Poison to Promise: The Resurgence of Organophosphorus Fluoride Chemistry.

Organophosphorus(V) fluorides have a long and tumultuous history, with early applications as toxins and nerve agents reflecting their poisonous past. Behind these very real safety considerations, there is also growing potential in a wide range of fields, from chemical biology to drug development. The recent inclusion of organophosphorus(V) fluorides in click chemistry exemplifies the promise these compounds possess and brings these molecules to the brink of a resurgence. In this Perspective, we delve into the history of P(V)-F compounds, discuss the precautions needed to work with them safely, and explore recent advancements in their synthesis and application. We conclude by discussing how this field can continue on a path toward innovation.

Mass spectrometry detection of organophosphorus pesticide adducts on butyrylcholinesterase and albumin.

This study established a method to prepare and detect OPs adducts on butyrylcholinesterase (BChE) and human serum albumin (HSA). OPs (methyl paraoxon, ethyl paraoxon, methyl parathion, parathion) were incubated with BChE or HSA in vitro, and the adducts of OPs-BChE or OPs-HSA were prepared and qualitatively analyzed by ultra-performance liquid chromatography data-dependent high-resolution tandem mass spectrometry (UPLC-ddHRMS/MS). The amounts of BChE and HSA in the incubating systems were varied and the resulting amounts of the adducts were determined using linear regression. OPs-BChE in the blood were isolated by immunomagnetic separation (IMS), and then digested into the OPs-nonapeptide adduct by pepsin. The proteins in the remaining blood plasma were precipitated and digested by pronase to OPs-tyrosines(OPs-Tyr), which were quantified by UPLC-ddHRMS/MS. 4 OPs-nonapeptides and 4 OPs-Tyr adducts were obtained through the process above. The relative mass deviation of incubated adducts between the actual and theoretical exact masses was less than 10 ppm, and further confirmed by fragmentation mass spectra analysis. Calibration curves were linear for all adducts with a coefficient of determination value (R2) ≥0.995. The limits of detection (LOD) and limits of quantification (LOQ) for adducts detected by MS ranged from 0.05 to 1.0 ng/mL, and from 0.1 to 2.0 ng/mL, respectively. The recovery percentages for adducts ranged from 76.1 % to 107.1 %, matrix effects ranged from 83.4 % to 102.1 %. The inter-day and intra-day precision were 6.1-10.1 % and 6.9-12.9 % for adducts. This study provides a new reference method for the detection of organophosphorus pesticide poisoning. In addition, two blood samples with organophosphorus poisoning were tested by the designed method, and the corresponding adducts were detected in both samples.

Computational studies on a selection of phosphite esters as antioxidants for polymeric materials.

CONTEXT: Phosphite esters, a class of organo-phosphorus compounds, are widely used as non-discolouring antioxidants in many polymeric products. Apart from normal radical scavenging, they prevent the splitting of hydroperoxides (ROOH), one of the initial products of autoxidation, from forming extremely reactive free radicals such as alkoxy (RO.) and hydroxy (.OH) radicals. The inherent molecular properties of antioxidants and the chemistry of their action are essential for researchers working in this field of science. Four organo-phosphorous compounds well-known for their antioxidant activity are selected here for theoretical analysis: Tri(m-methylphenyl) phosphite (m-TMPP), Tri(4-methyl-2,6-di-tert-butylphenyl) phosphite (TMdtBPP), Tri(allylphenyl) phosphite (TAPP) and Tri(mercaptobenzothiazoyl) thiophosphate (TMBTTP). The antioxidant activity exhibited by these compounds is theoretically verified, and the results are consistent with the available experimental data. Such theoretical predictions offer advantages in scientific research, particularly when researchers need to select certain molecules as antioxidants for experiments from a pool of molecular systems. METHODS: The chemical computations presented in this report are done in Gaussian 16 program package. The procedure of density functional theory (DFT) with the model chemistry B3LYP/6-31G(d,p) is used to generate computational data. Global reactivity indices, thermochemical data, Fukui functions, molecular electrostatic potential and NMR spectra are computed for the chosen molecular systems from their optimized geometries.

Diisodecyl phenyl phosphate promotes foam cell formation by antagonizing Liver X receptor alpha.

While the cardiovascular system is a primary target of organophosphorus flame retardants (OPFRs), particularly aryl-OPFRs, it is still exclusive whether the diisodecyl phenyl phosphate (DIDPP), widely used and broadly present in the environment at high concentrations, elicits atherosclerosis effects. Liver X receptors (LXRs) play a direct role in regulating the formation of atherosclerotic lesions. This study was the first to demonstrate that DIDPP acts as an LXRα ligand and functions as an LXRα antagonist with a half-maximal inhibitory concentration of 16.2 µM. We showed that treatment of an in vitro macrophage model with 1 to 10 µM of DIDPP resulted in the downregulation of direct targets of LXRα, namely ABCA1, ABCG1 and SR-B1, thereby leading to a 7.9-13.2 % reduction in cholesterol efflux. This caused dose-dependent, 24.1-43.1 % increases in the staining intensity of foam cells in the macrophage model. This atherosclerotic effect of DIDPP was proposed to be due to its antagonism of LXRα activity, as DIDPP treatment did not alter cholesterol influx. In conclusion, the findings of this study demonstrate that exposure to DIDPP may be a risk factor for atherosclerosis due to the LXRα-antagonistic activity of DIDPP and its ubiquity in the environment.

A ratiometric fluorescence sensor for detection of organophosphorus pesticides based on enzyme-regulated multifunctional Fe-based metal-organic framework.

The residues of organophosphorus pesticides (OPs) are increasing environmental pollution and public health concerns. Thus, the development of simple, convenient and sensitive method for detection of OPs is crucial. Herein, a multifunctional Fe-based MOF with fluorescence, catalytic and adsorption, is synthesized by a simple one-pot hydrothermal method. The ratiometric fluorescence sensor for detection of OPs is constructed by using only one multifunctional sensing material. The NH2-MIL-101(Fe) is able catalyze the o-phenylenediamine (OPD) into 2,3-diaminophenazine (DAP) in the presence of H2O2. The generated DAP can significantly quench the intrinsic fluorescence of NH2-MIL-101(Fe) by the fluorescence resonance energy transfer (FRET) and internal filtration effect (IFE), while producing a new measurable fluorescence. Without immobilization or molecular imprinting, pyrophosphate ion (PPi) can inhibit the peroxidase-like activity of the NH2-MIL-101(Fe) by chelating with Fe3+/Fe2+ redox couple. Moreover, PPi can also be hydrolyzed by alkaline phosphatase (ALP), the presence of OPs inhibits the activity of ALP, resulting in the increase of extra PPi preservation and signal changes of ratiometric fluorescence, the interactions of ALP with different OPs are explored by molecular docking, the OPs (e.g., glyphosate) interact with crucial amino acid residues (Asp, Ser, Ala, Lys and Arg) are indicated. The proposed sensor exhibits excellent detection performance for OPs with the detection limit of 18.7 nM, which provides a promising strategy for detection of OPs.

Degranulation and expression of cytokines were modulated by diazinon in activated mast cells.

Diazinon is an organophosphorus (OP) insecticides used in agriculture, home gardening and indoor pest control in Japan. It can activate macrophages and induce pro-inflammatory responses and has been reported to cause airway hyper-reactivity, suggesting the possibility of asthma exacerbation from exposure to OP insecticides. Despite the correlation between insecticide use and the pathogenesis of allergic diseases, there have been no reports on the effects of diazinon on mast cell function. Therefore, in this study, we investigated the effects of diazinon on mast cell function in rat basophilic leukemia (RBL)-2H3 cells. Surprisingly, we found that diazinon inhibited mast cell activation, although the degree of inhibition varied with concentration. Diazinon induced reactive oxygen species (ROS) generation and HO-1 expression at a concentration of 150µM without affecting cell viability. Diazinon inhibited A23187-mediated degranulation and Tnf and Il4 expression in RBL-2H3 cells but did not affect calcium influx. Suppression of degranulation by diazinon was reversed when the culture supernatant was removed. As a signaling event downstream of calcium influx, diazinon inhibited the phosphorylation of extracellular signal-regulated kinase (ERK) induced by A23187, whereas the phosphorylation of p38 had little effect. IgE cross-linking-mediated degranulation as well as the induction of Tnf and IL4 expression was significantly inhibited by diazinon, while diazinon had little effect on calcium influx. In conclusion, diazinon inhibited mast cell activation, including degranulation and cytokine expression. When evaluating the in vivo effects of diazinon, its potential to inhibit mast cell activation should be considered in the pathophysiology and development of allergic diseases in terms of basic and clinical aspects, respectively, although the effect of diazinon varies depending on the cell type.

Integrated Approach for Testing and Assessment for Developmental Neurotoxicity (DNT) to Prioritize Aromatic Organophosphorus Flame Retardants.

Organophosphorus flame retardants (OPFRs) are abundant and persistent in the environment but have limited toxicity information. Their similarity in structure to organophosphate pesticides presents great concern for developmental neurotoxicity (DNT). However, current in vivo testing is not suitable to provide DNT information on the amount of OPFRs that lack data. Over the past decade, an in vitro battery was developed to enhance DNT assessment, consisting of assays that evaluate cellular processes in neurodevelopment and function. In this study, behavioral data of small model organisms were also included. To assess if these assays provide sufficient mechanistic coverage to prioritize chemicals for further testing and/or identify hazards, an integrated approach to testing and assessment (IATA) was developed with additional information from the Integrated Chemical Environment (ICE) and the literature. Human biomonitoring and exposure data were identified and physiologically-based toxicokinetic models were applied to relate in vitro toxicity data to human exposure based on maximum plasma concentration. Eight OPFRs were evaluated, including aromatic OPFRs (triphenyl phosphate (TPHP), isopropylated phenyl phosphate (IPP), 2-ethylhexyl diphenyl phosphate (EHDP), tricresyl phosphate (TMPP), isodecyl diphenyl phosphate (IDDP), tert-butylphenyl diphenyl phosphate (BPDP)) and halogenated FRs ((Tris(1,3-dichloro-2-propyl) phosphate (TDCIPP), tris(2-chloroethyl) phosphate (TCEP)). Two representative brominated flame retardants (BFRs) (2,2'4,4'-tetrabromodiphenyl ether (BDE-47) and 3,3',5,5'-tetrabromobisphenol A (TBBPA)) with known DNT potential were selected for toxicity benchmarking. Data from the DNT battery indicate that the aromatic OPFRs have activity at similar concentrations as the BFRs and should therefore be evaluated further. However, these assays provide limited information on the mechanism of the compounds. By integrating information from ICE and the literature, endocrine disruption was identified as a potential mechanism. This IATA case study indicates that human exposure to some OPFRs could lead to a plasma concentration similar to those exerting in vitro activities, indicating potential concern for human health.

Covalent adduct formation of histone with organophosphorus pesticides in vitro.

It is established that organophosphorus pesticide (OPP) toxicity results from modification of amino acids in active sites of target proteins. OPPs can also modify unrelated target proteins such as histones and such covalent histone modifications can alter DNA-binding properties and lead to aberrant gene expression. In the present study, we report on non-enzymatic covalent modifications of calf thymus histones adducted to selected OPPs and organophosphate flame retardants (OPFRs) in vitro using a bottom-up proteomics method approach. Histones were not found to form detectable adducts with the two tested OPFRs but were avidly modified by a few of the seven OPPs that were tested in vitro. Dimethyl phosphate (or diethyl phosphate) adducts were identified on Tyr, Lys and Ser residues. Most of the dialkyl phosphate adducts were identified on Tyr residues. Methyl and ethyl modified histones were also detected. Eleven amino residues in histones showed non-enzymatic covalent methylation by exposure of dichlorvos and malathion. Our bottom-up proteomics approach showing histone-OPP adduct formation warrants future studies on the underlying mechanism of chronic illness from exposure to OPPs.

Unimolecular Decomposition Mechanism of Trimethyl Phosphate.

Trimethyl phosphate (TMP), an organophosphorus compound (OPC), is a promising fire-retardant candidate for lithium-ion battery (LIB) electrolytes to mitigate fire spread. This study aims to understand the mechanism of TMP unimolecular thermal decomposition to support the integration of a TMP chemical kinetic model into a LIB electrolyte surrogate model. Reactive intermediates and products of TMP thermal decomposition were experimentally detected using vacuum ultraviolet (VUV) synchrotron radiation and double imaging photoelectron photoion coincidence (i2PEPICO) spectroscopy. Phosphorus-containing intermediates such as PO, HPO and HPO2 were identified. Sampling effects could successfully be obviated thanks to photoion imaging, which also showed evidence for isomerization reactions upon wall collisions in the ionization chamber. Quantum chemical calculations performed for the unimolecular decomposition of TMP revealed for the first time that isomerization channels via hydrogen and methyl transfer (barrier heights of 65.9 and 72.6 kcal/mol, respectively) are the lowest-energy primary steps of TMP decomposition followed by CH3OH/CH3/CH2O or dimethyl ether (DME) production, respectively. We found an analogous DME production channel in the unimolecular decomposition of dimethyl methylphosphonate (DMMP), another important OPC fire-retardant additive with a similar molecular structure to TMP, which are not included in currently available chemical kinetic models.

Direct and specific detection of methyl-paraoxon using a highly sensitive fluorescence strategy combined with phosphatase-like nanozyme and molecularly imprinted polymer.

Methyl paraoxon (MP) is a highly toxic, efficient and broad-spectrum organophosphorus pesticide, which poses significant risks to ecological environment and human health. Many detection methods for MP are based on the enzyme catalytic or inhibition effect. But natural biological enzymes are relatively expensive and easy to be inactivated with a short service life. As a unique tool of nanotechnology with enzyme-like characteristics, nanozyme has attracted increasing concern. However, a large proportion of nanozymes lack the intrinsic specificity, becoming a main barrier of constraining their use in biochemical analysis. Here, we use a one-pot reverse microemulsion polymerization combine the gold nanoclusters (AuNCs) with molecularly imprinted polymers (MIPs), polydopamine (PDA) and hollow CeO2 nanospheres to synthesize the bright red-orange fluorescence probe (CeO2@PDA@AuNCs-MIPs) with high phosphatase-like activity for selective detection of MP. The hollow structure possesses a specific surface area and porous matrix, which not only increases the exposure of active sites but also enhances the efficiency of mass and electron transport. Consequently, this structure significantly enhances the catalytic activity by reducing transport distances. The introduced MIPs provide the specific recognition sites for MP. And Ce (III) can excite aggregation induced emission of AuNCs and enhance the fluorescent signal. The absolute fluorescence quantum yield (FLQY) of CeO2@PDA@AuNCs-MIPs (1.41 %) was 12.8-fold higher than that of the GSH-AuNCs (0.11 %). With the presence of MP, Ce (IV)/Ce (III) species serve as the active sites to polarize and hydrolyze phosphate bonds to generate p-nitrophenol (p-NP), which can quench the fluorescent signal through the inner-filter effect. The as-prepared CeO2@PDA@AuNCs-MIPs nanozyme-based fluorescence method for MP detection displayed superior analytical performances with wide linearities range of 0.45-125 nM and the detection limit of 0.15 nM. Furthermore, the designed method offers satisfactory practical application ability. The developed method is simple and effective for the in-field detection.

A new approach to monitoring typical organophosphorus compounds (OPs) in environmental media: From database building to suspect screening.

Organophosphorus compounds (OPs) are widely used as flame retardants (FRs) and plasticizers, yet strategies for comprehensively screening of suspect OPs in environmental samples are still lacking. In this work, a neoteric, robust, and general suspect screening technique was developed to identify novel chemical exposures by use of ultra-high performance liquid chromatography-Q Exactive hybrid quadrupole-Orbitrap high resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS). We firstly established a suspect chemical database which had 7,922 OPs with 4,686 molecular formulas, and then conducted suspect screening in n = 50 indoor dust samples, n = 76 sediment samples, and n = 111 water samples. By use of scoring criteria such as retention time prediction models, we successfully confirmed five compounds by comparison with their authentic standards, and prioritized three OPs candidates including a nitrogen/fluorine-containing compound, that is dimethyl {1H-indol-3-yl[3-(trifluoromethyl)anilino]methyl} phosphonate (DMITFMAMP). Given that the biodegradation half-life values in water (t1/2,w) of DMITFMAMP calculated by EPI Suite is 180 d, it is considered to be potentially persistent. This strategy shows promising potential in environmental pollution assessment, and can be expected to be widely used in future research.

Environmental exposures to organophosphorus flame retardants in early pregnancy and risks of gestational diabetes mellitus: a nested case-control study.

OPFRs are emerging environmental pollutants with reproductive and endocrine toxicity. This study aimed to examine the association between environmental exposure to OPFRs during early pregnancy and GDM. This nested case-control study was based on a birth cohort that was constructed at a maternal and child health hospital, including 74 cases of GDM among 512 pregnant women. The OPFRs, including TBP, TBEP, TCEP, TDCPP, TMCP, TOCP, and TPHP during 10-14 weeks of pregnancy were determined using GC-MS. The association between the OPFRs and GDM was assessed using WQS and BKMR models. The levels of OPFRs were significantly elevated in GDM patients (60) compared with the controls (90). The WQS analysis showed that mixtures of the OPFRs were significantly associated with GDM (OR 1.370, 95% CI 1.036-1.810, P = 0.027), and TBP, TPHP, and TMCP were the major contributors to the mixed exposure effect. In the BKMR model, individual exposure to TBP, TPHP, and TMCP, and the interaction of TMCP with TBP and TPHP were significantly associated with GDM. Environmental exposure to OPFRs is positively associated with GDM. These findings provide evidence for the adverse effects of OPFR exposure on the health of pregnant women.

Association between exposure to organophosphorus pesticide and suicidal ideation among U.S. adults: A population-based study.

OBJECTIVE: This study aims to investigate the potential link between exposure to organophosphorus pesticides (OPPs) and suicidal ideation (SI) among adults. METHODS: This study encompassed four cycles of the National Health and Nutrition Examination Survey (NHANES), involving 5244 participants aged 20 and above. SI was assessed using the Patient Health Questionnaire-9. The levels of exposure to OPPs were estimated by analyzing concentrations of OPP metabolites in urine samples. Multivariate logistic regression models were used to explore the association between exposure to each OPP and SI. Stratified analyses and interaction tests were conducted across various groups, including pairwise combinations of gender and age, as well as body mass index, smoking status, hypertension, and diabetes. Weighted Quantile Sum (WQS) regression and Bayesian Kernel Machine Regression (BKMR) models were applied to assess the cumulative impact of exposure to the four OPPs on SI, along with their respective contributions. Additionally, the potential interactions among these four OPPs were evaluated. RESULTS: Multivariate logistic regression revealed that only dimethylthiophosphate (DMTP) among OPPs demonstrated a statistically significant positive association with SI [OR: 1.18; 95 % CI: 1.02-1.37]. Stratified analyses indicated that the influence of OPPs on SI was particularly pronounced in young and older men. The WQS regression analysis revealed a statistically significant association between the mixed metabolites of OPPs and SI [OR = 1.10, 95 % CI: 1.04-1.16], with DMTP (weighted 0.63) contributing the most. Furthermore, the BKMR model supported a positive trend in the overall impact of these OPP metabolites on SI, displaying notable individual exposure-response relationships for DMTP (PIP: 0.77). CONCLUSIONS: Our study suggests an association between exposure to DMTP and an increased risk of SI. Specifically, young adult males and older males appear particularly susceptible to the effects of OPP exposure.

Recycling scale inhibitor wastes into pH-responsive complexes to treat wastewater produced from spent lithium-ion battery disposal.

A large amount of organophosphorus-containing wastewater is produced in spent lithium-ion battery disposal. Forward osmosis (FO) offers unique advantages in purifying this kind of wastewater if suitable draw solutes - the core of FO technology, are available. Herein we synthesize several pH-sensitive zinc complexes, namely ZnATMP-iNa (i = 0, 1, 2, 3, 4), from ZnSO4 and amino tris(methylene phosphonic acid) (ATMP) obtained from scale inhibitor wastes for organophosphorus-containing wastewater remediation. Among these ZnATMP-iNa, ZnATMP-3Na best meets the standards of an ideal draw solute. This makes ZnATMP-3Na outperform other reported draw solutes. 0.6 M ZnATMP-3Na produces a water flux of 12.7 LMH, 136 % higher than that of NaCl and a solute loss of 0.015 g/L, lower than that of NH4HCO3 (0.83 g/L). In organophosphorus-containing wastewater treatment, ZnATMP-3Na has higher water recovery efficiency (8.3 LMH) and sustainability than NaCl and NH4HCO3, and is sufficient to handle large quantities of wastewater. Remarkably, the pH-responsive property allows ZnATMP-3Na to be readily recovered through pH-control and reused in FO. The ionic property, expanded cage-like structure and easy-recycling make ZnATMP-3Na achieve sustainable FO separation and superior to other draw solutes. This study provides inspiration for draw solute design from wastes and extends FO application to organophosphorus-containing wastewater remediation.

Reproductive toxicology of environmental endocrine-disrupting chemicals in women: a cohort study protocol.

Introduction: Epidemiological evidence over the last few decades has consistently shown that exposure to endocrine-disrupting chemicals (EDCs) is associated with adverse reproductive health outcomes, including male and female infertility, poor-pregnancy outcomes, and increased risk of diseases in childhood and beyond. To investigate the effects of EDCs and lifestyle on all aspects of reproduction (including early oocyte development, fertilization, embryo development, embryo implantation, abortion, and preterm birth). Methods: We performed this cohort study on patients receiving in vitro fertilization (IVF) treatment. Biological samples including urine, serum, follicular fluid, semen, fetal tissue, decidua, and placenta, were obtained. Results: By studying the correlations between reproductive outcomes and environmental pollutant exposure and lifestyle, we determined the toxicological mechanisms and health effects of EDCs on female reproductive health. We found that higher concentrations of per- and polyfluoroalkyl substances were correlated with polycystic ovary syndrome (PCOS). Using specific biomarkers, we also detected the concentrations of organophosphorus flame retardants (OPFRs) in urine and found that OPFRs may disrupt hormone homeostasis. Discussion: All of these results reveal EDCs may disrupt female reproduction.

Recent progress on the functionalization of white phosphorus in China.

Direct synthesis of organophosphorus compounds from white phosphorus represents a significant but challenging subject, especially in the context of ongoing efforts to comprehensively improve the phosphorus-derived chemical industry driven by sustainability and safety concerns. China is the world's largest producer of white phosphorus, creating a significant demand for the green transformation of this crucial feedstock. This review provides an overview of advancements in white phosphorus activation by Chinese research teams, focusing on the direct construction of P‒C/N/O/S/M bonds from white phosphorus. Additionally, we offer some insights into prospective directions for the activation and transformation of white phosphorus in the future. This review paper aims to attract more researchers to engage in this area, stimulating follow-up exploration and fostering enduring advances.

Evaluation of the effectiveness of fresh frozen plasma transfusion as adjuvant treatment in acute organophosphate-poisoned patients: A randomized clinical trial.

Organophosphorus (OP) poisoning is a significant cause of morbidity and mortality worldwide. Recent research has explored new approaches to improving treatment options, which present several challenges. This study aimed to evaluate the role of fresh frozen plasma (FFP) as an adjunctive therapy for acute OP intoxication. A prospective single-blinded randomized clinical trial was conducted on patients of both sexes admitted to the Intensive Care Unit (ICU) of the Poison Control Center at Ain Shams University Hospital (PCC-ASUH) with acute OP toxicity during the period from the beginning of August 2022 to the end of July 2023. According to the Peradeniya score, Group I consisted of 48 patients (52%) with moderate OP poisoning, and Group II consisted of 44 patients (48%) with severe OP poisoning. Patients in the moderate group were assigned to receive either standard treatment (Group Ia, n = 24) or standard treatment plus FFP (Group Ib, n = 24). In addition, patients in the severe group were assigned to receive either standard treatment (Group IIa, n = 22) or standard treatment plus FFP (Group IIb, n = 22). A total of 46 patients received FFP transfusion. The authors demonstrated that the early use of a total of nine packs of FFP (250 mL each) over three consecutive days significantly reduced the total doses of atropine and oximes, the total hospitalization period, and the requirement for mechanical ventilation in patients with OP poisoning, both in the moderate and severe groups.

Chlorinated organophosphorus flame retardants induce the propagation of antibiotic resistance genes in sludge fermentation systems: Insight of chromosomal mutation and microbial traits.

Waste activated sludge (WAS) is a critical reservoir for antibiotic resistance genes (ARGs) due to the prevalent misuse of antibiotics. Horizontal gene transfer (HGT) is the primary mechanism for ARGs spread through mobile genetic elements (MGEs). However, the role of non-antibiotic organophosphorus flame retardants (Cl-OFRs) in ARG transmission in the WAS fermentation system remains unclear. This study examines the effects of tris(2-chloroethyl) phosphate (TCEP), a representative Cl-OFR, on ARG dynamics in WAS fermentation using molecular docking and metagenomic analysis. The results showed a 33.4 % increase in ARG abundance in the presence of TCEP. Interestingly, HGT did not appear to be the primary mechanism of ARG dissemination under TCEP stress, as evidenced by a 2.51 % decrease in MGE abundance. TCEP binds to sludge through hydrogen bonds with a binding energy of - 3.6 kJ/mol, leading to microbial damage and an increase in the proportion of non-viable cells. This interaction prompts a microbial shift toward Firmicutes with thick cell walls, which are significant ARG carriers. Additionally, TCEP induces chromosomal mutations through oxidative stress and the SOS response, contributing to ARG formation. Microorganisms also develop multidrug resistance mechanisms to expel TCEP and mitigate its toxicity. This study provides a comprehensive understanding of Cl-OFRs effects on the ARGs fates in WAS fermentation system and offers guidance for the safe and efficient treatment of Cl-OFRs and WAS.

Advancements in bioscavenger mediated detoxification of organophosphorus poisoning.

Background: Organophosphorus compounds, widely used in agriculture and industry, pose a serious threat to human health due to their acute neurotoxicity. Although traditional interventions for organophosphate poisoning are effective, they often come with significant side effects. Objective: This paper aims to evaluate the potential of enzymes within biological organisms as organophosphorus bioclearing agents. It analyses the technical challenges in current enzyme research, such as substrate specificity, stereoselectivity, and immunogenicity, while exploring recent advancements in the field. Methods: A comprehensive review of literature related to detoxifying enzymes or proteins was conducted. Existing studies on organophosphorus bioclearing agents were summarised, elucidating the biological detoxification mechanisms, with a particular focus on advancements in protein engineering and novel delivery methods. Results: Current bioclearing agents can be categorised into stoichiometric and catalytic bioclearing agents, both of which have shown some success in preventing organophosphate poisoning. Technological advancements have significantly improved various properties of bioclearing agents, yet challenges remain, particularly in substrate specificity, stereoselectivity, and immunogenicity. Future research will focus on expanding the substrate spectrum, enhancing catalytic efficiency, prolonging in vivo half-life, and developing convenient administration methods. Conclusion: With the progression of clinical trials, bioclearing agents are expected to become widely used as a new generation of therapeutic organophosphate detoxifiers.

The Role of Neutrophil-to-Lymphocyte Ratio in Predicting Outcomes of Acute Organophosphorus Poisoning: A Comprehensive Review.

Organophosphorus poisoning (OPP) poses a significant threat to human health, necessitating accurate prognostic markers for timely intervention and improved outcomes. This review evaluates the potential of the neutrophil-to-lymphocyte ratio (NLR) as a prognostic indicator in acute organophosphorus poisoning (AOPP). A comprehensive analysis of existing literature reveals that elevated NLR values correlate with increased severity of poisoning and adverse clinical outcomes, including mortality and morbidity. NLR assessment offers valuable prognostic information beyond traditional markers, aiding risk stratification and guiding clinical decision-making. Integration of NLR into clinical practice holds promise for optimizing patient care through the early identification of high-risk individuals and tailored therapeutic interventions. Further research is needed to validate the utility of NLR in larger patient cohorts and standardize its incorporation into clinical guidelines. Leveraging NLR as a prognostic tool can enhance risk stratification, optimize treatment strategies, and ultimately improve outcomes in AOPP.