Causal inference and mechanism for unraveling the removal of four pesticides from lettuce (Lactuca sativa L.) via ultrasonic processing and various immersion solutions.

This study explores the reduction of carbamates (CAs) and pyrethroids (PYs) - commonly used pesticides - in lettuce using various immersion solutions and ultrasonic processing. It also examines the role of machine learning and molecular docking in understanding the mechanisms of pesticide reduction. The results revealed that the highest reduction of both CAs and PYs exceeded 80 % on lettuce leaves. In most samples, the reduction increased with the power of ultrasonic processing and processing time. The results of machine learning models (XGBoost and SHAP) showed that during the immersion cleaning of CAs and PYs, as well as during both immersion cleaning and ultrasonic processing of CAs + PYs, the reduction was most influenced by the initial pesticide levels and immersion time. Gas Chromatography-Mass Spectrometry (GC-MS) analysis of lettuce's wax layer identified 24 compounds, including fatty alcohols, fatty acids, fatty acid esters, and triterpenoids. Despite the absence of active sites, the lipophilic nature of long-chain aliphatic compounds aids in pesticide binding, while triterpenoids form strong hydrogen bonds with pesticides, indicating a robust adsorption on the lettuce surface. This study aims to offer insights into the efficient removal of chemical pesticide residues from fruits and vegetables, addressing critical concerns for food safety and human health.

Consecutive high-performance removal of Cu2+ metal ions and Deltamethrin using multifunctional pyrolysis cuttlebone/cotton fabric nanocomposite.

A simple technique was developed for the modification of cotton materials that is inexpensive, environmentally friendly, and very effective. Waste Cotton fabrics (WCFs) are loaded with propolis extract (PE) for Cu2+ removal. Then, Cu2+ underwent a pyrolysis process with modified cuttlebone (CB) at 900 °C for 5 h. The surface of the prepared materials was characterized using X-ray diffraction (XRD), scanning electron microscopy with energy-dispersive X-ray (SEM-EDX), Fourier transform infrared (FTIR), BET, particle sizes, thermogravimetric analysis (TGA) and zeta potential analysis. The Cu2+ metal ions from an aqueous solution were removed using WCFs/PE, and DLM was subsequently removed using pyro WCFs/PE/Cu/CB. The as-prepared NPs exhibited the face-centered cubic structure of WCFs/PE/Cu/CB with crystallite sizes ranging from 386.70 to 653.10 nm. FTIR spectra revealed that CB was present on the surface of the resulting WCFs/PE/Cu. SEM revealed the dispersion of a uniformly flower-like morphology over a large area. Sorption studies were performed based on parameters that included pH, dose, contact time, and initial concentration. The adsorption isotherm and the kinetic studies of the DLM adsorption process were applied at a pH of 5.0 and a temperature of 25 °C using several isotherms and kinetic models. The results revealed qmax (20.51 mg/g) with R2 = 0.97, the Langmuir isotherm that best matches the experimental data. Hence, the Langmuir isotherm suggests that it is the model that best describes sorption on homogenous surfaces or surface-supporting sites with various affinities. The correlation coefficient R2, χ2, adjusted correlation coefficient, and error functions like root mean square (RMSE), normalized root mean square error (NRMES), and mean absolute error (MAE) were used to evaluate the best-fit models to the experimental adsorption data. Moreover, cost estimation for the prepared adsorbent WCFs/PE/Cu showed that it costs approximately 3 USD/g, which is a cheap adsorbent compared to other similar adsorbents reported in the literature. The examined WCFs/PE have significant applicability potential for Cu2+-laden wastewater treatment due to their superior Cu2+ metal ions adsorption capability and reusability. The cytotoxicity and safety study showed that at higher concentrations, it resulted in much less cell viability. Additionally, the removal efficiency of Cu2+ metal ions from synthetic, realistic industrial wastewater using WCFs/PE reached up to 96.29 %, demonstrating good adsorption capability. Thus, there is a huge possibility of accomplishing this and performing well. This study paves the way for the reuse and valorization of selected adsorbents following circular economy principles. Two green metrics were applied, the Analytical Eco-scale and the Analytical GREEnness Calculator (AGREE).

COF-SiO2@Fe3O4 Composite for Magnetic Solid-Phase Extraction of Pyrethroid Pesticides in Vegetables.

Pyrethroid pesticides (PYRs) have found widespread application in agriculture for the protection of fruit and vegetable crops. Nonetheless, excessive usage or improper application may allow the residues to exceed the safe limits and pose a threat to consumer safety. Thus, there is an urgent need to develop efficient technologies for the elimination or trace detection of PYRs from vegetables. Here, a simple and efficient magnetic solid-phase extraction (MSPE) strategy was developed for the simultaneous purification and enrichment of five PYRs in vegetables, employing the magnetic covalent organic framework nanomaterial COF-SiO2@Fe3O4 as an adsorbent. COF-SiO2@Fe3O4 was prepared by a straightforward solvothermal method, using Fe3O4 as a magnetic core and benzidine and 3,3,5,5-tetraaldehyde biphenyl as the two building units. COF-SiO2@Fe3O4 could effectively capture the targeted PYRs by virtue of its abundant π-electron system and hydroxyl groups. The impact of various experimental parameters on the extraction efficiency was investigated to optimize the MSPE conditions, including the adsorbent amount, extraction time, elution solvent type and elution time. Subsequently, method validation was conducted under the optimal conditions in conjunction with gas chromatography-mass spectrometry (GC-MS). Within the range of 5.00-100 µg·kg-1 (1.00-100 µg·kg-1 for bifenthrin and 2.5-100 µg·kg-1 for fenpropathrin), the five PYRs exhibited a strong linear relationship, with determination coefficients ranging from 0.9990 to 0.9997. The limits of detection (LODs) were 0.3-1.5 µg·kg-1, and the limits of quantification (LOQs) were 0.9-4.5 µg·kg-1. The recoveries were 80.2-116.7% with relative standard deviations (RSDs) below 7.0%. Finally, COF-SiO2@Fe3O4, NH2-SiO2@Fe3O4 and Fe3O4 were compared as MSPE adsorbents for PYRs. The results indicated that COF-SiO2@Fe3O4 was an efficient and rapid selective adsorbent for PYRs. This method holds promise for the determination of PYRs in real samples.

High selectivity molecularly imprinted polymer based on short amylose as bio-based functional monomers for selective extraction of λ-cyhalothrin.

Nowadays, the development of sustainable molecularly imprinted polymers (MIPs) with high selectivity is still challenging due to the limitations of bio-based functional monomers. In this study, the highly selective and porous MIPs (LC-TMIPs) were designed and prepared on short amylose (SAM) as bio-based functional monomers, λ-cyhalothrin (LC) as a template molecule, and tetrafluoroterephthalonitrile as a rigid crosslinking agent. Static, dynamic, and selective adsorption experiments were conducted to investigate the adsorption performance. The results indicated that, compared to MIPs prepared using epichlorohydrin as flexible crosslinking agents, LC-TMIPs exhibited higher imprinting factor (3.93), selectivity (5.78), and adsorption capacity (35.79 mg g-1), as well as faster adsorption/desorption kinetics. The LC-TMIPs were used as sorbents for the selective determination of LC in both apple and cucumber samples by high-performance liquid chromatography. Under the optimal extraction conditions, the recoveries of the method reached 92.1-106.1 %, with a linear range of 1.5-30 ng g-1 and a detection limit of 0.5 ng g-1. The proposed preparation method of LC-TMIPs is expected to open a new way to prepare highly selective and sustainable MIPs for hydrophobic compounds.

Innovative detection mechanism for deltamethrin based on a dual-emitting Fluoroprobe and its application in a smartphone-based photoelectric conversion device.

Pyrethroids are widely used insecticides worldwide, while their on-site and rapid detection still faces technological challenges. Herein, an innovative detection mechanism was designed for deltamethrin, a typical kind of type II pyrethroids, based on a dual-emitting fluoroprobe consisting of NH2-SiQDs and Eu3+. Deltamethrin can rapidly hydrolyze into 3-phenoxybenzaldehyde (3-PBD) and react specifically with fluoroprobe, causing fluorescence quenching of SiQDs while maintaining the fluorescent stability of Eu3+. Building upon the above fluorescence-responsive principle, SiQDs@Eu3+ provided satisfactorily dual-emitting signals, realizing the highly-selective and sensitive detection of deltamethrin. Correlation between the surface structure of SiQDs and their absorption spectra was in-depth unraveled by TD-DFT calculation and FT-IR analysis. As for the analytical performance, the recovery and LOD of deltamethrin in lettuce, provided by SiQDs@Eu3+, were comparable or even superior over conventional chromatographic analysis. Meanwhile, an innovative smartphone-based optical device was developed, which greatly decreased errors caused by the previously reported smartphone-based fluorescence detection.

Mechanistic insight into the impact of interaction between goethite and humic acid on the photooxidation and photoreduction of bifenthrin.

Numerous application of pyrethroid insecticides has led to their accumulation in the environment, threatening ecological environment and human health. Its fate in the presence of iron-bearing minerals and natural organic matter under light irradiation is still unknown. We found that goethite (Gt) and humic acid (HA) could improve the photodegradation of bifenthrin (BF) in proper concentration under light irradiation. The interaction between Gt and HA may further enhance BF degradation. On one hand, the adsorption of HA on Gt may decrease the photocatalytic activity of HA through decreasing HA content in solution and sequestering the functional groups related with the production of reactive species. On the other hand, HA could improve the photocatalytic activity of Gt through extending light absorption, lowing of bandgap energy, hindering the recombination of photo-generated charges, and promoting the oxidation and reduction reaction on Gt surface. The increased oxygen vacancies on Gt surface along with the reduction of trivalent iron and the nucleophilic attack of hole to surface hydroxyl group contributed to the increasing photocatalytic activity of Gt. Electron paramagnetic resonance and quenching studies demonstrated that both oxidation species, such as hydroxyl radical (•OH) and singlet oxygen (1O2), and reducing species, such as hydrogen atoms (H•) and superoxide anion radical (O2•-), contributed to BF degradation in UV-Gt-HA system. Mass spectrometry, ion chromatography, and toxicity assessment indicated that less toxic C23H22ClF3O3 (OH-BF), C9H10ClF3O (TFP), C14H14O2 (OH-MBP), C14H12O2 (MBP acid), C14H12O3 (OH-MBP acid), and chloride ions were the main degradation products. The production of OH-BF, MPB, and TFP acid through oxidation and the production of MPB and TFP via reduction were the two primary pathways of BF degradation.

Structural Exploration of Novel Pyrethroid Esters and Amides for Repellent and Insecticidal Activity against Mosquitoes.

The emergence of pyrethroid-resistant mosquitoes is a worldwide problem that necessitates further research into the development of new repellents and insecticides. This study explored the modification of existing pyrethroid acids to identify structural motifs that might not be affected by kdr active site mutations that elicit pyrethroid resistance. Because synthetic pyrethroids almost always contain activity-dependent chiral centers, we chose to focus our efforts on exploring alkoxy moieties of esters obtained with 1R-trans-permethrinic and related acids, which we showed in previous studies to have repellent and/or repellent synergistic properties. To this end, compounds were synthesized and screened for spatially acting repellency and insecticidal activity against the susceptible, Orlando, and pyrethroid-resistant, Puerto Rico, strains of Aedes aegypti mosquito. Screening utilized a high-throughput benchtop glass tube assay, and the compounds screened included a mixture of branched, unbranched, aliphatic, halogenated, cyclic, non-cyclic, and heteroatom-containing esters. Structure-activity relationships indicate that n-propyl, n-butyl, n-pentyl, cyclobutyl, and cyclopentyl substituents exhibited the most promising repellent activity with minimal kdr cross resistance. Preliminary testing showed that these small alcohol esters can be synergistic with phenyl amides and pyrethroid acids. Further derivatization of pyrethroid acids offer an interesting route to future active compounds, and while mosquitoes were the focus of this work, pyrethroid acids and esters have potential for use in reducing pest populations and damage in cropping systems as well.

Residue dynamics and dietary risk assessment of new formulation of novaluron and lambda cyhalothrin on tomato.

Presence of residues on food commodities is major bottleneck of insecticide use under good agricultural practices (GAPs). The use of less persistent with two different mode of action insecticide is novel approach of getting maximum insect control without developing insecticide resistance. Novaluron, an insect growth disruptor and lambda cyhalothrin, a nerve poison has been used widely for the management of lepidopteran pests. Dissipation and consumer risk analysis studies were carried out on a new combination product of novaluron and lambda cyhalothrin are used for control insects of tomato at recommended standard dose of 71 + 14 g/ha and double dose of 142 + 28 g/ha of active ingredients. Extraction and cleanup of sample residues was done using QuEChERS technique and analyzed in GC-ECD. The residues of novaluron were dissipated within 10 to 15 days, and the residues of lambda cyhalothrin were at 7 to 10 days, both at the standard and double the standard dose, following a first order reaction kinetics. Analysis of risk and hazard quotient revealed that the test insecticides do not pose any dietary risk to consumer as TMDI < MPI and HQ < 1.

Influence of the acaricide emulsion pH on the effectiveness of spray products to control the cattle tick: laboratory and field investigations.

The current work evaluated the efficacy of 10 commercial acaricides in different pHs (4.5, 5.5, and 6.5) in laboratory (adult immersion tests (AIT), pH evaluation over time) and field assays (tick counts and efficacy). In the AIT (n=70), higher efficacies were obtained when the acaricide emulsion had a more acidic pH (4.5), mainly for two combinations of pyrethroids + organophosphate (acaricide 3 and acaricide 9). For amidine, a higher pH (6.5) showed a higher efficacy. Over time, there was a trend in the pH of these emulsions increasing. When the efficacy of chlorpyrifos + cypermethrin + piperonyl butoxide (acaricide 3) at different pHs was evaluated over time (0, 6, 12, and 24h) by AIT, the less acidic pH (6.5) showed a strongly variation in the acaricide efficacy range. The mean pH of the water samples from different regions of Brazil was 6.5. In the field, the association of pyrethroid + organophosphates (acaricide 9) with pH of 4.5 and 5.5 were more effective in tick control than the emulsion prepared with this same spray formulation at pH 6.5. The pH of the acaricide emulsions is an important point of attention and is recommended that the veterinary industry start to develop/share information regarding how the pH can affect the acaricide efficacy.

Pyrethroid residues in Indonesian river Citarum: A simple analytical method applied for an ecological and human health risk assessment.

Pyrethroid residues in the Citarum River, Indonesia, was first investigated based on their occurrences, water assimilative capacity, and risk assessment. In this paper, first, a relatively simple and efficient method was built and validated for analysis of seven pyrethroids in a river water matrix: bifenthrin, fenpropathrin, permethrin, ß-cyfluthrin, cypermethrin, fenvalerate, and deltamethrin. Next, the validated method was used to analyze pyrethroids in the Citarum River. Three pyrethroids, ß-cyfluthrin, cypermethrin, and deltamethrin, were detected in some sampling points with concentration up to 0.01 mg/L. Water assimilative capacity evaluation shows that ß-cyfluthrin and deltamethrin pollution exceed the Citarum river water capacity. However, due to hydrophobicity properties of pyrethroids, removal through binding to sediments are expected. Ecotoxicity risk assessment shows that ß-cyfluthrin, cypermethrin and deltamethrin pose risks to the aquatic organisms in the Citarum River and its tributaries through bioaccumulation in food chain. Based on bioconcentration factors of the detected pyrethroids, ß-cyfluthrin poses the highest adverse effect to humans while cypermethrin is the safest. Human risk assessment based on hazard index suggests that acute non-carcinogenic risk associated to consuming fish from the study location polluted with ß-cyfluthrin, cypermethrin and deltamethrin is unlikely. However, hazard quotient shows that chronic non-carcinogenic risk associated to consuming fish from the study location polluted with ß-cyfluthrin is likely. However, since the risk assessment was performed separately for each pyrethroid, further assessment on the impact of mixture pyrethroid to aquatic organisms and humans should be performed to explore the real impact of pyrethroids to the river system.

Creating Pyrethrin Mimetic Phosphonates as Chemical Genetics Tools Targeting the GDSL Esterase/Lipase TcGLIP to Investigate Pyrethrin Biosynthesis.

Pyrethrins from Tanacetum cinerariifolium are natural pesticides that exhibit high knockdown and killing activities against flying insects such as disease-spreading mosquitoes. Despite the increasing demand for pyrethrins, the mechanism of pyrethrin biosynthesis remains elusive. To elucidate it, we for the first time created pyrethrin mimetic phosphonates targeting the GDSL esterase/lipase (GELP or TcGLIP) underpinning pyrethrin biosynthesis. The compounds were synthesized by reacting mono-alkyl or mono-benzyl-substituted phosphonic dichloride with pyrethrolone, the alcohol moiety of pyrethrin I and II, and then p-nitrophenol. n-Pentyl (C5) and n-octyl (C8)-substituted compounds were the most potent of the (S)p,(S)c, and (R)p,(S)c diastereomers, respectively. The (S)-pyrethrolonyl group is more effective than the (R)-pyrethrolonyl group in blocking TcGLIP, consistent with the features predicted by TcGLIP models complexed with the (S)p,(S)c-C5 and (R)p,(S)c-C8 probes. The (S)p,(S)c-C5 compound suppressed pyrethrin production in T. cinerariifolium, demonstrating potential as a chemical tool for unravelling pyrethrin biosynthesis.

Cypermethrin toxicity in the environment: analytical insight into detection methods and microbial degradation pathways.

The unrestricted utilization of xenobiotic compounds has sparked widespread concern by the world's growing population. A synthetic pyrethroid called cypermethrin (CP) is commonly utilized as an insecticide in horticulture, agriculture, and pest control. The high toxicity levels of accumulated CP have prompted environmental concerns; it damages soil fertility, and an ecosystem of essential bacteria, and causes allergic reactions and tremors in humans by affecting their nervous systems. The damage caused by CP to groundwater, food, and health makes it imperative that new effective and sustainable alternatives are investigated. Microbial degradation has been established as a reliable technique for mineralizing CP into less toxic chemicals. Among the many enzymes produced by bacteria, carboxylesterase enzymes are determined to be the most efficient in the CP breakdown process. High-performance liquid chromatography (HPLC) and gas chromatography-mass spectrometry (GC-MS) have been reported as the best methods for determining CP and its metabolized products, with detection limits as low as ppb from diverse environmental samples. The current study describes the ecotoxicological impact of CP and innovative analytical techniques for their detection. The newly isolated CP-degrading bacterial strains have been evaluated in order to develop an efficient bioremediation strategy. The proposed pathways and the associated critical enzymes in the bacterial mineralization of CP have also been highlighted. Additionally, the strategic action to control CP toxicity has been discussed.

Bifenthrin disrupts cytochrome c oxidase activity and reduces mitochondrial DNA copy number through oxidative damage in pool barb (Puntius sophore).

Bifenthrin (BF), a synthetic pyrethroid is used worldwide for both agricultural and non-agricultural purposes due to its high insecticidal activity and low toxicity in mammals. However, its improper usage implies a possible risk to aquatic life. The study was aimed to correlate the association of BF toxicity with mitochondrial DNA copy number variation in edible fish Punitus sophore. The 96-h LC50 of BF in P. sophore was 3.4 µg/L, fish was treated with sub-lethal doses ((⅒ and ⅕ of LC50;0.34 µg/L, 0.68 µg/L) of BF for 15 days. The activity and expression level of cytochrome c oxidase (Mt-COI) were measured to assess mitochondrial dysfunction caused by BF. Results showed BF reduced the level of Mt-COI mRNA in treated groups, hindered complex IV activity and increased ROS generation leading to oxidative damage. mtDNAcn was decreased in the muscle, brain and liver after BF treatment. Furthermore, BF induced neurotoxicity in brain and muscle cells through the inhibition of AchE activity. The treated groups showed elevated level of malondialdehyde (MDA) and an imbalance of antioxidant enzymes activity. Molecular docking and simulation analysis also predicted that BF binds to the active sites of the enzyme and restricts the fluctuation of its residues. Hence, outcome of the study suggests reduction of mtDNAcn could be a potential biomarker to assess Bifenthrin induced toxicity in aquatic ecosystem.

Broad-Specificity Screening of Pyrethroids Enabled by the Catalytic Function of Human Serum Albumin on Coumarin Hydrolysis.

Sensing systems based on cholinesterase and carboxylesterase coupled with different transduction technologies have emerged for pesticide screening owing to their simple operation, fast response, and suitability for on-site analysis. However, the broad spectrum and specificity screening of pyrethroids over organophosphates and carbamates remains an unmet challenge for current enzymatic sensors. Human serum albumin (HSA), a multifunctional protein, can promote various chemical transformations and show a high affinity for pyrethroids, which offer a route for specific and broad-spectrum pyrethroid screening. Herein, for the first time, we evaluated the catalytic hydrolysis function of human serum albumin (HSA) on the coumarin lactone bond and revealed that HSA can act as an enzyme to catalyze the hydrolysis of the coumarin lactone bond. Molecular docking and chemical modifications indicate that lysine 199 and tyrosine 411 serve as the catalytic general base and contribute to most of the catalytic activity. Utilizing this enzymatic activity, a broad specific ratiometric fluorescence pyrethroids sensing system was developed. The binding energetics and binding constants of pesticides and HSA show that pyrethroids bind to HSA more easily than organophosphates and carbamates, which is responsible for the specificity of the sensing system. This study provides a general sensor platform and strategy for screening pesticides and reveals the catalytic activity of HSA on the hydrolysis of the coumarin lactone bond, which may open innovative horizons for the chemical sensing and biomedical applications of HSA.

A novel thermostable and salt-tolerant carboxylesterase involved in the initial aerobic degradation pathway for pyrethroids in Glycomyces salinus.

The long-term and excessive use of pyrethroid pesticides poses substantial health risks and ecosystem concerns. Several bacteria and fungi have been reported that could degrade pyrethroids. The ester-bond hydrolysis using hydrolases is the initial regulatory metabolic reaction of pyrethroids. However, the thoroughly biochemical characterization of hydrolases involved in this process is limited. Here, a novel carboxylesterase, designated as EstGS1 that could hydrolyze pyrethroid pesticides was characterized. EstGS1 showed low sequence identity (<27.03%) compared to other reported pyrethroid hydrolases and belonged to the hydroxynitrile lyase family that preferred short short-chain acyl esters (C2 to C8). EstGS1 displayed the maximal activity of 213.38 U/mg at 60 °C and pH 8.5 using pNPC2 as substrate, with Km and Vmax were 2.21 ± 0.72 mM and 212.90 ± 41.78 µM/min, respectively. EstGS1 is a halotolerant esterase and remains stable in 5.1 M NaCl. Based on molecular docking and mutational analysis, the catalytic triad of S74-D181-H212 and three other substrate-binding residues I108, S159, and G75 are critical for the enzymatic activity of EstGS1. Additionally, 61 and 40 mg/L of deltamethrin and λ-cyhalothrin were hydrolyzed by 20 U of EstGS1 in 4 h. This work presents the first report on a pyrethroid pesticide hydrolase characterized from a halophilic actinobacteria.

Broad-spectrum portable magnetic relaxation switching immunosensor with gold-functionalized magnetic nanoprobes for the sensitive detection of multiple pyrethroids.

At present, the most available pyrethroid (PYR) detection methods still suffer from a narrow detection spectrum, low sensitivity, and less portability. Herein, a novel magnetic relaxation switching (MRS) sensor was elaboratively designed to detect multiple PYRs, combining a novel broad-spectrum antibody CL-CN/1D2 and synthesized immune gold-functionalized magnetic nanoparticles, with the inherent response of the sensor. A series of antibodies and the immune gold-functionalized magnetic nanoparticles were designed and synthesized. The broad-spectrum antibody CL-CN/1D2 and high-performance gold-functionalized magnetic nanoprobe were further selected. The target analytes were effectively captured by the gold-functionalized magnetic nanoparticles in 20% (v/v) ethanol, resulting in the number increase of the signaling probes in the supernatant after magnetic separation. This sensor can detect multiple PYRs with a detection limit of 2.72 µg/L for cypermethrin, 3.58 µg/L for ß-cypermethrin, 4.07 µg/L for cyfluthrin, 3.66 µg/L for λ-cyhalothrin, 4.42 µg/L for ß-cyhalothrin, 3.51 µg/L for fenpropathrin, 4.41 µg/L for fenvalerate, and 4.12 µg/L for deltamethrin in lake water and milk within 35 min. This study not only achieves broad-spectrum PYRs detection at a trace amount but also provides an effective and universal strategy for enhancing the sensitivity and stability of the portable MRS sensor when detecting hydrophobic analytes in the environment.

Determination of potential toxicodynamic differences of pyrethroid insecticides on native voltage-sensitive sodium channels in juvenile versus adult rat brain.

Microtransplantation of neurolemma tissue fragments from mammalian brain into the plasma membrane of Xenopus laevis oocytes is a tool to examine the endogenous structure and function of various ion channels and receptors associated with the central nervous system. Microtransplanted neurolemma can originate from a variety of sources, contain ion channels and receptors in their native configuration, and are applicable to examine diseases associated with different channelopathies. Here, we examined potential age-related differences in voltage-sensitive sodium channel (VSSC) expression and concentration-dependent responses to pyrethroids following the microtransplantation of juvenile or adult rat brain tissue (neurolemma) into X. laevis oocytes. Using automated western blotting, adult neurolemma exhibited a 2.5-fold higher level of expression of VSSCs compared with juvenile neurolemma. The predominant isoform expressed in both tissues was Nav1.2. However, adult neurolemma expressed 2.8-fold more Nav1.2 than juvenile and expressed Nav1.6 at a significantly higher level (2.2-fold). Microtransplanted neurolemma elicited ion currents across the plasma membrane of oocytes following membrane depolarization using two electrode voltage clamp electrophysiology. A portion of this current was sensitive to tetrodotoxin (TTX) and this TTX-sensitive current was abolished when external sodium ion was replaced by choline ion, functionally demonstrating the presence of native VSSC. Increasing concentrations of permethrin or deltamethrin exhibited concentration-dependent increases in inward TTX-sensitive current in the presence of niflumic acid from both adult and juvenile tissues following a pulsed depolarization of the oocyte plasma membrane. Concentration-dependent response curves illustrate that VSSCs associated with juvenile neurolemma were up to 2.5-fold more sensitive to deltamethrin than VSSCs in adult neurolemma. In contrast, VSSCs from juvenile neurolemma were less sensitive to permethrin than adult VSSCs at lower concentrations (0.6-0.8-fold) but were more sensitive at higher concentrations (up to 2.4-fold). Nonetheless, because the expected concentrations in human brains following realistic exposure levels are approximately 21- (deltamethrin) to 333- (permethrin) times below the threshold concentration for response in rat neurolemma-injected oocytes, age-related differences, if any, are not likely to be toxicologically relevant.

Systematic Stereoselectivity Evaluations of Tetramethrin Enantiomers: Stereoselective Cytotoxicity, Metabolism, and Environmental Fate in Earthworms, Soils, Vegetables, and Fruits.

Tetramethrin is a widely applied type I chiral pyrethroid insecticide that exists as a mixture of four isomers. In the present study, its stereoselective cytotoxicity, bioaccumulation, degradation, and metabolism were investigated for the first time at the enantiomeric level in detail by using a sensitive chiral high-performance liquid chromatography-tandem mass spectroscopy (HPLC-MS/MS) method. Results showed that among rac-tetramethrin and its four enantiomers, the trans (+)-1R,3R-tetramethrin had the strongest inhibition effect on the PC12 cells. In the earthworm exposure trial, the concentration of trans (-)-1S,3S-tetramethrin was 0.94-8.92 times in earthworms (cultivated in natural soil) and 1.67-5.01 times (cultivated in artificial soil) higher than trans (+)-1R,3R-tetramethrin, respectively. In the greenhouse experiment, the trans (+)-1R,3R-tetramethrin and cis (+)-1R,3S-tetramethrin were preferentially degraded. Furthermore, for rat liver microsome in vitro incubation, the maximum metabolism rate of cis (-)-1S,3R-tetramethrin was 1.50 times higher than its antipodes. Altogether, the aim of this study was to provide a scientific and reasonable reference for the possibility of developing a single enantiomer to replace the application of rac-tetramethrin, which could possess better bioactivity and lower ecotoxicity, and thus permit more reliable and accurate environmental monitoring and risk assessment.

Comparative behavioral ecotoxicology of Inland Silverside larvae exposed to pyrethroids across a salinity gradient.

Pyrethroids, a class of commonly used insecticides, are frequently detected in aquatic environments, including estuaries. The influence that salinity has on organism physiology and the partitioning of hydrophobic chemicals, such as pyrethroids, has driven interest in how toxicity changes in saltwater compared to freshwater. Early life exposures in fish to pyrethroids cause toxicity at environmentally relevant concentrations, which can alter behavior. Behavior is a highly sensitive endpoint that influences overall organism fitness and can be used to detect toxicity of environmentally relevant concentrations of aquatic pollutants. Inland Silversides (Menidia beryllina), a commonly used euryhaline model fish species, were exposed from 5 days post fertilization (~1-day pre-hatch) for 96 h to six pyrethroids: bifenthrin, cyfluthrin, cyhalothrin, cypermethrin, esfenvalerate and permethrin. Exposures were conducted at three salinities relevant to brackish, estuarine habitat (0.5, 2, and 6 PSU) and across 3 concentrations, either 0.1, 1, 10, and/or 100 ng/L, plus a control. After exposure, Inland Silversides underwent a behavioral assay in which larval fish were subjected to a dark and light cycle stimuli to determine behavioral toxicity. Assessment of total distanced moved and thigmotaxis (wall hugging), used to measure hyper/hypoactivity and anxiety like behavior, respectively, demonstrate that even at the lowest concentration of 0.1 ng/L pyrethroids can induce behavioral changes at all salinities. We found that toxicity decreased as salinity increased for all pyrethroids except permethrin. Additionally, we found evidence to suggest that the relationship between log KOW and thigmotaxis is altered between the lower and highest salinities.

The role of pyrethroid derivatives in autophagy and apoptosis crosstalk signaling and potential risk for malignancies.

Pyrethroids and its derivatives widespread and uncontrolled continuous use has influenced multiple deleterious effects resulting in as a potential risk factor causing damage to the organ systems. Allethrin and prallethrin are extensively used yet their influences on human primary cells are very limited or under reported. The potential mechanisms by which allethrin and prallethrin modulates human primary cells, especially the molecular mechanisms or interconnectivity of autophagy-apoptosis, their clinical relevance in human subjects or patients are not well defined. In this current study, we've furnished the evidence that both allethrin and prallethrin user samples significantly induced Ccl2 mRNA expression, increased amount of reactive oxygen intermediate, inhibited membrane bound enzymes and altered membrane fluidity. Pyrethroid derivative users had induced levels of lipid peroxidation and induced binding activities of transcription factors(tfs) like CEBP-ß and NF-AT. Pyrethroid derivatives induced autophagy, elicited intracellular Ca2+ concentration, calcineurin and regulated proapoptotic genes, DAPK1, Bim. Our current study presumably comprises the initial investigation of a very new mechanism of pyrethroid derivatives-moderated programed cell death in various cell sets or types, like human primary cells where-in this is a late event, is documented. Hence, current research-study might be significant in the various pyrethroid derivatives-allied hematological-related cancers and immunosuppressant or auto-immune disorders. In the foremost instance, we present data stating that pyrethroid derivatives induces multiple cell signaling cascades, like CEBP-ß, NF-AT, ERK and MAPK having a role in autophagy thereby; synchronously effectively impact on the apoptosis, therefore causing hematological tumors and toxic or immune related disorders.