Au- ZnFe2O4 hollow microspheres based gas sensor for detecting the mustard gas simulant 2-chloroethyl ethyl sulfide.

Mustard gas, a representative of blister agents, poses a severe threat to human health. Although the structure of 2-chloroethyl ethyl sulfide (2-CEES) is similar to mustard gas, 2-CEES is non-toxic, rendering it a commonly employed simulant in related research. ZnFe2O4-based semiconductor gas sensors exhibit numerous advantages, including structural stability, high sensitivities, and easy miniaturization. However, they exhibit insufficient sensitivity at low concentrations and require high operating temperatures. Owing to the effect of electronic and chemical sensitization, the gas-sensing performance of a sensor may be remarkably enhanced via the sensitization method of noble metal loading. In this study, based on the morphologies of ZnFe2O4 hollow microspheres, a solvothermal method was adopted to realize different levels of Au loading. Toward 1 ppm of 2-CEES, the gas sensor based on 2 wt.% Au-loaded ZnFe2O4 hollow microspheres exhibited a response sensitivity twice that of the gas sensor based on pure ZnFe2O4; furthermore, the response/recovery times decreased. Additionally, the sensor displayed excellent linear response to low concentrations of 2-CEES, outstanding selectivity in the presence of several common volatile organic compounds, and good repeatability, as well as long-term stability. The Au-loaded ZnFe2O4-based sensor has considerable potential for use in detecting toxic chemical agents and their simulants.

First Display of Haloalkane Dehalogenase LinB on the Surface of Bacillus subtilis Spore.

BACKGROUND: LinB, as a Haloalkane dehalogenase, has good catalytic activity for many highly toxic and recalcitrant compounds, and can realize the elimination of chemical weapons HD in a green non-toxic mode. OBJECTIVES: In order to display Haloalkane dehalogenase LinB on the surface of Bacillus subtilis spore. METHODS: We have constituted the B. subtilis spore surface display system of halogenated alkanes dehalogenase LinB by gene recombination. RESULTS: Data revealed that LinB can display on spore surface successfully. The hydrolyzing HD analogue 2-chloroethyl ethylsulfide (2-CEES) activity of displayed LinB spores was 4.30±0.09 U/mL, and its specific activity was 0.78±0.03U/mg. Meanwhile, LinB spores showed a stronger stress resistance activity on 2-CEES than free LinB. This study obtained B. subtilis spores of LinB (phingobium japonicum UT26) with enzyme activity that was not reported before. CONCLUSION: Spore surface display technology uses resistance spore as the carrier to guarantee LinB activity, enhances its stability, and reduces the production cost, thus expanding the range of its application.

Aramid nanofibers supported metal-organic framework aerogel for protection of chemical warfare agent.

Protective fabrics containing Zr-Based Metal-Organic Frameworks (Zr-MOFs) show great potential in the detoxification of chemical warfare agents (CWAs). However, the current studies still face the challenges of complicated fabrication processes, limited MOF loading mass, and insufficient protection. Herein, we developed a lightweight, flexible and mechanical robust aerogel by in situ growth of UiO-66-NH2 onto aramid nanofibers (ANFs) and assembly of UiO-66-NH2 loaded ANFs (UiO-66-NH2@ANFs) into 3D hierarchically porous architecture. The UiO-66-NH2@ANF aerogels feature high MOF loading of 261 %, high surface area of 589.349 m2 g-1, open and interconnected cellular structure, which provide efficient transfer channels and promote catalytic degradation of CWAs. As a result, the UiO-66-NH2@ANF aerogels demonstrate high 2-chloroethyl ethyl thioether (CEES) removal rate at 98.9 % and a short half-life of 8.15 min. Moreover, the aerogels present good mechanical stability (recovery rate of 93.3 % after 100 cycles under 30 % strain), low thermal conductivity (λ of 25.66 mW m-1 K-1), high flame resistance (LOI of 32 %) and good wearing comfortableness, indicating promising potential in multifunctional protection against CWAs.

Sulfur mustard analog 2-chloroethyl ethyl sulfide increases triglycerides by activating DGAT1-dependent biogenesis and inhibiting PGC1ɑ-dependent fat catabolism in immortalized human bronchial epithelial cells.

Using sulfur mustard analog 2-chloroethyl ethyl sulfide (CEES), we established an in vitro model by poisoning cultured immortalized human bronchial epithelial cells. Nile Red staining revealed lipids accumulated 24 h after a toxic dose of CEES (0.9 mM). Lipidomics analysis showed most of the increased lipids were triglycerides (TGs), and the increase in TGs was further confirmed using a Triglyceride-Glo™ Assay kit. Protein and mRNA levels of DGAT1, an important TG biogenesis enzyme, were increased following 0.4 mM CEES exposure. Under higher dose CEES (0.9 mM) exposure, protein and mRNA levels of PPARγ coactivator-1ɑ (PGC-1ɑ), a well-known transcription factor that regulates fatty acid oxidation, were decreased. Finally, application with DGAT1 inhibitor A 922500 or PGC1ɑ agonist ZLN005 was able to block the CEES-induced TGs increase. Overall, our dissection of CEES-induced TGs accumulation provides new insight into energy metabolism dysfunction upon vesicant exposure.HIGHLIGHTSIn CEES (0.9 mM)-injured cells:Triglycerides (TGs) were abundant in the accumulated lipids.Expression of DGAT1, not DGAT2, was increased.Expression of PGC1ɑ, not PGC1ß, was reduced.DGAT1 inhibitor or PGC1ɑ agonist blocked the CEES-mediated increase in TGs.

A review of chemical warfare agents linked to respiratory and neurological effects experienced in Gulf War Illness.

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.

Enhanced Catalytic Performance of a Ce/V Oxo Cluster through Confinement in Mesoporous SBA-15.

To increase catalytic efficiency, mesoporous supports have been widely applied to immobilize well-defined metal oxide clusters due to their ability to stabilize highly dispersed clusters. Herein, a redox-active heterometallic Ce12V6-oxo cluster (CeV) was first presynthesized and then incorporated into mesoporous silica, SBA-15, via a straightforward impregnation method. Scanning transmission electron microscopy (STEM) and Fourier transform infrared spectroscopy (FTIR), in concert with scanning electron microscopy and energy-dispersive X-ray spectroscopy (SEM-EDS), verified the successful introduction of the CeV cluster inside the pore of SBA-15. The 51V magic angle spinning solid-state nuclear magnetic resonance (51V MAS NMR) spectroscopy and differential pair distribution function (dPDF) analysis confirmed the structural integrity of the CeV cluster inside the SBA-15. The composite was then benchmarked for liquid-phase oxidation of 2-chloroethyl ethyl sulfide (CEES) under mild conditions and gas-phase oxidative dehydrogenation (ODH) of propane under high temperatures (up to 550 °C). The catalytic reactivity results demonstrated 8- and 14-fold increase in turnover frequency (TOF) values of the composite (CeV@10SBA-2) than the bulk CeV cluster under the same conditions for CEES oxidation and ODH, respectively. These results highlight the improved reactivity of the catalytically active CeV cluster as attributed to the higher dispersion of the discrete cluster upon immobilization within the SBA-15 support.

Acoustic Wave Sensors for Detection of Blister Chemical Warfare Agents and Their Simulants.

On-site detection and initial identification of chemical warfare agents (CWAs) remain difficult despite the many available devices designed for this type of analysis. Devices using well-established analytical techniques such as ion mobility spectrometry, gas chromatography coupled with mass spectrometry, or flame photometry, in addition to unquestionable advantages, also have some limitations (complexity, high unit cost, lack of selectivity). One of the emerging techniques of CWA detection is based on acoustic wave sensors, among which surface acoustic wave (SAW) devices and quartz crystal microbalances (QCM) are of particular importance. These devices allow for the construction of undemanding and affordable gas sensors whose selectivity, sensitivity, and other metrological parameters can be tailored by application of particular coating material. This review article presents the current state of knowledge and achievements in the field of SAW and QCM-based gas sensors used for the detection of blister agents as well as simulants of these substances. The scope of the review covers the detection of blister agents and their simulants only, as in the available literature no similar paper was found, in contrast to the detection of nerve agents. The article includes description of the principles of operation of acoustic wave sensors, a critical review of individual studies and solutions, and discusses development prospects of this analytical technique in the field of blister agent detection.

Ultrafast Sulfur Mustard Simulant Gas Fluorescent Chemosensors Based on Triazole AIEE Material with High Selectivity and Sensitivity at Room Temperature.

Herein, a novel blue aggregation-induced enhanced emission (AIEE) material 4-N-(naphthalen-l-yl)-3,5-bis(4-N-phenyl-1-naphthylamine)phenyl-4H-1,2,4-triazole (NDTAZ) is developed and used as a fluorescent chemosensor for sulfur mustard (SM) simulant 2-chloroethyl ethyl sulfide (2-CEES) vapor. The NDTAZ chemosensor is designed by introducing an electron-donating N-phenyl-1-naphthylamine group at 3 and 5 position of 4H-1,2,4-triazole (TAZ) to enhance the nucleophilicity of the TAZ group, and a naphthalene ring is connected to 4 position of the TAZ group to construct an AIEE molecule. The NDTAZ films show extraordinary stability and then are further used as reliable and portable fluorescent chemosensors. Upon exposure to 2-CEES vapor, the NDTAZ chemosensor exhibits an instantaneous fluorescence response (not more than 1 s). What should be noted is that this fluorescent chemosensor realizes the visualized detection of fluorescent color change from blue to green at "room temperature", which is rarely reported. The limit of detection is estimated to be 0.55 ppm, which is below the AEGL-1 (0.6 ppm for 1 min) safety ceiling level to SM exposure. Moreover, the NDTAZ chemosensor shows high selectivity toward 2-CEES vapor over closely related substances, including alkylating agents, aryl halide compounds, sulphur-containing compounds, and nerve agent mimics. More impressively, the NDTAZ chemosensor demonstrates good recyclability by water treatment. Also, the sensing mechanism is adequately proved by using multiple experimental methods and theoretical calculation. In addition, the NDTAZ-based facile filter paper-constructed test strips are fabricated for real-time and on-spot detection of leaked 2-CEES gas specifically. Therefore, this fluorescent chemosensor with excellent sensing performance greatly advances the practical detection of SM species at room temperature.

Is CEES a good analog of sulfur mustard? Macroscopic aspect, histology, and molecular biology comparisons between sulfur mustard and CEES-induced skin lesions.

Sulfur mustard (SM) is a chemical blistering warfare agent affecting multiple organs. SM is an ongoing chemical threat in addition to the accidental risk associated with World War I buried shells. As no specific treatments are available, only symptomatic therapies can be used. To test new medical countermeasures in standard laboratories, analogs such as 2-chloroethyl ethylsulfide (CEES) are currently used, although only a few studies compare its clinical effects with SM. In the present paper, skin lesions induced by SM and CEES are compared in terms of their macroscopic aspects, histology, and molecular biology to evaluate the pertinence of CEES as a SM analog. For this purpose, an in vivo model of CEES vapor exposure, similar to that of SM, is described in this paper. RESULTS: showed similar skin lesions with CEES and SM but with slight differences in the apparition delay and intensity of the lesions. Indeed, SM induced earlier, deeper, and stronger lesions. However, the same healing status was observed at the end of the study period (14 days). In conclusion, CEES appears a relevant analog of SM, leading to similar skin lesions. The CEES vapor exposure model therefore seems suitable for testing new medical countermeasures.

Evaluation of Decontamination Efficacy of Electrolytically Generated Hypochlorous Acid for the Vesicating Agent: A Multimodel Study.

BACKGROUND: Sulfur Mustard is a strong vesicant and chemical warfare agent that imposes toxicity to the lungs, eyes, and skin after accidental or intended exposure. OBJECTIVES: The current study was intended to explore in vitro and in vivo decontamination properties of electrolytically generated HOCl (hypochlorous acid) against CEES (2-chloroethyle ethyle sulphide), a known sulfur mustard simulant & vesicating agent. METHODS: in vitro studies were carried out using UV spectroscopy and GC-MS methods. In vivo studies were performed in Strain A and immune-compromised mice by subcutaneous as well as prophylactic topical administration of HOCl pretreated CEES. The blister formation and mortality were considered as end-point. Histopathological study was conducted on skin samples by H & E method. DNA damage studies measuring γ-H2AX and ATM have been carried out in human blood using flow cytometry. Anti-bacterial action was tested by employing broth micro dilution methods. A comparative study was also carried out with known oxidizing agents. RESULTS: The topical application of pre-treated CEES at 5, 30 min and 1 h time points showed significant (p<0.001) inhibition of blister formation. DNA damage study showed reduced mean fluorescence intensity of DSBs nearly 17-20 times, suggesting that HOCl plays a protective role against DNA damage. Histopathology showed no sign of necrosis in the epidermis upto 5 min although moderate changes were observed at 30 min. Pretreated samples were analyzed for detection of reaction products with m/z value of 75.04, 69.08, 83.93, 85.95, 123.99, 126.00, and 108.97. HOCl showed a strong bactericidal effect at 40 ppm. The absorbance spectra of HOCl treated CEES showed lowered peaks in comparison to CEES alone and other oxidizing agents. CONCLUSION: In a nutshell, our results signify the decontamination role of HOCl for biological surface application.

Materials for the Simultaneous Entrapment and Catalytic Aerobic Oxidative Removal of Sulfur Mustard Simulants.

Materials that both sequester chemical warfare agents (CWAs) and then catalytically decontaminate the entrapped CWAs are highly sought. This article reports such a system for air-based catalytic removal of the sulfur mustard (HD) simulant, 2-chloroethyl ethyl sulfide (CEES). Hypercrosslinked polymers (HCPs) sequester CEES, and an HCP-embedded oxidation system comprising tribromide, nitrate, and acid (NOxBrxH+) simultaneously catalyzes the aerobic and selective, oxidative conversion of the entrapped CEES to the desired far less-toxic sulfoxide under ambient conditions (air and temperature). (NOxBrxH+) has been incorporated into three HCPs, a fluorobenzene HCP (HCP-F), a methylated HCP (HCP-M), and an HCP with acidic moieties (HCP-A). HCP-A acts as both an absorbing material and a catalytic component due to its acidic side chains. All three HCP/NOxBrxH+ systems work rapidly under these optimally mild conditions. No light or added oxidants are required. The HCP/NOxBrxH+ systems are recyclable.

Efficient solar light facilitated photo-oxidative detoxification of gaseous 2-chloroethyl ethyl sulfide on ZrO2-doped g-C3N4 under dry and humid air.

Photo-oxidation of chemical warfare agents is considered a promising strategy to cope with threats from accidental or intentional release. In this study, heterostructure photocatalysts comprising different amounts of zirconium oxide (ZrO2) over carbon nitride (CN) were synthesized via simple thermal exfoliation, followed by a precipitation method. The successful photocatalytic detoxification activity of the as-prepared photocatalyst was analyzed against 2-chloroethyl ethyl sulfide (CEES) under simulated solar light and natural sunlight irradiation in dry and humid air. As the CN/ZrO2 demonstrated a high surface area and oxygen doping, the addition of small amounts of the ZrO2 phase could lead to enhanced photoreactivity in surface chemistry. The as-prepared (CN/ZrO2-II) degraded 95% of CEES under simulated solar light and 70% under natural sunlight within 90 min. The photo-detoxification of CEES was associated with the generation of holes (h+) and activation of oxygen to superoxide radicals (•O2). Based on analysis results, a reaction mechanism was suggested. The activity of the used photocatalyst could be recovered to 90% of the fresh photocatalyst activity via simple water washing. However, as sulfurous compounds were accumulated on the surface in subsequent cyclic tests, solvent washing was also suggested to maintain high detoxification performance.

Effective degradation of sulfur mustard simulant using novel sulfur-doped mesoporous zinc oxide under ambient conditions.

Sulfur doped metal oxides were synthesized using a two-step precipitation method. When reacted against neat 2-CEES (2-chloroethyl-ethyl sulfide, a mustard gas simulant) under ambient conditions, sulfur doped mesoporous zinc oxide (MS-Zn) showed higher catalytic activity than the other metal oxides with 92.7% overall conversion in 24 h for a 2.5 µL neat 2-CEES droplet added on top of 2 × 2 cm large 400 mg catalyst layer. The reaction proceeded mainly by hydrolysis and further solvolysis reaction also occurred depending on the extracting solvents. Cyclic sulfonium ion intermediate reaction was thought to be involved in this reaction, and metal oxide surfaces were thought to facilitate the formation of sulfonium ions from adsorbed 2-CEES. All other by-products were also found to form via sulfonium ions, reconfirming the well-known importance of this intermediate species for the degradation reaction to proceed. The sulfur content for MS-Zn was varied and tested for degradation of neat 2-CEES. This modification showed that there is an optimal amount of sulfur content for the peak catalytic activity of MS-Zn for 2-CEES degradation. Adsorption energy of a 2-CEES molecule was calculated on model sulfur doped and non doped zinc oxide surfaces and the different adsorption energy levels were correlated with the catalytic activity of sulfur doped zinc oxide.

Identification of creatine kinase and alpha-1 antitrypsin as protein targets of alkylation by sulfur mustard.

Sulfur mustard (SM) is a toxic chemical warfare agent deployed in several conflicts within the last 100 years and still represents a threat in terroristic attacks and warfare. SM research focuses on understanding the pathophysiology of SM and identifying novel biomarkers of exposure. SM is known to alkylate nucleophilic moieties of endogenous proteins, for example, free thiol groups of cysteine residues. The two-dimensional-thiol-differences in gel electrophoresis (2D-thiol-DIGE) technique is an initial proteomics approach to detect proteins with free cysteine residues. These amino acids are selectively labeled with infrared-maleimide dyes visualized after GE. Cysteine residues derivatized by alkylating agents are no longer accessible for the maleimide-thiol coupling resulting in the loss of the fluorescent signal of the corresponding protein. To prove the applicability of 2D-thiol-DIGE, this technology was exemplarily applied to neat human serum albumin treated with SM, to lysates from human cell culture exposed to SM as well as to human plasma exposed to CEES (chloroethyl ethyl sulfide, an SM analogue). Exemplarily, the most prominent proteins modified by SM were identified by matrix-assisted laser desorption/ionization time-of-flight (tandem) mass spectrometry, MALDI-TOF MS(/MS), as creatine kinase (CK) from human cells and as alpha-1 antitrypsin (A1AT) from plasma samples. Peptides containing the residue Cys282 of CK and Cys232 of A1AT were unambiguously identified by micro liquid chromatography-electrospray ionization high-resolution tandem-mass spectrometry (µLC-ESI MS/HR MS) as being alkylated by SM bearing the specific hydroxyethylthioethyl-(HETE)-moiety. Both peptides might represent potential biomarkers of SM exposure. This is the first report introducing these endogenous proteins as targets of SM alkylation.

Recent advances in process engineering and upcoming applications of metal-organic frameworks.

Progress in metal-organic frameworks (MOFs) has advanced from fundamental chemistry to engineering processes and applications, resulting in new industrial opportunities. The unique features of MOFs, such as their permanent porosity, high surface area, and structural flexibility, continue to draw industrial interest outside the traditional MOF field, both to solve existing challenges and to create new businesses. In this context, diverse research has been directed toward commercializing MOFs, but such studies have been performed according to a variety of individual goals. Therefore, there have been limited opportunities to share the challenges, goals, and findings with most of the MOF field. In this review, we examine the issues and demands for MOF commercialization and investigate recent advances in MOF process engineering and applications. Specifically, we discuss the criteria for MOF commercialization from the views of stability, producibility, regulations, and production cost. This review covers progress in the mass production and formation of MOFs along with future applications that are not currently well known but have high potential for new areas of MOF commercialization.

N-Acetylcysteine as a treatment for sulphur mustard poisoning.

In the long and intensive search for effective treatments to counteract the toxicity of the chemical warfare (CW) agent sulphur mustard (H; bis(2-chloroethyl) sulphide), the most auspicious and consistent results have been obtained with the drug N-acetylcysteine (NAC), particularly with respect to its therapeutic use against the effects of inhaled H. It is a synthetic cysteine derivative that has been used in a wide variety of clinical applications for decades and a wealth of information exists on its safety and protective properties against a broad range of toxicants and disease states. Its primary mechanism of action is as a pro-drug for the synthesis of the antioxidant glutathione (GSH), particularly in those circumstances where oxidative stress has exhausted intracellular GSH stores. It impacts a number of pathways either directly or through its GSH-related antioxidant and anti-inflammatory properties, which make it a prime candidate as a potential treatment for the wide range of deleterious cellular effects that H is acknowledged to cause in exposed individuals. This report reviews the available literature on the protection afforded by NAC against the toxicity of H in a variety of model systems, including its efficacy in treating the long-term chronic lung effects of H that have been demonstrated in Iranian veterans exposed during the Iran-Iraq War (1980-1988). Although there is overwhelming evidence supporting this drug as a potential medical countermeasure against this CW agent, there is a requirement for carefully controlled clinical trials to determine the safety, efficacy and optimal NAC dosage regimens for the treatment of inhaled H.

MicroRNA-mediated inflammation and coagulation effects in rats exposed to an inhaled analog of sulfur mustard.

Exposure of rats to 2-chloroethyl ethyl sulfide (CEES), an analog of sulfur mustard, can cause acute lung injury (ALI), resulting in increased inflammation and coagulation and altered levels of plasma microRNAs (miRNAs). Rats were exposed to aerosolized CEES and euthanized 12 h later for collection of tissue and plasma. Profiling of miRNAs in plasma, using a TaqMan-based RT-PCR array, revealed 14 differentially expressed miRNAs. Target gene prediction and pathway analysis revealed miRNA-mediated regulation of organismal injury, inflammation, and respiratory diseases. miR-140-5p, a marker of ALI, was downregulated in the plasma, lung, liver, and kidney of CEES-exposed rats, with a concomitant increase in the expression of the inflammation markers IL-6 and IL-1α and the coagulation marker tissue factor (F3). Exposure of rat airway epithelial cells (RL-65) to CEES (0.5 mM) caused cell death and a decrease in miR-140-5p both in cells and media supernatant. This was accompanied by an increase in cellular mRNA levels of IL-6, IL-1α, and F3, as well as FGF9 and EGR2, putative targets of miR-140. Knockdown of miR-140 by specific oligos in RL-65 cells mimicked the in vivo CEES-mediated effects, leading to significantly increased mRNA levels of IL-6, IL-1α, F3, FGF9, and EGR2. Our study identifies miR-140-5p as a mediator of CEES-induced ALI, which could potentially be targeted for therapy.

CEES-induced ROS accumulation regulates mitochondrial complications and inflammatory response in keratinocytes.

Reactive oxygen species (ROS) is mainly produced as a by-product from electron transport chain (ETC) of mitochondria and effectively eliminated by cellular antioxidants. However, 2-chloroethyl ethyl sulfide (CEES) exposure to keratinocytes declined antioxidant capacity and increased accumulation of ROS triggered alteration of mitochondrial activity and apoptosis is lacking. Our findings demonstrated that the electron leakage from the impaired ETC, leading to the accumulation of ROS was gradually elevating with increasing concentration of CEES exposure, which decline the activity of superoxide dismutase (SOD), manganese SOD (MnSOD) and copper-zinc SOD (Cu-ZnSOD) in keratinocytes. Further, excess accumulation of ROS, decreased the mitochondrial membrane potential (ΔΨm) and increased the mitochondrial mass with increasing dose of CEES. CEES exposure provoked the decrease in expression of transcription factor A mitochondrial (TFAM), augmented mitochondrial DNA (mtDNA) damage and altered the mtDNA-encoded oxidative phosphorylation (OXPHOS) subunits. Moreover, fragmented mtDNA translocated into cytosol, where it activated cGAS-STING and interferon regulatory factor3 (IRF3), coinciding with the increased expression of inflammatory mediators and alteration of cell-to-cell communication markers. Pre-treatment of N-acetyl-l-cysteine (NAC) or L-Nω-nitroarginine methyl ester (NAME), hydralazine hydrochloride (Hyd·HCl) or ERK1/2 or phosphoinositide3-kinase (PI3-K)/Akt inhibitors in keratinocyte cells significantly restored the CEES effect. Our findings suggest that CEES-induced mitochondrial ROS production and accumulation leads to mitochondrial dysfunction and inflammatory response in keratinocytes. However, treatment of antioxidants or ERK1/2 or PI3-K/Akt inhibitors is a novel therapeutic option for the keratinocytes complication.

Defectous UiO-66 MOF Nanocomposites as Reactive Media of Superior Protection against Toxic Vapors.

The composites of UiO-66 with nanographite or oxidized graphitic carbon nitride nanospheres (∼10 wt %) were synthesized and used as CEES decontamination media from a vapor phase. The materials were characterized using XRD, nitrogen adsorption, SEM, potentiometric titration, FTIR, and thermal analysis. The results showed a marked improvement of the detoxification capability against the vapors of CEES compared to those of pristine UiO-66, either in terms of the amount adsorbed or surface reactivity. The maximum weight uptake for the composites reached 632 mg g-1, which was higher than that on UiO-66. The improved adsorption and catalytic activity were linked to the new interface between the modifiers and MOF units/defects, which provided additional active sites formed as a result of modifiers' surface groups acting as MOF linkers. The morphology and porosity were also altered, positively affecting the sites' accessibility and their dispersion in the MOF particles. Dehydrohalogenation and oxidation were the predominant pathways of the composites' surface reactivity. The detoxification mechanisms involving CEES vapor-UiO-66 surface interactions differ from those reported for CEES liquid/dissolved liquid-UiO-66 interactions, and dehydrohalogenation, fragmentation, and oxidation predominate.

Time course study of oxidative stress in sulfur mustard analog 2­chloroethyl ethyl sulfide-induced toxicity.

Oxidative stress is the major mechanism impairing cell homeostasis, inducing cell death and tissue damage in sulfur mustard (SM)-exposed individuals. The aim of the present study was to evaluate time course changes of oxidative stress in the mice exposed with 2­chloroethyl ethyl sulfide (CEES) as SM analog. For this purpose, male BALB/c mice were divided into control groups and experimental groups that received CEES (10 mg/kg) through intraperitoneal injection. In both groups, animals were euthanized at three periods: short (12, 24 h and 1 week), medium (1, 2 and 3 months) and long-term (5 and 6 months) after CEES exposure. Oxidative stress indices and the antioxidant defense systems were evaluated in lung and liver tissues. The time course findings in both tissues showed a significant increase in oxidative damage markers such as malondialdehyde (lung P < 0.001, liver P < 0.001), protein carbonyl (lung P < 0.0001), and 8-hydroxy-deoxyguanosine (lung P < 0.0001, Liver P < 0.0001) and also a significant reduction in the antioxidant defense system including reduced glutathione level (lung P < 0.001, Liver P < 0.001,), activities of catalase (lung P < 0.01 and liver P < 0.05), superoxide dismutase (lung P < 0.05), glutathione S­transferase (lung P < 0.05, liver P < 0.01), glutathione peroxidase (lung, P < 0.05, Liver P < 0.05) and glutathione reductase (lung P < 0.001, liver P < 0.01) in the long-term. However, these changes occur with less intensity in the short-term and return to the normal status in the medium-term. Moreover, there was a positive time course correlation between oxidative damage indices and the percent of histopathological damage in both tissues (P < 0.05). This correlation finding confirms and supports the fact that time course oxidative-antioxidant imbalance plays an important role in the development of SM-induced acute and delayed injuries.