Lin Du's research while affiliated with China Agricultural University and other places

Strigolactones (SLs) are plant hormones that regulate several key agronomic traits, including shoot branching, leaf senescence, and stress tolerance. The artificial regulation of SL biosynthesis and signaling has been considered as a potent strategy in regulating plant architecture and combatting the infection of parasitic weeds to help improve crop yield. DL1b is a previously reported SL receptor inhibitor molecule that significantly promotes shoot branching. Here, we synthesized 18 novel compounds based on the structure of DL1b. We performed rice tillering activity assay and selected a novel small molecule, C6, as a candidate SL receptor inhibitor. In vitro bioassays demonstrated that C6 possesses various regulatory functions as an SL inhibitor, including inhibiting germination of the root parasitic seeds Phelipanche aegyptiaca, delaying leaf senescence and promoting hypocotyl elongation of Arabidopsis. ITC analysis and molecular docking experiments further confirmed that C6 can interact with SL receptor proteins, thereby interfering with the binding of SL to its receptor. Therefore, C6 is considered a novel SL receptor inhibitor with potential applications in plant architecture control and prevention of root parasitic weed infestation.

Strigolactone (SL) biosynthesis inhibitors have shown impressive activity in increasing shoot branching and inhibiting seed germination of the root parasitic plants Striga spp. and Orobanche spp. Herein, novel 1H-1,2,4-triazole derivatives were designed as SL biosynthesis inhibitors based on the backbone modification strategy, 33 target compounds were chemical synthesized and screened on Arabidopsis thaliana and Oryza sativa. The structure–activity relationship analysis enabled the discovery of a potential SL biosynthesis inhibitor B4 with the promising activity in increasing shoot branching, elongating taproot by inhibiting the biosynthesis of 4-deoxyorobanchol (4DO). We further found that B4-treated A. thaliana showed increased branching phenotype with the upregulated gene expression of AtMAX3 and AtMAX4. These results indicated that B4 might be a potent SL biosynthesis inhibitor and provide a unique scaffold for the development of new SL biosynthesis inhibitors.

Strigolactones (SLs) are a class of plant hormones and rhizosphere communication signals of great interest. They perform diverse biological functions including the stimulation of parasitic seed germination and phytohormonal activity. However, their practical use is limited by their low abundance and complex structure, which requires simpler SL analogues and mimics with maintained biological function. Here, new, hybrid-type SL mimics were designed, derived from Cinnamic amide, a new potential plant growth regulator with good germination and rooting-promoting activities. Bioassay results indicated that compound 6 not only displayed good germination activity against the parasitic weed O. aegyptiaca with an EC50 value of 2.36 × 10−8 M, but also exhibited significant inhibitory activity against Arabidopsis root growth and lateral root formation, as well as promoting root hair elongation, similar to the action of GR24. Further morphological experiments on Arabidopsis max2-1 mutants revealed that 6 possessed SL-like physiological functions. Furthermore, molecular docking studies indicated that the binding mode of 6 was similar to that of GR24 in the active site of OsD14. This work provides valuable clues for the discovery of novel SL mimics.

In our previous work, compound Y9k, 1-phenethyl-3- (3-(trifluoromethyl) phenyl) urea, displayed significant inhibition activity on root growth of Arabidopsis. To further investigate the application of urea compounds, a series of novel urea derivatives O1-O22 were designed and synthesized. The biological evaluation demonstrated that compounds O3, O11 and O13 exhibited excellent inhibition activity on root growth and the inhibition activity of O13 to the root growth of Arabidopsis was 2 orders of magnitude higher than that of the commercial herbicide clopyralid. Herbicidal activity assessment indicated that O13 displayed significant inhibition activity on weeds, especially in Amaranthus retroflexus. Furthermore, the morphological investigation of the auxin reporter (DR5::GUS) revealed that O13 could significantly enhanced transcriptional activity of auxin response reporter. These results suggested that O13 could be a promising scaffold for the discovery of novel auxin-related herbicide, and showed potentiality in crop protection from weeds.

Chronic mucocutaneous candidiasis (CMC) is characterized by recurrent or persistent infections with Candida of the skin, nails, and mucous membranes (e.g., mouth, esophagus, and vagina). Compared with that of other infectious diseases, the immune pathogenic mechanism of CMC is still poorly understood. We identified a signal transducer and activator of transcription 1 gain-of-function (c.Y289C) mutation in a CMC patient. Single-cell transcriptional profiling on peripheral blood mononuclear cells from this patient revealed decreases in immature B cells and monocytes. Further analysis revealed several differentially expressed genes related to immune regulation, including RGS1, TNFAIP3, S100A8/A9, and CTSS. In our review of the literature on signal transducer and activator of transcription 1 gain-of-function (c.Y289C) mutations, we identified seven cases in total. The median age of onset for CMC (n=4, data lacking for three cases) was 10.5 years (range: birth to 11 years), with an average onset age of 8 years. There were no reports linking tumors to the c.Y289C mutation, and the incidence of pre-existing clinical disease in patients with the c.Y289C mutation was similar to previous data.

The cotton defoliation strategy is highly appreciated in Xinjiang, where mechanical harvesting is limited by a large proportion of green leaves and unopened bolls at harvest due to an insufficient temperature sum. Because of a high plant density, the application of defoliants (harvest aids) by tractors is less efficient; thus, unmanned aerial vehicles (UAVs) for spraying harvest aids are becoming more and more popular. However, it is unknown if this method affects spraying quality and whether the spray is affected by the cotton plant type that was shaped by chemical topping. This study aims to address if chemical topping could enhance defoliation when harvest aids is sprayed using UAV. Field experiments were carried out in 2019 and 2020 in Alaer, Xinjiang, China. The topping treatments included manual topping (MT) as the control and chemical topping (CT) that inhibit apical growth of the stem by foliar application of mepiquat chloride (MC) at 90 (MC90), 180 (MC180), or 270 (MC270) g ha–1 in mid-July. The harvest aids was sprayed in mid-September using UAVs. The average droplet deposition and deposits of harvest aids within the canopy in CT and MT were not different in 2019. However, the average droplet deposition and deposits of CT were much higher than those of MT in 2020. Both droplet deposition and deposits decreased with canopy height, and the droplet distribution performance of CT was better than that of MT. The droplet deposition and deposits in the upper and middle canopy of CT were significantly higher than those of MT in 2020. At 21 days after harvest aids application, the number of leaves per plant in CT was significantly lower than that in MT, while there was no difference between the amounts of MC. CT did not affect boll opening. Moreover, the yield and quality were not affected by harvest aids application using UAVs and CT. We concluded that spraying harvest aids using UAVs combined with CT improved management efficiency and economic benefits by saving labor, without loss of cotton yield and quality. Our results demonstrate that applying harvest aids using UAVs in cotton with CT could improve the quality of defoliation and provide a reference for optimizing cotton managements globally.

Deeper and longer roots allow crops to survive and flourish, but our understanding of the plant growth regulators promoting root system establishment is limited. Here, we report that, a novel auxin receptor agonist, named K-10, had a remarkable promotive effect on root growth in both Arabidopsis thaliana and Oryza sativa through the enhancement of root-related signaling responses. Using computer-aided drug discovery approaches, we developed potent lead compound by screening artificial chemicals on the basis of the auxin receptor TIR1 (Transport Inhibitor Response 1), and a series of N-(benzo[d] [1,3] dioxol-5-yl)-2-(one-benzylthio) acetamides, K-1 to K-22, were designed and synthesized. The results of bioassay showed that K-10 exhibited an excellent root growth-promoting activity far exceeding that of NAA (1-naphthylacetic acid). A further morphological investigation of the auxin related mutants (yucQ, tir1) revealed that K-10 had auxin-like physiological functions and was recognized by TIR1, and K-10 significantly enhanced auxin response reporter’s (DR5:GUS) transcriptional activity. Consistently, transcriptome analysis showed that K-10 induced a common transcriptional response with auxin and down-regulated the expression of root growth-inhibiting genes. Further molecular docking analysis revealed that K-10 had a stronger binding ability with TIR1 than NAA. These results indicated that this class of derivatives could be a promising scaffold for the discovery and development of novel auxin receptor agonists, and the employment of K-10 may be effective for enhancing root growth and crop production.