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Marine Pollution Bulletin Jul 2023Biomarkers involved in detoxification process (GST), oxidative stress (SOD and MDA), immune response (Laccase) and neurotoxic disorders (AChE) were analysed in Pacific...
Biomarkers involved in detoxification process (GST), oxidative stress (SOD and MDA), immune response (Laccase) and neurotoxic disorders (AChE) were analysed in Pacific oysters and blue mussels collected from 4 locations within the Pertuis sea (France). Seasonal variations of total pesticide mean concentrations were found in seawater with metolachlor being the main pesticide measured (up to 32 ng/L). The majority of pesticide concentrations in sediment were below the LOD. Seasonal contamination differences were evidenced for chlortoluron, especially in mussels where concentrations reached 16 ng/g (wet weight) during the winter, in the Charente estuary, but no relationships with any of the biomarkers selected arisen. Actually, low concentrations of alpha-, beta-BHC and alachlor were correlated to GST activity, and low levels of hexachlorobenzene were linked to the AChE activity and MDA content in oysters. In mussels, low concentrations of methylparathion, parathion and beta-BHC were correlated to laccase.
Topics: Animals; Pesticides; Estuaries; Seasons; Laccase; Environmental Monitoring; Water Pollutants, Chemical; Mytilus edulis; Biomarkers
PubMed: 37216876
DOI: 10.1016/j.marpolbul.2023.114988 -
International Journal of Analytical... 2023Antibiotics and pesticides are widespread in most rivers and lakes due to the overuse of antibiotics and pesticides, but there are few methods for simultaneous analysis...
Antibiotics and pesticides are widespread in most rivers and lakes due to the overuse of antibiotics and pesticides, but there are few methods for simultaneous analysis of antibiotics and pesticides in aquatic environments. To address this knowledge gap, a concise and sensitive analytical method is proposed in which three classes of human and veterinary drugs (sulfonamides, macrolides, and hormones) and two classes of pesticides (organophosphorus and neonicotinoids) are simultaneously extracted and determined in surface water. The solid-phase extraction column with Cleanert PEP-2 was preconditioned sequentially with 6 mL of methanol, ultrapure water, and citric acid buffer (pH 3.0) each for simultaneous extraction and further purification. The forty-seven target analytes were analysed by LC-MS/MS in positive and negative ion modes. The LC separation was performed using a Sigma-Aldrich C column with 0.1% formic acid in water and acetonitrile as a gradient eluting mobile phase in positive ion mode. The internal standard method was used to overcome the inevitable matrix effects in LC-MS/MS analysis. The matrix effects of most target analytes were in the range of 27-151%. The recoveries of forty analytes in the three concentrations (10, 50, and 100 ng L) of surface water spiked samples ranged from 41 to 127%. The method quantitative limits of the analytes were in the range of 0.40-5.49 ng L. Application of the method to analyze samples in the eight runoff outlets of the Pearl River Delta showed that some antibiotics and pesticides were detected, and the concentration of parathion was as high as 154 ng L. A powerful tool for quickly and efficiently screening for contaminants in surface water has been presented.
PubMed: 37877028
DOI: 10.1155/2023/6350669 -
Journal of Biomolecular Structure &... Sep 2023Microbially induced calcite precipitation (MICP) through urease enzyme has attained a lot of recognition in various fields of civil engineering and geotechnology for...
Microbially induced calcite precipitation (MICP) through urease enzyme has attained a lot of recognition in various fields of civil engineering and geotechnology for stabilizing the strength of soil and various concrete materials. The activity of urease has been found to be affected by various factors like temperature, substrate concentrations, pH of the medium, presence of inhibitors, etc. Through this study, the outcome of the interaction of pesticides (commonly found in Indian coastal regions) on urease, a major organism reported for MICP studies has been investigated . The results from the study revealed that the enzyme has higher interactions of -4.1, -3.2, and -3.4 kJ/mol with common pesticides like dichloro diphenyl dichloro ethane(DDD), dichloro diphenyl trichloroe thane (DDT), and methyl parathion of organochlorides and organophosphates class. From the molecular dynamics simulation analysis, complex 1 (DDD -receptor) has been found to have the highest and more compact structure followed by methyl parathion -receptor. Prime MM-GBSA analysis also revealed the highest binding energy of -27.8 kcal/mol with the protein and DDD. Thus, it can be inferred from the current study that pesticides, particularly, DDD, DDT, and methyl parathion present in the coastal areas may have an impact on urease. This interaction can result in the inhibition of the urease activity of thus preventing the biomineralization process. This study would be the first report on the computational approach to understanding the interaction of prominent pesticides on the coastal region and urease.Communicated by Ramaswamy H. Sarma.
PubMed: 37691444
DOI: 10.1080/07391102.2023.2252089 -
Journal of Neurochemistry Apr 2024Millions of individuals globally suffer from inadvertent, occupational or self-harm exposures from organophosphate (OP) insecticides, significantly impacting human...
A single post-exposure oxime RS194B treatment rapidly reactivates acetylcholinesterase and reverses acute symptoms in macaques exposed to diethylphosphorothioate parathion and chlorpyrifos insecticides.
Millions of individuals globally suffer from inadvertent, occupational or self-harm exposures from organophosphate (OP) insecticides, significantly impacting human health. Similar to nerve agents, insecticides are neurotoxins that target and inhibit acetylcholinesterase (AChE) in central and peripheral synapses in the cholinergic nervous system. Post-exposure therapeutic countermeasures generally include administration of atropine with an oxime to reactivate the OP-inhibited AChE. However, animal model studies and recent clinical trials using insecticide-poisoned individuals have shown minimal clinical benefits of the currently approved oximes and their efficacy as antidotes has been debated. Currently used oximes either reactivate poorly, do not readily cross the blood-brain barrier (BBB), or are rapidly cleared from the circulation and must be repeatedly administered. Zwitterionic oximes of unbranched and simplified structure, for example RS194B, have been developed that efficiently cross the BBB resulting in reactivation of OP-inhibited AChE and dramatic reversal of severe clinical symptoms in mice and macaques exposed to OP insecticides or nerve agents. Thus, a single IM injection of RS194B has been shown to rapidly restore blood AChE and butyrylcholinesterase (BChE) activity, reverse cholinergic symptoms, and prevent death in macaques following lethal inhaled sarin and paraoxon exposure. The present macaque studies extend these findings and assess the ability of post-exposure RS194B treatment to counteract oral poisoning by highly toxic diethylphosphorothioate insecticides such as parathion and chlorpyrifos. These OPs require conversion by P450 in the liver of the inactive thions to the active toxic oxon forms, and once again demonstrated RS194B efficacy to reactivate and alleviate clinical symptoms within 60 mins of a single IM administration. Furthermore, when delivered orally, the Tmax of RS194B at 1-2 h was in the same range as those administered IM but were maintained in the circulation for longer periods greatly facilitating the use of RS194B as a non-invasive treatment, especially in isolated rural settings.
Topics: Animals; Mice; Acetamides; Acetylcholinesterase; Butyrylcholinesterase; Chlorpyrifos; Cholinesterase Inhibitors; Cholinesterase Reactivators; Insecticides; Macaca; Nerve Agents; Organophosphorus Compounds; Oximes; Parathion
PubMed: 36786545
DOI: 10.1111/jnc.15777 -
Talanta Dec 2023To determine parathion in cereals, hydrophilic and hydrophobic deep eutectic solvents (DESs) were used by digital image colorimetry with smartphones. In the solid-liquid...
To determine parathion in cereals, hydrophilic and hydrophobic deep eutectic solvents (DESs) were used by digital image colorimetry with smartphones. In the solid-liquid extraction part, hydrophilic DESs were used as extractants to extract parathion from cereals. In the liquid-liquid microextraction part, hydrophobic DESs dissociated into terpineol and tetrabutylammonium bromide in situ. The dissociated hydrophilic tetrabutylammonium ions reacted with parathion extracted in hydrophilic DESs under alkaline conditions to produce a yellow product, which was extracted and concentrated by dispersed organic phase terpinol. Digital image colorimetry integrated with the use of a smartphone was used for quantitative analysis. The limit of detection and quantification were 0.003 mg kg and 0.01 mg kg, respectively. The recoveries for parathion were 94.8-106.2% with a relative standard deviation less than 3.6%. The proposed method was applied to analyze parathion in cereal samples: the method has the potential to be applied to pesticide residue analysis in food products.
Topics: Solvents; Edible Grain; Smartphone; Deep Eutectic Solvents; Parathion; Colorimetry; Liquid Phase Microextraction; Limit of Detection
PubMed: 37339538
DOI: 10.1016/j.talanta.2023.124831 -
Neural Networks : the Official Journal... Aug 2023Depression, as a global mental health problem, is lacking effective screening methods that can help with early detection and treatment. This paper aims to facilitate the...
Depression, as a global mental health problem, is lacking effective screening methods that can help with early detection and treatment. This paper aims to facilitate the large-scale screening of depression by focusing on the speech depression detection (SDD) task. Currently, direct modeling on the raw signal yields a large number of parameters, and the existing deep learning-based SDD models mainly use the fixed Mel-scale spectral features as input. However, these features are not designed for depression detection, and the manual settings limit the exploration of fine-grained feature representations. In this paper, we learn the effective representations of the raw signals from an interpretable perspective. Specifically, we present a joint learning framework with attention-guided learnable time-domain filterbanks for depression classification (DALF), which collaborates with the depression filterbanks features learning (DFBL) module and multi-scale spectral attention learning (MSSA) module. DFBL is capable of producing biologically meaningful acoustic features by employing learnable time-domain filters, and MSSA is used to guide the learnable filters to better retain the useful frequency sub-bands. We collect a new dataset, the Neutral Reading-based Audio Corpus (NRAC), to facilitate the research in depression analysis, and we evaluate the performance of DALF on the NRAC and the public DAIC-woz datasets. The experimental results demonstrate that our method outperforms the state-of-the-art SDD methods with an F1 of 78.4% on the DAIC-woz dataset. In particular, DALF achieves F1 scores of 87.3% and 81.7% on two parts of the NRAC dataset. By analyzing the filter coefficients, we find that the most important frequency range identified by our method is 600-700Hz, which corresponds to the Mandarin vowels /e/ and /eˆ/ and can be considered as an effective biomarker for the SDD task. Taken together, our DALF model provides a promising approach to depression detection.
Topics: Depression; Methyl Parathion; Speech; Acoustics
PubMed: 37285730
DOI: 10.1016/j.neunet.2023.05.041 -
Small (Weinheim An Der Bergstrasse,... Dec 2023For the enzyme immobilization platform, enhancing enzyme activity retention while improving enzyme stability remains a challenge for sensitive sensing analysis. Herein,...
For the enzyme immobilization platform, enhancing enzyme activity retention while improving enzyme stability remains a challenge for sensitive sensing analysis. Herein, an in situ biomimetic immobilized enzyme carrier (metal-pyrimidine nanoflowers, MPNFs) synthesized by the coordination of DNA base derivative (2-aminopyrimidine) with Zn in the aqueous phase at room temperature is developed. The biocompatibility of 2-aminopyrimidine and the hydrophilicity and green synthetic conditions of MPNFs allows the immobilized enzymes to retain above 91.2% catalytic activity. On this basis, a cascade catalytic platform is constructed by simultaneously immobilizing acetylcholinesterase (AChE), choline oxidase (CHO), and horseradish peroxidase (HRP) in MPNFs (AChE/CHO/HRP@MPNFs) for organophosphorus pesticides (OPs) colorimetric biosensing detection. The assay could specifically detect parathion-methyl within 13 min with a wider linear range (0.1-1000.0 nm) and a lower limit of detection (LOD) (0.032 nm). The remarkable stability of the immobilized enzymes is also achieved under harsh environments, room temperature storage, and recycling. Furthermore, a portable and cost-effective biosensing platform is developed by integrating AChE/CHO/HRP@MPNFs with a smartphone-assisted paper device for the on-site detection of OPs. Overall, the high catalytic activity retention and the enhanced detection performance demonstrate that MPNF is a robust carrier in enzyme immobilization and holds great promise in biosensing and other field applications.
Topics: Pesticides; Acetylcholinesterase; Organophosphorus Compounds; Enzymes, Immobilized; Biomimetics; Metals; Horseradish Peroxidase; Pyrimidines; Biosensing Techniques; Colorimetry
PubMed: 37612822
DOI: 10.1002/smll.202304077 -
The Journal of Physical Chemistry. B Jun 2024Methyl-parathion hydrolase (MPH), which evolved from dihydrocoumarin hydrolase, offers one of the most efficient enzymes for the hydrolysis of methyl-parathion....
Methyl-parathion hydrolase (MPH), which evolved from dihydrocoumarin hydrolase, offers one of the most efficient enzymes for the hydrolysis of methyl-parathion. Interestingly, the substrate preference of MPH shifts from the methyl-parathion to the lactone dihydrocoumarin (DHC) after its mutation of five specific residues (R72L, L273F, L258H, T271I, and S193Δ, m5-MPH). Here, extensive QM/MM calculations and MM MD simulations have been used to delve into the structure-function relationship of MPH enzymes and plausible mechanisms for the chemical and nonchemical steps, including the transportation and binding of the substrate DHC to the active site, the hydrolysis reaction, and the product release. The results reveal that the five mutations remodel the active pocket and reposition DHC within the active site, leading to stronger enzyme-substrate interactions. The MM/GBSA-estimated binding free energies are about -20.7 kcal/mol for m5-MPH and -17.1 kcal/mol for wild-type MPH. Furthermore, this conformational adjustment of the protein may facilitate the chemical step of DHC hydrolysis and the product release, although there is a certain influence on the substrate transport. The hydrolytic reaction begins with the nucleophilic attack of the bridging OH with the energy barriers of 22.0 and 18.0 kcal/mol for the wild-type and m5-MPH enzymes, respectively, which is rate-determining for the entire process. Unraveling these mechanistic intricacies may help in the understanding of the natural evolution of enzymes for diverse substrates and establish the enzyme structure-function relationship.
Topics: Molecular Dynamics Simulation; Coumarins; Quantum Theory; Hydrolysis; Catalytic Domain; Substrate Specificity; Thermodynamics; Hydrolases
PubMed: 38814729
DOI: 10.1021/acs.jpcb.4c00970 -
Biomolecules May 2024Olesoxime, a cholesterol derivative with an oxime group, possesses the ability to cross the blood-brain barrier, and has demonstrated excellent safety and tolerability...
Olesoxime, a cholesterol derivative with an oxime group, possesses the ability to cross the blood-brain barrier, and has demonstrated excellent safety and tolerability properties in clinical research. These characteristics indicate it may serve as a centrally active ligand of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), whose disruption of activity with organophosphate compounds (OP) leads to uncontrolled excitation and potentially life-threatening symptoms. To evaluate olesoxime as a binding ligand and reactivator of human AChE and BChE, we conducted kinetic studies with the active metabolite of insecticide parathion, paraoxon, and the warfare nerve agents sarin, cyclosarin, tabun, and VX. Our results showed that both enzymes possessed a binding affinity for olesoxime in the mid-micromolar range, higher than the antidotes in use (i.e., 2-PAM, HI-6, etc.). While olesoxime showed a weak ability to reactivate AChE, cyclosarin-inhibited BChE was reactivated with an overall reactivation rate constant comparable to that of standard oxime HI-6. Moreover, in combination with the oxime 2-PAM, the reactivation maximum increased by 10-30% for cyclosarin- and sarin-inhibited BChE. Molecular modeling revealed productive interactions between olesoxime and BChE, highlighting olesoxime as a potentially BChE-targeted therapy. Moreover, it might be added to OP poisoning treatment to increase the efficacy of BChE reactivation, and its cholesterol scaffold could provide a basis for the development of novel oxime antidotes.
Topics: Humans; Butyrylcholinesterase; Acetylcholinesterase; Ligands; Oximes; Cholinesterase Reactivators; Cholinesterase Inhibitors; Cholestenones; Kinetics; Sarin; GPI-Linked Proteins; Antidotes; Cholesterol; Organophosphorus Compounds
PubMed: 38785995
DOI: 10.3390/biom14050588 -
Journal of Biomolecular Structure &... Sep 2023Organophosphorus pesticides (OPs) are widely used in agriculture and may contaminate food or water, leading to potential health risks. However, there are few reports on...
Organophosphorus pesticides (OPs) are widely used in agriculture and may contaminate food or water, leading to potential health risks. However, there are few reports on the effect of OPs on protein conformation and aggregation. Hence, in this paper, we have characterized the impact of two OPs, chlorpyrifos (CPF) and methyl parathion (Para), on the model protein HEWL using biophysical and computational methods. The steady-state and time-resolved spectroscopy, Circular dichroism (CD), molecular dynamics simulation, and isothermal titration calorimetry were employed to investigate the binding interactions between HEWL and OPs. The steady-state and time-resolved fluorescence spectroscopy confirm the presence of both static and dynamic quenching between OPs and proteins. Based on fluorescence, MD, and CD results, it was found that the OPs not only show strong binding but also destabilize the protein structure and alter the secondary and tertiary structure of the protein. The molecular docking results showed that OPs entered the binding pocket of the HEWL molecule and interacted through hydrophobic and hydrogen bond interactions. The thermodynamic studies indicated that the binding was spontaneous and OPs have shown an effect on the aggregation process of HEWL. Finally, the protein aggregation process was studied using fluorescence and SDS-PAGE studies in the presence of both the OPs and found to enhance the aggregation process in the presence of OPs. These results provide insights into the potential health risks associated with OPs and highlight the importance of understanding their interactions with biological macromolecules.Communicated by Ramaswamy H. Sarma.
PubMed: 37728535
DOI: 10.1080/07391102.2023.2259484