Antifungal Activity of Novel Isoindoline-2-yl Putrescines as Potential Autophagy-Activated Fungicide.

The exacerbation of plant fungal diseases necessitates the development of new fungicides to prevent outbreaks. In this study, five novel isoindoline-2-yl putrescines (ISPs) were synthesized, and their synthetic procedures and gram-scale preparation were explored. When tested at 50 µg mL-1, ISPs did not significantly inhibit mycelial growth on agar plates. However, at 100 µg mL-1, they demonstrated remarkable in vivo efficacy in mitigating Botrytis cinerea infection, especially ISP3 showed curative and protective activities of 91.9% and 92.6%, respectively. Moreover, ISP3 also effectively halted lesion expansion of gray mold, Sclerotic rot, and Fusarium scabs, while inducing excessive malformed top mycelial branches of B. cinerea and Sclerotinia sclerotiorum, suppressing sclerotia formation in S. sclerotiorum, and triggering autophagic vacuolization with numerous autophagosomes in the mycelia of these fungi. Molecular docking revealed that ISP3 effectively bound to the active site of BcAtg3, forming hydrogen bonds with Ser279, Gly343, Asp370, and Asp13, along with establishing a stable salt bridge with Asp13. Furthermore, ISP3 possessed favorable ADMET properties. These findings highlight ISP3 as a promising antifungal candidate through autophagy activation.

Novel quinazolin-6-yl Isoindolinone: Altering polysaccharide chemstructure for antibacterial efficacy against Staphylococcus aureus.

The ongoing development of novel strategies to combat Staphylococcus aureus and eliminate its biofilm formation has gained significant attention for human health. Antibiotic-resistant S. aureus necessitates the development of novel antibacterial agents with new mechanism of action. This study introduced a promising recently synthesized quinazolin-6-yl isoindolinone (IQE-X1), which exhibited potent antibacterial and antibiofilm efficacy with average median inhibitory concentration (IC50) of 3.37 µg mL-1 and minimal inhibitory concentration (MIC) of 12.5 µg mL-1, coupled with its ability to reduce cell surface hydrophobicity. IQE-X1 dose-dependently decreased extracellular polysaccharides (EPS) and its component monosaccharides, including rhamnose, arabinose, glucosamine, galactose, glucose, xylose, mannose, and ribose, accompanied by an increase in capsular polysaccharides (CP) and its individual monosaccharides, especially glucosamine. IQE-X1 demonstrated specificity in modulating the structural profiles of EPS and CP by altering the compositional ratios of their component monosaccharides. The potential mechanism of polysaccharide modulation was preliminarily elucidated through the response of ß-N-acetylaminoglucosidase to IQE-X1 and their direct binding interaction. These findings provide new insights into the potential manipulation of the chemstructure of these biologically important macromolecules, EPS and CP, and highlight the antibacterial potential of IQE-X1 as a polysaccharide modulator for the development of more effective polysaccharide-targeted strategies against S. aureus.

Finite Element Simulation and Microstructural Analysis of Roll Forming for DP590 High-Strength Dual-Phase Steel Wheel Rims.

In this study, finite element (FE) simulation by the software Abaqus was relied on to investigate the roll forming process of a wheel rim made of an innovative dual-phase steel, i.e., DP590, after flash butt welding (FBW). In the simulation, an FE model was generated, including the design of the dies for flaring, three-roll forming, and expansion, and detailed key processing parameters based on practical production of the selected DP590. Combined with the microstructures and properties of the weld zone (WZ) and heat-affected zones (HAZs) after FBW, the distribution of stress/strain and the change in thickness of the base metal (BM), WZ and HAZs were analyzed, and compared in the important stages of roll forming. Theoretically, the variation in the microstructure and the corresponding stress-strain behaviors of the BM, WZ, and HAZs after FBW have led to the thickness reduction of DP590 that originated from softening behaviors occurring at the region of subcritical HAZs (SCHAZs), and a small amount of tempered martensite has evidently reduced the hardness and strength of the SCHAZ. Meanwhile, the distribution of stress/strain has been influenced to some extent. Further, the study includes the influence of the friction coefficient on the forming quality of the wheel rim to guarantee the simulation accuracy in practical applications. In sum, the dual-phase steel has to be carefully applied to the wheel rim, which needs to experience the processes of FBW and roll forming, focusing on the performance of SCHAZs.

Optimising Two-Stage Vacuum Heat Treatment for a High-Strength Micro-Alloyed Steel in Railway Spring Clip Application: Impact on Microstructure and Mechanical Performance.

The heat treatment process is a vital step for manufacturing high-speed railway spring fasteners. In this study, orthogonal experiments were carried out to obtain reliable optimised heat treatment parameters through a streamlined number of experiments. Results revealed that a better comprehensive mechanical performance could be obtained under the following combination of heat treatment parameters: quenching temperature of 850 °C, holding time of 35 min, medium of 12% polyalkylene glycol (PAG) aqueous solution, tempering temperature of 460 °C, and holding time of 60 min. As one of the most important testing criteria, fatigue performance would be improved with increasing strength. Additionally, a high ratio of martensite to ferrite is proven to improve the fatigue limit more significantly. After this heat treatment process, the metallographic microstructure and mechanical properties satisfy the technical requirements for the high-speed railway practical operation. These findings provide a valuable reference for the practical forming process of spring fasteners.

Physical Simulation and Numerical Simulation of Flash Butt Welding for Innovative Dual Phase Steel DP590: A Comparative Study.

In this study, the microstructure and performance of newly designed dual-phase steel (DP590) after joining by flash butt welding (FBW) for vehicle wheel rims was analysed and compared by two simulations, i.e., physical simulation and numerical simulation, due to the high acceptance of these two methodologies. Physical simulation is regarded as a thermal-mechanical solution conducted by the Gleeble 3500 simulator and which can distribute the heat-affected zone (HAZ) of the obtained weld joint into four typical HAZs. These are coarse-grained HAZ, fine-grained HAZ, inter-critical HAZ and sub-critical HAZ. A combination of ferrite and tempered martensite leads to the softening behaviour at the sub-critical HAZ of DP590, which is verified to be the weakest area, and influences the final performance due to ~9% reduction of hardness and tensile strength. The numerical simulation, relying on finite element method (FEM) analysis, can distinguish the temperature distribution, which helps us to understand the relationship between the temperature distribution and real microstructure/performance. Based on this study, the combination of physical and numerical simulations can be used to optimise the flash butt welding parameters (flash and butt processes) from the points of temperature distribution (varied areas), microstructure and performance, which are guidelines for the investigation of flash butt welding for innovative materials.

Fungicidal activity of novel quinazolin-6-ylcarboxylates and mode of action on Botrytis cinerea.

BACKGROUND: Fungal diseases remain important causes of crop failure and economic losses. As the resistance toward current selective fungicides becomes increasingly problematic, it is necessary to develop efficient fungicides with novel chemotypes. RESULTS: A series of novel quinazolin-6-ylcarboxylates which combined the structures of pyridine or heterocyclic motif and the N-(3-chloro-4-fluorophenyl)quinazolin-4-amine moiety, a binding group of ATP-binding site of gefitinib, were evaluated for their fungicidal activity on different phytopathogenic fungi. Most of these compounds showed excellent fungicidal activities against Botrytis cinerea and Exserohilum rostratum, especially compound F17 displayed the highest activity with EC50 values as 3.79 µg mL-1 against B. cinerea and 2.90 µg mL-1 against E. rostratum, which was similar to or even better than those of the commercial fungicides, such as pyraclostrobin (EC50 , 3.68, 17.38 µg mL-1 ) and hymexazol (EC50 , 4.56, 2.13 µg mL-1 ). Moreover, compound F17 significantly arrested the lesion expansion of B. cinerea infection on tomato detached leaves and strongly suppressed grey mold disease on tomato seedlings in greenhouse. The abilities of compound F17 to induce cell apoptosis of the non-germinated spores, to limit oxalic acid production, to reduce malate dehydrogenase (MDH) expression, and to block the active pocket of MDH protein were demonstrated in B. cinerea. CONCLUSION: The novel quinazolin-6-ylcarboxylates containing ATP-binding site-directed moiety, especially compound F17, could be developed as a potential fungicidal candidate for further study. © 2023 Society of Chemical Industry.