The threat posed by chemical warfare agents (CWAs) in the modern era necessitates increased innovation in understanding new mechanisms to neutralize their lethality. By identifying novel materials and chemical reaction pathways, better protection can be offered. Single metal atoms supported on TiO2 represent a promising avenue of exploration in designing systems which can effectively capture and degrade the sulfur mustard agent. By modelling sulfur mustard and its simulant, 2-chloroethyl-ethylsulfide (2-CEES), this work provides a proof of concept for the facile decomposition pathways of sulfur-containing vesicant agents over Pt, Pd, and Ir single atoms on the anatase TiO2(101) surface with and without the presence of water. Under ambient conditions, 2-CEES will favorably be transformed into ethyl-vinylsulfide (EVS) through a dehydrochlorination reaction involving C-H and C-Cl bond cleavages. Notably, the single atom cleaves the α-C-H bond with a low calculated barrier. The reaction energetics are most favorable on the Pd system with barriers passable at a temperature of 298 K with EVS desorption facilitated by adsorption and a reaction of additional reactant molecules, and with the produced H and Cl fragments stored on the titania support. The Pd single atom is proposed to be able to degrade 2-CEES and sulfur mustard through a mechanism combining C-H bond cleavage at the Pd-O center and sorption of the H and Cl fragments from 2-CEES or mustard on TiO2, however with a larger reactivity for the removal of the second Cl of mustard than for dehydrochlorination of a second 2-CEES reactant. The reaction appears as a hybrid combination of catalytic steps evolving products in the gas phase with reactive sorption of the remaining fraction of products on the support.

Chemical agents, such as sulfur mustard (SM), are extremely toxic, and prolonged exposure can severely disrupt the metabolism of amino acids and nucleic acids in organisms. To effectively monitor agent exposure and identify specific biomarkers, we employed 2-chloroethyl ethyl sulfide (2-CEES) as a simulant to investigate the changes in metabolic characteristics within three bryophytes under different concentrations of 2-CEES exposure. Key metabolic pathways and enzymes affected by 2-CEES were analysed using theoretical calculations. Results demonstrated significant morphological changes in bryophytes following exposure to 2-CEES. Meanwhile, Chlorophyll fluorescence parameters revealed that 2-CEES markedly disrupted the photosynthetic activity of Physcomitrella patens and Taxiphyllum taxirameum. Metabolomic analysis showed pronounced changes in metabolite expression after 72 hr of 2-CEES (600 mg/m³) treatment across all three species. Pathway enrichment analysis of differentially expressed metabolites (DEMs) indicated that 2-CEES significantly perturbed amino acid, nucleic acid, carbohydrate, and lipid metabolism in Bryum argenteum and Physcomitrella patens. In contrast, Taxiphyllum taxirameum exhibited primary disruptions in lipid metabolism, terpenoid and polyketide metabolism, and membrane transport. Notably, aberrant synthesis of L-Glutamyl-tRNA(Glu) in the aminoacyl-tRNA biosynthesis pathway may correlate with impaired chlorophyll production. In addition, the significant changes of Gamma-Glutamyl-beta-(isoxazolin-5-on-2-yl)alanine, Trans-zeatin riboside, and Cytidine in bryophytes exposed to 600 mg/m³ 2-CEES suggest their potential as micro- and trace biochemical indicators for agent-induced stress. Molecular docking of 2-CEES with key enzymes (Glutathione S-transferase and Glu-tRNA synthetase) revealed that its chloro and methyl groups form hydrogen bonds with residues such as TYR and ARG, interfering with substrate-binding activity and consequently disrupting metabolic pathways.

Sulfur mustard (HD) undergoes elimination reactions in environmental and decontamination scenarios, generating diagnostic unsaturated degradation products including 2-hydroxyethyl-vinyl sulfide (2-HVS) and divinyl sulfide (DVS). The two compounds serve as critical chemical markers for HD verification under the Chemical Weapons Convention (CWC) framework. However, direct analysis of these chemicals by liquid chromatography-electrospray ionization source-mass spectrometry (LC-ESI-MS) faces great challenges because of their intrinsic properties of low polarity, high volatility, and inefficient ionization. A simple derivatization method using bis(pyridine) iodonium tetrafluoroborate (IPy2BF4) was developed to address these limitations simultaneously. ESI-MS signal was efficiently improved through introducing a permanent positive charge via quaternary ammonium formation after derivatization. Structural confirmation was achieved through high-resolution mass spectrometry in both full-scan and parallel reaction monitoring (PRM) modes. Derivatization conditions were systematically optimized, and the reaction was completed in 5min. The quantitative method was developed based on quaternization derivatization and LC-ESI-MS with the perdeuterated IPy2BF4 derivative as the internal standard. It exhibited a linear range of 0.100-300ng/mL (R2 ≥ 0.99). The sensitivity of this method in three MS scanning modes was assessed as the lowest limit of detection (LOD) of 0.0100ng/mL in MRM mode. In combination with a simple extraction protocol, DVS and 2-HVS spiked at 1.00ng/mL in soil, water, and the simulated 42nd Official OPCW Proficiency Test samples were successfully detected by the developed method. This derivatization strategy was also applied in the LC-ESI-MS detection of the oxidized unsaturated degradation products including divinyl sulfoxide (DVSO) and divinyl sulfone (DVSO2). This simple quaternization derivatization provides a novel analytical technique for sensitive detection of unsaturated HD degradation products in CWC verification.

We herein present the development and application of a forensic mass spectrometry-based procedure simultaneously targeting hard keratins from human hair adducted with sulfur mustard (SM) and its structural analogues sesquimustard (Q) and O-lost (T). These alkylating chemicals represent blister agents banned by the Chemical Weapons Convention (CWC). The procedure was applied to an authentic hair sample of an SM-poisoned patient and thus allowed for the first time the proof of exposure to SM based on keratin adducts in a real case of poisoning. Whereas adducts of SM were detected, those of Q and T were not found. Contact of SM, Q and T with hair induced the alkylation of side chains of glutamic acid (E*) residues in diverse hard keratins (adduct formation). For analysis hair proteins were subjected to lysis to make them soluble and subsequently to proteolysis with pepsin to generate adducted peptides. Micro liquid chromatography-electrospray ionization high-resolution tandem-mass spectrometry (µLC-ESI MS/HR MS) allowed the detection of the three biomarker peptides AE*IRSDL, FKTIE*EL and LE*TKLQF. The characteristic alkyl-chain hydroxyethylthioethyl (HETE) was attached by SM, hydroxyethylthioethylthioethyl (HETETE) derived from Q and the hydroxyethylthioethyloxyethylthioethyl (HETEOETE)-moiety originated from exposure to T. Accordingly, we herein present an extended and improved forensic method for the biomedical verification of hair exposure to blister agents. Due to the currently growing threat by chemical warfare agents we also included some general toxicological and bioanalytical remarks of SM poisoning helpful not only for physicians and toxicologists.

Repurposing the anesthetic dexmedetomidine: a novel antidote for sulfur mustard analog-induced acute lung injury via multi-mechanism modulation.

Bidentate/bis-bidentate ligands−contained polymolybdate−based hybrid copper compounds for capacitive performance and catalytic detoxification of sulfur mustard simulant

Sulfur mustard (SM) is a potent chemical warfare agent that causes severe cutaneous, ocular, and pulmonary injuries, with respiratory tract damage being the most life-threatening. Despite its well-documented toxicity, the cellular mechanisms driving SM-induced apoptosis remain poorly understood. This study seeks to elucidate the apoptotic pathways involved in SM-induced pulmonary injury using a rat model. We induced acute lung injury through two delivery methods: intraperitoneal injection (8 mg/kg) and intratracheal instillation (2 mg/kg) of SM, with both doses representing 1 LD50. We assessed apoptosis-related proteins and gene expression through TUNEL staining, immunohistochemistry, and quantitative real-time PCR analyses. Intraperitoneal administration of SM resulted in significantly elevated expression of apoptotic markers including annexin A1, annexin A2, cytochrome C, caspase-12, and JNK3, in alveolar epithelial cells compared to intratracheal delivery. Both TUNEL assays and immunohistochemical staining confirmed these findings. These results indicate that intraperitoneal SM exposure triggers more severe apoptotic responses in alveolar epithelial cells than intratracheal exposure at equivalent doses. These findings demonstrate that intraperitoneal models can effectively identify apoptosis-related molecular targets suitable for therapeutic development.

Sulfur mustard (SM), a highly reactive alkylating agent, remains a significant threat to both military personnel and civilian populations due to its toxic effects. Although substantial research has been conducted, the precise apoptotic mechanisms triggered by SM exposure are not yet fully understood. This study aimed to assess potential differences in the apoptosis following SM-induced acute pulmonary injury via the two routes. An acute pulmonary injury model was developed using SM at an equitoxic dose (1 LD50), administered via either a single intraperitoneal injection or intratracheal instillation. Protein expression levels and mRNA expressions of cysteinyl aspartate specific proteinase-2 (caspase-2), caspase-4, caspase-7, caspase-8, p53, and factor-associated suicide ligand (FasL) were evaluated using immunohistochemistry labeling and polymerase chain reaction analysis. At equitoxic doses, the intraperitoneal SM group exhibited significantly higher protein expression ratios and mRNA expression levels of caspase-2, caspase-4, caspase-7, caspase-8, p53, and FasL in the epithelial cells of the alveolar septa from the right lower lobe of the rat's lungs than the intratracheal SM group. Both protein and mRNA expression levels increased progressively over time in both groups. The findings indicate that SM in early-phase induces apoptosis through intrinsic and extrinsic pathways as well as possible endoplasmic reticulum stress-related pathway. These insights contribute to a deeper understanding of SM toxicity and offer a basis for developing targeted therapeutic strategies to mitigate its harmful effects.

In vitro methods for evaluation of sulfur mustard on cell senescence.

Accelerated senescence in sulfur mustard-exposed individuals: Evidence from oxidative DNA damage, telomere shortening, and dietary inflammatory index.

A highly efficient dual-functional fluorescent probe to sarin and sulfur mustard substitutes

Colorimetric sensor array based on gold nanoparticles for detection of mustard gas

Sulfur mustard, a highly toxic organosulfur-based chemical warfare agent (CWA), poses significant risks to both human health and the environment. While metal-organic frameworks (MOFs) have been widely explored for capturing and degrading CWA, hydrogen-bonded organic frameworks (HOFs) remain underexplored, despite their permanent porosity, water stability, and ease of synthesis. In this study, we demonstrate the photocatalytic oxidation of the sulfur mustard simulant 2-chloroethyl ethyl sulfide (CEES) using two distinct HOFs. The first, HOF-111, is a framework presented for the first time, synthesized from 2,3,6,7,10,11-hexakis(4-carboxyphenyl)triphenylene (HCPT) and achieves efficient CEES degradation under UV light irradiation. To extend the catalytic activity into the visible region, we synthesized the phenazine-based CPHATN-HOF, derived from hexaazatrinaphthylene (CPHATN), which features increased π-conjugation relative to HOF-111, thereby red-shifting absorption and enabling effective photocatalysis under both visible light and sunlight. In addition, CEES microbreakthrough studies reveal that HOF-111 exhibits identical kinetic uptake capacities for CEES vapor under both dry and humid conditions, likely due to its hydrophobic pore environment and inherent porosity. Collectively, this work establishes HOFs as promising dual-functional protective materials capable of capturing and detoxifying CEES under ambient conditions.

Prognostic value of erythropoietin in elderly and senile patients with heart failure and anemia OBJECTIVE: to study the prognostic value of erythropoietin (EPO) levels in elderly and senile patients with chronic heart failure (CHF) and anemia. MATERIAL AND METHODS. EPO levels in blood serum were determined once in 105 patients with CHF and anemia aged 65 to 90 years. The follow-up period was 24 months. The primary endpoint was death from all causes. The adequacy of endogenous EPO production was assessed by the ratio «observed EPO / predicted EPO» (O/P), calculated on the basis of EPO and hemoglobin levels in patients of the control group with iron deficiency anemia without CHF – [HR 1.004 ± 0.004 [95 % CI; (0.919–1.080)]. The value of O/P < 0.9 was considered insufficient production of EPO, O/P > 1.1 – excessive, O/P = 1.0 – adequate. The Kaplan – Meyer method was used to compare survival rates depending on the value of O/P levels of EPO. Regression analysis of proportional hazards of Cox was used to assess the effect of the value of O/P levels of EPO on the risk of death. RESULTS. In patients with CHF and anemia, the average EPO level was (35.900 ± 2.537) mIU/ml [8.46; 154.00]. According to the obtained ratio of O/P levels of EPO, 59 % of patients showed signs of excessive production of EPO (O/P > 1.1), 18 % – insufficient production (O/P < 0.9) and adequate – in 23 % (O/P = 1.0). The Kaplan – Mayer method showed significantly higher mortality in patients with O/P > 1.1 than in patients with O/P < 0.9 and O/P = 1 (p = 0.00418). The analysis of proportional hazards of Cox revealed an effect on the risk of death of the ratio O/P > 1.1 at the trend level in a single-factor analysis [HR 0.947 (95 % CI; 0.893–1.004), p = 0.069] and significant in a multifactorial [HR 0.924 (95 % CI; 0.859–0.994), p = 0.034]. CONCLUSION. Elderly and senile patients with CHF and anemia are characterized by marked variability in EPO levels, while there may be excessive, insufficient or adequate EPO production. The prognostic value of O/P levels of EPO as a marker of the discrepancy between the degree of anemia and the actual production of EPO was revealed, while the O/P value >1.1 indicates an unfavorable prognosis, since it correlates with an increased risk of death.

Proinflammatory macrophage polarization is driven by NOX4/PPARγ axis-mediated oxidative-inflammatory crosstalk in CEES-induced lung injury.

Sulfur mustard (SM) causes multi-organ toxicity, yet its impact on intestinal tissue and the associated gut microbiota remains poorly characterized. This study demonstrates that in a mouse model of SM exposure, gut microbial ecological collapse occurs, characterized by depletion of protective taxa (Bifidobacteriales, Gordonibacter, and Lachnospiraceae UCG010) while promoting a 302-fold expansion of inflammation-associated Escherichia/Shigella. Mendelian randomization analysis established causal relationships between these SM-perturbed taxa and human inflammatory bowel disease. Fecal microbiota transplantation effectively restored microbial diversity (Simpson index: 0.85 to 0.95), suppressed Escherichia/Shigella by 97.4%, and ameliorated intestinal pathology. Longitudinal tracking revealed persistent vulnerability of Bifidobacteriales compared to other depleted taxa. Our findings establish the gut microbiota as a key mediator in SM intestinal toxicity and provide new insights for microbiota-targeted interventions against chemical injuries.

BackgroundHuman umbilical cord blood (HUCB) serum eye drops contain growth factors, neurotrophic agents, and antimicrobial compounds that may promote ocular surface healing and regeneration. Sjögren’s syndrome is a chronic autoimmune condition characterized by reduced tear production and ocular surface damage, often resulting in severe dry eye symptoms. Mustard gas chemical veterans also suffer from similar debilitating ocular complications due to chronic inflammation and meibomian gland dysfunction. While conventional treatments offer symptomatic relief, they lack essential components of natural tears.Materials and methodsThis pilot randomized controlled trial will evaluate the efficacy of HUCB eye drops in three patient groups: (A) Sjögren’s patients treated with HUCB drops, (B) Sjögren’s patients receiving conventional treatment, and (C) mustard gas veterans receiving conventional treatment in the right eye and HUCB drops in the left eye. Patients will be assessed using subjective and objective tools, including the Ocular Surface Disease Index (OSDI), visual acuity, tear film breakup time (TBUT), SM tube test, and fluorescein staining based on SICCA criteria. Group allocation will follow a blocked randomization sequence for groups A and B; group C will follow a within-subject paired-eye design. Follow-up will occur at 30 and 60 days.DiscussionThis study aims to assess the regenerative potential of HUCB serum in patients with autoimmune and chemically induced dry eye. Its results may support broader clinical use of HUCB drops in treating severe ocular surface disorders, including conditions like Stevens-Johnson syndrome and industrial chemical exposures.Trial registrationThis trial was registered at the Iranian Registry of Clinical Trials (Registration number: IRCT20230925059512N1, Registration date: 2024-08-11).

Human umbilical cord blood (HUCB) serum eye drops contain growth factors, neurotrophic agents, and antimicrobial compounds that may promote ocular surface healing and regeneration. Sjögren's syndrome is a chronic autoimmune condition characterized by reduced tear production and ocular surface damage, often resulting in severe dry eye symptoms. Mustard gas chemical veterans also suffer from similar debilitating ocular complications due to chronic inflammation and meibomian gland dysfunction. While conventional treatments offer symptomatic relief, they lack essential components of natural tears. This pilot randomized controlled trial will evaluate the efficacy of HUCB eye drops in three patient groups: (A) Sjögren's patients treated with HUCB drops, (B) Sjögren's patients receiving conventional treatment, and (C) mustard gas veterans receiving conventional treatment in the right eye and HUCB drops in the left eye. Patients will be assessed using subjective and objective tools, including the Ocular Surface Disease Index (OSDI), visual acuity, tear film breakup time (TBUT), SM tube test, and fluorescein staining based on SICCA criteria. Group allocation will follow a blocked randomization sequence for groups A and B; group C will follow a within-subject paired-eye design. Follow-up will occur at 30 and 60 days. This study aims to assess the regenerative potential of HUCB serum in patients with autoimmune and chemically induced dry eye. Its results may support broader clinical use of HUCB drops in treating severe ocular surface disorders, including conditions like Stevens-Johnson syndrome and industrial chemical exposures. This trial was registered at the Iranian Registry of Clinical Trials (Registration number: IRCT20230925059512N1, Registration date: 2024-08-11).

Proteomic profiling and bioinformatics insights into lung tissue damage following whole-body exposure to sulfur mustard vapor.

Dual-responsive fluorescence probe for simultaneous detection of BF3 and sulfur mustard simulant in both solutions and gas phase