Rheumatoid arthritis(RA) is a chronic inflammatory disease with multi-system damage and autoimmune features.The main clinical manifestations of RA include joint pain,swelling,and stiffness,and RA may lead to joint def...Rheumatoid arthritis(RA) is a chronic inflammatory disease with multi-system damage and autoimmune features.The main clinical manifestations of RA include joint pain,swelling,and stiffness,and RA may lead to joint deformity and dysfunction in severe cases.The pathologic development of RA involves complex interactions of multiple biomarkers,and detecting a single biomarker may produce falsepositive results due to other confounding factors.Therefore,fluorescent probes that can detect multiple biomarkers simultaneously are crucial for precise RA diagnosis.Peroxynitrite(ONOO^(-)) and viscosity are inflammation-related factors in cells.In this study,we developed a dual responsive near-infrared fluorescent probe,YLS,for ONOO^(-) and viscosity.The probe features dual-channel turn-on fluorescence responses at 625 and 760 nm upon the presence of ONOO^(-) and viscosity,respectively.Supported by YLS,we found that during RA pathology,lymphocyte infiltration not only increases the concentration of proteins in the joint fluid resulting in elevated viscosity;at the same time,the overproduction of ONOO^(-) exacerbates oxidative stress and inflammatory responses.This multiparameter assay is expected to improve the diagnostic accuracy of the early stages of RA,thus providing a scientific basis for early intervention and personalized treatment.展开更多
Intracellular redox homeostasis is of indispensable importance in pathophysiology.In order to maintain the balance of the redox state within the cell,reactive oxygen species(ROS)and reactive sulfur species(RSS)react a...Intracellular redox homeostasis is of indispensable importance in pathophysiology.In order to maintain the balance of the redox state within the cell,reactive oxygen species(ROS)and reactive sulfur species(RSS)react and transform with each other,and their levels also directly reflect the degree of oxidative stress and disease.Hypochlorous acid(HClO)and cysteine(Cys)usually co-exist in organisms,interacting with each other in many important physiological processes and synergistically maintaining the dynamic redox balance in the body.To understand the relevance and pathophysiological effects of these two signaling molecules in oxidative stress,unique fluorescence imaging tools are required.Herein,we designed and developed a dual-channel fluorescent probe HP,for the individual and continuous detection of HClO and Cys.This probe could simultaneously monitor the changes in the concentrations of HClO and Cys in cells,and was characterized by a fast response,high sensitivity and high selectivity,especially compared with glutathione(GSH)and homocysteine(Hcy),the probe had a good specificity for Cys.Importantly,probe HP successfully observed dynamic changes in HCl O-and Cys-mediated redox status in the oxygenglucose deprivation/reperfusion(OGD/R)model of HeLa cells and dynamically monitored fluctuations in endogenous HClO levels in lipopolysaccharides(LPS)-induced peritonitis mice.展开更多
Excited-state intramolecular proton-transfer(ESIPT)based fluorescence probes are particularly attractive due to their unique properties including environmental sensitivity,a large Stokes shift,and potential for ratiom...Excited-state intramolecular proton-transfer(ESIPT)based fluorescence probes are particularly attractive due to their unique properties including environmental sensitivity,a large Stokes shift,and potential for ratiometric sensing.In general,ESIPT-based fluorophore incorporates an intramolecular hydrogen bonding interaction between a hydrogen bond donor(-OH and NH_(2)are common)and a hydrogen bond acceptor(C=N and C=O).More,protection-deprotection of hydroxyl group as hydrogen bond donor could induce an off-on switch of ESIPT-based emission.Therefore,protection-deprotection of hydroxyl group has been the widely used strategy to design fluorescent probes,where the potential key issue is selecting a protective group that can specifically leave in the presence of the target analyte.In this review,we mainly summarize the specific protecting groups(sites)and deprotection mechanisms for biologically important species(including reactive sulfur species(RSS),reactive oxygen species(ROS),enzymes,etc.),and analyze the advantages and disadvantages of different protection mechanisms from some aspects including probe stability,selectivity,response rate and assay system,etc.Based on the aforementioned,we further point out the current challenges and the potential future direction for developing ESIPT-based probes.展开更多
Focused on the performance promotion of organic small molecular dyes based photothermal agents via non-chemical modification,we found that heat-assisted binding of human serum albumin(HSA)to the dye causes shrinkage o...Focused on the performance promotion of organic small molecular dyes based photothermal agents via non-chemical modification,we found that heat-assisted binding of human serum albumin(HSA)to the dye causes shrinkage of the protein and encapsulate the dye to form nanoparticles.This revolutionizes the photostability of small molecule dyes which further improves their photothermal conversion effi-ciency and tumor ablation performance as photothermal agents significantly.In this work,the obtained photothermal agent named HSA-P2-T could accumulate in tumor and induce 22℃enhancement of the tumor in xenograft models upon ultra-low dose(0.1 W/cm^(2))laser irradiation,which,as far as we know,is the lowest laser dose used in vivo photothermal therapy.Utilizing HSA-P2-T,we realized tumor ablation upon twice intravenous injections of the nanoparticles and four photothermal treatments.展开更多
Hydrogen peroxide(H2 O2), as important products of oxygen metabolism, plays an important role in many biological processes, such as immune responses and cellular signal transduction. However, abnormal production of H2...Hydrogen peroxide(H2 O2), as important products of oxygen metabolism, plays an important role in many biological processes, such as immune responses and cellular signal transduction. However, abnormal production of H2 O2 can damage cellular biomolecules, which was closely associated with many diseases.Thus, it is urgent to monitor the level change of H2 O2 in living cells, particularly at subcellular levels.Toward this end, a wide variety of H2 O2 fluorescent probes have been designed, developed and applied for imaging of H2 O2 in subcellular levels. In this review, we highlight the representative cases of H2 O2 fluorescent probes with mitochondria, nuclei and lysosomes-targetable ability. The review contains organelle target strategies, structures, fluorescence behavior and biological applications of these probes.展开更多
Intracellular pH homeostasis is foundation of maintaining normal physiological functions.More and more evidences show that intracellular pH fluctuations were usually associated with many diseases(such as cancer,epilep...Intracellular pH homeostasis is foundation of maintaining normal physiological functions.More and more evidences show that intracellular pH fluctuations were usually associated with many diseases(such as cancer,epilepsy and neurodegenerative diseases).It is very important to develop in situ real-time determination of pH.In recent years,it has been verified that pH can regulate the isomerization process of spiropyran.Thus,we report a pH fluorescent probe BSL,which is a closed loop spiropyran structure by coupling benzothiazole derivatives with indole salts.We utilizes the process of spiropyran isomerization as the trigger of excited state intramolecular proton transfer(ESIPT)effect,and adjust the process of spiropyran isomerization through pH,and then the molecular transformation from enol to ketone(enol:525 nm,ketone:677 nm)through the ESIPT effect.This process achieved accurate measurement of pH.The probe BSL showed sensitive and reversible fluorescence response to pH in vitro.Ultimately,BSL was successfully applied to detect pH fluctuations in cell oxidative stress model.展开更多
The development of fluorescent probes enabling to distinguish Cys,Hcy and GSH has always been a considerable challenge,in particular the distinction of Hcy and other two biothiols,because Hcy has a very similar struct...The development of fluorescent probes enabling to distinguish Cys,Hcy and GSH has always been a considerable challenge,in particular the distinction of Hcy and other two biothiols,because Hcy has a very similar structure with Cys and a relatively lower concentration in living organisms.In this work,a special o-dialdehyde fluorescent probe,quinoline-2,3-dicarboxaldehyde(QDA),has been synthesized and demonstrated superior performance in differentiating detection of Hcy and GSH,which is different from the previous reported o-dialdehyde probes specifically detecting GSH.Furthermore,the probe can selectively distinguish Hcy and GSH from different signal channels in living cells and zebrafish,meaning it has great potential in biological applications.This finding will provide a novel idea for the design of fluorescent probes to distinguish biothiols.展开更多
A colorimetric and fluorometric dual-model probe for mercury (II) ion was developed employing fluorescein hydrazide (FH) in ethanol-HEPES solution (1:1, v/v, pH 8.0). The probe exhibited high selectivity and sensitivi...A colorimetric and fluorometric dual-model probe for mercury (II) ion was developed employing fluorescein hydrazide (FH) in ethanol-HEPES solution (1:1, v/v, pH 8.0). The probe exhibited high selectivity and sensitivity for Hg2+ detection using UV/Vis and fluorescence spectroscopy. Addition of Hg2+ caused a visual color change from colorless to coloured and a fluorescence change from colorless to bright green. Other metal ions did not interfere with the detection of Hg2+.展开更多
Mitochondria is the main organelle for the production of reactive sulfur species(RSS), such as homocysteine(Hcy), cysteine(Cys), glutathione(GSH) and sulfur dioxide(SO_(2)). These compounds participate in a large numb...Mitochondria is the main organelle for the production of reactive sulfur species(RSS), such as homocysteine(Hcy), cysteine(Cys), glutathione(GSH) and sulfur dioxide(SO_(2)). These compounds participate in a large number of physiological processes and play an extremely important role in maintaining the balance of life systems. Abnormal concentration and metabolism are closely related to many diseases. Due to their similarities in chemical properties, it is challenging to develop a single fluorescent probe to distinguish them simultaneously. Here, we synthesized the probe PI-CO–NBD with three fluorophores, NBD-Cl and benzopyranate as the reaction sites of GSH/Cys/Hcy and SO_(2), respectively. Three biothiols all could cleavage ether bond to release benzopyrylium and coumarin moiety, which emitted red and blue fluorescence,but Cys/Hcy also could do intramolecular rearrangement after nucleophilic substitution, resulting in yellow fluorescence. Thus the probe can distinguish Cys/Hcy and GSH. Subsequently, only SO_(2)could quench red fluorescence by adding C=C of benzopyrylium. The probe also could localize well in mitochondria by oxonium ion for all kinds of cells. The probe not only could detect above sulfur-containing active substances of intracellular and extracellular but also monitor the level of them under oxidative stress and apoptosis process in living cells and zebrafish.展开更多
Cysteine(Cys)plays an important role in regulating cellular redox balance.But due to the constant changes in the concentration of Cys in organisms,fast response sensors are urgent required for practical application.In...Cysteine(Cys)plays an important role in regulating cellular redox balance.But due to the constant changes in the concentration of Cys in organisms,fast response sensors are urgent required for practical application.In this work,a fluorescent probe with a fast response was developed by linking coumarin derivatives containingα,β-unsaturated ketones to NBD.The PET effect made the system non-fluorescent.When the probe reacted with Cys,the bond between the coumarin derivative and the NBD was cut off,meanwhile a rapid rearrangement and reactive site passivation occurred.Then two fluorophores with the same emission peak are released,among them,strong fluorescence signal of NBD dominated.Thus,although the similar reaction occurred for Hcy,the rate of NBD derivative rearrangement was slow,in a short time,fluorescence signal was still weak.As for GSH,cleavage could occur,but no rearrange within the NBD molecule due to GSH with large volume.Because of strong fluorescent emission,this probe was successfully used in biological imaging about cell and zebrafish.More importantly,the probe was successfully used to evaluate the oxidative stress caused by copper(Ⅱ)in living cells.This fluorescence strategy and application will provide a new way of studying intracellular oxidative stress processes and damage.展开更多
Fluorescence image for accurate tumor label still faces challenges in cancer detection and diagnostics.Emerging evidence is indicating that glucose-regulated protein 78(GRP78), a stress-inducible protein chaperone, is...Fluorescence image for accurate tumor label still faces challenges in cancer detection and diagnostics.Emerging evidence is indicating that glucose-regulated protein 78(GRP78), a stress-inducible protein chaperone, is a great potential biomarker and therapeutic target for cancer. However, currently available probe for image tumor based on GRP78 has not been reported, owning to no obvious strategy in probe design towards this protein. In this paper, a hairpin-shaped peptidyl probe(pep FAM) conjugated with a 5-FAM fluorophore and a dabcyl quencher at both ends was developed, respectively. The probe was designed by performing a traditional fluorescence resonance energy transfer mechanism and employing a GRP78 specifically-binding peptide. Furthermore, the probe was used to specifically image cancer cells,and accurately image xenograft tumors in mice models. The novel fluorescent probe is expected to be a useful tool for the diagnostics of cancer.展开更多
Due to the biological importance of cysteine(Cys),the development of organic fluorescence probes for Cys has been a wide,potent,and outstanding research field in most recent years.It has been used as a biomarker in tr...Due to the biological importance of cysteine(Cys),the development of organic fluorescence probes for Cys has been a wide,potent,and outstanding research field in most recent years.It has been used as a biomarker in treating various diseases;therefore,developing a sensing mechanism for detecting Cys is very important.In this Review,we focus on and summarize the specific results of recent exciting literature regarding the sensing mechanism of Cys-specific fluorescence probes and their applications in Cys recognition.Moreover,a design strategy of the sensing mechanism of Cys can be classified into seven reaction mechanisms,including the aromatic substitution rearrangement reaction,cyclization of aldehyde,Michael addition reaction,Se-N or S-S or bond cleavage reaction,addition cyclization of acrylate,metal complex reaction,and nucleophilic substitution reaction.In all sections,discussions have corresponded to Cys-specific sensing mechanisms,which consist of emission,color changes,and detection limits and deal with the application and recognition sites of molecules.Future directions and challenges have been proposed for the preparation of Cys-specific probes.展开更多
Multicolor fluorescent probes based on small organic molecules have the advantages of low cost, good biocompatibility, easily modifiable molecular structures and adjustable fluorescence performance. In addition, small...Multicolor fluorescent probes based on small organic molecules have the advantages of low cost, good biocompatibility, easily modifiable molecular structures and adjustable fluorescence performance. In addition, small molecule multicolor fluorescent probes generally undergo multi-site or multi-step reactions, which means that they can be used for the specific detection of structurally similar substances in complex bio-systems. In this review, we focus on the design and application of multicolor fluorescent probes based on small organic molecules: single fluorophores with multiple reaction sites, multiple fluorophores with single reaction sites, or multiple fluorophores with multiple reaction sites. Moreover, a design strategy for multicolor fluorescent probes and its application in biological imaging are also summarized, providing a systematic plan for future research on fluorescent probes functionalized by small organic molecules. It will also play an important role in the development of additional functions for small organic molecule fluorescent probes.展开更多
Heterocyclic compound quinoline and its derivatives exist in natural compounds and have a broad spectrum of biological activity.They play an important role in the design of new structural entities for medical applicat...Heterocyclic compound quinoline and its derivatives exist in natural compounds and have a broad spectrum of biological activity.They play an important role in the design of new structural entities for medical applications.Similarly,indoles and their derivatives are found widely in nature.Amino acids,alkaloids and auxin are all derivatives of indoles,as are dyes,and their condensation with aldehydes makes it easy to construct reaction sites for nucleophilic addition agents.In this work,we combine these two groups organically to construct a rapid response site(within 30 s)for H_(2)S,and at the same time,a ratiometric fluorescence response is presented throughout the process of H_(2)S detection.As such,the lower detection limit can reach 55.7 nmol/L for H_(2)S.In addition,cell imaging shows that this probe can be used for the mitochondrial targeted detection of endogenous and exogenous H_(2)S.Finally,this probe application was verified by imaging H_(2)S in nude mice.展开更多
Successful regenerative medicine strategies of xenogeneic extracellular matrix need a synergistic balance among inflammation,fibrosis,and remodeling process.Adaptive macrophage subsets have been identified to modulate...Successful regenerative medicine strategies of xenogeneic extracellular matrix need a synergistic balance among inflammation,fibrosis,and remodeling process.Adaptive macrophage subsets have been identified to modulate inflammation and orchestrate the repair of neighboring parenchymal tissues.This study fabricated PPARγ-primed CD68+CD206+M2 phenotype(M2γ),and firstly verified their anti-inflammatory and tissue-regenerating roles in xenogeneic bioengineered organ regeneration.Our results showed that Th1-type CD3^(+)CD8^(+)T cell response to xenogeneic-dentin matrix-based bioengineered root complex(xeno-complex)was significantly inhibited by M2γmacrophage in vitro.PPARγactivation also timely recruited CD68^(+)CD206^(+)tissue macrophage polarization to xeno-complex in vivo.These subsets alleviated proinflammatory cytokines(TNF-α,IFN-γ)at the inflammation site and decreased CD3^(+)CD8^(+)T lymphocytes in the periphery system.When translated to an orthotopic nonhuman primate model,PPARγ-primed M2 macrophages immunosuppressed IL-1β,IL-6,TNF-α,MMPs to enable xeno-complex to effectively escape immune-mediated rejection and initiate graft-host synergistic integrity.These collective activities promoted the differentiation of odontoblast-like and periodontal-like cells to guide pulp-dentin and cementum-PDLs-bone regeneration and rescued partially injured odontogenesis such as DSPP and periostin expression.Finally,the regenerated root showed structure-biomechanical and functional equivalency to the native tooth.The timely conversion of M1-to-M2 macrophage mainly orchestrated odontogenesis,fibrogenesis,and osteogenesis,which represents a potential modulator for intact parenchymal-stromal tissue regeneration of targeted organs.展开更多
Altered metabolism has long been recognized as a central hallmark of cancer;however,in the fluorescence imaging field,few studies have been conducted to label tumors by exploiting metabolic differences between cancer ...Altered metabolism has long been recognized as a central hallmark of cancer;however,in the fluorescence imaging field,few studies have been conducted to label tumors by exploiting metabolic differences between cancer cells and normal cells.In this work,we successfully developed a metabolic probe MB-C for specific imaging of glutathione(GSH)dynamic metabolic pathways.GSH was endogenously metabolized to produce SO_(2)via Na_(2)S_(2)O_(3) and thiosulfate sulfurtransferase,equilibrating with sulfites/bisulfites.MB-C was allowed to be activated by GSH along with multi-fluorescence emission increased in red and green channels and further sequence-response metabolites(SO_(2))of GSH in significant fluorescence ratio change of red and green channels.Furthermore,such evident fluorescence ratio changes could be used to distinguish cancer cells from normal cells and identify tumor and normal tissues.Therefore,GSH metabolic imaging was successfully applied to accurately label tumors,which provides a new idea and practical case for the precise visualization of malignant tumors.展开更多
基金the National Natural Science Foundation of China(Nos.22325703,22377071,U23A6009)Research Project Supported by Shanxi Scholarship Council of China(No.2022-002)+1 种基金the Shanxi Province Science Foundation(No.202203021221009)Shanxi Province Science and Technology activities for overseas people selected funding project(No.2024001)。
文摘Rheumatoid arthritis(RA) is a chronic inflammatory disease with multi-system damage and autoimmune features.The main clinical manifestations of RA include joint pain,swelling,and stiffness,and RA may lead to joint deformity and dysfunction in severe cases.The pathologic development of RA involves complex interactions of multiple biomarkers,and detecting a single biomarker may produce falsepositive results due to other confounding factors.Therefore,fluorescent probes that can detect multiple biomarkers simultaneously are crucial for precise RA diagnosis.Peroxynitrite(ONOO^(-)) and viscosity are inflammation-related factors in cells.In this study,we developed a dual responsive near-infrared fluorescent probe,YLS,for ONOO^(-) and viscosity.The probe features dual-channel turn-on fluorescence responses at 625 and 760 nm upon the presence of ONOO^(-) and viscosity,respectively.Supported by YLS,we found that during RA pathology,lymphocyte infiltration not only increases the concentration of proteins in the joint fluid resulting in elevated viscosity;at the same time,the overproduction of ONOO^(-) exacerbates oxidative stress and inflammatory responses.This multiparameter assay is expected to improve the diagnostic accuracy of the early stages of RA,thus providing a scientific basis for early intervention and personalized treatment.
基金the National Natural Science Foundation of China(Nos.22207069,22325703,22377071,22074084)Research Project Supported by Shanxi Scholarship Council of China(No.2022-002)+2 种基金the Shanxi Province Science Foundation(Nos.20210302124012,202203021221009)Key R&D and transformation plan of Qinghai Province(No.2020-GX-101)2023 Graduate Innovation Project of Shanxi University。
文摘Intracellular redox homeostasis is of indispensable importance in pathophysiology.In order to maintain the balance of the redox state within the cell,reactive oxygen species(ROS)and reactive sulfur species(RSS)react and transform with each other,and their levels also directly reflect the degree of oxidative stress and disease.Hypochlorous acid(HClO)and cysteine(Cys)usually co-exist in organisms,interacting with each other in many important physiological processes and synergistically maintaining the dynamic redox balance in the body.To understand the relevance and pathophysiological effects of these two signaling molecules in oxidative stress,unique fluorescence imaging tools are required.Herein,we designed and developed a dual-channel fluorescent probe HP,for the individual and continuous detection of HClO and Cys.This probe could simultaneously monitor the changes in the concentrations of HClO and Cys in cells,and was characterized by a fast response,high sensitivity and high selectivity,especially compared with glutathione(GSH)and homocysteine(Hcy),the probe had a good specificity for Cys.Importantly,probe HP successfully observed dynamic changes in HCl O-and Cys-mediated redox status in the oxygenglucose deprivation/reperfusion(OGD/R)model of HeLa cells and dynamically monitored fluctuations in endogenous HClO levels in lipopolysaccharides(LPS)-induced peritonitis mice.
基金National Natural Science Foundation of China(Nos.22277104,22325703,22074084)the Natural Science Foundation of Shanxi Province(No.202203021212184)+3 种基金Research Project supported by Shanxi Scholarship Council of China(No.2022-002)the Basic Research Program of Shanxi Province(Free Exploration)(No.202203021221009)2022 Lvliang City science and technology plan project(Nos.2022SHFZ51,2022GXYF15)Scientific Instrument Center of Shanxi University(No.201512)。
文摘Excited-state intramolecular proton-transfer(ESIPT)based fluorescence probes are particularly attractive due to their unique properties including environmental sensitivity,a large Stokes shift,and potential for ratiometric sensing.In general,ESIPT-based fluorophore incorporates an intramolecular hydrogen bonding interaction between a hydrogen bond donor(-OH and NH_(2)are common)and a hydrogen bond acceptor(C=N and C=O).More,protection-deprotection of hydroxyl group as hydrogen bond donor could induce an off-on switch of ESIPT-based emission.Therefore,protection-deprotection of hydroxyl group has been the widely used strategy to design fluorescent probes,where the potential key issue is selecting a protective group that can specifically leave in the presence of the target analyte.In this review,we mainly summarize the specific protecting groups(sites)and deprotection mechanisms for biologically important species(including reactive sulfur species(RSS),reactive oxygen species(ROS),enzymes,etc.),and analyze the advantages and disadvantages of different protection mechanisms from some aspects including probe stability,selectivity,response rate and assay system,etc.Based on the aforementioned,we further point out the current challenges and the potential future direction for developing ESIPT-based probes.
基金the National Natural Science Foundation of China(Nos.22277069,22074084)Program of the State Key Laboratory of Quantum Optics and Optical Quantum Devices of Shanxi University(No.KF202108).
文摘Focused on the performance promotion of organic small molecular dyes based photothermal agents via non-chemical modification,we found that heat-assisted binding of human serum albumin(HSA)to the dye causes shrinkage of the protein and encapsulate the dye to form nanoparticles.This revolutionizes the photostability of small molecule dyes which further improves their photothermal conversion effi-ciency and tumor ablation performance as photothermal agents significantly.In this work,the obtained photothermal agent named HSA-P2-T could accumulate in tumor and induce 22℃enhancement of the tumor in xenograft models upon ultra-low dose(0.1 W/cm^(2))laser irradiation,which,as far as we know,is the lowest laser dose used in vivo photothermal therapy.Utilizing HSA-P2-T,we realized tumor ablation upon twice intravenous injections of the nanoparticles and four photothermal treatments.
基金the National Natural Science Foundation of China (Nos. 21705102, 21775096)the Shanxi Province Science Foundation for Youths (No. 201701D221061)+1 种基金Shanxi Province Foundation for Returnees (No. 2017-026)Scientific Instrument Center of Shanxi University (No. 201512)
文摘Hydrogen peroxide(H2 O2), as important products of oxygen metabolism, plays an important role in many biological processes, such as immune responses and cellular signal transduction. However, abnormal production of H2 O2 can damage cellular biomolecules, which was closely associated with many diseases.Thus, it is urgent to monitor the level change of H2 O2 in living cells, particularly at subcellular levels.Toward this end, a wide variety of H2 O2 fluorescent probes have been designed, developed and applied for imaging of H2 O2 in subcellular levels. In this review, we highlight the representative cases of H2 O2 fluorescent probes with mitochondria, nuclei and lysosomes-targetable ability. The review contains organelle target strategies, structures, fluorescence behavior and biological applications of these probes.
基金the National Natural Science Foundation of China(No.22074084)One Hundred People Plan of Shanxi Province,Shanxi Province“1331 Project”Key Innovation Team Construction Plan Cultivation Team(No.2018-CT-1)+6 种基金Research Project Supported by Shanxi Scholarship Council of China(No.2022-002)Shanxi Province Foundation for Returness(No.2017-026)Shanxi Collaborative Innovation Center of High Value-added Utilization of Coalrelated Wastes(No.2015-10-B3)the Shanxi Province Foundation for Selected(2019),Innovative Talents of Higher Education Institutions of Shanxi,Scientific and Technological Innovation Programs of Higher Education Institutions in Shanxi(No.2019L0031)Key R&D Program of Shanxi Province(No.201903D421069),the Shanxi Province Science Foundation(No.201901D111015)Key R&D and Transformation Plan of Qinghai Province(No.2020-GX-101)Graduate Innovation Project of Shanxi Province and Scientific Instrument Center of Shanxi University(No.201512)。
文摘Intracellular pH homeostasis is foundation of maintaining normal physiological functions.More and more evidences show that intracellular pH fluctuations were usually associated with many diseases(such as cancer,epilepsy and neurodegenerative diseases).It is very important to develop in situ real-time determination of pH.In recent years,it has been verified that pH can regulate the isomerization process of spiropyran.Thus,we report a pH fluorescent probe BSL,which is a closed loop spiropyran structure by coupling benzothiazole derivatives with indole salts.We utilizes the process of spiropyran isomerization as the trigger of excited state intramolecular proton transfer(ESIPT)effect,and adjust the process of spiropyran isomerization through pH,and then the molecular transformation from enol to ketone(enol:525 nm,ketone:677 nm)through the ESIPT effect.This process achieved accurate measurement of pH.The probe BSL showed sensitive and reversible fluorescence response to pH in vitro.Ultimately,BSL was successfully applied to detect pH fluctuations in cell oxidative stress model.
基金the National Natural Science Foundation of China(Nos.21672131,21775096,21907062)One Hundred People Plan of Shanxi Province+10 种基金Shanxi Province"1331 Project"Key Innovation Team Construction Plan Cultivation Team(No.2018-CT-1)2018 Xiangyuan County Solid Waste Comprehensive Utilization Science and Technology Project(No.2018XYSDJS-05)the Shanxi Province Foundation for Selected(2019)Innovative Talents of Higher Education Institutions of Shanxi(2019)Scientific and Technological Innovation Programs of Higher Education Institutions in Shanxi(No.2019L0031)Key R&D Program of Shanxi Province(No.201903D421069)Natural Science Foundation of Shanxi Province of China(No.201901D111015)Shanxi Province Foundation for Returness(No.2017-026)Program for the Innovative Talents of Higher Education Institutions of Shanxi(2019)Shanxi Collaborative Innovation Center of High Value-added Utilization of Coalrelated Wastes(No.2015-10-B3)Scientific Instrument Center of Shanxi University(No.201512)。
文摘The development of fluorescent probes enabling to distinguish Cys,Hcy and GSH has always been a considerable challenge,in particular the distinction of Hcy and other two biothiols,because Hcy has a very similar structure with Cys and a relatively lower concentration in living organisms.In this work,a special o-dialdehyde fluorescent probe,quinoline-2,3-dicarboxaldehyde(QDA),has been synthesized and demonstrated superior performance in differentiating detection of Hcy and GSH,which is different from the previous reported o-dialdehyde probes specifically detecting GSH.Furthermore,the probe can selectively distinguish Hcy and GSH from different signal channels in living cells and zebrafish,meaning it has great potential in biological applications.This finding will provide a novel idea for the design of fluorescent probes to distinguish biothiols.
文摘A colorimetric and fluorometric dual-model probe for mercury (II) ion was developed employing fluorescein hydrazide (FH) in ethanol-HEPES solution (1:1, v/v, pH 8.0). The probe exhibited high selectivity and sensitivity for Hg2+ detection using UV/Vis and fluorescence spectroscopy. Addition of Hg2+ caused a visual color change from colorless to coloured and a fluorescence change from colorless to bright green. Other metal ions did not interfere with the detection of Hg2+.
基金the National Natural Science Foundation of China (Nos. 21775096, 22074084)One Hundred People Plan of Shanxi Province, Shanxi Province "1331 Project" Key Innovation Team Construction Plan Cultivation Team (No. 2018-CT-1)+4 种基金2018 Xiangyuan County Solid Waste Comprehensive Utilization Science and Technology Project (No. 2018XYSDJS-05)the Shanxi Province Foundation for Selected (2019), Innovative Talents of Higher Education Institutions of Shanxi, Scientific and Technological Innovation Programs of Higher Education Institutions in Shanxi (No. 2019L0031)Key R&D Program of Shanxi Province (No. 201903D421069)the Shanxi Province Science Foundation (No. 201901D111015)Scientific Instrument Center of Shanxi University (No. 201512)。
文摘Mitochondria is the main organelle for the production of reactive sulfur species(RSS), such as homocysteine(Hcy), cysteine(Cys), glutathione(GSH) and sulfur dioxide(SO_(2)). These compounds participate in a large number of physiological processes and play an extremely important role in maintaining the balance of life systems. Abnormal concentration and metabolism are closely related to many diseases. Due to their similarities in chemical properties, it is challenging to develop a single fluorescent probe to distinguish them simultaneously. Here, we synthesized the probe PI-CO–NBD with three fluorophores, NBD-Cl and benzopyranate as the reaction sites of GSH/Cys/Hcy and SO_(2), respectively. Three biothiols all could cleavage ether bond to release benzopyrylium and coumarin moiety, which emitted red and blue fluorescence,but Cys/Hcy also could do intramolecular rearrangement after nucleophilic substitution, resulting in yellow fluorescence. Thus the probe can distinguish Cys/Hcy and GSH. Subsequently, only SO_(2)could quench red fluorescence by adding C=C of benzopyrylium. The probe also could localize well in mitochondria by oxonium ion for all kinds of cells. The probe not only could detect above sulfur-containing active substances of intracellular and extracellular but also monitor the level of them under oxidative stress and apoptosis process in living cells and zebrafish.
基金the National Natural Science Foundation of China(Nos.21775096,21907062)One Hundred People Plan of Shanxi Province+10 种基金Shanxi Province"1331 Project"Key Innovation Team Construction Plan Cultivation Team(No.2018-CT-1)2018 Xiangyuan County Solid Waste Comprehensive Utilization Science and Technology Project(No.2018XYSDJS-05)the Shanxi Province Foundation for Selected(2019)Innovative Talents of Higher Education Institutions of Shanxi(2019)Scientific and Technological Innovation Programs of Higher Education Institutions in Shanxi(No.2019L0031)Key R&D Program of Shanxi Province(No.201903D421069)Natural Science Foundation of Shanxi Province of China(No.201901D111015)Shanxi Province Foundation for Returness(No.2017-026)Program for the Innovative Talents of Higher Education Institutions of Shanxi(2019)Shanxi Collaborative Innovation Center of High Value-added Utilization of Coalrelated Wastes(No.2015-10-B3)Scientific Instrument Center of Shanxi University(No.201512)。
文摘Cysteine(Cys)plays an important role in regulating cellular redox balance.But due to the constant changes in the concentration of Cys in organisms,fast response sensors are urgent required for practical application.In this work,a fluorescent probe with a fast response was developed by linking coumarin derivatives containingα,β-unsaturated ketones to NBD.The PET effect made the system non-fluorescent.When the probe reacted with Cys,the bond between the coumarin derivative and the NBD was cut off,meanwhile a rapid rearrangement and reactive site passivation occurred.Then two fluorophores with the same emission peak are released,among them,strong fluorescence signal of NBD dominated.Thus,although the similar reaction occurred for Hcy,the rate of NBD derivative rearrangement was slow,in a short time,fluorescence signal was still weak.As for GSH,cleavage could occur,but no rearrange within the NBD molecule due to GSH with large volume.Because of strong fluorescent emission,this probe was successfully used in biological imaging about cell and zebrafish.More importantly,the probe was successfully used to evaluate the oxidative stress caused by copper(Ⅱ)in living cells.This fluorescence strategy and application will provide a new way of studying intracellular oxidative stress processes and damage.
基金National Natural Science Foundation of China(Nos.21705102,21775096,22074084)the Basic Research Program of Shanxi Province(Free Exploration)(No.20210302123430)。
文摘Fluorescence image for accurate tumor label still faces challenges in cancer detection and diagnostics.Emerging evidence is indicating that glucose-regulated protein 78(GRP78), a stress-inducible protein chaperone, is a great potential biomarker and therapeutic target for cancer. However, currently available probe for image tumor based on GRP78 has not been reported, owning to no obvious strategy in probe design towards this protein. In this paper, a hairpin-shaped peptidyl probe(pep FAM) conjugated with a 5-FAM fluorophore and a dabcyl quencher at both ends was developed, respectively. The probe was designed by performing a traditional fluorescence resonance energy transfer mechanism and employing a GRP78 specifically-binding peptide. Furthermore, the probe was used to specifically image cancer cells,and accurately image xenograft tumors in mice models. The novel fluorescent probe is expected to be a useful tool for the diagnostics of cancer.
文摘Due to the biological importance of cysteine(Cys),the development of organic fluorescence probes for Cys has been a wide,potent,and outstanding research field in most recent years.It has been used as a biomarker in treating various diseases;therefore,developing a sensing mechanism for detecting Cys is very important.In this Review,we focus on and summarize the specific results of recent exciting literature regarding the sensing mechanism of Cys-specific fluorescence probes and their applications in Cys recognition.Moreover,a design strategy of the sensing mechanism of Cys can be classified into seven reaction mechanisms,including the aromatic substitution rearrangement reaction,cyclization of aldehyde,Michael addition reaction,Se-N or S-S or bond cleavage reaction,addition cyclization of acrylate,metal complex reaction,and nucleophilic substitution reaction.In all sections,discussions have corresponded to Cys-specific sensing mechanisms,which consist of emission,color changes,and detection limits and deal with the application and recognition sites of molecules.Future directions and challenges have been proposed for the preparation of Cys-specific probes.
基金This work was supported by the National Natural Science Foundation of China(21672131,21775096)One Hundred People Plan of Shanxi Province,Shanxi Province“1331 Project”Key Innovation Team Construction Plan Cultivation Team(2018-CT-1)+7 种基金2018 Xiangyuan County Solid Waste Comprehensive Utilization Science and Technology Project(2018XYSDJS-05)Shanxi Province Foundation for Returness(2017-026)Shanxi Collaborative Innovation Center of High Value-added Utilization of Coal-related Wastes(2015-10-B3)the Shanxi Province Foundation for Selected(No.2019)the Innovative Talents of Higher Education Institutions of Shanxi,Scientific and Technological Innovation Programs of Higher Education Institutions in Shanxi(2019L0031)the Key R&D Program of Shanxi Province(201903D421069)the Shanxi Province Science Foundation(201901D111015)China Institute for Radiation Production and Scientific Instrument Center of Shanxi University(201512).
文摘Multicolor fluorescent probes based on small organic molecules have the advantages of low cost, good biocompatibility, easily modifiable molecular structures and adjustable fluorescence performance. In addition, small molecule multicolor fluorescent probes generally undergo multi-site or multi-step reactions, which means that they can be used for the specific detection of structurally similar substances in complex bio-systems. In this review, we focus on the design and application of multicolor fluorescent probes based on small organic molecules: single fluorophores with multiple reaction sites, multiple fluorophores with single reaction sites, or multiple fluorophores with multiple reaction sites. Moreover, a design strategy for multicolor fluorescent probes and its application in biological imaging are also summarized, providing a systematic plan for future research on fluorescent probes functionalized by small organic molecules. It will also play an important role in the development of additional functions for small organic molecule fluorescent probes.
基金the National Natural Science Foundation of China(Grant Nos.21775096 and 21878180)One hundred people plan of Shanxi Province,Shanxi Province“1331 project”key innovation team construction plan cultivation team(No.2018-CT-1)+7 种基金2018 Xiangyuan County Solid Waste Comprehensive Utilization Science and Technology Project(No.2018XYSDJS-05)Key R&D Program of Shanxi Province(No.201903D421069)the Shanxi Province Science Foundation(No.201901D111015)Shanxi Collaborative Innovation Center of High Valueadded Utilization of Coal-related Wastes(No.2015-10-B3)the Shanxi Province Foundation for Selected Returnee(No.2019),Scientific and Technological Innovation Programs of Higher Education Institutions in Shanxi(No.2019L0031)Project of Graduate Innovation of Shanxi Province(No.2020)Key R&D and transformation plan of Qinghai Province(No.2020-GX-101)Scientific Instrument Center of Shanxi University(No.201512).
文摘Heterocyclic compound quinoline and its derivatives exist in natural compounds and have a broad spectrum of biological activity.They play an important role in the design of new structural entities for medical applications.Similarly,indoles and their derivatives are found widely in nature.Amino acids,alkaloids and auxin are all derivatives of indoles,as are dyes,and their condensation with aldehydes makes it easy to construct reaction sites for nucleophilic addition agents.In this work,we combine these two groups organically to construct a rapid response site(within 30 s)for H_(2)S,and at the same time,a ratiometric fluorescence response is presented throughout the process of H_(2)S detection.As such,the lower detection limit can reach 55.7 nmol/L for H_(2)S.In addition,cell imaging shows that this probe can be used for the mitochondrial targeted detection of endogenous and exogenous H_(2)S.Finally,this probe application was verified by imaging H_(2)S in nude mice.
基金This work was supported by the National Key Research and Development Program of China(Nos.2017YFA0104800),Nature Science Foundation of China(31771062,31971281,81901001),Key Research and Development Program of Sichuan Province(2017SZ0031).
文摘Successful regenerative medicine strategies of xenogeneic extracellular matrix need a synergistic balance among inflammation,fibrosis,and remodeling process.Adaptive macrophage subsets have been identified to modulate inflammation and orchestrate the repair of neighboring parenchymal tissues.This study fabricated PPARγ-primed CD68+CD206+M2 phenotype(M2γ),and firstly verified their anti-inflammatory and tissue-regenerating roles in xenogeneic bioengineered organ regeneration.Our results showed that Th1-type CD3^(+)CD8^(+)T cell response to xenogeneic-dentin matrix-based bioengineered root complex(xeno-complex)was significantly inhibited by M2γmacrophage in vitro.PPARγactivation also timely recruited CD68^(+)CD206^(+)tissue macrophage polarization to xeno-complex in vivo.These subsets alleviated proinflammatory cytokines(TNF-α,IFN-γ)at the inflammation site and decreased CD3^(+)CD8^(+)T lymphocytes in the periphery system.When translated to an orthotopic nonhuman primate model,PPARγ-primed M2 macrophages immunosuppressed IL-1β,IL-6,TNF-α,MMPs to enable xeno-complex to effectively escape immune-mediated rejection and initiate graft-host synergistic integrity.These collective activities promoted the differentiation of odontoblast-like and periodontal-like cells to guide pulp-dentin and cementum-PDLs-bone regeneration and rescued partially injured odontogenesis such as DSPP and periostin expression.Finally,the regenerated root showed structure-biomechanical and functional equivalency to the native tooth.The timely conversion of M1-to-M2 macrophage mainly orchestrated odontogenesis,fibrogenesis,and osteogenesis,which represents a potential modulator for intact parenchymal-stromal tissue regeneration of targeted organs.
基金supported by the National Natural Science Foundation of China(21705102,21775096,and 22074084)the Basic Research Program of Shanxi Province(Free Exploration,20210302123430).
文摘Altered metabolism has long been recognized as a central hallmark of cancer;however,in the fluorescence imaging field,few studies have been conducted to label tumors by exploiting metabolic differences between cancer cells and normal cells.In this work,we successfully developed a metabolic probe MB-C for specific imaging of glutathione(GSH)dynamic metabolic pathways.GSH was endogenously metabolized to produce SO_(2)via Na_(2)S_(2)O_(3) and thiosulfate sulfurtransferase,equilibrating with sulfites/bisulfites.MB-C was allowed to be activated by GSH along with multi-fluorescence emission increased in red and green channels and further sequence-response metabolites(SO_(2))of GSH in significant fluorescence ratio change of red and green channels.Furthermore,such evident fluorescence ratio changes could be used to distinguish cancer cells from normal cells and identify tumor and normal tissues.Therefore,GSH metabolic imaging was successfully applied to accurately label tumors,which provides a new idea and practical case for the precise visualization of malignant tumors.
