The tight association between nitrogen status and pathogenesis has been broadly documented in plant–pathogen interactions. However, the interface between primary metabolism and disease responses remains largely unclear. Here, we show that knockout of a single amino acid transporter, LYSINE HISTIDINE TRANSPORTER1 (LHT1), is sufficient for Arabidopsis thaliana plants to confer a broad spectrum of disease resistance in a salicylic acid–dependent manner. We found that redox fine-tuning in photosynthetic cells was causally linked to the lht1 mutant-associated phenotypes. Furthermore, the enhanced resistance in lht1 could be attributed to a specific deficiency of its main physiological substrate, Gln, and not to a general nitrogen deficiency. Thus, by enabling nitrogen metabolism to moderate the cellular redox status, a plant primary metabolite, Gln, plays a crucial role in plant disease resistance.

Baicalein, a widely used Chinese herbal medicine, has historically been used in anti-inflammatory and anti-cancer therapies. However, the anti-metastatic effect and molecular mechanism(s) of baicalein on hepatocellular carcinoma (HCC) remain poorly understood. Therefore, the purpose of this study was to assess the anti-metastatic effects of baicalein and related mechanism(s) on HCC. Based on assays utilized in both HCC cell lines and in an animal model, we found that baicalein inhibited tumor cell metastasis in vivo and in vitro. Furthermore, after treatment with baicalein for 24 hours, there was a decrease in the levels of matrix metalloproteinase-2 (MMP-2), MMP-9 and urokinase-type plasminogen activator (u-PA) expression as well as proteinase activity in hepatocellular carcinoma MHCC97H cells. Meanwhile, the expression of tissue inhibitor of metalloproteinase-1 (TIMP-1) and TIMP-2 were increased in a dose-dependent fashion. Moreover, baicalein treatment dramatically decreased the levels of the phosphorylated forms of MEK1 and ERK1/2. MEK1 overexpression partially blocked the anti-metastatic effects of baicalein. Combined treatment with an ERK inhibitor (U0126) and baicalein resulted in a synergistic reduction in MMP-2, MMP-9 and u-PA expression and an increase in TIMP-1 and TIMP-2 expression; the invasive capabilities of MHCC97H cells were also inhibited. In conclusion, baicalein inhibits tumor cell invasion and metastasis by reducing cell motility and migration via the suppression of the ERK pathway, suggesting that baicalein is a potential therapeutic agent for HCC.

Gene duplication provides resources for novel gene functions. Identification of the amino acids responsible for functional conservation and divergence of duplicated genes will strengthen our understanding of their evolutionary course. Here, we conducted a systemic functional investigation of phosphatidylethanolamine binding proteins (PEBPs) in soybean (Glycine max) and Arabidopsis thaliana. Our results demonstrated that after the ancestral duplication, the lineage of the common ancestor of the FLOWERING LOCUS T (FT) and TERMINAL FLOWER1 (TFL1) subfamilies functionally diverged from the MOTHER OF FT AND TFL1 (MFT) subfamily to activate flowering and repress flowering, respectively. They also underwent further specialization after subsequent duplications. Although the functional divergence increased with duplication age, we observed rapid functional divergence for a few pairs of young duplicates in soybean. Association analysis between amino acids and functional variations identified critical amino acid residues that led to functional differences in PEBP members. Using transgenic analysis, we validated a subset of these differences. We report clear experimental evidence for the functional evolution of the PEBPs in the MFT, FT, and TFL1 subfamilies, which predate the origin of angiosperms. Our results highlight the role of amino acid divergence in driving evolutionary novelty after duplication.