1,2,4,5-Tetraoxane derivatives/hybrids as potent antimalarial endoperoxides: Chronological advancements, structure-activity relationship (SAR) studies and future perspectives.

Malaria is a life-threatening disease that affects tropical and subtropical regions worldwide. Various drugs were used to treat malaria, including artemisinin and derivatives, antibiotics (tetracycline, doxycycline), quinolines (chloroquine, amodiaquine), and folate antagonists (sulfadoxine and pyrimethamine). Since the malarial parasites developed drug resistance, there is a need to develop new chemical entities with high efficacy and low toxicity. In this context, 1,2,4,5-tetraoxanes emerged as an essential scaffold and have shown promising antimalarial activity. To improve activity and overcome resistance to various antimalarial drugs; 1,2,4,5-tetraoxanes were fused with various aryl/heteroaryl/alicyclic/spiro moieties (steroid-based 1,2,4,5-tetraoxanes, triazine-based 1,2,4,5-tetraoxanes, aminoquinoline-based 1,2,4,5-tetraoxanes, dispiro-based 1,2,4,5-tetraoxanes, piperidine-based 1,2,4,5-tetraoxanes and diaryl-based 1,2,4,5-tetraoxanes). The present review aims to focus on covering the relevant literature published during the past 30 years (1992-2022). We summarize the most significant in vitro, in vivo results and structure-activity relationship studies of 1,2,4,5-tetraoxane-based hybrids as antimalarial agents. The structural evolution of different hybrids can provide the framework for the future development of 1,2,4,5-tetraoxane-based hybrids to treat malaria.

Ferroptosis: underlying mechanisms and involvement in neurodegenerative diseases.

Ferroptosis, a mode of cell death that was recently identified in 2012, is driven by iron-dependent lipid peroxidation and distinct from other mechanisms of cell death such as autophagy and apoptosis. Ferroptosis has the unique features of disruptions in iron equilibrium, iron-induced lipid peroxidation, and the accumulation of glutamate-induced cellular toxicity. The regulation of ferroptosis mainly involves the iron, lipid, and amino acid metabolic pathways, which are controlled by system Xc-, voltage-dependent anion channels, p53 and other pathways. Neurodegenerative diseases involve gradual neuronal loss predominantly within the central nervous system and are categorized into both sporadic and rare hereditary disorders. These diseases result in the progressive decline of specific neuron populations and their interconnections. Recent investigations have revealed a strong correlation between the manifestation and progression of neurodegenerative diseases and ferroptosis. The pharmacological modulation of ferroptosis, whether by induction or inhibition, exhibits promising prospects for therapeutic interventions for these diseases. This review aims to examine the literature on ferroptosis and its implications in various neurodegenerative diseases. We hope to offer novel insights into the potential therapies targeting ferroptosis in central nervous system neurodegenerative diseases. However, there are still limitations of this review. First, despite our efforts to maintain objectivity during our analysis, this review does not cover all the studies on ferroptosis and neurodegenerative diseases. Second, cell death in neurodegenerative diseases is not solely caused by ferroptosis. Future research should focus on the interplay of different cell death mechanisms to better elucidate the specific disease pathogenesis.

FSP1-mediated ferroptosis in cancer: from mechanisms to therapeutic applications.

Ferroptosis is a new discovered regulated cell death triggered by the ferrous ion (Fe2+)-dependent accumulation of lipid peroxides associated with cancer and many other diseases. The mechanism of ferroptosis includes oxidation systems (such as enzymatic oxidation and free radical oxidation) and antioxidant systems (such as GSH/GPX4, CoQ10/FSP1, BH4/GCH1 and VKORC1L1/VK). Among them, ferroptosis suppressor protein 1 (FSP1), as a crucial regulatory factor in the antioxidant system, has shown a crucial role in ferroptosis. FSP1 has been well validated to ferroptosis in three ways, and a variety of intracellular factors and drug molecules can alleviate ferroptosis via FSP1, which has been demonstrated to alter the sensitivity and effectiveness of cancer therapies, including chemotherapy, radiotherapy, targeted therapy and immunotherapy. This review aims to provide important frameworks that, bring the regulation of FSP1 mediated ferroptosis into cancer therapies on the basis of existing studies.

Simultaneously Producing H2 and H2O2 by Photocatalytic Water Splitting: Recent Progress and Future.

The solar-driven overall water splitting (2H2O→2H2 + O2) is considered as one of the most promising strategies for reducing carbon emissions and meeting energy demands. However, due to the sluggish performance and high H2 cost, there is still a big gap for the current photocatalytic systems to meet the requirements for practical sustainable H2 production. Economic feasibility can be attained through simultaneously generating products of greater value than O2, such as hydrogen peroxide (H2O2, 2H2O→H2 + H2O2). Compared with overall water splitting, this approach is more kinetically feasible and generates more high-value products of H2 and H2O2. In several years, there has been an increasing surge in exploring the possibility and substantial progress has been achieved. In this review, a concise overview of the importance and underlying principles of PIWS is first provided. Next, the reported typical photocatalysts for PIWS are discussed, including commonly used semiconductors and cocatalysts, essential design features of these photocatalysts, and connections between their structures and activities, as well as the selected approaches for enhancing their stability. Then, the techniques used to quantify H2O2 and the operando characterization techniques that can be employed to gain a thorough understanding of the reaction mechanisms are summarized. Finally, the current existing challenges and the direction needing improvement are presented. This review aims to provide a thorough summary of the most recent research developments in PIWS and sets the stage for future advancements and discoveries in this emerging area.

Zinc-Based ROS Amplifiers Trigger Cancer Chemodynamic/Ion Interference Therapy Through Self-Cascade Catalysis.

Nanozyme-mediated chemodynamic therapy has emerged as a promising strategy due to its tumor specificity and controlled catalytic activity. However, the poor efficacy caused by low hydrogen peroxide (H2O2) levels in the tumor microenvironment (TME) poses challenges. Herein, an H2O2 self-supplying nanozyme is constructed through loading peroxide-like active platinum nanoparticles (Pt NPs) on zinc peroxide (ZnO2) (denoted as ZnO2@Pt). ZnO2 releases H2O2 in response to the acidic TME. Pt NPs catalyze the hydroxyl radical generation from H2O2 while reducing the mitigation of oxidative stress by glutathione, serving as a reactive oxygen (ROS) amplifier through self-cascade catalysis. In addition, Zn2+ released from ZnO2 interferes with tumor cell energy supply and metabolism, enabling ion interference therapy to synergize with chemodynamic therapy. In vitro studies demonstrate that ZnO2@Pt induces cellular oxidative stress injury through enhanced ROS generation and Zn2+ release, downregulating ATP and NAD+ levels. In vivo assessment of anticancer effects showed that ZnO2@Pt could generate ROS at tumor sites to induce apoptosis and downregulate energy supply pathways associated with glycolysis, resulting in an 89.7% reduction in tumor cell growth. This study presents a TME-responsive nanozyme capable of H2O2 self-supply and ion interference therapy, providing a paradigm for tumor-specific nanozyme design.

Bioluminescence - The Vibrant Glow of Nature and its Chemical Mechanisms.

Bioluminescence, the mesmerizing natural phenomenon where living organisms produce light through chemical reactions, has long captivated scientists and laypersons alike, offering a rich tapestry of insights into biological function, ecology, evolution as well as the underlying chemistry. This comprehensive introductory review systematically explores the phenomenon of bioluminescence, addressing its historical context, geographic dispersion, and ecological significance with a focus on their chemical mechanisms. Our examination begins with terrestrial bioluminescence, discussing organisms from different habitats. We analyze thefireflies of Central Europe's meadows and the fungi in the Atlantic rainforest of Brazil. Additionally, we inspect bioluminescent species in New Zealand, specifically river-dwelling snails and mosquito larvae found in Waitomo Caves. Our exploration concludes in the Siberian Steppes, highlighting the area's luminescent insects and annelids. Transitioning to the marine realm, the second part of this review examines marine bioluminescent organisms. We explore this phenomenon in deep-sea jellyfish and their role in the ecosystem. We then move to Toyama Bay, Japan, where seasonal bioluminescence of dinoflagellates and ostracods present a unique case study. We also delve into the bacterial world, discussing how bioluminescent bacteria contribute to symbiotic relationships. For each organism, we contextualize its bioluminescence, providing details about its discovery, ecological function, and geographical distribution. A special focus lies on the examination of the underlying chemical mechanisms that enables these biological light displays. Concluding this review, we present a series of practical bioluminescence and chemiluminescence experiments, providing a resource for educational demonstrations and student research projects. Our goal with this review is to provide a summary of bioluminescence across the diverse ecological contexts, contributing to the broader understanding of this unique biological phenomenon and its chemical mechanisms serving researchers new to the field, educators and students alike.

Molecular mechanisms of ferroptosis in cardiovascular disease.

Ferroptosis is a newly recognized type of regulated cell death that is characterized by the accumulation of iron and lipid peroxides in cells. Studies have shown that ferroptosis plays a significant role in the pathogenesis of various diseases, including cardiovascular diseases. In cardiovascular disease, ferroptosis is associated with ischemia-reperfusion injury, myocardial infarction, heart failure, and atherosclerosis. The molecular mechanisms underlying ferroptosis include the iron-dependent accumulation of lipid peroxidation products, glutathione depletion, and dysregulation of lipid metabolism, among others. This review aims to summarize the current knowledge of the molecular mechanisms of ferroptosis in cardiovascular disease and discuss the potential therapeutic strategies targeting ferroptosis as a treatment for cardiovascular disease.

Structure elucidation, absolute configuration, and biological evaluation of cyclic peroxides from the sponge Plakinastrella sp.

Two cyclic peroxides, plakortides V (1) and W (2) were purified from the organic extract of the sponge Plakinastrella sp. Their planar structures were established based on extensive NMR and MS analysis and the absolute configurations of the three stereogenic centers of the 1,2-dioxane moiety were determined to be 3R,4S,6S by comparative analysis of the 1H NMR spectral data of the R- or S-MTPA Mosher esters. Compounds 1 and 2 exhibited potent cytotoxic activity against LOX IMVI (melanoma), UO-31 (renal), and HL-60 (TB) (leukemia) cell lines in the NCI-60 cytotoxicity assay.

Photochemistry of Imidazole-2-carbaldehyde in Droplets as a Potential Source of H2O2 and Its Oxidation of SO2.

Hydrogen peroxide (H2O2) plays a crucial role as an oxidizing agent within the tropospheric environment, making a substantial contribution to sulfate formation in hydrated aerosols and cloud and fog droplets. Field observations show that high levels of H2O2 are often observed in heavy haze events and polluted air. However, the source of H2O2 remains unclear. Here, using the droplets formed in situ by the deliquescence of hygroscopic compounds under a high relative humidity (RH), the formation of H2O2 by the photochemistry of imidazole-2-carbaldehyde (2-IC) under ultraviolet irradiation was explored. The results indicate that 2-IC produces IM-C•-OH and IM-C•═O radicals via H transfer itself to its excited triplet state and generates H2O2 and organic peroxides in the presence of O2, which has an evident oxidizing effect on SO2, suggesting the potential involvement of this pathway in the formation of atmospheric sulfate. H2O2 formation is limited in acidic droplets or droplets containing ammonium ions, and no H2O2 is detected in droplets containing nitrate, whereas droplets containing citric acid have an obvious promotion effect on H2O2 formation. These findings provide valuable insights into the behaviors of atmospheric photosensitizers, the source of H2O2, and the formation of sulfate in atmospheric droplets.

Iron-Containing Seed Particles Enhance α-Pinene Secondary Organic Aerosol Mass Concentration and Dimer Formation.

Secondary organic aerosol (SOA) comprises the majority of submicron particles and is important for air pollution, health, and climate. When SOA mixes with inorganic particles containing transition metals (e.g., Fe), chemical reactions altering physicochemical properties can occur. Here, we study Fe's impact on the formation and chemical composition of SOA formed via dark α-pinene ozonolysis on either (NH4)2SO4 or Fe-containing (NH4)2SO4 seed particles and aged at varying relative humidities (RHs). Aerosol composition was determined using online extractive electrospray ionization mass spectrometry, providing high-resolution chemical and temporal identification of monomers and dimers in the SOA. At high RH, Fe's presence resulted in higher particulate SOA mass concentrations (117 ± 14 µg m-3) than those formed in its absence (70 ± 1 µg m-3). Enhanced mass is coupled with more dimers (C15-20's), attributed to Fenton-driven oligomerization reactions. Experiments with Fe3+-containing seeds showed similar chemical composition and enhanced SOA mass, suggesting a dark reduction pathway to form Fe2+ in the presence of SOA. Overall, Fe's presence at high RH lowers SOA volatility and enhances particulate organic mass and condensed phased reactions of higher volatility species that would normally not participate in SOA formation, which may be important when considering its formation in air quality and climate models.

Photooxidation-Initiated Aqueous-Phase Formation of Organic Peroxides: Delving into Formation Mechanisms.

Formation of highly oxygenated molecules (HOMs) such as organic peroxides (ROOR, ROOH, and H2O2) is known to degrade food and organic matter. Gas-phase unimolecular autoxidation and bimolecular RO2 + HO2/RO2 reactions are prominently renowned mechanisms associated with the formation of peroxides. However, the reaction pathways and conditions favoring the generation of peroxides in the aqueous phase need to be evaluated. Here, we identified bulk aqueous-phase ROOHs in varying organic precursors, including a laboratory model compound and monoterpene oxidation products. Our results show that formation of ROOHs is suppressed at enhanced oxidant concentrations but exhibits complex trends at elevated precursor concentrations. Furthermore, we observed an exponential increase in the yield of ROOHs when UV light with longer wavelengths was used in the experiment, comparing UVA, UVB, and UVC. Water-soluble organic compounds represent a significant fraction of ambient cloud-water components (up to 500 µM). Thus, the reaction pathways facilitating the formation of HOMs (i.e., ROOHs) during the aqueous-phase oxidation of water-soluble species add to the climate and health burden of atmospheric particulate matter.

Design and synthesis of visible light-activatable photocaged peroxides for optical control of ROS-mediated cellular signaling.

We designed and synthesized two novel photocaged peroxide compounds, N5TBHP and N6TBHP, featuring nitrogen-containing fused ring coumarin skeletons. Notably, a tetrahydroquinoline fused coumarin derivative, N6TBHP demonstrated significantly higher photocleavage efficiency under visible light at 455 nm compared to N5TBHP, which contains an indoline fused coumarin. This process effectively releases the oxidative stress inducer tert-butylhydroperoxide (TBHP). Additionally, N6TBHP exhibits high resistance to glutathione (GSH), and its UV spectral analysis suggests enhanced intracellular stability due to reduced reactivity with GSH through self-assembly. Furthermore, N6TBHP can release an optimal amount of TBHP into cells under visible light irradiation with minimal cell damage. These properties position N6TBHP as a promising tool for advancing research in intracellular redox signaling.

Salivary assessment of the immune/inflammatory responses and oxidative stress in older adults vaccinated with CoronaVac or ChadOx-1.

BACKGROUND: Although important information concerning COVID-19 vaccination is available, the effects of the CoronaVac and ChadOx-1 vaccines on immunity and the redox balance in the upper airway mucosa of the aged population are not fully understood. Therefore, the aim of this study was to investigate the impacts of two doses of the CoronaVac or ChadOx-1 vaccine on immune/inflammatory responses and oxidative stress in the airway mucosa of older adults. METHODS: Seventy-six older adults of both sexes, with a mean age of 75.1 ± 6.4 years, were separated according to vaccination status into the CoronaVac (n = 52) and ChadOx-1 (n = 24) groups. Saliva samples were collected before (pre) and 30 days after (post) the administration of the second dose of the CoronaVac or ChadOx-1 vaccine to assess the levels of antibodies (sIgA and IgG), antimicrobial peptides, cytokines, and oxidant/antioxidant agents. RESULTS: The immunogenicity in the ChadOx-1 group was 37.5% for sIgA and 25% for IgG, while that in the CoronaVac group was 18.9% for sIgA and 13.2% for IgG. Intergroup analysis revealed that (1) lower levels of IFN-α, IFN-γ, and IL-10 and a greater IFN-γ/IL-10 ratio, in addition to a greater IL-6/IL-10 ratio, were found in both the pre- and postvaccination periods, and (2) lower levels of total sIgA, IL-12p70, IL-17A, TNF-α, and the IL-12p70/IL-10 ratio, in addition to higher levels of specific sIgA for SARS-CoV-2 antigens and lysozyme, were observed only in the postvaccination period in the ChadOx-1 group than in the CoronaVac group. Intragroup analysis revealed (1) a significant increase in the salivary levels of total peroxides in the postvaccination period compared to those in the prevaccination period in both volunteer groups; (2) a decrease in the levels of lysozyme and the ratio between total antioxidant capacity (TAC) and total peroxides in the postvaccination period in the CoronaVac group compared with those in the prevaccination period; and (3) decreases in the TNF-α, IL-6, and IL-12p70 levels, and the IL-12p70/IL-10 ratio in the ChadoX-1 group, as well as a higher lactoferrin concentration in the postvaccination period than in the prevaccination period. Several positive and negative correlations between the parameters assessed here were found. CONCLUSIONS: In general, the ChadOx-1 group exhibited improvements in both immune/inflammatory responses and redox balance and greater immunogenicity than did the CoronaVac group.

Natural Peroxides from Plants: Historical Discovery, Biosynthesis, and Biological Activities.

Naturally occurring peroxides received great interest and attention from scientific research groups worldwide due to their structural diversity, versatile biological activities, and pharmaceutical properties. In the present review, we describe the historical discovery of natural peroxides from plants systematically and update the researchers with recently explored ones justifying their structural caterogrization and biological/pharmaceutical properties intensively. Till the end of 2023, 192 peroxy natural products from plants were documented herein for the first time implying most categories of natural scaffolds (e. g. terpenes, polyketides, phenolics and alkaloids). Numerically, the reported plants' peroxides have been classified into seventy-four hydro-peroxides, hundred seven endo-peroxides and eleven acyl-peroxides. Endo-peroxides (cyclic alkyl peroxides) are an important group due to their high variety of structural frameworks, and we have further divided them into "four-, five-, six and seven"-membered rings. Biosynthetically, a shedding light on the intricate mechanisms behind the formation of plant-derived peroxides are addressed as well.

Chemical Diversity, Pharmacology, Synthesis and Detection of Naturally Occurring Peroxides.

Natural occurring peroxides are interesting bioprospecting targets due to their molecular structural diversity and the wide range of pharmacological activities. In this systematic review, a total of 123 peroxide compounds were analysed from 99 published papers with the compounds distributed in 31 plants, 18 animals and 41 microorganisms living in land and water ecosystems. The peroxide moiety exists as both cyclic and acyclic entities and can include 1,2-dioxolanes, 1,2-dioxane rings and common secondary metabolites with a peroxo group. These peroxides possessed diverse bioactivities including anticancer, antimalarial, antimicrobial, anti-inflammatory, neuroprotective, adipogenic suppressor, antituberculosis, anti-melanogenic and anti-coagulant agents. Biosynthetic pathways and mechanisms of most endoperoxides have not been well established. Method development in peroxide detection has been a challenging task requiring multidisciplinary investigation and exploration on peroxy-containing secondary metabolites are necessary.

Mechanistic study of electroacupuncture preconditioning in alleviating myocardial ischemia-reperfusion injury in rats: involvement of mTOR/ROS signaling pathway to inhibit ferroptosis.

PURPOSE: The objective of this study was to investigate the mechanism of electroacupuncture pretreatment in reducing myocardial ischemia-reperfusion injury in rats. MATERIALS AND METHODS: The comparison of HR among the different groups did not yield statistically significant differences (p > 0.05). Additionally, the trend of HR change at different time points within each group was not statistically significant (p > 0.05). In contrast, the comparison of SBP among the different groups showed statistically significant differences (p < 0.05). Furthermore, the trend of SBP change at different time points within each group exhibited significant differences (p < 0.05). RESULTS: Compared to the Sham group, rats in the I/R group and EA control group showed a significant decrease in EF, FS, SOD, p-mTOR/mTOR, GPX4, and FTH1, and an increase in CK-MB, cTnI, LDH, iron, ROS, MDA, ACSL4, and NCOA4 (p < 0.05). Compared to EA control group, rats in the EA group exhibited a significant increase in EF, FS, SOD, p-mTOR/mTOR, GPX4, and FTH1, and a decrease in CK-MB, cTnI, LDH, iron, ROS, MDA, ACSL4, and NCOA4 (p < 0.05). Compared to the EA group, rats in the EA + RAP group showed a significant decrease in EF, FS, SOD, p-mTOR/mTOR, GPX4, and FTH1, and an increase in CK-MB, cTnI, LDH, iron, ROS, MDA, ACSL4, and NCOA4 (p < 0.05). CONCLUSIONS: Electroacupuncture preconditioning confers protective effects against myocardial ischemia-reperfusion injury in rats. Its mechanism may involve the activation of the mTOR/ROS signaling pathway by electroacupuncture to inhibit ferroptosis.

Effect of incorporation of calcium polyphosphate sub-microparticles in low-concentration bleaching gels on physical properties of dental enamel.

AIM: To evaluate the bleaching efficacy and effects on enamel properties of experimental gels with carbamide peroxide (CP; 10%) or hydrogen peroxide (HP; 6%) containing calcium polyphosphate sub-microparticles (CaPPs). METHODS: A total of 216 bovine tooth specimens were divided for microhardness and color analyses (n = 108) and block randomized into nine groups (n = 12): (G1) commercial CP (Whiteness Perfect, FGM; Brazil); (G2) experimental CP; (G3) CP-0.5%CaPPs; (G4) CP-1.5%CaPPs; (G5) commercial HP (Potenza Bianco, PHS; Brazil); (G6) experimental HP; (G7) HP-0.5%CaPPs; (G8) HP-1.5%CaPPs; (G9) artificial saliva. The gels' pH values were determined with a bench pH meter. Color (ΔE, ΔE00, ΔWID) and microhardness variation were evaluated before and after the therapy. Part of the specimens used for microhardness was submitted to the scanning electron microscopy (SEM) (n = 3) and energy-dispersive X-ray spectroscopy EDX (n = 3) analyses. Statistical analyses were performed in the R statistical software (α = 0.05). Linear mixed models for repeated measures in time were used to analyze microhardness and L* values. Generalized linear models were used to analyze the a*, b*, ΔE, ΔE00, and ΔWID, considering a group effect. The EDX data were analyzed using a one-way ANOVA with Tukey's test. RESULTS: The gels' pH remained over 6,0. All gels effectively bleached the specimens and did not differ significantly. When compared to the control group, the hardness was significantly lower in the G1, G2, G6, and G7 groups. The G3, G4, G5, and G8 groups did not differ significantly (p > 0.05). CONCLUSION: The incorporation of CaPPs in low-concentration whitening gels reduces its negative effects on microhardness without interfering with their bleaching efficacy.

A Recyclable Polypropylene Multilayer Film Maintaining the Quality and the Aroma of Coffee Pods during Their Shelf Life.

Films for coffee-pod packaging usually contain aluminium as an impermeable foil that is not recyclable and has to be discharged as waste. In this study, a recyclable polypropylene multilayer film is proposed as an alternative. The performance on the chemical composition of coffee was evaluated and compared to that of film containing aluminium (standard). The oxygen in the headspace, moisture, lipidic oxidation, and volatile organic compounds were studied in coffee pods during storage for 12 months at 25 and 40 °C. In addition, the acidity and acceptability of extracted coffee were evaluated. In the polypropylene-packaged pods, the percentage of oxygen during storage at 25 °C was lower than that in the standard. Moisture was not affected by the type of packaging materials. No differences were found between the peroxide values, except in pods stored for 3, 10, and 11 months at 25 °C, where they were even lower than the standard. Furans and pyrazines were the main volatile organic compounds detected. No differences were found in the pH and titratable acidity of the coffee brew either. All samples were well accepted by consumers without any perceived difference related to the packaging film. The polypropylene multilayer film is a sustainable recyclable material with high performance, in particular, against oxygen permeation.

A DFT and kinetic study: Is it possible to prepare epoxides without catalysts using the in-situ generated peroxy radicals or peroxides by one-step method?

DFT calculations and kinetic analysis have been employed to comprehensively explore the possibility to prepare epoxides by one-step method using the in-situ generated peroxy radicals or hydroperoxides as epoxidizing agents. Computational studies demonstrated that the selectivities for the reaction systems of O2 /R2/R1, O2 /CuH/R1, O2 /CuH/styrene, O2 /AcH/R1 were 68.2%, 69.6%, 100% and 93.3%, respectively. The in-situ generated peroxide radicals, such as HOO˙, CuOO˙ and AcOO˙, could react with R1 or styrene by attacking the CC double bond to form a CO bond and subsequently undergoing a cleavage of OO bond to yield epoxides. Peroxide radicals could abstract a hydrogen atom from methyl group on R1, forming unwanted by-products. It should be noted that the hydrogen atoms of HOO˙ is easy to be abstracted by CC double bond and simultaneously the oxygen atom is connected to the CH moiety to form an alkyl peroxy radical (Rad11), greatly limiting the selectivity. The comprehensive mechanistic studies provide a deep understanding on preparing epoxides by one-step method.

The Role of Ferroptosis in the Pathogenesis of Osteoarthritis.

Osteoarthritis (OA) is the most common type of arthritis. Its high prevalence, especially in the elderly, and its negative impact on physical function make it a leading cause of disability in the elderly. Joint pain as well joint stiffness are the common classic signs of OA. Chondrocyte death together with loss of articular cartilage integrity are the main pathologic changes in OA. Non-steroidal anti-inflammatory drugs (NSAIDs) and glucocorticoids are commonly used for the management of OA; still, their effectiveness is limited, and no therapeutic strategy is able to fully stop OA progression. Ferroptosis is a kind of cell death, distinct from apoptosis and necroptosis, caused by iron-dependent peroxidation of membrane phospholipids that terminates cell life by disintegrating all plasma membranes. It has been suggested that ferroptosis has a critical role in decreased viability of chondrocytes in OA, and here, we review recent findings regarding the pathologic pathways that lead to chondrocyte ferroptosis, and discuss the possible therapeutic utility of ferroptosis inhibition in OA.