Fluorescent probes,with their superior optical properties and labeling versatility,have greatly advanced the visualization of intracellular molecules and subcellular structures.However,poor cytoplasmic delivery,caused...Fluorescent probes,with their superior optical properties and labeling versatility,have greatly advanced the visualization of intracellular molecules and subcellular structures.However,poor cytoplasmic delivery,caused by charge,size,or targeting groups,limits the effective use of many fluorescent probes in live cells.Recently,cell-penetrating peptides(CPPs)have emerged as efficient carriers,offering great potential for the cytoplasmic delivery of fluorescent probes in live cells.This review provides a comprehensive overview of CPPs as vehicles for probe delivery,outlining advances in their development,conjugation chemistries,and intracellular delivery mechanisms.Recent applications in live-cell imaging are highlighted and organized according to major CPP modification strategies,including sequence engineering,cyclization,hybrid design and enhancement by chemical reagents.Finally,the challenges that remain and the future outlook of this rapidly evolvingfield are discussed.展开更多
Natural products(NPs)are an important source of new drugs for the treatment of stroke.Identifying cellular targets for bioactive molecules is a major challenge and critical issue in the development of new drugs for st...Natural products(NPs)are an important source of new drugs for the treatment of stroke.Identifying cellular targets for bioactive molecules is a major challenge and critical issue in the development of new drugs for stroke.Small-molecule probes play a unique role in target discovery.However,drawbacks to these probes include non-specificity,unstable activity,and difficulty in synthesis.Small-molecule probes based on NPs at least partially compensate for these shortcomings.NPs feature rich chemical and structural diversity,biocompatibility,and unique biological activities.These features could be exploited to provide new ideas and tools for target discovery.Small-molecule probes based on NPs provide a precise and direct search for interacting protein targets of NPs-active small molecules.This review explores the properties of small-molecule probes based on NPs and their applications in mechanistic studies of stroke and other diseases.We hope that this review will bring new perspectives to the mechanistic study of NPs-active small molecules and accelerate the translation of these ingredients into drug candidates for the treatment of stroke.展开更多
The thoracic duct(TD),the largest lymphatic vessel in the human body,plays a critical role in returning lymph to the circulatory system.However,its dynamic,distensible nature and concealed anatomical location make int...The thoracic duct(TD),the largest lymphatic vessel in the human body,plays a critical role in returning lymph to the circulatory system.However,its dynamic,distensible nature and concealed anatomical location make intraoperative visualization critically challenging and increase the risk of injury.Real-time,high-resolution assessment of TD leaks remains an urgent clinical need.Here,we present a breakthrough molecular engineering strategy that leverages an intestinally lipophilic fluorescent formulation for dynamic in vivo TD imaging.Our rationally designed cyanine derivative IR790+,known for its rapid membrane permeability and endoplasmic reticulum(ER)targeting localization,demonstrates unprecedented chylomicron affinity,which subsequently transports the dye through the lymphatic system to the TD.Notably,dynamic,high-contrast intraoperative TD imaging is achieved from rat models to swine models.Administered orally as near-infrared(NIR)fluorescent contrast agent,this ultra-stable IR790+@oil formulation,engineered via flash nanoprecipitation,surpasses conventional counterparts by enabling non-invasive,real-time identification of TD.Intriguingly,this first-reported ER-targeting NIR formulation,delivered orally,represents a paradigm shift in fluorescence-guided surgery,significantly improving intraoperative accuracy.展开更多
The detection of amino acid enantiomers holds significant importance in biomedical,chemical,food,and other fields.Traditional chiral recognition methods using fluorescent probes primarily rely on fluorescence intensit...The detection of amino acid enantiomers holds significant importance in biomedical,chemical,food,and other fields.Traditional chiral recognition methods using fluorescent probes primarily rely on fluorescence intensity changes,which can compromise accuracy and repeatability.In this study,we report a novel fluorescent probe(R)-Z1 that achieves effective enantioselective recognition of chiral amino acids in water by altering emission wavelengths(>60 nm).This water-soluble probe(R)-Z1 exhibits cyan or yellow-green luminescence upon interaction with amino acid enantiomers,enabling reliable chiral detection of 14 natural amino acids.It also allows for the determination of enantiomeric excess through monitoring changes in luminescent color.Additionally,a logic operation with two inputs and three outputs was constructed based on these optical properties.Notably,amino acid enantiomers were successfully detected via dual-channel analysis at both the food and cellular levels.This study provides a new dynamic luminescence-based tool for the accurate sensing and detection of amino acid enantiomers.展开更多
Butyrylcholinesterase(BChE)is a pivotal enzyme that degrades the neurotransmitter acetylcholine,which is related to learning and memory,into choline and acetic acid.BChE activity is strongly associated with various di...Butyrylcholinesterase(BChE)is a pivotal enzyme that degrades the neurotransmitter acetylcholine,which is related to learning and memory,into choline and acetic acid.BChE activity is strongly associated with various diseases,including Alzheimer’s disease,multiple sclerosis,diabetes,and lipid metabolism disorders.It also possesses pharmacological properties for combating cocaine addiction and detoxifying organophosphate poisoning.Given the significant importance of BChE in the biological and medical fields,detecting its activity and understanding its expression in the body are crucial for advancing related research.Herein,a brief review of recently reported specific fluorescence or chemiluminescence probes for quantifying and real-time monitoring BChE is provided.By utilizing unique recognition groups,these probes achieve highly selective identification of BChE and effectively resist interference from other biological factors.Probes demonstrate excellent performance in measuring BChE activity,screening BChE inhibitors,and locating BChE in cells and mice.These also offer strong technical support for early diagnosis,precise intervention,and effective treatment of diseases with pathological changes in BChE.展开更多
1 If astronauts want to stay on the Moon for more than a few days,they must find local resources,and water is one of the most crucial ones.Scientists believe there's water on the Moon,but they're unsure of whe...1 If astronauts want to stay on the Moon for more than a few days,they must find local resources,and water is one of the most crucial ones.Scientists believe there's water on the Moon,but they're unsure of where it lies.2 Two probes are on their way to the Moon to solve this mystery.They will be launched on the same SpaceX Falcon 9 rocket from Cape Canaveral.If everything goes as planned,the first probe to reach the Moon will be Athena.Timothy Crain,the chief technology officer of Intuitive Machines,says it will take about 3 to 4 days,depending on the launch time.They'll orbit the Moon for 2 to 3 days to wait for the Sun to reach the landing site,because the lander's solar panels need sunlight to generate power.It only takes about 15 minutes to land softly after the engine is started.展开更多
Recent advances in drug development and bioactive molecules that covalently target lysine residues have shown substantial progress.Both reversible and irreversible covalent inhibitors are developed for targeting lysin...Recent advances in drug development and bioactive molecules that covalently target lysine residues have shown substantial progress.Both reversible and irreversible covalent inhibitors are developed for targeting lysine residues.The identification of protein targets and binding sites of these lysine-targeting molecules in the whole proteome is crucial to understand their proteome-wide selectivity.For covalent inhibitors,the pull down-based methods including activity-based protein profiling(ABPP)are commonly used to profile their target proteins.For covalent reversible inhibitors,it is not easy to pull down the potential protein targets as the captured proteins may get off beads because of the reversible manner.Here,we report a pair of isotope-labelled click-free probes to competitively identify the protein targets of lysine-targeting covalent reversible small molecules.This pair of isotopic probes consists of a lysinereactive warhead,a desthiobiotin moiety and isotopicable linker.This integrated probe could eliminate the background proteins induced by the click chemistry during the pull-down process.To demonstrate the feasibility of our newly-developed probes for the protein target identification,we selected the natural product Gossypol in that we proved for the first time that it could modify the lysine residue in a covalent reversible manner.Finally,we confirmed that this pair of integrated probes can be used in a competitive manner to precisely identify the protein target as well as binding sites of Gossypol.Interestingly,pretreatment of Gossypol could stop the antibody from recognizing Gossypol-binding proteins.Together,our isotope-labeled click-free probes could be used for whole-proteome profiling of lysine-targeting covalent reversible small molecules.展开更多
Fluorescent probes have revolutionized optical imaging and biosensing by enabling real-time visualization, quantification, and tracking of biological processes at molecular and cellular levels. These probes, ranging f...Fluorescent probes have revolutionized optical imaging and biosensing by enabling real-time visualization, quantification, and tracking of biological processes at molecular and cellular levels. These probes, ranging from organic dyes to genetically encoded proteins and nanomaterials, provide unparalleled specificity, sensitivity, and multiplexing capabilities. However, challenges such as brightness, photobleaching, biocompatibility, and emission range continue to drive innovation in probe design and application. This special issue, comprising four review papers and seven original research studies, highlights cutting-edge advancements in fluorescent probe technologies and their transformative roles in super-resolution imaging, in vivo diagnostics, and cancer therapeutics.展开更多
The intricate pathological mechanisms of ischemia-reperfusion injury(IRI)are intimately associated with the imbalance of metabolic substance supply and demand.Investigation of the fluctuated molecules reveals the prog...The intricate pathological mechanisms of ischemia-reperfusion injury(IRI)are intimately associated with the imbalance of metabolic substance supply and demand.Investigation of the fluctuated molecules reveals the progression of reperfusion injury,facilitating earlier diagnosis and treatments.Fluorescence imaging is a powerful technique in fluorescent optical diagnosis,essential for detecting biomarker levels both in vitro and in vivo.By integrating multifunctional scaffolds with specific recognition groups,smallmolecule fluorescent probes(SMFPs)effectively monitor biomarkers related to IRI,providing valuable insights into pathological mechanisms and enhancing early diagnostic capabilities.This review systemically summarizes the recent developments of SMFPs,focusing on design strategies and their applications in the main types of IRI.Furthermore,we discuss the challenges and propose prospects based on existing SMFP applications in this area.We aim to provide a comprehensive analysis of SMFPs for disease diagnosis and inspire researchers to further innovate and develop effective tools for clinical applications.展开更多
The cell membrane,a fluid interface composed of self-assembled phospholipid molecules,is a vital component of biological systems that maintains cellular stability and prevents the invasion of foreign toxins.Due to its...The cell membrane,a fluid interface composed of self-assembled phospholipid molecules,is a vital component of biological systems that maintains cellular stability and prevents the invasion of foreign toxins.Due to its inherent fluidity,the cell membrane can undergo bending,shearing,and stretching,making membrane deformation crucial in processes like cell adhesion,migration,phagocytosis,and signal transduction.Within the plasma membrane are highly ordered dynamic structures formed by lipid molecules,known as“lipid rafts,”whose dynamic dissociation and reorganization are prerequisites for membrane deformation.Fluorescent probes have emerged as vital tools for studying these dynamic processes,offering a non-destructive,in situ,and real-time imaging method.By strategically designing these probes,researchers can image not only the microdomains of cell membranes but also explore more complex processes such as membrane fusion and fission.This review systematically summarizes the latest advancements in the application of fluorescent probes for cell membrane imaging.It also discusses the current challenges and provides insights into future research directions.We hope this review inspires further studies on the dynamic processes of complex cell membranes using fluorescent probes,ultimately advancing our understanding of the mechanisms underlying membrane dissociation,reorganization,fusion,and separation,and fostering research and therapeutic development for membrane-associated diseases.展开更多
In space probes,anomaly detection of sequence data collected by various sensors is essential to help detect potential faults promptly,improve the reliability of equipment operation,and ensure the smooth operation of t...In space probes,anomaly detection of sequence data collected by various sensors is essential to help detect potential faults promptly,improve the reliability of equipment operation,and ensure the smooth operation of the mission.However,sensors'signals often contain a superposition of various frequencies,changing fluctuations,and correlations between features.This complexity of data attributes makes building effective models challenging.This paper proposes a TimeEvolving Multi-Period Observational(TEMPO)anomaly detection method for space probes.First,fusing wavelet analysis and natural periods improves the ability to capture multi-period features in data.Then,the feature extraction framework proposed enhances the effectiveness of anomaly detection by comprehensively extracting the complex features of data through the multi-module synergy of temporal and channel.The results demonstrate that the proposed method enhances anomaly detection accuracy and its effectiveness is confirmed.Additionally,the ablation experiment results further validate the efficacy of each module.An evaluation of the algorithm's computational complexity confirms its suitability for real-time processing.展开更多
Fluorescent probes have wide applications in biological and environmental analysis due to their advantages of simple operation, convenient flexibility, high sensitivity and efficiency. They are considered to be promis...Fluorescent probes have wide applications in biological and environmental analysis due to their advantages of simple operation, convenient flexibility, high sensitivity and efficiency. They are considered to be promising tools for accurate analysis of agriculture- and food-related hazardous substances. In this review, the types and characteristics of the near-infrared fluorescence probes (NIFPs) are briefly described. The recent advances of NIFPs for precisely detecting various hazardous substances including heavy metals, sulfite and related sulfiting agents and hydrogen peroxide are summarized. Finally, the present challenges and future perspectives faced by NIFPs in food safety analysis are discussed.展开更多
Prodrugs need to be converted to active drugs to exert their pharmacological activities.Identifying the direct targets of active drugs is essential to elucidate the pharmacological mechanisms of prodrugs,but remains c...Prodrugs need to be converted to active drugs to exert their pharmacological activities.Identifying the direct targets of active drugs is essential to elucidate the pharmacological mechanisms of prodrugs,but remains challenging,especially for active drugs with low stability.展开更多
Amphiphiles,including surfactants,have emerged as indispensable elements in materials science and pharmaceutical science,and their functions are highly relying on the critical micelle concentration(CMC)[1,2].Numerous ...Amphiphiles,including surfactants,have emerged as indispensable elements in materials science and pharmaceutical science,and their functions are highly relying on the critical micelle concentration(CMC)[1,2].Numerous fluorimetry-based probes have been developed to measure CMCs[3](Fig.S1).However,CMC measurements using these probes suffer from a time-consuming and laborious procedure and large uncertainties,primarily due to their poor photo-stabilities and highly fluctuating fluorescence backgrounds.展开更多
The overuse of surfactants has made them well-known environmental pollutants.So far,it is still a challenge to simultaneously distinguish cationic,anionic,zwitterionic,nonionic surfactants and surfactants with similar...The overuse of surfactants has made them well-known environmental pollutants.So far,it is still a challenge to simultaneously distinguish cationic,anionic,zwitterionic,nonionic surfactants and surfactants with similar structures based on traditional analytical techniques.We developed a high-throughput method for distinguishing various surfactants based on the adaptive emission profile as fingerprints(AEPF).The fluorescence response of the sensor was based on the interaction between surfactants and 1,3-diacetylpyrene(o-DAP)probe.The interaction affected the reversible conversion of free molecules and two aggregates in the solution,thereby changing the relative abundance and the fluorescence intensity ratio of two aggregates emitting different fluorescence.The o-DAP sensor can distinguish four types of surfactants(16 surfactants),especially surfactants of the same type with similar structures.The o-DAP sensor sensitively determined the critical micelle concentration(CMC)of 16 surfactants based on the interaction between o-DAP and surfactants.Additionally,the o-DAP sensor can detect and distinguish artificial vesicles made from different surfactants.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
Liver cancer, specifically hepatocellular carcinoma (HCC), is a malignant neoplasm of the digestive system, characterized by exceptionally high morbidity and mortality rates on a global scale. Early detection and diag...Liver cancer, specifically hepatocellular carcinoma (HCC), is a malignant neoplasm of the digestive system, characterized by exceptionally high morbidity and mortality rates on a global scale. Early detection and diagnosis are critical measures for enhancing the prognosis of patients diagnosed with HCC. An improved prognosis is significantly reliant on the timely diagnosis of the disease and effective therapeutic monitoring. Activatable fluorescent probes are essential for detecting and imaging biomarkers related to disease diagnosis and in vivo imaging. This paper reviews the fluorescent probes developed over the past five years for the detection and imaging of HCC. This noninvasive optical imaging modality demonstrates significant promise in targeting pathological sites and is anticipated to facilitate potential clinical translation.展开更多
To understand the gene-based biological processes in-depth,the single-molecule real-time sequencing has drawn increasing attention with promoted by the Human Genome Project.Herein,a set of newly designed canonical flu...To understand the gene-based biological processes in-depth,the single-molecule real-time sequencing has drawn increasing attention with promoted by the Human Genome Project.Herein,a set of newly designed canonical fluorescent bases(A_(y),tC,G_(b),T_(p))are proposed for four-color DNA sequencing.These quasi-intrinsic probes are derived from the fluorophore replacement and ring expansion on natural bases,which still keep the pyrimidine or purine underlying skeleton and Watson–Crick hydrogen bonding face to allow minimal perturbation to the native DNA duplex.More importantly,these nucleobase analogues possess red-shifted absorption and efficient photoluminescence due to the enhancedπ-conjugation in character.Meanwhile,the four analogues could generate distinct emission wavelength(Δλ~50 nm)for real-time sequencing.To assess the biological employment of the proposed biosensors,the effects of base pairing and linking deoxyribose are also considered.展开更多
Monoamine oxidases(MAOs)are a class of flavin enzymes that are mainly present in the outer membrane of mitochondria and play a crucial role in maintaining the homeostasis of monoamine neurotransmitters in the central ...Monoamine oxidases(MAOs)are a class of flavin enzymes that are mainly present in the outer membrane of mitochondria and play a crucial role in maintaining the homeostasis of monoamine neurotransmitters in the central nervous system.Furthermore,expression of MAOs is associated with the functions of peripheral organs.Dysfunction of MAOs is relevant in a variety of diseases such as neurodegenerative diseases,heart failure,metabolic disor-ders,and cancers.Monoamine oxidases have two isoenzymes,namely,monoamine oxidase A(MAO-A)and monoamine oxidase B(MAO-B).Therefore,the development of reliable and specific methods to detect these two isoenzymes is of great significance for the in-depth understanding of their functions in biological systems,and for further promoting the clinical diag-nosis and treatment of MAO-related diseases.This review mainly focuses on the advances in small molecular probes for the specific imaging of MAO-A and MAO-B,including radiolabeled probes,fluorescent probes,and a 19F magnetic resonance imaging probe.In addition,applications of these probes for detecting MAO expression levels in cells,tissues,animal models,and patients are described.Finally,the challenges and perspectives of developing novel MAO imaging probes are also highlighted.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
基金supported by the following grants:National Natural Science Foundation of China(Grant Nos.92354305 and 32271428),National Key R&D Program of China(Grant No.2022YFC3401100)Young Talent Program of Hubei Provincial Health Commission(WJ2025Q037)+1 种基金Interdisciplinary Research Program of HUST(Grant No.2023JCY5045)Director Fund of WNLO.
文摘Fluorescent probes,with their superior optical properties and labeling versatility,have greatly advanced the visualization of intracellular molecules and subcellular structures.However,poor cytoplasmic delivery,caused by charge,size,or targeting groups,limits the effective use of many fluorescent probes in live cells.Recently,cell-penetrating peptides(CPPs)have emerged as efficient carriers,offering great potential for the cytoplasmic delivery of fluorescent probes in live cells.This review provides a comprehensive overview of CPPs as vehicles for probe delivery,outlining advances in their development,conjugation chemistries,and intracellular delivery mechanisms.Recent applications in live-cell imaging are highlighted and organized according to major CPP modification strategies,including sequence engineering,cyclization,hybrid design and enhancement by chemical reagents.Finally,the challenges that remain and the future outlook of this rapidly evolvingfield are discussed.
基金supported by the Tianjin Science and Technology Plan Project(Project No.:23ZYJDSS00020)the National Natural Science Foundation of China(Grant No.:82004331)the Key Research and Development Program of HuBei Province of China(Program No.:2022ACA003-02-002).
文摘Natural products(NPs)are an important source of new drugs for the treatment of stroke.Identifying cellular targets for bioactive molecules is a major challenge and critical issue in the development of new drugs for stroke.Small-molecule probes play a unique role in target discovery.However,drawbacks to these probes include non-specificity,unstable activity,and difficulty in synthesis.Small-molecule probes based on NPs at least partially compensate for these shortcomings.NPs feature rich chemical and structural diversity,biocompatibility,and unique biological activities.These features could be exploited to provide new ideas and tools for target discovery.Small-molecule probes based on NPs provide a precise and direct search for interacting protein targets of NPs-active small molecules.This review explores the properties of small-molecule probes based on NPs and their applications in mechanistic studies of stroke and other diseases.We hope that this review will bring new perspectives to the mechanistic study of NPs-active small molecules and accelerate the translation of these ingredients into drug candidates for the treatment of stroke.
基金supported by the National Natural Science Foundation of China(22225805,81400681,32394001,32121005)the Shanghai Science and Technology Innovation Action Plan(22Y11907200,23J21901600)the Innovation Program of Shanghai Municipal Education Commission,Shanghai Municipal Health Commission(2024ZZ2025)。
文摘The thoracic duct(TD),the largest lymphatic vessel in the human body,plays a critical role in returning lymph to the circulatory system.However,its dynamic,distensible nature and concealed anatomical location make intraoperative visualization critically challenging and increase the risk of injury.Real-time,high-resolution assessment of TD leaks remains an urgent clinical need.Here,we present a breakthrough molecular engineering strategy that leverages an intestinally lipophilic fluorescent formulation for dynamic in vivo TD imaging.Our rationally designed cyanine derivative IR790+,known for its rapid membrane permeability and endoplasmic reticulum(ER)targeting localization,demonstrates unprecedented chylomicron affinity,which subsequently transports the dye through the lymphatic system to the TD.Notably,dynamic,high-contrast intraoperative TD imaging is achieved from rat models to swine models.Administered orally as near-infrared(NIR)fluorescent contrast agent,this ultra-stable IR790+@oil formulation,engineered via flash nanoprecipitation,surpasses conventional counterparts by enabling non-invasive,real-time identification of TD.Intriguingly,this first-reported ER-targeting NIR formulation,delivered orally,represents a paradigm shift in fluorescence-guided surgery,significantly improving intraoperative accuracy.
基金the financial support from the National Natural Science Foundation of China(Nos.22377097,22307036,22074114)Natural Science Foundation of Hubei Province of China(Nos.2020CFB623,2021CFB556)Engineering Research Center of Phosphorus Resources Development and Utilization of Ministry of Education(No.LCX202305)。
文摘The detection of amino acid enantiomers holds significant importance in biomedical,chemical,food,and other fields.Traditional chiral recognition methods using fluorescent probes primarily rely on fluorescence intensity changes,which can compromise accuracy and repeatability.In this study,we report a novel fluorescent probe(R)-Z1 that achieves effective enantioselective recognition of chiral amino acids in water by altering emission wavelengths(>60 nm).This water-soluble probe(R)-Z1 exhibits cyan or yellow-green luminescence upon interaction with amino acid enantiomers,enabling reliable chiral detection of 14 natural amino acids.It also allows for the determination of enantiomeric excess through monitoring changes in luminescent color.Additionally,a logic operation with two inputs and three outputs was constructed based on these optical properties.Notably,amino acid enantiomers were successfully detected via dual-channel analysis at both the food and cellular levels.This study provides a new dynamic luminescence-based tool for the accurate sensing and detection of amino acid enantiomers.
基金financial support from the National Natural Science Foundation of China(Nos.82173652 and 81872728)the Natural Science Foundation of Jiangsu Province(No.BK20221522)+1 种基金Support from Jiangsu“333 High Level Talents Cultivation”Leading Talents(No.2022-3-16-203)the Qing Lan Project is also appreciated.
文摘Butyrylcholinesterase(BChE)is a pivotal enzyme that degrades the neurotransmitter acetylcholine,which is related to learning and memory,into choline and acetic acid.BChE activity is strongly associated with various diseases,including Alzheimer’s disease,multiple sclerosis,diabetes,and lipid metabolism disorders.It also possesses pharmacological properties for combating cocaine addiction and detoxifying organophosphate poisoning.Given the significant importance of BChE in the biological and medical fields,detecting its activity and understanding its expression in the body are crucial for advancing related research.Herein,a brief review of recently reported specific fluorescence or chemiluminescence probes for quantifying and real-time monitoring BChE is provided.By utilizing unique recognition groups,these probes achieve highly selective identification of BChE and effectively resist interference from other biological factors.Probes demonstrate excellent performance in measuring BChE activity,screening BChE inhibitors,and locating BChE in cells and mice.These also offer strong technical support for early diagnosis,precise intervention,and effective treatment of diseases with pathological changes in BChE.
文摘1 If astronauts want to stay on the Moon for more than a few days,they must find local resources,and water is one of the most crucial ones.Scientists believe there's water on the Moon,but they're unsure of where it lies.2 Two probes are on their way to the Moon to solve this mystery.They will be launched on the same SpaceX Falcon 9 rocket from Cape Canaveral.If everything goes as planned,the first probe to reach the Moon will be Athena.Timothy Crain,the chief technology officer of Intuitive Machines,says it will take about 3 to 4 days,depending on the launch time.They'll orbit the Moon for 2 to 3 days to wait for the Sun to reach the landing site,because the lander's solar panels need sunlight to generate power.It only takes about 15 minutes to land softly after the engine is started.
基金supported by funding from The National Natural Science Foundation of China(No.22177136)the CAMS Innovation Fund for Medical Sciences(CIFMS)(No.2022-I2M-2-002).
文摘Recent advances in drug development and bioactive molecules that covalently target lysine residues have shown substantial progress.Both reversible and irreversible covalent inhibitors are developed for targeting lysine residues.The identification of protein targets and binding sites of these lysine-targeting molecules in the whole proteome is crucial to understand their proteome-wide selectivity.For covalent inhibitors,the pull down-based methods including activity-based protein profiling(ABPP)are commonly used to profile their target proteins.For covalent reversible inhibitors,it is not easy to pull down the potential protein targets as the captured proteins may get off beads because of the reversible manner.Here,we report a pair of isotope-labelled click-free probes to competitively identify the protein targets of lysine-targeting covalent reversible small molecules.This pair of isotopic probes consists of a lysinereactive warhead,a desthiobiotin moiety and isotopicable linker.This integrated probe could eliminate the background proteins induced by the click chemistry during the pull-down process.To demonstrate the feasibility of our newly-developed probes for the protein target identification,we selected the natural product Gossypol in that we proved for the first time that it could modify the lysine residue in a covalent reversible manner.Finally,we confirmed that this pair of integrated probes can be used in a competitive manner to precisely identify the protein target as well as binding sites of Gossypol.Interestingly,pretreatment of Gossypol could stop the antibody from recognizing Gossypol-binding proteins.Together,our isotope-labeled click-free probes could be used for whole-proteome profiling of lysine-targeting covalent reversible small molecules.
文摘Fluorescent probes have revolutionized optical imaging and biosensing by enabling real-time visualization, quantification, and tracking of biological processes at molecular and cellular levels. These probes, ranging from organic dyes to genetically encoded proteins and nanomaterials, provide unparalleled specificity, sensitivity, and multiplexing capabilities. However, challenges such as brightness, photobleaching, biocompatibility, and emission range continue to drive innovation in probe design and application. This special issue, comprising four review papers and seven original research studies, highlights cutting-edge advancements in fluorescent probe technologies and their transformative roles in super-resolution imaging, in vivo diagnostics, and cancer therapeutics.
基金financially supported by the National Natural Science Foundation of China(Nos.62288102 and 62475216)Natural Science Foundation of Shaanxi Province(No.2022JM-130)+7 种基金Key Research and Development Program of Shaanxi(No.2024GHZDXM-37)Innovation Capability Support Program of Shaanxi(No.2023-CX-PT-23)Natural Science Basic Research Program of Shaanxi(No.2024JC-YBQN-0919)Fujian Provincial Natural Science Foundation of China(No.2024J01060)National High Level Hospital Clinical Research Funding(No.2023-NHLHCRF-YSPY-01)the Postdoctoral Fellowship Program of CPSF(No.GZC20240889)Innovation Foundation for Doctor Dissertation of Northwestern Polytechnical University(No.CX2023098)Fundamental Research Funds for the Central Universities。
文摘The intricate pathological mechanisms of ischemia-reperfusion injury(IRI)are intimately associated with the imbalance of metabolic substance supply and demand.Investigation of the fluctuated molecules reveals the progression of reperfusion injury,facilitating earlier diagnosis and treatments.Fluorescence imaging is a powerful technique in fluorescent optical diagnosis,essential for detecting biomarker levels both in vitro and in vivo.By integrating multifunctional scaffolds with specific recognition groups,smallmolecule fluorescent probes(SMFPs)effectively monitor biomarkers related to IRI,providing valuable insights into pathological mechanisms and enhancing early diagnostic capabilities.This review systemically summarizes the recent developments of SMFPs,focusing on design strategies and their applications in the main types of IRI.Furthermore,we discuss the challenges and propose prospects based on existing SMFP applications in this area.We aim to provide a comprehensive analysis of SMFPs for disease diagnosis and inspire researchers to further innovate and develop effective tools for clinical applications.
基金supported by the National Nature Science Foundation of China(22107028)State Key Laboratory of Fine Chemicals,Dalian University of Technology(KF2307)+4 种基金Central Guidance Fund for Local Science and Technology Development Project(2024FRD05069)Natural Science Foundation of Chongqing(CSTB2023NSCQ-MSX0335)ML.wishes to thank the support of the National Natural Science Foundation of China(22308220)Shenzhen Uni-versity Third-Phase Project of Constructing High-Level University(000001032104)the Research Team Culti-vation Program of Shenzhen University(2023QNT005).
文摘The cell membrane,a fluid interface composed of self-assembled phospholipid molecules,is a vital component of biological systems that maintains cellular stability and prevents the invasion of foreign toxins.Due to its inherent fluidity,the cell membrane can undergo bending,shearing,and stretching,making membrane deformation crucial in processes like cell adhesion,migration,phagocytosis,and signal transduction.Within the plasma membrane are highly ordered dynamic structures formed by lipid molecules,known as“lipid rafts,”whose dynamic dissociation and reorganization are prerequisites for membrane deformation.Fluorescent probes have emerged as vital tools for studying these dynamic processes,offering a non-destructive,in situ,and real-time imaging method.By strategically designing these probes,researchers can image not only the microdomains of cell membranes but also explore more complex processes such as membrane fusion and fission.This review systematically summarizes the latest advancements in the application of fluorescent probes for cell membrane imaging.It also discusses the current challenges and provides insights into future research directions.We hope this review inspires further studies on the dynamic processes of complex cell membranes using fluorescent probes,ultimately advancing our understanding of the mechanisms underlying membrane dissociation,reorganization,fusion,and separation,and fostering research and therapeutic development for membrane-associated diseases.
基金supported by the National Natural Science Foundation of China(Nos.92467108,62141604,62032016,92467206)Beijing Nova Program,China No.(20220484106,20230484451)。
文摘In space probes,anomaly detection of sequence data collected by various sensors is essential to help detect potential faults promptly,improve the reliability of equipment operation,and ensure the smooth operation of the mission.However,sensors'signals often contain a superposition of various frequencies,changing fluctuations,and correlations between features.This complexity of data attributes makes building effective models challenging.This paper proposes a TimeEvolving Multi-Period Observational(TEMPO)anomaly detection method for space probes.First,fusing wavelet analysis and natural periods improves the ability to capture multi-period features in data.Then,the feature extraction framework proposed enhances the effectiveness of anomaly detection by comprehensively extracting the complex features of data through the multi-module synergy of temporal and channel.The results demonstrate that the proposed method enhances anomaly detection accuracy and its effectiveness is confirmed.Additionally,the ablation experiment results further validate the efficacy of each module.An evaluation of the algorithm's computational complexity confirms its suitability for real-time processing.
基金supported by the National Natural Science Foundation of China (Nos. 81925019, 81801817 and U22A20333)the National Key Research and Development Program of China (Nos. 2023YFB3810000 and 2023YFB3810003)+1 种基金the Fundamental Research Funds for the Central Universities and the Fujian Basic Research Foundation (Nos. 2022J011403, 2023XAKJ0101009, B2302014 and 2020Y4003)the Program for New Century Excellent Talents in University, China (No. NCET-13-0502).
文摘Fluorescent probes have wide applications in biological and environmental analysis due to their advantages of simple operation, convenient flexibility, high sensitivity and efficiency. They are considered to be promising tools for accurate analysis of agriculture- and food-related hazardous substances. In this review, the types and characteristics of the near-infrared fluorescence probes (NIFPs) are briefly described. The recent advances of NIFPs for precisely detecting various hazardous substances including heavy metals, sulfite and related sulfiting agents and hydrogen peroxide are summarized. Finally, the present challenges and future perspectives faced by NIFPs in food safety analysis are discussed.
基金support from the National Natural Science Foundation of China(Grant Nos.:U21A20407 and 81973467).
文摘Prodrugs need to be converted to active drugs to exert their pharmacological activities.Identifying the direct targets of active drugs is essential to elucidate the pharmacological mechanisms of prodrugs,but remains challenging,especially for active drugs with low stability.
基金supported by Shanghai Municipal Commission of Science and Technology,China(Grant No.:19XD1400300)the National Natural Science Foundation of China(Grant Nos.:821040821,82273867,and 82030107).
文摘Amphiphiles,including surfactants,have emerged as indispensable elements in materials science and pharmaceutical science,and their functions are highly relying on the critical micelle concentration(CMC)[1,2].Numerous fluorimetry-based probes have been developed to measure CMCs[3](Fig.S1).However,CMC measurements using these probes suffer from a time-consuming and laborious procedure and large uncertainties,primarily due to their poor photo-stabilities and highly fluctuating fluorescence backgrounds.
基金supported by the National Natural Science Foundation of China(Nos.22225806,22078314,22278394,22378385)Dalian Institute of Chemical Physics(Nos.DICPI202142,DICPI202436).
文摘The overuse of surfactants has made them well-known environmental pollutants.So far,it is still a challenge to simultaneously distinguish cationic,anionic,zwitterionic,nonionic surfactants and surfactants with similar structures based on traditional analytical techniques.We developed a high-throughput method for distinguishing various surfactants based on the adaptive emission profile as fingerprints(AEPF).The fluorescence response of the sensor was based on the interaction between surfactants and 1,3-diacetylpyrene(o-DAP)probe.The interaction affected the reversible conversion of free molecules and two aggregates in the solution,thereby changing the relative abundance and the fluorescence intensity ratio of two aggregates emitting different fluorescence.The o-DAP sensor can distinguish four types of surfactants(16 surfactants),especially surfactants of the same type with similar structures.The o-DAP sensor sensitively determined the critical micelle concentration(CMC)of 16 surfactants based on the interaction between o-DAP and surfactants.Additionally,the o-DAP sensor can detect and distinguish artificial vesicles made from different surfactants.
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supported by the National Natural Science Foundation of China (Grant Nos. 82202296, 82302277, and 32271520)Natural Science Foundation of Hunan Province (Grant Nos. 2022JJ30756, 2023JJ40087, and 2022RC1232)the Scientific Research Fund of Hunan Provincial Education Department (Grant No. 22B0896).
文摘Liver cancer, specifically hepatocellular carcinoma (HCC), is a malignant neoplasm of the digestive system, characterized by exceptionally high morbidity and mortality rates on a global scale. Early detection and diagnosis are critical measures for enhancing the prognosis of patients diagnosed with HCC. An improved prognosis is significantly reliant on the timely diagnosis of the disease and effective therapeutic monitoring. Activatable fluorescent probes are essential for detecting and imaging biomarkers related to disease diagnosis and in vivo imaging. This paper reviews the fluorescent probes developed over the past five years for the detection and imaging of HCC. This noninvasive optical imaging modality demonstrates significant promise in targeting pathological sites and is anticipated to facilitate potential clinical translation.
基金Project supported by the National Natural Science Foundation of China(Grant Nos.11804195,11847224,11674198,and 12274265)the Natural Science Foundation of Shandong Province,China(Grant Nos.ZR2018BA034 and ZR2022MA006)。
文摘To understand the gene-based biological processes in-depth,the single-molecule real-time sequencing has drawn increasing attention with promoted by the Human Genome Project.Herein,a set of newly designed canonical fluorescent bases(A_(y),tC,G_(b),T_(p))are proposed for four-color DNA sequencing.These quasi-intrinsic probes are derived from the fluorophore replacement and ring expansion on natural bases,which still keep the pyrimidine or purine underlying skeleton and Watson–Crick hydrogen bonding face to allow minimal perturbation to the native DNA duplex.More importantly,these nucleobase analogues possess red-shifted absorption and efficient photoluminescence due to the enhancedπ-conjugation in character.Meanwhile,the four analogues could generate distinct emission wavelength(Δλ~50 nm)for real-time sequencing.To assess the biological employment of the proposed biosensors,the effects of base pairing and linking deoxyribose are also considered.
基金Natural Science Foundation of Jiangsu Province,Grant/Award Number:BK20210062National Natural Science Foundation of China,Grant/Award Number:82172054Project of Key Laboratory of Organic Synthesis of Jiangsu Province,College of Chemistry,Chemical Engineering and Materials Science,Soochow University,Grant/Award Number:KJS2326。
文摘Monoamine oxidases(MAOs)are a class of flavin enzymes that are mainly present in the outer membrane of mitochondria and play a crucial role in maintaining the homeostasis of monoamine neurotransmitters in the central nervous system.Furthermore,expression of MAOs is associated with the functions of peripheral organs.Dysfunction of MAOs is relevant in a variety of diseases such as neurodegenerative diseases,heart failure,metabolic disor-ders,and cancers.Monoamine oxidases have two isoenzymes,namely,monoamine oxidase A(MAO-A)and monoamine oxidase B(MAO-B).Therefore,the development of reliable and specific methods to detect these two isoenzymes is of great significance for the in-depth understanding of their functions in biological systems,and for further promoting the clinical diag-nosis and treatment of MAO-related diseases.This review mainly focuses on the advances in small molecular probes for the specific imaging of MAO-A and MAO-B,including radiolabeled probes,fluorescent probes,and a 19F magnetic resonance imaging probe.In addition,applications of these probes for detecting MAO expression levels in cells,tissues,animal models,and patients are described.Finally,the challenges and perspectives of developing novel MAO imaging probes are also highlighted.
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.
