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This study addresses a comprehensive assessment of the interaction between chemical warfare agents (CWA) and acetylcholinesterase (AChE) systems, focus on the intriguing pnictogen‐bond interaction (PnB). Utilizing the crystallographic data from the Protein Data Bank pertaining to the AChE‐CWA complex involving Sarin (GB), Cyclosarin (GF), 2‐[fluoro(methyl)phosphoryl]oxy‐1,1‐dimethylcyclopentane (GP) and venomous agent X (VX) agents, the CWA is systematically displaced by increments of 0.1 Å along the PO bond axis, extending its distance by 4 Å from the original position. The AIM analysis was carried out and consistently revealed the presence of a significant interaction along the PO bond. Investigating the intrinsic nature of the PnB, the NBO and the EDA analysis unearthed the contribution of orbital factors to the overall energy of the system. Strikingly, this observation challenges the conventional σ‐hole explanation commonly associated with such interactions. This finding adds a layer of complexity to understanding of PnB, encouraging further exploration into the underlying mechanisms governing these intriguing chemical phenomena. [ABSTRACT FROM AUTHOR]

Nerve agents are the most notorious substances, which can be fatal to an individual because they block the activity of acetylcholinesterase. Fighting against unpredictable terrorist assaults and wars requires the simple and quick detection of chemical warfare agent vapor. In the present contribution, we have introduced a rhodamine-based chemosensor, BDHA, for the detection of nerve gas-mimicking agents diethylchlorophosphate (DCP) and diethylcyanophosphonate (DCNP) and mustard gas-mimicking agent 2-chloroethyl ethyl sulfide (CEES), both in the liquid and vapor phase. Probe BDHA provides the ability for detection by the naked eye in terms of colorimetric and fluorometric changes. It has been revealed that the interaction between nerve agents mimics and probe BDHA facilitates spirolactam ring opening due to the phosphorylation process. Thus, the highly fluorescent and colored species developed while probe BDHA is colorless and non-fluorescent due to the intramolecular spirolactam ring. Moreover, probe BDHA can effectively recognize DCP, DCNP, and CEES in the µM range despite many toxic analytes and could be identified based on the response times and quantum yield values. Inexpensive, easily carried paper strips-based test kits were developed for the quick, on-location solid and vapor phase detection of these mustard gas imitating agents (CEES) and nerve gas mimicking agents (DCP and DCNP) without needing expensive equipment or skilled personnel. More remarkably, the test strips' color and fluorescence can be rapidly restored, exposing them to triethyl amine (TEA) for cyclic use, suggesting a potential application in the real-time identification of chemical warfare agents. To accomplish the on-location application of BDHA, we have experimented with soil samples to find traces of DCP. Therefore, the chromo-fluorogenic probe BDHA is a promising, instantaneous, and on-the-spot monitoring tool for the selective detection of DCP, DCNP, and CEES in the presence of others. [ABSTRACT FROM AUTHOR]

RNA viruses of the genera Ambivirus, Mitovirus, Sclerotimonavirus, and Partitivirus were found in a single isolate of Fusarium graminearum. The genomes of the mitovirus, sclerotimonavirus, and partitivirus were assigned to previously described viruses, whereas the ambivirus genome putatively represents a new species, named Fusarium graminearum ambivirus 1 (FgAV1). To investigate the effect of mycoviruses on the fungal phenotype, the spontaneous loss of mycoviruses during meiosis and the transmission of mycoviruses into a new strain via anastomosis were used to obtain isogenic F. graminearum strains both with and without mycoviruses. Notable effects observed in mycovirus-harboring strains were (i) the suppression of the synthesis of trichothecene mycotoxins and their precursor trichodiene, (ii) the suppression of the synthesis of the defense compound aurofusarin, (iii) the stimulation of the emission of 2-methyl-1-butanol and 3-methyl-1-butanol, and (iv) the increased attractiveness of fungal mycelia for fungivorous collembolans. The increased attractiveness of mycovirus-infected filamentous fungi to animal predators opens new perspectives on the ecological implications of the infection of fungi with viruses. [ABSTRACT FROM AUTHOR]

Precision-cut lung slices (PCLS) are a suitable model for analyzing the acetylcholinesterase (AChE) activity and subsequent effects after exposure to organophosphorus (OP) compounds. In this study, the AChE activity was determined in intact PCLS for the first time. Since the current standard therapy for OP poisoning (atropine + oxime + benzodiazepine) lacks efficiency, reliable models to study novel therapeutic substances are needed. Models should depict pathophysiological mechanisms and help to evaluate the beneficial effects of new therapeutics. Here PCLS were exposed to three organophosphorus nerve agents (OPNAs): sarin (GB), cyclosarin (GF), and VX. They were then treated with three reactivators: HI-6, obidoxime (OBI), and a non-oxime (NOX-6). The endpoints investigated in this study were the AChE activity and the airway area (AA) change. OPNA exposure led to very low residual AChE activities. Depending on the reactivator properties different AChE reactivation results were measured. GB-inhibited PCLS-AChE was reactivated best, followed by VX and GF. To substantiate these findings and to understand the connection between the molecular and the functional levels in a more profound way the results were correlated to the AA changes. These investigations underline the importance of reactivator use and point to the possibilities for future improvements in the treatment of OPNA-exposed victims. • Acetylcholinesterase (AChE) activity determination in precision-cut lung slices (PCLS): Use of PCLS as an ex vivo model. • Comprehensive OPNA exposure and reactivation study: Exposure of PCLS to GB, GF, and VX, followed by reactivation with HI-6, OBI, and aNOX-6. • AChE reactivation results: Revealing varying reactivation efficiencies for different nerve agents: GB > VX > GF. • Correlation of molecular and functional levels: Correlating AChE activities with airway area (AA) changes. [ABSTRACT FROM AUTHOR]

A selective and reliable modified glassy carbon sensor, based on a 1.0% Cd zeolitic imidazole framework-67 modified glassy carbon sensor (GCS2), has been developed for ultrasensitive detection of dimethyl methyl phosphonate (DMMP) in human biological fluid. The synthesis of porous nanoparticles of Cd zeolitic imidazole framework-67 (Cd ZIF-67) was carried out via the hydrothermal method. The resulting Cd ZIF-67 powder emerges with good crystallinity, a rhombic dodecahedral morphology with particle size in the range 300 ~ 500 nm, and a specific surface area of 1780 m2·g−1. Furthermore, the fabricated sensor exhibited superior performance in the detection of DMMP with two linearity ranges of 0.02–2.0 nM and 2.0–9.0 nM and a limit of detection (LOD) of 0.06 pM. The fabricated sensor exhibited good reliability, long-term stability, and repeatability, which are favourable attributes for electroanalytical detection. In addition, the fabricated sensor displayed superior performance without significant interference during the assay of DMMP in a biological fluid (human serum sample) within two linearity ranges of 0.1–1.0 nM and 1.0–6.0 nM and a LOD of 0.03 nM. [ABSTRACT FROM AUTHOR]

AbstractChemical warfare agents (CWAs) are the most feared toxic chemicals intended to debilitate the general human population and regional civilians. Therefore, prompt and urgent decontamination is needed to protect millions of lives and the associated hazardous implications. In this present study, our main goal is to evaluate the performance of Zeolite-Alpha and its various metal oxide composites as novel adsorbents for the decontamination of CWA simulants, 2-chloroethyl ethyl sulfide (CEES), and dimethyl methyl phosphonate (DMMP). Synthesized Zeolite-Alpha and their composites were characterized by XRD, FTIR, SEM-EDS, and BET analysis techniques. The CWA simulants’ decontamination (adsorption and desorption) was monitored using GC-FID and GC-MS analysis techniques. A possible reaction mechanism toward the adsorption and destruction of CWA simulants, CEES, and DMMP was also proposed. Nanocrystalline Zeolite-Alpha and its metal oxide composites are powerful adsorbents, and they showed more significant decontamination potential toward the above CWA simulants. The Cr-O-Alpha and Ag-O-Alpha showed promising results (93–98% decontamination) among all other synthesized metal oxide composites. [ABSTRACT FROM AUTHOR]

The bispyridinium oxime HI-6 DMS is in development as an improved therapy for the treatment of patients exposed to organophosphorus nerve agents. The aim of the work described in this paper was to provide non-clinical data to support regulatory approval of HI-6 DMS, by demonstrating efficacy against an oxime-sensitive agent, GB and an oxime-resistant agent, GD. We investigated the dose-dependent protection afforded by therapy including atropine, avizafone and HI-6 DMS in guinea-pigs challenged with GB or GD. We also compared the efficacy of 30 mg.kg−1 of HI-6 DMS to an equimolar dose of the current in-service oxime P2S and the dichloride salt of HI-6 (HI-6 Cl 2). In the treatment of GB or GD poisoning there was no significant difference between the salt forms. The most effective dose of HI-6 DMS in preventing lethality following challenge with GB was 100 mg.kg−1; though protection ratios of at least 25 were obtained at 10 mg.kg−1. Protection against GD was lower, and there was no significant increase in effectiveness of HI-6 DMS doses of 30 or 100 mg.kg−1. For GD, the outcome was improved by the addition of pyridostigmine pre-treatment. These data demonstrate the benefits of HI-6 DMS as a component of nerve agent therapy. © Crown copyright (2023), Dstl. • A comprehensive assessment in the guinea-pig of the efficacy of HI-6 DMS. • HI-6 was given in combination with atropine and an anticonvulsant. • Therapy including HI-6 DMS was superior to the current oxime P2S for GB and GD. • Pyridostigmine pretreatment enhanced protection against GD poisoning. [ABSTRACT FROM AUTHOR]

Dried urine spot (DUS) is a micro-sample collection technique, known for its advantages in handling, storage and shipping. It also uses only a small volume of urine, an essential consideration in working with small animals, or in acute medical situations. Alkyl-phosphonic acids are the direct and indicative metabolites of organophosphorus chemical warfare agents (OP-CWAs) and are present in blood and urine shortly after exposure. They are therefore crucially important for monitoring casualties in war and terror scenarios. We report here a new approach for the determination of the metabolites of five CWAs in urine using DUS. The method is based on a simple and rapid sample preparation, using only 50 µL of urine, spotted and dried on DBS paper, extracted using 300 µL methanol/water and analyzed via targeted LC-MS/MS. The detection limits for the five CWAs, sarin (GB), soman (GD), cyclosarin (GF), VX and RVX in human urine were from 0.5 to 5 ng/mL. Recoveries of (40–80%) were obtained in the range of 10–300 ng/mL, with a linear response (R2 > 0.964, R > 0.982). The method is highly stable, even with DUS samples stored up to 5 months at room temperature before analysis. It was implemented in a sarin in vivo exposure experiment on mice, applied for the time course determination of isopropyl methylphosphonic acid (IMPA, sarin hydrolysis product) in mice urine. IMPA was detectable even with samples drawn 60 h after the mice's (IN) exposure to 1 LD50 sarin. This method was also evaluated in a non-targeted screening for multiple potential CWA analogs (LC-Orbitrap HRMS analysis followed by automatic peak detection and library searches). The method developed here is applicable for rapid CWA casualty monitoring. [ABSTRACT FROM AUTHOR]

INTRODUCTION: We simulated an on-site, multi-hospital mass casualty incident (MCI) to educate emergency medicine providers in the principles of trauma resuscitation and collaboration with administration and staff during an MCI. METHODS: We implemented high-fidelity manikins, inflatable manikins, and actors to simulate a sarin gas bombing. Learners triaged patients at a decontamination tent using the simple triage and rapid treatment (START) tool, or they participated in a simulation in a resuscitation bay. RESULTS: Forty participants anonymously rated the learning impact of the exercise, the clinical relevance to emergency medicine, and the effectiveness of the faculty facilitation and debriefing on a 1-5 Likert scale. The average responses to all questions were 4.45 or greater, and 98% of respondents recommended adding the scenario to the standard curriculum. DISCUSSION: We successfully executed a novel, multihospital, MCI drill that was rated to be a better alternative to sequential simulation in a simulation center. [ABSTRACT FROM AUTHOR]

The host–guest chemistry of O,O′-diisopropyl fluorophosphate (DFP), a phosphonofluoridate G-series chemical warfare agent simulant, was investigated in the presence of a number of octanuclear cubic coordination cage hosts. The aim was to demonstrate cage-catalysed hydrolysis of DFP at near neutral pH: however, two octanuclear coordination cages, HPEG (containing water-solubilising PEG groups) and HW (containing water-solubilising hydroxymethyl groups), were actually found to increase the lifetime of DFP in aqueous buffer solution (pH 8.7). Crystallographic analysis of DFP with a structurally related host cage revealed that DFP binds to windows in the cage surface, not in the internal cavity. The phosphorus–fluorine bond is directed into the cavity rather than towards the external environment, with the cage/DFP association protecting DFP from hydrolysis. Initial studies with the chemical warfare agent (CWA) sarin (GB) with HPEG cage in a buffered solution also showed a drastically reduced rate of hydrolysis for sarin when bound in the host cage. The ability of these cages to inhibit hydrolysis of these P–F bond containing organophosphorus guests, by encapsulation, may have applications in forensic sample preservation and analysis. [ABSTRACT FROM AUTHOR]

Context: In contrast to un-catalyzed hydrolysis of organophosphorus (OP) compounds, metal ions or/and their complexes with chelating ligands show catalytic effects in several ways depending upon the nature of the metal, ligand, substrate, and medium. It is known that Cu(II)-en chelate containing copper complexes accelerate the hydrolysis of OP compounds. However, the mechanism for this rate enhancement in the Cu(II)-en chelate catalytic hydrolysis reaction of sarin remains unexplored. We have examined possible mechanisms involving a Cu(II)-en with hydroxide nucleophile for the reaction pathway of the hydrolysis of O-isopropyl methylphosphonofluoridate (sarin) computationally. The density functional (B3LYP) employed in this study has reproduced the experimental Gibb's free energy of activation value 15.5 kcal/mol for alkaline hydrolysis of sarin. Earlier proposal of push–pull mechanism for metal ion chelate-catalyzed hydrolysis of OP compounds has been found to be unfavorable in the present study. The role of water molecules in catalyzing the hydrolysis of sarin with Cu(II)-en chelate is crucial. The catalytic process involving Cu(II)-en chelate with one water molecule is the more plausible pathway to achieve the hydrolysis of sarin with Cu(II)-en chelate complexes. Methods: The most popular B3LYP method was used for optimization of given geometries. Except LANL2DZ for Cu atom, all the atoms are described using the 6–31 + G(d) basis set. The stability test has been performed for the wave functions as we are dealing with the open-shell molecules in order to ensure stable electronic configuration form, and the stable wavefunction is used as the initial configuration for the subsequent optimization. Harmonic frequency calculations and thermodynamic corrections were performed at the same level of theory. PCM method has been used for solvation effects. In order to ensure that each saddle point is linked to a minimum, IRC calculations were performed in forward and reverse directions to ensure the eigenvectors associated with the unique negative eigenvalues of the Hessian matrix. All energies discussed are solvated Gibbs free energies corrected to 298.15 K for the relative stability of the chemical structure. All calculations were performed using the Gaussian 09 code. [ABSTRACT FROM AUTHOR]

The name of Korkut has long attracted the attention of the world scientific community. In the folklore of many Turkic peoples related to the ancient Oghuz tribes, there are legends and myths about Korkut, which describe the heroic deeds of the Oghuz heroes. The legacy of the legendary Korkut's music and epic has attracted the attention of researchers since the middle of the 19th century. Scholars from Russia, Türkiye, Azerbaijan, Turkmenistan and Kazakhstan have written a wide number of research papers, which highlighted the problems associated with the main epic legacy of Oghuz antiquity -- "The Book of Dede Korkut" or "The Book of Korkut Ata". The literary artifacts associated with the name of the legendary Korkut have gained worldwide fame. Both versions of the Oghuz manuscript "Kitab-ı Dede Korkut Ala Lisan-ı Taife-i Oğuzan" (Dresden) and "Hikâyat-i Oğuznâme-i, Kazan Beğ ve Gayrı" (Vatican), which have come down to us, are now the focus of scientific consideration. The abundance of cognitive information and onomastic names in the epic increasingly attracts the attention of folklorists. It is no secret that in the Kazakh folklore of the early 20th century, the Soviet ideology imposed a ban on the development of the epic heritage of Korkut. Moreover, closer to the middle of the 20th century, the Oghuz heroic epic was evaluated as a creative product of the feudal era. For this reason, some peoples of Oghuz origin openly ignored the folk heritage. Korkut is a representative of the Oghuz tribe. In addition, his name has existed in Kazakh folklore for a very long time. Even before the 1917 Revolution, several legends about the Korkut tombstone were recorded by famous ethnographers. Kazakh scholars began to study folklore materials about Korkut at the turn of the 1970s. This topic was first voiced by Professor Auelbek Konratbayev, who published several articles, then translated V. V. Bartold's edition of "The Book of my grandfather Korkut" into Kazakh. In recent decades, especially after the gaining of independence, folklorists, musicologists, and performing musicians have begun to deal with this problem. It got to the point that some of them started talking about the newly found legacy of the legendary Korkut - musical compositions for the bowed instrument - kylkobyz. Without referring to reliable sources, without arguing the origin of the newly discovered musical compositions attributed to Korkut, individual authors began to publish their rather detailed research in the form of scientific articles and even books. Despite the existing criticism in international publications, the wave of pseudo-researchers is growing. The questions related to the heritage of Korkut are overgrown with all sorts of tall tales of indefinite origin. This article attempts to conduct a scientific analysis of numerous studies published in the recent years on the pages of both foreign and local press. The works of individual novice authors who are engaged in inflating the number of legends associated with the name of Korkut are subjected to special consideration. In this regard, the article emphasizes that the classic version of the Kazakh legend of Korkut was published by V. Velyaminov- Zernov in the second half of the 19th century. Despite the presence of a published text, this legend has been freely interpreted by individual authors. Another legend, once published by A. Zhubanov without reference to the original source, also requires close study. This article is based on scientific problems related to the music and epic heritage of Korkut. It highlights the stages of mastering the musical heritage of Korkut and the legends associated with them. Much attention is paid to detailed, comparative analysis and the study of primary sources. In the process of developing the theme, all the changes that have occurred since the beginning of the development of the musical heritage of Korkut are identified. The legends that allegedly arose in connection with his music are also subjected to scientific analysis. Through the prism of hermeneutical analysis, the musical melodies attributed to Korkut are also studied. A special attention is drawn to the reliability of previ ously unknown primary sources that have begun to enter scientific realm. At the same time, the artistic features and scientific significance of these musical tunes are analyzed. Only in recent years, several articles about Korkut's musical heritage have been published on the pages of foreign scientific publications. They have become the focus of this article. In the recent years previously unknown legends, which have been claimed to be preserved in Kazakh folklore, have appeared in the literature. The admirers of Korkut's name are trying hard to connect these immature plots with the name of the legendary Korkut. Moreover, some researchers started talking about the musical heritage of Korkut, which is not known not only to the Turkic world, but also to the scientific world. As the primary source, they began to refer to the religious and mystical tunes of Nishan Shamenuly, who lived in the second half of the 20th century, from whom the musical tunes "saryn" and "sarnau" were recorded. This article attempts to determine the origin of the music and religious tunes of Nishan, because the aforementioned sweeping statements are circulated without taking into account the centuries-old performing tradition of the kobyz, some of which has not even reached our times. Without much detailed research so-called previously unknown musical heritage of medieval Korkut have been introduced to the whole world. Moreover, these same tunes, which have nothing to do with the legendary Korkut, were included in the UNESCO list as an example of the intangible culture of medieval antiquity. All these questions formed the main problem of the given article. [ABSTRACT FROM AUTHOR]

A new Mean Sea Surface (MSS) called DTU21MSS for referencing sea level anomalies from satellite altimetry is introduced in this paper and a suite of evaluations are performed. One of the reasons for updating the existing Mean Sea Surface is the fact, that during the last 6 years nearly three times as much data have been made available by the space agencies, resulting in more than 15 years of altimetry from Long Repeat Orbits or Geodetic Missions. This includes the two interleaved long repeat cycles of Jason-2 with a systematic cross-track distance as low as 4 km. A new processing chain with updated filtering and editing has been implemented for DTU21MSS. This way, the DTU21MSS has been computed from 2Hz altimetry in contrast to the former DTU15MSS/DTU18MSS which were computed from 1 Hz altimetry. The new DTU21MSS is computed over the same 20-year averaging time from 1993.01.01 to 2012.12.31 with a well-specified central time of 2003.01.01 and is available from the following site; https://doi.org/10.11583/DTU.19383221.v1, Andersen, 2022) Cryosat-2 employs SAR and SARin modes in a large part of the Arctic Ocean due to the presence of sea ice. For SAR and SARin mode data we applied the SAMOSA+ physical retracking in order to make it compatible with the physical retracker used for conventional Low-Resolution Mode data in other parts of the ocean. [ABSTRACT FROM AUTHOR]

Simple Summary: Sarin is a potent organophosphate nerve agent that is a representative of a chemical weapon and poses a threat to human health. In this study, the effects of repeated low-level sarin exposure on the cognitive behavior of rats were studied, and the activity of AChE activity and dendritic spine density in the hippocampus were measured. Whole-transcriptome and bioinformatics methods were used to analyze the related molecular mechanisms, and finally, the ceRNA regulatory network was constructed and analyzed. These newly discovery techniques provide a theoretical basis for the mechanism of sarin-induced cognitive impairment and also offer new insights for the research of other organophosphorus toxicants. Sarin is a potent organophosphorus nerve agent that causes cognitive dysfunction, but its underlying molecular mechanisms are poorly understood. In this study, a rat model of repeated low-level sarin exposure was established using the subcutaneous injection of 0.4 × LD50 for 21 consecutive days. Sarin-exposed rats showed persistent learning and memory impairment and reduced hippocampal dendritic spine density. A whole-transcriptome analysis was applied to study the mechanism of sarin-induced cognitive impairment, and a total of 1035 differentially expressed mRNA (DEmRNA), including 44 DEmiRNA, 305 DElncRNA, and 412 DEcircRNA, were found in the hippocampus of sarin-treated rats. According to Gene Ontology (GO) annotation, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, and Protein–Protein Interaction (PPI) analysis, these DERNAs were mainly involved in neuronal synaptic plasticity and were related to the pathogenesis of neurodegenerative diseases. The circRNA/lncRNA–miRNA–mRNA ceRNA network was constructed, in which Circ_Fmn1, miR-741-3p, miR-764-3p, miR-871-3p, KIF1A, PTPN11, SYN1, and MT-CO3 formed one circuit, and Circ_Cacna1c, miR-10b-5p, miR-18a-5p, CACNA1C, PRKCD, and RASGRP1 constituted another circuit. The balance between the two circuits was crucial for maintaining synaptic plasticity and may be the regulatory mechanism by which sarin causes cognitive impairment. Our study reveals the ceRNA regulation mechanism of sarin exposure for the first time and provides new insights into the molecular mechanisms of other organophosphorus toxicants. [ABSTRACT FROM AUTHOR]

Over 40% of veterans from the Persian Gulf War (GW) (1990–1991) suffer from Gulf War Illness (GWI). Thirty years since the GW, the exposure and mechanism contributing to GWI remain unclear. One possible exposure that has been attributed to GWI are chemical warfare agents (CWAs). While there are treatments for isolated symptoms of GWI, the number of respiratory and cognitive/neurological issues continues to rise with minimum treatment options. This issue does not only affect veterans of the GW, importantly these chronic multisymptom illnesses (CMIs) are also growing amongst veterans who have served in the Afghanistan-Iraq war. What both wars have in common are their regions and inhaled exposures. In this review, we will describe the CWA exposures, such as sarin, cyclosarin, and mustard gas in both wars and discuss the various respiratory and neurocognitive issues experienced by veterans. We will bridge the respiratory and neurological symptoms experienced to the various potential mechanisms described for each CWA provided with the most up-to-date models and hypotheses. [ABSTRACT FROM AUTHOR]

A series of oxovanadium(V) compounds 1–4 were prepared and explored as stereodynamic chiroptical probes to detect a simulant of sarin known as diethyl chlorophosphate (DCP) without any interference from the competing analytes. Simultaneous CD cum UV/vis based bimodal instant recognition of DCP using optically active probes is unprecedented. Upon fabricating the vanadium compound with a polymer has yielded a chiroptical membrane, which showed a change in its dichroic as well as colorimetric signals on interaction with DCP vapour at 1 ppm. EPR and UV/vis studies revealed an irreversible change of the CD-active V(V) to the CD-silent ternary V(V) species in presence of DCP via a transient V(IV) species. Nucleophilic attack of the alkoxo oxygen of 1–4 to the electrophilic P atom of DCP resulted in the formation of ternary V(V) compounds as confirmed by 51V/31P NMR. [ABSTRACT FROM AUTHOR]

Sarin was used as a chemical weapon due to its high neurotoxicity and mortality. Subacute sarin induced cognitive and behavioral disorder. However, the underlying mechanism is still unclear. Here we offered a multi-omic approach for the analysis of altered metabolites, lipids, and proteins to explore the neurotoxicity of subacute sarin. Guinea pigs were administered between the shoulder blades 16.8 μg/kg of sarin in a volume of 1.0 ml/kg body weight by subcutaneous injection once daily for 14 days. At the end of the final injection, guinea pigs were sacrificed, and striatum were dissected for analysis. A total of 138 different metabolites were identified in the metabolome analysis. Lipids and lipid-like molecules is the largest group (38.41%). For lipidomic analysis, a total of 216 lipids were identified. In proteomic study, over 4300 proteins were identified and quantified. By integrating these enriched components, we demonstrated that the joint pathways disturbed by subacute sarin mainly involving lipid, purine and pyrimidine metabolism in guinea pig striatum. Overall, this study highlights the powerfulness of omics platforms to deepen the understanding of nerve agents caused neurotoxicity. [Display omitted] • Subacute sarin disturbed the cognitive and motor abilities in guinea pigs. • Subacute sarin disturbed purine and pyrimidine metabolism in striatum. • Nucleotides play important roles in alleviating neurotoxicity of nerve agents. • Omics platforms are useful to deepen the understanding of nerve agents caused neurotoxicity. [ABSTRACT FROM AUTHOR]

This study proposes a predictive model for assessing adsorber performance in gas purification processes, specifically targeting the removal of chemical warfare agents (CWAs) using breakthrough curve analysis. Conventional parameter estimation methods, such as Brunauer-Emmett-Teller analysis, encounter challenges due to the limited availability of kinetic and equilibrium data for CWAs. To overcome these challenges, we implement a Bayesian parametric inference method, facilitating direct parameter estimation from breakthrough curves. The model's efficacy is confirmed by applying it to H 2 S purification in a fixed-bed setup, where predicted breakthrough curves aligned closely with previous experimental and numerical studies. Furthermore, the model is applied to sarin with ASZM-TEDA carbon, estimating key parameters that could not be assessed through conventional experimental techniques. The reconstructed breakthrough curves closely match actual measurements, highlighting the model's accuracy and robustness. This study not only enhances filter performance prediction for CWAs but also offers a streamlined approach for evaluating gas purification technologies under limited experimental data conditions. [Display omitted] • This study introduces a novel Bayesian model to analyze the gas purification process. • The model accurately estimates elusive adsorption parameters for toxic gas. • The model enables a single-step adsorption analysis using breakthrough curves. • The model's validity is confirmed through a successful application to sarin gas. [ABSTRACT FROM AUTHOR]

A phenanthroimidazole-based luminogen, BIB , has been introduced for specific and selective detection of sarin gas surrogate diethylchlorophosphate (DCP) within the stores of various analogous toxic analytes. [Display omitted] • A phenanthroimidazole-based luminogen, BIB , has been introduced to detect sarin gas surrogate diethylchlorophosphate (DCP). • BIB displayed a highly distinct ratiometric fluorescence response. • The fluorogenic response is wholly reversed in the presence of triethylamine. • BIB can selectively detect DCP with a low detection limit to µM range. • BIB has been employed as a portable and displayable photonic sensing tool for on-site detection. The nerve agent's extreme toxicity makes it a prominent target to detect them to save global harmony. In the present contribution, we have introduced a phenanthroimidazole-based luminogen, BIB , for specific and selective detection of sarin gas surrogate diethylchlorophosphate (DCP) within the stores of various analogous toxic analytes. BIB displayed a highly distinct ratiometric fluorescence response toward detecting toxic sarin gas, mimicking DCP among all the other guest analytes showing a fluorogenic color change from blue to bluish-green color fluorescence under the exposure of a 365 nm UV lamp irradiation, which is wholly reversed due to the introduction of triethylamine (TEA). The reversibility is prominent in both the liquid and vapor states of DCP. Our probe BIB can selectively detect DCP with a low detection limit to µM range and superior to many available literatures. BIB 's reversible and ratiometric response for detecting DCP provides a potential application as a portable and displayable photonic sensing tool for on-site detection. The successful demonstrations of BIB for practical application in detecting sarin gas encourage the researcher to explore the probable applications of imidazole-based luminogen as a photonic sensing device for recognizing various target analytes. [ABSTRACT FROM AUTHOR]

• A selective chromo-fluorogenic probe (AMP) has been introduced to detect sarin & tabun mimics. • A ratiometric UV–visible absorption spectral and colorimetric change from yellow to bright pink is observed. • A "turn-off" photoluminescence from yellow color to non-fluorescence is noticed in the presence of both mimics. • The spectral and chromo-fluorgenic behavior is reversed in the presence of triethyl amine (TEA). • The sensitivity of AMP towards the detection is found in the μM range. The abuse of nerve agents has become a severe threat to peaceful modern civilization. Hence, it is of paramount importance to the scientific communities to detect and degrade them for a modern society. In the present contribution, we have introduced a selective chromo-fluorogenic probe (AMP) based on neutral red dye for visual detection of the solution and vapor phase of sarin & tabun mimics, namely diethyl chlorophosphate (DCP) and diethyl cyanophosphonate (DCNP), respectively. A ratiometric UV–visible absorption spectral change with colorimetric visualization from yellow to bright pink is observed in the presence of both mimics. A "turn-off" photoluminescence from yellow color to non-fluorescence is observed in the presence of both mimics. The spectral and chromo-fluorgenic behavior is reversed in the presence of triethylamine (TEA). The sensitivity of AMP towards the detection of targeted analytes is recorded in the μM range. Additionally, filter paper-based strips are fabricated for the actual applicability of the current probe to identify trace amounts of both analytes in the presence of various types of analogous target analytes. The vapor phase sensing and two types of soil analysis are also employed to check the sensor's potential in real-life applications. The present report has revealed prompt, sensitive, selective, in-situ, accurate sample detectors of sarin & tabun gas in actual threatening situations. A selective chromo-fluorogenic probe (AMP) based on neutral red dye has been introduced for visual detection of the solution and vapor phase of sarin & tabun mimics, namely diethyl chlorophosphate (DCP) and diethyl cyanophosphate (DCNP), respectively displaying a colorimetric change from yellow to bright pink and "turn-off" photoluminescence behavior. [Display omitted] [ABSTRACT FROM AUTHOR]

An exceptionally effective phthalimide-chromone coupled fluorogenic probe, CMAD has been introduced to detect sarin gas surrogate diethylchlorophosphate (DCP), both in solution and vapor phase, respectively, with quick response, excellent sensitivity, and specificity having detection and quantification limit in the μM range which is very lower than LD 50 value. [Display omitted] • A phthalimide-based fluorogenic probe, CMAD has been introduced to detect sarin gas mimics diethylchlorophosphate (DCP). • CMAD is effective in detecting DCP in the solution and vapor phase, respectively. • The detection and quantification limit is in the μM range much lower than the LD 50 value. • The demonstrations of practical usage, including soil analysis, inspire additional applications in different fields. • CMAD could be used in identifying DCP in the presence of other competing nerve agents. Nerve agents are particularly hazardous substances and can result in fatality due to suppressing acetylcholinesterase function. This article introduced a fluorescent probe, (E)-5-(((4-hydroxy-2-methoxy-2H-chromen-3-yl)methylene)amino)isoindoline-1,3-dione (CMAD) , which was exceptionally effective at detecting the sarin replacement diethylchlorophosphate (DCP), both in solution and vapor phase, respectively which exhibited quick response, excellent sensitivity and specificity. As a result of the gradual addition of DCP into the solution of the probe, the photoluminescence intensity at 476 nm is markedly increased, exhibiting bright cyan color fluorescence because of inhibition of the excited state intramolecular proton transfer (ESIPT) process, which is also clearly reflected in the estimation of photoluminescence quantum yield of phosphorylated CMAD (0.55 relatives to 4-aminophalimide) and the color chromaticity (CIE) diagram. The lowest detection limit and limit of quantification are 3.25 µM and 10.8 µM, respectively, within the stockpiles of other analogous analytes. Additionally, for on-the-spot detection, the probe may also be utilized in the test strips with superior selectivity for DCP. The ability to identify and measure DCP in the gas phase has also been established using a dip-stick and dipped-vial-conical-flask analysis. Moreover, we also performed the smartphone-based technique for the practical utility of CMAD for the on-spot quantification and detection of sarin gas in real threat situations. The effective demonstrations of practical usage, including soil analysis, inspire additional applications in different fields. Therefore, probe CMAD is a reliable, on-site monitoring fluorescence probe for precisely identifying DCP in the presence of additional competing nerve agents. [ABSTRACT FROM AUTHOR]

The European Food Safety Authority is currently evaluating the risks related to the presence of emerging mycotoxins in food and feeds. The aim of this study was to investigate the role of soil fertility, resulting from different nitrogen fertilization rates, on the contamination of regulated mycotoxins and emerging fungal metabolites in maize grains. The trial was carried out in the 2012–2013 growing seasons as part of a long-term (20-year) experimental platform area in North-West Italy, where five different N rates, ranging from 0 to 400 kg N ha−1, were applied to maize each year. Maize samples were analyzed by means of a dilute-and-shoot multi-mycotoxin LC-MS/MS method, and more than 25 of the most abundant mycotoxins and fungal metabolites were detected. Contamination by fumonisins and other fungal metabolites produced by Fusarium spp. of the section Liseola was observed to have increased in soils that showed a poor fertility status. On the other hand, an overload of nitrogen fertilization was generally associated with higher deoxynivalenol and zearalenone contamination in maize kernels, as well as a higher risk of other fungal metabolites produced by Fusarium spp. sections Discolor and Roseum. A balanced application of N fertilizer, in accordance with maize uptake, generally appears to be the best solution to guarantee an overall lower contamination by regulated mycotoxins and emerging fungal metabolites. [ABSTRACT FROM AUTHOR]

Diisopropyl methylphosphonate (DIMP) is an organophosphorus compound used as a simulant for the chemical weapon Sarin. One of the means of destruction of Sarin is incineration at high temperature, which requires a clear understanding of the high‐temperature reaction kinetics of Sarin. In this work, we study the reaction rate for thermal decomposition of DIMP in the temperature range of 762–1059 K at a pressure near 1 atm. Test conditions are carefully chosen to minimize interferences from other reactions and intermediates formed during the decomposition process. The experimental rates obtained have been fitted for the Arrhenius rate expression to get the rate parameters of the reaction r1, DIMP (C7H17O3P) = IMP (C4H11O3P) + propene (C3H6) as r1(s−1)=1015.058±0.5e−(47497±1935(calmol))/RT\begin{equation*} {r_1}\;({{s^{ - 1}}}) = {10^{15.058 \pm 0.5}}\;{e^{ - ({47497 \pm 1935({\frac{{cal}}{{mol}}})})/RT}} \end{equation*}The rate obtained in this work extended the temperature range of previous measurements (up to 800 K) and can be used in reaction kinetic models for combustion of DIMP. [ABSTRACT FROM AUTHOR]

Gastro‐oesophageal varices are the major clinical manifestations of cirrhosis and portal hypertension. Although less frequent than oesophageal varices (EV), bleeding from gastric varices (GV) is generally more severe and associated with higher mortality and a greater risk to rebleed. According to Sarin's classification, GVs are categorized into four types based on their location within the stomach and relationship with EV. Currently, treatment options for the management of GV include beta‐blockers, endoscopic band ligation, endoscopic cyanoacrylate injection, EUS‐guided coil/cyanoacrylate injection, transjugular intrahepatic portosystemic shunts and balloon‐occluded retrograde transvenous obliteration. The best treatment strategy of GV remains controversial because of the heterogeneity of GV, lack of high‐quality data and suboptimal trial design of the studies available. The proper treatment algorithm may require adequate endoscopic and imaging evaluation by a multidisciplinary team with multiple treatment options available. This review describes the hemodynamic features of GV, pharmacological, endoscopic and interventional radiological treatment options for GV. [ABSTRACT FROM AUTHOR]

Sarin is a highly toxic nerve agent classified by the Chemical Weapon Convention as a Schedule 1 chemical with no use other than to kill or injure. Moreover, in recent times, chemical warfare agents have been deployed against both military and civilian populations. Chemical warfare agents always contain minor impurities that can provide important chemical attribution signatures (CAS) that can aid in forensic investigations. In order to understand the trace molecular composition of sarin, various analytical approaches including GC–MS, LC–MS and NMR were used to determine the chemical markers of a set of sarin samples. Precursor materials were studied and the full characterisation of a synthetic process was undertaken in order to provide new insights into potential chemical attribution signatures for this agent. Several compounds that were identified in the precursor were also found in the sarin samples linking it to its method of preparation. The identification of these CAS contributes critical information about a synthetic route to sarin, and has potential for translation to related nerve agents. [ABSTRACT FROM AUTHOR]

The degradation of chemical warfare agent (CWA) sarin using plate-to-plate and plate-to-pin electrode structure dielectric barrier discharges (DBDs) was studied in this work. The discharge characteristics, optical emission, decomposition efficiency, and decomposition products in the above apparatus were well investigated. With initial pure sarin of $20 ~\mu \text{L}$ , the decomposition amount per unit time and decomposition efficiency were obtained to be $14.68 \times 10^{-3}$ mg/s and $0.25 ~\mu \text{g}$ /J, for plate-to-plate DBD, and $9.16 \times 10^{-3}$ mg/s and $0.167 ~\mu \text{g}$ /J, for plate-to-pin DBD, respectively. The decomposition products containing isopropyl methylphosphoric acid (IMPA), methylphosphoric acid (MPA), fluoro(methyl)phosphinic acid (MPFA), di-isopropyl methane phosphate (DIMP), and phosphoric acid (PA) were observed in both DBD devices, with MPA and PA as the final products. The production level of PA was highest among all the products in plate-to-plate DBD. However, in plate-to-pin DBD, the concentration of PA and MPA were at the same level. The different decomposition efficiency between two DBD devices were mainly ascribed to the different input energy and their configuration. Our results confirmed that plate-to-plate DBD was a high-efficiency decomposition technology for sarin decomposition. [ABSTRACT FROM AUTHOR]

Tandem mass spectrometry (HPLC-MS/MS) was used to analyze biologically active compounds in extracts of the tuber and roots of Rhodiola rosea (family Crassulaceae) and in the pharmaceutical formulation Multiphytoadaptogen (MPA). Chromatography was run on Acquity UPLC BEH C18 columns with gradient elution. A TSQ Vantage ternary quadrupole mass spectrometer with electrospray ionization was used. MPA, like the Rhodiola rosea tuber/root extract, was found to contain salidroside, rosavin, rosarin, rosiridin, and rhodionin. These results can be used for standardization, identification, and quality control of phytocomplexes containing these Rhodiola rosea compounds to identify grounds for the mechanisms of the biological actions of MPA and studying its novel properties, taking account of the components identified. The PASS computer program was used for in silico evaluation of the spectra of the antitumor activities of these compounds. Antitumor effects were predicted with high probability for all five phytocomponents; the specific characteristic of the actions of individual compounds suggested that combinations might be used for treating a wide spectrum of malignant neoplasms. [ABSTRACT FROM AUTHOR]

An efficient imine-linkage simple chromogenic probe, BPDA, has been introduced to detect sarin gas mimic diethylchlorophosphate (DCP), with a nanomolar range detection limit. [Display omitted] • A symmetrical imine-linkage simple chromogenic probe, BPDA, has been introduced to detect DCP. • The detection limit of BDPA with DCP has been estimated in the nanomolar range. • A paper strips-based portable test kit experiment has been demonstrated for on-spot detection of DCP. • A smartphone-based methods has been executed for on-spot detection and quantification of DCP. The severe toxicity and easy availability of nerve agents have caused an increase in the need to develop effective methods for identifying these lethal substances. Among the traditional platforms employed for this kind of purpose, chromophore-based chemosensors have garnered a significant amount of attention. In this study, we have designed, prepared, and characterized (N1E,N4E)-N1,N4-bis((Z)-3-(4-(dimethylamino)phenyl) allylidene)benzene-1,4-diamine, BDPA , a simple chromogenic probe of symmetrical diimine, having the extreme capability to sensing diethylchlorophosphate (DCP), the mimic of chemical warfare agent sarin not only in solution but also in solid and vapor phases with highly selective and sensitive manner. In the presence of DCP, a remarkable color change from light yellow to blue is observed in pure acetonitrile solvent and also shows pink color in 10 % acetonitrile–water by the naked eye, comes back to its former state after the introduction of triethylamine (TEA) which is found to be five times recyclability by alternately adding DCP and TEA. The detection limit of BDPA with DCP has been estimated in the nanomolar range, and also, response time towards sarin surrogate DCP is withina few minutes (∼5–6 min.).To determine its practical usability, we have developed a portable test kit that uses paper strips to assess the capability of BDPA for in-situ recognition and measurement of DCP. A dipstick method has also been executed to recognize gaseous DCP within the stores of analogous hazardous analytes to prove the effectiveness of the sensor, BDPA. A smartphone-based readout novel technique, i.e., RGB analysis, has provided an innovative platform for the instant, on-site, visual identification and measurement of DCP in remote areas. The current work presented an incredible probe and method for conveniently and instantly detecting and quantifying sarin gas mimics in actual dangerous circumstances. [ABSTRACT FROM AUTHOR]

The development of refractory status epilepticus (SE) following sarin intoxication presents a therapeutic challenge. Here, we evaluated the efficacy of delayed combined double or triple treatment in reducing abnormal epileptiform seizure activity (ESA) and the ensuing long-term neuronal insult. SE was induced in rats by exposure to 1.2 LD 50 sarin followed by treatment with atropine and TMB4 (TA) 1 min later. Double treatment with ketamine and midazolam or triple treatment with ketamine, midazolam and levetiracetam was administered 30 min post-exposure, and the results were compared to those of single treatment with midazolam alone or triple treatment with ketamine, midazolam, and valproate, which was previously shown to ameliorate this neurological insult. Toxicity and electrocorticogram activity were monitored during the first week, and behavioral evaluations were performed 2 weeks post-exposure, followed by biochemical and immunohistopathological analyses. Both double and triple treatment reduced mortality and enhanced weight recovery compared to TA-only treatment. Triple treatment and, to a lesser extent, double treatment significantly ameliorated the ESA duration. Compared to the TA-only or the TA+ midazolam treatment, both double and triple treatment reduced the sarin-induced increase in the neuroinflammatory marker PGE 2 and the brain damage marker TSPO and decreased gliosis, astrocytosis and neuronal damage. Finally, both double and triple treatment prevented a change in behavior, as measured in the open field test. No significant difference was observed between the efficacies of the two triple treatments, and both triple combinations completely prevented brain injury (no differences from the naïve rats). Delayed double and, to a greater extent, triple treatment may serve as an efficacious delayed therapy, preventing brain insult propagation following sarin-induced refractory SE. • Exposure to the nerve agent sarin induces prolonged refractory seizures. • Late benzodiazepine treatment is insufficient in mitigating seizures. • Dual therapy of midazolam & ketamine attenuates seizures. • Triple therapy of midazolam, ketamine & levetiracetam or valproate rapidly suppresses seizures. • Dual & triple therapy prevent the biochemical and histopathological neurotoxicity. [ABSTRACT FROM AUTHOR]

The simplicity of synthesis, significant toxicity of organophosphorus-containing nerve agents, and ease of use of their in-terrorism attacks highlight the necessity to create efficient probes and precise methods for detecting these chemicals. This study developed luminogenic probe 4-(1 H-phenanthrene imidazole-2-yl) benzaldehyde, PB for selectively recognizing lethal chemical sarin mimicking diethylchlorophosphate (DCP) with µM detection limit. Following the addition of DCP to the PB solution, the fluorescence changed from bluish-cyan to green simultaneously; after the insertion of triethylamine (TEA) into the PB-DCP phosphorylated solution, the fluorescence of the original one came back, and it occurred five times. A paper strip-based test kit and dip-stick experiments have been executed to demonstrate the practical applicability of our sensor PB and instant, on-site recognition of the target analyte DCP. An experiment has been investigated using a smartphone and red-green-blue (RGB) color analysis, which offers a novel way for the fast, on-site visual detection and quantification of DCP in actual samples. It also reduces equipment costs, speeds up detection times, and substantially simplifies the operation procedure. [ABSTRACT FROM AUTHOR]

Chemical warfare agents continue to pose a real threat to humanity, despite their prohibition under the Chemical Weapons Convention. Sarin is one of the most toxic and lethal representatives of nerve agents. The methodology for the targeted analysis of known sarin metabolites has reached great heights, but little attention has been paid to the untargeted analysis of biological samples of victims exposed to this deadly poisonous substance. At present, the development of computational and statistical methods of analysis offers great opportunities for finding new metabolites or understanding the mechanisms of action or effect of toxic substances on the organism. This study presents the targeted LC-MS/MS determination of methylphosphonic acid and isopropyl methylphosphonic acid in the urine of rats exposed to a non-lethal dose of sarin, as well as the untarget urine analysis by LC-HRMS. Targeted analysis of polar acidic sarin metabolites was performed on a mixed-mode reversed-phase anion-exchange column, and untargeted analysis on a conventional reversed-phase C18 column. Isopropyl methylphosphonic acid was detected and quantified within 5 days after subcutaneous injection of sarin at a dose of 1/4 LD50. A combination of generalized additive mixed models and dose-response analysis with database searches using accurate mass of precursor ions and corresponding MS/MS spectra enabled us to propose new six potential biomarkers of biological response to exposure. The results confirm the well-known fact that sarin poisoning has a significant impact on the victims' metabolome, with inhibition of acetylcholinesterase being just the first step and trigger of the complex toxicodynamic response. [ABSTRACT FROM AUTHOR]

The review considers and summarizes separation and preconcentration methods used in the determination of toxicants of the 1st hazard class, namely, organophosphorus nerve agents (a group of Vx isomers, sarin, cyclosarin, soman, and tabun) and blister agents (sulfur mustard). [ABSTRACT FROM AUTHOR]

Long-term retrospective monitoring of exposure to organophosphorus nerve agents is challenging. We recently developed two highly sensitive analytical methods for regenerated sarin (GB) nerve agent in blood and its primary metabolite, isopropyl-methylphosphonic acid (IMPA), in urine. These methods were implemented in a toxicokinetics study carried out with sarin injected (i.v.) to rabbits at doses corresponding to 0.1, 0.5 or 0.9 LD50. The time frame for monitoring regenerated sarin from blood was 70 days for 0.1 LD50 and 0.5 LD50 and 77 days for 0.9 LD50, where rapid elimination occurred in the first 8 days with an initial average half-life of 1.2 days, followed by a second, slower elimination, with a terminal average half-life of 8.4 days. The time frame for monitoring IMPA in urine was 7, 15 and 16 days for 0.1 LD50, 0.5 LD50 and 0.9 LD50 intoxications, respectively. Rapid elimination of IMPA in urine occurred after exposure, with an average half-life of ~ 0.8 days on days 2–6. For the first time, a slower elimination route for IMPA, with an average half-life of ~ 4 days from day 6 onwards, was revealed. Both IMPA and regenerated sarin pharmacokinetics exhibit linearity with dose. The overlaid pharmacokinetic profiles of regenerated sarin in blood along with IMPA in urine emphasize the dominance of IMPA with a rapid decay in urine in the first week and the slower long-term decay of protein-bound sarin later in blood. To our knowledge, the two new sensitive methods exhibit the longest monitoring time frame reported in biological samples. [ABSTRACT FROM AUTHOR]

This work presents a literature review concerning the construction, properties and application of different sensors used to detect dimethyl methylphonate (DMMP), which is the simulant of sarin. Sensors sensitive to mass are described, together with such sensors as: SAW, QCM, MEMS, also chemical capacitors, semiconductors, and field effect transistors. [ABSTRACT FROM AUTHOR]

CryoSat-2 (CS2) is the first mission equipped with a pulse-limited radar altimeter capable of operating in Synthetic Aperture Radar (SAR) Interferometric (SARIn) mode. Over ice sheets and ice caps, CS2 SARIn data have been used to retrieve surface elevations over an across-track ground “swath.” This work demonstrates that retracking multiple coherent peaks of CS2 SARIn waveforms, in combination with the interferometric phase, enables to obtain more than one valid height estimate from single SARIn waveforms over Arctic sea ice. For some SARIn waveforms, the scattering from sea ice at the satellite nadir is successfully separated from returns originating from off-nadir leads. An average bias of −1.8 cm is found for absolute sea ice elevations when using a 50% threshold retracker. It is shown that including multiple SARIn peaks and the associated phase difference in the processing does not introduce any bias on the average sea ice freeboard heights compared with the estimates from regular SAR processing schemes, while significantly increasing the number of valid sea surface height retrievals (+55%) and the number of freeboard estimates in the coastal domain and in multi-year ice regions (~3 times). This results in an average ~34% reduction of the gridded random freeboard uncertainty, corresponding to a ~20% reduction of the gridded total sea ice thickness uncertainty. The results of this work show that SARIn acquisitions over Arctic sea ice provide improved spatial coverage and denser sampling of sea level and sea ice freeboard compared with the SAR mode, with accuracy being largely driven by the retracking algorithm. [ABSTRACT FROM AUTHOR]

Both human and animal studies have been used to study sarin, and several literature reviews on the long-term neurological effects of sarin have been published. Keywords: Sarin; Ketamine; Carfentanyl; Lithium toxicity; Health informatics EN Sarin Ketamine Carfentanyl Lithium toxicity Health informatics 227 231 5 04/03/21 20210401 NES 210401 Article #1: Jett DA, Sibrizzi CA, Blain RB, et al: A national toxicology program systematic review of the evidence for long-term effects after acute exposure to sarin nerve agent. The naloxone groups had significantly lower unresponsive time compared to untreated animals: 11.7 ± 2.9 minute (HED 5 mg naloxone) and 7.0 ± 2.9 minute (HED 10 mg naloxone) vs 99.7 ± 24.6 minute (untreated) and 89.7 ± 11.6 minute (sham). Methods National Toxicology Program (NTP) performed a systematic review search for evidence of long-term neurological effects associated with acute sarin exposure from human studies, controlled exposure animal studies, and mechanistic/in vitro studies. [Extracted from the article]

• Repeated low-dose sarin disturbed the cognitive ability in guinea pigs. • Sarin disturbed phospholipid and sphingolipid metabolism in hippocampus. • Neuropathy target esterase plays an important role on phospholipid metabolism. • Biological function of identified metabolites that against sarin lesions need to be studied. Repeated low-level exposure to sarin results to hippocampus dysfunction. Metabonomics involves a holistic analysis of a set of metabolites in an organism in the search for a relationship between these metabolites and physiological or pathological changes. The objective of the present study was to evaluate the effects of repeated exposure to low-level sarin on the metabonomics in hippocampus of a guinea pig model. Guinea pigs were divided randomly into control and sarin treated groups (n = 14). Guinea pigs in the control group received saline; while the sarin-treated group received 0.4×LD 50 (16.8 μg/kg) sarin. Daily injections (a total of 14 days) were administered sc between the shoulder blades in a volume of 1.0 ml/kg body weight. At the end of the final injection, 6 animals in each group were chosen for Morris water maze test. The rest guinea pigs (n = 8 for each group) were sacrificed by decapitation, and hippocampus were dissected for analysis. Compared with the control-group, the escape latency in sarin-group was significantly (p < 0.05) longer while the crossing times were significantly decreased in the Morris water task (p < 0.05). Sarin inhibited activities of acetylcholinesterase (AChE) and neuropathy target esterase (NTE) in hippocampus. The AChE activity of hippocampus from sarin-treated groups is equivalent to 59.9 ± 6.4 %, and the NTE activity of hippocampus from sarin-groups is equivalent to 78.1 ± 8.3 % of that from control-group. Metabolites were identified and validated. A total of 14 variables were selected as potential biomarkers. Phospholipids [phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidic acid (PA), phosphatidylglycerol (PG), phosphatidylinositol (PI), Lysophosphatidylethanolamine (LysoPE or LPE)] and sphingolipids (SPs) [sphinganine (SA), phytosphingosine (PSO) and sphinganine-1-phosphate (SA1P)] were clearly modified. In conclusion, repeated low-dose exposures to sarin disrupted the homeostasis of phospholipid and sphingolipid metabolism in guinea pig hippocampus and may lead to a neuronal-specific function disorders. Identified metabolites such as SA1P need to be studied more deeply on their biological function that against sarin lesions. In future research, we should pay more attention to characterize the physiological roles of lipid metabolism enzymes as well as their involvement in pathologies induced by repeated low-level sarin exposure. [ABSTRACT FROM AUTHOR]

A chromone-coumarin coupled fluorogenic probe MATC that can selectively detect sarin gas mimicking diethylchlorophosphate (DCP) with the detection and quantification limit in the nM range. MATC solution with DCP exhibits remarkable fluorescence intensity displaying bright cyan color photoluminosity under the exposure of a 365 nm UV lamp as a result of disruption of the excited state intramolecular proton (ESIPT) process due to the phosphorylation process. [Display omitted] • A chromone-coumarin coupled fluorogenic probe, MATC has been introduced to detect diethylchlorophosphate. • A cyan color photoluminescence enhancement is found due to the phosphorylation process. • The detection and quantification limit is in the nM range. • A paper strips-based test kit has been fabricated for the on-spot detection of sarin. • A dip-stick experiment has been demonstrated to identify and quantify DCP in the vapor phase. Extremely toxic G-series nerve agents are used as weapons for mass destruction in wars and terrorist attacks. So, rapid and accurate detection of these dangerous nerve agents is immediately required to save our environment and nation. In this article, we have designed and developed a chromone-coumarin coupled fluorogenic probe MATC that can selectively detect sarin gas mimicking diethylchlorophosphate (DCP) with the detection and quantification limit in the nM range. MATC solution with DCP exhibits remarkable fluorescence intensity at wavelength 465 nm, displaying bright cyan color photoluminosity under the exposure of 365 nm UV lamp, which is also manifested from the color chromaticity diagram as a result of disruption of excited state intramolecular proton (ESIPT) process due to the phosphorylation process. Straining our probe, MATC, on Whatman-41 filter paper, we fabricated a paper strips-based test kit for on-the-spot recognition of sarin gas as a movable and displayable photonic device. A dip-stick and dipped-vial-conical-flask experiment has also been demonstrated to recognize and quantify DCP in the vapor phase. The present report completely describes a fluorogenic and specific chemosensor to identify and quantify deadly nerve agents within the stores of analogous organophosphates and inorganic phosphates. [ABSTRACT FROM AUTHOR]

[Display omitted] • Thermal decomposition of DIMP vapors serves to quantify decomposition of sarin, a chemical agent. • In air heated to 200–350 °C, DIMP decomposes much faster than in nitrogen. • Despite measured thermal decomposition of DIMP, FTIR does not detect expected gas products. Diisopropyl methylphosphonate (DIMP) is a chemical weapon agent surrogate. Quantifying the rates of thermal decomposition of such compounds is important to enable predictions of spread of respective toxic vapors in different scenarios. An experimental setup is designed and built to quantify the rate of decomposition of DIMP at temperatures of 200–350 °C. Liquid DIMP is fed from a brass evaporator heated to 140 °C and vented with argon. It is mixed with a pre-heated carrier gas (air or nitrogen) in a steel flow reactor. The gas is sampled from the reactor after a certain residence time and sent to a Fourier transform infrared (FTIR) analyzer. Under 350 °C, the thermal decomposition of DIMP in air occurs much faster than in nitrogen. In air, the decomposition of DIMP can be described as the first order reaction with the rate constant k T s - 1 = 10 7.4 ± 2.5 · exp - 21.4 ± 6.6 kcal / m o l RT . Despite measuring substantial reduction in the DIMP concentration due to its thermal decomposition, present measurements could not detect the presence of propene and other decomposition products. [ABSTRACT FROM AUTHOR]

Portable gas sensing has become an important technology in preventive and protective measures for users working with the disposal of nerve agents. The use of powerful benchtop instruments is not adequate for those situations where a single individual or a group needs to be informed of the presence of toxic substances and need to implement protection measures. Portable sensors are the right technology that can be used as an early warning system in military operations and for public health. The aim of the work presented in this review is to present a detailed summary of the current sensing technology available within the scientific literature for the detection of nerve agent simulants in the gas phase, focussing on the recognised sarin surrogate: dimethyl methylphonate (DMMP). The use of real chemical warfare agents for testing is highly restricted to government agencies and much of the work is kept secret. The use of simulants for the development of sensing technology has been widely established for nerve agents to reduce the potential risk to personnel and to offer a realistic, simple molecule to try and test the technology. The present review compiles a comparison of different sensors and their respective sensing mechanisms based on different chemical, spectroscopic, or electrochemical and biological properties. These sensing technologies are then compared to the U.S environmental protection agencies standard for concentration of Sarin at 15 ppb (known lethal dose). Surface acoustic wave, quartz crystal microbalance, semiconductor, chemicapacitor and colorimetric sensors have proven to show potential with desirable properties for fast response times and high sensitivity. However, only some work developed using semiconductor detectors present a reliable system able to detect DMMP with low limit of detection (0.05 ppb), fast response time (0.02 min) and good recovery times (0.5 min) and adequate portability that makes them suitable to be integrated in drone systems, wearables, and low-weight devices. • Review compiles different gas sensors and their respective sensing performance. • Dimethyl MethylPhosphonate widely used as simulant for sarin gas in sensor tests. • Performance compared to U.S environmental protection agencies standard for Sarin (15 ppb). • Semiconductor detectors present the best performance to detect DMMP. • Critical assessment of future needs described, as more research is needed for field systems. [ABSTRACT FROM AUTHOR]

We proposed a method for determining the presence of trace amounts of adducts of isopropylmethylphosphonic acid (IMPA) and cyclohexylmethylphosphonic acid (CMPA), biomarkers of exposure to sarin and cyclosarin in a body, with a tripeptide (Tyr-Thr-Lys). The method is based on plasma trypsinolysis with the formation of stable adducts IMPA–Tyr-Thr-Lys and СMPA–Tyr-Thr-Lys and their detection by high-performance liquid chromatography (HPLC) with high-resolution tandem mass spectrometry detection. The following conditions for the sample preparation of human blood plasma exposed to sarin and cyclosarin were optimized: aliquot portion volume, enzymatic hydrolysis conditions, mass spectrometric detection (selection of optimal pairs of ion reactions and detection modes), and gradient elution programs in the HPLC separation of the test mixture. The limit of detection for sarin and cyclosarin in human blood plasma was 5 ng mL–1. The proposed approach was tested in the analysis of blood plasma samples submitted to analysis in the framework of the Fourth Official Biomedical Test of the Organization for the Prohibition of Chemical Weapons; the results showed good determination specificity. [ABSTRACT FROM AUTHOR]

A novel SWIFT-based strategy for fluorimetric detection of practical amounts (minimal effective dose or lower) of chemical warfare agents is reported. This strategy employs readily available reagents and allows distinguishing between the V and G agents, as well as their discrimination from potential interferents. [ABSTRACT FROM AUTHOR]

π–π Stacking is omnipresent not only in nature but in a wide variety of practical fields applied to our lives. Because of its importance in a performance of natural and artificial systems, such as light harvesting system and working layer in device, many researchers have put intensive effort into identifying its underlying nature. However, for the case of π–π stacked systems composed of antiaromatic units, the understanding of the fundamental mechanisms is still unclear. Herein, we synthesized a new type of planar β,β'‐phenylene‐bridged hexaphyrin (1.0.1.0.1.0), referred as naphthorosarin which possesses the 24π‐electron conjugated pathway. Especially, the corresponding antiaromatic porphyrinoid shows the unique property to form dimeric species adopting the face‐to‐face geometry which is unprecedented in cases of known annulated naphthorosarins. In order to elucidate the intriguing properties derived from the stacked dimer, the current study focuses on the experimental support to rationalize the observed π–π interactions between the two subunits. [ABSTRACT FROM AUTHOR]

Phosphylation of the pivotal enzyme acetylcholinesterase (AChE) by nerve agents (NAs) leads to irreversible inhibition of the enzyme and accumulation of neurotransmitter acetylcholine, which induces cholinergic crisis, that is, overstimulation of muscarinic and nicotinic membrane receptors in the central and peripheral nervous system. In severe cases, subsequent desensitisation of the receptors results in hypoxia, vasodepression, and respiratory arrest, followed by death. Prompt action is therefore critical to improve the chances of victim's survival and recovery. Standard therapy of NA poisoning generally involves administration of anticholinergic atropine and an oxime reactivator of phosphylated AChE. Anticholinesterase compounds or NA bioscavengers can also be applied to preserve native AChE from inhibition. With this review of 70 years of research we aim to present current and potential approaches to counteracting NA poisoning. [ABSTRACT FROM AUTHOR]

We present a simple method for chiral separation and analysis of organophosphorus nerve agents and apply it to monitor the enantioselective blood elimination kinetics of sarin in-vitro. The method is implemented in standard reverse phase LC–MS operating conditions, relieving the user of the dedicated operating conditions frequently demanded in chiral LC–MS analysis. The method consists of formation of diastereomers by a rapid derivatization with (R)—2-(1 aminoethyl) phenol, followed by LC–MS/MS analysis. Derivatization enantioselectivity was studied by comparing the reaction of optically pure sarin and racemic sarin, proving no substantial enantiomeric preference in the reaction and demonstrating the enantiomeric discrimination abilities of the technique. Enantioselective sarin elimination pathways were probed in-vitro by following the fast elimination kinetics of the two sarin enantiomers as well as its hydrolysis metabolite (isopropyl methyl-phosphonic acid, IMPA) in whole blood and plasma compared to water. Sarin enantiomers showed the known marked differences in elimination kinetics with rapid elimination of the (+) enantiomer and slower elimination of the (−) enantiomer in whole blood and plasma as well as dose-dependent kinetics (faster elimination at lower concentrations). We found that small amounts of acetonitrile in plasma prevent the rapid elimination of the (+) enantiomer, resulting in similar, slower elimination kinetics for both enantiomers. [ABSTRACT FROM AUTHOR]

This study provides details of the electronic and optical structures and binding energies of sarin (SF) and chlorosarin (SC) with Al–N and Al–P surfaces of Al12N12 and Al12P12 nanoclusters in the gas phase. The adsorption mechanism of SF and SC on these nanoclusters containing the Al3+ central cation was studied. Optimized geometries and thermodynamic parameters of SF and SC adsorption complexes were calculated. SF and SC are chemisorbed on these nanoclusters because of the formation of PO···Al bonds. The chemical bond is formed between an oxygen atom of SF and SC and an aluminum atom of fullerene‐likes (chemisorption). However, the binding energies of the complexes with the Al12N12 nanocluster are larger than these values for the Al12P12 nanocluster. The interaction enthalpy and Gibbs free energy of all studied systems were found to be negative. We can conclude that SF and SC will be adsorbed preferably on Al12N12 nanocluster. [ABSTRACT FROM AUTHOR]

Organophosphorus agents (OP) are widely used as pesticides due to their cost effectiveness, yet they present a significant public health risk owing to their high toxicity, especially in cases of occupational exposure in agriculture, during suicide attempts using pesticides, and as nerve agents in warfare. Their vigorous permeability through inhalation, ingestion, and dermal exposure results in a high number of reported OP poisoning cases and alarming mortality rates. Initial first-aid management involves decontamination, ventilation, and hemodialysis. Additionally, current treatment guidelines recommend prompt administration of atropine as a first-line antidote, oximes as a follow-up, benzodiazepines for seizure control, and pyridostigmine for prophylaxis. Nevertheless, current treatment options are associated with several challenges. Thus, recent research has focused on investigating novel approaches for their potential in improving current management strategies. This article intends to review recent advances in OP poisoning treatment, including agents investigated for their use as an alternative or adjunctive therapy, novel formulations such as nasal drops or sublingual tablets for emergency administration of atropine, as well as innovative strategies for enhanced oximes delivery and overall efficacy. However, two major barriers may limit these innovations, ethical issues associated with their clinical assessment in emergencies, and limited profitability in countries where most cases occur. [ABSTRACT FROM AUTHOR]

This article examines responses to the Syrian government's possession and eventual use of chemical weapons (CW) in that country's civil war from 2012 to 2013. During this time, the United States and other outside powers applied coercive strategies, in both deterrent and compellent modes. Outcomes varied: compellence in the form of coercive diplomacy achieved a partial success, getting Syria to give up much of its chemical stockpile, but there were multiple deterrence failures, culminating in a large-scale sarin gas attack in August 2013. We examine this record to draw lessons about factors associated with the effectiveness of coercion. Our analysis draws on insights from existing research on both deterrence and coercive diplomacy to develop an integrated analytical framework involving the interplay of three factors: credibility, motivations, and assurance. We find the typical default approach to coercion, based on demonstrating toughness and threatening to impose costs using airpower—an approach we call the "resolve plus bombs" formula—was not sufficient to change Syria's calculations regarding chemical use. [ABSTRACT FROM AUTHOR]