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Oxygen activation leading to the generation of reactive oxygen species (ROS) is essential for photocatalytic environmental remediation. The limited efficiency of O2 adsorption and reductive activation significantly limits the production of ROS when employing C3N4 for the degradation of emerging pollutants. Doping with metal single atoms may lead to unsatisfactory efficiency, due to the recombination of photogenerated electron-hole pairs. Here, Mn and S single atoms were introduced into C3N4, resulting in the excellent photocatalytic performances. Mn/S-C3N4 achieved 100% removal of bisphenol A, with a rate constant 11 times that of pristine C3N4. According to the experimental results and theoretical simulations, S-atoms restrict holes, facilitating the photo-generated carriers' separation. Single-atom Mn acts as the O2 adsorption site, enhancing the adsorption and activation of O2, resulting the generation of ROS. This study presents a novel approach for developing highly effective photocatalysts that follows a new mechanism to eliminate organic pollutants from water.

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The accumulation of photosensitizers (PSs) in lesion sites but not in other organs is an important challenge for efficient image guiding in photodynamic therapy. Cancer cells are known to express a significant number of albumin-binding proteins that take up albumin as a nutrient source. Here, we converted albumin to a novel BODIPY-like PS by generating a tetrahedral boron environment via a flick reaction. The formed albumin PS has almost the same 3-dimensional structural feature as free albumin because binding occurs at Sudlow Site 1, which is located in the interior space of albumin. An i.v. injection experiment in tumor-bearing mice demonstrated that the human serum albumin PS effectively accumulated in cancer tissue and, more surprisingly, albumin PS accumulated much more in the cancer tissue than in the liver and kidneys. The albumin PS was effective at killing tumor cells through the generation of reactive oxygen species under light irradiation. The crystal structure of the albumin PS was fully elucidated by X-ray crystallography; thus, further tuning of the structure will lead to novel physicochemical properties of the albumin PS, suggesting its potential in biological and clinical applications.

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Accurate and early detection of atherosclerosis (AS) is imperative for their effective treatment. However, fluorescence probes for efficient diagnosis of AS often encounter insufficient deep tissue penetration, which hinders the reliable assessment of plaque vulnerability. In this work, a reactive oxygen species (ROS) activated near-infrared (NIR) fluorescence and photoacoustic (FL/PA) dual model probe TPA-QO-B is developed by conjugating two chromophores (TPA-QI and O-OH) and ROS-specific group phenylboronic acid ester. The incorporation of ROS-specific group not only induces blue shift in absorbance, but also inhibits the ICT process of TPA-QO-OH, resulting an ignorable initial FL/PA signal. ROS triggers the convertion of TPA-QO-B to TPA-QO-OH, resulting in the concurrent amplification of FL/PA signal. The exceptional selectivity of TPA-QO-B towards ROS makes it effectively distinguish AS mice from the healthy. The NIR emission can achieve a tissue penetration imaging depth of 0.3 cm. Moreover, its PA775 signal possesses the capability to penetrate tissues up to a thickness of 0.8 cm, ensuring deep in vivo imaging of AS model mice in early stage. The ROS-triggered FL/PA dual signal amplification strategy improves the accuracy and addresses the deep tissue penetration problem simultaneously, providing a promising tool for in vivo tracking biomarkers in life science and preclinical applications.

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Osteomyelitis is an osseous infectious disease that primarily affects children and the elderly with high morbidity and recurrence. The conventional treatments of osteomyelitis contain long-term and high-dose systemic antibiotics with debridements, which are not effective and lead to antibiotic resistance with serious side/adverse effects in many cases. Hence, developing novel antibiotic-free interventions against osteomyelitis (especially antibiotic-resistant bacterial infection) is urgent and anticipated. Here, a bone mesenchymal stem cell membrane-constructed nanocell (CFE@CM) was fabricated against osteomyelitis with the characteristics of acid-responsiveness, hydrogen peroxide self-supplying, enhanced chemodynamic therapeutic efficacy, bone marrow targeting and cuproptosis induction. Notably, mRNA sequencing was applied to unveil the underlying biological mechanisms and found that the biological processes related to copper ion binding, oxidative phosphorylation, peptide biosynthesis and metabolism, etc., were disturbed by CFE@CM in bacteria. This work provided an innovative antibiotic-free strategy against osteomyelitis through copper-enhanced Fenton reaction and distinct cuproptosis, promising to complement the current insufficient therapeutic regimen in clinic.

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Intervertebral disc degeneration (IVDD) may lead to an increase in extracellular matrix (ECM) stiffness, contributing to the progression of the disease. Melatonin reportedly mitigates IVDD; while its potential to attenuate elevated matrix stiffness-induced IVDD remains unexplored. Therefore, we aimed to investigate whether melatonin can alleviate the progression of IVDD triggered by increased matrix stiffness and elucidate its mechanisms. Nucleus pulposus (NP) tissues were collected from patients, and ECM stiffness, reactive oxygen species (ROS) levels, apoptosis rates, and p65 expression in these tissues with varying Pfirrmann scores were determined. In vitro experiments were conducted to investigate the effects of melatonin on the NP cells cultured on soft substrate with differing stiffness levels. Our findings revealed a positive correlation between ECM stiffness in human NP tissue and degree of IVDD. Additionally, phosphorylation of P65 exhibited a strong association with matrix stiffness. Enhanced levels of ROS and cellular apoptosis were observed within degenerated intervertebral discs. In vitro experiments demonstrated that melatonin significantly inhibited catabolism and apoptosis induced by stiff matrices, along with elevated ROS levels. Furthermore, we observed that melatonin inhibited NP cell catabolism and apoptosis by reducing the melatonin receptors mediated activation of the PI3K/AKT and NF-κB pathways. Also, we found that the reduction of ROS by melatonin can assist in inhibiting the activation of the NF-κB pathway. The outcomes of the in vivo experiments corroborated the results of the in vitro experiments. Collectively, melatonin can potentially alleviate high matrix stiffness-induced IVDD by reducing intracellular ROS levels and inhibiting the PI3K/AKT/NF-κB pathway.

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Photodynamic therapy (PDT) and sonodynamic therapy (SDT), using nonionizing light and ultrasound to generate reactive oxygen species, offer promising localized treatments for cancers. However, the effectiveness of PDT is hampered by inadequate tissue penetration, and SDT largely relies on pyrolysis and sonoluminescence, which may cause tissue injury and imprecise targeting. To address these issues, we have proposed a mechanochemical dynamic therapy (MDT) that uses free radicals generated from mechanophore-embedded polymers under mechanical stress to produce reactive oxygen species for cancer treatment. Yet, their application in vivo is constrained by the bulk form of the polymer and the need for high ultrasound intensities for activation. In this study, we developed injectable, nanoscale mechanophore particles with enhanced ultrasound sensitivity by leveraging a core-shell structure comprising silica nanoparticles (NPs) whose interfaces are linked to polymer brushes by an azo mechanophore moiety. Upon focused ultrasound (FUS) treatment, this injectable NP generates reactive oxygen species (ROS), demonstrating promising results in both an in vitro 4T1 cell model and an in vivo mouse model of orthotopic breast cancers. This research offers an alternative therapy technique, integrating force-responsive azo mechanophores and FUS under biocompatible conditions.

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Luminous marine bacteria are traditionally used as a bioassay due to the convenience and high rate of registering the intensity of their physiological function - luminescence. This study aimed to develop the application of Photobacterium phosphoreum in traditional and novel fields - toxicity monitoring and biotechnology. We demonstrated (1) effects of selenite ions on bioluminescence, and (2) biotransformation of selenite to selenium(0) in the form of nanoparticles. The effects of selenite (SeO32-) on the intensity of bacterial bioluminescence were studied, and its dependencies on exposure time and concentration of Na2SeO3 were analyzed. Bioluminescence activation and inhibition were revealed; dose-effect dependencies corresponded to the hormesis model. The toxicity of SeO32- was characterized by an effective concentration of 10-3 M. Effects of SeO32- on reactive oxygen species (ROS) in bacterial suspensions were studied. High positive correlations were found between the bioluminescence intensity and ROS content, which indicates the decisive role of ROS and associated redox processes in the bioeffects of selenite ions. Scanning and transmission electron microscopy revealed the presence of nano-structures in the bacteria exposed to selenite. The energy dispersion spectrum detected a high content of selenium in the nanoparticles. The particle size distribution depended on Na2SeO3 concentration; maxima of the distribution varied within 45-55 nm.

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Glomalin-related soil protein (GRSP) has demonstrated significant potential for water purification and remediation of heavy metals in soils; however, its redox reactivity for As(III) sequestration and the corresponding redox-active component are still poorly understood. This study investigated the photochemical properties of GRSP and its mechanism of oxidation/adsorption of As(III). The results showed that UV irradiation triggered electron transfer and the production of reactive oxygen species (ROS) in GRSP, thereby facilitating As(III) oxidation with promotion rates ranging from 43.34 % to 111.1 %. The oxidation of As(III) occurred both on the GRSP photoforming holes and in the ROS reaction from the oxygen reduction products of the photoforming electrons. OH• and H2O2 played an important role in the oxidation of As(III) by GRSP, especially under alkaline conditions. Moreover, the presence of Fe(III) in GRSP facilitated the formation of OH• and its the oxidation capacity towards As(III). The binding of As(III) to the -COOH, -OH, and -FeO groups on the GRSP surface occurred through surface complexation. Overall, these findings provided new insights into the roles of the redox-active moieties and Fe(III) on GRSP in the promoted oxidation of As(III), which would help to deepen our understanding of the migration and transformation of As(III) in soils.

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OBJECTIVE: The objective of this review is to qualitatively appraise the available literature to evaluate the efficacy of circulatory systemic oxidative stress markers (OSMx) in determining the diagnosis and outcome of TBI. METHODS: A systematic review was conducted of PubMed/Medline, Embase and Google Scholar databases per the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) for studies which employed serum or plasma OSMx analysis for diagnostic or prognostic purposes in patients with TBI. RESULTS: Eight studies were included. There were 654 patients across the eight studies, of which 518 (79.2%) patients had sustained a TBI. The heterogeneity between studies in terms of OSMxs analyzed ultimately made collective analysis inappropriate. Nevertheless, several studies highlighted the potential role of circulatory OSMx levels in determining the diagnosis (presence and severity) and prognosis (functional outcome and mortality) of TBI. CONCLUSION: The care for patients with TBI remains a complex clinical challenge with a high morbidity and mortality profile. Evidenced by this review, circulatory OSMxs appear to have the potential to supplement current diagnostic measures, in addition to identifying new treatment strategies and monitoring recovery. Despite early promise, the evidence for such markers remains in its infancy and robust prospective studies are needed.

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Carbon monoxide (CO) poisoning presents a substantial public health challenge that necessitates the identification of its pathological mechanisms and therapeutic targets. CO toxicity arises from tissue hypoxia-ischemia secondary to carboxyhemoglobin formation, and cellular damage mediated by CO at the cellular level. The mitochondria are the major targets of neuronal damage caused by CO. Under normal physiological conditions, mitochondria produce reactive oxygen species (ROS), which are byproducts of aerobic metabolism. While low ROS levels are crucial for essential cellular functions, including signal transduction, differentiation, responses to hypoxia and immunity, transcriptional regulation, and autophagy, excess ROS become pathological and exacerbate CO poisoning. This review presents the evidence of elevated ROS being associated with the progression of CO poisoning. Antioxidant treatments targeting ROS removal have been proven effective in mitigating CO poisoning, underscoring their therapeutic potential. In this review, we highlight the latest advances in the understanding of the role and the clinical implications of ROS in CO poisoning. We focus on cellular sources of ROS, the molecular mechanisms underlying mitochondrial oxidative stress, and potential therapeutic strategies for targeting ROS in CO poisoning.

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Endometrial cancer (EC) is a common gynecological cancer worldwide, often associated with a poor prognosis after recurrence or metastasis. Ovatodiolide (OVA) is a macrocyclic diterpenoid derived from Anisomeles indica that shows anticancer effects in various malignancies. This study aimed to evaluate the cytotoxic effects of OVA on EC cell proliferation and cancer stem cell (CSC) activity and explore its underlying molecular mechanisms. OVA treatment dose-dependently reduced the viability and colony formation of three EC cell lines (AN3CA, HEC-1A, and EMC6). It induced G2/M phase cell cycle arrest, associated with decreased cell division cycle 25C (CDC25C) expression and reduced activation of cyclin-dependent kinases 1 (CDK1) and 2 (CDK2). OVA also increased reactive oxygen species (ROS) production and DNA damage, activating the DNA damage-sensitive cell cycle checkpoint kinases 1 (CHK1) and 2 (CHK2) and upregulating the DNA damage marker γ-H2A.X variant histone (H2AX). It also suppressed the activation of mechanistic target of rapamycin kinase (mTOR) and nuclear factor kappa B (NF-κB) and downregulated glutathione peroxidase 1 (GPX1), an antioxidant enzyme counteracting oxidative stress. Moreover, OVA reduced the self-renewal capacity of CSCs, reducing the expression of key stemness proteins Nanog homeobox (NANOG) and octamer-binding transcription factor 4 (OCT4). The ROS inhibitor N-acetylcysteine attenuated the anti-proliferative and anti-CSC effects of OVA. Our findings suggest that OVA acts via ROS generation, leading to oxidative stress and DNA damage, culminating in cell cycle arrest and the suppression of CSC activity in EC. Therefore, OVA is a promising therapeutic agent for EC, either as a standalone treatment or an adjunct to existing therapies.

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Ameliorating the deleterious impact of systemic or tissue-level hypoxia or ischemia is key to preventing or treating many human diseases and pathologies. Usefully, environmental hypoxia is also a common challenge in many natural habitats; animals that are native to such hypoxic niches often exhibit strategies that enable them to thrive with limited O2 availability. Studying how such species have evolved to tolerate systemic hypoxia offers a promising avenue of discovery for novel strategies to mitigate the deleterious effects of hypoxia in human diseases and pathologies. Of particular interest are naked mole-rats, which are among the most hypoxia-tolerant mammals. Naked mole-rats that tolerate severe hypoxia in a laboratory setting are also protected against clinically relevant mimics of heart attack and stroke. The mechanisms that support this tolerance are currently being elucidated but results to date suggest that metabolic rate suppression, reprogramming of metabolic pathways, and mechanisms that defend against deleterious perturbations of cellular signaling pathways all provide layers of protection. Herein, we synthesize and discuss what is known regarding adaptations to hypoxia in the naked mole-rat cardiopulmonary system and brain, as these systems comprise both the primary means of delivering O2 to tissues and the most hypoxia-sensitive organs in mammals.

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Alzheimer's disease (AD) is one of the most common neurodegenerative diseases characterized by cognitive and memory impairment. Metal ion imbalance and Mitochondrial dysfunction, leading to abnormal aggregation of ß-amyloid protein (Aß), are key factors in the pathogenesis of AD. Therefore, we designed a composite nanometer system of red blood cell (RBC) membranes-encapsulated Prussian blue nanoparticles (PB/RBC). Prussian blue nanoparticles (PBNPs) can chelate Cu2+ and reduce reactive oxygen species (ROS). The RBC membranes are a kind of natural long-lasting circulating carrier. At the same time, through NIR irradiation, the excellent photothermal ability of PBNPs can also temporarily open the blood-brain barrier (BBB), enhance the transmission efficiency of PB/RBC across the BBB, and depolymerize the formed Aß deposits, thereby achieving the optimal therapeutic effect. In vitro and in vivo studies demonstrated that PB/RBC could inhibit Cu2+-induced Aß monomers aggregation, eliminate the deposition of Aß plaques, improve the quality of mitochondria, restore the phagocytic function of microglia, alleviate neuroinflammation in APP/PS1 mice, and repair memory damage. In conclusion, our biofilm-camouflaged nano-delivery system provides significant neuroprotection by inhibiting Cu2+-induced Aß monomers aggregation, photothermally depolymerizing Aß fibrils and reducing the level of ROS, thus effectively ameliorating and treating AD.

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Chlorpyrifos (CPF) is one of the organophosphorus pesticides widely used throughout the world. Epidemiological studies suggested a link between CPF exposure and neurologic disorders, while the molecular mechanisms remain inconclusive. In the present study, we investigated the impacts of chlorpyrifos-oxon (CPO), the major toxic CPF metabolite, on cell apoptosis, and explored possible mechanism associated with endoplasmic reticulum (ER) stress in SH-SY5Y cells. Results showed that CPO exposure induced dose-dependent apoptosis and expression of ER stress-related proteins in SH-SY5Y cells. Pretreatment with 4-PBA (an ER stress inhibitor) effectively inhibited the expression of GRP78, GRP94, p-IRE1α, and XBP1-s, and apoptotic events. Pretreatment with STF-083010 (an IRE1α inhibitor) partially attenuated CPO-induced apoptosis. In addition, CPO exposure significantly evoked the generation of reactive oxygen species (ROS) which could be eliminated by pretreatment of 4-PBA. Of note, buffering the ROS generation with antioxidant NAC had little impact on the expression of p-IRE1α, and only partially attenuated CPO-induced apoptosis. In contrast, co-pretreatment with NAC and STF-083010 effectively inhibited CPO-induced apoptotic events. Collectively, our results indicate that CPO exposure exerts neuronal cytotoxicity via ER stress downstream-regulated IRE1α/XBP1 signaling pathway and ROS generation-triggered apoptosis. These findings highlight the role of ER stress in CPF-induced neurotoxicity, and provide a promising target for the intervention of organophosphate-associated neurodegenerative diseases.

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With global warming, drought stress is becoming increasingly severe, causing serious impacts on crop yield and quality. In order to survive under adverse conditions such as drought stress, plants have evolved a certain mechanism to cope. The tolerance to drought stress is mainly improved through the synergistic effect of regulatory pathways, such as transcription factors, phytohormone, stomatal movement, osmotic substances, sRNA, and antioxidant systems. This study summarizes the research progress on plant drought resistance, in order to provide a reference for improving plant drought resistance and cultivating drought-resistant varieties through genetic engineering technology.

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Skin-nerve interaction plays an important role in promoting wound healing. However, in diabetic ulcers (DUs), the diabetic periphery neuropathy and excessive levels of reactive oxygen species (ROS) block skin-nerve interaction and further impede the DUs healing. Herein, we developed a nanoscale metal-organic framework loaded with nerve growth factor (NGF/Ce-UiO-66, denoted NGF/CU) for the treatment of DUs. The Ce-UiO-66 (CU) was applied as an antioxidant to scavenge ROS and reduce the inflammatory response while the NGF aided in the recovery of cutaneous nerves to further promote DUs healing. Both in vitro and in vivo experiments revealed the effective ability of NGF/CU for DUs healing. Subsequent RNA sequencing analysis revealed the mechanism that NGF/CU can improve wound healing by inhibiting the NF-κB signaling pathway and recovering the neuroendocrine system of the skin. This strategy of nerve regulation will provide more ideas for the treatment of DUs and other organ injuries.

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Nanozymes, a category of nanomaterials with enzyme-like activity, have garnered growing interest in various biomedical contexts. Notably, nanozymes that are capable of regulating reactive oxygen species levels by emulating antioxidant or prooxidant enzymes within cells hold significant therapeutic potential for a range of disorders. Herein, we overview the catalytic mechanisms of four exemplary nanozymes within the orthopedic domain. Subsequently, we emphasize recent groundbreaking advancements in nanozyme applications in orthopaedics, encompassing osteoarthritis, osteoporosis, intervertebral disc degeneration, bone defects, spinal cord injury, gout, rheumatoid arthritis, osteosarcoma and bone infection. Furthermore, we discuss the emerging area's future prospects and several noteworthy challenges in biomedical application. This review not only fosters the ongoing development of nanozyme research but also fosters the emergence of more potent nanozymes for the treatment of orthopaedical diseases in the future.

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Hesperidin is a citrus bioflavonoid and has numerous pharmacological actions. Hesperidin's effect on testicular dysfunction has not been well researched. Hence, the present study is aims to investigate the effect of hesperidin on aluminium chloride (AlCl3)-induced testicular dysfunction in rats. Both vitamin C (200 mg/kg) and hesperidin (50, 100, and 200 mg/kg) were administered orally for 21 days. At the end of the study, the blood samples were obtained from all animals for investigation of biochemical and hematological parameters. Then, bilateral orchiectomy was carried out to remove testicles from the animals, and sperm was collected and examined under a microscope. Finally, organs such as the liver, kidney, and testicles were also collected and utilized for histopathological analysis. Part of the liver sample was used for determination of antioxidant enzymes such as reduced glutathione (GSH) and catalase (CAT) levels. The rats administered with AlCl3 showed elevated levels of biochemical and hematological parameters and a reduction in levels of sperm count, sperm motility, and oxidative stress parameters, whereas the rats administered with vitamin C/hesperidin (200 and 400 mg/kg) were able to ameliorate AlCl3-induced testicular dysfunction by attenuating AlCl3-induced changes in biochemical and hematological parameters, sperm motility, sperm count, and oxidative stress. Both vitamin C and hesperidin had significant ameliorative effects against AlCl3-induced testicular dysfunction.

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High-temperature (HT) stress can induce male sterility in wheat; however, the underlying mechanisms remain poorly understood. This study examined proteomic alterations across three developmental stages between normal and HT-induced male-sterile (HT-ms) anthers in wheat. Utilizing tandem mass tags-based proteomics, we identified 2532 differentially abundant proteins (DAPs): 27 in the tetrad stage, 157 in the binuclear stage, and 2348 in the trinuclear stage. Analyses through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways indicated significant enrichment of these DAPs in seven pathways, namely phenylpropanoid biosynthesis, flavonoid biosynthesis, sphingolipid metabolism, MAPK signaling pathway, starch and sucrose metabolism, response to heat, and response to reactive oxygen species (ROS). Our results indicated the downregulation of DAPs associated with phenylpropanoid biosynthesis and starch and sucrose metabolism, which aligns with anther indehiscence and the lack of starch in HT-ms anthers. By contrast, DAPs in the ROS pathway were upregulated, which aligns with excessive ROS accumulation in HT-ms anthers. Additionally, we conducted protein-protein interaction analysis for the DAPs of these pathways, identifying 15 hub DAPs. The abundance of these hub proteins was confirmed through qRT-PCR, assessing mRNA expression levels of the corresponding transcripts. Collectively, these results offer insights into the molecular mechanisms underlying HT-induced male sterility in wheat at the proteomic level, providing a valuable resource for further research in plant sexual reproduction.

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The KEAP1-NFE2L2 axis is essential for the cellular response against metabolic and oxidative stress. KEAP1 is an adaptor protein of CUL3 (cullin 3) ubiquitin ligase that controls the cellular levels of NFE2L2, a critical transcription factor of several cytoprotective genes. Oxidative stress, defective autophagy and pathogenic infections activate NFE2L2 signaling through phosphorylation of the autophagy receptor protein SQSTM1, which competes with NFE2L2 for binding to KEAP1. Here we show that phosphoribosyl-linked serine ubiquitination of SQSTM1 catalyzed by SidE effectors of Legionella pneumophila controls NFE2L2 signaling and cell metabolism upon Legionella infection. Serine ubiquitination of SQSTM1 sterically blocks its binding to KEAP1, resulting in NFE2L2 ubiquitination and degradation. This reduces NFE2L2-dependent antioxidant synthesis in the early phase of infection. Levels of serine ubiquitinated SQSTM1 diminish in the later stage of infection allowing the expression of NFE2L2-target genes; causing a differential regulation of the host metabolome and proteome in a NFE2L2-dependent manner.