In this study,a self-calibrating near-infrared fluorescence probe was designed and synthesized based on the dual-fluorophore strategy utilizing methylene blue and coumarin.The probe utilized methylene blue(emission sp...In this study,a self-calibrating near-infrared fluorescence probe was designed and synthesized based on the dual-fluorophore strategy utilizing methylene blue and coumarin.The probe utilized methylene blue(emission spectrum range:640-740 nm)and coumarin fluorophore(emission spectrum range:440-600 nm)as signal output units,thereby achieving effective spectral separation and highly selective detection of HClO.Under physiological pH conditions,HClO triggers an oxidation-cleavage reaction,releasing methylene blue and coumarin,which emit distinct red and green fluorescence,respectively.This dual-emission feature enabled rapid HClO detection with two-channel detection limits of 25.13 nmol·L^(-1)(green channel)and 31.55 nmol·L^(-1)(red channel).Furthermore,in cell imaging experiments,this probe demonstrated excellent cell membrane permeability and low cytotoxicity,successfully enabling the monitoring of both endogenous and exogenous HClO in living cells.By incorporating a twochannel self-calibration system,the probe effectively mitigated signal variations caused by instrumental or environmental interference,substantially improving detection sensitivity and reliability.展开更多
Development of exquisitely selective and sensitive HClO/ClO^(-)sensor in living system is of the utmost importance.To achieve near-infrared(NIR)-responsive detection of HClO/ClO^(-),a new nanoprobe(csUCNP-Cy820) is co...Development of exquisitely selective and sensitive HClO/ClO^(-)sensor in living system is of the utmost importance.To achieve near-infrared(NIR)-responsive detection of HClO/ClO^(-),a new nanoprobe(csUCNP-Cy820) is composed of the ClO^(-)sensitive Cy820(energy acceptor),and NaLuF4:20%Yb,1%Tm@NaLuF4core@shell upconversion nanoparticles(csUCNP,energy donor) capable of emitting NIR upconversion luminescence(UCL) of Tm^(3+)(800 nm).Through the mechanism of F?rster resonance energy transfer(FRET),the UCL emission can be recovered in the presence of HClO/CIO^(-).The csUCNP-Cy820 nanoprobe is effectively adapted as a precise ClO^(-)detection sensor with a low limit of detection(LoD) of 58 nmol/L in vitro.Moreover,owing to excitation and emission wavelengths both falling within the NIR region,the nanoprobe facilitates high quality imaging in mice models of peritonitis and arthritis,thereby enabling deeper penetration depth for imaging detection in vivo.展开更多
It has been shown clinically that continuous removal of ischemia/reperfusion-induced reactive oxygen species is not conducive to the recovery of late stroke.Indeed,previous studies have shown that excessive increases ...It has been shown clinically that continuous removal of ischemia/reperfusion-induced reactive oxygen species is not conducive to the recovery of late stroke.Indeed,previous studies have shown that excessive increases in hypochlorous acid after stroke can cause severe damage to brain tissue.Our previous studies have found that a small amount of hypochlorous acid still exists in the later stage of stroke,but its specific role and mechanism are currently unclear.To simulate stroke in vivo,a middle cerebral artery occlusion rat model was established,with an oxygen-glucose deprivation/reoxygenation model established in vitro to mimic stroke.We found that in the early stage(within 24 hours)of ischemic stroke,neutrophils produced a large amount of hypochlorous acid,while in the recovery phase(10 days after stroke),microglia were activated and produced a small amount of hypochlorous acid.Further,in acute stroke in rats,hypochlorous acid production was prevented using a hypochlorous acid scavenger,taurine,or myeloperoxidase inhibitor,4-aminobenzoic acid hydrazide.Our results showed that high levels of hypochlorous acid(200μM)induced neuronal apoptosis after oxygen/glucose deprivation/reoxygenation.However,in the recovery phase of the middle cerebral artery occlusion model,a moderate level of hypochlorous acid promoted the proliferation and differentiation of neural stem cells into neurons and astrocytes.This suggests that hypochlorous acid plays different roles at different phases of cerebral ischemia/reperfusion injury.Lower levels of hypochlorous acid(5 and 100μM)promoted nuclear translocation ofβ-catenin.By transfection of single-site mutation plasmids,we found that hypochlorous acid induced chlorination of theβ-catenin tyrosine 30 residue,which promoted nuclear translocation.Altogether,our study indicates that maintaining low levels of hypochlorous acid plays a key role in the recovery of neurological function.展开更多
Hypochlorous acid(HClO)is a critical biomolecule in living organisms,playing an essential role in numerous physiological or pathological processes.Abnormal levels of HClO in the body may lead to a series of diseases,f...Hypochlorous acid(HClO)is a critical biomolecule in living organisms,playing an essential role in numerous physiological or pathological processes.Abnormal levels of HClO in the body may lead to a series of diseases,for instance,inflammation and cancer.Thus,accurate measurement of HClO levels should be more beneficial for understanding its role in diseases and gaining a deeper insight into the pathogenesis of diseases.In this work,we designed a near-infrared two-photon fluorescent probe(HDM-Cl-HClO)for detecting fluctuations in HClO levels in inflammatory and tumor-bearing mice.Notably,the probe can respond to HClO within 5 s and trigger a brilliant red fluorescence at 660 nm.It exhibits high specificity and sensitivity for HClO.The superior spectral capability of the probe has enabled the detection of HClO levels in cells and zebrafish,as well as achieved the detection of HClO in inflammatory and tumor mice.This work not only provides a novel strategy and tool for HClO imaging in living systems,but also holds great potential for the diagnosis of inflammation and cancer.展开更多
Elevated level of hypochlorous acid(HClO)is closely associated with cancer development.Identifying HClO level in cancer cells would provide important evidence in either early-stage cancer diagnostics or monitoring of ...Elevated level of hypochlorous acid(HClO)is closely associated with cancer development.Identifying HClO level in cancer cells would provide important evidence in either early-stage cancer diagnostics or monitoring of its treatment efficiency.In this work,a new pyronine-based fluorescent probe for rapid and sensitive detection of HClO was developed by condensing meso-formyl pyronine(PyCHO)with 2-hydrazinopyridine to form meso-pyridylhydrazone-functionalized pyronine PyHP,PyHP is nonfluorescent due to the excited-state C=N isomerization nonradiative decay,whereas the HClO-triggered formation of meso-triazolopyridyl pyronine PyTP abolishes the C=N isomerization and thus greatly enhances the fluorescence.With the probe,the cancer cells/tumor were distinguished with high-contrast from normal ones by laser confocal fluorescence imaging,and the tumor-to-normal(T/N)ratios obtained exceed the clinically acceptable threshold of 2.0.Moreover,its capability of in vivo imaging tumor was also demonstrated.These results indicate the potential of PyHP as an effective tool in the early clinical diagnosis of cancers.展开更多
A ratiometric fluorescence probe,NClO,for the rapid and selective detection of HClO had been designed and synthesized based on a 1,8-naphthalimide derivative.Probe NClO displayed a red emission(λmax=615 nm).In the pr...A ratiometric fluorescence probe,NClO,for the rapid and selective detection of HClO had been designed and synthesized based on a 1,8-naphthalimide derivative.Probe NClO displayed a red emission(λmax=615 nm).In the presence of HClO,the solution of probe NClO gave off a strong green fluorescence(λem,max=520 nm)with a rapid response(within seconds).This probe had been applied to image HClO in living cells and zebra fish.展开更多
Fluorescent probes have been widely employed in biological imaging and sensing.However,it is always a challenge to design probes with high sensitivity.In this work,based on rhodamine skeleton,we developed a general st...Fluorescent probes have been widely employed in biological imaging and sensing.However,it is always a challenge to design probes with high sensitivity.In this work,based on rhodamine skeleton,we developed a general strategy to construct sensitivity-enhanced fluorescent probe with the help of theoretical calculation for the first time.As a proof of concept,we synthesized a series of HOCl probes.Experiment results showed that with the C-9 of pyronin moiety of rhodamine stabilized by an electron donor group,probe DQF-S exhibited an importantly enhanced sensitivity(LOD:0.2 nmol/L)towards HOCl together with fast response time(<10 s).Moreover,due to the breaking symmetrical electron distribution by another electron donor group,the novel rhodamine probe DQF-S displayed a far red to near-infrared emission(>650 nm)and large Stokes shift.Bioimaging studies indicated that DQF-S can not only effectively detect basal HOCl in various types of cells,but also be successfully applied to image tumor tissue in vivo.These results demonstrate the potential of our design as a useful strategy to develop excellent fluorescent probes for bioimaging.展开更多
The works on the procedure of fluorescent sensors for the detection of biological analytes are extremely momentous.Among diverse analytical approaches,fluorescence is the most eye-catching due to its high sensitivity,...The works on the procedure of fluorescent sensors for the detection of biological analytes are extremely momentous.Among diverse analytical approaches,fluorescence is the most eye-catching due to its high sensitivity,selectivity,rapidity,robustness,ease of measurement and non-destructive approaches.Herein,we show different fluorescent probes synthesized for estimation and detection of biological analytes(H_(2)S,SO_(3)^(2-)/HSO_(3)^(-),H_(2)O_(2),HOCl,HNO,ONOO^(-)).These probes were constructed by masking the functional groups (hydroxyl and amino) of fluorophore and formation of active C=C,C=N,C=O and N=N for specific analytes.In this review we concentrate on synthesis of the probe,their photophysical properties and applications to biological studies.展开更多
Hypochlorous acid（HOCl） plays a vital role in many physiological and pathological processes as one of reactive oxygen species（ROS）. Developing highly sensitive and selective methods for HOCl detection is of signif...Hypochlorous acid（HOCl） plays a vital role in many physiological and pathological processes as one of reactive oxygen species（ROS）. Developing highly sensitive and selective methods for HOCl detection is of significant interest. In this work, we developed a benzothiazole based probe 1 for ratiometric fluorescence detection of hypochlorite in living cells. The probe can detect HOCl with high selectivity, fast response（within 30 s） as well as low detection limit（0.18 mmol/L）. Fluorescence co-localization studies demonstrated that probe 1 was a mitochondria-targeted fluorescent probe. Furthermore, confocal fluorescence images of He La cell indicated that probe 1 could be used for monitoring intracellular HOCl in living cells. Finally, test strips experiment suggests that the probe 1 can detect the hypochlorous acid in tap water accompanied by remarkable color change.展开更多
Recent studies revealed that the increased level of hypochlorous acid(HOCl)may be deemed to be one of the signs of chronic inflammatory joint disease.Accordingly,the development of effective methods for rapid and accu...Recent studies revealed that the increased level of hypochlorous acid(HOCl)may be deemed to be one of the signs of chronic inflammatory joint disease.Accordingly,the development of effective methods for rapid and accurate detection or monitoring of HOCl in vivo is of great significance for further understanding the role of HOCl in rheumatoid arthritis(RA).Herein,a ratiometric near-infrared(NIR)fluorescent probe(PTA)was reported for the detection and monitoring of HOCl.In the presence of HOCl,the electron-rich S atom and C=C double bond of probe PTA were oxidized in sequence,resulting in the significant hypochromatic shift and decline of absorption spectra.Simultaneously,the intramolecular charge transfer(ICT)process of PTA is inhibited,causing the intrinsic fluorescence emission of PTA shift from 680 to 550 nm.PTA-based test paper strips were successfully prepared and applied to determinate HOCl in actual water samples by“naked eye”colorimetric method.PTA features NIR emission,large Stokes shift(200 nm),low cytotoxicity,high sensitivity(33.9 nM),and short response time(45 s),which enable it to be successfully utilized for imaging endogenous and exogenous HOCl in living zebrafish and mice.More importantly,PTA shows remarkable effectiveness for the monitoring of HOCl-mediated treatment response to RA.Consequently,PTA provides a new approach to further understand the role of HOCl in RA and evaluate the drug treatment efficiency of RA.展开更多
Optical properties and responsive mechanisms of three newly synthesized fluorescent probes for hypochlorous acid （HOC1） are investigated by employing time-dependent density functional theory. The computational resul...Optical properties and responsive mechanisms of three newly synthesized fluorescent probes for hypochlorous acid （HOC1） are investigated by employing time-dependent density functional theory. The computational results show that the absorption and emission properties of these probes change obviously when they react with hypochlorous acid. It is found that the probe FHZ has the best performance according to the probing behavior. Moreover, the responsive mechanisms of the probes are studied by analyzing the distributions of molecular orbitals and charge transfer, which are shown as the photon- induced electron transfer （PET） for FHZ and the intramolecular charge transfer OCT） for the other two probes. Specially, solvent effect on optical properties of the probe FHZ before and after reaction is studied within the polarizable continuum model （PCM）. It is shown that performance of the probe depends crucially on the solvent polarity. Our computational results agree well with the experimental measurement, and provide information for design of efficient two-photon fluorescent probes.展开更多
Triazolopyridines are an important kind of fused-ring compounds.A HOCl-promoted triazolopyridine formation strategy is reported here for the first time in which hypochlorous acid(HOCl)mildly and efficiently promotes t...Triazolopyridines are an important kind of fused-ring compounds.A HOCl-promoted triazolopyridine formation strategy is reported here for the first time in which hypochlorous acid(HOCl)mildly and efficiently promotes the formation of 1,2,4-triazolo[4,3-a]pyridines NT1-NT6 from various 2-pyridylhydrazones N1-N6.N6,a rhodol-pyridylhydrazone hybrid,was developed into a fluorescent probe for the selective detection of HOCl,and successfully applied to probe endogenous HOCl in living cells and zebrafish in situ and in real time.The present intramolecular cyclization reaction is selective and atom-economical,thereby not only providing an important approach for the convenient synthesis of triazolopyridines,but also offering a general strategy for sensitive,selective and biocompatible detection of endogenous HOCl in complex biosystems.展开更多
Background: Septic open abdomens occur in trauma, burn and surgery. Currently, multiple concentrations of hypochlorous acid solutions have effectively decreased the microbiotic burden in wounds. We hypothesized that V...Background: Septic open abdomens occur in trauma, burn and surgery. Currently, multiple concentrations of hypochlorous acid solutions have effectively decreased the microbiotic burden in wounds. We hypothesized that Vashe?, a neutral hypochlorous acid solution (V-HOCL), would be safe as an intraperitoneal irrigation or washout disinfectant for septic open abdomens utilizing negative pressure wound therapy. Methods: This is a retrospective observational review of patients who required delayed abdominal closures after exploratory laparotomies. Group A (n = 8) had cyclical V-HOCL irrigation to their open abdomens combining AbtheraTM and V.A.C. Dressing System for negative pressure wound therapy with irrigation (NPWT-i) and Group B (n = 9) had intra-abdominal V-HOCL washouts. Results: Fifty percent of both groups had either septic or hemorrhagic shock on admission. Compared to Group B, Group A patients were older (median 50 vs 37 years), and had a median hospitalization of 28 vs 8 days, 4 times as many operations, more acute renal failure and co-morbidities. No statistically significant differences were detected be-tween the two treatment methods with the V-HOCL delivery and removal. Conclusion: There were no episodes of electrolyte imbalance, hypotension, hypertension, anaphylaxis, hemorrhage, visceral injury or systemic toxicity. V-HOCL with/without NPWT-i irrigation was a safe modality and tolerated well in this study.展开更多
Raised myeloperoxidase (MPO) serum levels are associated with endothelial dysfunction and cigarette smoking is a risk factor for cardiovascular diseases. Since myocardial infarction is associated with leukocytosis and...Raised myeloperoxidase (MPO) serum levels are associated with endothelial dysfunction and cigarette smoking is a risk factor for cardiovascular diseases. Since myocardial infarction is associated with leukocytosis and smokers present increased levels of neutrophils, here we hypothesized that the levels of serum MPO in smokers could be also raised. We carried out a study on sixty eight adult healthy volunteers. The control group consisted of thirty four non-smokers and the test group was thirty four heavy smokers. The hemogram, interleukin-8 (IL-8) and MPO serum levels were measured. Neutrophil, monocyte and lymphocyte counts were higher展开更多
Hypochlorous acid (HOCl) is a strong oxidant produced by activated neutrophils via the myeloperoxidase (MPO) enzyme in order to fight against infections. Because of their antimicrobial and antiviral properties, stabil...Hypochlorous acid (HOCl) is a strong oxidant produced by activated neutrophils via the myeloperoxidase (MPO) enzyme in order to fight against infections. Because of their antimicrobial and antiviral properties, stabilized HOCl solutions were produced to be used as a disinfectant and became a recommended disinfectant against COVID-19 by the US Environmental Protection Agency. Aberrant MPO enzyme activity results in abundant HOCl production which is related to the development and/or progression of several diseases including atherosclerosis, cardiovascular and neurodegenerative diseases. Previous studies investigating the effect of HOCl on the mode of cell death in different cell types reported that HOCl induces both apoptosis and necrosis depending on its concentration. However, the data on the apoptotic pathway triggered by HOCl is controversial. In this study, we investigated the <span><span style="font-family:Verdana;">mode of cell death induced by different concentrations of HOCl in <i></i></span><i><i><span style="font-family:Verdana;">Saccharomyces</span></i></i></span><i><i><span style="font-family:Verdana;"> cerevisiae</span></i><span style="font-family:Verdana;"></span></i>. Our data revealed that HOCl leads to cell death within 1 minute at 170 <span style="line-height:102%;font-family:Verdana;">μ</span><span style="font-family:Verdana;">M and above. At 340 </span><span style="line-height:102%;font-family:Verdana;">μ</span><span style="font-family:Verdana;">M, HOCl causes a rapid necrosis, while 170 μM HOCl leads to apoptosis. HOCl-induced apoptosis is mostly caspase dependent and Aif1 doesn’t have a significant role.</span>展开更多
Utilization of negative pressure wound therapy with instillation (NPWTi) for sternal dehiscence wounds secondary to sternal wound infection after surgery has become an accepted therapy. NPWTi accelerates wound healing...Utilization of negative pressure wound therapy with instillation (NPWTi) for sternal dehiscence wounds secondary to sternal wound infection after surgery has become an accepted therapy. NPWTi accelerates wound healing through macrostrain, microstrain, and cyclic fluid instillation. Wounds benefit from additional superficial infection control with the removal of microorganisms, the release of proinflammatory mediators, stimulation of angiogenesis, as well as mechanical debridement. However, very few cases of utilizing NPWTi in the treatment of sternal wound infections have been reported in the literature. This case study describes the use of NPWTi with hypochlorous acid for the treatment of a sternal wound infection.展开更多
Objectives:This study investigated the effects of processing parameters,specifically the flow rate and the combination of diluted HCI and salt(NaCl)at different concentrations,on the properties of slightly acidic elec...Objectives:This study investigated the effects of processing parameters,specifically the flow rate and the combination of diluted HCI and salt(NaCl)at different concentrations,on the properties of slightly acidic electrolyzed water(SAEW)that was produced.Materials and Methods:The properties of the SAEW that were analyzed included pH,oxidation-reduction potential(ORP),available chlorine concentration(ACC),and generated hypochlorous acid(HCIO)concentration.Meanwhile,the total aerobic bacteria and total phenolic content retention were determined.Results:NaCl alone resulted in the lowest pH(<4)and the highest ORP values(>1000 mV).Increasing the HCI concentration significantly raised the pH to greater than 5 and lowered the ORP values of SAEW,with the highest pH(5.7)observed with 1.5%HCI and 5%NaCl.The highest HCIO concentration of 19.65±1.03 mg/L was obtained with 1.5%HCI:5%NaCl.Interestingly,the concentration of NaCl had no significant effect on the production of HCIO.Furthermore,different concentrations of combined NaCl and HCI significantly influenced the inactivation efficiency on total aerobic bacteria count and changes in phenolic compound content.Increasing HCI concentrations from 0.5% to 2.0%led toan increase in the reduction of aerobic bacteria counts from 2.51 to 4.22 log colony-forming units(CFU)/g with 5%NaCl and from 2.49 to 3.52 log CFU/g with 10%NaCl.Flow rates significantly contributed to the change in HCIO formation and altered the properties of the produced SAEW.The results indicated that SAEW treatment significantly reduced total aerobic bacteria counts.A lower flow rate(O.3 L/min)produced the highest log reduction.Additionally,SAEW treatment led to a reduction in phenolic content,even though a considerable amount was retained at lower HCIO concentrations.Conclusions:These findings offer valuable information on optimizing SAEW treatment protocols for enhancing microbial safety and extending the shelf life of fresh produce,while considering the impact on the content of phenolic compounds.展开更多
Levels of reactive oxygen species(ROS)in cancer cells or in the tumor microenvironment differ noticeably from those in normal cells and cellular microenvironments because ROS play important roles in all aspects of tum...Levels of reactive oxygen species(ROS)in cancer cells or in the tumor microenvironment differ noticeably from those in normal cells and cellular microenvironments because ROS play important roles in all aspects of tumor physiology.However,due to the lack of adequate tools,it is difficult to study the relationship between ROS,especially certain types of ROS(e.g.,HOCl),and cancer.We report herein an HOCl-specific fluorescent probe,FDOCl-20,containing a thiocarbamide group as a receptor,for the visualization of HOCl in solid tumors in vivo.This probe displays high selectivity and sensitivity to HOCl,and is appropriate for use in acidic conditions,including the tumor microenvironment.Using FDOCl-20 as a tool,we can visualize HOCl in solid tumors in vivo.Importantly,the fluorescent intensity of FDOCl-20 is proportional to tumor volume.Thus,FDOCl-20 is a useful tool to investigate the relationship between HOCl and the physiological processes of tumors.展开更多
Probes for in vivo imaging of hypochlorous acid(HOCl),one of the most important reactive oxygen species in innate immunity,are urgently needed to understand the pathogenesis of autoimmune and neuroinflammatory disorde...Probes for in vivo imaging of hypochlorous acid(HOCl),one of the most important reactive oxygen species in innate immunity,are urgently needed to understand the pathogenesis of autoimmune and neuroinflammatory disorders.As a strong oxidant,HOCl could bleach near-infrared sensors and inactivate luciferase readily,making in vivo imaging overwhelmingly challenging.Via fine-tuning of a selective HOCl sensing moiety,HOCl stable spacer,and bright chemiluminescent scaffold,we have developed HOCl-CL-510 as a highly selective and sensitive probe for HOCl detection both in vitro and in vivo.In particular,we achieved recurring real-time monitoring of HOCl in both acute and chronic inflammation models in living mice,providing a new chemical tool for dynamic monitoring of disease development with reduced usage of experimental animals.展开更多
文摘In this study,a self-calibrating near-infrared fluorescence probe was designed and synthesized based on the dual-fluorophore strategy utilizing methylene blue and coumarin.The probe utilized methylene blue(emission spectrum range:640-740 nm)and coumarin fluorophore(emission spectrum range:440-600 nm)as signal output units,thereby achieving effective spectral separation and highly selective detection of HClO.Under physiological pH conditions,HClO triggers an oxidation-cleavage reaction,releasing methylene blue and coumarin,which emit distinct red and green fluorescence,respectively.This dual-emission feature enabled rapid HClO detection with two-channel detection limits of 25.13 nmol·L^(-1)(green channel)and 31.55 nmol·L^(-1)(red channel).Furthermore,in cell imaging experiments,this probe demonstrated excellent cell membrane permeability and low cytotoxicity,successfully enabling the monitoring of both endogenous and exogenous HClO in living cells.By incorporating a twochannel self-calibration system,the probe effectively mitigated signal variations caused by instrumental or environmental interference,substantially improving detection sensitivity and reliability.
基金Project supported by the National Key R&D Program of China (2022YFF0710000)。
文摘Development of exquisitely selective and sensitive HClO/ClO^(-)sensor in living system is of the utmost importance.To achieve near-infrared(NIR)-responsive detection of HClO/ClO^(-),a new nanoprobe(csUCNP-Cy820) is composed of the ClO^(-)sensitive Cy820(energy acceptor),and NaLuF4:20%Yb,1%Tm@NaLuF4core@shell upconversion nanoparticles(csUCNP,energy donor) capable of emitting NIR upconversion luminescence(UCL) of Tm^(3+)(800 nm).Through the mechanism of F?rster resonance energy transfer(FRET),the UCL emission can be recovered in the presence of HClO/CIO^(-).The csUCNP-Cy820 nanoprobe is effectively adapted as a precise ClO^(-)detection sensor with a low limit of detection(LoD) of 58 nmol/L in vitro.Moreover,owing to excitation and emission wavelengths both falling within the NIR region,the nanoprobe facilitates high quality imaging in mice models of peritonitis and arthritis,thereby enabling deeper penetration depth for imaging detection in vivo.
基金supported by the Natural Science Foundation of Jiangsu Province of China,No.BK20211348(to SHQ)Xuzhou Basic Research Program,No.KC21030(to LYH)+1 种基金Leadership Program of Xuzhou Medical University,No.JBGS202203(to SHQ)Research Grant Council GRF of Hong Kong Special Administrative Region of China,No.17105220(to JGS)。
文摘It has been shown clinically that continuous removal of ischemia/reperfusion-induced reactive oxygen species is not conducive to the recovery of late stroke.Indeed,previous studies have shown that excessive increases in hypochlorous acid after stroke can cause severe damage to brain tissue.Our previous studies have found that a small amount of hypochlorous acid still exists in the later stage of stroke,but its specific role and mechanism are currently unclear.To simulate stroke in vivo,a middle cerebral artery occlusion rat model was established,with an oxygen-glucose deprivation/reoxygenation model established in vitro to mimic stroke.We found that in the early stage(within 24 hours)of ischemic stroke,neutrophils produced a large amount of hypochlorous acid,while in the recovery phase(10 days after stroke),microglia were activated and produced a small amount of hypochlorous acid.Further,in acute stroke in rats,hypochlorous acid production was prevented using a hypochlorous acid scavenger,taurine,or myeloperoxidase inhibitor,4-aminobenzoic acid hydrazide.Our results showed that high levels of hypochlorous acid(200μM)induced neuronal apoptosis after oxygen/glucose deprivation/reoxygenation.However,in the recovery phase of the middle cerebral artery occlusion model,a moderate level of hypochlorous acid promoted the proliferation and differentiation of neural stem cells into neurons and astrocytes.This suggests that hypochlorous acid plays different roles at different phases of cerebral ischemia/reperfusion injury.Lower levels of hypochlorous acid(5 and 100μM)promoted nuclear translocation ofβ-catenin.By transfection of single-site mutation plasmids,we found that hypochlorous acid induced chlorination of theβ-catenin tyrosine 30 residue,which promoted nuclear translocation.Altogether,our study indicates that maintaining low levels of hypochlorous acid plays a key role in the recovery of neurological function.
基金National Natural Science Foundation of China(No.22264013)Hainan Province Clinical Medical Center(No.2021)Hainan Province Science and Technology Special Fund(No.ZDYF2024SHFZ104).
文摘Hypochlorous acid(HClO)is a critical biomolecule in living organisms,playing an essential role in numerous physiological or pathological processes.Abnormal levels of HClO in the body may lead to a series of diseases,for instance,inflammation and cancer.Thus,accurate measurement of HClO levels should be more beneficial for understanding its role in diseases and gaining a deeper insight into the pathogenesis of diseases.In this work,we designed a near-infrared two-photon fluorescent probe(HDM-Cl-HClO)for detecting fluctuations in HClO levels in inflammatory and tumor-bearing mice.Notably,the probe can respond to HClO within 5 s and trigger a brilliant red fluorescence at 660 nm.It exhibits high specificity and sensitivity for HClO.The superior spectral capability of the probe has enabled the detection of HClO levels in cells and zebrafish,as well as achieved the detection of HClO in inflammatory and tumor mice.This work not only provides a novel strategy and tool for HClO imaging in living systems,but also holds great potential for the diagnosis of inflammation and cancer.
基金Scientific and Technological Innovation Program of Colleges and Universities in Shanxi Province(Nos.2021L529,2021L530)the Fund for Shanxi“1331 Project”。
文摘Elevated level of hypochlorous acid(HClO)is closely associated with cancer development.Identifying HClO level in cancer cells would provide important evidence in either early-stage cancer diagnostics or monitoring of its treatment efficiency.In this work,a new pyronine-based fluorescent probe for rapid and sensitive detection of HClO was developed by condensing meso-formyl pyronine(PyCHO)with 2-hydrazinopyridine to form meso-pyridylhydrazone-functionalized pyronine PyHP,PyHP is nonfluorescent due to the excited-state C=N isomerization nonradiative decay,whereas the HClO-triggered formation of meso-triazolopyridyl pyronine PyTP abolishes the C=N isomerization and thus greatly enhances the fluorescence.With the probe,the cancer cells/tumor were distinguished with high-contrast from normal ones by laser confocal fluorescence imaging,and the tumor-to-normal(T/N)ratios obtained exceed the clinically acceptable threshold of 2.0.Moreover,its capability of in vivo imaging tumor was also demonstrated.These results indicate the potential of PyHP as an effective tool in the early clinical diagnosis of cancers.
基金supported by the National Natural Science Foundation of China(No.U1608222)the State Key Laboratory of Fine Chemicals(No.KF1606)the financial support from Fundamental Research Funds for the Central Universities of Central South University(No.2018zzts109)
文摘A ratiometric fluorescence probe,NClO,for the rapid and selective detection of HClO had been designed and synthesized based on a 1,8-naphthalimide derivative.Probe NClO displayed a red emission(λmax=615 nm).In the presence of HClO,the solution of probe NClO gave off a strong green fluorescence(λem,max=520 nm)with a rapid response(within seconds).This probe had been applied to image HClO in living cells and zebra fish.
基金the National Natural Science Foundation of China(Nos.21877029,21735001)the National Key R&D Program of China(No.2019YFA0210103)+1 种基金the National Postdoctoral Program for Innovative Talents(No.BX20190110)the China Postdoctoral Science Foundation(No.2019M662758)。
文摘Fluorescent probes have been widely employed in biological imaging and sensing.However,it is always a challenge to design probes with high sensitivity.In this work,based on rhodamine skeleton,we developed a general strategy to construct sensitivity-enhanced fluorescent probe with the help of theoretical calculation for the first time.As a proof of concept,we synthesized a series of HOCl probes.Experiment results showed that with the C-9 of pyronin moiety of rhodamine stabilized by an electron donor group,probe DQF-S exhibited an importantly enhanced sensitivity(LOD:0.2 nmol/L)towards HOCl together with fast response time(<10 s).Moreover,due to the breaking symmetrical electron distribution by another electron donor group,the novel rhodamine probe DQF-S displayed a far red to near-infrared emission(>650 nm)and large Stokes shift.Bioimaging studies indicated that DQF-S can not only effectively detect basal HOCl in various types of cells,but also be successfully applied to image tumor tissue in vivo.These results demonstrate the potential of our design as a useful strategy to develop excellent fluorescent probes for bioimaging.
基金the National Science Foundation of China (No. 21907025)。
文摘The works on the procedure of fluorescent sensors for the detection of biological analytes are extremely momentous.Among diverse analytical approaches,fluorescence is the most eye-catching due to its high sensitivity,selectivity,rapidity,robustness,ease of measurement and non-destructive approaches.Herein,we show different fluorescent probes synthesized for estimation and detection of biological analytes(H_(2)S,SO_(3)^(2-)/HSO_(3)^(-),H_(2)O_(2),HOCl,HNO,ONOO^(-)).These probes were constructed by masking the functional groups (hydroxyl and amino) of fluorophore and formation of active C=C,C=N,C=O and N=N for specific analytes.In this review we concentrate on synthesis of the probe,their photophysical properties and applications to biological studies.
基金supported by the National Natural Science Foundation of China(Nos.21376117,21406109 and 31401588)the Jiangsu Natural Science Funds for Distinguished Young Scholars(No.BK20140043)+1 种基金the Natural Science Foundation of the Jiangsu Higher Education Institutions of China(No.14KJA150005)the Qing Lan Project and the Project of Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)
文摘Hypochlorous acid（HOCl） plays a vital role in many physiological and pathological processes as one of reactive oxygen species（ROS）. Developing highly sensitive and selective methods for HOCl detection is of significant interest. In this work, we developed a benzothiazole based probe 1 for ratiometric fluorescence detection of hypochlorite in living cells. The probe can detect HOCl with high selectivity, fast response（within 30 s） as well as low detection limit（0.18 mmol/L）. Fluorescence co-localization studies demonstrated that probe 1 was a mitochondria-targeted fluorescent probe. Furthermore, confocal fluorescence images of He La cell indicated that probe 1 could be used for monitoring intracellular HOCl in living cells. Finally, test strips experiment suggests that the probe 1 can detect the hypochlorous acid in tap water accompanied by remarkable color change.
基金supported by“the Key and General research Project of Education Department of Liaoning Province(LJKZ0277)”“Liaoning BaiQianWan Talents Program.”。
文摘Recent studies revealed that the increased level of hypochlorous acid(HOCl)may be deemed to be one of the signs of chronic inflammatory joint disease.Accordingly,the development of effective methods for rapid and accurate detection or monitoring of HOCl in vivo is of great significance for further understanding the role of HOCl in rheumatoid arthritis(RA).Herein,a ratiometric near-infrared(NIR)fluorescent probe(PTA)was reported for the detection and monitoring of HOCl.In the presence of HOCl,the electron-rich S atom and C=C double bond of probe PTA were oxidized in sequence,resulting in the significant hypochromatic shift and decline of absorption spectra.Simultaneously,the intramolecular charge transfer(ICT)process of PTA is inhibited,causing the intrinsic fluorescence emission of PTA shift from 680 to 550 nm.PTA-based test paper strips were successfully prepared and applied to determinate HOCl in actual water samples by“naked eye”colorimetric method.PTA features NIR emission,large Stokes shift(200 nm),low cytotoxicity,high sensitivity(33.9 nM),and short response time(45 s),which enable it to be successfully utilized for imaging endogenous and exogenous HOCl in living zebrafish and mice.More importantly,PTA shows remarkable effectiveness for the monitoring of HOCl-mediated treatment response to RA.Consequently,PTA provides a new approach to further understand the role of HOCl in RA and evaluate the drug treatment efficiency of RA.
基金supported by the National Natural Science Foundation of China(Grant Nos.11374195 and 11404193)the Taishan Scholar Program of Shandong Province,China
文摘Optical properties and responsive mechanisms of three newly synthesized fluorescent probes for hypochlorous acid （HOC1） are investigated by employing time-dependent density functional theory. The computational results show that the absorption and emission properties of these probes change obviously when they react with hypochlorous acid. It is found that the probe FHZ has the best performance according to the probing behavior. Moreover, the responsive mechanisms of the probes are studied by analyzing the distributions of molecular orbitals and charge transfer, which are shown as the photon- induced electron transfer （PET） for FHZ and the intramolecular charge transfer OCT） for the other two probes. Specially, solvent effect on optical properties of the probe FHZ before and after reaction is studied within the polarizable continuum model （PCM）. It is shown that performance of the probe depends crucially on the solvent polarity. Our computational results agree well with the experimental measurement, and provide information for design of efficient two-photon fluorescent probes.
基金the National Natural Science Foundation of China(Nos.21977082,21472148 and 21807088)Open Funding Project of the State Key Laboratory of Bioreactor Engineering(No.2018OPEN12)+2 种基金Special Foundation of the Education Committee of Shaanxi Province(No.18JK0702)Technology Plan Project of Xi’an(Nos.201805040YD18CG24 and GXYD18.1)Academic Backbone of Northwest University Outstanding Youth Support Program。
文摘Triazolopyridines are an important kind of fused-ring compounds.A HOCl-promoted triazolopyridine formation strategy is reported here for the first time in which hypochlorous acid(HOCl)mildly and efficiently promotes the formation of 1,2,4-triazolo[4,3-a]pyridines NT1-NT6 from various 2-pyridylhydrazones N1-N6.N6,a rhodol-pyridylhydrazone hybrid,was developed into a fluorescent probe for the selective detection of HOCl,and successfully applied to probe endogenous HOCl in living cells and zebrafish in situ and in real time.The present intramolecular cyclization reaction is selective and atom-economical,thereby not only providing an important approach for the convenient synthesis of triazolopyridines,but also offering a general strategy for sensitive,selective and biocompatible detection of endogenous HOCl in complex biosystems.
文摘Background: Septic open abdomens occur in trauma, burn and surgery. Currently, multiple concentrations of hypochlorous acid solutions have effectively decreased the microbiotic burden in wounds. We hypothesized that Vashe?, a neutral hypochlorous acid solution (V-HOCL), would be safe as an intraperitoneal irrigation or washout disinfectant for septic open abdomens utilizing negative pressure wound therapy. Methods: This is a retrospective observational review of patients who required delayed abdominal closures after exploratory laparotomies. Group A (n = 8) had cyclical V-HOCL irrigation to their open abdomens combining AbtheraTM and V.A.C. Dressing System for negative pressure wound therapy with irrigation (NPWT-i) and Group B (n = 9) had intra-abdominal V-HOCL washouts. Results: Fifty percent of both groups had either septic or hemorrhagic shock on admission. Compared to Group B, Group A patients were older (median 50 vs 37 years), and had a median hospitalization of 28 vs 8 days, 4 times as many operations, more acute renal failure and co-morbidities. No statistically significant differences were detected be-tween the two treatment methods with the V-HOCL delivery and removal. Conclusion: There were no episodes of electrolyte imbalance, hypotension, hypertension, anaphylaxis, hemorrhage, visceral injury or systemic toxicity. V-HOCL with/without NPWT-i irrigation was a safe modality and tolerated well in this study.
文摘Raised myeloperoxidase (MPO) serum levels are associated with endothelial dysfunction and cigarette smoking is a risk factor for cardiovascular diseases. Since myocardial infarction is associated with leukocytosis and smokers present increased levels of neutrophils, here we hypothesized that the levels of serum MPO in smokers could be also raised. We carried out a study on sixty eight adult healthy volunteers. The control group consisted of thirty four non-smokers and the test group was thirty four heavy smokers. The hemogram, interleukin-8 (IL-8) and MPO serum levels were measured. Neutrophil, monocyte and lymphocyte counts were higher
文摘Hypochlorous acid (HOCl) is a strong oxidant produced by activated neutrophils via the myeloperoxidase (MPO) enzyme in order to fight against infections. Because of their antimicrobial and antiviral properties, stabilized HOCl solutions were produced to be used as a disinfectant and became a recommended disinfectant against COVID-19 by the US Environmental Protection Agency. Aberrant MPO enzyme activity results in abundant HOCl production which is related to the development and/or progression of several diseases including atherosclerosis, cardiovascular and neurodegenerative diseases. Previous studies investigating the effect of HOCl on the mode of cell death in different cell types reported that HOCl induces both apoptosis and necrosis depending on its concentration. However, the data on the apoptotic pathway triggered by HOCl is controversial. In this study, we investigated the <span><span style="font-family:Verdana;">mode of cell death induced by different concentrations of HOCl in <i></i></span><i><i><span style="font-family:Verdana;">Saccharomyces</span></i></i></span><i><i><span style="font-family:Verdana;"> cerevisiae</span></i><span style="font-family:Verdana;"></span></i>. Our data revealed that HOCl leads to cell death within 1 minute at 170 <span style="line-height:102%;font-family:Verdana;">μ</span><span style="font-family:Verdana;">M and above. At 340 </span><span style="line-height:102%;font-family:Verdana;">μ</span><span style="font-family:Verdana;">M, HOCl causes a rapid necrosis, while 170 μM HOCl leads to apoptosis. HOCl-induced apoptosis is mostly caspase dependent and Aif1 doesn’t have a significant role.</span>
文摘Utilization of negative pressure wound therapy with instillation (NPWTi) for sternal dehiscence wounds secondary to sternal wound infection after surgery has become an accepted therapy. NPWTi accelerates wound healing through macrostrain, microstrain, and cyclic fluid instillation. Wounds benefit from additional superficial infection control with the removal of microorganisms, the release of proinflammatory mediators, stimulation of angiogenesis, as well as mechanical debridement. However, very few cases of utilizing NPWTi in the treatment of sternal wound infections have been reported in the literature. This case study describes the use of NPWTi with hypochlorous acid for the treatment of a sternal wound infection.
基金funded by the A-Base Research Project(J-1276)of Agriculture and Agri-Food Canada.
文摘Objectives:This study investigated the effects of processing parameters,specifically the flow rate and the combination of diluted HCI and salt(NaCl)at different concentrations,on the properties of slightly acidic electrolyzed water(SAEW)that was produced.Materials and Methods:The properties of the SAEW that were analyzed included pH,oxidation-reduction potential(ORP),available chlorine concentration(ACC),and generated hypochlorous acid(HCIO)concentration.Meanwhile,the total aerobic bacteria and total phenolic content retention were determined.Results:NaCl alone resulted in the lowest pH(<4)and the highest ORP values(>1000 mV).Increasing the HCI concentration significantly raised the pH to greater than 5 and lowered the ORP values of SAEW,with the highest pH(5.7)observed with 1.5%HCI and 5%NaCl.The highest HCIO concentration of 19.65±1.03 mg/L was obtained with 1.5%HCI:5%NaCl.Interestingly,the concentration of NaCl had no significant effect on the production of HCIO.Furthermore,different concentrations of combined NaCl and HCI significantly influenced the inactivation efficiency on total aerobic bacteria count and changes in phenolic compound content.Increasing HCI concentrations from 0.5% to 2.0%led toan increase in the reduction of aerobic bacteria counts from 2.51 to 4.22 log colony-forming units(CFU)/g with 5%NaCl and from 2.49 to 3.52 log CFU/g with 10%NaCl.Flow rates significantly contributed to the change in HCIO formation and altered the properties of the produced SAEW.The results indicated that SAEW treatment significantly reduced total aerobic bacteria counts.A lower flow rate(O.3 L/min)produced the highest log reduction.Additionally,SAEW treatment led to a reduction in phenolic content,even though a considerable amount was retained at lower HCIO concentrations.Conclusions:These findings offer valuable information on optimizing SAEW treatment protocols for enhancing microbial safety and extending the shelf life of fresh produce,while considering the impact on the content of phenolic compounds.
基金supported by the National Natural Science Foundation of China(21877013,21671043)the Initial Research Funds for Young Teachers of Donghua University。
文摘Levels of reactive oxygen species(ROS)in cancer cells or in the tumor microenvironment differ noticeably from those in normal cells and cellular microenvironments because ROS play important roles in all aspects of tumor physiology.However,due to the lack of adequate tools,it is difficult to study the relationship between ROS,especially certain types of ROS(e.g.,HOCl),and cancer.We report herein an HOCl-specific fluorescent probe,FDOCl-20,containing a thiocarbamide group as a receptor,for the visualization of HOCl in solid tumors in vivo.This probe displays high selectivity and sensitivity to HOCl,and is appropriate for use in acidic conditions,including the tumor microenvironment.Using FDOCl-20 as a tool,we can visualize HOCl in solid tumors in vivo.Importantly,the fluorescent intensity of FDOCl-20 is proportional to tumor volume.Thus,FDOCl-20 is a useful tool to investigate the relationship between HOCl and the physiological processes of tumors.
基金supported by The University of Hong Kong,Morningside Foundation,Hong Kong Research Grants Council Area of Excellence Scheme(grant no.AoE/P-705/16 to D.Y.)National Natural Science Foundation of China(grant no.21961142011 to D.Y.)the Israel Science Foundation-China Joint Funding Program.
文摘Probes for in vivo imaging of hypochlorous acid(HOCl),one of the most important reactive oxygen species in innate immunity,are urgently needed to understand the pathogenesis of autoimmune and neuroinflammatory disorders.As a strong oxidant,HOCl could bleach near-infrared sensors and inactivate luciferase readily,making in vivo imaging overwhelmingly challenging.Via fine-tuning of a selective HOCl sensing moiety,HOCl stable spacer,and bright chemiluminescent scaffold,we have developed HOCl-CL-510 as a highly selective and sensitive probe for HOCl detection both in vitro and in vivo.In particular,we achieved recurring real-time monitoring of HOCl in both acute and chronic inflammation models in living mice,providing a new chemical tool for dynamic monitoring of disease development with reduced usage of experimental animals.
