N-acetyl-β-d-hexosaminidase (Hex) is potential target for pesticide design. Here, a series of thiazolylhydrazone derivatives were designed, synthesized and evaluated as competitive inhibitors of OfHex1, a Hex from the agricultural pest Ostrinia furnacalis. The derivative 3k, with a (benzyloxy)methyl group at the N3 atom, demonstrated greater potency with a Ki of 10.2 µM. Molecular docking analysis indicated that the (benzyloxy)methyl group of 3k was bound to a previously unexplored pocket formed by Loop478-496. Then further optimization around naphthalene ring led to find the more potency substituent phenyl. The derivative 7, with phenoxyethyl group at R1 and a phenyl group at R2, demonstrated an augmented potency with a Ki of 2.1 µM. Molecular docking analysis indicated that 7 was bound to the active pocket of OfHex1 more favorably than 3k. This work suggests a novel scaffold for developing specific Hex inhibitors.

Cocoa is one of the major cash crops in Nigeria and its production is directly related to the effective utilization of agrochemicals. This paper analysed the factors influencing cocoa farmers’ compliance with agrochemical safety regulations. The data were collected from 326 cocoa farmers from Ogun and Osun states, using multi-stage sampling procedures. The data were analysed with Principal Component Analysis (PCA) and an Endogenous Tobit Regression model. The results showed that majority of the farmers were primarily growing cocoa and average ownership of personal protective equipment (PPE) was less than two. Awareness of manufacturers’ instructions was high for insecticides and fungicides, while majority of the farmers were not eating or drinking while handling agrochemicals. Safety compliance indicators were significantly influenced (p < 0.10) by farmers’ ownership of PPE, education, age, awareness of manufacturers’ safety instructions and health status. It was concluded that utilization of PPE was very low among the farmers and efforts to facilitate safety training on the use of different agrochemicals will facilitate safety compliance through proper understanding of manufacturers’ instructions.

Botrytis cinerea is a destructive plant pathogenic ascomycete that causes serious pre- and post-harvest losses worldwide. The novel sterol 14α-demethylase inhibitor (DMI) pyrisoxazole was recently registered for the control of tomato gray mold caused by B. cinerea in China. Baseline sensitivity of 110 B. cinerea isolates collected from nine provinces in China to pyrisoxazole was demonstrated, with a mean EC50 of 0.057 ± 0.029 μg/ml. Eleven stable mutants resistant to pyrisoxazole were generated via UV irradiation (RU-mutants) and spontaneous selection (RS-mutants) of conidia. The efficacy of pyrisoxazole against the resistant mutants was significantly lower than that of the sensitive isolates. Most of the pyrisoxazole- resistant mutants were less fit than the sensitive isolates, with reduced sporulation, conidia germination, sclerotium production, and pathogenicity, which was confirmed by the competitive ability test. Positive cross-resistance was only observed between pyrisoxazole and the DMIs tebuconazole and prochloraz, but not between pyrisoxazole and non-DMIs iprodione, procymidone, diethofencarb, fluazinam, pyrimethanil, or fludioxonil. A two-point mutation, at G476S and K104E in the RU-mutants, and a one point mutation, M231T, in the RS-mutants, were detected in the CYP51 protein of the resistant mutants. When exposed to pyrisoxazole, the induced expression level of CYP51 increased in the resistant isolates as compared to sensitive ones. Molecular docking suggested that G476S and M231T mutations both led to the loss of electrostatic interactions between CYP51 and pyrisoxazole, while no change was found with the K104E mutation. Thus, two point mutations on CYP51 protein combined with induced expression of its target gene appeared to mediate the pyrisoxazole resistance of B cinerea.

The use of agrochemicals in vegetable production could influence the selection for insecticide resistance in malaria vectors. Unfortunately, there is a dearth of information on the potential contribution of agrochemicals to insecticide resistance in Anopheles mosquitoes breeding on vegetable farms in southern Benin. A Knowledge, Attitudes and Practices study was conducted with 75 vegetable farmers from Houeyiho and Seme to determine the main agrochemicals used in vegetable production, and the concentration and frequency of application, among other details. Mosquitoes and breeding water were sampled from the farms for analysis. Bioassays were conducted on mosquitoes, while breeding water was screened for heavy metal and pesticide residue contamination. Lambda-cyhalothrin was the main insecticide (97.5%) used by farmers, and Anopheles coluzzii was the main mosquito identified. This mosquito species was resistant (30-63% mortality rate) to λ-cyhalothrin. It was also observed that 16.7% of the examined breeding sites were contaminated with λ-cyhalothrin residues. Furthermore, copper contamination detected in mosquito breeding sites showed a positive correlation (r = 0.81; P = 0.0017) with mosquito resistance to λ-cyhalothrin. The presence of copper in λ-cyhalothrin-free breeding sites, where mosquitoes have developed resistance to λ-cyhalothrin, suggests the involvement of copper in the insecticide resistance of malaria vectors; this, however, needs further investigation.

Bumblebees are a key pollinator. Understanding the factors that influence the timing of sleep and foraging trips is important for efficient foraging and pollination. Here, we illustrate how individual locomotor activity monitoring and colony-wide radio frequency identification tracking can be combined to analyze the effects of agrochemicals like neonicotinoids on locomotor and foraging rhythmicity and sleep quantity/quality in bumblebees. We also highlight aspects of the design that can be adapted for other invertebrates or agrochemicals, allowing broader application of these techniques. For complete details on the use and execution of this protocol, please refer to Tasman et al. (2020).

The type III secretion system (T3SS) in many Gram-negative bacterial pathogens is regarded as the most critical virulence determinant and an attractive target for novel anti-virulence drugs. In this study, we constructed a T3SS secretion reporter containing the β-lactamase gene fused with a signal peptide sequence of the T3SS effector gene, and established a high-throughput screening system for T3SS inhibitors in the plant pathogenic bacterium Acidovorax citrulli. From a library of 12,000 chemical compounds, we identified a series of benzyloxy carbonimidoyl dicyanide (BCD) derivatives that effectively blocked T3SS-dependent β-lactamase secretion. Substitution of halogens or nitro groups at the para-position on the benzene ring contributed to an increased inhibitory activity. One representative compound, BCD03 (3,4-dichloro-benzyloxy carbonimidoyl dicyanide), dramatically reduced pathogenicity of A. citrulli on melon seedlings, and attenuated hypersensitive responses in the non-host Nicotiana tabacum caused by pathogenic bacteria A. citrulli, Xanthomonas oryzae pv. oryzae and Pseudomonas syringae pv. tomato at sub-MIC concentrations. Western blotting assay further confirmed that BCD03 inhibited effector secretion from the above bacteria via T3SS in the liquid medium. Taken together, our data suggest that BCD derivatives act as novel inhibitors of T3SS in multiple plant bacterial pathogens.

4-Hydroxyphenylacetic acid (4HPAA) is an important building block for synthesizing drugs, agrochemicals, biochemicals, etc. 4HPAA is currently produced exclusively via petrochemical processes and the process is environmentally unfriendly and unsustainable. Microbial cell factory would be an attractive approach for 4HPAA production.

Identifying the fate of agrochemicals is important to understand their potential risk for living organisms. We report here new photodegradation products (PPs) of the fungicide fluopyram. The PPs were produced by irradiating a fluopyram standard in 0.1% acetonitrile aqueous media by a 150-W medium pressure Hg-lamp that emits wavelengths between 200⁻280 nm. The structural elucidation of PPs was achieved by combining the retention time, isotopic pattern, targeted fragmentation, and accurate mass measurements using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and high resolution-MS (HRMS). In addition to previously known PPs, seven new PPs of fluopyram were identified in this work: mainly dihydroxyl and hydroxylimide fluopyram as well as mono, di, and trihydroxyl lactam. Additionally, two PPs were found to be formed by rearrangement after the loss of H₂C=CH₂. Hence, the results of the work contribute to extending the current knowledge regarding the photoinduced fate of agrochemicals, and fluopyram in particular.

The vestibular system is responsible for body balance. There are substances that damage it, causing dizziness; these are termed vestibulotoxic substances. Agrochemicals have been investigated for ototoxicity because of studies that identified dizziness as a recurrent symptom among rural workers' complaints.

The ortho-substituted phenyl ring is a basic structural element in chemistry. It is found in more than three hundred drugs and agrochemicals. During the past decade, scientists have tried to replace the phenyl ring in bioactive compounds with saturated bioisosteres to obtain novel patentable structures. However, most of the research in this area has been devoted to the replacement of the para-substituted phenyl ring. Here we have developed saturated bioisosteres of the ortho-substituted phenyl ring with improved physicochemical properties: 2-oxabicyclo[2.1.1]hexanes. Crystallographic analysis revealed that these structures and the ortho-substituted phenyl ring indeed have similar geometric properties. Replacement of the phenyl ring in marketed agrochemicals fluxapyroxad (BASF) and boscalid (BASF) with 2-oxabicyclo[2.1.1]hexanes dramatically improved their water solubility, reduced lipophilicity and most importantly retained bioactivity. This work suggests an opportunity for chemists to replace the ortho-substituted phenyl ring in bioactive compounds with saturated bioisosteres in medicinal chemistry and agrochemistry.

Object. To test whether preoperative immunonutrition is efficacious in reducing postoperative complications in patients of thymoma with myasthenia gravis (MG). Material and Methods. A total of 244 patients operated on for thymoma with myasthenia gravis were prospectively assigned to two groups, each receiving seven-day preoperative and seven-day postoperative nutrition. The patients in immunonutrition group were given oral immunonutrition (IN). The patients in control group received oral standard nutrition. Immunonutritional and inflammatory biomarkers (IgA, IgG, IgM, CD3t, CD4t, CD8t, CD4t/CD8t ratio, NK-cell, prealbumin, albumin, white blood cells counts, and C-reactive protein) and clinical variables (age, gender, BMI, performance status, type of thymoma, type of MG, operative time, pathology, operative approach, postoperative complications, quantity of drainage, hospital stays) were examined. Results. A significant reduction in the length of hospital stay, quantity of drainage, and postoperative complications was observed in the IN group (p < 0.05). An increase in the level of IgA, IgG, IgM, CD3+T, CD4+T, CD4+T/CD8+T, WBC, CRP, and NK-cell in the IN group was observed after thymectomy, while a decrease was seen with regard to prealbumin and albumin (p < 0.05). Conclusion. Preoperative immunonutrition support is effective in reducing postoperative complications in patients of thymoma with MG. It helps to lower the risk of postoperative infectious complications and hospital stays.

QYR301, 1,3-Dimethyl-1H-pyrazole-4-carboxylic acid 4-[2-chloro-3-(3,5-dimethyl-pyrazol-1-ylmethyl)-4-methanesulfonyl-benzoyl]-2,5-dimethyl-2H-pyrazol-3-yl ester, is a novel HPPD-inhibiting herbicide and was evaluated to provide a reference for post-emergence (POST) application under greenhouse and field conditions. The crop safety (180 and 360 g active ingredient (a.i.) ha-1 treatments) experiment revealed that wheat, paddy, garlic and corn were the only four crops without injury at both examined herbicide rates. The weed control efficacy (60 and 120 g a.i. ha-1) experiment showed that QYR301 exhibited high efficacy against many weeds, especially weeds infesting paddy fields. Furthermore, it is interesting that both susceptible and multiple herbicide resistant Echinochloa crus-galli (L.) Beauv. and Echinochloa phyllopogon (Stapf) Koss, two notorious weed species in paddy field, remained susceptible to QYR301. Further crop tolerance results indicated that 20 tested paddy hybrids displayed different levels of tolerance to QYR301, with the japonica paddy hybrids having more tolerance than indica paddy hybrids under greenhouse conditions. Results obtained from field experiments showed that QYR301 POST at 135 to 180 g a.i. ha-1 was recommended to provide satisfactory full-season control of E. crus-galli and Leptochloa chinensis (L.) Nees and to maximize rice yields. These findings indicate that QYR301 possesses great potential for the management of weeds in paddy fields.

To determine whether exposure to occupational levels of agrochemicals is associated with a range of low- (contrast and colour) and higher-level visual functions, particularly the detection of global form and motion coherence. We compared the performance of workers exposed to occupational levels of pesticides and non-exposed individuals on visual tasks that measured colour discrimination (Farnsworth Munsell 100 and Lanthony D15 desaturated) and the contrast sensitivity function (1-16 cpd). Global form and motion detection thresholds were measured using Glass-pattern and global dot motion stimuli. Neurotoxicity symptoms and biological markers associated with pesticide exposure were quantified using the Q16 modified questionnaire and via tests for levels of acetylcholinesterase in blood and substance P from the tear film, respectively. Workers exposed to pesticides had significantly more neurotoxic symptoms than non-exposed workers. No significant difference between groups for acetylcholinesterase levels was found, but there was a significant group difference in Substance P. The exposed group also had significantly poorer contrast sensitivity, colour discrimination and higher coherence detection thresholds for global form and motion perception. Exposure to occupational levels of agrochemicals in workers with signs of neurotoxicity is associated with low and high visual perception deficits.

Cross-resistance to medical azoles by exposure to azole pesticides is well documented for Aspergillus family fungi but is poorly evaluated for other environmental pathogen fungi, particularly for yeasts belonging to the Cryptococcus neoformans/Cryptococcus gattii species complexes.

During the screening programme for new agrochemicals from Chinese medicinal herbs and local wild plants, the essential oil of dried bulbs of Allium macrostemon Bunge (Liliaceae) was found to possess larvicidal activity against mosquitoes. The aim of this research was to determine the larvicidal activity of the essential oil and its major constituent compounds against the larvae of the Culicidae mosquito, Aedes albopictus.

Fusarium stalk rot (FSR) caused by Fusarium graminearum (FG) significantly affects the productivity of maize grain crops. Application of agrochemicals to control the disease is harmful to environment. In this regard, use of biocontrol agent (BCA) is an alternative to agrochemicals. Although Trichoderma species are known as BCA, the selection of host-pathogen specific Trichoderma is essential for the successful field application. Hence, we screened a total of 100 Trichoderma isolates against FG, selected Trichoderma harzianum (CCTCC-RW0024) for greenhouse experiments and studied its effect on changes of maize rhizosphere microbiome and biocontrol of FSR. The strain CCTCC-RW0024 displayed high antagonistic activity (96.30%), disease reduction (86.66%), biocontrol-related enzyme and gene expression. The root colonization of the strain was confirmed by eGFP tagging and qRT-PCR analysis. Pyrosequencing revealed that exogenous inoculation of the strain in maize rhizosphere increased the plant growth promoting acidobacteria (18.4%), decreased 66% of FG, and also increased the plant growth. In addition, metabolites of this strain could interact with pathogenicity related transcriptional cofactor FgSWi6, thereby contributing to its inhibition. It is concluded that T. harzianum strain CCTCC-RW0024 is a potential BCA against FSR.

Anthropogenic environmental change is a powerful and ubiquitous evolutionary force, so it is critical that we determine the extent to which organisms can evolve in response to anthropogenic environmental change and whether these evolutionary responses have associated costs. This issue is particularly relevant for species of conservation concern including many amphibians, which are experiencing global declines from many causes including widespread exposure to agrochemicals. We used a laboratory toxicity experiment to assess variation in sensitivity to two pesticides among wood frog (Lithobates sylvaticus) populations and a mesocosm experiment to ascertain whether resistance to pesticides is associated with decreased performance when animals experience competition and fear of predation. We discovered that wood frog populations closer to agriculture were more resistant to a common insecticide (chlorpyrifos), but not to a common herbicide (Roundup). We also found no evidence that this resistance carried a performance cost when facing competition and the fear of predation. To our knowledge, this is the first study demonstrating that organophosphate insecticide (the most commonly applied class of insecticides in the world) resistance increases with agricultural land use in an amphibian, which is consistent with an evolutionary response to agrochemicals.

Plant diseases cause enormous economic losses in agriculture and threaten global food security, and application of agrochemicals is an important method of crop disease control. Exploration of disease-resistance mechanisms and synthesis of highly bioactive agrochemicals are thus important research objectives. Here, we show that propranolol, a phosphatidate phosphatase (Pah) inhibitor, effectively suppresses fungal growth, sporulation, sexual reproduction, and infection of diverse plants. The MoPah1 enzyme activity of the rice blast fungus Magnaporthe oryzae is inhibited by propranolol. Alterations in lipid metabolism are associated with inhibited hyphal growth and appressorium formation caused by propranolol in M. oryzae. Propranolol inhibits a broad spectrum of 12 plant pathogens, effectively inhibiting infection of barley, wheat, maize, tomato, and pear. To improve antifungal capacity, we synthesized a series of propranolol derivatives, one of which shows a 16-fold increase in antifungal ability and binds directly to MoPah1. Propranolol and its derivatives can also reduce the severity of rice blast and Fusarium head blight of wheat in the field. Taken together, our results demonstrate that propranolol suppresses fungal development and infection through mechanisms involved in lipid metabolism. Propranolol and its derivatives may therefore be promising candidates for fungicide development.

Pesticide-resistant plant pathogens are an increasing threat to the global food supply and have generated a need for novel, efficacious agrochemicals. The current regulatory process for approving new agrochemicals is a tedious but necessary process. One way to accelerate the safety evaluation process is to utilize in vitro systems to demonstrate pesticide degradation by soil microbes prior to ex vivo soil evaluations. This approach may have the capability to generate metabolic profiles free of inhibitory substances, such as humic acids, commonly present in ex vivo soil systems. In this study, we used a packed-bed microbial bioreactor to assess the role of the natural soil microbial community during biodegradation of the triazolopyrimidine fungicide, ametoctradin. Metabolite profiles produced during in vitro ametoctradin degradation were similar to the metabolite profiles obtained during environmental fate studies and demonstrated the degradation of 81% of the parent compound in 72 h compared to a half-life of 2 weeks when ametoctradin was left in the soil. The microbial communities of four different soil locations and the bioreactor microbiome were compared using high throughput sequencing. It was found that biodegradation of ametoctradin in both ex vivo soils and in vitro in the bioreactor correlated with an increase in the relative abundance of Burkholderiales, well characterized microbial degraders of xenobiotic compounds.

Agrochemicals provide vast potential to improve plant productivity, because they are easy to implement at low cost while not being restricted by species barriers as compared with breeding strategies. Despite the general interest, only a few compounds with growth-promoting activity have been described so far. Here, we add cis-cinnamic acid (c-CA) to the small portfolio of existing plant growth stimulators. When applied at low micromolar concentrations to Arabidopsis roots, c-CA stimulates both cell division and cell expansion in leaves. Our data support a model explaining the increase in shoot biomass as the consequence of a larger root system, which allows the plant to explore larger areas for resources. The requirement of the cis-configuration for the growth-promoting activity of CA was validated by implementing stable structural analogs of both cis- and trans-CA in this study. In a complementary approach, we used specific light conditions to prevent cis/trans-isomerization of CA during the experiment. In both cases, the cis-form stimulated plant growth, whereas the trans-form was inactive. Based on these data, we conclude that c-CA is an appealing lead compound representing a novel class of growth-promoting agrochemicals. Unraveling the underlying molecular mechanism could lead to the development of innovative strategies for boosting plant biomass.