Search Results (142)

The rapid evolution of metabolic resistance to chemical insecticides and the adaptation to plant allelochemicals in insect pests have become major challenges in global pest management. While the overexpression of cytochrome P450 monooxygenases (P450s) is a well-recognized classic detoxification mechanism, the upstream epigenetic and post-transcriptional regulatory networks governing this process have only recently been elucidated. In this narrative review, the latest research progress on microRNAs (miRNAs) as crucial “fine-tuners” in insect detoxification networks is systematically summarized. The classic regulatory model is highlighted: the induced or constitutive downregulation of specific miRNAs relieves the translational repression of their target P450 genes, thereby contributing to metabolic resistance to major insecticide classes, including neonicotinoids, diamides, and pro-insecticides. Furthermore, the evolutionary recruitment mechanisms of conserved miRNAs in host plant adaptation are explored, and how endocrine signals, such as juvenile hormone (JH) and 20-hydroxyecdysone (20E), synergistically regulate the miRNA–P450 axis is analyzed. The “sponge effect”, wherein highly expressed P450 mRNAs act as competitive endogenous RNAs (ceRNAs) to sequester miRNAs, and the consequent physiological trade-offs (fitness costs) resulting from the prioritization of metabolic resources toward the detoxification system are comprehensively discussed. Finally, the current core methodologies for miRNA functional validation are critically evaluated, and the application potential and ecological safety prerequisites of miRNA-based nanobiopesticides for targeted and sustainable pest management are discussed. By integrating mechanistic insights with translational perspectives, this review highlights miRNA–P450 regulatory networks as key determinants of insecticide resistance evolution and as promising targets for developing more precise, environmentally compatible pest-management strategies. Full article

This study aimed to isolate, characterize, and evaluate bacterial consortia capable of degrading the diamide insecticide cyantraniliprole in aqueous systems and to assess their bioremediation potential under environmentally relevant conditions. Four bacterial consortia, each comprising six isolates, demonstrated significant growth in mineral media containing cyantraniliprole as the sole carbon source, and the isolates were identified using conventional microbiological techniques in combination with MALDI-TOF-MS analysis. The bacterial consortia were enriched from pesticide-contaminated environments and systematically evaluated using microbiological, physiological, and analytical approaches to determine their degradation potential and environmental adaptability. The degradation performance of the consortia was systematically assessed under varying environmental parameters, including temperature, pH, salinity, and incubation time, with optimal degradation observed at 30–35 °C, pH 7.0–8.0, 0.5–5.0% NaCl, and 11 days of incubation at 150 rpm using an initial cyantraniliprole concentration of 50 mg/L. Biodegradation efficiency was further evaluated using DCPIP reduction assays, alongside measurements of biofilm formation and biomass production, indicating enhanced metabolic activity and adaptive responses under pesticide-induced stress. The consortia also exhibited the capacity to degrade structurally related diamide pesticides, including flubendiamide, chlorantraniliprole, cyclaniliprole, and fluchlordiniliprole, suggesting broad-spectrum biodegradation potential. Their performance was further validated in a simulated water microcosm system designed to mimic environmentally relevant contamination scenarios. In simulated contaminated water (60 mg/L cyantraniliprole), bacterial inoculants standardized to 10⁷ CFU/mL achieved substantial degradation after 20 days of incubation at 30 °C, as confirmed by HPLC analysis, with the six-strain consortium (T4), comprising Bacillus subtilis subsp. subtilis AZFS3, Bacillus pumilus AZFS5, Bacillus mojavensis AZFS15, Bacillus paramycoides AZFS18, Pseudomonas aeruginosa KZFS4, and Alcaligenes aquatilis KZFS11, demonstrating the highest removal efficiency (98.27%) and reducing the pesticide concentration to 1.00 mg/L, followed by consortium T3 (96.72%), which consisted of Bacillus subtilis Ht1, Bacillus subtilis Ht2, Bacillus mojavensis Ht3, Pseudomonas aeruginosa Ht4, Pseudomonas aeruginosa Ht5, and Pseudomonas aeruginosa Ht6. Residue analysis and predictive bioinformatic assessment further supported the biodegradation capacity of the selected bacterial communities and suggested the formation of simpler transformation products. Overall, the investigated bacterial consortia exhibited high degradation efficiency and environmental adaptability, highlighting their potential as effective and eco-friendly agents for the bioremediation of cyantraniliprole-contaminated water systems. Full article

Kelch-like ECH-associated protein 1 (Keap1) acts as a repressor of nuclear factor-erythroid 2-related factor 2 (Nrf2), a major transcription factor regulating cellular antioxidant response. Keap1 is the substrate adaptor subunit of the cullin 3-RING E3 ubiquitin ligase complex that specifically facilitates Nrf2 ubiquitination and its proteasomal degradation. Keap1 is rich in cysteine residues, and several of them undergo various modifications, such as sulphydration, nitrosylation and glutathionylation under cellular stress conditions. Some of these modifications alter the conformation of Keap1, preventing Nrf2 from ubiquitination and subsequent proteasome-mediated degradation. As a result, newly synthesised Nrf2 translocates to the nucleus to induce the expression of diverse genes involved in protecting cells against oxidative stress. Protein CoAlation is a reversible redox-dependent post-translational modification (PTM) in which coenzyme A (CoA) forms disulphide bonds with oxidised cysteine residues under oxidative or metabolic stress. In this study, we demonstrate for the first time that disulphide Keap1 dimer undergoes CoAlation in cellular response to oxidative stress induced by various oxidising compounds. Furthermore, glucose deprivation also induces CoAlation of the disulphide Keap1 dimer in HEK293/Pank1β cells. We also demonstrate that the Keap1^{11 Cys-less} mutant is not CoAlated in response to diamide treatment or glucose deprivation. In summary, this study uncovers a novel PTM of Keap1 by the key metabolic integrator CoA, which provides new insights into the regulation of the Keap1-Nrf2 antioxidant pathway under oxidative and metabolic stress. Full article

This work focuses on rapid, catalyst-free synthesis of a new series of acetylenic phosphonates as promising building blocks for creating antiviral and anticancer agents. A comprehensive assessment of the biological activity of the synthesized compounds was conducted. Dialkyl phosphonates 4d, 4e, and 4g were found to exhibit pronounced antiproliferative activity against human cancer cell lines, with the greatest IC₅₀ = 6 μg/mL against the K562 cell line. Further studies revealed that these compounds cause significant disorganization of the actin cytoskeleton, leading to the loss of stress fibers and reduced cell motility. In contrast, diamide derivatives demonstrated a more favorable safety profile, with low cytotoxicity and moderate antiviral activity against influenza A (H1N1) virus, among which compound 6b achieved a selectivity index of 5 with IC₅₀ = 56.9 μg/mL. Screening studies of both dialkyl and diamide acetylenic phosphonates revealed some features of the interaction with kinase and nonkinase targets used for drug development and provide a basis for the subsequent rational design of novel selective anticancer agents based on the acetylenic phosphonate scaffold. Full article

Chromene derivatives are important structural motifs in biologically active compounds and functional materials, and the development of efficient strategies for their synthesis remains of considerable interest. In this work, simple and sustainable methodologies were developed for the synthesis of chromene dimers linked through short amidine/geminal diamine spacers or long, flexible alkyl diamine linkers. The amidine and geminal diamine linkers were obtained from 3-aminochromene derivatives via nucleophilic addition of the amino group to triethyl orthoformate or non-phenolic aldehydes in ethanol, at room temperature or under reflux, affording the corresponding dimers in moderate to very good yields. In a complementary approach, flexible alkyl diamide linkers were prepared from diamines and ethyl cyanoacetate, followed by condensation with salicylaldehydes in aqueous hydrogen carbonate solution and subsequent acidic hydrolysis, leading to new chromene dimers in excellent yields. These mild and operationally simple protocols provide efficient access to structurally diverse chromene dimers with potential applications in medicinal chemistry and materials science. Full article

The preservation of biological control agents in agroecosystems while simultaneously ensuring the use of insecticides with selective chemical profiles is crucial for sustainable pest management. In this study, we aimed to evaluate the selectivity of insecticides used in the management of Phthorimaea (Tuta) absoluta in tomato crops during the adult stage of Trichogramma pretiosum. The selectivity tests were conducted according to the standards of the International Organization for Biological and Integrated Control/West Palearctic Regional Section. The bioassay was used to assess the direct effects of treatments on T. pretiosum adults through tarsal contact. Specifically, 42 chemical and/or biological insecticides commonly applied in tomato cultivation were used to manage P. absoluta. The insecticides identified as selective (Class 1) for adult T. pretiosum under laboratory conditions were recommended for use in integrated pest management (IPM) programs in tomato crops. These included Hayate^®, Agree^®, Dipel^®, Xentari^®, Tarik^®, Bioexos^®, Verpavex^®, Spodovir^®, Verpavex^® + Spodovir^®, Tuta Vir^®, BioBrev^®, Diplomata^®, VirControl C.i^®, and VirControl S.F^®. Insecticides belonging to the following chemical groups were not selective, that is, they were harmful to T. pretiosum adults: avermectins, milbemycins, diacylhydrazines, oxadiazines, semicarbazones, spinosyns, diamides, chlorfenapyr, nereistoxin analogs, pyrethroids, carbamates, butenolides, isoxazoline, azadirachtin, quinolizidine alkaloids, METI, and benzoylureas. Therefore, these insecticides should be used with caution in IPM programs that target P. absoluta in tomato crops. Full article

Cyantraniliprole, a second-generation diamide insecticide, exhibits broad-spectrum efficacy against numerous insect pests due to its selective activation of insect ryanodine receptors (RyRs). This activation triggers uncontrolled calcium release from the sarcoplasmic reticulum, resulting in sustained muscle contraction, paralysis, and ultimately death. Its unique mode of action, which is different from that of organophosphates, carbamates, pyrethroids, and neonicotinoids, helps minimize cross-resistance, making it a valuable component of integrated pest management (IPM). However, continuous field use has led to the development of resistance, primarily mediated by target-site mutations within the RyR transmembrane domain (e.g., G4946E, I4743M, and I4790K) and by enhanced metabolic detoxification via cytochrome P450 monooxygenases, carboxylesterases, and glutathione S-transferases. These mechanisms often confer cross-resistance to other diamide insecticides, thereby complicating resistance management. Moreover, sublethal exposures can disrupt insect growth, development, and reproduction, potentially accelerating resistance evolution. In addition, cyantraniliprole poses ecological risks due to its toxicity to non-target organisms such as aquatic species, including zebrafish and water fleas, pollinators such as honeybees, and soil fauna, as well as the environmental persistence of its major metabolite, J9Z38. This review comprehensively integrated current knowledge on the molecular mechanisms of action, genetic and metabolic bases of resistance, sublethal effects, and ecotoxicological impacts of cyantraniliprole, along with its environmental fate, plant uptake and translocation, and residue dynamics in agricultural systems. Finally, we discuss potential risk-mitigation strategies, including formulation optimization, application-method improvements, and resistance monitoring. Overall, this review aims to provide a comprehensive scientific foundation for the sustainable use, resistance management, and regulatory assessment of this widely used insecticide. Full article

The tomato leaf miner, Tuta absoluta (Meyrick) (Lepidoptera: Gelechiidae), poses a significant threat to global tomato production. However, environmentally sustainable management strategies for this pest, as well as its mechanisms of insecticide resistance, remain insufficiently understood. Broflanilide, a novel meta-diamide compound, can bind specifically to the transmembrane domain of the RDL subunit, causing prolonged opening of the chloride channel, disruption of neurotransmission, and ultimately insect paralysis and death. This study employed the leaf immersion method to conduct bioassays on the second-instar larvae of T. absoluta to evaluate physiological responses to sublethal concentrations of the novel amide insecticide broflanilide. Subsequently, high-throughput transcriptome sequencing was performed to investigate changes in gene expression and metabolic pathways. Bioassay results determined the larval sublethal concentrations of broflanilide to be 0.136 mg/L (LC₁₀) and 0.210 mg/L (LC₃₀). Sublethal exposure significantly prolonged the larval period, reduced pupal weight, and inhibited fecundity of female adults. Transcriptomic and qPCR analyses revealed that, compared with the control (CK), expression of the vitellogenin gene Vg decreased by 15.99% and 30.27% under LC₁₀ and LC₃₀ treatments, respectively, while its receptor gene VgR decreased by 11.56% and 24.49%. Similarly, expression of chitin synthase genes chs1 and chs2 declined by 13.56% and 30.17% (chs1), and 7.85% and 19.45% (chs2), respectively. Gene expression analysis elucidated how sublethal insecticides treatment impact larval development and fecundity. Furthermore, the study revealed upregulation of cytochrome P450-mediated detoxification pathways and Toll/Imd immune signaling pathways under broflanilide stress, indicating activation of a coordinated defense response in T. absoluta. Sublethal broflanilide exposure modulated larval gene expression to balance growth, development, and stress adaptation. Such exposure exerts selective pressure on susceptible populations, potentially driving adaptive shifts in detoxification metabolism and contributing to the development of field resistance. These findings advance our understanding of the sublethal effects of novel insecticides and provide valuable insights for insecticide deployment strategies and resistance management. Full article

Insecticide resistance in Aedes aegypti (Linnaeus, 1762), the primary vector of several arboviruses, threatens vector control efficacy and motivates evaluation of current and candidate public health insecticides, such as imidacloprid and broflanilide, and their molecular impacts. Here, we used RNA sequencing (RNA-seq) to characterize the transcriptomic response to one-hour acute exposure to an operational partial-mortality concentration (<50%) of imidacloprid and broflanilide in two Ae. aegypti strains: a field-derived, pyrethroid-resistant population from San Nicolás and a susceptible laboratory strain (New Orleans). Adults were exposed for 1 h to partial-mortality concentration (<50%) doses of each insecticide or acetone control, and differential gene expression and Gene Ontology (GO) enrichment were assessed with DESeq2-based workflows. We detected pronounced baseline transcriptomic differences between strains and extensive activation of gene expression after insecticide exposure, with a strong bias toward up-regulation. A shared transcriptional core involving proteolysis, transmembrane transport, detoxification pathways, and structural remodeling of the cuticle and cytoskeleton was identified across contrasts. Despite these common elements, broflanilide elicited largely conserved early responses between strains, whereas imidacloprid amplified pre-existing divergence and produced marked population-specific transcriptional signatures. These findings suggest greater transcriptional changes in the field-derived strain, particularly in response to imidacloprid, and highlight the importance of integrating population-specific molecular information when designing insecticide rotation schemes and resistance management strategies targeting Ae. aegypti. Full article

The fall armyworm (FAW) Spodoptera frugiperda is a polyphagous pest that causes significant damage to various crops and rapidly develops resistance to insecticides. Broflanilide, a novel meta-diamide insecticide, has shown effectiveness against lepidopteran pests, but the risk of resistance and associated fitness costs in FAW remain unclear. This study evaluated the development of resistance to broflanilide over nine generations of selection using the diet incorporation method at the 70% lethal concentration (LC₇₀) concentration. Following nine generations of selection, the LC₅₀ value increased from 0.134 mg/kg to 0.232 mg/kg, showing a 1.73-fold increase in resistance ratio (RR). The calculated heritability of resistance (h²) was 0.084, which suggested that resistance of FAW against broflanilide is evolving at a slow rate. Based on the projected rate of resistance progression, a 10-fold increase in LC₅₀ would take between 30.1 and 66.4 generations, assuming selection mortality rates of 90% and 50%, respectively. Fitness costs were evaluated using age-stage, two-sex life table analysis, revealing reduced fecundity and pupal weight in the broflanilide-selected (Brof-SEL) strain compared to the wild-type. The relative fitness of the Brof-SEL strain was 0.38, indicating trade-offs in biological traits. These findings suggested a low risk of rapid resistance development against broflanilide. However, effective integrated pest management strategies against FAW require the judicious use of this insecticide in combination with biological control measures, including the deployment of parasitoids and predators, to promote a more environmentally sustainable approach. Full article

Spodoptera frugiperda J.E. Smith (Lepidoptera: Noctuidae) represents a major threat to maize production across Pakistan, with chemical control serving as the predominant management approach. The intensive application of insecticides, particularly diamide compounds such as chlorantraniliprole, has escalated concerns regarding resistance evolution in field populations. This study evaluated the insecticidal efficacy of seven commonly used compounds against geographically diverse field-collected populations of S. frugiperda from major maize-growing regions of Pakistan, revealing significant inter-population variability in susceptibility profiles. Chlorantraniliprole was selected for comprehensive transgenerational screening based on moderate baseline LC₅₀ values and optimal laboratory colony establishment parameters. A representative field strain underwent six consecutive generations of selection pressure at LC₇₀ concentrations, resulting in a 4.48-fold increase in resistance levels with a realized heritability (h²) of 0.198. Predictive modeling using established quantitative genetic frameworks demonstrated that resistance evolution rates are critically dependent on both selection intensity and genetic parameters. Under constant h² = 0.198, increasing selection intensity substantially accelerated resistance development, with 10-fold resistance achievable in approximately 18 generations at 80% selection intensity (slope = 2.696) compared to 36 generations at lower intensities (slope = 4.696). Sensitivity analysis revealed that heritability variations from 0.148 to 0.248 could reduce generation requirements from >40 to ~25 generations when slope was maintained at 3.696. Life table analyses of the chlorantraniliprole-selected strain demonstrated significant fitness costs manifested as extended developmental periods, reduced reproductive output, and decreased intrinsic rate of population increase (r), indicating evolutionary trade-offs associated with resistance acquisition. These findings provide crucial insights for developing sustainable management strategies, highlighting the importance of integrating resistance monitoring, refuge-based approaches, and rotation with insecticides of different modes of action to delay resistance buildup in field populations. Such data-driven management frameworks are vital for maintaining the long-term efficacy of diamides in Pakistan’s maize production systems. Full article

The Diamondback moth (DBM), Plutella xylostella (L.), the most significant worldwide pest of Brassica crops, is notorious for resistance to a diverse number of insecticides. Field populations bioassayed in Georgia and Florida, USA, in 2018 were resistant to chlorantraniliprole but susceptible to cyantraniliprole. Subsequently, populations assayed in 2021, 2022, and 2023 were cross-resistant to both diamides. We used NextSeq analysis of the ryanodine receptor PxRyR, the target of diamides, to quantify target site mutations associated with resistance. Three populations sampled in 2018 had a high prevalence (75.0–98.3% of total reads) of the G4946E mutation, associated with resistance to chlorantraniliprole, and additionally, in one population, a very low (2.7%) prevalence of another mutation, I4790K, was associated with diamide cross-resistance. Populations sampled in 2021 had a decreased prevalence of G4946E (0.7 and 8.4%) and increased prevalence of I4790K (9.3 and 18.0%). The G4946E allele was almost absent (0.2% to 3.9%) in populations sampled in 2022 and 2023, while I4790K was present at frequencies from 34.1% to 84.0%. These data suggest a remarkable shift in PxRyR target site mutations, replacing G4946E with I4790K, which occurred between 2018 and 2022, and were associated with the recent occurrence of cross-resistance in DBM populations in the Southeastern USA. Full article

Drone insecticide spraying is generating increasing concern and interest among academics and the public. However, the differences in the quantity of insecticide delivered by this method, and its efficacy in pest control for individual plants, remain to be evaluated. We examined the distribution and quantity of an insecticide sprayed on sweet potato plants and the method’s efficacy in controlling a subterranean weevil infestation. To evaluate delivery patterns, water-sensitive paper was placed on the canopy of the plants, and the insecticide was sprayed from a drone at the registered concentration. Although there was minimal deflection of flight paths (under crosswinds ≤ 3.0 m/s), the distribution varied across the field. The quantity administered was within the regulated range for the insecticide. Efficacy was not significantly influenced by either the quantity administered or pattern of spraying, and the drone application resulted in an equivalent level of control as a conventional ground-based application. While the quantity of the insecticide applied to the canopy was uneven, the method’s efficacy was satisfactory at the field scale. These findings can be used to develop safe and cost-effective methods for the drone application of pesticides. Full article

Introduction: According to research data, 1,3-oxazines are pharmacologically active substances, as well as the substrates for the synthesis of heterocyclic and acyclic compounds. However, bis(1,3-oxazin-6-one) derivatives are little studied class of compounds, which makes their research a promising direction for the development of modern synthetic chemistry and pharmacy. The aim of this work is to obtain bis(4-hydroxy-6H-1,3-oxazin-6-ones), study their alcoholysis reaction, prove the structure of the obtained products and evaluate their pharmacological potential in silico. Methods: The reflux of isophthalic acid diamide with a twofold excess of substituted malonyl chloride in 1,2-dichloroethane for 15 h led to the production of bis(4-hydroxy-6H-1,3-oxazin-6-ones) (1, 2). As a result of their reflux with absolute ethanol for 5 h acyclic esters of malonamic acids (3, 4) formed. The structure of the obtained compounds was proved by ¹H and ¹³C NMR spectroscopy. The prediction of biological activity was carried out using the GUSAR and PASS online web resources. Results: The yields of compounds 1–4 were 90%, 90%, 93%, 89%, respectively, depending on the nature of the substituent at position C₅ of the oxazine cycle. According to the in silico assessment of biological activity, bis(1,3-oxazine-6-ones) exhibited high probability of antitumor activity, while ethyl esters of malonamic acids showed promising anxiolytic, antieczematous, fibrinolytic activities. Conclusions: New bridging 1,3-oxazin-6-ones were synthesized. The reaction of their cleavage by absolute ethanol to malonamic acid esters was studied. The potential biological activity was predicted in silico. Full article

Systena frontalis (Fabricius) (Coleoptera: Chrysomelidae) is a challenging pest to manage in ornamental container nurseries, affecting over 50 plant species, particularly panicled hydrangea (Hydrangea paniculata Siebold). Because S. frontalis produces multiple generations and there is a risk of developing resistance to the insecticides currently used, growers urgently seek new tools, especially new active ingredients with different modes of action or new insecticide products. Isocycloseram (Plinazolin^® Technology) and cyantraniliprole + thiamethoxam (Mainspring^® Xtra) are new potential insecticides for managing adult S. frontalis. However, the effective rates and application frequencies and intervals of isocycloseram and cyantraniliprole + thiamethoxam are not well understood. Therefore, the objectives of this study were to determine how rates and application intervals of these insecticides affect feeding damage when applied as foliar sprays. In laboratory assays, applying isocycloseram 1.67 SC at 59.1, 118.3, 177.4, 236.6, and 295.7 mL in 378.5 L of water, as well as cyantraniliprole + thiamethoxam at 70.9, 141.7, 212.6, and 303.3 g, reduced feeding damage compared to nontreated controls. In field trials conducted in 2024 and 2025, leaves treated with isocycloseram at 118.3 and 147.9 mL in 378.5 L of water showed significantly less damage than nontreated controls. Cyantraniliprole + thiamethoxam at 226.8 and 283.5 g in 378.5 L of water also significantly reduced the number of damaged leaves compared to nontreated controls. Two to three repeated applications of isocycloseram 1.67 SC and cyantraniliprole + thiamethoxam, administered at 7 d intervals, significantly reduced leaf damage compared to two applications at 14 d intervals. Full article