Design, synthesis biological activity, and docking of novel fluopyram derivatives containing guanidine group.

Succinate dehydrogenase (SDH), a crucial bridge enzyme between the respiratory electron transfer chain and tricarboxylic acid (or Krebs) cycle, has been identified as an ideal target for the development of effective fungicide. In this study, a series of 24 novel SDH inhibitors (SDHIs) were designed, synthesized, and characterized by 1H NMR, 13C NMR, and HRMS. In vitro fungicidal activity experiments, most of the compounds exhibited broad-spectrum antifungal activities against five plant pathogenic fungi. Compounds 9j and 9k showed excellent activities against Pythium aphanidermatum with EC50 values of 9.93 mg/L and 10.50 mg/L, respectively, which were superior to the lead compound Fluopyram with an EC50 value of 19.10 mg/L. Furthermore, the toxicity of these compounds was also tested against Meloidogyne incognita J2 nematodes. The results indicated that compound 9x exhibited moderate nematicidal activity (LC50/48 h = 71.02 mg/L). Molecular docking showed that novel guanidine amide of 9j formed hydrogen bonds with crucial residues, which was crucial to the binding of an inhibitor and SDH. This present work indicates that these derivatives may serve as novel potential fungicides targeting SDH.

Micro particle launcher/cleaner based on optical trapping technology.

Efficient and controllable launching function of an optical tweezers is a challenging task. We present and demonstrate a novel single fiber optical tweezers which can trap and launch (clean) a target polystyrene (PS) microsphere (diameter~10µm) with independent control by using two wavelengths beams: 980nm and 1480nm. We employ 980nm laser beam to trap the target PS microsphere by molding the fiber tip into a special tapered-shape; and we employ 1480nm laser beam to launch the trapped PS microsphere with a certain velocity by using the thermophoresis force generated from the thermal effect due to the high absorption of the 1480nm laser beams in water. When the launching force is smaller than the trapping force, the PS microsphere will be trapped near the fiber tip, and the launching force will blow away other PS microspheres in the workspace realizing the cleaning function; When the launching force is larger than the trapping force, the trapped PS microsphere will be launched away from the fiber tip with a certain velocity and towards a certain direction, realizing the launching function. The launching velocity, acceleration and the distance can be measured by detecting the interference signals generated from the PS microsphere surface and the fiber tip end-face. This PS microsphere launching and cleaning functions expanded new features of single fiber optical tweezers, providing for the possibility of more practical applications in the micro manipulation research fields.

All-fiber self-accelerating Bessel-like beam generator and its application.

We demonstrate an all-fiber transverse self-accelerating Bessel-like beam generator and its optical trapping application. The theoretical and experimental studies have been provided to verify this beam properties. We produce the Bessel-like beam by splicing the single-mode fiber and multimode fiber with a defined offset and then modulating the output light beam phase by fabricating a small hemispherical-lens fiber tip; therefore, the phase-modulated Bessel-like beam generates the properties of transverse self-accelerating. The transverse acceleration of the the Bessel-like beam generated here is ∼10(-4) µm(-1), which is almost 100 times larger than that of the beam generated in the free-space optical circuit based on the lens. The experimental and simulated results have good consistencies. The realization of the microparticle transverse acceleration transporting with this Bessel-like beam provides a new method for microparticles to be transported in a bending trajectory. This all-fiber transverse self-accelerating Bessel-like beam generator structure is simple, with high integration and small size, and constitutes a new development for high-precision biological cell experiments and manipulations.

Design of Inhibitors Targeting Chitin-Degrading Enzymes by Bioisostere Substitutions and Scaffold Hopping for Selective Control of Ostrinia furnacalis.

Chitin-degrading enzymes are critical components in regulating the molting process of the Asian corn borer and serve as potential targets for controlling this destructive pest of maize. Here, we used a scaffold-hopping strategy to design a series of efficient naphthylimide insecticides. Among them, compound 8c exhibited potent inhibition of chitinase from OfChi-h and OfChtI at low nanomolar concentrations (IC50 = 1.51 and 9.21 nM, respectively). Molecular docking simulations suggested that 8c binds to chitinase by mimicking the interaction of chitin oligosaccharide substrates with chitinase. At low ppm concentrations, compound 8c performed comparably to commercial insecticides in controlling the highly destructive plant pest, the Asian corn borer. Tests on a wide range of nontarget organisms indicate that compound 8c has very low toxicity. In addition, the effect of inhibitor treatment on the expression of genes associated with the Asian corn borer chitin-degrading enzymes was further investigated by quantitative real-time polymerase chain reaction. In conclusion, our study highlights the potential of 8c as a novel chitinase-targeting insecticide for effective control of the Asian corn borer, providing a promising solution in the quest for sustainable pest management.

Mode division multiplexing technology for single-fiber optical trapping axial-position adjustment.

We demonstrate trapped yeast cell axial-position adjustment without moving the optical fiber in a single-fiber optical trapping system. The dynamic axial-position adjustment is realized by controlling the power ratio of the fundamental mode beam (LP01) and the low-order mode beam (LP11) generated in a normal single-core fiber. In order to separate the trapping positions produced by the two mode beams, we fabricate a special fiber tapered tip with a selective two-step method. A yeast cell of 6 µm diameter is moved along the optical axis direction for a distance of ~3 µm. To the best of our knowledge, this is the first demonstration of the trapping position adjustment without moving the fiber for single-fiber optical tweezers. The excitation and utilization of multimode beams in a single fiber constitutes a new development for single-fiber optical trapping and makes possible more practical applications in biomedical research fields.

o-Nitrobenzyl-Based Caged exo-16,17-Dihydro-gibberellin A5-13-acetate for Photocontrolled Release of Plant Growth Regulators.

Caged plant growth regulators (caged PGRs) that release bioactive molecules under irradiation are critical in enhancing the efficacy and mitigating the negative environmental effects of PGRs. The synthetically derived plant growth inhibitor exo-16,17-dihydro-gibberellin A5-13-acetate (DHGA5) regulates the development and stress resilience of plants. We report here the conception of novel caged DHGA5 derivatives wherein the photoremovable protecting groups (PRPGs) serve not only to enable light-controlled release but also to protect the carboxyl group during chemical synthesis. Three o-nitrobenzyl-based caged DHGA5 derivatives with different substituents on the nitrobenzyl moiety were obtained and evaluated for their properties in vitro and in vivo. The photolysis half-life values of caged DHGA5 derivatives 7a, 7b, and 7c under a UV lamp were 15.6 h, 1.2 h, and 28.2 h, respectively. Experiments in vivo showed that 0.2 mM of the caged compounds significantly inhibited the growth of the model plant Arabidopsis thaliana and important crop rice in a precise photoactivated form.

Application of Natural Bioresources to Sustainable Agriculture: A C-Glycoside Insecticide Based on N-Acetyl-glucosamine for Regulating Insect Molting of Ostrinia furnacalis.

In order to increase the application of natural bioresources in drug discovery and development, a study on N-acetyl-glucosamine (GlcNAc) derivatives of chitin as green pesticides was necessary. In this study, we designed and synthesized a series of novel C-glycoside naphthalimides using GlcNAc as a starting material. Compound 10l showed high inhibitory activity against OfHex1 (IC50 = 1.77 µM), with a nearly 30-fold increase in activity over our previously reported C-glycoside CAUZL-A (IC50 = 47.47 µM). By observing the morphology of the Ostrinia furnacalis, we found that the synthesized compounds significantly inhibited the molting process. In addition, we further explored the morphological changes of the inhibitor-treated O. furnacalis cuticle using scanning electron microscopy. This is the first study to validate the insecticidal mechanism of OfHex1 inhibitors at the microscale level. Several compounds also exhibited excellent larvicidal activity against Plutella xylostella. Moreover, the toxicity measurements and predictions indicated that the C-glycoside naphthalimides have little effect on the natural enemy Trichogramma ostriniae and rats. Together, our results highlight an approach for the design of green pesticides, taking advantage of natural bioresources to control pests in agriculture.

Identification of novel nematode succinate dehydrogenase inhibitors: Virtual screening based on ligand-pocket interactions.

To discover new nematicidal succinate dehydrogenase (SDH) inhibitors with novel structures, we conducted a virtual screening of the ChemBridge library with 1.7 million compounds based on ligand-pocket interactions. The homology model of Caenorhabditis elegans SDH was established, along with a pharmacophore model based on ligand-pocket interactions. After the pharmacophore-based and docking-based screening, 19 compounds were selected for the subsequent enzymatic assays. The results showed that compound 1 (ID: 7607321) exhibited inhibitory activity against SDH with a determined IC50 value of 19.6 µM. Structural modifications and nematicidal activity studies were then carried out, which provided further evidence that compound 1 exhibited excellent nematicidal activity. Molecular dynamics simulations were then conducted to investigate the underlying molecular basis for the potency of these inhibitors against SDH. This work provides a reliable strategy and useful information for the future design of nematode SDH inhibitors.

Design, synthesis, biologically evaluation and molecular docking of C-glycosidic oximino carbamates as novel OfHex1 inhibitors.

The inhibition of function-specific ß-N-acetyl-D-hexosaminidases, such as OfHex1 from the Asian corn borer (Ostrinia furnacalis), is a promising strategy for the development of green pesticides. Among reported OfHex1 inhibitors, glycosyl inhibitors show especially high inhibitory activity. In this study, a series of novel C-glycosidic oximino carbamate derivatives were designed using the OfHex1 crystal structure and synthesized. Among the C-Glycoside derivatives studied, compound 7k exhibited the best inhibitory activity against OfHex1 (IC50 = 47.47 µM). Compound 7k also exhibited excellent larvicidal activity against Plutella xylostella. The potential inhibitory mechanism of 7k was studied using molecular docking. Notably, compound 7k is the first reported C-glycoside inhibitor of OfHex1. These results provide direction for the rational design of novel OfHex1 inhibitors.

Exposure to Umbelliferone Reduces Ralstonia solanacearum Biofilm Formation, Transcription of Type III Secretion System Regulators and Effectors and Virulence on Tobacco.

Ralstonia solanacearum is one of the most devastating phytopathogens and causes bacterial wilt, which leads to severe economic loss due to its worldwide distribution and broad host range. Certain plant-derived compounds (PDCs) can impair bacterial virulence by suppressing pathogenic factors of R. solanacearum. However, the inhibitory mechanisms of PDCs in bacterial virulence remain largely unknown. In this study, we screened a library of coumarins and derivatives, natural PDCs with fused benzene and α-pyrone rings, for their effects on expression of the type III secretion system (T3SS) of R. solanacearum. Here, we show that umbelliferone (UM), a 7-hydroxycoumarin, suppressed T3SS regulator gene expression through HrpG-HrpB and PrhG-HrpB pathways. UM decreased gene expression of six type III effectors (RipX, RipD, RipP1, RipR, RipTAL, and RipW) of 10 representative effector genes but did not alter T2SS expression. In addition, biofilm formation of R. solanacearum was significantly reduced by UM, though swimming activity was not affected. We then observed that UM suppressed the wilting disease process by reducing colonization and proliferation in tobacco roots and stems. In summary, the findings reveal that UM may serve as a plant-derived inhibitor to manipulate R. solanacearum T3SS and biofilm formation, providing proof of concept that these key virulence factors are potential targets for the integrated control of bacterial wilt.