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To determine the effects of microbial proteins on Qingzhuan tea sensory quality during tea pile fermentation, tea leaf metabolomic and microorganism proteomic analyses were performed. In total, 1835 differential metabolites and 443 differentially expressed proteins of the microorganisms were identified. Correlation analysis between metabolomics and proteomics data revealed that the levels of microbial proteins EG II and CBH I cellulase may play important roles in cell wall construction and permeability, which were crucial for the interaction between tea leaves and microorganisms. Microbial proteins heat shock proteins (HSP), alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH), and CuAO related to detoxification and stress responses showed a positive correlation with tea theanine, glutamine, γ-aminobutyric acid, glutamic acid, catechin, (-)-gallocatechin gallate, and (-)-catechin gallate, suggesting their effects on tea characteristic compound accumulation, thus affecting Qingzhuan tea sensory quality.

Weed resistance is a critical issue in crop production. Among the known herbicides, 4-hydroxyphenylpyruvate dioxygenase (HPPD) inhibitors are crucial for addressing weed resistance. HPPD inhibitors constitute a pivotal aspect of contemporary crop protection strategies. The advantages of these herbicides are their broad weed spectrum, flexible application, and excellent compatibility with other herbicides. They also exhibit satisfactory crop selectivity and low toxicity and are environmentally friendly. An increasing number of new HPPD inhibitors have been designed by combining computer-aided drug design with conventional design approaches. Herein, the molecular design and structural features of innovative HPPD inhibitors are reviewed to guide the development of new HPPD inhibitors possessing an enhanced biological efficacy.

4-Hydroxyphenylpyruvate dioxygenase (HPPD) is a crucial target enzyme in albino herbicides. The inhibition of HPPD activity interferes with the synthesis of carotenoids, blocking photosynthesis and resulting in bleaching and necrosis. To develop herbicides with excellent activity, a series of 3-hydroxy-2-(6-substituted phenoxynicotinoyl)-2-cyclohexen-1-one derivatives were designed via active substructure combination. The title compounds were characterized via infrared spectroscopy, 1 H and 13 C nuclear magnetic resonance spectroscopies, and high-resolution mass spectrometry. The structure of compound III-17 was confirmed via single-crystal X-ray diffraction. Preliminary tests demonstrated that some compounds had good herbicidal activity. Crop safety tests revealed that compound III-29 was safer than the commercial herbicide mesotrione in wheat and peanuts. Moreover, the compound exhibited the highest inhibitory activity against Arabidopsis thaliana HPPD ( At HPPD), with a half-maximal inhibitory concentration of 0.19 μM, demonstrating superior activity compared with mesotrione (0.28 μM) in vitro. A three-dimensional quantitative structure-activity relationship study revealed that the introduction of smaller groups to the 5-position of cyclohexanedione and negative charges to the 3-position of the benzene ring enhanced the herbicidal activity. A molecular structure comparison demonstrated that compound III-29 was beneficial to plant absorption and conduction. Molecular docking and molecular dynamics simulations further verified the stability of the complex formed by compound III-29 and At HPPD. Thus, this study may provide insights into the development of green and efficient herbicides.

Mesosulfuron-methyl, an inhibitor of acetolactate synthase (ALS), has been extensively used in wheats. However, it can damage wheat ( Triticum aestivum ) and even lead to crop death. Herbicide safeners selectively shield crops from such damage without compromising weed control. To mitigate the phytotoxicity of mesosulfuron-methyl in crops, several purine derivatives were developed based on active substructure splicing. The synthesized title compounds underwent thorough characterization using infrared spectroscopy, 1 H nuclear magnetic resonance ( 1 H NMR), 13 C nuclear magnetic resonance ( 13 C NMR), and high-resolution mass spectrometry. We evaluated chlorophyll and glutathione contents as well as various enzyme activities to evaluate the safer activity of these compounds. Compounds III-3 and III-7 exhibited superior activity compared with the safener mefenpyr-diethyl. Molecular structure analysis, along with predictions of absorption, distribution, metabolism, excretion, and toxicity, indicated that compound III-7 shared pharmacokinetic traits with the commercial safener mefenpyr-diethyl. Molecular docking simulations revealed that compound III-7 competitively bound to the ALS active site with mesosulfuron-methyl, elucidating the protective mechanism of the safeners. Overall, this study highlights purine derivatives as potential candidates for novel safener development.

Protoporphyrinogen oxidase (PPO, EC 1.3.3.4) catalyzes the oxidation of protoporphyrinogen IX to protoporphyrin IX, which is a key step in the synthesis of porphyrins in vivo. PPO inhibitors use protoporphyrinogen oxidase as the target and block the biosynthesis process of porphyrin by inhibiting the activity of the enzyme, eventually leading to plant death. In this paper, phenyl triazolinone was used as the parent structure, and the five-membered heterocycle with good herbicidal activity was introduced by using the principle of substructure splicing. According to the principle of bioisosterism, the sulfur atoms on the thiophene ring were replaced with oxygen atoms. Finally, 33 phenyl triazolinones and their derivatives were designed and synthesized, and their characterizations and biological activities were investigated. The in vitro PPO inhibitory activity and greenhouse herbicidal activity of 33 target compounds were determined, and compound D4 with better activity was screened out. The crop safety determination, field weeding effect determination, weeding spectrum determination, and crop metabolism study were carried out. The results showed that compound D4 showed good safety to corn, soybean, wheat, and peanut but poor selectivity to cotton. The field weeding effect of this compound is comparable to that of the commercial herbicide sulfentrazone. The herbicidal spectrum experiment showed that compound D4 had a wide herbicidal spectrum and a good growth inhibition effect on dicotyledonous weeds. Molecular docking results showed that compound D4 forms a hydrogen bond with amino acid residue Arg-98 in the tobacco mitochondria ( mt PPO)-active pocket and forms two π-π stacking interactions with Phe-392. This indicates that compound D4 has stronger PPO inhibitory activity. This indicates that compound D4 has wide prospects for development.

4-Hydroxyphenylpyruvate dioxygenase (EC 1.13.11.27, HPPD) is one of the most widely studied herbicide targets and has gained significant attention. To identify potential effective HPPD inhibitors, a rational multistep virtual screening workflow was built, which included CBP models (based on the receptor-ligand interactions in the crystal complex), Hypogen models with activity prediction ability (according to the derivation of structure-activity relationships from a set of molecules with reported activity values), and a consensus docking procedure (consisting of LibDock, Glide, and CDOCKER). About 1 million molecules containing diketone or β-keto-enol substructures were filtered by Lipinski's rules, CBP model, and Hypogen model. A total of 12 compounds with similar docking postures were generated by consensus docking. Eventually, four molecules were screened based on the specific binding pattern and affinity of the HPPD inhibitor. The biological evaluation in vivo displayed that compounds III-1 and III-2 exhibited comparable herbicidal activity to isoxaflutole and possessed superior safety on various crops (wheat, rice, sorghum, and maize). The ADMET prediction (absorption, distribution, metabolism, excretion, and toxicity) showed that compound III possessed relatively good toxicological results. This work provides a theoretical basis and valuable reference for the virtual screening and molecular design of novel HPPD inhibition herbicides.

Leptographium procerum has been demonstrated to play important roles in the invasive success of red turpentine beetle (RTB), one of the most destructive invasive pests in China. Our previous studies found that bacterial volatile ammonia plays an important role in the maintenance of the RTB- L. procerum invasive complex. In this study, we found a GPCR gene Gpr-1 that was a response to ammonia but not involved in the ammonia-induced carbohydrate metabolism. Deletion of Gpr-1 significantly inhibited the growth and pathogenicity but thickened the cell wall of L. procerum, resulting in more resistance to cell wall-perturbing agents. Further analyses suggested that Gpr-1 deletion caused growth defects that might be due to the dysregulation of the amino acid and lipid metabolisms. The thicker cell wall in the Δ Gpr-1 mutant was induced through the cell wall remodeling process. Our results indicated that Gpr-1 is essential for the growth of L. procerum by regulating the nutritional metabolism, which can be further explored for potential applications in the management of RTB.

Herbicide safeners, highly effective antidotes, find widespread application in fields for alleviating the phytotoxicity of herbicides to crops. Designing new herbicide safeners remains a notable issue in pesticide research. This review focuses on discussing and summarizing the structure-activity relationships, molecular structures, physicochemical properties, and molecular docking of herbicide safeners in order to explore how different structures affect the safener activities of target compounds. It also provides insights into the application prospects of computer-aided drug design for designing and synthesizing new safeners in the future.

4-Hydroxyphenylpyruvate dioxygenase inhibitors ( Echinochloa crus-galli 1.13.11.27, HPPD) have gained significant popularity as one of the best-selling herbicides worldwide. To identify highly effective HPPD inhibitors, a rational design approach utilizing bioisosterism was employed to create a series of 2-(arylformyl)cyclohexane-1,3-dione derivatives. A total of 29 novel compounds were synthesized and characterized through various techniques, including IR, 1 H NMR, 13 C NMR, and HRMS. Evaluation of their inhibitory activity against Arabidopsis thaliana HPPD ( At HPPD) revealed that certain derivatives exhibited superior potency compared to mesotrione (IC 50 = 0.204 μM). Initial herbicidal activity tests demonstrated that compounds 27 and 28 were comparable to mesotrione in terms of weed control and crop safety, with compound 28 exhibiting enhanced safety in canola crops. Molecular docking analyses indicated that the quinoline rings of compounds 27 and 28 formed more stable π-π interactions with the amino acid residues Phe-360 and Phe-403 in the active cavity of At HPPD, surpassing the benzene ring of mesotrione. Molecular dynamics simulations and molecular structure comparisons confirmed the robust binding capabilities of compounds 27 and 28 to At HPPD. This study provides a valuable reference for the development of novel triketone herbicide structures, serving as a blueprint for future advancements in this field.

Protoporphyrinogen oxidase (PPO, EC 1.3.3.4) inhibitor herbicides have attracted widespread attention in recent years as ideal herbicides due to their high efficiency, low toxicity, and low pollution. In this article, 30 phenylpyrazole derivatives containing five-membered heterocycles were designed and synthesized according to the principle of bioelectronic isoarrangement and active substructure splicing. A series of structural characterizations were performed on the synthesized compounds. The herbicide activity in greenhouse was evaluated to determine their growth inhibition effect on weeds, their IC 50 value through in vitro PPO enzyme activity measurement was calculated, and target compounds 2i and 3j that have herbicide effects comparable to pyraflufen-ethyl were selected. Crop safety experiments have shown that when the spraying concentration is 300 g of ai/ha, gramineous crops such as wheat, corn, and rice are more tolerant to compound 2i , with wheat exhibiting high tolerance, which is equivalent to the crop safety of pyraflufen-ethyl. Compound 2i can be used as a candidate herbicide for wheat, corn, and paddy fields, and the results are consistent with the cumulative concentration experiment. Molecular docking results showed that compound 2i interacted with the amino acid residue ARG-98 by forming two hydrogen bonds and interacted with the amino acid residue PHE-392 by forming two π-π stacking interactions, indicating that compound 2i has more excellent herbicidal activity than pyraflufen-ethyl and is expected to become a potential lead compound of phenylpyrazole PPO inhibitor herbicides.

The phytotoxicity of herbicides on crops is a major dilemma in agricultural production. Fortunately, the emergence of herbicide safeners is an excellent solution to this challenge, selectively enhancing the performance of herbicides in controlling weeds while reducing the phytotoxicity to crops. But owing to their potential toxicity, only a tiny proportion of safeners are commercially available. Natural products as safeners have been extensively explored, which are generally safe to mammals and cause little pollution to the environment. They are typically endogenous signal molecules or phytohormones, which are generally difficult to extract and synthesize, and exhibit relatively lower activity than commercial products. Therefore, it is necessary to adopt rational design approaches to modify the structure of natural safeners. This paper reviews the application, safener effects, structural characteristics, and modifications of natural safeners and provides insights on the discovery of natural products as potential safeners in the future.

Nicosulfuron is the leading herbicide in the global sulfonylurea (SU) herbicide market; it was jointly developed by DuPont and Ishihara. Recently, the widespread use of nicosulfuron has led to increasingly prominent agricultural production hazards, such as environmental harm and influence on subsequent crops. The use of herbicide safeners can significantly alleviate herbicide injury to protect crop plants and expand the application scope of existing herbicides. A series of novel aryl-substituted formyl oxazolidine derivatives were designed using the active group combination method. Title compounds were synthesized using an efficient one-pot method and characterized by infrared (IR) spectrometry, 1 H and 13 C nuclear magnetic resonance (NMR), and high-resolution mass spectrometry (HRMS). The chemical structure of compound V-25 was further identified by X-ray single crystallography. The bioactivity assay and structure-activity relationship proved that nicosulfuron phytotoxicity to maize could be reduced by most title compounds. The glutathione S -transferase (GST) activity and acetolactate synthase (ALS) in vivo were determined, and compound V-12 showed inspiring activity comparable to that of the commercial safener isoxadifen-ethyl. The molecular docking model indicated that compound V-12 competed with nicosulfuron for the acetolactate synthase active site and that this is the protective mechanism of safeners. Absorption, distribution, metabolism, excretion, and toxicity (ADMET) predictions demonstrated that compound V-12 exhibited superior pharmacokinetic properties to the commercialized safener isoxadifen-ethyl. The target compound V-12 shows strong herbicide safener activity in maize; thus, it may be a potential candidate compound that can help further protect maize from herbicide damage.

Tembotrione, a 4-hydroxyphenylpyruvate dioxygenase (HPPD) inhibitor, has been widely used in many types of plants. Tembotrione has been reported for its likelihood of causing injury and plant death to certain corn hybrids. Safeners are co-applied with herbicides to protect certain crops without compromising weed control efficacy. Alternatively, herbicide safeners may effectively improve herbicide selectivity. To address tembotrione-induced Zea mays injury, a series of novel ester-substituted cyclohexenone derivatives were designed using the fragment splicing method. In total, 35 title compounds were synthesized via acylation reactions. All the compounds were characterized using infrared spectroscopy, 1 H and 13 C nuclear magnetic resonance spectroscopy, and high-resolution mass spectrometry. The configuration of compound II-15 was confirmed using single-crystal X-ray diffraction. The bioactivity assay proved that tembotrione phytotoxicity to maize could be reduced by most title compounds. In particular, compound II-14 exhibited the highest activity against tembotrione. The molecular structure comparisons as well as absorption, distribution, metabolism, excretion, and toxicity predictions demonstrated that compound II-14 exhibited pharmacokinetic properties similar to those of the commercial safener isoxadifen-ethyl. The molecular docking model indicated that compound II-14 could prevent tembotrione from reaching or acting with Z. mays HPPD (PDB: 1SP8). Molecular dynamics simulations showed that compound II-14 maintained satisfactory stability with Z. mays HPPD. This research revealed that ester-substituted cyclohexenone derivatives can be developed as potential candidates for discovering novel herbicide safeners in the future.

Herbicide safeners are agricultural chemicals that protect crops from herbicide injury and improve the safety of herbicides and the effectiveness of weed control. Safeners induce and enhance the tolerance of crops to herbicides through the synergism of multiple mechanisms. The principal mechanism is that the metabolic rate of the herbicide in the crop is accelerated by safeners, resulting in the damaging concentration at the site of action being reduced. We focused on discussing and summarizing the multiple mechanisms of safeners to protect crops in this review. It is also emphasized how safeners alleviate herbicide phytotoxicity to crops by regulating the detoxification process and conducting perspectives on future research on the action mechanism of safeners at the molecular level.

Inflammatory bowel disease (IBD) is a global chronic disease with a long duration and repeated relapse. Currently, there is still a lack of effective approaches to prevent IBD. Food-derived oryzanol (ORY) possesses extensive biological activities, such as ameliorating bowel diseases, antioxidation, and antiobesity. However, the mechanism of ORY in preventing colitis remains unclear. The present research aims to explore the potential mechanism of ORY in dextran sulfate sodium (DSS)-stimulated colitis in a rat model. The results showed that the symptoms of colitis were significantly improved with the administration of ORY. Mechanismly, the expression levels of Zonula occludens-1 (ZO-1), Claudin-1, Occludin, MUC2, and TFF3 were elevated through ORY treatment, suggesting that oral ORY relieved the degree of gut barrier damage of colitis rats. Meanwhile, 16S sequencing results found that ORY supplementation increased the abundances of Alloprevotella , Roseburia , Treponema , Muribaculaceae , and Ruminococcus , which are associated with the synthesis of short-chain fatty acids (SCFAs). Moreover, GC-MS results confirmed that ORY supplementation reversed the DSS-induced reduction of acetic acid, butyric acid, and total acid. Further research indicated that ORY intervention downregulated the TLR4/NF-κB/NLRP3 pathway, which is closely linked to the expression of proinflammatory cytokines and colon injury. Taken together, ORY ameliorates DSS-stimulated gut barrier damage and inflammatory responses via the gut microbiota-TLR4/NF-κB/NLRP3 signaling axis.

Pyrimethanil (PMT) is an anilinopyrimidine bactericide with poor water solubility, which limits its applications. To improve the physical and chemical properties of PMT, hydroxypropyl-β-cyclodextrin/pyrimethanil inclusion compound nanofibers (HPβCD/PMT-IC-NFs) were fabricated via electrospinning. A variety of analytical techniques were used to confirm the formation of the inclusion compound. Scanning electron microscopy image displayed that HPβCD/PMT-IC-NF was homogeneous without particles. Thermogravimetric analysis indicated that the formation of the inclusion compound improved the thermostability of PMT. In addition, the phase solubility test illustrated that the inclusion compound formed by PMT and HPβCD had a stronger water solubility. The antifungal effect test exhibited that HPβCD/PMT-IC-NF had better antifungal properties. The release experiment confirmed that HPβCD/PMT-IC-NF had a sustained-release effect, and the release curve conformed to the first-order kinetic model equation. In short, the fabrication HPβCD/PMT-IC-NF inhibited improved solubility and thermostability of PMT, thus promoting the development of pesticide dosage form to water-based and low-pollution direction.

Detoxification plays an important role in herbicide action. Herbicide safeners selectively protect crops from herbicide injury without reducing the herbicidal efficiency against the target weeds. With the large-scale use of herbicides, herbicide safeners have been widely used in sorghum, wheat, rice, corn, and other crops. In recent years, an increasing number of unexpected new herbicide safeners have been designed. The varieties, structural characteristics, uses, and synthetic routes of commercial herbicide safeners are reviewed in this paper. The design ideas and structural characteristics of novel herbicide safeners are summarized, which provide a basis for the design of bioactive molecules as new herbicide safeners in the future.

Protoporphyrinogen oxidase (PPO, EC 1.3.3.4) is an important target for discovering novel herbicides, and it causes bleaching symptoms by inhibiting the synthesis of chlorophyll and heme. In this study, the active fragments of several commercial herbicides were joined by substructure splicing and bioisosterism, and a series of novel diphenyl ether derivatives containing five-membered heterocycles were synthesized. The greenhouse herbicidal activity and the PPO inhibitory activity in vitro were discussed in detail. The results showed that most compounds had good PPO inhibitory activity, and target compounds containing trifluoromethyl groups tended to have higher activity. Among them, compound G4 showed the best inhibitory activity, with a half-maximal inhibitory concentration (IC 50 ) of 0.0468 μmol/L, which was approximately 3 times better than that of oxyfluorfen (IC 50 = 0.150 μmol/L). In addition, molecular docking indicated that compound G4 formed obvious π-π stacking interactions and hydrogen bond interactions with PHE-392 and ARG-98, respectively. Remarkably, compound G4 had good safety for corn, wheat, rice, and soybean, and the cumulative concentration in crops was lower than that of oxyfluorfen. Therefore, compound G4 can be used to develop potential lead compounds for novel PPO inhibitors.

In this paper, a dual-functional probe, 2-(benzothiazol)-4-(3-hydroxy-4-methylphenyl) imino phenol ( BHMH ), was synthesized and characterized for the simultaneous detection of Cu 2+ and Fe 3+ in dimethyl sulfoxide/4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (DMSO/HEPES) (1:4, v/v, pH = 6.0). The limits of detections (LODs) for Cu 2+ and Fe 3+ were 9.05 and 48 nM, respectively. Based on the competitive coordination, the complex BHMH-Cu 2+ /Fe 3+ exhibited good sensitivity and selectivity for glyphosate. The LODs of BHMH-Cu 2+ and BHMH-Fe 3+ for glyphosate were 0.41 and 0.63 μM, respectively. The probe quantitatively detected glyphosate in tap water, Songhua River water, local water and soil, and food samples. The colorimetric on-site glyphosate sensing through the probe BHMH-Cu 2+ was also studied based on smartphones. BHMH and BHMH-Cu 2+ /Fe 3+ exhibited outstanding imaging capabilities for Cu 2+ , Fe 3+ , and glyphosate in living cells with low cytotoxicity, especially the first time for glyphosate.

Cinnamic acid, isolated from cinnamon bark, is a natural product with excellent bioactivity, and it effectively binds with cyclohexanedione to form novel 4-hydroxyphenylpyruvate dioxygenase (HPPD) inhibitors. According to the active sub-structure combination principle, a series of novel 3-hydroxy-2-cinnamoyl-2-en-1-one derivatives were designed and synthesized. The title compounds were characterized by infrared, 1 H NMR, 13 C NMR, and HRMS. The in vitro inhibitory activity of At HPPD verified that compound II-13 showed the most activity with a half-maximal inhibitory concentration (IC 50 ) value of 0.180 μM, which was superior to that of mesotrione (0.206 μM) in vitro. The preliminary herbicidal activity tests demonstrated that some compounds had good herbicidal activity especially compound II-13 at a concentration of 150 g ai/ha. The binding mode of At HPPD through molecular docking indicated that two oxygens of compounds II-13 formed bidentate interactions with metal ions, and the benzene ring formed π-π accumulation effects with Phe-381 and Phe-424. The results of molecular dynamics simulations showed that compound II-13 exhibited a more stable binding ability with At HPPD than mesotrione. This study provided insights into the development of natural and efficient herbicides in the future.

Fenoxaprop- p -ethyl (FE), a type of acetyl-CoA carboxylase (ACCase) inhibitor, has been extensively applied to a variety of crop plants. It can cause damage to wheat ( Triticum aestivum ) even resulting in the death of the crop. On the prerequisite of not reducing herbicidal efficiency on target weed species, herbicide safeners selectively protect crops from herbicide injury. Based on fragment splicing, a series of novel substituted pyrazole derivatives was designed to ultimately address the phytotoxicity to wheat caused by FE. The title compounds were synthesized in a one-pot way and characterized via infrared spectroscopy, 1 H nuclear magnetic resonance, 13 C nuclear magnetic resonance, and high-resolution mass spectrometry. The bioactivity assay proved that the FE phytotoxicity to wheat could be reduced by most of the title compounds. The molecular docking model indicated that compound IV-21 prevented fenoxaprop acid (FA) from reaching or acting with ACCase. The absorption, distribution, metabolism, excretion, and toxicity predictions demonstrated that compound IV-21 exhibited superior pharmacokinetic properties to the commercialized safener mefenpyr-diethyl. The current work revealed that a series of newly substituted pyrazole derivatives presented strong herbicide safener activity in wheat. This may serve as a potential candidate structure to contribute to the further protection of wheat from herbicide injury.

In this study, flexible and self-standing hydroxypropyl-β-cyclodextrin/difenoconazole inclusion complex (HPβCD/DZ-IC) nanofibers were prepared by polymer-free electrospinning, which exhibited potential to be a new fast-dissolving pesticide formulation. Scanning electron microscopy and optical microscopy were applied to evaluate the morphology of nanofibers, which showed that the resulting HPβCD/DZ-IC nanofibers were bead-free and uniform. In addition, the proton nuclear magnetic resonance ( 1 H NMR) spectrum suggested a stoichiometric ratio of 1:0.9 (HPβCD/DZ). Other characterization methods, such as UV-vis absorption, fluorescence spectroscopy, Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), and thermogravimetric analysis (TGA), were applied in this study. On the one hand, UV-vis absorption, fluorescence spectroscopy, FT-IR, XRD, and TGA provided useful information for the successful formation of an inclusion complex; on the other hand, the results of TGA indicated the thermal stability of DZ was enhanced after the formation of inclusion complexes. Besides, the phase solubility test could explain the increased water solubility of the nanofibers of inclusion complexes formed by DZ and HPβCD. The results of molecular docking studies demonstrated the most favorable binding interactions when HPβCD combined with DZ. The dissolution test and the antifungal performance test exhibited the characteristics of fast dissolution and the excellent antifungal performance of HPβCD/DZ-IC nanofibers, respectively.

Herbicide safeners enhance herbicide detoxification in crops without reducing their herbicidal efficacy against target weeds. To alleviate maize injury caused by the sulfonylurea herbicide nicosulfuron, a series of 1,3-disubstituted imidazolidine or hexahydropyrimidine derivatives were rationally designed via bioisosterism and active subunit combinations. Thirty novel compounds were synthesized using an efficient one-pot method and low-cost raw materials and characterized by IR, 1 H NMR, 13 C NMR, and high-resolution mass spectrometer (HRMS). Bioactivity and structure-activity relationship (SAR) were evaluated for herbicide safeners tested against nicosulfuron injury. Most of the compounds effectively protected sensitive maize against nicosulfuron damage. The parent skeletons and substituents of the target compounds both substantially influenced their safener activity. Compound I-3 exhibited superior bioactivity compared to the safener isoxadifen-ethyl. Molecular docking simulations disclosed that compound I-3 competed with nicosulfuron for the acetolactate synthase active site and demonstrated that this is the protective mechanism of safeners. The target compound I-3 presented with strong herbicide safener activity in maize and is, therefore, a potential candidate for the development of a novel herbicide safener.

Herbicide safeners enhance herbicide detoxification in crops without affecting target weed sensitivity. To enhance crop tolerance to the toxicity-related stress caused by the herbicide acetochlor (ACT), a new class of substituted phenyl isoxazole derivatives was designed by an intermediate derivatization method as herbicide safeners. Microwave-assisted synthesis was used to prepare the phenyl isoxazole analogues, and all of the structures were confirmed via IR, 1 H NMR, 13 C NMR, and HRMS. Compound I-1 was further characterized by X-ray diffraction analysis. Bioassay results showed that most of the obtained compounds provided varying degrees of safening against ACT-induced injury by increasing the corn growth recovery, glutathione content, and glutathione S -transferase activity. In particular, compound I-20 showed excellent safener activity against ACT toxicity, comparable to that of the commercial safener benoxacor. Gaussian calculations have been performed and the results indicated that the nucleophilic ability of compound I-20 is higher than that of benoxacor, thus the activity is higher than that of benoxacor. These findings demonstrate that phenyl isoxazole derivatives possess great potential for protective management in cornfields.

In this study, sugary maize dendrimer-like glucan (SMDG) was used as a delivery carrier for improving the bioavailability of resveratrol (RES). After optimization, the solubility of RES in RES-SMDG markedly increased to approximately 9.1 times that of the raw RES solution. The structural characterizations of the RES-SMDG formulation showed crystal RES was entrapped in the SMDG matrix for the amorphous state due to the strong intermolecular hydrogen bonds between the -OH of RES and glucan chains. In this case, antioxidant activity of RES-SMDG was markedly higher than that of the raw RES solution. In the Caco-2 cell model, the P app value of RES in the RES-SMDG group was slightly higher than those of common permeable compounds, while the cellular uptake was significantly improved. RES-SMDG also exhibited protective effects against cellular damage under oxidative stress. The results indicated that SMDG is an attractive carrier to encapsulate and protect hydrophilic bioactive ingredients.

To seek new protoporphyrinogen oxidase (PPO) inhibitors with better biological activity, a series of novel diphenyl ether derivatives containing tetrahydrophthalimide were designed based on the principle of substructure splicing and bioisomerization. PPO inhibition experiments exhibited that 6c is the most potential compound, with the half-maximal inhibitory concentration (IC 50 ) value of 0.00667 mg/L, showing 7 times higher activity than Oxyfluorfen (IC 50 = 0.0426 mg/L) against maize PPO and similar herbicidal activities to Oxyfluorfen in weeding experiments in greenhouses and field weeding experiments. In view of the inspected bioactivities, the structure-activity relationship (SAR) of this series of compounds was also discussed. Crop selection experiments demonstrate that compound 6c is safe for soybeans, maize, rice, peanuts, and cotton at a dose of 300 g ai/ha. Accumulation analysis experiments showed that the accumulation of 6c in some crops (soybeans, peanuts, and cotton) was significantly lower than Oxyfluorfen. Current work suggests that compound 6c may be developed as a new herbicide candidate in fields.

Herbicide safeners selectively protect crops from herbicide damage without reducing the herbicidal efficiency on target weed species. The title compounds were designed by the intermediate derivatization approach and fragment splicing to exploit novel potential safeners. A total of 31 novel diazabicyclo derivatives were synthesized by the microwave-assistant method using isoxazole-4-carbonyl chloride and diazabicyclo derivatives. All synthetic compounds were confirmed by infrared, 1 H and 13 C nuclear magnetic resonance, and high-resolution mass spectrometry. The bioassay results demonstrated that most of the title compounds could reduce the nicosulfuron phytotoxicity on maize. The glutathione S -transferase (GST) activity in vivo was assayed, and compound 4 ( S15 ) revealed an inspiring safener activity comparable to commercialized safeners isoxadifen-ethyl and BAS-145138. The molecular docking model exhibited that the competition at the active sites of target enzymes between compound 4 ( S15 ) and nicosulfuron was investigated with respect to herbicide detoxification. The current work not only provided a powerful supplement to the intermediate derivatization approach and fragment splicing in design pesticide bioactive molecules but also assisted safener development and optimization.

4-Hydroxyphenylpyruvate dioxygenase (HPPD, EC 1.13.11.27) is an important target site for discovering new bleaching herbicides. To explore novel HPPD inhibitors with excellent herbicidal activity, a series of novel N -aroyl diketone/triketone derivatives were rationally designed by splicing active groups and bioisosterism. Bioassays revealed that most of these derivatives displayed preferable herbicidal activity against Echinochloa crus-galli (EC) at 0.045 mmol/m 2 and Abutilon juncea (AJ) at 0.090 mmol/m 2 . In particular, compound I-f was more potent compared to the commercialized compound mesotrione. Molecular docking indicated that the corresponding active molecules of target compounds and mesotrione shared similar interplay with surrounding residues, which led to a perfect interaction with the active site of Arabidopsis thaliana HPPD.

Tribenuron-methyl (TM), as one of the sulfonylurea (SU) herbicides, has been widely and effectively applied for many kinds of plants. SUs inhibit plant growth by restraining the biosynthetic pathway of branched-chain amino acids (BCAAs) catalyzed by acetolactate synthase (ALS). Safeners are agrochemicals that protect crops from herbicide injuries. To improve the crop tolerance under TM toxicity stress, this paper evaluated the protective effect of N -tosyloxazolidine-3-carboxamide. It turned out that most of the tested compounds showed significant protection against TM via enhancing the glutathione (GSH) content and glutathione S -transferase (GST) activity. Among all of the tested compounds, compound 16 exhibited more excellent protection than the contrast safener R-28725 and other target compounds. A positive correlation between the growth level, endogenous GSH content, and GST activity was observed in this research. The GST kinetic parameter V max of the maize was increased by 29.6% after treatment with compound 16 , while K m was decreased by 51.9% compared to the untreated control. The molecular docking model indicated that compound 16 could compete with TM in the active site of ALS, which could interpret the protective effects of safeners. The present work demonstrated that N -tosyloxazolidine-3-carboxamide derivatives could be considered as potential candidates for developing new safeners in the future.

The core-shell structured micelles from octenylsuccinated oat β-glucan (OSβG) are able to solubilize β-carotene (βC). This study reveals molecular interactions governing the formation, stabilization, and βC uptake of OSβG micelles (OSβG-Ms) by means such as water contact angle, 1 H nuclear magnetic resonance, dynamic light scattering, and confocal laser scanning microscopy. The results indicated that the micellization of OSβG molecules is triggered by hydrophobic interactions between octenylsuccinate (OSA) moieties, while OSβG-Ms are stabilized via both hydrophobic interactions and hydrogen bonds. For their uptake of βC, βC molecules are first adsorbed onto OSβG-Ms by interacting with OSA moieties scattered on micelle surface. By further interacting with OSA moieties located in micelle shell, βC molecules travel across the shell and finally are trapped in the hydrophobic core. In simulated gastrointestinal fluids, βC is controlled released from OSβG-Ms as an integrated consequence of its diffusion as well as the swelling and erosion of OSβG-Ms. As a result, this study first uncovered the mechanism underlying the uptake of βC by OSβG-Ms, which will certainly facilitate the effective loading of hydrophobic ingredients by OSβG-Ms.

Egg yolk immunoglobulins (IgY), as nutraceutical supplement for therapeutic or prophylactic intervention, have been extensively studied. The effects of IgY on small molecular toxin-induced toxicity in animals are unclear. In the present study, the protection of highly purified and specific anti-AFB 1 IgY against AFB 1 -induced genotoxicity and oxidative damage on the rat liver model were investigated. Our results revealed that AFB 1 induced significant oxidative damage markers, as well as AFB 1 -induced protein expression in antioxidant, pro- and antiapoptosis processes in rat liver. These effects could be significantly inhibited by cogavage with anti-AFB 1 IgY in a dose-dependent manner. However, anti-AFB 1 IgY did not significantly induce hepatic CAT and SOD1. To explore mechanisms, metabolite experiments were established to evaluate the influence of anti-AFB 1 IgY on the absorption of AFB 1 in rats. Middle and high doses of anti-AFB 1 IgY reduced hepatic AFB 1 -DNA adducts by 43.3% and 52.9%, AFB 1 - N 7 -guanine urinary adducts by 19.6% and 34.4%, and AFB 1 -albumin adducts by 10.5% and 21.1%, respectively. The feces of high dose anti-AFB 1 IgY cogavaged rats contained approximately 2-fold higher AFB 1 equivalents at 3-6 h after ingestion than AFB 1 group feces, indicating IgY inhibited AFB 1 uptake. These results had provided insight that anti-AFB 1 IgY could prevent animal organs from damage caused by AFB 1 and will be beneficial for the application of detoxification antibody as a supplement in food.

Boronate affinity materials have been widely used for enrichment of cis-diol molecules. In this work, phenylboronic acid functionalized adsorbents were prepared via a simple and efficient procedure grafting phenylboronic acid groups onto amino macroporous resins. Elemental analysis has confirmed the successful functionalization of AR-1M and AR-2M with approximately 2.17% and 0.73% weight percentage of boron. Comparatively, AR-1M possessed higher lactulose adsorption capacity ( q e-Lu , 84.78 ± 0.95 mg/g dry resin) under neutral conditions (pH = 7), while the introduced glutaraldehyde spacer arms on AR-2M resulted in excellent adsorption selectivity (α ≈ 23), high adsorption efficiency (π ≈ 22%), and fast adsorption/desorption rate. The purity of lactulose (Pu D Lu ) through pH-driven adsorption (pH 7-8) and desorption (pH 1.5) can be effectively improved depending on the ratio of lactulose to lactose. When lactulose/lactose ≥ 1:1, Pu D Lu ≈ 95% was achieved. No significant drop in q e-Lu (>90%) was observed after ten-consecutive repeats. Results demonstrated that the newly developed method may achieve satisfactory performance in lactulose purification.

The granules of sweet potato starch were size fractionated into three portions with significantly different median diameters ( D 50 ) of 6.67 (small-sized), 11.54 (medium-sized), and 16.96 μm (large-sized), respectively. Each portion was hydrophobized at the mass-based degrees of substitution (DS m ) of approximately 0.0095 (low), 0.0160 (medium), and 0.0230 (high). The Pickering emulsion-stabilizing capacities of modified granules were tested, and the resultant emulsions were characterized. The joint effects of granule size and DS m on emulsifying capacity (EC) were investigated by response surface methodology. For small-, medium-, and large-sized fractions, their highest emulsifying capacities are comparable but, respectively, encountered at high (0.0225), medium (0.0158), and low (0.0095) DS m levels. The emulsion droplet size increased with granule size, and the number of freely scattered granules in emulsions decreased with DS m . In addition, the term of surface density of the octenyl succinic group (SD -OSG ) was first proposed for modified starch granules, and it was proved better than DS m in interpreting the emulsifying capacities of starch granules with varying sizes. The present results implied that, as the particulate stabilizers, the optimal DS m of modified starch granules is size specific.

An amphiphilic fatty acid oat β-glucan ester (FAOGE) was first synthesized, and its structure-curcumin loading capacity (CLC) relationship was investigated. The DS of product increased with the addition of acyl imidazole, decreased with Mw of β-glucan, and did not relate to the acyl chain length. Characterizations by FT-IR and (1)H NMR evidenced the presence of ester groups in FAOGE and confirmed its successful synthesis. The aqueous self-aggregation behavior of FAOGE was revealed by transmission electron microcopy and dynamic light scattering. With the aid of response surface methodology, a quadratic polynomial equation was obtained to quantitatively describe the structure-CLC relationship of FAOGE by using Mw of β-glucan, acyl chain length, and DS as variables. The CLC increased with Mw of β-glucan and acyl chain length but maximized at a medium DS. The maximum CLC value was obtained as 4.05 μg/mg. Hence, FAOGE is a potential candidate in solubilizing and delivering hydrophobic food ingredients.

The octenylsuccinic groups in esterification-modified sugary maize soluble starches with a low (0.0191) or high (0.0504) degree of substitution (DS) were investigated by amyloglucosidase hydrolysis followed by a combination of chemical and physical analysis. The results showed the zeta-potential remained at approximately the same value regardless of excessive hydrolysis. The weight-average molecular weight decreased rapidly and reached 1.22 × 10(7) and 1.60 × 10(7) g/mol after 120 min for low-DS and high-DS octenylsuccinic anhydride (OSA) modified starch, respectively. The pattern of z-average radius of gyration as well as particle size change was similar to that of Mw, and z-average radius of gyration decreased much more slowly, especially for high-DS OSA starch. Compared to native starch, two characteristic absorption peaks at 1726.76 and 1571.83 cm(-1) were observed in FT-IR spectra, and the intensity of absorption peaks increased with increasing DS. The NMR results showed that OSA starch had several additional peaks at 0.8-3.0 ppm and a shoulder at 5.56 ppm for OSA substituents, which were grafted at O-2 and O-3 positions in soluble starch. The even distribution of OSA groups in the center area of soluble starch particle has been directly shown under CLSM. Most substitutions were located near branching points of soluble starch particles for a low-DS modified starch, whereas the substituted ester groups were located near branching points as well as at the nonreducing ends in OSA starch with a high DS.

The effects of mechanical and jet grindings on the proximate composition, phenolics, and antioxidant capacity of insoluble antioxidant dietary fiber powder from citrus pomace (IADFP-CP) were investigated in comparison with ordinary grinding. IADFP-CP from jet grinding showed higher levels of crude fat, total sugar, and free phenolics and lower levels of crude protein and bound phenolics than that from ordinary grinding. Totally, 14 phenolics (9 free, 1 bound, and 4 free/bound) in IADFP-CP were identified by RP-HPLC-DAD/ESI-Q-TOF-MS/MS. Hesperidin accounted for >57% of total phenolics in IADFP-CP. Among IADFP-CPs, the jet-ground presented the highest free phenolics but the lowest bound phenolics. The IADFP-CP from jet grinding presented the highest antioxidant capacity of free phenolics (by DPPH and FRAP assays), followed by the ones from mechanical and then ordinary grinding. The present study suggests that jet grinding could improve the extraction of phenolic compounds from IADFP-CP and increase the antioxidant capacities of free phenolics and the resultant powder.

The interaction between ε-polylysine (ε-PL) and anionic polysaccharides has gained considerable attention recently because of its scientific impact on the stability and appearance of liquid food systems. The purpose of this study was to characterize the interactions between ε-PL and carboxymethyl sweet potato starch (CSS) using isothermal titration calorimetry (ITC), electrical charge, and turbidity measurements. The results showed that the interaction between ε-PL and CSS was electrostatic and mainly dependent on the molar ratio of amino groups in ε-PL to carboxyl groups in CSS. Additionally, the interaction between ε-PL and CSS was also associated with pH, degree of substitution (DS) of CSS, and ionic strength of the system. For the interaction of ε-PL with high DS (>0.235) CSS, three states of the ε-PL/CSS mixture were observed as transparent, turbid, and precipitated with a successive increase in amino/carboxyl molar ratio. Distinguishingly, a transparent mixture could be obtained for CSS with low DS (0.114) at a sufficiently high amino/carboxyl molar ratio. The present study provided basic guidance in designing liquid food systems containing both ε-PL and CSS.

Ultraperformance liquid chromatography coupled with hybrid quadrupole/ion mobility/orthogonal acceleration time-of-flight (oa-TOF) mass spectrometry (UPLC-IM-MS) was used to study the isomeric transformations of trans-5-caffeoylquinic acid, an extremely active compound present in multiple vegetables, fruits, and beverages. The UPLC/oa-TOF MS results proved that in phosphate buffer (pH 7.4), plasma, or urine sample, trans-5-caffeoylquinic acid first isomerizes to trans-4-caffeoylquinic acid and then to trans-3-caffeoylquinic acid by intramolecular acyl migration. When exposed to UV light, trans-3-, -4-, and -5-caffeoylquinic acids undergo cis/trans isomerization to form cis isomers. The isomerization was solely dependent on the pH of the matrix, as well as the incubation temperature, and was independent of metabolic enzymes. UPLC-IM-MS results revealed that a reversible cis/trans isomerization of caffeoylquinic acids could also be induced by the electric field in an electrospray source. Thus, understanding the possible role of electric field-induced isomerization of caffeoylquinic acids may help lessen the confusion between gas phase phenomena and liquid state chemistry when applying IM-MS analysis. The comprehensive understanding of caffeoylquinic acid isomerization transformations is crucial for the appropriate handling of samples and interpretation of experimental data.