Search Results (268)

Resistance to apoptosis, metabolic plasticity, and redox adaptation are major contributors to cancer progression and treatment failure. Ferroptosis and cuproptosis have therefore emerged as metal-dependent forms of regulated cell-death programs with potential relevance for tumours that survive conventional therapy. Ferroptosis is driven by iron-dependent phospholipid peroxidation when glutathione peroxidase 4 (GPX4)-dependent and parallel antioxidant systems fail, whereas cuproptosis depends on mitochondrial copper engagement of lipoylated tricarboxylic-acid-cycle proteins, lipoylated-protein aggregation, iron–sulfur protein destabilization, and proteotoxic stress. This review integrates the molecular basis, genetic architecture, long non-coding RNA (lncRNA)-mediated regulation, mechanistic crosstalk, and therapeutic implications of ferroptosis and cuproptosis in cancer. It emphasizes a critical evidence hierarchy: expression association, computational signature construction, metal accumulation, reactive oxygen species (ROS) generation, or reduced viability should not be interpreted as pathway dependency without pathway-defining biochemical endpoints and rescue experiments. The most credible translational opportunities will depend on functional stratification, tumour-selective delivery, and pharmacodynamic confirmation that distinguishes pathway-defined ferroptosis or cuproptosis from nonspecific metal-induced and oxidative cytotoxicity. Full article

Recent research has demonstrated the important role of hydrogen sulfide (H₂S) and its derivatives, reactive sulfur species (RSS), as modulators of various redox-regulated physiological processes in bacteria. Bacterial cells are equipped with enzymes that synthesize and catabolize H₂S and RSS, and sensors that control the expression of genes whose products ensure the maintenance of safe levels of these compounds in cells and the survival of bacteria in the host environment. With the rapid growth of resistant pathogens, the impact of H₂S and RSS on bacterial virulence and antibiotic sensitivity is attracting increasing attention. The possibility of enhancing the efficacy of widely used antibiotics by artificially modulating H₂S levels is being explored. This review summarizes current data on the sources and conditions of endogenous H₂S and RSS production, the molecular mechanisms of action of various concentrations of exogenous and endogenous H₂S, and the regulatory factors that control the expression of virulence and antibiotic resistance genes. Possible reasons for the conflicting results obtained by different research groups regarding the possibility of modulating bacterial sensitivity to antibiotics by altering the production of endogenous H₂S are discussed. Full article

Ascorbate (AsA), or vitamin C, is a central redox metabolite that functions as an antioxidant, enzyme cofactor, and electron donor. Its cellular function depends not only on biosynthesis or dietary uptake, but also on rapid recycling from its oxidized forms, monodehydroascorbate (MDHA) and dehydroascorbate (DHA). This requirement is especially evident in high-demand systems such as plant chloroplasts, which face continuous photosynthetic reactive oxygen species (ROS) production under illumination, and human neutrophils, which accumulate millimolar ascorbate to withstand NADPH oxidase-driven oxidative bursts in pathogen defense. Here, we revisit ascorbate recycling from a sulfur-centered perspective. Historical studies of plant, animal, and solution-chemistry pathways show that many DHA-reducing systems converge on sulfur chemistry, including glutathione (GSH), cysteine-dependent enzymes, H₂S, and modified thiols. We propose that ascorbate recycling is organized as a multilayered system in which nonenzymatic reactions are accelerated by enzymes, localized within cellular or extracellular compartments, and integrated with broader NAD(P)H-, glutathione-, sulfur-, and diet-dependent redox networks. Within this framework, the AsA/DHA couple can be viewed as a molecular redox capacitor that buffers transient oxidative pressure. Reactive sulfur species (RSS), including persulfides and polysulfides, represent chemically plausible but experimentally unresolved contributors to DHA reduction. Full article

Antibiotics have been extensively used in medicine and aquaculture, leading to severe environmental contamination. Among them, chlortetracycline (CTC) has attracted considerable attention due to its large consumption and high residual risk. MIL-125(Ti), as a representative titanium-based metal–organic framework, exhibits good structural stability and tunability; however, its intrinsically weak visible-light response and rapid charge recombination limit further photocatalytic applications. To improve its photocatalytic performance, MIL-125 was first synthesized via a hydrothermal method, and then Fe and S species were introduced through a combination of in situ coprecipitation and mild sulfuration, yielding an Fe/S-modified MIL-125 photocatalyst. The introduction of Na₂S induced defect sites and coordinatively unsaturated centers on the MIL-125 surface, while the cooperative participation of Fe species further regulated the surface electronic structure and active-site distribution, thereby enhancing visible-light absorption and interfacial charge transfer. Under AM 1.5 irradiation, the optimized Fe/S-MIL-125 achieved a CTC degradation efficiency of 98.6% within 120 min at an initial concentration of 40 mg L−1. In addition, the material exhibited broad applicability toward multiple antibiotics, with degradation efficiencies exceeding 87% for ciprofloxacin (CIP) and clindamycin (CLI). Cycling tests demonstrated that the catalyst retained high activity after five successive runs, indicating excellent stability. Radical scavenging experiments and ESR analyses revealed that superoxide radicals (·O²⁻) were the dominant reactive species. Overall, the Fe/S-modified strategy significantly enhanced the photocatalytic performance of MIL-125 through defect engineering and interfacial charge regulation, offering a promising approach for the design of MOF-based materials for antibiotic removal. Full article

Mononuclear nonheme iron(IV)–oxo species supported by mixed nitrogen–sulfur (N/S) ligands remain scarce, despite the prevalence of sulfur donors in biological iron sites and their expected impact on ferryl reactivity and catalyst design. In this work, a seven-coordinate iron(II) complex, [(N₃S₂)Fe^II(ClO₄)₂], bearing a rigid 15-membered N₃S₂ macrocycle, is shown to rapidly generate a mononuclear nonheme Fe^IV=O intermediate upon reaction with m-chloroperbenzoic (m-CPBA) acid in acetonitrile. The Fe^IV=O species forms within ≤2 s and is thermally persistent (t₁/₂ = 4.3 h at 25 °C), albeit in partial yield (~39% Fe^IV=O by Mössbauer spectroscopy), placing it in an intermediate regime between highly reactive but short-lived ferryl species and more inert, long-lived analogues. The intermediate is characterized by Mössbauer spectroscopy (δ = 0.35 mm s⁻¹, ΔE_Q = 0.90 mm s⁻¹, Γ_FWHM = 0.30 mm s⁻¹, relative area = 39.4%), EPR silence, a UV–vis absorption band at 428 nm, and cryogenic high-resolution ESI–MS (m/z 223.510, (N₃S₂)Fe^IV=O²⁺). Stopped-flow kinetic studies reveal saturation behavior that is well described by a pre-equilibrium oxidant-association model and subsequent O–O bond activation, with apparent activation parameters of ΔH^‡ = 17.7 kJ mol⁻¹ and ΔS^‡ = −155 J mol⁻¹ K⁻¹, indicating a highly ordered transition state within the seven-coordinate N₃S₂ framework under the conditions employed. Functionally, the Fe^IV=O species mediates clean oxygen-atom transfer to triphenylphosphine (k₂ = 8.1 × 10⁻² M⁻¹ s⁻¹) with an effective turnover number of ~12 after correction for the Fe^IV=O yield, establishing that this mixed N/S platform is catalytically competent under mild conditions, though less reactive than state-of-the-art all-nitrogen systems. Collectively, these findings identify the seven-coordinate N₃S₂ macrocycle as a mixed-donor platform that moderately extends ferryl lifetime while retaining measurable oxo-transfer reactivity, providing mechanistic guidance for the development of nonheme iron oxidation catalysts that incorporate sulfur donors. Full article

Sulfur-containing amino acids (SCAA) and their metabolites constitute an integrated metabolic network essential for central nervous system (CNS) function. In mammals, sulfur metabolism links one-carbon metabolism, the methionine cycle and the transsulfuration pathway, thereby connecting nutrient availability with redox regulation, methylation reactions, neurotransmitter synthesis and cellular adaptation to stress. Among these metabolites, methionine, cysteine, glutathione, taurine, homocysteine and hydrogen sulfide play key roles in neuronal physiology, mitochondrial homeostasis, synaptic plasticity and antioxidant defense. Alterations in SCAA metabolism have been increasingly associated with neurological and neurodevelopment disorders, which share common features such as oxidative stress, mitochondrial dysfunction, altered glutamatergic signaling, impaired methylation capacity and neuroinflammation. These pathological mechanisms are also observed following exposure to toxic metals, suggesting the existence of convergent pathways between environmental neurotoxicity and neurological diseases. Several studies showed that chronic exposure to arsenic, mercury, cadmium, lead, and other toxic metals disrupts sulfur amino acid homeostasis by affecting methionine remethylation, transsulfuration activity, glutathione synthesis and reactive sulfur species production. Due to sulfur-containing metabolites possessing antioxidant and metal-binding properties, these pathways are also involved in adaptive detoxification response. However, sustained disruption of sulfur metabolism may compromise neuronal resilience and increase vulnerability to neurological dysfunction. This narrative review integrates current evidence on the physiological roles of SCAA in the CNS, and examines how toxic metals disrupt sulfur metabolic pathways. By combining findings from experimental studies, human data and exploratory transcriptomic analyses, we propose that disruption of SCAA homeostasis represents a mechanistic link between environmental metal exposure and increased vulnerability to neurological disease. Full article

The environmentally sustainable decontamination of chemical warfare agents (CWAs) remains a critical challenge. This study reports the solar-driven photocatalytic degradation of live CWAs—GD, HD, HN1, and HN2—using titanium dioxide (TiO₂) under natural sunlight. Experiments were conducted in an OPCW-designated laboratory to ensure authenticity and practical relevance. TiO₂ exhibited substantial photocatalytic activity, achieving 60% degradation of GD, 63% of HD, 76% of HN1, and 93% of HN2 after 6 h. High-resolution mass spectrometry (HR-MS) analysis suggested plausible degradation pathways for nitrogen mustards consistent with the higher apparent reactivity of HN2; detailed identification of intermediates and reactive oxygen species remains a subject for future investigation. These findings provide mechanistic insights into the photocatalytic behavior of nitrogen-based agents and address a notable gap in studies that have largely focused on sulfur mustards and nerve agents. Beyond military applications, this solar-assisted photocatalytic approach provides mechanistic information relevant to the green remediation of highly toxic organic contaminants and broader chemical hazard mitigation. This work contributes foundational knowledge toward eco-friendly decontamination technologies capable of mitigating diverse CWA threats. Full article

Bacterial infections and excessive reactive oxygen species (ROS) severely impede wound healing. However, traditional hydrogels often lack the integrated antibacterial and antioxidant properties required for effective treatment. To overcome these limitations, a natural thioctic acid (TA)-based multifunctional composite hydrogel (PTA-Arg/SAS) was developed. Arginine (Arg) served as a green inducer for the aqueous ring-opening polymerization of TA. Concurrently, salicylic acid-grafted sericin (SAS) was introduced to inhibit poly(thioctic acid) (PTA) depolymerization via the formation of stable sulfur-aryl (S-Ar) bonds. The hydrogel exhibits self-healing capability, injectability, and robust tissue adhesion to porcine skin (1877 Pa dry; 1663 Pa wet). Furthermore, SAS endowed the system with potent antibacterial (99.1% against E. coli, 97% against S. aureus) and antioxidant activities (98.2% ABTS and 72.7% DPPH radical scavenging rates). In vitro evaluations confirmed the viability of L929 cells (>98% over 3 days) and a negligible hemolysis ratio (<5%). Consequently, this study provides a strategy for fabricating next-generation bioactive dressings for complex wound management. Full article

The skin serves as the body’s first line of defense against environmental threats, acting as a barrier between external aggressors and internal systems. Current evidence regarding the roles of sulfur dioxide (SO₂) in biology and medicine is limited. Environmental pollutants, including SO₂, can increase the production of reactive oxygen species in the skin, leading to oxidative damage that may worsen various dermatological conditions. Endogenous SO₂, proposed as the fourth member of the gasotransmitter family, functions as a biological signaling molecule. It is generated in various human skin cells, including vascular smooth muscle cells, endothelial cells, mast cells, keratinocytes, macrophages, adipocytes, fibroblasts, dermal immune cell population, etc, where it performs multiple functions at physiologically relevant concentrations. Endogenous SO₂ plays a crucial role in regulating cell signaling and maintaining skin homeostasis through its antioxidant, anti-inflammatory, and cytoprotective effects. Abnormal generation and metabolism of SO₂ are linked to several critical processes in the skin, including vascular biology, immune response, cell proliferation, pigmentation, malignancy, protective barriers, senescence, and resistance to stress. This paper provides a narrative review of the significant roles of SO₂ in skin health and disease. A comprehensive understanding of the complex molecular effects and mechanisms mediated by SO₂ in human skin, along with the development of gas therapy, will be essential for translating fundamental research into clinical applications. Full article

Chronic kidney disease (CKD) affects approximately 700 million people worldwide and is a major contributor to end-stage renal disease (ESRD), cardiovascular morbidity, and premature mortality. Although oxidative stress has long been considered central to CKD progression, conventional antioxidant strategies have not consistently improved clinical outcomes, suggesting that excess reactive oxygen species (ROS) alone cannot fully account for the underlying disease pathophysiology. Emerging evidence supports a broader paradigm of redox network failure, characterized by the disruption of coordinated signaling among ROS, nitric oxide (NO), and reactive sulfur species (RSS). Within this framework, hydrogen sulfide (H₂S), a major endogenous RSS, functions as a key regulator of renal redox homeostasis. CKD is consistently associated with systemic and renal H₂S deficiency, accompanied by downregulation of cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE), and 3-mercaptopyruvate sulfurtransferase (3-MST), as well as impaired transsulfuration and disrupted mitochondrial sulfide oxidation. Importantly, this deficiency cannot be explained solely by reduced renal function but instead reflects active suppression of H₂S biosynthesis. Uremic toxins, particularly indoxyl sulfate (IS), contribute to this process through activation of the aryl hydrocarbon receptor (AhR), which inhibits specificity protein 1 (Sp1)-dependent transcription of H₂S-producing enzymes. This IS–AhR–Sp1 axis provides a mechanistic link between toxin accumulation and disruption of the sulfur arm of the redox network, amplifying oxidative stress, endothelial dysfunction, mitochondrial impairment, ferroptotic vulnerability, and fibrotic remodeling. Beyond H₂S itself, downstream RSS, including persulfides, polysulfides, and thiosulfate, may represent the principal bioactive mediators of sulfur-dependent redox signaling, and their coordinated depletion in CKD may impair redox buffering capacity beyond what H₂S measurement alone reflects. This review integrates current evidence to propose a conceptual model in which CKD progression involves failure of coordinated redox signaling—characterized by feed-forward network collapse and threshold-dependent transition to a self-sustaining high-ROS state—with H₂S deficiency representing one mechanistically supported component of this broader network disruption. This framework highlights the therapeutic potential of targeting redox network restoration rather than isolated oxidative pathways in CKD. Full article

Spent lithium-ion battery electrolytes contain fluorine-, sulfur-, and phosphorus-bearing toxins, necessitating deep detoxification and directional conversion into C₁–C₆ light hydrocarbons. To elucidate the specific catalytic roles and sequential activation of cathode metals (Li, Ni, Co, Mn), this work systematically deconvolutes their mono- and multi-metallic migration mechanisms over a CaO-ZSM-5* catalyst during vacuum catalytic pyrolysis (530 °C, 100 Pa). Results reveal that Li⁺ and Ni²⁺ dominate C–O bond cleavage in carbonates and CaO-ZSM-5*-assisted decarboxylation and oxygen fixation, significantly increasing the relative hydrocarbon content. Conversely, Co^2/3+ and Mn⁴⁺ release reactive oxygen species, causing deep oxidation of hydrocarbons into CO₂ and antagonizing the targeted conversion. In multi-metallic systems, forming composite metal oxides (M_xN_yO_z) increases the energy barrier for releasing active catalytic ions, hindering carbonate cleavage and leaving unreacted carbonate feedstocks. For detoxification, F and P are effectively immobilized as CaF₂ and Ca₂P₂O₇. The relative content of detected gas-phase nitriles is minimized to <2% due to the strong antagonistic effect of Ni²⁺ on Li⁺-promoted hexanedinitrile cleavage, while sulfur species derived from 1,3-propane sultone are converted to SO₂ and ultimately mineralized as calcium and metal-sulfur salts. Mechanistically, product distributions and crystallographic properties suggest a hypothesized sequential activation model—Li⁺ → Ni²⁺ → Mn⁴⁺—governing reactivity, whereas Co^2/3+ does not participate in the synergistic detoxification and selective upgrading process. This migration–reaction coupling framework provides critical insights for cathode-assisted in situ catalytic pyrolysis and closed-loop electrolyte recycling. Full article

Iron-exchanged bentonites derived from a natural montmorillonite-rich clay (Taganskoe deposit, Kazakhstan) were prepared through a simple aqueous ion-exchange route using Fe(II) or Fe(III) inorganic salt precursors, yielding final Fe contents of ca. 5–7 wt.%, while preserving the smectite layered framework. A mild thermal treatment under air was applied to tune iron coordination without triggering major structural collapse. The resulting materials were characterized by ED-XRF, PXRD, FE-SEM/EDX, DLS/ζ-potential and DR UV–Vis–NIR spectroscopy, revealing predominantly exchanged Fe species with a limited fraction of surface iron-oxide clusters, whose contribution increases after activation. Structure–reactivity relationships were probed under mild conditions in liquid-phase ethyl acetate using dimethyl methylphosphonate (DMMP) and 2-chloroethyl ethyl sulfide (2-CEES) as organophosphorus and organosulfur hazardous chemicals and chemical warfare agent simulants, respectively. Fe(III)-bentonite enabled very fast DMMP removal (ca. 93% within 0.5 h) with a remarkable improved performance with respect to Fe(II)-bentonite and the pristine mineral clay. For 2-CEES, the presence of H₂O₂ markedly enhanced oxidation on Fe-containing clays, reaching quantitative abatement within 24 h (up to >90%), with strong retention of oxidized sulfur products by the clay matrix. These results highlight Fe-exchanged natural bentonites as robust, cheap and multifunctional adsorption/catalytic solids for decontamination and water-treatment applications. Full article

We designed a supervised machine learning framework to predict standard Gibbs free energies, ΔG°, of formal hydrogen atom transfer (f-HAT) for phenolic antioxidants across different radicals and media, enabling rapid and chemically interpretable screening. We curated a DFT dataset of 71 molecules (phenolic compounds and anthocyanidins), with 207 reaction sites, 10 radical reactive oxygen/sulfur species, and three environments (leading to a total of 6210 ΔG° values). The models amass 106 numerical RDKit descriptors, augmented with one-hot encodings of medium, site, radical, and structural class, and were evaluated through a leave-one-molecule-out protocol. Among the tested regression algorithms, the random forest regressor provides the best balance of accuracy and robustness with both R² test (≈0.94) and MAE (2.74 kcal mol⁻¹; RMSE (≈5.0 kcal mol⁻¹)), close to DFT chemical accuracy. The feature-importance analysis revealed that “electronic” and “experimental” (site/group) descriptors primarily drive predictions, with the radical’s maximum absolute partial charge being the most important descriptor in the prediction of a radical’s ΔG°. These results suggest that descriptor-driven RF (Random Forest) models can generalize across chemical space to provide interpretable ΔG° predictions, providing a path for chemists towards a scalable route to prioritize antioxidant candidates for broader molecular families. Full article

The reaction of the HS^•/S^•− radical (pKa ~3.4), generated selectively from H₂S by γ-irradiated N₂-flushed aqueous solutions at pH 5, with purine nucleosides (dG or dA), a 10-mer double-stranded oligodeoxynucleotide (ds-ODNs), and calf thymus (ct) DNA was investigated, under various experimental conditions. Concurrent quantification of the four purine 5′,8-cyclo-2′-deoxynucleosides (cPu) and two 8-oxo-7,8-dihydro-2′-deoxypurines (8-oxo-Pu) by LC-MS/MS analysis using isotopomeric internal standards was achieved. The formation of 8-oxo-Pu is several tens of times larger than cPu. Mechanistic schemes for the formation of the two product groups are proposed. Hydrogen atom abstraction from C5′–H by S^•− produces the cPu via cyclization of the C5′ radical onto C8, forming a new covalent bond, C5′–C8. The unexpected formation of 8-oxo-Pu should be mechanistically more complex. We propose that an S^•− (coupled with H⁺) adds to the base rings, followed by the elimination of HS⁻ to form the corresponding radical cation; subsequent reactions with H₂O and radical disproportionation with another S^•− lead to 8-oxo-Pu. A comparison of S^•− with the available literature data for HO^• reactivity towards ct-DNA in de-oxygenated aqueous solutions is also presented. Before the present findings, cPu lesions were attributed exclusively to HO^• reactivity toward ct-DNA. The reaction of the thiyl radical (HOCH₂CH₂S^•) with ct-DNA was also investigated, yielding results similar to those of S^•− obtained under comparable experimental conditions. Our results contributed to a better understanding of DNA damage induced by reactive sulfur species (RSS), particularly the formation of purine lesions and the relative abundance of cPu versus 8-oxo-Pu. Full article

The increasing scarcity of freshwater in mining regions of Chile has promoted the use of low-quality water as an alternative in flotation processes, significantly modifying their operating conditions. In particular, high salt concentrations and the presence of dissolved ionic species may interfere with the adsorption of collectors on chalcopyrite, thereby reducing its hydrophobicity. In this context, the present study analyzes the adsorption characteristics and the mechanistic role of selected representative ionic species on the chalcopyrite surface. To this end, simulations based on density functional theory (DFT) were employed to describe the interaction between the chalcopyrite (112) surface and Na⁺, Ca²⁺, Mg²⁺, and OH⁻ ions. After geometric convergence of the optimized structures was achieved, adsorption energies, charge redistribution based on Mulliken population analysis, and the final structural configurations were evaluated for each case. The results revealed clearly differentiated behaviors among the ionic species considered. The OH⁻ ion exhibited a localized and specific interaction with metal-centered sites. By contrast, Ca²⁺ and Mg²⁺ show stable adsorption near sulfur atoms, indicating a higher affinity that may lead to the occupation or blocking of active surface sites. Meanwhile, Na⁺ displays a weak interaction without inducing significant structural modifications. Overall, these findings provide an atomistic-level interpretation of how ionic species present in low-quality water can influence the surface reactivity of chalcopyrite under flotation operating conditions. Full article