Electrocatalytic nitric oxide(NO)reduction reaction(NORR)is a promising and sustainable process that can simultaneously realize green ammonia(NH3)synthesis and hazardous NO removal.However,current NORR performances ar...Electrocatalytic nitric oxide(NO)reduction reaction(NORR)is a promising and sustainable process that can simultaneously realize green ammonia(NH3)synthesis and hazardous NO removal.However,current NORR performances are far from practical needs due to the lack of efficient electrocatalysts.Engineering the lattice of metal-based nanomaterials via phase control has emerged as an effective strategy to modulate their intrinsic electrocatalytic properties.Herein,we realize boron(B)-insertion-induced phase regulation of rhodium(Rh)nanocrystals to obtain amorphous Rh_(4)B nanoparticles(NPs)and hexagonal close-packed(hcp)RhB NPs through a facile wet-chemical method.A high Faradaic efficiency(92.1±1.2%)and NH_(3) yield rate(629.5±11.0μmol h^(−1) cm^(−2))are achieved over hcp RhB NPs,far superior to those of most reported NORR nanocatalysts.In situ spectro-electrochemical analysis and density functional theory simulations reveal that the excellent electrocatalytic performances of hcp RhB NPs are attributed to the upshift of d-band center,enhanced NO adsorption/activation profile,and greatly reduced energy barrier of the rate-determining step.A demonstrative Zn-NO battery is assembled using hcp RhB NPs as the cathode and delivers a peak power density of 4.33 mW cm−2,realizing simultaneous NO removal,NH3 synthesis,and electricity output.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
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
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
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
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
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
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
Microneedle technology is valuable in wound treatment.Current studies focus on optimizing the function of microneedles and screening for effective encapsulated actives.Herein,we develop innovative MXene hydrogel micro...Microneedle technology is valuable in wound treatment.Current studies focus on optimizing the function of microneedles and screening for effective encapsulated actives.Herein,we develop innovative MXene hydrogel microneedles with nitric oxide(NO)and hypoxia-inducible factor-1α(HIF-1α)plasmid controllable release for diabetic wound treatment.These microneedles consist of gelatin coupled with tert-butyl nitrite(Gel-SNO)polymers obtained by conjugating the-SNO group on the gelatin side chain,therefore,NO can be generated and released under near-infra red(NIR)light irradiation owing to the thermal effect.Simultaneously,by harnessing the enhanced photothermal conversion efficiency of the MXene additive,the microneedle patch can quickly dissolve and liberate the enclosed HIF-1αplasmid nanoparticles into the dermis when exposed to NIR radiation.The released NO effectively reduced the inflammatory response and released HIF-1αplasmid induced neovascularization.Thus,in vivo experiments showed that these microneedles could accelerate wound closure by alleviating inflammation,and promoting re-epithelialization and angiogenesis.These results indicated the potential value of MXene hydrogel microneedles in wound healing and other related biomedical fields.展开更多
Scientists have devoted considerable effort overs several decades to reduce automobile exhaust emissions,and one practical and important strategy is the catalytic conversion of nitric oxide(NO)[1].Previous studies hav...Scientists have devoted considerable effort overs several decades to reduce automobile exhaust emissions,and one practical and important strategy is the catalytic conversion of nitric oxide(NO)[1].Previous studies have shown that lanthanide(Ln)metals can catalytically reduce NO.Thus,the reactions of NO with Ln to form lanthanide-nitric oxide(LnNO)complexes have been designed and served as the simplest prototype molecules for studying NO chemisorption on metal surfaces[2].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
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
AIM To investigate the potential effect of inhibitors of phosphodiesterase-5(PDE-5) for therapy of portal hypertension in liver cirrhosis.METHODS In the rat model of thioacetamide-induced liver fibrosis/cirrhosis the ...AIM To investigate the potential effect of inhibitors of phosphodiesterase-5(PDE-5) for therapy of portal hypertension in liver cirrhosis.METHODS In the rat model of thioacetamide-induced liver fibrosis/cirrhosis the nitric oxide-cyclic guanosine monophosphate(NO-cGMP) pathway was investigated. Expression and localization of PDE-5, the enzyme that converts vasodilating cGMP into inactive 5'-GMP, was in the focus of the study. Hepatic gene expression of key components of the NO-cGMP pathway was determined by qRT-PCR: Endothelial NO synthase(eNOS), inducible NO synthase(iNOS), soluble guanylate cyclase subunits α1 and β1(sGCa1, sGCb1), and PDE-5. Hepatic PDE-5 protein expression and localization were detected by immunohistochemistry. Serum cGMP concentrations were measured using ELISA. Acute effects of the PDE-5 inhibitor Sildenafil(0.1 mg/kg or 1.0 mg/kg) on portal and systemic hemodynamics were investigated using pressure transducers.RESULTS Hepatic gene expression of eNOS(2.2-fold; P = 0.003), sGCa1(1.7-fold; P = 0.003), sGCb1(3.0-fold; P = 0.003), and PDE-5(11-fold; P = 0.003) was increased in cirrhotic livers compared to healthy livers. Overexpression of PDE-5(7.7-fold; P = 0.006) was less pronounced in fibrotic livers. iNOS expression was only detected in fibrotic and cirrhotic livers. In healthy liver, PDE-5 protein was localized primarily in zone 3 hepatocytes and to a lesser extent in perisinusoidal cells. This zonation was disturbed in cirrhosis: PDE-5 protein expression in perisinusoidal cells was induced approximately 8-fold. In addition, PDE-5-expressing cells were also found in fibrous septa. Serum cGMP concentrations were reduced in rats with cirrhotic livers by approximately 40%. Inhibition of PDE-5 by Sildenafil caused a significant increase in serum cGMP concentrations [+ 64% in healthy rats(P = 0.024), + 85% in cirrhotic rats(P = 0.018)]. Concomitantly, the portal venous pressure was reduced by 19% in rats with liver cirrhosis. CONCLUSION Overexpression and abrogated zonation of PDE-5 likely contribute to the pathogenesis of cirrhotic portal hypertension. PDE-5 inhibition may therefore be a reasonable therapeutic approach for portal hypertension.展开更多
ObjectiveTo search and analyze nitric oxide synthase (NOS) and similar proteins from Plasmodium berghei(Pb).MethodsThe structure and function of nitric oxide synthase and similar proteins from Plasmodium berghei were ...ObjectiveTo search and analyze nitric oxide synthase (NOS) and similar proteins from Plasmodium berghei(Pb).MethodsThe structure and function of nitric oxide synthase and similar proteins from Plasmodium berghei were analyzed and predicted by bioinformatics.ResultsPbNOS were not available, but nicotinamide adenine dinucleotide 2′–phosphate reduced tetrasodium (NADPH)–cytochrome p450 reductase(CPR) were gained. PbCPR was in the nucleus of Plasmodium berghei, while 134aa–229aa domain was localize in nucleolar organizer. The amino acids sequence of PbCPR had the closest genetic relationship with Plasmodium vivax showing a 73% homology. The tertiary structure of PbCPR displayed the forcep–shape with wings, but no wings existed in the tertiary structure of its' host, Mus musculus(Mm). 137aa–200aa, 201aa–218aa, 220aa–230aa, 232aa–248, 269aa–323aa, 478aa–501aa and 592aa–606aa domains of PbCPR showed no homology with MmCPRs', and all domains were exposed on the surface of the protein.ConclusionsNOS can't be found in Plasmodium berghei and other Plasmodium species. PbCPR may be a possible resistance site of antimalarial drug, and the targets of antimalarial drug and vaccine. It may be also one of the mechanisms of immune evasion. This study on Plasmodium berghei may be more suitable to Plasmodium vivax. And 137aa–200aa, 201aa–218aa, 220aa–230aa, 232aa–248, 269aa–323aa, 478aa–501aa and 592aa–606aa domains of PbCPR are more ideal targets of antimalarial drug and vaccine.展开更多
Subclinical endometritis is a physiological inflammation that serves to clear persistent contaminants from the uterus. To investigate the alteration of antioxidant, such as vitamin E（VE） and vitamin C（VC）, total o...Subclinical endometritis is a physiological inflammation that serves to clear persistent contaminants from the uterus. To investigate the alteration of antioxidant, such as vitamin E（VE） and vitamin C（VC）, total oxidant capacity（TOC） and nitric oxide（NO） in cows with normal and subclinical endometritis（SCE）, we examined the concentrations of NO, VC and VE, TOC and polymorphonuclear neutrophils（PMN） percentage in uterine secretion. The cows were divided into two groups, normal（n=20） and subclinical endometritis（SCE, n=60）, based on endometrial cytology（presence of PMN≥5%）. Uterine secretion and blood were collected as described previously. Griess reaction was used to determine the concentration of NO. The concentrations of TOC, VC and VE were detected by a commercially available assay kit. The results showed that the concentrations of NO, TOC and PMN percentage were significantly higher（P〈0.01, P〈0.05, and P〈0.01, respectively） in uterine secretion with SCE compared to those from normal; however, the levels of VC and VE were significantly lesser（P〈0.01）. In conclusion, the concentrations of NO, TOC, VC, VE and PMN percentage differed between normal and SCE cows. Meanwhile, the relationship between the concentration of NO and PMN percentage from uterine secretion in cows with subclinical endometritis were positively correlated. Consequently, these alterations in NO, TOC, VC, VE levels and PMN percentage contributed to as a diagnostic index of the uterine inflammation, with the aim to increase the reproduction of the cows and the decrease economic losses.展开更多
Objective: Highland natives adapt well to the hypoxic environment at high altitude(HA). Several genes have been reported to be linked to HA adaptation. Previous studies showed that the endothelial nitric oxide synthas...Objective: Highland natives adapt well to the hypoxic environment at high altitude(HA). Several genes have been reported to be linked to HA adaptation. Previous studies showed that the endothelial nitric oxide synthase(ENOS) G894 T polymorphism contributed to the physiology and pathophysiology of humans at HA by regulating the production of NO. In this meta-analysis, we evaluate the association between the ENOS G894 T polymorphism and HA adaptation through analyzing the published data. Methods: We searched all relevant literature about the ENOS G894 T polymorphism and HA adaptation in Pub Med, Medline, and Embase before Step 2015. A random-effects model was applied(Revman 5.0), and study quality was assessed in duplicate. Six studies with 634 HA native cases and 621 low-altitude controls were included in this meta-analysis. Results: From the results, we observed that the wild-type allele G was significantly overrepresented in the HA groups(OR=1.85; 95% CI, 1.47–2.33; P<0.0001). In addition, the GG genotype was significantly associated with HA adaptation(OR=1.99; 95% CI, 1.54–2.57; P<0.0001). Conclusion: Our results showed that in 894 G allele carriers, the GG genotype might be a beneficial factor for HA adaptation through enhancing the level of NO. However, more studies were needed to confirm our findings due to the limited sample size.展开更多
A modular and efficient synthesis of the biologically significant C-methylisoflavones isosideroxylin（1）,6,8-dimethylgenistein（2） and their analogues（3-8） is established for the first time.The synthesis is realiz...A modular and efficient synthesis of the biologically significant C-methylisoflavones isosideroxylin（1）,6,8-dimethylgenistein（2） and their analogues（3-8） is established for the first time.The synthesis is realized in 7-8 steps in overall yields of 16%-24%from commercially inexpensive phloroglucinol and features a high yielding Vilsmeier-Haack reaction,Friedel-Crafts acylation,Gammill＇s protocol and Suzuki coupling as the pivotal transformations.Next,these compounds evaluated for their inhibitory potency on the production of nitric oxide（NO） in lipopolysaccharide（LPS）-activated RAW-264.7 cells as an indicator of anti-inflammatory activity.The results showed that all the compounds decreased NO production in a dose-dependent manner without marked cytotoxicity and IC_（50） values are found in the range of 10.17-33.88 μmol/L.Of note,compounds 3 followed by 1,7 and 8 show comparable inhibitory activity with positive control（N-monomethyl-L-arginine,L-NMMA）.展开更多
A mathematical model for the inactivation of nitric oxide by rat cerebellar slices under non-steady state condition has been analyzed. This diffusion-inactivation model was used to estimate the kinetics of NO consumpt...A mathematical model for the inactivation of nitric oxide by rat cerebellar slices under non-steady state condition has been analyzed. This diffusion-inactivation model was used to estimate the kinetics of NO consumption by the rat cerebellar slices. He’s Homotopy perturbation method is used to solve the first order nonlinear differential equations which describe the concentrations given by net of diffusion and inactivation by the slices. Analytical expressions for the concentration of nitric oxide have been derived for all values of parameters. The obtained analytical results are compared with the simulation results (Matlab/Scilab program) and are found to be in good agreement.展开更多
In this work, nitric oxide （NO） release coatings designed for intravenous amperometric glucose sensors are optimized through the use ofa polylactic acid （PLA） layer doped with a lipophilic diazeniumdiolated specie...In this work, nitric oxide （NO） release coatings designed for intravenous amperometric glucose sensors are optimized through the use ofa polylactic acid （PLA） layer doped with a lipophilic diazeniumdiolated species that releases NO through a proton-driven mechanism. An Elast-Eon E2As polyurethane coating is used to both moderate NO release from the sensor surface and increase the sensor＇s linear detection range toward glucose. These sensors were evaluated for thromboresistance and in vivo glucose performance through implantation in rabbit veins. By maintaining NO flux on a similar scale to endogenous endothelial cells, implanted glucose sensors exhibited reduced surface clot formation which enables more accurate quantitative glucose measurements continuously. An in vivo time trace of implanted venous sensors demonstrated glucose values that correlated well with the discrete measurements of blood samples on a benchtop point-of-care sensor-based instrument. The raw measured currents from the implanted glucose sensors over 7 h time periods were converted to glucose concentration through use of both a one-point in vivo calibration and a calibration curve obtained in vitro within a bovine serum solution. Control sensors, assembled without NO release functionality, exhibit distinctive surface clotting over the 7 h in vivo implantation period.展开更多
基金funding support from General Research Fund[Project No.14300525]from the Research Grants Council(RGC)of Hong Kong SAR,Chinafunding support from Natural Science Foundation of China(NSFC)Young Scientists Fund(Project No.22305203)+2 种基金NSFC Projects Nos.22309123,22422303,22303011,22033002,92261112 and U21A20328support from the Hong Kong Branch of National Precious Metals Material Engineering Research Center(NPMM)at City University of Hong Kongsupport from Young Collaborative Research Grant[Project No.C1003-23Y]support from RGC of Hong Kong SAR,China.
文摘Electrocatalytic nitric oxide(NO)reduction reaction(NORR)is a promising and sustainable process that can simultaneously realize green ammonia(NH3)synthesis and hazardous NO removal.However,current NORR performances are far from practical needs due to the lack of efficient electrocatalysts.Engineering the lattice of metal-based nanomaterials via phase control has emerged as an effective strategy to modulate their intrinsic electrocatalytic properties.Herein,we realize boron(B)-insertion-induced phase regulation of rhodium(Rh)nanocrystals to obtain amorphous Rh_(4)B nanoparticles(NPs)and hexagonal close-packed(hcp)RhB NPs through a facile wet-chemical method.A high Faradaic efficiency(92.1±1.2%)and NH_(3) yield rate(629.5±11.0μmol h^(−1) cm^(−2))are achieved over hcp RhB NPs,far superior to those of most reported NORR nanocatalysts.In situ spectro-electrochemical analysis and density functional theory simulations reveal that the excellent electrocatalytic performances of hcp RhB NPs are attributed to the upshift of d-band center,enhanced NO adsorption/activation profile,and greatly reduced energy barrier of the rate-determining step.A demonstrative Zn-NO battery is assembled using hcp RhB NPs as the cathode and delivers a peak power density of 4.33 mW cm−2,realizing simultaneous NO removal,NH3 synthesis,and electricity output.
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.
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.
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.
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supported by the National Key Research and Development Program of China(2022YFA1105300)the Key Research&Developement(R&D)Program of Jiangsu Province(BE2022853)+2 种基金the Joint Fund of Henan Province Science and Technology R&D Program(225200810021)the Clinical Trials from Nanjing Drum Tower Hospital(2022-LCYJ-ZD-01)theJiangsu Funding Program for Excellent Postdoctoral Talent(2024ZB003)。
文摘Microneedle technology is valuable in wound treatment.Current studies focus on optimizing the function of microneedles and screening for effective encapsulated actives.Herein,we develop innovative MXene hydrogel microneedles with nitric oxide(NO)and hypoxia-inducible factor-1α(HIF-1α)plasmid controllable release for diabetic wound treatment.These microneedles consist of gelatin coupled with tert-butyl nitrite(Gel-SNO)polymers obtained by conjugating the-SNO group on the gelatin side chain,therefore,NO can be generated and released under near-infra red(NIR)light irradiation owing to the thermal effect.Simultaneously,by harnessing the enhanced photothermal conversion efficiency of the MXene additive,the microneedle patch can quickly dissolve and liberate the enclosed HIF-1αplasmid nanoparticles into the dermis when exposed to NIR radiation.The released NO effectively reduced the inflammatory response and released HIF-1αplasmid induced neovascularization.Thus,in vivo experiments showed that these microneedles could accelerate wound closure by alleviating inflammation,and promoting re-epithelialization and angiogenesis.These results indicated the potential value of MXene hydrogel microneedles in wound healing and other related biomedical fields.
基金the National Key Research and Development Program of China(No.2021YFB3501501)the National Natural Science Foundation of China(No.22276013)the Beijing Natural Science Foundation(No.2242009)for financial support,and thank Tianhe2-JK HPC for generous computer time.
文摘Scientists have devoted considerable effort overs several decades to reduce automobile exhaust emissions,and one practical and important strategy is the catalytic conversion of nitric oxide(NO)[1].Previous studies have shown that lanthanide(Ln)metals can catalytically reduce NO.Thus,the reactions of NO with Ln to form lanthanide-nitric oxide(LnNO)complexes have been designed and served as the simplest prototype molecules for studying NO chemisorption on metal surfaces[2].
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.
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.
文摘AIM To investigate the potential effect of inhibitors of phosphodiesterase-5(PDE-5) for therapy of portal hypertension in liver cirrhosis.METHODS In the rat model of thioacetamide-induced liver fibrosis/cirrhosis the nitric oxide-cyclic guanosine monophosphate(NO-cGMP) pathway was investigated. Expression and localization of PDE-5, the enzyme that converts vasodilating cGMP into inactive 5'-GMP, was in the focus of the study. Hepatic gene expression of key components of the NO-cGMP pathway was determined by qRT-PCR: Endothelial NO synthase(eNOS), inducible NO synthase(iNOS), soluble guanylate cyclase subunits α1 and β1(sGCa1, sGCb1), and PDE-5. Hepatic PDE-5 protein expression and localization were detected by immunohistochemistry. Serum cGMP concentrations were measured using ELISA. Acute effects of the PDE-5 inhibitor Sildenafil(0.1 mg/kg or 1.0 mg/kg) on portal and systemic hemodynamics were investigated using pressure transducers.RESULTS Hepatic gene expression of eNOS(2.2-fold; P = 0.003), sGCa1(1.7-fold; P = 0.003), sGCb1(3.0-fold; P = 0.003), and PDE-5(11-fold; P = 0.003) was increased in cirrhotic livers compared to healthy livers. Overexpression of PDE-5(7.7-fold; P = 0.006) was less pronounced in fibrotic livers. iNOS expression was only detected in fibrotic and cirrhotic livers. In healthy liver, PDE-5 protein was localized primarily in zone 3 hepatocytes and to a lesser extent in perisinusoidal cells. This zonation was disturbed in cirrhosis: PDE-5 protein expression in perisinusoidal cells was induced approximately 8-fold. In addition, PDE-5-expressing cells were also found in fibrous septa. Serum cGMP concentrations were reduced in rats with cirrhotic livers by approximately 40%. Inhibition of PDE-5 by Sildenafil caused a significant increase in serum cGMP concentrations [+ 64% in healthy rats(P = 0.024), + 85% in cirrhotic rats(P = 0.018)]. Concomitantly, the portal venous pressure was reduced by 19% in rats with liver cirrhosis. CONCLUSION Overexpression and abrogated zonation of PDE-5 likely contribute to the pathogenesis of cirrhotic portal hypertension. PDE-5 inhibition may therefore be a reasonable therapeutic approach for portal hypertension.
基金Supported in part by the Research Program in Higher Educational Institutes of the Education Department in Hainan(No.Hjkj2009-50)Scientific Research Funds of Hainan Medical University in 2011(No.2010-014)
文摘ObjectiveTo search and analyze nitric oxide synthase (NOS) and similar proteins from Plasmodium berghei(Pb).MethodsThe structure and function of nitric oxide synthase and similar proteins from Plasmodium berghei were analyzed and predicted by bioinformatics.ResultsPbNOS were not available, but nicotinamide adenine dinucleotide 2′–phosphate reduced tetrasodium (NADPH)–cytochrome p450 reductase(CPR) were gained. PbCPR was in the nucleus of Plasmodium berghei, while 134aa–229aa domain was localize in nucleolar organizer. The amino acids sequence of PbCPR had the closest genetic relationship with Plasmodium vivax showing a 73% homology. The tertiary structure of PbCPR displayed the forcep–shape with wings, but no wings existed in the tertiary structure of its' host, Mus musculus(Mm). 137aa–200aa, 201aa–218aa, 220aa–230aa, 232aa–248, 269aa–323aa, 478aa–501aa and 592aa–606aa domains of PbCPR showed no homology with MmCPRs', and all domains were exposed on the surface of the protein.ConclusionsNOS can't be found in Plasmodium berghei and other Plasmodium species. PbCPR may be a possible resistance site of antimalarial drug, and the targets of antimalarial drug and vaccine. It may be also one of the mechanisms of immune evasion. This study on Plasmodium berghei may be more suitable to Plasmodium vivax. And 137aa–200aa, 201aa–218aa, 220aa–230aa, 232aa–248, 269aa–323aa, 478aa–501aa and 592aa–606aa domains of PbCPR are more ideal targets of antimalarial drug and vaccine.
基金Supported by Funding(RCB22)from the Doctoral Research Foundation of Northeast Agricultural University(2012)the Postdoctoral Fund of Heilongjiang Province(LBH-Z11239)
文摘Subclinical endometritis is a physiological inflammation that serves to clear persistent contaminants from the uterus. To investigate the alteration of antioxidant, such as vitamin E（VE） and vitamin C（VC）, total oxidant capacity（TOC） and nitric oxide（NO） in cows with normal and subclinical endometritis（SCE）, we examined the concentrations of NO, VC and VE, TOC and polymorphonuclear neutrophils（PMN） percentage in uterine secretion. The cows were divided into two groups, normal（n=20） and subclinical endometritis（SCE, n=60）, based on endometrial cytology（presence of PMN≥5%）. Uterine secretion and blood were collected as described previously. Griess reaction was used to determine the concentration of NO. The concentrations of TOC, VC and VE were detected by a commercially available assay kit. The results showed that the concentrations of NO, TOC and PMN percentage were significantly higher（P〈0.01, P〈0.05, and P〈0.01, respectively） in uterine secretion with SCE compared to those from normal; however, the levels of VC and VE were significantly lesser（P〈0.01）. In conclusion, the concentrations of NO, TOC, VC, VE and PMN percentage differed between normal and SCE cows. Meanwhile, the relationship between the concentration of NO and PMN percentage from uterine secretion in cows with subclinical endometritis were positively correlated. Consequently, these alterations in NO, TOC, VC, VE levels and PMN percentage contributed to as a diagnostic index of the uterine inflammation, with the aim to increase the reproduction of the cows and the decrease economic losses.
基金supported by the National Natural Science Foundation of China(81372125)
文摘Objective: Highland natives adapt well to the hypoxic environment at high altitude(HA). Several genes have been reported to be linked to HA adaptation. Previous studies showed that the endothelial nitric oxide synthase(ENOS) G894 T polymorphism contributed to the physiology and pathophysiology of humans at HA by regulating the production of NO. In this meta-analysis, we evaluate the association between the ENOS G894 T polymorphism and HA adaptation through analyzing the published data. Methods: We searched all relevant literature about the ENOS G894 T polymorphism and HA adaptation in Pub Med, Medline, and Embase before Step 2015. A random-effects model was applied(Revman 5.0), and study quality was assessed in duplicate. Six studies with 634 HA native cases and 621 low-altitude controls were included in this meta-analysis. Results: From the results, we observed that the wild-type allele G was significantly overrepresented in the HA groups(OR=1.85; 95% CI, 1.47–2.33; P<0.0001). In addition, the GG genotype was significantly associated with HA adaptation(OR=1.99; 95% CI, 1.54–2.57; P<0.0001). Conclusion: Our results showed that in 894 G allele carriers, the GG genotype might be a beneficial factor for HA adaptation through enhancing the level of NO. However, more studies were needed to confirm our findings due to the limited sample size.
基金financially supported by industrial co-work program with Sun Chem(Sun Kyung Chemical Co.,South Korea)
文摘A modular and efficient synthesis of the biologically significant C-methylisoflavones isosideroxylin（1）,6,8-dimethylgenistein（2） and their analogues（3-8） is established for the first time.The synthesis is realized in 7-8 steps in overall yields of 16%-24%from commercially inexpensive phloroglucinol and features a high yielding Vilsmeier-Haack reaction,Friedel-Crafts acylation,Gammill＇s protocol and Suzuki coupling as the pivotal transformations.Next,these compounds evaluated for their inhibitory potency on the production of nitric oxide（NO） in lipopolysaccharide（LPS）-activated RAW-264.7 cells as an indicator of anti-inflammatory activity.The results showed that all the compounds decreased NO production in a dose-dependent manner without marked cytotoxicity and IC_（50） values are found in the range of 10.17-33.88 μmol/L.Of note,compounds 3 followed by 1,7 and 8 show comparable inhibitory activity with positive control（N-monomethyl-L-arginine,L-NMMA）.
文摘A mathematical model for the inactivation of nitric oxide by rat cerebellar slices under non-steady state condition has been analyzed. This diffusion-inactivation model was used to estimate the kinetics of NO consumption by the rat cerebellar slices. He’s Homotopy perturbation method is used to solve the first order nonlinear differential equations which describe the concentrations given by net of diffusion and inactivation by the slices. Analytical expressions for the concentration of nitric oxide have been derived for all values of parameters. The obtained analytical results are compared with the simulation results (Matlab/Scilab program) and are found to be in good agreement.
文摘In this work, nitric oxide （NO） release coatings designed for intravenous amperometric glucose sensors are optimized through the use ofa polylactic acid （PLA） layer doped with a lipophilic diazeniumdiolated species that releases NO through a proton-driven mechanism. An Elast-Eon E2As polyurethane coating is used to both moderate NO release from the sensor surface and increase the sensor＇s linear detection range toward glucose. These sensors were evaluated for thromboresistance and in vivo glucose performance through implantation in rabbit veins. By maintaining NO flux on a similar scale to endogenous endothelial cells, implanted glucose sensors exhibited reduced surface clot formation which enables more accurate quantitative glucose measurements continuously. An in vivo time trace of implanted venous sensors demonstrated glucose values that correlated well with the discrete measurements of blood samples on a benchtop point-of-care sensor-based instrument. The raw measured currents from the implanted glucose sensors over 7 h time periods were converted to glucose concentration through use of both a one-point in vivo calibration and a calibration curve obtained in vitro within a bovine serum solution. Control sensors, assembled without NO release functionality, exhibit distinctive surface clotting over the 7 h in vivo implantation period.
