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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 1 H 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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Ltd.)

We made structural modifications on the A-ring of camptothecin (CPT) by incorporating methyl substituents on positions 9 and 12. This allows conversion of the camptothecin-derivative to an endoperoxide (ENDO-CPT). The endoperoxide obtained this way thermally releases singlet oxygen, reverting back to the original 9,12-dimethylcamptothecin (DM-CPT) with a half-life of 1.4 hours at 37 °C. Endoperoxide modification yields a significant improvement in cytotoxicity against MDR-cell lines, compared to both CPT and DM-CPT. It appears that the simultaneous action of singlet oxygen and CPT is highly effective due to the targeting of P-glycoprotein by singlet oxygen.

L-Arginine (LA), a semi-essential amino acid in the human body, holds significant potential in cancer therapy due to its ability to generate nitric oxide (NO) continuously in the presence of inducible NO synthase (iNOS) or reactive oxygen species (ROS). However, the efficiency of NO production in tumor tissue is severely constrained by the hypoxic and H 2 O 2 -deficient tumor microenvironment (TME). To address this issue, we have developed calcium peroxide (CaO 2 ) nanoparticles capable of supplying O 2 /H 2 O 2 , which encapsulate and oxidize an LA-modified lipid bilayer to enable controlled localized NO generation in the presence of ROS, synergising with a ferroptosis inducer, RSL-3 (CPIR NPs). The synthesized nanoparticles were tested in vitro for their anticancer activity in 4T1 cells. To address challenges related to specificity and frequent dosing, we developed an in situ thermosensitive injectable hydrogel incorporating CPIR nanoparticles. Cross-linking at 60 °C creates a self-sufficient formulation, releasing NO/H 2 O 2 to combat tumor hypoxia. RSL-3 induces ferroptosis, contributing to a synergistic photothermal effect and eliminating tumor in vivo .

Bacterial biofilms represent a prominent biological barrier against physical and chemical attacks. Disturbing the anaerobic microenvironment within biofilms by co-delivery of oxygen appears as a promising strategy to enhance the activity of an antibiotic. Here, we report the effect of oxygen-producing calcium peroxide nanoparticles (CaO 2 NP) in combination with tobramycin sulfate (Tob). On Pseudomonas aeruginosa PAO1 biofilms in vitro, the additive effect of CaO 2 NP towards Tob activity enhanced biofilm eradication by 2 log compared to Tob alone. For natural biofilms grown in the oral cavity of human volunteers in situ, treatment by CaO 2 NP alone slightly increased the fraction of dead bacteria from 44% in various controls, including Tob alone, to 57%. However, the combination of CaO 2 NP with Tob further increased the fraction of dead bacteria to 69%. These data confirm the intrinsic antimicrobial and antibiotic-potentiating effect of CaO 2 NP also in a clinically relevant setting., (© 2024. The Author(s).)

Wound infection is a major factor affecting the speed and quality of wound healing. While hydrogen peroxide (H 2 O 2 ) is recognized for its antibacterial capacity and facilitation of wound healing, its administration requires careful dosage differentiation. Inappropriately matched dosages can protract the healing of infected wounds. Herein, a calcium peroxide-based hydrogel (CPO-Alg hydrogel) is fabricated to enable a biphasic tapered release of H 2 O 2 , ensuring robust initial antimicrobial activity followed by sustained promotion of cellular proliferation of wound healing. The design of the hydrogel allowed for the calcium peroxide nanoparticles (CPO NPs) being in two spatial niches within the gel framework. When applied to infectious wounds, CPO NPs with weak constraints are promptly released out of the gel, penetrating into infected regions to serve as antibacterial agents that eliminate bacteria and biofilms at high concentrations. Conversely, the entrapped CPO NPs structurally integrated into the gel remain confined, thus gradually degrading and allowing a mild release of H 2 O 2 through hydrolysis in a moist environment that contributes to the cell growth in the later stage. The CPO-Alg hydrogel represents an innovative and practical solution for the antimicrobial protection of chronic wounds, offering promising prospects for advancing wound healing., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

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., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

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., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

We report an endoperoxide compound (E5) which can deliver three therapeutic components by a thermal cycloreversion, namely, singlet oxygen, triplet oxygen and 3-methyl-N-phenyl-2-pyridone (P5), thus targeting multiple mechanisms for treating non-small cell lung cancer and idiopathic pulmonary fibrosis. In aqueous environment, E5 undergoes clean reaction to afford three therapeutic components with a half-life of 8.3 hours without the generation of other by-products, which not only achieves good cytotoxicity toward lung cancer cells and decreases the levels of hypoxia-inducible factor 1α (HIF-1α) protein, but also inhibits the transforming growth factor β1 (TGF-β1) induced fibrosis in vitro. In vivo experiments also demonstrated the efficacy of E5 in inhibiting tumor growth and relieving idiopathic pulmonary fibrosis, while exhibiting good biocompatibility. Many lines of evidence reveal the therapeutic efficacy of singlet oxygen and 3-methyl-N-phenyl-2-pyridone for these two lung diseases, and triplet oxygen could downregulate HIF-1α and relieve tumor hypoxia which is a critical issue in photodynamic therapy (PDT). Unlike other combination therapies, in which multiple therapeutic agents are given in independent formulations, our work demonstrates single molecule endoperoxide prodrugs could be developed as new platforms for treatment of cancers and related diseases., (© 2024 Wiley-VCH GmbH.)

Calcium ions (Ca 2+ ) participate in the regulation of cellular apoptosis as a second messenger. Calcium overload, which refers to the abnormal elevation of intracellular Ca 2+ concentration, is a factor that can lead to cell death. Here, based on the unique biological effects of Ca 2+ , hollow mesoporous calcium peroxide nanoparticles (HMCPN) were developed by a facile hydrolysis-precipitation method for drug-free tumor calcicoptosis therapy. The average pore size of the optimized HMCPN17 is 6.4 nm, and the surface area is 81.3 m 2 /g, which enables HMCPN17 with high drug loading capability. The Ca 2+ release from HMCPN17 is much faster at pH 6.8 than that at pH 7.4, which can be ascribed to the acid-triggered conversion of HMCPN17 to Ca 2+ and H 2 O 2 , indicating a pH-responsive decomposition behavior of HMCPN17. The high drug loading contents of doxorubicin (DOX) and/or sorafenib (SFN) indicate that HMCPN17 can be employed as a generic drug delivery system (DDS). The in vitro and in vivo results reinforce the high calcicoptosis therapeutic efficacy of tumors by our HMCPN17 without drug loading, which can be attributed to the efficient accumulation in tumors and the ability of H 2 O 2 and Ca 2+ production at acidic TME. Our HMCPN17 has broad application prospect for construction of multi-drug-loaded composite nanomaterials with diversified functions for the treatment of tumors. STATEMENT OF SIGNIFICANCE: The combination of hollow mesoporous nanomaterials and calcium peroxide nanoparticles has a wide range of applications in the synergistic treatment of tumors. In this study, hollow mesoporous calcium peroxide nanoparticles (HMCPN) were developed based on a simple hydrolysis-precipitation method for tumor calcicoptosis therapy without drug loading. The high drug loading contents of DOX and/or SFN indicate that our HMCPN can serve as a generic DDS. The experimental results demonstrated the high calcicoptosis therapeutic efficacy of HMCPN on tumors even without drug loading., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

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., (© 2024 Wiley Periodicals LLC.)

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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Oxygen (O 2 )-delivering tissue substitutes have shown tremendous potential for enhancing tissue regeneration, maturation, and healing. As O 2 is both a metabolite and powerful signaling molecule, providing controlled delivery is crucial for optimizing its beneficial effects in the treatment of critical-sized injuries. Here, we report the design and fabrication of 3D-printed, biodegradable, O 2 -generating bone scaffold comprising calcium peroxide (CPO) that once hydrolytically activated, provides long-term generation of oxygen at a controlled, concentration-dependent manner, and polycaprolactone (PCL), a hydrophobic polymer that regulate the interaction of CPO with water, preventing burst release of O 2 at early time points. When anoxic conditions were simulated in vitro, CPO-PCL scaffolds maintained the survival and proliferation of human adipose-derived stem/stromal cells (hASCs) relative to PCL-only controls. We assessed the in vivo osteogenic efficacy of hASC-seeded CPO-PCL scaffolds implanted in a non-healing critical-sized 4-mm calvarial defects in nude mice for 8 weeks. Even without exogenous osteoinductive factors, CPO-PCL scaffolds demonstrated increased new bone volume compared to PCL-only scaffolds as verified by both microcomputed tomography analysis and histological assessments. Lastly, we employed a quantitative 3D lightsheet microscopy platform to determine that O 2 -generating scaffolds had similar vascular volumes with slightly higher presence of CD31 hi Emcn hi pro-osteogenic, type H vessels and increased number of Osterix + skeletal progenitor cells relative to PCL-only scaffolds. In summary, 3D-printed O 2 generating CPO-PCL scaffolds with tunable O 2 release rates provide a facile, customizable strategy for effectively treating, craniofacial bone defects. STATEMENT OF SIGNIFICANCE: Oxygen(O 2 )-delivering bone substitutes show promise in defect repair applications by supplying O 2 to the cells within or around the graft, improving cell survivability and enhancing bone matrix mineralization. A novel O 2 -generating bone scaffold has been 3D printed for the first-time which ensures patient and defect specificity. 3D printed calcium peroxide-polycaprolactone (CPO-PCL) bone scaffold provides uninterrupted O 2 supply for 22 days allowing cell survival in deprived O 2 and nutrient conditions. For the first time, O 2 -driven bone regenerative environment in mice calvaria has been captured by light-sheet imaging which illuminates abundance of Osterix+ cells, angiogenesis at a single cell resolution indicating active site of bone remodeling and growth in the presence of O 2 ., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Wound healing represents a complex biological process crucial for tissue repair and regeneration. In recent years, biomaterial-based scaffolds loaded with bioactive compounds have emerged as promising therapeutic strategies to accelerate wound healing. In this study, we investigated the properties and wound healing effects of cryogels loaded with calcium peroxide (CP) and berberine (BB). The cryogels were synthesized through a cryogenic freezing technique and displayed pore diameters of 83 ± 39 μm, with porosity exceeding 90%. Following 20 days of degradation, the percentage of remaining weight for GPC and GPC-CP-BB cryogels was determined to be 12.42 ± 2.45% and 10.78 ± 2.08%, respectively. Moreover, the swelling ratios after 3 minutes for GPC and GPC-CP-BB were found to be 22.10 ± 0.05 and 21.00 ± 0.07, respectively. In vitro investigations demonstrated the cytocompatibility of the cryogels, with sufficient adhesion and proliferation of fibroblast (NIH-3T3) cells observed on the scaffolds, along with their hemocompatibility. Furthermore, the cryogels exhibited sustained release kinetics of both calcium peroxide and berberine, ensuring prolonged therapeutic effects at the wound site. In vivo assessment using a rat model of full-thickness skin wounds demonstrated accelerated wound closure rates in animals treated with the GPC-CP-BB scaffold compared to controls. Histological analysis revealed enhanced granulation tissue formation, re-epithelialization, and collagen deposition in the GPC-CP-BB group. Overall, our findings suggest that the scaffold loaded with CP and BB holds great promise as a therapeutic approach for promoting wound healing. Its multifaceted properties offer a multifunctional platform for localized delivery of therapeutic agents while providing mechanical support and maintaining a favorable microenvironment for tissue regeneration.

The coexistence of antibiotic resistance genes (ARGs) and antibiotic-resistant bacteria (ARB) in the environment poses a potential threat to public health. In our study, we have developed a novel advanced oxidation process for simultaneously removing ARGs and ARB by two types of iron and nitrogen-doped biochar derived from rice straw (FeN-RBC) and sludge (FeN-SBC). All viable ARB (approximately 10 8 CFU mL -1 ) was inactivated in the FeN-RBC/ peroxymonosulfate (PMS) system within 40 min and did not regrow after 48 h even in real water samples. Flow cytometry identified 96.7 % of dead cells in the FeN-RBC/PMS system, which verified the complete inactivation of ARB. Thorough disinfection of ARB was associated with the disruption of cell membranes and intracellular enzymes related to the antioxidant system. Whereas live bacteria (approximately 200 CFU mL -1 ) remained after FeN-SBC/PMS treatment. Intracellular and extracellular ARGs (tetA and tetB) were efficiently degraded in the FeN-RBC/PMS system. The production of active species, primarily •OH, SO 4 •- and Fe (IV), as well as electron transfer, were essential to the effective disinfection of FeN-RBC/PMS. In comparison with FeN-SBC, the better catalytic performance of FeN-RBC was mainly ascribed to its higher amount of pyridine-N and Fe 0 , and more reactive active sites (such as CO group and Fe-N sites). Density functional theory calculations indicated the greater adsorption energy and Bader charge, more stable Fe-O bond, more easily broken OO bond in FeN-RBC/PMS, which demonstrated the stronger electron transfer capacity between FeN-RBC and PMS. To encapsulate, our study provided an efficient and dependable method for the simultaneous elimination of ARGs and ARB in water., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Nanotheranostic platforms, which can respond to tumor microenvironments (TME, such as low pH and hypoxia), are immensely appealing for photodynamic therapy (PDT). However, hypoxia in solid tumors harms the treatment outcome of PDT which depends on oxygen molecules to generate cytotoxic singlet oxygen ( 1 O 2 ). Herein, we report the design of TME-responsive smart nanotheranostic platform (DOX/ZnO 2 @Zr-Ce6/Pt/PEG) which can generate endogenously hydrogen peroxide (H 2 O 2 ) and oxygen (O 2 ) to alleviate hypoxia for improving photodynamic-chemo combination therapy of tumors. DOX/ZnO 2 @Zr-Ce6/Pt/PEG nanocomposite was prepared by the synthesis of ZnO 2 nanoparticles, in-situ assembly of Zr-Ce6 as typical metal-organic framework (MOF) on ZnO 2 surface, in-situ reduction of Pt nanozymes, amphiphilic lipids surface coating and then doxorubicin (DOX) loading. DOX/ZnO 2 @Zr-Ce6/Pt/PEG nanocomposite exhibits average sizes of ∼78 nm and possesses a good loading capacity (48.8 %) for DOX. When DOX/ZnO 2 @Zr-Ce6/Pt/PEG dispersions are intratumorally injected into mice, the weak acidic TEM induces the decomposition of ZnO 2 core to generate endogenously H 2 O 2 , then Pt nanozymes catalyze H 2 O 2 to produce O 2 for alleviating tumor hypoxia. Upon laser (630 nm) irradiation, the Zr-Ce6 component in DOX/ZnO 2 @Zr-Ce6/Pt/PEG can produce cytotoxic 1 O 2 , and 1 O 2 generation rate can be enhanced by 2.94 times due to the cascaded generation of endogenous H 2 O 2 /O 2 . Furthermore, the generated O 2 can suppress the expression of hypoxia-inducible factor α, and further enable tumor cells to become more sensitive to chemotherapy, thereby leading to an increased effectiveness of chemotherapy treatment. The photodynamic-chemo combination therapy from DOX/ZnO 2 @Zr-Ce6/Pt/PEG nanoplatform exhibits remarkable tumor growth inhibition compared to chemotherapy or PDT. Thus, the present study is a good demonstration of a TME-responsive nanoplatform in a multimodal approach for cancer therapy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Aim: This study compared the effectiveness of several techniques in restoring compromised bonding to recently bleached enamel., Methods: Seventy-five healthy bovine incisors were divided into five groups (n = 15). Fifteen teeth (Group 1) remained intact, whereas 60 (Groups 2 to 5) underwent at-home bleaching with 16% carbamide peroxide. The bonding procedures were as follows: Group 1: Bonding of resin composite to unbleached enamel; Group 2: Bonding immediately after bleaching; Group 3: Application of a 10% sodium ascorbate solution for 10 min before bonding; Group 4: Enamel removal to the depth of 0.5 mm; and Group 5: Increased curing time of the bonding agent to 80 instead of 20 s. After 24 h, the specimens were subjected to micro-shear testing, and the failure mode was determined., Results: ANOVA revealed a significant difference in bond strength among the groups (P < 0.001). The mean bond strength was significantly lower in group 2 than in other groups (P < 0.05), which showed comparable bond strength to each other (P > 0.05). Adhesive failure was the most predominant failure type in all groups. The mixed failure occurred with a frequency of 26.7% in groups 3 and 5. The Fisher's exact test revealed a significant difference in failure modes among the groups (P = 0.047)., Conclusions: The three experimental procedures used in this study, including the application of 10% sodium ascorbate before bonding, enamel removal to the depth of 0.5 mm, and increasing the curing time of the bonding agent to 80 s, were effective in restoring the compromised bonding to recently bleached enamel., (© 2024. The Author(s).)

Bacterial infection and tissue hypoxia always prevent wound healing, so multifunctional platforms with antimicrobial and oxygen-supplying functions were developed. However, they face many difficulties such as complex preparation and low oxygen release. To address this challenge, a copper peroxide loaded gelatin/oxide dextran hydrogel (CGO) was prepared. Surprisingly, CGO hydrogel as a wound dressing not only had good biocompatibility, injectivity, and mechanical properties, but also exhibited mild photothermal properties, temperature responsiveness, and pH responsiveness. After being applied to wounds infected with bacteria, CGO hydrogel released copper peroxide under near-infrared laser irradiation, which produced copper ions and hydrogen peroxide, combined with PTT to kill bacteria. After the bacteria were cleared from the wound and the pH of the wound was changed to be acidic, CGO hydrogel released copper peroxide via pH response. Copper ions and oxygen produced from copper peroxide accelerated wound healing by promoting angiogenesis. The multi-responsive and multi-mode treatment platform provided a potential strategy for treating bacteria-infected wounds., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: To evaluate the effectiveness of desensitizing toothpastes in reducing post-bleaching tooth sensitivity., Materials and Methods: A systematic review of randomized clinical trials was conducted based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist. Electronic searches were conducted in the PubMed/MEDLINE, Scopus, Web of Science, The Cochrane Library and Embase databases, using the following terms: (dentifrices OR toothpaste) AND (sensitive OR sensitivity OR dental sensitivity) AND (dental bleaching OR tooth bleaching OR dental whitening OR tooth whitening)., Results: Five studies involving 387 individuals undergoing in-office or at-home teeth bleaching were reviewed. Desensitizing toothpastes reduced sensitivity effectively after home bleaching with 22% carbamide peroxide and single-session in-office bleaching with 35% hydrogen peroxide. However, they were ineffective for home bleaching with 16% carbamide peroxide and in-office bleaching across two sessions with 35% or 38% hydrogen peroxide., Conclusion: Desensitizing toothpastes are effective for home bleaching with high concentration carbamide peroxide and single-session in-office bleaching with highly concentrated hydrogen peroxide, but ineffective for home bleaching with low concentration carbamide peroxide and two-session in-office bleaching with concentrated hydrogen peroxide., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The widespread use of antibiotics often increases bacterial resistance. Herein, we reported a silver peroxide-incorporated carbon dots (defined as Ag 2 O 2 -CDs) with high photothermal conversion efficiency via in situ oxidation process. The prepared Ag 2 O 2 -CDs exhibited ultra-small size of 2.0 nm and hybrid phase structure. Meanwhile, the Ag 2 O 2 -CDs were of a similar optical performance comparing with traditional carbon dots (CDs). Importantly, the incorporation of Ag 2 O 2 into CDs significantly enhanced photothermal conversion efficiency from 3.8% to 28.5%. By combining silver ion toxicity and photothermal ablation, the Ag 2 O 2 -CDs were capable of destroying gram-positive and gram-negative bacterium effectively. These findings demonstrated that the Ag 2 O 2 -CDs could be served as a potential antibacterial agent for clinical applications., (Creative Commons Attribution license.)

In response to the spread of artemisinin (ART) resistance, ART-based hybrid drugs were developed, and their activity profile was characterized against drug-sensitive and drug-resistant Plasmodium falciparum parasites. Two hybrids were found to display parasite growth reduction, stage-specificity, speed of activity, additivity of activity in drug combinations, and stability in hepatic microsomes of similar levels to those displayed by dihydroartemisinin (DHA). Conversely, the rate of chemical homolysis of the peroxide bonds is slower in hybrids than in DHA. From a mechanistic perspective, heme plays a central role in the chemical homolysis of peroxide, inhibiting heme detoxification and disrupting parasite heme redox homeostasis. The hybrid exhibiting slow homolysis of peroxide bonds was more potent in reducing the viability of ART-resistant parasites in a ring-stage survival assay than the hybrid exhibiting fast homolysis. However, both hybrids showed limited activity against ART-induced quiescent parasites in the quiescent-stage survival assay. Our findings are consistent with previous results showing that slow homolysis of peroxide-containing drugs may retain activity against proliferating ART-resistant parasites. However, our data suggest that this property does not overcome the limited activity of peroxides in killing non-proliferating parasites in a quiescent state., Competing Interests: The authors declare no conflict of interest.

Background: The discovery of artemisinin, an endoperoxide, encouraged the scientific community to explore endoperoxides as potential anti-parasitic molecules. Although artemisinin derivatives are rapidly evolving as potent anti-malarials, their potential as anti-leishmanials is emerging gradually. The treatment of leishmaniasis, a group of neglected tropical diseases is handicapped by lack of effective vaccines, drug toxicities and drug resistance. The weak antioxidant defense mechanism of the Leishmania parasites due to lack of catalase and a selenium dependent glutathione peroxidase system makes them vulnerable to oxidative stress, and this has been successful exploited by endoperoxides., Purpose: The study aimed to review the available literature on the anti-leishmanial efficacy of natural endoperoxides with a view to achieve insights into their mode of actions., Methods: We reviewed more around 110 research and review articles restricted to the English language, sourced from electronic bibliographic databases including PubMed, Google, Web of Science, Google scholar etc. RESULTS: Natural endoperoxides could potentially augment the anti-leishmanial drug library, with artemisinin and ascaridole emerging as potential anti-leishmanial agents. Due to higher reactivity of the cyclic peroxide moiety, and exploiting the compromised antioxidant defense of Leishmania, endoperoxides like artemisinin and ascaridole potentiate their leishmanicidal efficacy by creating a redox imbalance. Furthermore, these molecules minimally impair oxidative phosphorylation; instead inhibit glycolytic functions, culminating in depolarization of the mitochondrial membrane and depletion of ATP. Additionally, the carbon-centered free radicals generated from endoperoxides, participate in chain reactions that can generate even more reactive organic radicals that are toxic to macromolecules, including lipids, proteins and DNA, leading to cell cycle arrest and apoptosis of Leishmania parasites. However, the precise target(s) of the toxic free radicals remains open-ended., Conclusion: In this overview, the spectrum of natural endoperoxide molecules as major anti-leishmanials and their mechanism of action has been delineated. In view of the substantial evidence that natural endoperoxides (e.g., artemisinin, ascaridole) exert a noxious effect on different species of Leishmania, identification and characterization of other natural endoperoxides is a promising therapeutic option worthy of further pharmacological consideration., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier GmbH.)

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, ΔE 00 , ΔWI D ) 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, ΔE 00 , and ΔWI D, 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., (© 2023. The Author(s), under exclusive licence to The Society of The Nippon Dental University.)

A chemical investigation of the dichloromethane extract from the Xisha sponge Diacarnus sp. revealed seven undescribed norterpene cyclic peroxides, named diacarperoxides T-Z, and five unreported related norterpenes, named diacarnoids E-I, and eleven previously reported compounds. The structures of these isolated compounds, including their absolute configurations, were elucidated based on extensive spectroscopic analyses, electronic circular dichroism (ECD) calculations, Snatzke's method, [Rh 2 (OCOCF 3 ) 4 ]-induced ECD spectra, and modified Mosher's method. Bioassays were performed to assess the antibacterial activity against six pathogenic bacteria, cytotoxicities toward three cancer cell lines, and antimalarial activity against Plasmodium parasites. Most of the cyclic peroxides exhibited substantial antibacterial activity (MIC 1-8 μg/mL). Diacarperoxide W and nuapapuin A showed substantial antimalarial activity with IC 50 values of 0.98 and 2.83 μM. Moreover, many compounds exhibited <50% cell survival rates, and IC 50 values of 0.22-6.33 μM. The apoptosis assay showed that nuapapuin A induced cancer cell apoptosis in a dose-dependent manner., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The emergence of nanomotor provides an innovative concept for tumor treatment strategies. Conventional chemotherapeutic agents for tumors exit various therapeutic constraints due to the unique microenvironment of the tumor itself. Calcium overload, the aberrant accumulation of free calcium ions in the cytoplasm, is a well-recognized contributor to damage and even cell death in numerous cell types. Such undesired destructive processes can be a novel means applicable to cancer ion interference therapy. Herein, the chemotherapeutic drug doxorubicin (DOX) and calcium peroxide as the driving force into nanomotors through a facile and understandable experimental scheme are successfully assembled. The modification of nucleic acid aptamer and NIR-II fluorescent molecules on its surface simultaneously strengthens both the active targeting and imaging capability of tumor loci. Therefore, by a comprehensive assessment of nanomotors both in vitro and in vivo experiments, CaO 2 /DOX@HPS-IR-1061-AS1411 demonstrates superior killing effects on tumor cells, and the intracellular reactive oxygen species produced by nanomotors is verified by molecular biology experiments to induce apoptosis of tumor cells and further achieve tumor therapeutic effects., (© 2024 Wiley‐VCH GmbH.)

Nonhealing diabetic wounds are predominantly attributed to the inhibition of angiogenesis, re-epithelialization, and extracellular matrix (ECM) synthesis caused by hypoxia. Although oxygen therapy has demonstrated efficacy in promoting healing, its therapeutic impact remains suboptimal due to unsustainable oxygenation. Here, this work proposes an oxygen-releasing hydrogel patch embedded with polyethylene glycol-modified calcium peroxide microparticles, which sustainably releases oxygen for 7 days without requiring any supplementary conditions. The released oxygen effectively promotes cell migration and angiogenesis under hypoxic conditions as validated in vitro. The in vivo tests in diabetic mice models show that the sustainably released oxygen significantly facilitates the synthesis of ECM, induces angiogenesis, and decreases the expression of inflammatory cytokines, achieving a diabetic wound healing rate of 84.2% on day 7, outperforming the existing oxygen-releasing approaches. Moreover, the proposed hydrogel patch is designed with porous, soft, antibacterial, biodegradable, and storage stability for 15 days. The proposed hydrogel patch is expected to be promising in clinics treating diabetic wounds., (© 2024 Wiley‐VCH GmbH.)

Ten ergostane-type steroids, including seven undescribed ones named spectasteroids A-G, were obtained from Aspergillus spectabilis. Their structures and absolute configurations were determined based on HRESIMS, NMR, ECD calculations, and single-crystal X-ray diffraction analyses. Structurally, spectasteroid A was a unique example of aromatic ergostane-type steroid that featured a rare peroxide ring moiety; spectasteroid B contained a rare oxetane ring system formed between C-9 and C-14; and spectasteroid C was an unusual 3,4-seco-ergostane steroid with an extra lactone ring between C-3 and C-9. Spectasteroids F and G specifically showed inhibitory effects against concanavalin A-induced T lymphocyte proliferation and lipopolysaccharide-induced B lymphocyte proliferation, with IC 50 values ranging from 2.33 to 4.22 μM. Spectasteroid F also showed excellent antimultidrug resistance activity, which remarkable enhanced the inhibitory activity of PTX on the colony formation of SW620/Ad300 cells., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Of the most common, hypoxia, overexpressed glutathione (GSH), and insufficient H 2 O 2 concentration in the tumor microenvironment (TME) are the main barriers to the advancment of reactive oxygen species (ROS) mediated Xdynamic therapies (X = photo, chemodynamic, chemo). Maximizing Fenton catalytic efficiency is crucial in chemodynamic therapy (CDT), yet endogenous H 2 O 2 levels are not sufficient to attain better anticancer efficacy. Specifically, there is a need to amplify Fenton reactivity within tumors, leveraging the unique attributes of the TME. Herein, for the first time, we design Ru x Cu 1- x O 2 -Ce6/CPT (RCpCCPT) anticancer nanoagent for TME-mediated synergistic therapy based on heterogeneous Ru-Cu peroxide nanodots (Ru x Cu 1- x O 2 NDs) and chlorine e6 (Ce6), loaded with ROS-responsive thioketal (TK) linked-camptothecin (CPT). The Ru-Cu peroxide NDs (RCp NDs, x = 0.50) possess the highest oxygen vacancy (O V ) density, which grants them the potential to form massive Lewis's acid sites for peroxide adsorption, while the dispersibility and targetability of the NDs were improved via surface modification using hyaluronic acid (HA). In TME, RCpCCPT degrades, releasing H 2 O 2 , Ru 2+/3+ , and Cu +/2+ ions, which cooperatively facilitate hydroxyl radical (•OH) formation and deactivate antioxidant GSH enzymes through a cocatalytic loop, resulting in excellent tumor therapeutic efficacy. Furthermore, when combined with laser treatment, RCpCCPT produces singlet oxygen ( 1 O 2 ) for PDT, which induces cell apoptosis at tumor sites. Following ROS generation, the TK linkage is disrupted, releasing up to 92% of the CPT within 48 h. In vitro investigations showed that laser-treated RCpCCPT caused 81.5% cell death from PDT/CDT and chemotherapy (CT). RCpCCPT in cancer cells produces red-blue emission in images of cells taking them in, which allows for fluorescence image-guided Xdynamic treatment. The overall results show that RCp NDs and RCpCCPT are more biocompatible and have excellent Xdynamic therapeutic effectiveness in vitro and in vivo.

In this work, we investigated the oxidative stress-related biochemical alterations in red blood cells (RBCs) and their membranes with the use of spectroscopic techniques. We aimed to show their great advantage for the in situ detection of lipid classes and secondary structures of proteins without the need for their extraction in the cellular environment. The exposition of the cells to peroxides, t-butyl hydroperoxide (tBOOH) or hydrogen peroxide (H 2 O 2 ) led to different degradation processes encompassing the changes in the composition of membranes and structural modifications of hemoglobin (Hb). Our results indicated that tBOOH is generally a stronger oxidizing agent than H 2 O 2 and this observation was congruent with the activity of superoxide and glutathione peroxidase. ATR-FTIR and Raman spectroscopies of membranes revealed that tBOOH caused primarily the partial loss and peroxidation of the lipids resulting in loss of the integrity of membranes. In turn, both peroxides induced several kinds of damage in the protein layer, including the partial decrease of their content and irreversible aggregation of spectrin, ankyrin, and membrane-bound globin. These changes were especially pronounced on the membrane surface where stress conditions induced the formation of β-sheets and intramolecular aggregates, particularly for tBOOH. Interestingly, nano-FTIR spectroscopy revealed the lipid peroxidative damage on the membrane surface in both cases. As far as hemoglobin was concerned, tBOOH and H 2 O 2 caused the increase of the oxyhemoglobin species and conformational alterations of its polypeptide chain into β-sheets. Our findings confirm that applied spectroscopies effectively track the oxidative changes occurring in the structural components of red blood cells and the simplicity of conducting measurements and sample preparation can be readily applied to pharmacological and clinical studies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The treatment of chronic wounds involves precise requirements and complex challenges, as the healing process cannot go beyond the inflammatory phase, therefore increasing the healing time and implying a higher risk of opportunistic infection. Following a better understanding of the healing process, oxygen supply has been validated as a therapeutic approach to improve and speed up wound healing. Moreover, the local implications of antimicrobial agents (such as silver-based nano-compounds) significantly support the normal healing process, by combating bacterial contamination and colonization. In this study, silver (S) and tannylated calcium peroxide (CaO 2 @TA) nanoparticles were obtained by adapted microfluidic and precipitation synthesis methods, respectively. After complementary physicochemical evaluation, both types of nanoparticles were loaded in (Alg) alginate-based gels that were further evaluated as possible dressings for wound healing. The obtained composites showed a porous structure and uniform distribution of nanoparticles through the polymeric matrix (evidenced by spectrophotometric analysis and electron microscopy studies), together with a good swelling capacity. The as-proposed gel dressings exhibited a constant and suitable concentration of released oxygen, as shown for up to eight hours (UV-Vis investigation). The biofilm modulation data indicated a synergistic antimicrobial effect between silver and tannylated calcium peroxide nanoparticles, with a prominent inhibitory action against the Gram-positive bacterial biofilm after 48 h. Beneficial effects in the human keratinocytes cultured in contact with the obtained materials were demonstrated by the performed tests, such as MTT, LDH, and NO.

Purpose: To evaluate how fluoride- or chitosan-based toothpaste used during at-home bleaching affects enamel roughness, tooth color, and staining susceptibility., Methods: Bovine enamel blocks were submitted to a 14-day cycling regime considering a factorial design (bleaching agent x toothpaste, 2 x 3), with n=10: (1) bleaching with 16% carbamide peroxide (CP) or 6% hydrogen peroxide (HP), and (2) daily exposure of a fluoride (1,450 ppm F-NaF) toothpaste (FT), chitosan-based toothpaste (CBT), or distilled water (control). Then, 24 hours after the last day of bleaching procedure the samples were exposed to a coffee solution. Color (ΔEab, ΔE₀₀, L*, a*, b*) and roughness (Ra, µm) analyses were performed to compare the samples initially (baseline), after bleaching, and after coffee staining. The results were evaluated by linear models for repeated measures (L*, a*, b*, and Ra), 2-way ANOVA (ΔEab, ΔE₀₀) and Tukey's test (α= 0.05)., Results: After the at-home bleaching procedure (toothpaste vs. time, P< 0.0001), the toothpaste groups presented a statistically lower Ra than the control (CBT 0.05). After coffee exposure, CBT presented lower ΔEab and ΔE₀₀ values in the HP groups (toothpaste, P< 0.0001), and lower b* and a* values in the CP groups (toothpaste vs. time, P= 0.004)., Clinical Significance: Fluoride or chitosan delivered by toothpaste can reduce surface alterations of the enamel during at-home bleaching, without affecting bleaching efficacy., Competing Interests: The authors declared no conflict of interest. This study was funded in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior ‑ Brasil (CAPES), Funding Code 001., (Copyright©American Journal of Dentistry.)

Objective: To investigate the effect of tooth whitening on biomechanical properties of vacuum-formed retainers (VFRs)., Methods: Using a split-mouth, randomised controlled trial design, thirty participants were randomly allocated to receive whitening on either the upper or the lower arch, using 10 % carbamide peroxide for two weeks. Biomechanical properties such as hardness, tensile strength, and surface roughness were assessed two weeks after whitening was completed., Results: Tensile strength of the whitening arch (mean ± SD: 40.93 ± 3.96 MPa) was significantly lower than that of the control (47.40 ± 5.03 MPa) (difference 6.47 MPa, 95 % CI 4.51 - 8.42, p < 0.001). Hardness and internal roughness of the whitening arch (VHN = 14.63 ± 2.29 N/mm 2 and Ra = 1.33 ± 0.35 µm, respectively) were significantly greater than those of the control (12.22 ± 1.86 N/mm 2 and 0.96 ± 0.29 µm, respectively) (differences 2.41 N/mm 2 , 95 % CI 1.56 - 3.25, p < 0.001 and 0.37 µm, 95 % CI 0.23 - 0.51, p < 0.001, respectively). The whitening arch showed greater tooth colour change (ΔE = 6.00 ± 3.32) than the control (ΔE = 2.50 ± 1.70) (difference = 3.50, 95 % CI 2.43 - 4.56, p < 0.001)., Conclusions: Based on this short-term study, marked tooth colour change was achieved by whitening with VFRs as the whitening trays, but this changed the VFRs' biomechanical properties, including a decrease in tensile strength and an increase in hardness and internal roughness., Clinical Significance: The application of carbamide peroxide in VFRs may compromise their mechanical properties., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objectives: To evaluate the bleaching efficacy and permeability of hydrogen peroxide (HP) in the pulp chamber of human teeth bleached with lower concentrations of carbamide peroxide gel (4%, 5% and 7% CP)., Materials and Methods: Bleaching gels with lower concentrations were formulated and a commercial standard gel, 10% CP, was used as a reference. Fifty-six human premolars were randomly divided into four groups. Applications of the bleaching gel were made for 3 h for 21 days. The bleaching efficacy was evaluated by digital spectrophotometry on 1, 7, 14 and 21 days, with analysis in the ∆E ab , ∆E 00 and WI D color spaces. The concentration of HP in the pulp chamber was measured in the same periods by UV-Vis spectrophotometry (µg/mL). Two-way repeated analysis of variance (ANOVA) examined bleaching efficacy and HP permeability, followed by Tukey's post-hoc test (α = 0.05)., Results: All groups showed significant color changes, with no statistical differences after the second and third week of bleaching (p > 0.05). The 'time' factor was statistically different (p < 0.05), increasing the bleaching efficacy throughout the treatment. The 4% CP group had lower HP levels in the pulp chamber (p < 0.05)., Conclusions: The results seem promising, revealing that low concentration gels are as effective as 10% CP with the benefit of reducing the amount of HP in the pulp chamber., Clinical Relevance: Low concentration 4% PC and 5% PC maintains bleaching efficacy, reduces the penetration of HP peroxide into the pulp chamber, and may reduce tooth sensitivity., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Water pollution in developing countries continues to be a major health problem due to various anthropological activities that contribute to the spread of many parasitic diseases, including those caused by helminths. The aim of this study is to explore the ability of ozone and peroxone to disinfect drinking water contaminated samples with Toxocara canis eggs. The oxidants used were ozone and ozone-hydrogen peroxide combination. The treatment of Toxocara canis eggs was carried out in a 50 ml reactor with an operating volume of 10 ml. The pH conditions (5, 7 and 10) were varied for each treatment. The treatment effect was calculated by counting eggs and examining the condition of the larvae larval condition (whole, broken and hatched larvae) using an optical microscope. The experiment was carried out by exposing the eggs for 60 and 120 minutes to ozone and peroxone. The best results were obtained for helminths treated with the ozone/hydrogen peroxide combination at pH 10, with an inactivation of 79.2%. The synergistic effect of ozone combined with hydrogen peroxide allows higher helminth egg inactivation rates, demonstrating that advanced oxidation processes are a real alternative to apply in the inactivation of Toxocara canis eggs. The results obtained in this study show that the ozone and peroxone treatment could be a useful disinfection process to destroy or inactivate Toxocara canis eggs in processes commonly applied in water treatment.

Bioassay-guided isolation of the extract from the marine sponge Diacarnus spinipoculum showing inhibitory activity against human transient receptor potential ankyrin 1 (hTRPA1) resulted in the isolation of 12 norditerpene cyclic peroxides ( 1 - 12 ) and eight norsesterterpene cyclic peroxides ( 13 - 20 ). Among these, 10 ( 5 - 7 , 11 , 12 , 16 - 20 ) are unprecedented analogs. Compounds with either a hydroxy ( 5 , 11 ) or a methoxy ( 6 , 12 ) group attached to the cyclohexanone moiety were obtained as epimeric mixtures at C-11, while compounds 4 , 6 , 10 , and 12 are likely the artifacts of isolation. The absolute configurations of the new compounds were established based on an NMR-based empirical method and comparison of specific rotation values. Mosher ester analysis revealed the absolute configurations of compounds 17 - 20 . The inhibitory activity of the isolated compounds against hTRPA1 varied significantly depending on their structures, with the norsesterterpenoid 19 displaying the most potent activity (IC 50 2.0 μM).

This clinical trial investigated the effects of pre-application enamel moistening on the impact of a 37% carbamide peroxide whitener on tooth color changes and the influence of repositioning guide colors. Forty participants were randomly assigned to in-office tooth bleaching with either moistened enamel (experimental) or dry enamel (control). The whitener was applied for 45 min over two sessions. Tooth color was visually measured or assessed using a spectrophotometer with purple or green silicone guides. Tooth bleaching was assessed using CIE76 (ΔE ab ) and CIEDE2000 (ΔE 00 ) formulas and by whitening and bleaching index score changes. Moistening the enamel did not significantly affect tooth color. However, the guide color choice only impacted tooth color when measured instrumentally. At baseline, the green guide resulted in statistically significantly whiter teeth than the purple guide. Less pronounced differences in the b* coordinate between baseline and final measurements were found using the green guide. The green guide also produced lower ΔE ab values and less change in indexes. In conclusion, moistening the enamel did not significantly impact tooth color changes. However, the repositioning guide color influenced the tooth bleaching measured instrumentally, except for ΔE 00 ., (© 2023 Scandinavian Division of the International Association for Dental Research. Published by John Wiley & Sons Ltd.)

In recent years, the antihypertensive drug Valsartan (VAL) has been detected in surface waters up to concentrations of 6300 ng/L, due to its high consumption and its mostly unchanged excretion. Moreover, wastewater treatment plants fail to completely mineralize/transform it, as evidenced by findings of up to 3800 ng/L in some effluents. In this paper, the possible degradation of VAL was evaluated through Fenton-like reaction with activation of peroxymonosulfate in the presence of Fe(II) under neutral conditions. Fourteen degradation byproducts were isolated and completely identified by both nuclear magnetic resonance and mass spectrometry, five of which were discovered for the first time, and a mechanism of their formation was proposed. Furthermore, the potential acute and chronic toxicity of valsartan and its byproducts in the aquatic environment were evaluated in key organisms of the freshwater trophic chain belonging to producers and consumers, the alga Raphidocelis subcapitata and the rotifer Brachionus calyciflorus, respectively. Acute effects occurred at concentrations in the order of tens/hundreds of mg/L, far from those of environmental concern. As regards chronic effects, algae were not particularly affected by the parent compound and its derivatives, while rotifers were less affected by derivatives (effective concentrations at units/tens of μg/L) compared to valsartan (effective concentrations at hundreds of ng/L)., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

A feature in neurodegenerative disorders is the loss of neurons, caused by several factors including oxidative stress induced by reactive oxygen species (ROS). In this work, static magnetic field (SMF) was applied in vitro to evaluate its effect on the viability, proliferation, and migration of human neuroblastoma SH-SY5Y cells, and on the toxicity induced by hydrogen peroxide (H 2 O 2 ), tert-butyl hydroperoxide (tBHP), H 2 O 2 /sodium azide (NaN 3 ) and photosensitized oxidations by photodynamic therapy (PDT) photosensitizers. The SMF increased almost twofold the cell expression of the proliferation biomarker Ki-67 compared to control cells after 7 days of exposure. Exposure to SMF accelerated the wound healing of scratched cell monolayers and significantly reduced the H 2 O 2 -induced and the tBHP-induced cell deaths. Interestingly, SMF was able to revert the effects of NaN 3 (a catalase inhibitor), suggesting an increased activity of catalase under the influence of the magnetic field. In agreement with this hypothesis, SMF significantly reduced the oxidation of DCF-H2, indicating a lower level of intracellular ROS. When the redox imbalance was triggered through photosensitized oxidation, no protection was observed. This observation aligns with the proposed role of catalase in cellular proctetion under SMF.  Exposition to SMF should be further validated in vitro and in vivo as a potential therapeutic approach for neurodegenerative disorders., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: This in vitro study evaluated the efficacy and the effect over the dental enamel surface of violet LED dental bleaching associated to different concentrations of carbamide and hydrogen peroxide., Methods: Human dental blocks (n = 100) were randomly distributed into 5 groups: 10% hydrogen peroxide (HP10), 10% carbamide peroxide (CP10), 10% hydrogen peroxide with violet LED (VHP10), 10% carbamide peroxide with violet LED (VCP10) and 35% hydrogen peroxide (HP35). The specimens were analyzed by Vickers microhardness test (n = 50) initially, immediately after and seven days after ending the bleaching protocol. For color analysis (n = 50), the specimens were evaluated for bleaching effectiveness (ΔE2000, ΔE1976) and whiteness index (ΔWID) with EasyShade spectrophotometer, before bleaching protocol and seven days after ending the bleaching protocol. The microhardness and color data were analyzed using one-way ANOVA with post-hoc Tukey test (α = 0.05)., Results: The microhardness values showed difference among the investigated groups only immediately after the end of the dental bleaching (p < 0.05), with reduction for the groups HP35 (p < 0.01) and HP10 (p < 0.05), however the microhardness values were reestablished after seven days. Regarding the color changes, a difference between VHP10 and the others groups evaluated for ΔE2000 and ΔE1976 index was observed (p < 0.05). For ΔWID, there was no difference between the studied groups., Conclusions: Violet LED associated with low concentration bleaching agents did not show a negative effect on dental enamel regarding the surface microhardness. All bleaching protocols were effective, therefore, perceptible to human eyes., Competing Interests: Declaration of Competing Interest The authors declare no known competing financial interests or personal relationships in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Aim: The purpose of the present study was to understand the possible events involved in the toxicity of hydrogen peroxide (H2O2) to wild and sporulene-deficient spores of Bacillus subtilis, as H2O2 was previously shown to have deleterious effects., Methods and Results: The investigation utilized two strains of B. subtilis, namely the wild-type PY79 (WT) and the sporulene-deficient TB10 (ΔsqhC mutant). Following treatment with 0.05% H2O2 (v/v), spore viability was assessed using a plate count assay, which revealed a significant decrease in cultivability of 80% for the ΔsqhC mutant spores. Possible reasons for the loss of spore viability were investigated with microscopic analysis, dipicholinic acid (DPA) quantification and propidium iodide (PI) staining. Microscopic examinations revealed the presence of withered and deflated morphologies in spores of ΔsqhC mutants treated with H2O2, indicating a compromised membrane permeability. This was further substantiated by the absence of DPA and a high frequency (50%-75%) of PI infiltration. The results of fatty acid methyl ester analysis and protein profiling indicated that the potentiation of H2O2-induced cellular responses was manifested in the form of altered spore composition in ΔsqhC B. subtilis. The slowed growth rates of the ΔsqhC mutant and the heightened sporulene biosynthesis pathways in the WT strain, both upon exposure to H2O2, suggested a protective function for sporulenes in vegetative cells., Conclusions: Sporulenes serve as a protective layer for the inner membrane of spores, thus assuming a significant role in mitigating the adverse effects of H2O2 in WT B. subtilis. The toxic effects of H2O2 were even more pronounced in the spores of the ΔsqhC mutant, which lacks this protective barrier of sporulenes., (© The Author(s) 2023. Published by Oxford University Press on behalf of Applied Microbiology International.)

Reactive oxygen species (ROS) generation, using photodynamic therapy (PDT) and chemodynamic therapy (CDT), is a promising strategy for cancer treatment. However, the production of ROS in tumor cells is often limited by hypoxia, insufficient substrates, and high level of ROS scavengers in a tumor microenvironment, which seriously affects the efficacy of ROS-related tumor therapies. Herein, we report a lipid-supported manganese oxide nanozyme, MLP@DHA&Ce6, by decorating a MnO 2 nano-shell on the liposome loaded with dihydroartemisinin (DHA) and photosensitizer Ce6 for generating multisource ROS to enhance cancer therapy. MLP@DHA&Ce6 can be accumulated in tumors and can release active components, Mn 2+ ions, and O 2 . The conjugate generates ROS via nanozyme-catalyzed CDT using DHA as a substrate, PDT through Ce6, and the Fenton reaction catalyzed by Mn 2+ ions. The production of O 2 from MnO 2 enhanced Ce6-mediated PDT under near-infrared light irradiation. Meanwhile, MLP@DHA&Ce6 showed prominent glutathione depletion, which allowed ROS to retain high activity in tumor cells. In addition, the release of Mn 2+ ions and DHA in tumor cells induced ferroptosis. This multisource ROS generation and ferroptosis effect of MLP@DHA&Ce6 led to enhanced therapeutic effects in vivo.

Ferroptosis has appealing antitumor potential that is mainly based on the accumulation of lipid peroxide to a lethal level. The cytotoxic singlet oxygen ( 1 O 2 ) generated from nanoscale X-ray-induced photodynamic therapy (X-PDT) may facilitate glutathione (GSH) depletion and further activate ferroptosis. To realize combined X-PDT and ferroptosis, a nanocarrier (D-NP VR ) was engineered with a hyperbranched copolymer with 1 O 2 -sensitive linkers, where both the photosensitizer (verteporfin) and ferroptosis inducer RAS-selective lethal small molecule 3 (RSL3) were encapsulated. Upon X-ray radiation, D-NP VR could produce a large amount of 1 O 2 for apoptosis. Subsequently, 1 O 2 triggered D-NP dissociation by cleavage of 1,2-bis(2-hydroxyethylthio)ethylene bonds to boost payload release and decrease levels of intracellular GSH via thiol oxidation. Liberated RSL3 is a covalent inhibitor for glutathione peroxide 4 (GPX4), which is responsible for detoxifying lipid peroxides to lipid alcohols with GSH assistance, and both 1 O 2 -induced GSH depletion and GPX4 inactivation thereby produced ferroptotic cell death. Tumor growth inhibition in murine 4T1 tumor-bearing mice demonstrated that D-NP VR produced pronounced therapeutic efficiency where ferroptosis induction was supported by the GPX4 content and expression. This study highlights the contribution of 1 O 2 -sensitive nanocarriers for promoting the potency of combined X-PDT and ferroptosis.

This study evaluated the effect of propolis as an antioxidant agent on bond strength to enamel after intracoronal bleaching. A total of 160 incisors were endodontically treated. Sixteen teeth were served as control, and the remaining teeth were randomly divided into three main groups according to the bleaching agent used; group 1: Sodium perborate (SP); group 2: Carbamide peroxide (CP); group 3: Hydrogen peroxide (HP). After bleaching, the samples were divided into three subgroups; subgroup A: no antioxidant agent application, subgroup B: sodium ascorbate (SA), subgroup C: propolis (PP). After the antioxidant agents application, the sample's surfaces were washed and dried. After adhesive application, composite resin cylinders were applied to enamel surfaces using tygon tubes and a shear bond strength test was performed. The use of PP significantly decreased the bond strength of composite resin to the enamel (p < 0.05). Using propolis as an antioxidant agent adversely affects the bond strength to enamel after intracoronal bleaching., (© 2023 Australian Society of Endodontology Inc.)

Introduction: This study aimed to assess the efficacy of chemical agents in removing Candida albicans and Streptococcus mutans biofilm from invisible aligners., Methods: The samples were made of EX30 Invisalign trays, biofilm was cultured by standardized suspensions of C. albicans ATCC strain and S. mutans clinical strain on the sample. The treatments used were 0.5% sodium hypochlorite (NaClO) (20 minutes), 1% NaClO (10 minutes), chlorhexidine (5 minutes), peroxide (15 minutes), and orthophosphoric acid (15 seconds). The control group received phosphate-buffered saline for 10 minutes. The colony-forming units per milliliter of each microorganism were determined by serial dilutions seeded in plates with selective culture mediums for each one. Data were analyzed by the Kruskal-Wallis and Conover-Iman tests at an α of 0.05., Results: For the C. albicans biofilm group, the control group had 9.7 Log10 of microorganism growth, and all treatment groups had statistically significant biofilm reduction, in which chlorhexidine presented the highest inhibition of 3 Log10, followed by alkaline peroxide and orthophosphoric acid both with 2.6 Log10, 1% NaClO (2.5 Log10), and 0.5% NaClO (2 Log10). As for S. mutans, the control group had 8.9 Log10 of growth, and a total microorganism inhibition was reached by chlorhexidine, 1% NaClO, and orthophosphoric acid, whereas alkaline peroxide inhibited growth to 7.9 Log10 and 0.5% NaClO 5.1 Log10., Conclusions: Within the limitations, chlorhexidine and orthophosphoric acid had greater efficacy in both biofilms. In addition, 1% NaClO and alkaline peroxide also had significant effects; therefore, their incorporation aligners disinfection protocols are valid., (Copyright © 2023 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.)

We developed a caged hydroperoxide, BhcTBHP, releasing prooxidant TBHP under blue light irradiation. MitoTBHP with triphenylphosphonium at position 7 triggered selective oxidative stress and membrane depolarization in mitochondria upon photoirradiation. This study presents a powerful tool for studying redox signaling and oxidative stress in living cells.

Purpose: To evaluate the effectiveness of five alkaline peroxide-based effervescent tablets in reducing both biofilms and the food layer adhered on the cobalt-chromium surface., Methods: Cobalt-chromium metal alloy specimens were contaminated with Candida albicans, Candida glabrata, Streptococcus mutans and Staphylococcus aureus. After biofilm maturation, the specimens were immersed in Polident 3 Minute, Polident for Partials, Efferdent, Steradent, Corega Tabs or distilled water (control). Residual biofilm rates were determined by colony forming units counts and biofilm biomass. In parallel, to investigate the denture cleaning capability of effervescent tablets, artificially contaminated removable partial dentures were treated with each cleanser. Data were analyzed by Kruskal-Wallis followed by Dunn post hoc test or ANOVA followed by Tukey post hoc test (α= 0.05)., Results: None of the hygiene solutions reduced C. albicans biofilm. Efferdent and Corega Tabs promoted reduction of C. glabrata biofilm, while Steradent was favorable against S. aureus biofilm. For S. mutans, lower biofilm rates were observed after immersion in Polident for Partials and Steradent. The effervescent tablets showed good cleaning performance, removing an artificial layer with carbohydrates, proteins, and fats, however, they were not effective in removing aggregated mature biofilm., Clinical Significance: The different effervescent tablets presented favorable antimicrobial activity against C. glabrata, S. mutans and S. aureus on cobalt-chromium surfaces and showed cleaning capability. However, for an appropriate biofilm control, a complementary method should be evaluated since none of the peroxide-based solutions reduced C. albicans biofilms or substantially removed aggregated biofilm., Competing Interests: The authors declared no conflict of interest. This study was supported in part by the Coordination for the Improvement of Higher Education Personnel – Brazil (CAPES) - Finance Code 001. VG Morelli and VC Oliveira contributed equally to the work., (Copyright©American Journal of Dentistry.)

Objective: Assess the effects of activated charcoal-based products on whitening and changes on dental enamel surface., Material and Methods: Fifty-two blocks of bovine dental enamel were randomly distributed in four groups (n = 13): brushing with activated charcoal-based powder (PW); brushing with activated charcoal-based dentifrice (AC); brushing with a conventional dentifrice containing 1450 ppm of fluoride (CD); and whitening with 10% carbamide peroxide (CP). Color, microhardness, and surface alteration were analyzed at baseline and after 14 days of treatment. Three samples per group were randomly selected and examined using scanning electron microscopy (SEM) to analyze the morphology., Results: PW exhibited greater color change for the ΔE 00 , ΔWID, Δb* and ΔL* parameters than other groups (p < 0.05). After treatment, microhardness decreased in AC and CP groups (p < 0.05). Also, PW and AC groups showed more surface alteration than CD and CP (p < 0.001). Changes in the morphology of dental enamel were observed by SEM in PW and AC groups., Conclusion: Activated charcoal-based products showed a lower whitening effect than 10% carbamide peroxide. These products also influenced dental enamel microhardness, resulting in greater surface alteration., Clinical Significance: Activated charcoal-based products promoted minimum whitening effects with significant enamel surface alteration. The 10% carbamide peroxide was more effective for whitening and caused slight enamel surface alteration., (© 2022 Wiley Periodicals LLC.)

Natrosol and Aristoflex® AVC polymers are widely applied in the cosmetic industry and have recently been applied as a thickener option in the composition of dental bleaching gels, with the purpose to reduce the adverse effects on enamel mineral components. The aim of this study was to evaluate the color variation (ΔE* ab, ΔE00, ∆WID), surface roughness (Ra), and mineral content quantification (Raman Spectroscopy) of dental enamel after bleaching treatment with experimental gel-based on 10% carbamide peroxide (CP), containing Carbopol, Natrosol, and Aristoflex® AVC. Sixty bovine teeth were randomly divided into 6 groups (n=10): Negative Control (NC) - no treatment; Positive Control (PC) - Whiteness Perfect 10% - FGM; CP with Carbopol (CPc); CP with Natrosol (CPn); CP with Aristoflex® AVC (CPa); NCP - no thickener. Data were analyzed, and generalized linear models (∆WID -T0 x T1) were used for repeated measurements in time for Ra and with a study factor for ΔE* ab and ΔE00. For the evaluation of the mineral content, data were submitted to one-way ANOVA and Tukey tests. For enamel topographic surface analysis the Scanning Electron Microscope (SEM) was performed. A significance level of 5% was considered. ΔE* ab and ΔE00 were significantly higher for CPc, CPn, CPa, and NCP groups. (∆WID) showed a significantly lower mean than the other groups for NC in T1. After bleaching (4-hour daily application for 14 days), Ra was higher in the CPc, CPn, and PC groups. For CPa, Ra was not altered. No significant difference was found in the quantification of mineral content. CPa preserved the surface smoothness more effectively. Aristoflex® AVC is a viable option for application as a thickener in dental bleaching gels, presenting satisfactory performance, and maintaining the whitening efficacy of the gel, with the advantage of preserving the surface roughness of tooth enamel without significant loss of mineral content.

The facultative anaerobe Shewanella oneidensis respires an extensive set of electron acceptors and, as a consequence, can leak electrons to produce reactive oxygen species such as hydrogen peroxide (H2O2). However, the effects of respiration on cytoplasmic redox homeostasis are poorly characterized in comparison. In the present study, the H2O2 sensor HyPer-3 was deployed to interrogate cytoplasmic peroxide levels of both wild-type and gene deletion mutants lacking peroxide scavenging enzymes following exposure to H2O2. HyPer-3 signals were validated in the S. oneidensis wild-type strain and exhibited a dynamic range of 0-250 μM H2O2. As reported by the HyPer-3 sensor, the cytoplasm of H2O2-perturbed mutant strains lacking periplasmic glutathione peroxidase (PgpD) and double deletion mutants lacking catalase (KatB) and bifunctional catalase-peroxidases (KatG1 or KatG2) contained high H2O2 concentrations. The high cytoplasmic H2O2 concentrations correlated with impaired H2O2 removal rates displayed by the mutant strains. Results of the present study provide the first in vivo interrogation of the redox environment of the S. oneidensis cytoplasm with HyPer-3 sensors and indicate that proper redox conditions in minimal growth medium are maintained by the concerted action of both well-known (periplasmic PgpD, cytoplasmic KatB and KatG1) and previously overlooked (cytoplasmic KatG2) peroxidases and catalases., (© The Author(s) 2023. Published by Oxford University Press on behalf of FEMS.)

The aim of this in situ study was to evaluate color change, surface roughness, gloss, and microhardness in tooth enamel submitted to whitening and remineralizing toothpastes. Fifteen healthy adults (REBEC - RBR-7p87yr) (with unstimulated salivary flow ≥ 1.5 ml for 5 minutes, pH=7) wore two intraoral devices containing four bovine dental fragments (6 x 6 x 2 mm). Participants were randomly assigned and instructed to toothbrush the devices with the tested toothpastes (30 days): CT: conventional; WT: whitening; WTP: whitening with peroxide, and RT: remineralizing toothpaste. A washout period of 7 days was established. Readouts of color, gloss, surface roughness, and microhardness were performed before and after brushing. The results demonstrated no color, gloss, and microhardness differences (p>0.5). The samples brushed with WTP (0.2(0.7) showed higher surface roughness (p=0.0493) than those with WT (-0.5(1.0). The toothpastes did not alter the properties of the dental enamel, except for the roughness. Toothpaste with an abrasive system based on sodium bicarbonate and silica, and that contains sodium carbonate peroxide increased the surface roughness of the enamel.

Objectives: To investigate the physical-chemical properties of home bleaching gels based on Carbamide Peroxide (CP) and Hydrogen Peroxide (HP) after accelerated stability (AS) and its effects on enamel., Materials and Methods: A total of 360 bovine teeth blocks were divided (n = 12): Control, CP10%-Whiteness Perfect, CP10%-Pola Night, HP7.5%-Pola Day, and HP7.5%-White Class Calcium. Microhardness (KHN), roughness (Ra), color (ΔE and ΔE 00 ), hardness, compressibility, elasticity, cohesiveness, adhesiveness, weight, pH, and calcium (Ca) quantification in enamel were analyzed without storage of the bleaching gels and after AS at 1 and 3 months. Data of Ca, KHN, and Ra were analyzed through mixed models for repeated measurements and the Tukey-Kramer test. Values of weight, hardness, compressibility, and elasticity were analyzed with two-way ANOVA and Tukey's test. ΔE/ΔE 00 data, cohesiveness, and adhesiveness were analyzed with Kruskal-Wallis and Dunn tests (α = 0.05)., Results: Groups subject to AS had lower ΔE and ΔE 00 compared to those without storage. Lower KHN and higher Ra values were found after bleaching treatment in all groups compared to controls. Higher amounts of Ca were found on the first day of evaluation in the gels subject to AS for 3 months, regardless of the bleaching agent used., Conclusions: Incorrectly stored bleaching gel accentuates adverse effects on enamel. Temperature and humidity interfere directly with the chemical stability of bleaching agents, reducing their properties., Clinical Relevance: HP is an unstable oxidizing agent when stored at high temperatures. Therefore, pH becomes more acidic and potentiates the demineralizing effect on enamel., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)