Attenuation of LPS-Induced Lung Injury by Benziodarone via Reactive Oxygen Species Reduction.

As overproduction of reactive oxygen species (ROS) causes various diseases, antioxidants that scavenge ROS, or inhibitors that suppress excessive ROS generation, can be used as therapeutic agents. From a library of approved drugs, we screened compounds that reduced superoxide anions produced by pyocyanin-stimulated leukemia cells and identified benzbromarone. Further investigation of several of its analogues showed that benziodarone possessed the highest activity in reducing superoxide anions without causing cytotoxicity. In contrast, in a cell-free assay, benziodarone induced only a minimal decrease in superoxide anion levels generated by xanthine oxidase. These results suggest that benziodarone is an inhibitor of NADPH oxidases in the plasma membrane but is not a superoxide anion scavenger. We investigated the preventive effect of benziodarone on lipopolysaccharide (LPS)-induced murine lung injury as a model of acute respiratory distress syndrome (ARDS). Intratracheal administration of benziodarone attenuated tissue damage and inflammation via its ROS-reducing activity. These results indicate the potential application of benziodarone as a therapeutic agent against diseases caused by ROS overproduction.

Inhibition of ROS-Scavenging Enzyme System Is a Key Event in Tomato Genetic Resistance against Root-Knot Nematodes.

Genetic resistance in plants against incompatible pests is expressed by the activation of an immune system; however, the molecular mechanisms of pest recognition and expression of immunity, although long the object of investigation, are far from being fully understood. The immune response triggered by the infection of soil-borne parasites, such as root-knot nematodes (RKNs), to incompatible resistant tomato plants was studied and compared to the compatible response that occurred when RKNs attacked susceptible plants. In compatible interactions, the invading nematode juveniles were allowed to fully develop and reproduce, whilst that was impeded in incompatible interactions. In crude root extracts, a first assay of reactive oxygen species (ROS)-scavenging enzymatic activity was carried out at the earliest stages of tomato-RKN incompatible interaction. Membrane-bound and soluble CAT, which is the most active enzyme in hydrogen peroxide (H2O2) scavenging, was found to be specifically inhibited in roots of inoculated resistant plants until 5 days after inoculation, with respect to uninoculated plants. The expression of genes encoding for antioxidant enzymes, such as CAT and glutathione peroxidase (GPX), was not always inhibited in roots of nematode-infected resistant tomato. Therefore, the biochemical mechanisms of CAT inhibition were further investigated. Two CAT isozymes were characterized by size exclusion HPLC as a tetrameric form with a molecular weight of 220,000 dalton and its subunits (55,000 dalton). Fractions containing such isozymes were tested by their sensitivity to both salicylic acid (SA) and H2O2. It was evidenced that elevated concentrations of both chemicals led to a partial inactivation of CAT. Elevated concentrations of H2O2 in incompatible interactions have been suggested to be produced by membrane-bound superoxide anion generating, SOD, and isoperoxidase-enhanced activities. Such partial inactivation of CAT has been depicted as one of the earliest key metabolic events, which is specifically associated with tomato immunity to RKNs. Enhanced ROS production and the inhibition of ROS-scavenging systems have been considered to trigger all the metabolic events leading to cell death and tissue necrosis developed around the head of the invading juveniles by which this special type of plant resistance is exerted.

Formation of organic chloride in the treatment of textile dyeing sludge by Fenton system.

In the oxidation treatment of textile dyeing sludge, the quantitative and transformation laws of organic chlorine are not clear enough. Thus, this study mainly evaluated the treatment of textile dyeing sludge by Fenton and Fenton-like system from the aspects of the influence of Cl-, the removal of polycyclic aromatic hydrocarbons (PAHs) and organic carbon, and the removal and formation mechanism of organic chlorine. The results showed that the organic halogen in sludge was mainly hydrophobic organic chlorine, and the content of adsorbable organic chlorine (AOCl) was 0.30 mg/g (dry sludge). In the Fenton system with pH=3, 500 mg/L Cl-, 30 mmol/L Fe2+ and 30 mmol/L H2O2, the removal of phenanthrene was promoted by chlorine radicals (•Cl), and the AOCl in sludge solid phase increased to 0.55 mg/g (dry sludge) at 30 min. According to spectral analysis, it was found that •Cl could chlorinate aromatic and aliphatic compounds (excluding PAHs) in solid phase at the same time, and eventually led to the accumulation of aromatic chlorides in solid phase. Strengthening the oxidation ability of Fenton system increased the formation of organic chlorines in liquid and solid phases. In weak acidity, the oxidation and desorption of superoxide anion promoted the removal and migration of PAHs and organic carbon in solid phase, and reduced the formation of total organic chlorine. The Fenton-like system dominated by non-hydroxyl radical could realize the mineralization of PAHs, organic carbon and organic chlorines instead of migration. This paper builds a basis for the selection of sludge conditioning methods.

The Copper Chaperone CcsA, Coupled with Superoxide Dismutase SodA, Mediates the Oxidative Stress Response in Aspergillus fumigatus.

Superoxide dismutases (SODs) are important metalloenzymes that protect fungal pathogens against the toxic effects of reactive oxygen species (ROS) generated by host defense mechanisms during the infection process. The activation of Cu/Zn-SOD1 is found to be dependent on copper chaperone for SOD1 (Ccs1). However, the role of the Ccs1 ortholog in the human pathogen Aspergillus fumigatus and how these SODs coordinate to mediate oxidative stress response remain elusive. Here, we demonstrated that A. fumigatus CcsA, a Saccharomyces cerevisiae Ccs1 ortholog, is required for cells in response to oxidative response and the activation of Sod1. Deletion of ccsA resulted in increased ROS accumulation and enhanced sensitivity to oxidative stress due to the loss of SodA activity. Molecular characterization of CcsA revealed that the conserved CXC motif is required not only for the physical interaction with SodA but also for the oxidative stress adaption. Notably, addition of Mn2+ or overexpression of cytoplasmic Mn-SodC could rescue the defects of the ccsA or sodA deletion mutant, indicating the important role of Mn2+ and Mn-SodC in ROS detoxification; however, deletion of the CcsA-SodA complex could not affect A. fumigatus virulence. Collectively, our findings demonstrate that CcsA functions as a Cu/Zn-Sod1 chaperone that participates in the adaptation to oxidative stress in A. fumigatus and provide a better understanding of the CcsA-SodA complex-mediated oxidative stress response in filamentous fungi. IMPORTANCE Reactive oxygen species (ROS) produced by phagocytes have been reported to participate in the killing of fungal pathogens. Superoxide dismutases (SODs) are considered to be the first line of defense against superoxide anions. Characterizing the regulatory mechanisms of SOD activation is important for understanding how fungi adapt to oxidative stress in hosts. Our findings demonstrated that CcsA functions as a SodA chaperone in A. fumigatus and that the conserved CXC motif within CcsA is required for its interaction with SodA and the CcsA-SodA-mediated oxidative response. These data may provide new insights into how fungal pathogens adapt to oxidative stress via the CcsA-SodA complex.

Treatment of simulated textile sludge using the Fenton/Cl- system: The roles of chlorine radicals and superoxide anions on PAHs removal.

The main content of this work is to investigate the removal of polycyclic aromatic hydrocarbons (PAHs: phenanthrene, anthracene, and fluoranthene) from simulated sludge solid phase employing an Fenton/Cl- system under various Cl- contents and pH values. The steady-state concentrations of the hydroxyl, chlorine, and dichloride anion radicals ([·OH]ss, [·Cl]ss, and [Cl2·-]ss) in heterogeneous system were first measured using tert-butanol, nitrobenzene, and benzoic acid. The outcomes exhibited that increasing the Cl- content from 50 to 2000 mg/L (pH = 3.0) or raising the pH from 3.0 to 5.0 (1000 mg/L Cl-) caused [·OH]ss to continuously decrease and [Cl2·-]ss and the concentration of superoxide anions (HO2·/O2·-) to continuously increase. When the pH was 3.0 and the Cl- concentration was 1000 mg/L, [·Cl]ss had a maximum value of 9.27 × 10-14 M. Combining the results of PAH removal, radical quenching, and product analysis, it was found that ·Cl in the Fenton/Cl- system promoted the oxidative degradation of phenanthrene without forming chlorination byproducts. Furthermore, HO2·/O2·- was helpful in removing anthracene and fluoranthene. Under the environment of high Cl- content (≥1000 mg/L), PAHs could be removed more effectively by using HO2·/O2·-. This investigation underpins further study on the regulation of reactive species and the efficient degradation of target organic matter in Fenton/Cl- system, and provides a basis for studying the formation of chlorinated or toxic byproducts in the process of treating textile dyeing sludge by Fenton.

FLTX2: A Novel Tamoxifen Derivative Endowed with Antiestrogenic, Fluorescent, and Photosensitizer Properties.

Tamoxifen is the most widely used selective modulator of estrogen receptors (SERM) and the first strategy as coadjuvant therapy for the treatment of estrogen-receptor (ER) positive breast cancer worldwide. In spite of such success, tamoxifen is not devoid of undesirable effects, the most life-threatening reported so far affecting uterine tissues. Indeed, tamoxifen treatment is discouraged in women under risk of uterine cancers. Recent molecular design efforts have endeavoured the development of tamoxifen derivatives with antiestrogen properties but lacking agonistic uterine tropism. One of this is FLTX2, formed by the covalent binding of tamoxifen as ER binding core, 7-nitrobenzofurazan (NBD) as the florescent dye, and Rose Bengal (RB) as source for reactive oxygen species. Our analyses demonstrate (1) FLTX2 is endowed with similar antiestrogen potency as tamoxifen and its predecessor FLTX1, (2) shows a strong absorption in the blue spectral range, associated to the NBD moiety, which efficiently transfers the excitation energy to RB through intramolecular FRET mechanism, (3) generates superoxide anions in a concentration- and irradiation time-dependent process, and (4) Induces concentration- and time-dependent MCF7 apoptotic cell death. These properties make FLTX2 a very promising candidate to lead a novel generation of SERMs with the endogenous capacity to promote breast tumour cell death in situ by photosensitization.

High Enzyme Activity of a Binuclear Nickel Complex Formed with the Binding Loops of the NiSOD Enzyme*.

Detailed equilibrium, spectroscopic and superoxide dismutase (SOD) activity studies are reported on a nickel complex formed with a new metallopeptide bearing two nickel binding loops of NiSOD. The metallopeptide exhibits unique nickel binding ability and the binuclear complex is a major species with 2×(NH2 ,Namide ,S- ,S- ) donor set even in an equimolar solution of the metal ion and the ligand. Nickel(III) species were generated by oxidizing the NiII complexes with KO2 and the coordination modes were identified by EPR spectroscopy. The binuclear complex formed with the binding motifs exhibits superior SOD activity, in this respect it is an excellent model of the native NiSOD enzyme. A detailed kinetic model is postulated that incorporates spontaneous decomposition of the superoxide ion, the dismutation cycle and fast redox degradation of the binuclear complex. The latter process leads to the elimination of the SOD activity. A unique feature of this system is that the NiIII form of the catalyst rapidly accumulates in the dismutation cycle and simultaneously the NiII form becomes a minor species.

Angiotensin-(1-7) in Paraventricular Nucleus Contributes to the Enhanced Cardiac Sympathetic Afferent Reflex and Sympathetic Activity in Chronic Heart Failure Rats.

BACKGROUND/AIMS: Cardiac sympathetic afferent reflex (CSAR) enhancement contributes to exaggerated sympathetic activation in chronic heart failure (CHF). The current study aimed to investigate the roles of angiotensin (Ang)-(1-7) in CSAR modulation and sympathetic activation and Ang-(1-7) signaling pathway in paraventricular nucleus of CHF rats. METHODS: CHF was induced by coronary artery ligation. Responses of renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) to epicardial application of capsaicin were used to evaluate CSAR in rats with anesthesia. RESULTS: Ang-(1-7) increased RSNA, MAP, CSAR activity, cAMP level, NAD(P)H oxidase activity and superoxide anion level more significantly in CHF than in sham-operated rats, while Mas receptor antagonist A-779 had the opposite effects. Moreover, Ang-(1-7) augmented effects of Ang II in CHF rats. The effects of Ang-(1-7) were blocked by A-779, adenylyl cyclase inhibitor SQ22536, protein kinase A inhibitor Rp-cAMP, superoxide anion scavenger tempol and NAD(P)H oxidase inhibitor apocynin. Mas and AT1 receptor protein expressions, Ang-(1-7) and Ang II levels in CHF increased. CONCLUSIONS: These results indicate that Ang-(1-7) in paraventricular nucleus enhances CSAR and sympathetic output not only by exerting its own effects but also by augmenting the effects of Ang II through Mas receptor in CHF. Endogenous Ang-(1-7)/Mas receptor activity contributes to CSAR enhancement and sympathetic activation in CHF, and NAD(P)H oxidase-derived superoxide anions and the cAMP-PKA signaling pathway are involved in mediating the effects of Ang-(1-7) in CHF.

Superoxide Anions and NO in the Paraventricular Nucleus Modulate the Cardiac Sympathetic Afferent Reflex in Obese Rats.

This study was conducted to explore the hypothesis that the endogenous superoxide anions (O2-) and nitric oxide (NO) system of the paraventricular nucleus (PVN) regulates the cardiac sympathetic afferent reflex (CSAR) contributing to sympathoexcitation in obese rats induced by a high-fat diet (42% kcal as fat) for 12 weeks. CSAR was evaluated by monitoring the changes of renal sympathetic nerve activity (RSNA) and the mean arterial pressure (MAP) responses to the epicardial application of capsaicin (CAP) in anaesthetized rats. In obese rats with hypertension (OH group) or without hypertension (OB group), the levels of PVN O2-, angiotensinII (Ang II), Ang II type 1 receptor (AT1R), and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase were elevated, whereas neural NO synthase (nNOS) and NO were significantly reduced. Moreover, CSAR was markedly enhanced, which promoted the elevation of plasma norepinephrine levels. The enhanced CSAR was attenuated by PVN application of the superoxide scavenger polyethylene glycol-superoxide dismutase (PEG-SOD) and the NO donor sodium nitroprusside (SNP), and was strengthened by the superoxide dismutase inhibitor diethyldithiocarbamic acid (DETC) and the nNOS inhibitor N(ω)-propyl-l-arginine hydrochloride (PLA); conversely, there was a smaller CSAR response to PLA or SNP in rats that received a low-fat (12% kcal) diet. Furthermore, PVN pretreatment with the AT1R antagonist losartan or with PEG-SOD, but not SNP, abolished Ang II-induced CSAR enhancement. These findings suggest that obesity alters the PVN O2- and NO system that modulates CSAR and promotes sympathoexcitation.

Mitochondrial dysfunction, oxidative stress and apoptotic induction in microglial BV-2 cells treated with sodium arsenate.

The treatment of microglial BV-2 cells with sodium arsenate (As(V): 0.1-400µmol/L - 48hr) induces a dose-dependent response. The neurotoxic effects of high concentrations of As(V) (100, 200 and 400µmol/L) are characterized by increased levels of mitochondrial complexes I, II, and IV followed by increased superoxide anion generation. Moreover, As(V) triggers an apoptotic mode of cell death, demonstrated by an apoptotic SubG1 peak, associated with an alteration of plasma membrane integrity. There is also a decrease in transmembrane mitochondrial potential and mitochondrial adenosine triphosphate ATP. It is therefore tempting to speculate that As(V) triggers mitochondrial dysfunction, which may lead to defective oxidative phosphorylation subsequently causing mitochondrial oxidative damage, which in turn induces an apoptotic mode of cell death.

Surface Superoxide Complex Defects-Boosted Ultrasensitive ppb-Level NO2 Gas Sensors.

Sn(4+) -O2 (-•) centers are intentionally created in SnO2 nanoflowers by a thermodynamically instable synthetic process. The resulting SnO2 nanoflower-based sensor is confirmed to be the most sensitive ppb-level chemiresistor NO2 sensor to date. The Sn(4+) -O2 (-•) centers with strong gas-adsorbing and high eletron-donating capability towards NO2 molecules decisively determine the sensor sensitivity.

Uncoupling of endothelial nitric oxide synthase in cerebral vasculature of Tg2576 mice.

In this study, we tested the hypothesis that reduced bioavailability of tetrahydrobiopterin (BH4) is a major mechanism responsible for pathogenesis of endothelial dysfunction in cerebral microvessels of transgenic mice expressing the Swedish double mutation of human amyloid precursor protein (APP) (Tg2576 mice). Endothelial nitric oxide synthase (eNOS) protein expression was significantly increased in cerebral vasculature of Tg2576 mice. In contrast, bioavailability of BH4 was significantly reduced (p < 0.05). Moreover, superoxide anion production was increased in cerebral microvessels of Tg2576 mice (p < 0.05). Incubation with NOS inhibitor, Nω-nitro-L-arginine methyl ester, decreased superoxide anion indicating that uncoupled eNOS is most likely the source of superoxide anion. Increasing BH4 bioavailability either exogenously by BH4 supplementation or endogenously by treatment with the selective peroxisome proliferator-activated receptor--delta activator GW501516 (2 mg/kg/day, 14 days) attenuated eNOS uncoupling and decreased superoxide anion production in cerebral microvessels of Tg2576 mice (p < 0.05). Treatment with GW501516 restored the biological activity of endothelial nitric oxide in cerebral microvessels of Tg2576 mice, as indicated by the increased nitrite/nitrate content and 3,5-cyclic guanosine monophosphate levels (p < 0.05). Our studies indicate that sub-optimal BH4 bioavailability in cerebral vasculature is an important contributor to oxidant stress and endothelial dysfunction in Tg2576 mouse model of Alzheimer's disease. Existing evidence suggests that Aß peptides-induced up-regulation of expression and activity of NADPH oxidase causes increased production of superoxide anion (.O2(-)). .O2(-) can also be converted to hydrogen peroxide (H2O2) by enzymatic activity of superoxide dismutase (SOD) or spontaneous dismutation. Elevation of .O2(-) and H2O2 might cause oxidation of tetrahydrobiopterin (BH4) to dihydrobiopterin (BH2) and subsequent uncoupling of endothelial nitric oxide synthase (eNOS) (a) thus reducing levels of nitric oxide (NO) and 3',5'-cyclic guanosine monophosphate (cGMP). Supplementation of BH4 or activation of PPARδ prevents detrimental effects of eNOS uncoupling by restoring bioavailability of BH4 and scavenging of .O2(-), respectively (b). Activation of PPARδ also increases expression of catalase thereby inactivating H2O2. Generation of H2O2 by uncoupled eNOS in cerebral microvessels of Tg2576 mice is hypothetical.

Bimodal effect of oxidative stress in internal anal sphincter smooth muscle.

Changes in oxidative stress may affect basal tone and relaxation of the internal anal sphincter (IAS) smooth muscle in aging. We examined this issue by investigating the effects of the oxidative stress inducer 6-anilino-5,8-quinolinedione (LY-83583) in basal as well as U-46619-stimulated tone, and nonadrenergic, noncholinergic (NANC) relaxation in rat IAS. LY-83583, which works via generation of reactive oxygen species in living cells, produced a bimodal effect in IAS tone: lower concentrations (0.1 nM to 10 µM) produced a concentration-dependent increase, while higher concentrations (50-100 µM) produced a decrease in IAS tone. An increase in IAS tone by lower concentrations was associated with an increase in RhoA/Rho kinase (ROCK) activity. This was evident by the increase in RhoA/ROCK in the particulate fractions, in ROCK activity, and in the levels of phosphorylated (p) (Thr696)-myosin phosphatase target subunit 1 and p(Thr18/Ser19)-20-kDa myosin light chain. Conversely, higher concentrations of LY-83583 produced inhibitory effects on RhoA/ROCK. Interestingly, both the excitatory and inhibitory effects of LY-83583 in the IAS were reversed by superoxide dismutase. The excitatory effects of LY-83583 were found to resemble those with neuronal nitric oxide synthase (nNOS) inhibition by l-NNA, since it produced a significant increase in the IAS tone and attenuated NANC relaxation. These effects of LY-83583 and l-NNA were reversible by l-arginine. This suggests the role of nNOS inhibition and RhoA/ROCK activation in the increase in IAS tone by LY-83583. These data have important implications in the pathophysiology and therapeutic targeting of rectoanal disorders, especially associated with IAS dysfunction.

Oxygen Targets in Neonatal Pulmonary Hypertension: Individualized, "Precision-Medicine" Approach.

Oxygen is a specific pulmonary vasodilator. Hypoxemia causes pulmonary vasoconstriction, and normoxia leads to pulmonary vasodilation. However, hyperoxia does not enhance pulmonary vasodilation but causes oxidative stress. There are no clinical trials evaluating optimal oxygen saturation or Pao2 in pulmonary hypertension. Data from translational studies and case series suggest that oxygen saturation of 90% to 97% or Pao2 between 50 and 80 mm Hg is associated with the lowest pulmonary vascular resistance.

Cascade enzyme-mimicking with spatially separated gold-ceria for dual-mode detection of superoxide anions.

Metal-semiconductor nanozyme of dumbbell Au-CeO2 with spatially separated heterostructure has cascade superoxide dismutase (SOD)-like and peroxidase (POD)-like activities for superoxide anions detection. It was synthesized by selective growth of CeO2 at the ends of Au nanorod (Au NR). Taking advantage of the excellent local surface plasmon resonance (LSPR) effect of Au NR, the spatially separated Au-CeO2 has a higher photothermal effect than the continuously growing core-shell structure of Au@CeO2. Meanwhile, the hot electrons of Au NR could transfer to CeO2 under 808 nm laser irradiation, changing the ratio of Ce3+/Ce4+ redox couples over CeO2 and facilitating H2O2 decomposition thus enhancing POD-like activity. Based on the SOD-like activity of Au-CeO2, superoxide anion (O2·-) can be transformed into hydrogen peroxide (H2O2). Dual-mode including absorbance and temperature sensing detection of O2·-, with the detection range from nM to µM i.e., 0.1-150 µM and LOD of 0.033 µM (S/N = 3) was achieved through the cascade catalysis and photothermal effect. The as-proposed method was applicable to both cancer and normal cell samples with satisfactory accuracy and recovery.

Superoxide dismutase and neurological disorders.

Superoxide dismutase (SOD) is a common antioxidant enzyme found majorly in living cells. The main physiological role of SOD is detoxification and maintain the redox balance, acts as a first line of defence against Reactive nitrogen species (RNS), Reactive oxygen species (ROS), and other such potentially hazardous molecules. SOD catalyses the conversion of superoxide anion free radicals (O 2 -.) into molecular oxygen (O 2) and hydrogen peroxide (H 2O 2) in the cells. Superoxide dismutases (SODs) are expressed in neurons and glial cells throughout the CNS both intracellularly and extracellularly. Endogenous oxidative stress (OS) linked with enlarged production of reactive oxygen metabolites (ROMs), inflammation, deregulation of redox balance, mitochondrial dysfunction and bioenergetic crisis are found to be prerequisite for neuronal loss in neurological diseases. Clinical and genetic studies indicate a direct correlation between mutations in SOD gene and neurodegenerative diseases, like Amyotrophic Lateral Sclerosis (ALS), Huntington's disease (HD), Parkinson's Disease (PD) and Alzheimer's Disease (AD). Therefore, inhibitors of OS are considered as an optimistic approach to prevent neuronal loss. SOD mimetics like Metalloporphyrin Mn (II)-cyclic polyamines, Nitroxides and Mn (III)- Salen complexes are designed and used as therapeutic extensively in the treatment of neurological disorders. SODs and SOD mimetics are promising future therapeutics in the field of various diseases with OS-mediated pathology.

Persulfate adsorption and activation by carbon structure defects provided new insights into ofloxacin degradation by biochar.

Cellulose and lignin derived biochars with significant differences in persistent free radicals (PFRs), oxygen-containing functional groups, and defective structure were prepared to explore the mechanism of biochar mediated persulfate (PS) activation. EPR spin trapping and quenching technique coupled with degradation experiments confirmed that the defective structures could activate PS to generate superoxide anions (O2•-), which was converted to singlet oxygen (1O2), especially in the acidic condition. 1O2 dominated the degradation of ofloxacin (OFL, a fluoroquinolone antibiotic). An improved iodometric measurement was applied for direct quantification of adsorbed PS on biochar. The amounts of adsorbed PS were consistent with the degradation of OFL and the measured electric current during the reaction indicated that PS adsorption was a prerequisite for PS activation, which may be neglected in previous studies. The results of this study highlighted the key roles of defective structure and adsorption of PS on biochar for the activation of PS.

Pulmonary hypertension and oxidative stress: Where is the link?

Oxidative stress can be associated with hyperoxia and hypoxia and is characterized by an increase in reactive oxygen (ROS) and nitrogen (RNS) species generated by an underlying disease process or by supplemental oxygen that exceeds the neutralization capacity of the organ system. ROS and RNS acting as free radicals can inactive several enzymes and vasodilators in the nitric oxide pathway promoting pulmonary vasoconstriction resulting in persistent pulmonary hypertension of the newborn (PPHN). Studies in animal models of PPHN have shown high ROS/RNS that is further increased by hyperoxic ventilation. In addition, antioxidant therapy increased PaO2 in these models, but clinical trials are lacking. We recommend targeting preductal SpO2 between 90 and 97%, PaO2 between 55 and 80 mmHg and avoiding FiO2 > 0.6-0.8 if possible during PPHN management. This review highlights the role of oxidative and nitrosative stress markers on PPHN and potential therapeutic interventions that may alleviate the consequences of increased oxidant stress during ventilation with supplemental oxygen.

Two-dimensional mesoporous nitrogen-rich carbon nanosheets loaded with CeO2 nanoclusters as nanozymes for the electrochemical detection of superoxide anions in HepG2 cells.

Two-dimensional (2D) porous carbon-based composite nanosheets loaded with metal oxide nanoclusters are expected to be promising electrocatalysts for high-performance electrochemical sensors. However, for this complicated composite material, strict reaction conditions and complex synthesis steps limit its general application in electrochemical detection. Here we present a facile method to fabricate 2D mesoporous nitrogen-rich carbon nanosheets loaded with CeO2 nanoclusters (2D-mNC@CeO2), for fabricating superoxide anions (O2•-) electrochemical sensor. The method is based on block copolymers self-assembly and the affinity of polydopamine to metal ions to obtain organic-inorganic hybrid, which can be directly converted into 2D-mNC@CeO2 through carbonization strategy without structural deterioration. Characterizations demonstrate that the 2D-mNC@CeO2 owned the 2D N-doped carbon structure with an interlinked hierarchical mesoporous and the uniformly dispersed CeO2 nanoclusters on the surface. Benefitted from the unique structure, the 2D-mNC@CeO2 shortens electron transfer distance, enhances mass transfer efficiency, exposes numerous active sites, and obtain a high Ce3+/Ce4+ ratio for improving electrocatalytic performance. The 2D-mNC@CeO2/SPCEs sensors for O2•- detection has a detection limit of 0.179 µM (S/N = 3) and sensitivity of 401.4 µA cm-2 mM-1. The sensors can be applied to capture electrochemical signals of O2•- released from HepG2 cells, demonstrating the application potential of the sensors to monitor O2•- in biological fields.

Facile synthesis of ultrathin two-dimensional graphene-like CeO2-TiO2 mesoporous nanosheet loaded with Ag nanoparticles for non-enzymatic electrochemical detection of superoxide anions in HepG2 cells.

Here we presented a new facile strategy to fabricate ultrathin two-dimensional (2D) metal oxide nanosheets, by using polydopamine-coated graphene (rGO@PDA) as a template under simply wet-chemical conditions. Based on the strategy, graphene-like CeO2-TiO2 mesoporous nanosheet (MNS-CeO2-TiO2) was prepared and was loaded with dispersive Ag nanoparticles (AgNPs) to obtain effective electrocatalysts (denoted as Ag/MNS-CeO2-TiO2) for electrochemical detection of superoxide anion (O2•-). Characterizations demonstrated that MNS-CeO2-TiO2 exhibited ultrathin thickness, larger specific surface area, and pore volume in comparison with its bulk counterpart. The above properties of MNS-CeO2-TiO2 shorten electron transmission distance, promotes mass transfer, and is conducive to the dispersion of post-modified AgNPs. Therefore, the recommended Ag/MNS-CeO2-TiO2 sensors (denoted as Ag/MNS-CeO2-TiO2/SPCE) exhibited satisfactory properties, including the sensitivity of 737.1 µA cm-2 mM-1, the detection limit of 0.0879 µM (S/N = 3), and good selectivity. Meanwhile, the sensors also successfully realized in the online monitoring of O2•- released from HepG2 cells, meaning the prepared sensors had practical application potential towards the analysis of O2•- in biological samples.