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 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
Histone H3K79 modifications are essential to regulate chromatin structure and gene transcription,but understanding of the molecular mechanisms is limited.Because H3K79 is at globular domain,short histone peptide canno...Histone H3K79 modifications are essential to regulate chromatin structure and gene transcription,but understanding of the molecular mechanisms is limited.Because H3K79 is at globular domain,short histone peptide cannot mimic H3K79 in chromatin.Instead,reconstituted nucleosome-based chemical tools are ideally used to investigate H3K79 modifications.In consequence,H3K79-modified histone H3 with additional chemical handles are required,but such synthesis is challenging and laborious.Here we report a facile semisynthesis method that enables multifunctional histone H3 readily available.H3K79-containing fragment is short for straight peptide synthesis that was later ligated to recombinant expressed H3 fragments for full-length product in large scale.As a result,nucleosomes with H3K79 modifications as well as photo-reactive group and affinity tag were obtained to investigate potential binding proteins.We believe this method that enhances synthetic accessibility of nucleosome probes will accelerate understanding of the underexplored H3K79 modifications.展开更多
Humanβ-galactosidase(β-gal)is recognized as a crucial biomarker for evaluating senescence at the cellular and tissue levels in humans.However,tools to precisely track the endogenousβ-gal are still limited.Herein,we...Humanβ-galactosidase(β-gal)is recognized as a crucial biomarker for evaluating senescence at the cellular and tissue levels in humans.However,tools to precisely track the endogenousβ-gal are still limited.Herein,we present two novel self-calibratingβ-gal probes 7a and 7b which were constructed on a unique green/red dual-emissive fluorescence platform.The two probes inherently exhibited a stable green fluorescence signal impervious toβ-gal activity,serving as a reliable internal reference.They also displayed a progressively diminishing red fluorescence signal with the increasing ofβ-gal expression levels.The dual behavior endows them with self-calibration capacity and then renders excellently selective and sensitive for precisely monitoringβ-gal activity.Notably,compared with E.coliβ-gal,the two probes are more effectively response to A.oryzaeβ-gal homologous to humanβ-gal,indicating their unique species-selectivity.Furthermore,7a was validated for its effectiveness in determining senescenceassociatedβ-galactosidase(SA-β-gal)expression in senescent NRK-52E and HepG2 cells,underscoring its practical applicability in senescence research.展开更多
Implanted neural probes can detect weak discharges of neurons in the brain by piercing soft brain tissue,thus as important tools for brain science research,as well as diagnosis and treatment of brain diseases.However,...Implanted neural probes can detect weak discharges of neurons in the brain by piercing soft brain tissue,thus as important tools for brain science research,as well as diagnosis and treatment of brain diseases.However,the rigid neural probes,such as Utah arrays,Michigan probes,and metal microfilament electrodes,are mechanically unmatched with brain tissue and are prone to rejection and glial scarring after implantation,which leads to a significant degradation in the signal quality with the implantation time.In recent years,flexible neural electrodes are rapidly developed with less damage to biological tissues,excellent biocompatibility,and mechanical compliance to alleviate scarring.Among them,the mechanical modeling is important for the optimization of the structure and the implantation process.In this review,the theoretical calculation of the flexible neural probes is firstly summarized with the processes of buckling,insertion,and relative interaction with soft brain tissue for flexible probes from outside to inside.Then,the corresponding mechanical simulation methods are organized considering multiple impact factors to realize minimally invasive implantation.Finally,the technical difficulties and future trends of mechanical modeling are discussed for the next-generation flexible neural probes,which is critical to realize low-invasiveness and long-term coexistence in vivo.展开更多
Organelles are specialized areas where cells perform specific processes necessary for life and actively communicate with each other to keep the whole cell func-tioning.Disorders of the organelle networks are associate...Organelles are specialized areas where cells perform specific processes necessary for life and actively communicate with each other to keep the whole cell func-tioning.Disorders of the organelle networks are associated with multiple patho-logical processes.However,clearly and intuitively visualizing the highly dynamic interactions between ultrafine organelles is challenging.Fluorescence imaging technology provides opportunities due to the distinct advantages of facile,non-invasiveness and dynamic detection,making it particularly well-suited for appli-cations in uncovering the mysterious veil of organelle interactions.Regrettably,the lack of ideal fluorescence agents has always been an obstacle in imaging the intricate behaviors of organelles.In this review,we provide a systematic discussion on the existing dual-color and dual-targetable molecular sensors used in moni-toring organelle interactions,with a specific focus on their targeting strategies,imaging mechanisms and biological applications.Additionally,the current limi-tations and future development directions of dual-targetable probes and dual-emissives are briefly discussed.This review aims to provide guidance for re-searchers to develop more improved probes for studying organelle interactions in the biomedical field.展开更多
In situ precise detection of bioactive molecules with high sensitivity and spatiotemporal resolution is essential for studying physiological events and disease diagnosis.The utilization of versatile fluorescent probes...In situ precise detection of bioactive molecules with high sensitivity and spatiotemporal resolution is essential for studying physiological events and disease diagnosis.The utilization of versatile fluorescent probes in fluorescence imaging offers a powerful tool for in vivo imaging of biomarkers closely associated with pathological conditions.However,the dynamic behavior leading to rapid clearance of small molecule probes from regions of interest severely compromises their potential for precise imaging.Notably,self-immobilizing fluorescent probes that selectively recognize diseased tissues while improving in situ retention and enrichment enable accurate high-fidelity fluorescence imaging.In this review,we aim to summarize the strategies employed for recent advances in the performance and precision of in vivo fluorescence imaging using self-immobilizing techniques.Lastly,we discuss the prospects and potential challenges associated with selfimmobilizing fluorescent probes to promote further development and application of more delicate fluorescent probes.展开更多
Rheumatoid arthritis(RA)is a systemic autoimmune disease that is primarily manifested as synovitis and polyarticular opacity and typically leads to serious joint damage and irreversible disability,thus adversely affec...Rheumatoid arthritis(RA)is a systemic autoimmune disease that is primarily manifested as synovitis and polyarticular opacity and typically leads to serious joint damage and irreversible disability,thus adversely affecting locomotion ability and life quality.Consequently,good prognosis heavily relies on the early diagnosis and effective therapeutic monitoring of RA.Activatable fluorescent probes play vital roles in the detection and imaging of biomarkers for disease diagnosis and in vivo imaging.Herein,we review the fluorescent probes developed for the detection and imaging of RA biomarkers,namely reactive oxygen/nitrogen species(hypochlorous acid,peroxynitrite,hydroxyl radical,nitroxyl),pH,and cysteine,and address the related challenges and prospects to inspire the design of novel fluorescent probes and the improvement of their performance in RA studies.展开更多
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support from National Natural Science Foundation of China(Nos.22077103 and 22161132006)Westlake University startup。
文摘Histone H3K79 modifications are essential to regulate chromatin structure and gene transcription,but understanding of the molecular mechanisms is limited.Because H3K79 is at globular domain,short histone peptide cannot mimic H3K79 in chromatin.Instead,reconstituted nucleosome-based chemical tools are ideally used to investigate H3K79 modifications.In consequence,H3K79-modified histone H3 with additional chemical handles are required,but such synthesis is challenging and laborious.Here we report a facile semisynthesis method that enables multifunctional histone H3 readily available.H3K79-containing fragment is short for straight peptide synthesis that was later ligated to recombinant expressed H3 fragments for full-length product in large scale.As a result,nucleosomes with H3K79 modifications as well as photo-reactive group and affinity tag were obtained to investigate potential binding proteins.We believe this method that enhances synthetic accessibility of nucleosome probes will accelerate understanding of the underexplored H3K79 modifications.
基金the financial support from the National Natural Science Foundation of China(Nos.21977082,22037002and 21472148)the Natural Science Basic Research Program of Shaanxi(No.2020JC-38)。
文摘Humanβ-galactosidase(β-gal)is recognized as a crucial biomarker for evaluating senescence at the cellular and tissue levels in humans.However,tools to precisely track the endogenousβ-gal are still limited.Herein,we present two novel self-calibratingβ-gal probes 7a and 7b which were constructed on a unique green/red dual-emissive fluorescence platform.The two probes inherently exhibited a stable green fluorescence signal impervious toβ-gal activity,serving as a reliable internal reference.They also displayed a progressively diminishing red fluorescence signal with the increasing ofβ-gal expression levels.The dual behavior endows them with self-calibration capacity and then renders excellently selective and sensitive for precisely monitoringβ-gal activity.Notably,compared with E.coliβ-gal,the two probes are more effectively response to A.oryzaeβ-gal homologous to humanβ-gal,indicating their unique species-selectivity.Furthermore,7a was validated for its effectiveness in determining senescenceassociatedβ-galactosidase(SA-β-gal)expression in senescent NRK-52E and HepG2 cells,underscoring its practical applicability in senescence research.
基金support received from the National Natural Science Foundation of China(GrantNos.62204204 and 52175148)Science and Technology Innovation 2030-Major Project(Grant No.2022ZD0208601)+1 种基金Shanghai Sailing Program(Grant No.21YF1451000)Presidential Foundation of CAEP(Grant No.YZJJZQ2022001).
文摘Implanted neural probes can detect weak discharges of neurons in the brain by piercing soft brain tissue,thus as important tools for brain science research,as well as diagnosis and treatment of brain diseases.However,the rigid neural probes,such as Utah arrays,Michigan probes,and metal microfilament electrodes,are mechanically unmatched with brain tissue and are prone to rejection and glial scarring after implantation,which leads to a significant degradation in the signal quality with the implantation time.In recent years,flexible neural electrodes are rapidly developed with less damage to biological tissues,excellent biocompatibility,and mechanical compliance to alleviate scarring.Among them,the mechanical modeling is important for the optimization of the structure and the implantation process.In this review,the theoretical calculation of the flexible neural probes is firstly summarized with the processes of buckling,insertion,and relative interaction with soft brain tissue for flexible probes from outside to inside.Then,the corresponding mechanical simulation methods are organized considering multiple impact factors to realize minimally invasive implantation.Finally,the technical difficulties and future trends of mechanical modeling are discussed for the next-generation flexible neural probes,which is critical to realize low-invasiveness and long-term coexistence in vivo.
基金support from the National Natural Science Foundation of China(22122701,22477054,22293050,91953201,92153303,22377050)the Excellent Research Program of Nanjing University(ZYJH004)the Natural Science Foundation of Jiangsu Province(BK20232020).
文摘Organelles are specialized areas where cells perform specific processes necessary for life and actively communicate with each other to keep the whole cell func-tioning.Disorders of the organelle networks are associated with multiple patho-logical processes.However,clearly and intuitively visualizing the highly dynamic interactions between ultrafine organelles is challenging.Fluorescence imaging technology provides opportunities due to the distinct advantages of facile,non-invasiveness and dynamic detection,making it particularly well-suited for appli-cations in uncovering the mysterious veil of organelle interactions.Regrettably,the lack of ideal fluorescence agents has always been an obstacle in imaging the intricate behaviors of organelles.In this review,we provide a systematic discussion on the existing dual-color and dual-targetable molecular sensors used in moni-toring organelle interactions,with a specific focus on their targeting strategies,imaging mechanisms and biological applications.Additionally,the current limi-tations and future development directions of dual-targetable probes and dual-emissives are briefly discussed.This review aims to provide guidance for re-searchers to develop more improved probes for studying organelle interactions in the biomedical field.
基金support from the National Natural Science Foundation of China(No.22274005,U2167222)the Science Fund for Creative Research Groups of Nature Science Foundation of Hebei Province(B2021201038)+4 种基金Natural Science Foundation of Hebei Province(B2023201108)Hebei Province Higher Education Science and Technology Research Project(JZX2023001)Research and Innovation Team of Hebei University(IT2023A01)Hebei Province Innovation Capability Enhancement Plan Project(22567632H)Open Research Fund of School of Chemistry and Chemical Engineering,Henan Normal University.
文摘In situ precise detection of bioactive molecules with high sensitivity and spatiotemporal resolution is essential for studying physiological events and disease diagnosis.The utilization of versatile fluorescent probes in fluorescence imaging offers a powerful tool for in vivo imaging of biomarkers closely associated with pathological conditions.However,the dynamic behavior leading to rapid clearance of small molecule probes from regions of interest severely compromises their potential for precise imaging.Notably,self-immobilizing fluorescent probes that selectively recognize diseased tissues while improving in situ retention and enrichment enable accurate high-fidelity fluorescence imaging.In this review,we aim to summarize the strategies employed for recent advances in the performance and precision of in vivo fluorescence imaging using self-immobilizing techniques.Lastly,we discuss the prospects and potential challenges associated with selfimmobilizing fluorescent probes to promote further development and application of more delicate fluorescent probes.
基金supported by the National Natural Science Foundation of China(82072432)the China-Japan Friendship Hospital Horizontal Project/Spontaneous Research Funding(2022-HX-JC-7)+1 种基金the National High Level Hospital Clinical Research Funding(2022-NHLHCRF-PY-20)the Elite Medical Professionals project of China-Japan Friendship Hospital(ZRJY2021-GG12).
文摘Rheumatoid arthritis(RA)is a systemic autoimmune disease that is primarily manifested as synovitis and polyarticular opacity and typically leads to serious joint damage and irreversible disability,thus adversely affecting locomotion ability and life quality.Consequently,good prognosis heavily relies on the early diagnosis and effective therapeutic monitoring of RA.Activatable fluorescent probes play vital roles in the detection and imaging of biomarkers for disease diagnosis and in vivo imaging.Herein,we review the fluorescent probes developed for the detection and imaging of RA biomarkers,namely reactive oxygen/nitrogen species(hypochlorous acid,peroxynitrite,hydroxyl radical,nitroxyl),pH,and cysteine,and address the related challenges and prospects to inspire the design of novel fluorescent probes and the improvement of their performance in RA studies.
