With an increase in global aging,the number of people affected by cerebrovascular diseases is also increasing,and the incidence of vascular dementia-closely related to cerebrovascular risk-is increasing at an epidemic...With an increase in global aging,the number of people affected by cerebrovascular diseases is also increasing,and the incidence of vascular dementia-closely related to cerebrovascular risk-is increasing at an epidemic rate.However,few therapeutic options exist that can markedly improve the cognitive impairment and prognosis of vascular dementia patients.Similarly in Alzheimer’s disease and other neurological disorders,synaptic dysfunction is recognized as the main reason for cognitive decline.Nitric oxide is one of the ubiquitous gaseous cellular messengers involved in multiple physiological and pathological processes of the central nervous system.Recently,nitric oxide has been implicated in regulating synaptic plasticity and plays an important role in the pathogenesis of vascular dementia.This review introduces in detail the emerging role of nitric oxide in physiological and pathological states of vascular dementia and summarizes the diverse effects of nitric oxide on different aspects of synaptic dysfunction,neuroinflammation,oxidative stress,and blood-brain barrier dysfunction that underlie the progress of vascular dementia.Additionally,we propose that targeting the nitric oxide-sGC-cGMP pathway using certain specific approaches may provide a novel therapeutic strategy for vascular dementia.展开更多
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 expre...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.展开更多
BACKGROUND Esophageal cancer(ESCA)is among the most prevalent and lethal tumors globally.While nitric oxide synthase 1(NOS1)is recognized for its important in-volvement in various cancers,its specific function in ESCA...BACKGROUND Esophageal cancer(ESCA)is among the most prevalent and lethal tumors globally.While nitric oxide synthase 1(NOS1)is recognized for its important in-volvement in various cancers,its specific function in ESCA remains unclear.AIM To explore the potential role and underlying mechanisms of NOS1 in ESCA.METHODS Survival rates were analyzed using GeneCards and Gene Expression Profiling Interactive Analysis.The effects and mechanisms of NOS1 on ESCA cells were evaluated via the Cell Counting Kit-8 assay,scratch assay,Transwell assay,flow cytometry,quantitative polymerase chain reaction,western blotting,and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling staining.The protein interaction network was used to screen the interacting proteins of NOS1 and validate these interactions through co-immuno-precipitation and dual luciferase assays.Additionally,a nude mouse xenograft model was established to evaluate the effect of NOS1 in vivo.RESULTS The survival rate of patients with ESCA with high NOS1 expression was higher than that of patients with low NOS1 expression.NOS1 expression in ESCA cell lines was lower than that in normal esophageal epithelial cells.Overexpression of NOS1(oe-NOS1)inhibited proliferation,invasion,and migration abilities in ESCA cell lines,resulting in decreased autophagy levels and increased apoptosis,pyroptosis,and ferroptosis.Protein interaction studies confirmed the interaction between NOS1 and NOS1 adaptor protein(NOS1AP).Following oe-NOS1 and the silencing of NOS1AP,levels of P62 and microtubule-associated protein 1 light chain 3 beta increased both in vitro and in vivo.Furthermore,the expression levels of E-cadherin,along with the activation of phosphatidylinositol 3-kinase(PI3K)and protein kinase B(AKT),were inhibited in ESCA cell lines.CONCLUSION NOS1 and NOS1 proteins interact to suppress autophagy,activate the PI3K/AKT pathway,and exert anti-cancer effects in ESCA.展开更多
Background:Under hypoxia,exaggerated compensatory responses may lead to acute mountain sickness.The excessive vasodilatory effect of nitric oxide(NO)can lower the hypoxic pulmonary vasoconstriction(HPV)and peripheral ...Background:Under hypoxia,exaggerated compensatory responses may lead to acute mountain sickness.The excessive vasodilatory effect of nitric oxide(NO)can lower the hypoxic pulmonary vasoconstriction(HPV)and peripheral blood pressure.While NO is catalyzed by various nitric oxide synthase(NOS)isoforms,the regulatory roles of these types in the hemodynamics of pulmonary and systemic circulation in living hypoxic animals remain unclear.Therefore,this study aims to investigate the regu-latory effects of different NOS isoforms on pulmonary and systemic circulation in hypoxic rats by employing selective NOS inhibitors and continuously monitoring hemodynamic parameters of both pulmonary and systemic circulation.Methods:Forty healthy male Sprague–Dawley(SD)rats were randomly divided into four groups:Control group(NG-nitro-D-arginine methyl ester,D-NAME),L-NAME group(non-selective NOS inhibitor,NG-nitro-L-arginine methyl ester),AG group(in-ducible NOS inhibitor group,aminoguanidine),and 7-NI group(neurological NOS in-hibitor,7-nitroindazole).Hemodynamic parameters of rats were monitored for 10 min after inhibitor administration and 5 min after induction of hypoxia[15%O2,2200 m a.sl.,582 mmHg(76.5 kPa),Xining,China]using the real-time dynamic monitoring model for pulmonary and systemic circulation hemodynamics in vivo.Serum NO concentra-tions and blood gas analysis were measured.Results:Under normoxia,mean arterial pressure and total peripheral vascular resist-ance were increased,and ascending aortic blood flow and serum NO concentration were decreased in the L-NAME and AG groups.During hypoxia,pulmonary arterial pressure and pulmonary vascular resistance were significantly increased in the L-NAME and AG groups.Conclusions:This compensatory mechanism activated by inducible NOS and en-dothelial NOS effectively counteracts the pulmonary hemodynamic changes induced by hypoxic stress.It plays a crucial role in alleviating hypoxia-induced pulmonary arte-rial hypertension.展开更多
Nitric oxide(NO),which generally originates from vehicle exhaust and industrial flue gases,is one of the most serious air pollutants.In this case,the electrochemical NO reduction reaction(NORR)not only removes the atm...Nitric oxide(NO),which generally originates from vehicle exhaust and industrial flue gases,is one of the most serious air pollutants.In this case,the electrochemical NO reduction reaction(NORR)not only removes the atmospheric pollutant NO but also produces valuable ammonia(NH_(3)).Hence,through the synthesis and modification of Fe_(3)C nanocrystal cata-lysts,the as-obtained optimal sample of Fe_(3)C/C-900 was adopted as the NORR catalyst at ambient conditions.As a result,the Fe_(3)C/C-900 catalyst showed an NH_(3)Faraday efficiency of 76.5%and an NH_(3)yield rate of 177.5μmol·h^(-1)·cm^(-2)at the working potentials of-0.8 and-1.2 V versus reversible hydrogen electrode(vs.RHE),respectively.And it delivered a stable NORR activity during the electrolysis.Moreover,we attribute the high NORR properties of Fe_(3)C/C-900 to two aspects:one is the enhanced intrinsic activity of Fe_(3)C nanocrystals,including the lowering of the energy barrier of rate-limiting step(*NOH→*N)and the inhibition of hydrogen evolution;on the other hand,the favorable dispersion of active components,the effective adsorption of gaseous NO,and the release of liquid NH_(3)products facilitated by the porous carbon substrate.展开更多
Lung cancer is the most frequent cause of cancer-related mortality worldwide.Nitric oxide(NO),prostaglandins(PGs),thromboxanes(TXs),and endothelins(ETs)participate in numerous physiological processes.These agents play...Lung cancer is the most frequent cause of cancer-related mortality worldwide.Nitric oxide(NO),prostaglandins(PGs),thromboxanes(TXs),and endothelins(ETs)participate in numerous physiological processes.These agents play an important role in lung carcinogenesis by regulating cancer cell proliferation,apoptosis,invasion,and angiogenesis.NO is a gaseous free radical with tumo-ricidal and tumorigenic activities in lung cancer.Arachidonic acid-derived PGs,including PGD2,PGE2,8-iso-PGF2α,and PGI2,are related to the development of lung cancer.PGD2 and PGI2 act as tumor suppressors,while PGE2 and 8-iso-PGF2αpromote tumor progression.TXA2 catalyzed by cyclooxygenase induces prolif-eration as well as angiogenesis.Elevated levels of TXB2,an inactive metabolite of TXA2,are positively correlated with lung carcinoma stages.ET-1 and ET-2 are 21 amino acid polypeptides;their silencing hinders lung cancer cell proliferation and invasion.ET-2 depletion also triggers apoptotic death.This chapter review aims to provide a comprehensive overview of the role of NO,PGs,TXs,and ETs in lung cancer.展开更多
Nitric oxide(NO)modulates several cancer-related physiological processes and has advanced the development of green methods for cancer treatment and integrated platforms for combination or synergistic therapies.Althoug...Nitric oxide(NO)modulates several cancer-related physiological processes and has advanced the development of green methods for cancer treatment and integrated platforms for combination or synergistic therapies.Although a nanoengineering strategy has been proposed to overcome deficiencies of NO gas or small NO donor molecules,such as short half-life,lipophilicity,non-selectivity,and poor stability,it remains challenging to prepare NO nanomedicines with simple composition,multiple functions and enhanced therapeutic efficacy.Herein,we build a liquid metal nanodroplet(LMND)-based NO nanogenerator(LMND@HSG)that is stabilized by a bioreducible guanylated hyperbranched poly(amido amine)(HSG)ligand.Mechanically,the tumor microenvironment specifically triggers a cascade process of glutathione elimination,reactive oxygen species(ROS)generation,and NO release.According to actual demand,the ROS and NO concentrations could be readily controlled by tuning the LMND and HSG feed amounts.Along with the intrinsic anticancer property of LMND(ROS-mediated apoptosis and anti-angiogenesis),LMND@HSG administration could further enhance tumor growth suppression compared with LMND and HSG alone.Fromthis study,leveraging LMND for NO gas therapy provides more possibilities for the prospect of LMND-based anticancer nanomedicines.展开更多
Electrochemical nitrate reduction(eNO_(3)RR)and nitric oxide reduction(eNORR)to ammonia have emerged as promising and sustainable alternatives to the traditional Haber-Bosch method for ammonia production,particularly ...Electrochemical nitrate reduction(eNO_(3)RR)and nitric oxide reduction(eNORR)to ammonia have emerged as promising and sustainable alternatives to the traditional Haber-Bosch method for ammonia production,particularly within the recently proposed reverse artificial nitrogen cycle route:N_(2)→NO_(x)→NH_(3).Notably,experimental studies have demonstrated that eNORR exhibits superior performance over eNO_(3)RR on Cu6Sn5 catalysts.However,the fundamental mechanisms underlying this difference remain poorly understood.Herein,we performed systematic theoretical calculations to explore the reaction pathways,electronic structure effects,and potential-dependent Faradic efficiency associated with ammonia production via these two distinct electrochemical pathways(eNORR and eNO_(3)RR)on Cu6Sn5.By implementing an advanced‘adaptive electric field controlled constant potential(EFC-CP)’methodology combined with microkinetic modeling,we successfully reproduced the experimental observations and identified the key factors affecting ammonia production in both reaction pathways.It was found that eNORR outperforms eNO_(3)RR because it circumvents the ^(*)NO_(2) dissociation and ^(*)NO_(2) desorption steps,leading to distinct surface coverage of key intermediates between the two pathways.Furthermore,the reaction rates were found to exhibit a pronounced dependence on the surface coverage of ^(*)NO in eNORR and ^(*)NO_(2) in eNO_(3)RR.Specifically,the facile desorption of ^(*)NO_(2) on the Cu6Sn5 surface in eNO_(3)RR limits the attainable surface coverage of ^(*)NO,thereby impeding its performance.In contrast,the eNORR can maintain a high surface coverage of adsorbed ^(*)NO species,contributing to its enhanced ammonia production performance.These fundamental insights provide valuable guidance for the rational design of catalysts and the optimization of reaction routes,facilitating the development of more efficient,sustainable,and scalable techniques for ammonia production.展开更多
Background Persistent pulmonary hypertension(PPHN)of the newborn is one of the major contributors to neonatal mortality.Current conventional treatments for PPHN primarily encompass mechanical ventilation,inhaled nitri...Background Persistent pulmonary hypertension(PPHN)of the newborn is one of the major contributors to neonatal mortality.Current conventional treatments for PPHN primarily encompass mechanical ventilation,inhaled nitric oxide(iNO),sildenafil,and magnesium sulfate.In confirmed cases of neonatal respiratory distress syndrome,pulmonary surfactant(PS)can be considered as a potential treatment option;However,the optimal dosage and administration frequency of PS remain subjects of ongoing debate.This study aimed to assess the efficacy of early repeated endotracheal PS administration combined with iNO therapy in the management of newborns with PPHN.Methods Twenty-three neonates with PPHN received iNO alongside foundational treatments,including anti-infection therapy,mechanical ventilation,acidosis correction,and blood pressure stabilization.The observation group(n=13)received endotracheal instillation of PS three times,with each administration spaced six hours apart;The control group(n=10)received endotracheal instillation of PS once.Parameters compared included blood gas indices,oxygenation index(OI),alveolar-arterial oxygen partial pressure difference(PA-aDO,),pulmonary artery systolic pressure(PAP),and N-terminal pro-brain natriuretic peptide(NT-pro-BNP).Mechanical ventilation duration,oxygen therapy time,hospitalization length,and survival outcomes were recorded and compared between groups.Results The blood gas parameters,OI,and PA-aDO,showed no significant differences between the two groups of children before treatment(P>0.05).By 24-hour post-treatment,both groups exhibited significant increases in partial pressure of oxygen(PaO,)and potential of hydrogen(PH)levels,alongside significant decreases in lactate,partial pressure of carbon dioxide(PaCO,),OI,and PA-aDO2,with statistically significant differences(P<0.05).By 48-hour post-treatment,the observation group demonstrated significantly better improvements in blood gas parameters,OI,and PA-aDO,compared to the control group,and these differences were statistically significant(P<0.05).There was no statistically significant difference in PAP and NT-pro-BNP levels between the two groups before treatment(P>0.05).After treatment,both groups showed significant decreases in PAP and NT-pro-BNP levels(P<0.05),with a more pronounced reduction observed in the observation group(P<0.05).The observation group had significantly shorter durations of mechanical ventilation and oxygen therapy compared to the control group,with statistically significant differences(P<0.05).Additionally,the observation group exhibited a shorter total hospital stay and a lower mortality rate than the control group,though these differences were not statistically significant(P>0.05).Conclusions Early consecutive multiple doses of PS combined with iNO,compared to a single dose,better improves respiratory function indices,maintains stability,reduces pulmonary artery pressure,enhances cardiac function,shortens ventilator dependency,and increases cure rates in PPHN neonates.This approach is particularly suitable for severe PPHN cases,especially those with underlying pulmonary conditions.展开更多
OBJECTIVE:To explore the therapeutic effect and target of atractylenolide I(AT-I)on post-infectious irritable bowel syndrome(PI-IBS)rats.METHODS:Therefore,the preliminarily mechanism of AT-I in anti-PI-IBS were first ...OBJECTIVE:To explore the therapeutic effect and target of atractylenolide I(AT-I)on post-infectious irritable bowel syndrome(PI-IBS)rats.METHODS:Therefore,the preliminarily mechanism of AT-I in anti-PI-IBS were first predicted by network pharmacology and molecular docking,then the possible signaling pathways were systematically analyzed.Finally,the potential therapeutic targets and possible signaling pathways of AT-I on PI-IBS in Sprague-Dawley(SD)rat model were verified by experiments.RESULTS:AT-I could alleviate PI-IBS symptoms and reduce the expression of tumor necrosis factorα,interleukin-6 and Interferon-gamma in PI-IBS SD rat model and inhibit the c-Jun N-terminal kinase/inducible nitric oxide synthase(JNK/iNOS)pathway.Notably,AT-I treatment could inhibit the overexpression of polymeraseⅠand transcript release factor(PTRF).CONCLUSION:AT-I could alleviate PI-IBS symptoms through downregulation of PTRF and inhibiting the JNK/iNOS pathway.This study not only provides a scientific basis to clarify the anti-PI-IBS effect of AT-I and its mechanism but also suggests a novel promising therapeutic strategy to treat the PI-IBS.展开更多
Carbon monoxide(CO)and nitric oxide(NO)are signal molecules that enhance plant adaptation to environmental stimuli.Auxin is an essential phytohormone for plant growth and development.CO and NO play crucial roles in mo...Carbon monoxide(CO)and nitric oxide(NO)are signal molecules that enhance plant adaptation to environmental stimuli.Auxin is an essential phytohormone for plant growth and development.CO and NO play crucial roles in modulating the plant’s response to iron deficiency.Iron deficiency leads to an increase in the activity of heme oxygenase(HO)and the subsequent generation of CO.Additionally,it alters the polar subcellular distribution of Pin-Formed 1(PIN1)proteins,resulting in enhanced auxin transport.This alteration,in turn,leads to an increase in NO accumulation.Furthermore,iron deficiency enhances the activity of ferric chelate reductase(FCR),as well as the expression of the Fer-like iron deficiency-induced transcription factor 1(FIT)and the ferric reduction oxidase 2(FRO2)genes in plant roots.Overexpression of the long hypocotyl 1(HY1)gene,which encodes heme oxygenase,or the CO donor treatment resulted in enhanced basipetal auxin transport,higher FCR activity,and the expression of FIT and FRO2 genes under Fe deficiency.Here,a potential mechanism is proposed:CO and NO interact with auxin to address iron deficiency stress.CO alters auxin transport,enhancing its accumulation in roots and up-regulating key iron-related genes like FRO2 and IRT1.Elevated auxin levels affect NO signaling,leading to greater sensitivity in root development.This interplay promotes FCR activity,which is crucial for iron absorption.Together,these molecules enhance iron uptake and root growth,revealing a novel aspect of plant physiology in adapting to environmental stress.展开更多
BACKGROUND With advancements in the diagnosis and treatment of lung diseases,lung segment surgery has become increasingly common.Postoperative rehabilitation is critical for patient recovery,yet challenges such as com...BACKGROUND With advancements in the diagnosis and treatment of lung diseases,lung segment surgery has become increasingly common.Postoperative rehabilitation is critical for patient recovery,yet challenges such as complications and adverse outcomes persist.Incorporating humanized nursing modes and novel treatments like nitric oxide inhalation may enhance recovery and reduce postoperative complications.AIM To evaluate the effects of a humanized nursing mode combined with nitric oxide inhalation on the rehabilitation outcomes of patients undergoing lung surgery,focusing on pulmonary function,recovery speed,and overall treatment costs.METHODS A total of 79 patients who underwent lung surgery at a tertiary hospital from March 2021 to December 2021 were divided into a control group(n=39)receiving a routine nursing program and an experimental group(n=40)receiving additional humanized nursing interventions and atomized inhalation of nitric oxide.Key indicators were compared between the two groups alongside an analysis of treatment costs.RESULTS The experimental group demonstrated significant improvements in pulmonary function,reduced average recovery time,and lower total treatment costs compared to the control group.Moreover,the quality of life in the experimental group was significantly better in the 3 months post-surgery,indicating a more effective rehabilitation process.CONCLUSION The combination of humanized nursing mode and nitric oxide inhalation in postoperative care for lung surgery patients significantly enhances pulmonary rehabilitation outcomes,accelerates recovery,and reduces economic burden.This approach offers a promising reference for improving patient care and rehabilitation efficiency following lung surgery.展开更多
Background:Treatment of methicillin-resistant Staphylococcus aureus(MRSA)biofilm infections in implant placement surgery is limited by the lack of antimicrobial activity of titanium(Ti)implants.There is a need to expl...Background:Treatment of methicillin-resistant Staphylococcus aureus(MRSA)biofilm infections in implant placement surgery is limited by the lack of antimicrobial activity of titanium(Ti)implants.There is a need to explore more effective approaches for the treatment of MRSA biofilm infections.Methods:Herein,an interfacial functionalization strategy is proposed by the integration of mesoporous polydopamine nanoparticles(PDA),nitric oxide(NO)release donor sodium nitroprusside(SNP)and osteogenic growth peptide(OGP)onto Ti implants,denoted as Ti-PDA@SNP-OGP.The physical and chemical properties of Ti-PDA@SNP-OGP were assessed by scanning electron microscopy,X-ray photoelectron spectroscope,water contact angle,photothermal property and NO release behavior.The synergistic antibacterial effect and elimination of the MRSA biofilms were evaluated by 2′,7′-dichlorofluorescein diacetate probe,1-N-phenylnaphthylamine assay,adenosine triphosphate intensity,O-nitrophenyl-β-D-galactopyranoside hydrolysis activity,bicinchoninic acid leakage.Fluorescence staining,assays for alkaline phosphatase activity,collagen secretion and extracellular matrix mineralization,quantitative real‑time reverse transcription‑polymerase chain reaction,and enzyme-linked immunosorbent assay(ELISA)were used to evaluate the inflammatory response and osteogenic ability in bone marrow stromal cells(MSCs),RAW264.7 cells and their co-culture system.Giemsa staining,ELISA,micro-CT,hematoxylin and eosin,Masson's trichrome and immunohistochemistry staining were used to evaluate the eradication of MRSA biofilms,inhibition of inflammatory response,and promotion of osseointegration of Ti-PDA@SNP-OGP in vivo.Results:Ti-PDA@SNP-OGP displayed a synergistic photothermal and NO-dependent antibacterial effect against MRSA following near-infrared light(NIR)irradiation,and effectively eliminated the formed MRSA biofilms by inducing reactive oxygen species(ROS)-mediated oxidative stress,destroying bacterial membrane integrity and causing leakage of intracellular components(P<0.01).In vitro experiments revealed that Ti-PDA@SNP-OGP not only facilitated osteogenic differentiation of MSCs,but also promoted the polarization of pro-inflammatory M1 macrophages to the anti-inflammatory M2-phenotype(P<0.05 or P<0.01).The favorable osteo-immune microenvironment further facilitated osteogenesis of MSCs and the anti-inflammation of RAW264.7 cells via multiple paracrine signaling pathways(P<0.01).In vivo evaluation confirmed the aforementioned results and revealed that Ti-PDA@SNP-OGP induced ameliorative osseointegration in an MRSA-infected femoral defect implantation model(P<0.01).Conclusions:Ti-PDA@SNP-OGP is a promising multi-functional material for the high-efficient treatment of MRSA infections in implant replacement surgeries.展开更多
During wet complexation denitrification of flue gas,Fe^(Ⅱ)EDTA regeneration,also known as reducing Fe^(Ⅱ)EDTA and Fe^(Ⅱ)EDTA-nitric oxide(NO)to Fe^(Ⅱ)EDTA,is crucial.In this paper,ultraviolet(UV)light was used for...During wet complexation denitrification of flue gas,Fe^(Ⅱ)EDTA regeneration,also known as reducing Fe^(Ⅱ)EDTA and Fe^(Ⅱ)EDTA-nitric oxide(NO)to Fe^(Ⅱ)EDTA,is crucial.In this paper,ultraviolet(UV)light was used for the first time to reduce Fe^(Ⅱ)EDTA-NO.The experimental result demonstrated that Fe^(Ⅱ)EDTA-NO reduction rate increased with UV power increasing,elevated temperature,and initial Fe^(Ⅱ)EDTA-NO concentration decreasing.Fe^(Ⅱ)EDTA-NO reduction rate increased first and then decreased as pH value increased(2.0-10.0).Fe^(Ⅱ)EDTA-NO reduction with UV irradiation presented a first order reaction with respect to Fe^(Ⅱ)EDTA-NO.Compared with other Fe^(Ⅱ)EDTA regeneration methods,Fe^(Ⅱ)EDTA regeneration with UV show more superiority through comprehensive consideration of regeneration rate and procedure.Subsequently,NO absorption experiment by Fe^(Ⅱ)EDTA solution with UV irradiation confirmed that UV can significantly promote the NO removal performance of Fe^(Ⅱ)EDTA.Appropriate oxygen concentration(3%(vol))and acidic environment(pH=4)was favorable for NO removal.With UV power increasing as well as temperature decreasing,NO removal efficiency rose.In addition,the mechanism research indicates that NO from flue gas is mostly converted to NO_(2)-,NO_(3)-,NH_(4)^(+),N_(2),and N_(2)O with Fe^(Ⅱ)EDTA absorption liquid with UV irradiation.UV strengthens NO removal in Fe^(Ⅱ)EDTA absorption liquid by forming a synergistic effect of oxidation-reduction-complexation.Finally,compared with NO removal methods with Fe^(Ⅱ)EDTA,Fe^(Ⅱ)EDTA combined UV system shows prominent technology advantage in terms of economy and secondary pollution.展开更多
The reactive oxygen species(ROS) generation efficiency is always limited by the extreme tumor microenvironment(TME), leading to unsatisfactory antitumor effects in photodynamic therapy(PDT). As a promising gas therapy...The reactive oxygen species(ROS) generation efficiency is always limited by the extreme tumor microenvironment(TME), leading to unsatisfactory antitumor effects in photodynamic therapy(PDT). As a promising gas therapy molecule, nitric oxide(NO) is independent of oxygen and could even synergize ROS to enhance the therapeutic effect. However, the short half-life, instability, and uncontrollable release of exogenous NO limited the application of tumor synergistic therapy. Herein, we reported a novel kind of red-emissive carbon dots(CDs) that was capable of lysosome-targeted and light-controlled NO delivery. The CDs were synthesized by using metformin and methylene blue(MB) via a hydrothermal method.The obtained metformin-MB CDs(MMCDs) exhibited a higher1O2quantum yield and NO generation efficiency under light emitting diode(LED) light irradiation. Noteworthily, the1O2could further in situ oxidize NO into peroxynitrite anions(ONOO-), which own the higher cytotoxicity against cancer cells.Cell experiments indicate that MMCDs could destruct lysosome membrane integrity and kill almost 80%of Hep G2 cells under light irradiation while very low cytotoxicity in the dark. Moreover, MMCDs significantly decreased tumor volume and weight after phototherapy in hepatoma Hep G2-bearing mice. Our study provides a new strategy for light-controlled NO generation as well as precise lysosome-targeting for enhancement of PDT efficiency.展开更多
The integer-order interdependent calcium([Ca^(2+)])and nitric oxide(NO)systems are unable to shed light on the influences of the superdiffusion and memory in triggering Brownian motion(BM)in neurons.Therefore,a mathem...The integer-order interdependent calcium([Ca^(2+)])and nitric oxide(NO)systems are unable to shed light on the influences of the superdiffusion and memory in triggering Brownian motion(BM)in neurons.Therefore,a mathematical model is constructed for the fractional-order nonlinear spatiotemporal systems of[Ca^(2+)]and NO incorporating reaction-diffusion equations in neurons.The two-way feedback process between[Ca^(2+)]and NO systems through calcium feedback on NO production and NO feedback on calcium through cyclic guanosine monophosphate(cGMP)with plasmalemmal[Ca^(2+)]-ATPase(PMCA)was incorporated in the model.The Crank–Nicholson scheme(CNS)with Grunwald approximation along spatial derivatives and L1 scheme along temporal derivatives with Gauss–Seidel(GS)iterations were employed.The numerical outcomes were analyzed to get insights into superdiffusion,buffer,and memory exhibiting BM of[Ca^(2+)]and NO systems.The conditions,events and mechanisms leading to dysfunctions in calcium and NO systems and causing different diseases like Parkinson’s were explored in neurons.展开更多
Perylenequinones(PQs)from bambusicolous Shiraia fungi serve as excellent photosensitizers for photodynamic therapy.However,the lower yield of PQ production in mycelium cultures is an important bottleneck for their cli...Perylenequinones(PQs)from bambusicolous Shiraia fungi serve as excellent photosensitizers for photodynamic therapy.However,the lower yield of PQ production in mycelium cultures is an important bottleneck for their clinical application.Light has long been recognized as a pivotal regulatory signal for fungal secondary metabolite biosynthesis.In this study,we explored the role of nitric oxide(NO)in the growth and PQ biosynthesis in mycelium cultures of Shiraia sp.S9 exposed to red light.The continuous irradiation with red light(627 nm,200 lx)suppressed fungal conidiation,promoted hyphal branching,and elicited a notable increase in PQ accumulation.Red light exposure induced NO generation,peaking to 81.7μmol/g FW on day 8 of the culture,with the involvement of nitric oxide synthase(NOS)-or nitrate reductase(NR)-dependent pathways.The application of a NO donor sodium nitroprusside(SNP)restored conidiation of Shiraia sp.S9 under red light and stimulated PQ production,which was mitigated upon the introduction of NO scavenger carboxy-PTIO or soluble guanylate cyclase inhibitor NS-2028.These results showed that red light-induced NO,as a signaling molecule,was involved in the regulation of growth and PQ production in Shiraia sp.S9 through the NO-cGMP-PKG signaling pathway.While mycelial H2O2 content exhibited no significant alternations,a transient increase of intracellular Ca2+and extracellular ATP(eATP)content was detected upon exposure to red light.The generation of NO was found to be interdependent on cytosolic Ca2+and eATP concentration.These signal molecules cooperated synergistically to enhance membrane permeability and elevate the transcript levels of PQ biosynthetic genes in Shiraia sp.S9.Notably,the combined treatment of red light with 5μM SNP yielded a synergistic effect,resulting in a substantially higher level of hypocrellin A(HA,254 mg/L),about 3.0-fold over the dark control.Our findings provide valuable insights into the regulation of NO on fungal secondary metabolite biosynthesis and present a promising strategy involving the combined elicitation with SNP for enhanced production of photoactive PQs and other valuable secondary metabolites in fungi.展开更多
AIM: To study the distribution of the constitutive nitric oxide synthase (NOS) in the jejunum of adult rat. METHODS: The distribution of endothelial NOS (eNOS) was detected by immunohistochemistry. Immunofluorescence ...AIM: To study the distribution of the constitutive nitric oxide synthase (NOS) in the jejunum of adult rat. METHODS: The distribution of endothelial NOS (eNOS) was detected by immunohistochemistry. Immunofluorescence histochemical dual staining technique were used for studying the distribution of neuronal NOS (nNOS) and eNOS. The dual stained slides were observed under a confocal laser scanning microscope. RESULTS: Positive neuronal NOS (nNOS) and endothelial NOS (eNOS) cells were found to be distributed in lamina propria of villi, and the epithelial cell was not stained. eNOS was mainly located in submucosal vascular endothelia, while nNOS was mainly situated in myenteric plexus. Some cells in the villi had both nNOS and eNOS. More than 80% of the cells were positive for both nNOS and eNOS, the rest cells were positive either for nNOS or for eNOS. CONCLUSION: The two constitutive nitric oxide synthases are distributed differently in the jejunum of rat. nNOS distributed in myenteric plexus is a neurotransmitter in the non-adrenergic non-cholinergic (NANC) inhibitory nerves. eNOS distributed in endothelial and smooth muscle cells of blood vessels plays vasodilator role. eNOS and nNOS are coexpressed in some cells of lamina propria of villi. NO generated by those NOS is very important in the physiological and pathological process of small intestine.展开更多
Hepatic ischemia-reperfusion injury(HIRI)is a major clinical cause of morbidity and mortality in liver surgery and transplantation.Many studies have found that nitric oxide(NO)plays an important role in the HIRI and i...Hepatic ischemia-reperfusion injury(HIRI)is a major clinical cause of morbidity and mortality in liver surgery and transplantation.Many studies have found that nitric oxide(NO)plays an important role in the HIRI and its increase or decrease can affect the progression and outcome of HIRI.However,the role of NO in HIRI is controversial and complicated.NO derived by endothelial NO synthase(eNOS)shows a protective role in HIRI,while excessive NO derived by inducible NO synthase(iNOS)accelerates inflammation and increases oxidative stress,further aggravating HIRI.Nevertheless,the overexpression of eNOS may exacerbate HIRI and iNOS-derived NO in some cases reduces HIRI.Here we review the new progress in the understanding of the roles of NO during HIRI:(1)NO possesses different roles in HIRI by increasing NO bioavailability,down-regulating leukotriene C4 synthase,inhibiting the activation of the nuclear factorκB(NFκB)pathway,enhancing cell autophagy,and reducing inflammatory cytokines and reactive oxygen species(ROS).And NO has both protective and deleterious effects by regulating apoptotic factors;(2)eNOS promotes NO production and suppresses its own overexpression,exerting a hepatoprotective effect reversely.Its activation is regulated by the PI3K/Akt and KLF2/AMPK pathways;and(3)iNOS derived NO mainly has deteriorating effects on HIRI,while it may have a protective function under some conditions.Their expression should reach a balance to reduce the adverse side and make NO protective in the treatment of HIRI.Thus,it can be inferred that NO modulating drugs may be a new direction in the treatment of HIRI or may be used as an adjunct to mitigate HIRI for the purpose of protecting the liver.展开更多
AIM:To study the cell-type specific subcellular distribution of the three isoforms of nitric oxide synthase(NOS) in the rat duodenum.METHODS:Postembedding immunoelectronmicroscopy was performed,in which primary antibo...AIM:To study the cell-type specific subcellular distribution of the three isoforms of nitric oxide synthase(NOS) in the rat duodenum.METHODS:Postembedding immunoelectronmicroscopy was performed,in which primary antibodies for neuronal NOS(nNOS),endothelial NOS(eNOS),and inducible NOS(iNOS),were visualized with protein A-gold-conjugated secondary antibodies.Stained ultrathin sections were examined and photographed with a Philips CM10 electron microscope equipped with a MEGAVIEW II camera.The specificity of the immunoreaction in all cases was assessed by omitting the primary antibodies in the labeling protocol and incubating the sections only in the protein A-gold conjugated secondary antibodies.RESULTS:Postembedding immunoelectronmicroscopy revealed the presence of nNOS,eNOS,and iNOS immunoreactivity in the myenteric neurons,the enteric smooth muscle cells,and the endothelium of capillariesrunning in the vicinity of the myenteric plexus of the rat duodenum.The cell type-specific distributions of the immunogold particles labeling the three different NOS isozymes were revealed.In the control experiments,in which the primary antiserum was omitted,virtually no postembedding gold particles were observed.CONCLUSION:This postembedding immunoelectronmicroscopic study provided the first evidence of celltype-specific differences in the subcellular distributions of NOS isoforms.展开更多
基金supported by the National Key R&D Program of China,No.2019YFE0121200(to LQZ)the National Natural Science Foundation of China,Nos.82325017(to LQZ),82030032(to LQZ),82261138555(to DL)+2 种基金the Natural Science Foundation of Hubei Province,No.2022CFA004(to LQZ)the Natural Science Foundation of Jiangxi Province,No.20224BAB206040(to XZ)Research Project of Cognitive Science and Transdisciplinary Studies Center of Jiangxi Province,No.RZYB202201(to XZ).
文摘With an increase in global aging,the number of people affected by cerebrovascular diseases is also increasing,and the incidence of vascular dementia-closely related to cerebrovascular risk-is increasing at an epidemic rate.However,few therapeutic options exist that can markedly improve the cognitive impairment and prognosis of vascular dementia patients.Similarly in Alzheimer’s disease and other neurological disorders,synaptic dysfunction is recognized as the main reason for cognitive decline.Nitric oxide is one of the ubiquitous gaseous cellular messengers involved in multiple physiological and pathological processes of the central nervous system.Recently,nitric oxide has been implicated in regulating synaptic plasticity and plays an important role in the pathogenesis of vascular dementia.This review introduces in detail the emerging role of nitric oxide in physiological and pathological states of vascular dementia and summarizes the diverse effects of nitric oxide on different aspects of synaptic dysfunction,neuroinflammation,oxidative stress,and blood-brain barrier dysfunction that underlie the progress of vascular dementia.Additionally,we propose that targeting the nitric oxide-sGC-cGMP pathway using certain specific approaches may provide a novel therapeutic strategy for vascular dementia.
文摘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.
基金Supported by the National Natural Science Foundation of China,No.81000201.
文摘BACKGROUND Esophageal cancer(ESCA)is among the most prevalent and lethal tumors globally.While nitric oxide synthase 1(NOS1)is recognized for its important in-volvement in various cancers,its specific function in ESCA remains unclear.AIM To explore the potential role and underlying mechanisms of NOS1 in ESCA.METHODS Survival rates were analyzed using GeneCards and Gene Expression Profiling Interactive Analysis.The effects and mechanisms of NOS1 on ESCA cells were evaluated via the Cell Counting Kit-8 assay,scratch assay,Transwell assay,flow cytometry,quantitative polymerase chain reaction,western blotting,and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling staining.The protein interaction network was used to screen the interacting proteins of NOS1 and validate these interactions through co-immuno-precipitation and dual luciferase assays.Additionally,a nude mouse xenograft model was established to evaluate the effect of NOS1 in vivo.RESULTS The survival rate of patients with ESCA with high NOS1 expression was higher than that of patients with low NOS1 expression.NOS1 expression in ESCA cell lines was lower than that in normal esophageal epithelial cells.Overexpression of NOS1(oe-NOS1)inhibited proliferation,invasion,and migration abilities in ESCA cell lines,resulting in decreased autophagy levels and increased apoptosis,pyroptosis,and ferroptosis.Protein interaction studies confirmed the interaction between NOS1 and NOS1 adaptor protein(NOS1AP).Following oe-NOS1 and the silencing of NOS1AP,levels of P62 and microtubule-associated protein 1 light chain 3 beta increased both in vitro and in vivo.Furthermore,the expression levels of E-cadherin,along with the activation of phosphatidylinositol 3-kinase(PI3K)and protein kinase B(AKT),were inhibited in ESCA cell lines.CONCLUSION NOS1 and NOS1 proteins interact to suppress autophagy,activate the PI3K/AKT pathway,and exert anti-cancer effects in ESCA.
基金This work was supported by the National Natural Science Foundation of China(grant numbers 81560301 and 81160012)the Natural Science Foundation of Qinghai Province(grant number 2022-ZJ-905)‘2022 Qinghai Province Kunlun Talents High-end Innovation and Entrepreneurship Talents’Outstanding Talent Project.
文摘Background:Under hypoxia,exaggerated compensatory responses may lead to acute mountain sickness.The excessive vasodilatory effect of nitric oxide(NO)can lower the hypoxic pulmonary vasoconstriction(HPV)and peripheral blood pressure.While NO is catalyzed by various nitric oxide synthase(NOS)isoforms,the regulatory roles of these types in the hemodynamics of pulmonary and systemic circulation in living hypoxic animals remain unclear.Therefore,this study aims to investigate the regu-latory effects of different NOS isoforms on pulmonary and systemic circulation in hypoxic rats by employing selective NOS inhibitors and continuously monitoring hemodynamic parameters of both pulmonary and systemic circulation.Methods:Forty healthy male Sprague–Dawley(SD)rats were randomly divided into four groups:Control group(NG-nitro-D-arginine methyl ester,D-NAME),L-NAME group(non-selective NOS inhibitor,NG-nitro-L-arginine methyl ester),AG group(in-ducible NOS inhibitor group,aminoguanidine),and 7-NI group(neurological NOS in-hibitor,7-nitroindazole).Hemodynamic parameters of rats were monitored for 10 min after inhibitor administration and 5 min after induction of hypoxia[15%O2,2200 m a.sl.,582 mmHg(76.5 kPa),Xining,China]using the real-time dynamic monitoring model for pulmonary and systemic circulation hemodynamics in vivo.Serum NO concentra-tions and blood gas analysis were measured.Results:Under normoxia,mean arterial pressure and total peripheral vascular resist-ance were increased,and ascending aortic blood flow and serum NO concentration were decreased in the L-NAME and AG groups.During hypoxia,pulmonary arterial pressure and pulmonary vascular resistance were significantly increased in the L-NAME and AG groups.Conclusions:This compensatory mechanism activated by inducible NOS and en-dothelial NOS effectively counteracts the pulmonary hemodynamic changes induced by hypoxic stress.It plays a crucial role in alleviating hypoxia-induced pulmonary arte-rial hypertension.
基金supported by the Guangxi Natural Science Fund for Distinguished Young Scholars(2024GXNSFFA010008)Shenzhen Science and Technology Program(JCYJ20230807112503008).
文摘Nitric oxide(NO),which generally originates from vehicle exhaust and industrial flue gases,is one of the most serious air pollutants.In this case,the electrochemical NO reduction reaction(NORR)not only removes the atmospheric pollutant NO but also produces valuable ammonia(NH_(3)).Hence,through the synthesis and modification of Fe_(3)C nanocrystal cata-lysts,the as-obtained optimal sample of Fe_(3)C/C-900 was adopted as the NORR catalyst at ambient conditions.As a result,the Fe_(3)C/C-900 catalyst showed an NH_(3)Faraday efficiency of 76.5%and an NH_(3)yield rate of 177.5μmol·h^(-1)·cm^(-2)at the working potentials of-0.8 and-1.2 V versus reversible hydrogen electrode(vs.RHE),respectively.And it delivered a stable NORR activity during the electrolysis.Moreover,we attribute the high NORR properties of Fe_(3)C/C-900 to two aspects:one is the enhanced intrinsic activity of Fe_(3)C nanocrystals,including the lowering of the energy barrier of rate-limiting step(*NOH→*N)and the inhibition of hydrogen evolution;on the other hand,the favorable dispersion of active components,the effective adsorption of gaseous NO,and the release of liquid NH_(3)products facilitated by the porous carbon substrate.
文摘Lung cancer is the most frequent cause of cancer-related mortality worldwide.Nitric oxide(NO),prostaglandins(PGs),thromboxanes(TXs),and endothelins(ETs)participate in numerous physiological processes.These agents play an important role in lung carcinogenesis by regulating cancer cell proliferation,apoptosis,invasion,and angiogenesis.NO is a gaseous free radical with tumo-ricidal and tumorigenic activities in lung cancer.Arachidonic acid-derived PGs,including PGD2,PGE2,8-iso-PGF2α,and PGI2,are related to the development of lung cancer.PGD2 and PGI2 act as tumor suppressors,while PGE2 and 8-iso-PGF2αpromote tumor progression.TXA2 catalyzed by cyclooxygenase induces prolif-eration as well as angiogenesis.Elevated levels of TXB2,an inactive metabolite of TXA2,are positively correlated with lung carcinoma stages.ET-1 and ET-2 are 21 amino acid polypeptides;their silencing hinders lung cancer cell proliferation and invasion.ET-2 depletion also triggers apoptotic death.This chapter review aims to provide a comprehensive overview of the role of NO,PGs,TXs,and ETs in lung cancer.
基金the National Natural Science Foundation of China(22075114,32371434,82301630)the Natural Science Foundation of Jiangsu Province(BK20211034)the financial support from Jiangsu Provincial Medical Key Laboratory(Key Laboratory of Nuclear Medicine).
文摘Nitric oxide(NO)modulates several cancer-related physiological processes and has advanced the development of green methods for cancer treatment and integrated platforms for combination or synergistic therapies.Although a nanoengineering strategy has been proposed to overcome deficiencies of NO gas or small NO donor molecules,such as short half-life,lipophilicity,non-selectivity,and poor stability,it remains challenging to prepare NO nanomedicines with simple composition,multiple functions and enhanced therapeutic efficacy.Herein,we build a liquid metal nanodroplet(LMND)-based NO nanogenerator(LMND@HSG)that is stabilized by a bioreducible guanylated hyperbranched poly(amido amine)(HSG)ligand.Mechanically,the tumor microenvironment specifically triggers a cascade process of glutathione elimination,reactive oxygen species(ROS)generation,and NO release.According to actual demand,the ROS and NO concentrations could be readily controlled by tuning the LMND and HSG feed amounts.Along with the intrinsic anticancer property of LMND(ROS-mediated apoptosis and anti-angiogenesis),LMND@HSG administration could further enhance tumor growth suppression compared with LMND and HSG alone.Fromthis study,leveraging LMND for NO gas therapy provides more possibilities for the prospect of LMND-based anticancer nanomedicines.
文摘Electrochemical nitrate reduction(eNO_(3)RR)and nitric oxide reduction(eNORR)to ammonia have emerged as promising and sustainable alternatives to the traditional Haber-Bosch method for ammonia production,particularly within the recently proposed reverse artificial nitrogen cycle route:N_(2)→NO_(x)→NH_(3).Notably,experimental studies have demonstrated that eNORR exhibits superior performance over eNO_(3)RR on Cu6Sn5 catalysts.However,the fundamental mechanisms underlying this difference remain poorly understood.Herein,we performed systematic theoretical calculations to explore the reaction pathways,electronic structure effects,and potential-dependent Faradic efficiency associated with ammonia production via these two distinct electrochemical pathways(eNORR and eNO_(3)RR)on Cu6Sn5.By implementing an advanced‘adaptive electric field controlled constant potential(EFC-CP)’methodology combined with microkinetic modeling,we successfully reproduced the experimental observations and identified the key factors affecting ammonia production in both reaction pathways.It was found that eNORR outperforms eNO_(3)RR because it circumvents the ^(*)NO_(2) dissociation and ^(*)NO_(2) desorption steps,leading to distinct surface coverage of key intermediates between the two pathways.Furthermore,the reaction rates were found to exhibit a pronounced dependence on the surface coverage of ^(*)NO in eNORR and ^(*)NO_(2) in eNO_(3)RR.Specifically,the facile desorption of ^(*)NO_(2) on the Cu6Sn5 surface in eNO_(3)RR limits the attainable surface coverage of ^(*)NO,thereby impeding its performance.In contrast,the eNORR can maintain a high surface coverage of adsorbed ^(*)NO species,contributing to its enhanced ammonia production performance.These fundamental insights provide valuable guidance for the rational design of catalysts and the optimization of reaction routes,facilitating the development of more efficient,sustainable,and scalable techniques for ammonia production.
文摘Background Persistent pulmonary hypertension(PPHN)of the newborn is one of the major contributors to neonatal mortality.Current conventional treatments for PPHN primarily encompass mechanical ventilation,inhaled nitric oxide(iNO),sildenafil,and magnesium sulfate.In confirmed cases of neonatal respiratory distress syndrome,pulmonary surfactant(PS)can be considered as a potential treatment option;However,the optimal dosage and administration frequency of PS remain subjects of ongoing debate.This study aimed to assess the efficacy of early repeated endotracheal PS administration combined with iNO therapy in the management of newborns with PPHN.Methods Twenty-three neonates with PPHN received iNO alongside foundational treatments,including anti-infection therapy,mechanical ventilation,acidosis correction,and blood pressure stabilization.The observation group(n=13)received endotracheal instillation of PS three times,with each administration spaced six hours apart;The control group(n=10)received endotracheal instillation of PS once.Parameters compared included blood gas indices,oxygenation index(OI),alveolar-arterial oxygen partial pressure difference(PA-aDO,),pulmonary artery systolic pressure(PAP),and N-terminal pro-brain natriuretic peptide(NT-pro-BNP).Mechanical ventilation duration,oxygen therapy time,hospitalization length,and survival outcomes were recorded and compared between groups.Results The blood gas parameters,OI,and PA-aDO,showed no significant differences between the two groups of children before treatment(P>0.05).By 24-hour post-treatment,both groups exhibited significant increases in partial pressure of oxygen(PaO,)and potential of hydrogen(PH)levels,alongside significant decreases in lactate,partial pressure of carbon dioxide(PaCO,),OI,and PA-aDO2,with statistically significant differences(P<0.05).By 48-hour post-treatment,the observation group demonstrated significantly better improvements in blood gas parameters,OI,and PA-aDO,compared to the control group,and these differences were statistically significant(P<0.05).There was no statistically significant difference in PAP and NT-pro-BNP levels between the two groups before treatment(P>0.05).After treatment,both groups showed significant decreases in PAP and NT-pro-BNP levels(P<0.05),with a more pronounced reduction observed in the observation group(P<0.05).The observation group had significantly shorter durations of mechanical ventilation and oxygen therapy compared to the control group,with statistically significant differences(P<0.05).Additionally,the observation group exhibited a shorter total hospital stay and a lower mortality rate than the control group,though these differences were not statistically significant(P>0.05).Conclusions Early consecutive multiple doses of PS combined with iNO,compared to a single dose,better improves respiratory function indices,maintains stability,reduces pulmonary artery pressure,enhances cardiac function,shortens ventilator dependency,and increases cure rates in PPHN neonates.This approach is particularly suitable for severe PPHN cases,especially those with underlying pulmonary conditions.
基金The University Collaborative Innovation Project of Anhui:Creation of a Combined Animal Model of Coronary Heart Disease based on the Theory of Xin'an Medicine(No.GXXT-2020-024)Start-up Funding for Doctoral Research at Wannan Medical College(WYRCQD2018009)Horizontal Project of South Anhui Medical College(H202003)。
文摘OBJECTIVE:To explore the therapeutic effect and target of atractylenolide I(AT-I)on post-infectious irritable bowel syndrome(PI-IBS)rats.METHODS:Therefore,the preliminarily mechanism of AT-I in anti-PI-IBS were first predicted by network pharmacology and molecular docking,then the possible signaling pathways were systematically analyzed.Finally,the potential therapeutic targets and possible signaling pathways of AT-I on PI-IBS in Sprague-Dawley(SD)rat model were verified by experiments.RESULTS:AT-I could alleviate PI-IBS symptoms and reduce the expression of tumor necrosis factorα,interleukin-6 and Interferon-gamma in PI-IBS SD rat model and inhibit the c-Jun N-terminal kinase/inducible nitric oxide synthase(JNK/iNOS)pathway.Notably,AT-I treatment could inhibit the overexpression of polymeraseⅠand transcript release factor(PTRF).CONCLUSION:AT-I could alleviate PI-IBS symptoms through downregulation of PTRF and inhibiting the JNK/iNOS pathway.This study not only provides a scientific basis to clarify the anti-PI-IBS effect of AT-I and its mechanism but also suggests a novel promising therapeutic strategy to treat the PI-IBS.
基金Open Project of Jiangsu Key Laboratory for Eco-Agricultural Biotechnology around Hongze Lake,Grant Number HZHLAB2201.
文摘Carbon monoxide(CO)and nitric oxide(NO)are signal molecules that enhance plant adaptation to environmental stimuli.Auxin is an essential phytohormone for plant growth and development.CO and NO play crucial roles in modulating the plant’s response to iron deficiency.Iron deficiency leads to an increase in the activity of heme oxygenase(HO)and the subsequent generation of CO.Additionally,it alters the polar subcellular distribution of Pin-Formed 1(PIN1)proteins,resulting in enhanced auxin transport.This alteration,in turn,leads to an increase in NO accumulation.Furthermore,iron deficiency enhances the activity of ferric chelate reductase(FCR),as well as the expression of the Fer-like iron deficiency-induced transcription factor 1(FIT)and the ferric reduction oxidase 2(FRO2)genes in plant roots.Overexpression of the long hypocotyl 1(HY1)gene,which encodes heme oxygenase,or the CO donor treatment resulted in enhanced basipetal auxin transport,higher FCR activity,and the expression of FIT and FRO2 genes under Fe deficiency.Here,a potential mechanism is proposed:CO and NO interact with auxin to address iron deficiency stress.CO alters auxin transport,enhancing its accumulation in roots and up-regulating key iron-related genes like FRO2 and IRT1.Elevated auxin levels affect NO signaling,leading to greater sensitivity in root development.This interplay promotes FCR activity,which is crucial for iron absorption.Together,these molecules enhance iron uptake and root growth,revealing a novel aspect of plant physiology in adapting to environmental stress.
文摘BACKGROUND With advancements in the diagnosis and treatment of lung diseases,lung segment surgery has become increasingly common.Postoperative rehabilitation is critical for patient recovery,yet challenges such as complications and adverse outcomes persist.Incorporating humanized nursing modes and novel treatments like nitric oxide inhalation may enhance recovery and reduce postoperative complications.AIM To evaluate the effects of a humanized nursing mode combined with nitric oxide inhalation on the rehabilitation outcomes of patients undergoing lung surgery,focusing on pulmonary function,recovery speed,and overall treatment costs.METHODS A total of 79 patients who underwent lung surgery at a tertiary hospital from March 2021 to December 2021 were divided into a control group(n=39)receiving a routine nursing program and an experimental group(n=40)receiving additional humanized nursing interventions and atomized inhalation of nitric oxide.Key indicators were compared between the two groups alongside an analysis of treatment costs.RESULTS The experimental group demonstrated significant improvements in pulmonary function,reduced average recovery time,and lower total treatment costs compared to the control group.Moreover,the quality of life in the experimental group was significantly better in the 3 months post-surgery,indicating a more effective rehabilitation process.CONCLUSION The combination of humanized nursing mode and nitric oxide inhalation in postoperative care for lung surgery patients significantly enhances pulmonary rehabilitation outcomes,accelerates recovery,and reduces economic burden.This approach offers a promising reference for improving patient care and rehabilitation efficiency following lung surgery.
基金financially supported by the National Natural Science Foundation of China(82101069,82102537,82160411,82002278)the Natural Science Foundation of Chongqing Science and Technology Commission(CSTC2021JCYJ-MSXMX0170,CSTB2022BSXM-JCX0039)+2 种基金the First Affiliated Hospital of Chongqing Medical University Cultivating Fund(PYJJ2021-02)the Beijing Municipal Science&Technology Commission(Z221100007422130)the Youth Incubation Program of Medical Science and Technology of PLA(21QNPY116).
文摘Background:Treatment of methicillin-resistant Staphylococcus aureus(MRSA)biofilm infections in implant placement surgery is limited by the lack of antimicrobial activity of titanium(Ti)implants.There is a need to explore more effective approaches for the treatment of MRSA biofilm infections.Methods:Herein,an interfacial functionalization strategy is proposed by the integration of mesoporous polydopamine nanoparticles(PDA),nitric oxide(NO)release donor sodium nitroprusside(SNP)and osteogenic growth peptide(OGP)onto Ti implants,denoted as Ti-PDA@SNP-OGP.The physical and chemical properties of Ti-PDA@SNP-OGP were assessed by scanning electron microscopy,X-ray photoelectron spectroscope,water contact angle,photothermal property and NO release behavior.The synergistic antibacterial effect and elimination of the MRSA biofilms were evaluated by 2′,7′-dichlorofluorescein diacetate probe,1-N-phenylnaphthylamine assay,adenosine triphosphate intensity,O-nitrophenyl-β-D-galactopyranoside hydrolysis activity,bicinchoninic acid leakage.Fluorescence staining,assays for alkaline phosphatase activity,collagen secretion and extracellular matrix mineralization,quantitative real‑time reverse transcription‑polymerase chain reaction,and enzyme-linked immunosorbent assay(ELISA)were used to evaluate the inflammatory response and osteogenic ability in bone marrow stromal cells(MSCs),RAW264.7 cells and their co-culture system.Giemsa staining,ELISA,micro-CT,hematoxylin and eosin,Masson's trichrome and immunohistochemistry staining were used to evaluate the eradication of MRSA biofilms,inhibition of inflammatory response,and promotion of osseointegration of Ti-PDA@SNP-OGP in vivo.Results:Ti-PDA@SNP-OGP displayed a synergistic photothermal and NO-dependent antibacterial effect against MRSA following near-infrared light(NIR)irradiation,and effectively eliminated the formed MRSA biofilms by inducing reactive oxygen species(ROS)-mediated oxidative stress,destroying bacterial membrane integrity and causing leakage of intracellular components(P<0.01).In vitro experiments revealed that Ti-PDA@SNP-OGP not only facilitated osteogenic differentiation of MSCs,but also promoted the polarization of pro-inflammatory M1 macrophages to the anti-inflammatory M2-phenotype(P<0.05 or P<0.01).The favorable osteo-immune microenvironment further facilitated osteogenesis of MSCs and the anti-inflammation of RAW264.7 cells via multiple paracrine signaling pathways(P<0.01).In vivo evaluation confirmed the aforementioned results and revealed that Ti-PDA@SNP-OGP induced ameliorative osseointegration in an MRSA-infected femoral defect implantation model(P<0.01).Conclusions:Ti-PDA@SNP-OGP is a promising multi-functional material for the high-efficient treatment of MRSA infections in implant replacement surgeries.
基金supported by National Natural Science Foundation of China(52260012)Natural Science Foundation of Jiangxi Province(20232BAB203053,20212ACB213001,20232BAB203033)+1 种基金General Project of Jiangxi Province Key Research and Development Program(20192BBG70008)Training Plan for Academic and Technical Leaders of Major Disciplines in Jiangxi Province-youth Talent Project(20232BCJ23047).
文摘During wet complexation denitrification of flue gas,Fe^(Ⅱ)EDTA regeneration,also known as reducing Fe^(Ⅱ)EDTA and Fe^(Ⅱ)EDTA-nitric oxide(NO)to Fe^(Ⅱ)EDTA,is crucial.In this paper,ultraviolet(UV)light was used for the first time to reduce Fe^(Ⅱ)EDTA-NO.The experimental result demonstrated that Fe^(Ⅱ)EDTA-NO reduction rate increased with UV power increasing,elevated temperature,and initial Fe^(Ⅱ)EDTA-NO concentration decreasing.Fe^(Ⅱ)EDTA-NO reduction rate increased first and then decreased as pH value increased(2.0-10.0).Fe^(Ⅱ)EDTA-NO reduction with UV irradiation presented a first order reaction with respect to Fe^(Ⅱ)EDTA-NO.Compared with other Fe^(Ⅱ)EDTA regeneration methods,Fe^(Ⅱ)EDTA regeneration with UV show more superiority through comprehensive consideration of regeneration rate and procedure.Subsequently,NO absorption experiment by Fe^(Ⅱ)EDTA solution with UV irradiation confirmed that UV can significantly promote the NO removal performance of Fe^(Ⅱ)EDTA.Appropriate oxygen concentration(3%(vol))and acidic environment(pH=4)was favorable for NO removal.With UV power increasing as well as temperature decreasing,NO removal efficiency rose.In addition,the mechanism research indicates that NO from flue gas is mostly converted to NO_(2)-,NO_(3)-,NH_(4)^(+),N_(2),and N_(2)O with Fe^(Ⅱ)EDTA absorption liquid with UV irradiation.UV strengthens NO removal in Fe^(Ⅱ)EDTA absorption liquid by forming a synergistic effect of oxidation-reduction-complexation.Finally,compared with NO removal methods with Fe^(Ⅱ)EDTA,Fe^(Ⅱ)EDTA combined UV system shows prominent technology advantage in terms of economy and secondary pollution.
基金financially supported by the National Natural Science Foundation of China (Nos.52172033 and 22005280)the support from the support of the Key Laboratory of Structure and Functional Regulation of Hybrid Materials of the Ministry of Education, Anhui University, China+1 种基金the support from the Key Laboratory of Environment Friendly Polymer Materials of Anhui Province, ChinaKey Laboratory of Functional Inorganic Material Chemistry of Anhui Province, Anhui University, China。
文摘The reactive oxygen species(ROS) generation efficiency is always limited by the extreme tumor microenvironment(TME), leading to unsatisfactory antitumor effects in photodynamic therapy(PDT). As a promising gas therapy molecule, nitric oxide(NO) is independent of oxygen and could even synergize ROS to enhance the therapeutic effect. However, the short half-life, instability, and uncontrollable release of exogenous NO limited the application of tumor synergistic therapy. Herein, we reported a novel kind of red-emissive carbon dots(CDs) that was capable of lysosome-targeted and light-controlled NO delivery. The CDs were synthesized by using metformin and methylene blue(MB) via a hydrothermal method.The obtained metformin-MB CDs(MMCDs) exhibited a higher1O2quantum yield and NO generation efficiency under light emitting diode(LED) light irradiation. Noteworthily, the1O2could further in situ oxidize NO into peroxynitrite anions(ONOO-), which own the higher cytotoxicity against cancer cells.Cell experiments indicate that MMCDs could destruct lysosome membrane integrity and kill almost 80%of Hep G2 cells under light irradiation while very low cytotoxicity in the dark. Moreover, MMCDs significantly decreased tumor volume and weight after phototherapy in hepatoma Hep G2-bearing mice. Our study provides a new strategy for light-controlled NO generation as well as precise lysosome-targeting for enhancement of PDT efficiency.
文摘The integer-order interdependent calcium([Ca^(2+)])and nitric oxide(NO)systems are unable to shed light on the influences of the superdiffusion and memory in triggering Brownian motion(BM)in neurons.Therefore,a mathematical model is constructed for the fractional-order nonlinear spatiotemporal systems of[Ca^(2+)]and NO incorporating reaction-diffusion equations in neurons.The two-way feedback process between[Ca^(2+)]and NO systems through calcium feedback on NO production and NO feedback on calcium through cyclic guanosine monophosphate(cGMP)with plasmalemmal[Ca^(2+)]-ATPase(PMCA)was incorporated in the model.The Crank–Nicholson scheme(CNS)with Grunwald approximation along spatial derivatives and L1 scheme along temporal derivatives with Gauss–Seidel(GS)iterations were employed.The numerical outcomes were analyzed to get insights into superdiffusion,buffer,and memory exhibiting BM of[Ca^(2+)]and NO systems.The conditions,events and mechanisms leading to dysfunctions in calcium and NO systems and causing different diseases like Parkinson’s were explored in neurons.
基金supported by the National Natural Science Foundation of China(No.82073955 and 81773696)the Priority Academic Program Development of the Jiangsu Higher Education Institutes(PAPD).
文摘Perylenequinones(PQs)from bambusicolous Shiraia fungi serve as excellent photosensitizers for photodynamic therapy.However,the lower yield of PQ production in mycelium cultures is an important bottleneck for their clinical application.Light has long been recognized as a pivotal regulatory signal for fungal secondary metabolite biosynthesis.In this study,we explored the role of nitric oxide(NO)in the growth and PQ biosynthesis in mycelium cultures of Shiraia sp.S9 exposed to red light.The continuous irradiation with red light(627 nm,200 lx)suppressed fungal conidiation,promoted hyphal branching,and elicited a notable increase in PQ accumulation.Red light exposure induced NO generation,peaking to 81.7μmol/g FW on day 8 of the culture,with the involvement of nitric oxide synthase(NOS)-or nitrate reductase(NR)-dependent pathways.The application of a NO donor sodium nitroprusside(SNP)restored conidiation of Shiraia sp.S9 under red light and stimulated PQ production,which was mitigated upon the introduction of NO scavenger carboxy-PTIO or soluble guanylate cyclase inhibitor NS-2028.These results showed that red light-induced NO,as a signaling molecule,was involved in the regulation of growth and PQ production in Shiraia sp.S9 through the NO-cGMP-PKG signaling pathway.While mycelial H2O2 content exhibited no significant alternations,a transient increase of intracellular Ca2+and extracellular ATP(eATP)content was detected upon exposure to red light.The generation of NO was found to be interdependent on cytosolic Ca2+and eATP concentration.These signal molecules cooperated synergistically to enhance membrane permeability and elevate the transcript levels of PQ biosynthetic genes in Shiraia sp.S9.Notably,the combined treatment of red light with 5μM SNP yielded a synergistic effect,resulting in a substantially higher level of hypocrellin A(HA,254 mg/L),about 3.0-fold over the dark control.Our findings provide valuable insights into the regulation of NO on fungal secondary metabolite biosynthesis and present a promising strategy involving the combined elicitation with SNP for enhanced production of photoactive PQs and other valuable secondary metabolites in fungi.
基金Natural Science Foudation of Hebei ProvinceEducation Department Foundation of Hebei Province.No.2002136.
文摘AIM: To study the distribution of the constitutive nitric oxide synthase (NOS) in the jejunum of adult rat. METHODS: The distribution of endothelial NOS (eNOS) was detected by immunohistochemistry. Immunofluorescence histochemical dual staining technique were used for studying the distribution of neuronal NOS (nNOS) and eNOS. The dual stained slides were observed under a confocal laser scanning microscope. RESULTS: Positive neuronal NOS (nNOS) and endothelial NOS (eNOS) cells were found to be distributed in lamina propria of villi, and the epithelial cell was not stained. eNOS was mainly located in submucosal vascular endothelia, while nNOS was mainly situated in myenteric plexus. Some cells in the villi had both nNOS and eNOS. More than 80% of the cells were positive for both nNOS and eNOS, the rest cells were positive either for nNOS or for eNOS. CONCLUSION: The two constitutive nitric oxide synthases are distributed differently in the jejunum of rat. nNOS distributed in myenteric plexus is a neurotransmitter in the non-adrenergic non-cholinergic (NANC) inhibitory nerves. eNOS distributed in endothelial and smooth muscle cells of blood vessels plays vasodilator role. eNOS and nNOS are coexpressed in some cells of lamina propria of villi. NO generated by those NOS is very important in the physiological and pathological process of small intestine.
文摘Hepatic ischemia-reperfusion injury(HIRI)is a major clinical cause of morbidity and mortality in liver surgery and transplantation.Many studies have found that nitric oxide(NO)plays an important role in the HIRI and its increase or decrease can affect the progression and outcome of HIRI.However,the role of NO in HIRI is controversial and complicated.NO derived by endothelial NO synthase(eNOS)shows a protective role in HIRI,while excessive NO derived by inducible NO synthase(iNOS)accelerates inflammation and increases oxidative stress,further aggravating HIRI.Nevertheless,the overexpression of eNOS may exacerbate HIRI and iNOS-derived NO in some cases reduces HIRI.Here we review the new progress in the understanding of the roles of NO during HIRI:(1)NO possesses different roles in HIRI by increasing NO bioavailability,down-regulating leukotriene C4 synthase,inhibiting the activation of the nuclear factorκB(NFκB)pathway,enhancing cell autophagy,and reducing inflammatory cytokines and reactive oxygen species(ROS).And NO has both protective and deleterious effects by regulating apoptotic factors;(2)eNOS promotes NO production and suppresses its own overexpression,exerting a hepatoprotective effect reversely.Its activation is regulated by the PI3K/Akt and KLF2/AMPK pathways;and(3)iNOS derived NO mainly has deteriorating effects on HIRI,while it may have a protective function under some conditions.Their expression should reach a balance to reduce the adverse side and make NO protective in the treatment of HIRI.Thus,it can be inferred that NO modulating drugs may be a new direction in the treatment of HIRI or may be used as an adjunct to mitigate HIRI for the purpose of protecting the liver.
基金Supported by Hungarian National Grant Agency, Grant#F46201to Bagyánszki M
文摘AIM:To study the cell-type specific subcellular distribution of the three isoforms of nitric oxide synthase(NOS) in the rat duodenum.METHODS:Postembedding immunoelectronmicroscopy was performed,in which primary antibodies for neuronal NOS(nNOS),endothelial NOS(eNOS),and inducible NOS(iNOS),were visualized with protein A-gold-conjugated secondary antibodies.Stained ultrathin sections were examined and photographed with a Philips CM10 electron microscope equipped with a MEGAVIEW II camera.The specificity of the immunoreaction in all cases was assessed by omitting the primary antibodies in the labeling protocol and incubating the sections only in the protein A-gold conjugated secondary antibodies.RESULTS:Postembedding immunoelectronmicroscopy revealed the presence of nNOS,eNOS,and iNOS immunoreactivity in the myenteric neurons,the enteric smooth muscle cells,and the endothelium of capillariesrunning in the vicinity of the myenteric plexus of the rat duodenum.The cell type-specific distributions of the immunogold particles labeling the three different NOS isozymes were revealed.In the control experiments,in which the primary antiserum was omitted,virtually no postembedding gold particles were observed.CONCLUSION:This postembedding immunoelectronmicroscopic study provided the first evidence of celltype-specific differences in the subcellular distributions of NOS isoforms.
