters and mTOR signaling pathway in pigs.

Amino acid transporter plays an important role in regulating mTOR signaling pathway. This study investigated the effects of reduced dietary protein levels on amino acid transporters and mTOR signaling pathway. A total of 54 weaning pigs were randomly allocated into a 3 × 3 factorial design, followed by slaughtering the pigs separately after 10-, 25- and 45-day feeding, with 18 pigs from each feeding period divided into three subgroups for treatment with three different protein-level diets: 20% crude protein (CP) diet (normal recommended, high protein, HP), 17% CP diet (medium protein, MP) and 14% CP diet (low protein, LP).

Elucidating a molecular mechanism that the deterioration of porcine meat quality responds to increased cortisol based on transcriptome sequencing.

Stress response is tightly linked to meat quality. The current understanding of the intrinsic mechanism of meat deterioration under stress is limited. Here, male piglets were randomly assigned to cortisol and control groups.