Injectable reactive oxygen and nitrogen species-controlling hydrogels for tissue regeneration:current status and future perspectives

The dual role of reactive oxygen and nitrogen species(RONS)in physiological and pathological processes in biological systems has been widely reported.It has been recently suggested that the regulation of RONS levels under physiological and pathological conditions is a potential therapy to promote health and treat diseases,respectively.Injectable hydrogels have been emerging as promising biomaterials for RONS-related biomedical applications owing to their excellent biocompatibility,three-dimensional and extracellular matrix-mimicking structures,tunable properties and easy functionalization.These hydrogels have been developed as advanced injectable platforms for locally generating or scavenging RONS,depending on the specific conditions of the target disease.In this review article,the design principles and mechanism by which RONS are generated/scavenged from hydrogels are outlined alongside a discussion of their in vitro and in vivo evaluations.Additionally,we highlight the advantages and recent developments of these injectable RONS-controlling hydrogels for regenerativemedicines and tissue engineering applications.

Scavenging of reactive oxygen and nitrogen species with nanomaterials

Reactive oxygen and nitrogen species （RONS） are essential for normal physiological processes and play important roles in cell signaling, immunity, and tissue homeostasis. However, excess radical species are implicated in the development and augmented pathogenesis of various diseases. Several antioxidants may restore the chemical balance, but their use is limited by disappointing results of clinical trials. Nanoparticles are an attractive therapeutic alternative because they can change the biodistribution profile of antioxidants, and possess intrinsic ability to scavenge RONS. Herein, we review the types of RONS, how they are implicated in several diseases, and the types of nanoparticles with inherent antioxidant capability, their mechanisms of action, and their biological applications.

MEASUREMENTS OF REACTIVE NITROGEN SPECIES IN THE EASTERN CHINA DURING THE EXPERIMENT PEM-WEST A

Measurements of NO_x(NO+NO_2),HNO_3,particulate nitrate,and total odd nitrogen NO_y were made at Lin atmosphere regional background station during the NASA GTE/PEM-WEST A in the fall of 1991.NO_x and N were measured using chemiluminescence detectors.HNO_3 and aerosol nitrate(NO_3^-)were collected by a filter syst NO_x concentration exhibits a significant diurnal variation:maximum occurring in the evening and postsunrise w peak occurring following sunrise.Unlike NO_x,NO_y does not show distinct diurnal variations.From the ratios day/night NO_x concentration and the diurnal cycles of two kinds of weather conditions,it is clear that photochemical production of NO_x varies with solar radiation.NO_x is the major component of total odd nitro NO_y and NO_2 is the major portion of NO_x as well.The regional background concentrations of NO_x,NO_y,aerosol trate(NO_3^-)and HNO_3 range from 4.77 to 7.02 ppb,9.24 to 10.95 ppb,0.33 to 2.38 ppb and 0.31 to 0.97 ppb in a day average,respectively.In the eastern China,the biomass burning is an important local emission source of nitro species.The ratios of NO/NO_2,NO_x/NO_y,HNO_3/NO_y,NO_3^-/NO_y and HNO_3/NO_x are also discussed in paper.

Reactive oxygen and nitrogen species regulate porcine embryo development during pre-implantation period:A mini-review

Significant porcine embryonic loss occurs during conceptus morphological elongation and attachment from d 10 to 20 of pregnancy,which directly decreases the reproductive efficiency of sows.A successful establishment of pregnancy mainly depends on the endometrium receptivity,embryo quality,and utero-placental microenvironment,which requires complex cross-talk between the conceptus and uterus.The understanding of the molecular mechanism regulating the uterine-conceptus communication during porcine conceptus elongation and attachment has developed in the past decades.Reactive oxygen and nitrogen species,which are intracellular reactive metabolites that regulate cell fate decisions and alter their biological functions,have recently reportedly been involved in porcine conceptus elongation and attachment.This mini-review will mainly focus on the recent researches about the role of reactive ox-ygen and nitrogen species in regulating porcine embryo development during the pre-implantation period.

The relationship between the high-frequency performance of supercapacitors and the type of doped nitrogen in the carbon electrode

Nitrogen doping has been widely used to improve the performance of carbon electrodes in supercapacitors,particularly in terms of their high-frequency response.However,the charge storage and electrolyte ion response mechanisms of different nitrogen dopants at high frequencies are still unclear.In this study,melamine foam carbons with different configurations of surfacedoped N were formed by gradient carbonization,and the effects of the configurations on the high-frequency response behavior of the supercapacitors were analyzed.Using a combination of experiments and first-principle calculations,we found that pyrrolic N,characterized by a higher adsorption energy,increases the charge storage capacity of the electrode at high frequencies.On the other hand,graphitic N,with a lower adsorption energy,increases the speed of ion response.We propose the use of adsorption energy as a practical descriptor for electrode/electrolyte design in high-frequency applications,offering a more universal approach for improving the performance of N-doped carbon materials in supercapacitors.

Generation and Distribution of Fast Atomic Species(N^+,N_f)in Nitrogen Glow Discharge

Using a combination of the Monte Carlo models of fast electrons, of molecular ions （N＋） and of atomic species （N^＋, Nf）, the influence of the discharge pressure （P） and voltage （Vc） on the energy distributions of fast atomic species （N^＋, Nf） produced by e^--N2s and N2^＋- N2s dissociation reactions at the cathode in a nitrogen dc glow discharge was investigated. Both the angular distributions and the density distributions along the radius of the species （N^＋, Nf） produced by the two dissociations at the cathode were calculated. The results show that： （1） there is an optimum discharge condition for P and Vc in order to obtain the species （N^＋, Nf） at the cathode with high a density and energy, （2） when the voltage is above 800 V, the species （N^＋, Nf） bombarding the cathode are mainly produced by the N^＋-N2s dissociation, whereas when the voltage is below 300 V, they are mainly produced by the e-N2s dissociation, and （3） at high Voltages the incident angles of a considerable number of Nf into the cathode are quite small. The density of the species （N^＋ Nf） at the cathode increases with the voltage, and when the pressure goes up to about 133 Pa, it decreases with the increasing pressure.

Comparison of Mechanisms of N-Nitrosation and N-Nitration of Ammonia and Dimethylamine by Reactive Nitrogen Oxygen Species:A Theoretical Study

Reactive nitrogen oxygen species（RNOS） implicate damage in biological systems,especially leading to inflammation,neurodegenerative and cardiovascular diseases,and cancer by altering the functions of biomolecules through the N-nitrosation and N-nitration reactions.The mechanisms of N-nitrosation and N-nitration reactions of ammonia and dimethylamine by RNOS,i.e.,N2O3,N2O4,N2O5 and ONOOH,were investigated at the CBS-QB3 level of theory.The computational results indicate that the N-nitrosation reaction prefers a concerted mechanism,in which a H-abstraction and ON-addition occur simultaneously,whereas a stepwise mechanism（also called a free radical mechanism） is more favorable for most nitrating agents in the N-nitration reaction,where NO2 first abstracts a hydrogen atom from the nitrogen of amines and then the induced intermediate reacts with NO2 once more to form the nitration products.However,the concerted pathway is still a feasible process for some nitrating agents such as N2O5.In addition,the relationship between the structures of different RNOS and their nitrosating or nitrating abilities was also investigated.

Role of nitric oxide in cerebral ischemia/reperfusion injury:A biomolecular overview

Nitric oxide(NO)is a gaseous molecule produced by 3 different NO synthase(NOS)isoforms:Neural/brain NOS(nNOS/bNOS,type 1),endothelial NOS(eNOS,type 3)and inducible NOS(type 2).Type 1 and 3 NOS are constitutively expressed.NO can serve different purposes:As a vasoactive molecule,as a neurotransmitter or as an immunomodulator.It plays a key role in cerebral ischemia/reperfusion injury(CIRI).Hypoxic episodes simulate the production of oxygen free radicals,leading to mitochondrial and phospholipid damage.Upon reperfusion,increased levels of oxygen trigger oxide synthases;whose products are associated with neuronal damage by promoting lipid peroxidation,nitrosylation and excitotoxicity.Molecular pathways in CIRI can be altered by NOS.Neuroprotective effects are observed with eNOS activity.While nNOS interplay is prone to endothelial inflammation,oxidative stress and apoptosis.Therefore,nNOS appears to be detrimental.The interaction between NO and other free radicals develops peroxynitrite;which is a cytotoxic agent.It plays a main role in the likelihood of hemorrhagic events by tissue plasminogen activator(t-PA).Peroxynitrite scavengers are currently being studied as potential targets to prevent hemorrhagic transformation in CIRI.

Study on the protective effect of Tadehaginoside on the damage of endothelial cell mitochondria induced by reactive nitrogen

Objective:To investigate the protective effect of Tadehaginoside on vascular endothelial cell injury induced by reactive nitrogen.Methods:MTT colorimetry was used to detect the effect of Tadehaginoside on the survival rate of EA.hy 926 endothelial cells in the concentration range of 5~160μmol/L;1 h after pre-administration of Tadehaginoside,0.5 mM GSNO was given to damage endothelial cells.Detect the mitochondrial specific factors COX-1,ND-1 and inflammatory factor IL-1βof EA.hy 926 cells damaged by GSNO by Real time-PCR method gene intervention.At the same time,Western blot was used to detect the changes in Bax and Bcl-2 protein expression.The mitochondrial membrane potential kit(JC-1)was used to detect the change of Tadehaginoside on the mitochondrial membrane potential after GSNO induced EA.hy 926 cell injury.Results:The results of the MTT method showed that Tadehaginoside had no obvious cytotoxicity on EA.hy 926 cells in the range of 5~160μmol/L,and the optimal protective concentration of the drug was 40μmol/L.Western Blot method showed that BAX protein expression increased in a time-dependent manner after GSNO damaged EA.hy 926 cells over time,while Bcl-2 protein expression was the opposite.Real time-PCR results showed that Tadehaginoside can significantly up-regulate COX-1 gene(P<0.05),and can significantly inhibit GSNO induced ND-1(P<0.05)and IL-1βgene up-regulation(P<0.01).At the same time,the results of JC-1 showed that Tadehaginoside could significantly protect the mitochondrial membrane potential from GSNO damage.Conclusion:The GSNO damage model may induce the increase of Bax and other pro-apoptotic proteins through mitochondrial DNA damage and reduce the expression of anti-apoptotic factor Bcl-2.Tadehaginoside has a certain protective effect on endothelial cell mitochondrial damage induced by reactive nitrogen,and its mechanism is related to inhibiting the expression of ND-1 and IL-1βgenes and upregulating the expression of COX-1 genes.

Functional relationships of nodulation response and biomass production at nursery stages of two fast-growing, leguminous-multipurpose tree species in Bangladesh: Albizia saman and Leucaena leucocephala

This study was carried out to assess the relationship of the status of nodulation(i.e., the number of nodules, their shape and size) in root and biomass production of plant growth parameters(i.e., number of leaves, root and shoot lengths, root biomass and shoot biomass) in Albizia saman and Leucaena leucocephala. The assessment started 60 days after seeding. The study revealed that nodulation response and biomass production in both species showed significant differences over time(p < 0.05) in all variables except in the root-shoot ratio(oven-dry) of L. leucocephala. The study also showed significant differences(p < 0.05) in nodule formation and biomass production at the end of the study period between the two species except in the number of nodules and leaves and the green root-shoot ratio. There were strong positive correlations between nodule formation and biomass production, i.e., the number of nodules and the age of plants, the number of nodules and leaves, as well as the number of nodules and biomass(root biomass and shoot biomass) in both species. The results obtained using principal component analysis(PCA) and correlation coefficients of the different characteristics of nodulation and biomass production were similar in both species. The PCA showed that shoot biomass(shoot green weight and shoot oven-dry weight) is positively correlated with PC1(with an eigenvalue of 7.50) and root length is positively correlated with PC2(with an eigenvalue of 0.19) in the case of A. saman. In the case of L. leucocephala, the PCA revealed that root biomass(root green weight and root oven-dry weight), shoot biomass and shoot length are also positively correlated with PC1, while nodule formation and the number of leaves are positively correlated with PC2(with an eigenvalue PC1 of 6.92 and PC2 of 0.49).

Hydrogeochemical and isotopic assessment of the origin of NO_(3)^(−)and N-NH_(3)contents in the aquifer located in a closed lacustrine volcano-sedimentary basin in the metropolitan area of Mexico City

To explain the presence and spatial distribution of NO_(3)^(−)and N-NH_(3)in the Aquifer of the Metropolitan Area of Mexico City(AMAMC),a hydrogeochemical and isotopic analysis using^(13)C DIC(as well as the stable isotopes^(18)O and^(2)H)in groundwater was conducted.This aquifer is located in an old closed lacustrine volcano-sedimentary basin;some wells hosted in the semi-confined zone contain high N-NH_(3)concentrations,while others present NO_(3)^(−)contents in the recharge zones(hosted in an oxidizing environment).In this study,a change in the isotopic signature(primarily in^(18)O and^(2)H)was observed from the recharge zones to the basin center in some of the wells with high NO_(3)^(−)concentrations,this behavior can be attributed to evaporation during the incorporation of recently infiltrated water.In addition,the results for^(13)C(along with ^(2) H)in wells with the highest N-NH_(3)concentrations exhibited an atypically broad range of values.Results indicated the occurrence of hydrogeochemical and/or biochemical processes in the aquifer(in an oxidizing or reducing environment),such as organic degradation,bacterial decomposition(primarily in the ancient Lake Texcoco and which acts as a natural sink for carbon,nitrogen,sulfur,and phosphorus),besides rock weathering and dissolution,which may be responsible for a very marked isotopic modification of the^(13)C(and,to a lesser extent,2 H).Methanotrophic bacterial activity and methanogenic activity may be related to N-NH_(3)removal processes by oxidation and residual water incorporation respectively,whereas the increase in the NO_(3)^(−)content in some wells is due to the recent contribution of poor-quality water due to contamination.

NIR-triggered on-site NO/ROS/RNS nanoreactor:Cascade-amplified photodynamic/photothermal therapy with local and systemic immune responses activation

Photothermal and photodynamic therapies(PTT/PDT)hold promise for localized tumor treatment,yet their full potential is hampered by limitations such as the hypoxic tumor microenvironment and inadequate systemic immune activation.Addressing these challenges,we present a novel near-infrared(NIR)-triggered RNS nanoreactor(PBNO-Ce6)to amplify the photodynamic and photothermal therapy efficacy against triple-negative breast cancer(TNBC).The designed PBNOCe6 combines sodium nitroprusside-doped Prussian Blue nanoparticles with Chlorin e6 to enable on-site RNS production through NIR-induced concurrent NO release and ROS generation.This not only enhances tumor cell eradication but also potentiates local and systemic antitumor immune responses,protecting mice from tumor rechallenge.Our in vivo evaluations revealed that treatment with PBNO-Ce6 leads to a remarkable 2.7-fold increase in cytotoxic T lymphocytes and a 62%decrease in regulatory T cells in comparison to the control PB-Ce6(Prussian Blue nanoparticles loaded with Chlorin e6),marking a substantial improvement over traditional PTT/PDT.As such,the PBNO-Ce6 nanoreactor represents a transformative approach for improving outcomes in TNBC and potentially other malignancies affected by similar barriers.

Regulatory role of peroxynitrite in advanced glycation end products mediated diabetic cardiovascular complications

The Advanced Glycation End Products(AGE)binding with its receptor can increase reactive oxygen species(ROS)generation through specific signaling mediators.The effect of superoxide(O2-)and O2-mediated ROS and reactive nitrogen species depends on their concentration and location of formation.Nitric oxide(NO)has anti-inflammatory and anticoagulant properties and a vasodilation effect,but NO can be deactivated by reacting with O_(2)^(-).This reaction between NO and O2-produces the potent oxidant ONOO−.Therefore,ONOO-'s regulatory role in AGEs in diabetic cardiovascular complications must considered as a regulator of cardiovascular complications in diabetes.

Electrocatalytic synthesis of C-N coupling compounds from CO_(2) and nitrogenous species

The electrocatalytic synthesis of C-N coupling compounds from CO_(2) and nitrogenous species not only offers an effective avenue to achieve carbon neutral-ity and reduce environmental pollution,but also establishes a route to synthesize valuable chemicals,such as urea,amide,and amine.This innovative approach expands the application range and product categories beyond simple carbona-ceous species in electrocatalytic CO_(2) reduction,which is becoming a rapidly advancing field.This review summarizes the research progress in electrocatalytic urea synthesis,using N_(2),NO_(2)^(-),and NO_(3)^(-)as nitrogenous species,and explores emerging trends in the electrosynthesis of amide and amine from CO_(2) and nitro-gen species.Additionally,the future opportunities in this field are highlighted,including electrosynthesis of amino acids and other compounds containing C-N bonds,anodic C-N coupling reactions beyond water oxidation,and the catalytic mechanism of corresponding reactions.This critical review also captures the insights aimed at accelerating the development of electrochemical C-N coupling reactions,confirming the superiority of this electrochemical method over the traditional techniques.

The influence of the type of N dopping on the performance of bifunctional N-doped ordered mesoporous carbon electrocatalysts in oxygen reduction and evolution reaction

To develop more ideal bifunctional heteroatom-doped carbon electrocatalysts toward the oxygen reduction reaction(ORR) and oxygen evolution reaction(OER) for regenerative fuel cells and rechargeable metal–air batteries, herein, tobacco-derived N-containing ordered mesoporous carbon(N-OMC) electrocatalysts with different N species distributions are designed. Results indicate that the as-prepared N-OMC with more pyrrolic and pyridinic Ns exhibits much higher activities for the ORR and OER than N-OMC with more graphitic N in both acidic and alkaline media, suggesting that the increase of pyrrolic and pyridinic Ns favors the improvement of ORR and OER activities of the N-containing carbon catalysts, and showing a great potential for the designing of more effective, lower-cost ORR and OER bifunctional electrocatalysts for future regenerative fuel cells and rechargeable metal–air batteries.

Quality enhancement and microbial reduction of mung bean(Vigna radiata)sprouts by non-thermal plasma pretreatment of seeds

Mung bean(Vigna radiata)sprouts are widely consumed worldwide due to their high nutritional value.However,the low yield and microbial contamination of mung bean sprouts seriously reduces their economic value.This study investigates the effects of non-thermal plasma on the quality and microbial reduction of mung bean sprouts by pretreatment of seeds in water for different times(0,1,3 and 6 min).The quality results showed that short-time plasma treatment(1 and 3 min)promoted seed germination and seedling growth,whereas long-time plasma treatment(6 min)had inhibitory effects.Plasma also had a similar dose effects on the total flavonoid and phenolic contents of mung bean sprouts.The microbiological results showed that plasma treatment achieved a reduction of native microorganisms ranging from 0.54 to 7.09 log for fungi and 0.29 to 6.80 log for bacteria at 96 h incubation.Meanwhile,plasma treatment could also efficiently inactivate artificially inoculated Salmonella typhimurium(1.83–6.22 log)and yeast(0.53–3.19 log)on mung bean seeds.The results of seed coat permeability tests and scanning electron microscopy showed that plasma could damage the seed coat structure,consequently increasing the electrical conductivity of mung bean seeds.The physicochemical analysis of plasma-treated water showed that plasma generated various long-and short-lived active species[nitric oxide radicals(NO·),hydroxyl radicals(·OH),singlet oxygen(1O2),hydrogen peroxide(H_(2)O_(2)),nitrate(NO_(3)^(-)),and nitrite(NO_(2)^(-))]in water,thus the oxidizability,acidity and conductivity of plasma-treated water were all increased in a treatment timedependent manner.The result for mimicked chemical mixtures confirmed the synergistic effect of activity of H_(2)O_(2),NO_(3)^(-)and NO_(2)^(-)on bacterial inactivation and plant growth promotion.Taken together,these results imply that plasma pretreatment of mung bean seeds in water with moderate oxidizability and acidity is an effective method to improve the yield of mung bean sprouts and reduce microbial contamination.

Effect of low-temperature plasma on the degradation of omethoate residue and quality of apple and spinach

Dielectric barrier corona discharge was developed to generate low-temperature plasma(LTP) to treat apple and spinach samples contaminated with omethoate. Experimental results showed that,after 20 min exposure, the degradation rate of omethoate residue in apple and spinach was(94.55± 0.01)% and(95.55 ± 0.01)%, respectively. When the treatment time was shorter than 20 min,the contents of moisture, vitamin C and beta-carotene were not affected by LTP. Exploration of related mechanisms suggested that LTP might destroy unsaturated double bonds of omethoate and produce phosphate ion, eventually leading to omethoate destruction. It is concluded that appropriate dosage of LTP can effectively degrade omethoate residue in fruits and vegetables without affecting their quality.

Effects of nitrogen dioxide and its acid mist on reactive oxygen species production and antioxidant enzyme activity in Arabidopsis plants

Nitrogen dioxide（NO2） is one of the most common and harmful air pollutants. To analyze the response of plants to NO2 stress, we investigated the morphological change, reactive oxygen species（ROS） production and antioxidant enzyme activity in Arabidopsis thaliana（Col-0） exposed to 1.7, 4, 8.5, and 18.8 mg/m3NO2. The results indicate that NO2 exposure affected plant growth and chlorophyll（Chl） content, and increased oxygen free radical（O2-）production rate in Arabidopsis shoots. Furthermore, NO2 elevated the levels of lipid peroxidation and protein oxidation, accompanied by the induction of antioxidant enzyme activities and change of ascorbate（As A） and glutathione（GSH） contents. Following this, we mimicked nitric acid mist under experimental conditions, and confirmed the antioxidant mechanism of the plant to the stress. Our results imply that NO2 and its acid mist caused pollution risk to plant systems. During the process, increased ROS acted as a signal to induce a defense response, and antioxidant status played an important role in plant protection against NO2/nitric acid mist-caused oxidative damage.

H_2O_2-induced Leaf Cell Death and the Crosstalk of Reactive Nitric/Oxygen Species

In plants, the chloroplast is the main reactive oxygen species （ROS） producing site under high light stress. Catalase （CAT）, which decomposes hydrogen peroxide （H2O2）, is one of the controlling enzymes that maintains leaf redox homeostasis. The catalase mutants with reduced leaf catalase activity from different plant species exhibit an H2O2-induced leaf cell death phenotype. This phenotype was differently affected by light intensity or photoperiod, which may be caused by plant species, leaf redox status or growth conditions. In the rice CAT mutant nitric oxide excess 1 （noe1）, higher H2O2 levels induced the generation of nitric oxide （NO） and higher S-nitrosothiol （SNO） levels, suggesting that NO acts as an important endogenous mediator in H2O2-induced leaf cell death. As a free radical, NO could also react with other intracellular and extracellular targets and form a series of related molecules, collectively called reactive nitrogen species （RNS）. Recent studies have revealed that both RNS and ROS are important partners in plant leaf cell death. Here, we summarize the recent progress on H2O2-induced leaf cell death and the crosstalk of RNS and ROS signals in the plant hypersensitive response （HR）, leaf senescence, and other forms of leaf cell death triggered by diverse environmental conditions.

Photoactivatable nanogenerators of reactive species for cancer therapy

In recent years,reactive species-based cancer therapies have attracted tremendous attention due to their simplicity,controllability,and effectiveness.Herein,we overviewed the state-of-art advance for photo-controlled generation of highly reactive radical species with nanomaterials for cancer therapy.First,we summarized the most widely explored reactive species,such as singlet oxygen,superoxide radical anion(O2●-),nitric oxide(●NO),carbon monoxide,alkyl radicals,and their corresponding secondary reactive species generated by interaction with other biological molecules.Then,we discussed the generating mechanisms of these highly reactive species stimulated by light irradiation,followed by their anticancer effect,and the synergetic principles with other therapeutic modalities.This review might unveil the advantages of reactive species-based therapeutic methodology and encourage the pre-clinical exploration of reactive species-mediated cancer treatments.