Peptide-based probes play prominent roles in biomedical research due to their promising properties such as high biocompatibility,fast excretion, favorable pharmacokinetics as well as easy and robust preparation. Consi...Peptide-based probes play prominent roles in biomedical research due to their promising properties such as high biocompatibility,fast excretion, favorable pharmacokinetics as well as easy and robust preparation. Considering the translation of imaging probes into clinical applications, peptide-based probes remain to be the most desirable and optimal candidates. This review summarized the development of peptide-based probes with promising imaging modalities and highlighted the successful applications for in vivo biomedical imaging.展开更多
Peptide-based therapies have attracted considerable interest in the treatment of cancer, diabetes, bacterial infections, and neurodegenerative diseases due to their promising therapeutic properties and enhanced safety...Peptide-based therapies have attracted considerable interest in the treatment of cancer, diabetes, bacterial infections, and neurodegenerative diseases due to their promising therapeutic properties and enhanced safety profiles. This review provides a comprehensive overview of the major trends in peptide drug discovery and development, emphasizing preclinical strategies aimed at improving peptide stability, specificity, and pharmacokinetic properties. It assesses the current applications and challenges of peptide-based drugs in these diseases, illustrating the pharmaceutical areas where peptide-based drugs demonstrate significant potential. Furthermore, this review analyzes the obstacles that must be overcome in the future,aiming to provide valuable insights and references for the continued advancement of peptidebased drugs.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
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
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
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
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
Fluorogenic probes with"off-on"fluorescence signals have emerged as powerful tools for biosensing and bioimaging of biomolecules in living systems.Conventional single-target probes,however,often suffer from ...Fluorogenic probes with"off-on"fluorescence signals have emerged as powerful tools for biosensing and bioimaging of biomolecules in living systems.Conventional single-target probes,however,often suffer from false-positive signals due to non-specific activation in non-target tissues or the diffusion of activated fluorescent products.To address these limitations,dual-targeted fluorogenic probes(DTFPs)have been developed,which simultaneously target two biomarkers to enhance detection specificity and minimize false-positive outcomes.DTFPs are designed to activate or retain fluorescence only when both biomarkers are present within a targeted region,enabling precise in vivo imaging of pathological conditions such as tumors and inflammation.This review highlights recent advances in DTFP development,focusing on their design principles,activation mechanisms,and applications in biosensing and bioimaging.We also discuss current challenges and future directions for DTFP research,aiming to inspire the design of next-generation probes with improved accuracy and specificity.By providing a comprehensive overview of DTFPs,this review seeks to advance their potential for transformative applications in biomedical imaging and diagnostics.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 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
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
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 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
As a hydrolase,chymotrypsin(CHT)is involved in many physiological activities,and its abnormal activity is closely related to diabetes,pancreatic fibrosis,chronic pancreatitis and pancreatic cancer.In this work,an inno...As a hydrolase,chymotrypsin(CHT)is involved in many physiological activities,and its abnormal activity is closely related to diabetes,pancreatic fibrosis,chronic pancreatitis and pancreatic cancer.In this work,an innovative long-wavelength emission fluorescent probe TCF-CHT was designed and synthesized for the high specificity detection of CHT,which utilized TCF-OH and a mimetic peptide substrate 4-bromobutyryl as chromogenic group and recognition group,respectively.TCF-CHT exhibited excellent selectivity and eye-catching sensitivity(8.91 ng/m L)towards CHT,“off-on”long-wavelength emission at 670 nm and large Stokes shift(140 nm).Furthermore,the successful fulfillment and perfect performance in imaging endogenous CHT in complex organisms(P815 cells,HepG2 cells,zebrafish and tumor-bearing mice)verified its potential as a powerful tool for the recognition of CHT in complicated biological environments.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
Fluorescence imaging in the second near-infrared window(NIR-Ⅱ,1000-1700 nm)is a promising modality for real-time imaging of cancer and image-guided surgery with superior in vivo optical properties.So far,very few NIR...Fluorescence imaging in the second near-infrared window(NIR-Ⅱ,1000-1700 nm)is a promising modality for real-time imaging of cancer and image-guided surgery with superior in vivo optical properties.So far,very few NIR-Ⅱfluorophores have been reported for in vivo biomedical imaging of chemically-induced spontaneous breast carcinoma.Herein,a NIR-Ⅱfluorescent probe CH1055-F3 with the nucleolin-targeted tumor-homing peptide F3 was demonstrated to prefe rentially accumulate in 4 T1 tumors.More importantly,CH1055-F3 exhibited specific NIR-Ⅱsignals with high spatial and temporal resolution,strong tumor uptake,and remarkable NIR-Ⅱimage-guided surgery in dimethylbenzanthracene(DMBA)-induced spontaneous breast tumor rats.This report presents the first tumor-homing peptide-based NIR-Ⅱprobe to diagnose transplantable and spontaneous breast tumors by the active targeting.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
BACKGROUND Malnutrition is common in critically ill patients,and it is associated with an increased risk of complications.Early enteral nutrition with adequate caloric and protein intake is critical nevertheless it is...BACKGROUND Malnutrition is common in critically ill patients,and it is associated with an increased risk of complications.Early enteral nutrition with adequate caloric and protein intake is critical nevertheless it is difficult to achieve.Peptide-based formulas have been shown to be beneficial in patients with feeding intolerance.However,there are limited studies showing the efficacy and safety of high-protein peptide-based formula in critically ill surgical patients.AIM To determine the effects of a high-protein peptide formulation on gastrointestinal tolerance,nutritional status,biochemical changes,and adverse events in patients in the surgery intensive care unit(SICU)compared to an isocaloric isonitrogenous standard polymeric formulation.METHODS This study was a multi-center double-blind,randomized controlled trial.We enrolled adult patients in the surgical intensive care unit,age≥15 years and expected to receive enteral feeding for at least 5-14 d post-operation.They were randomly assigned to receive either the high-protein peptide-based formula or the isocaloric isonitrogenous standard formula for 14 d.Gastric residual volume(GRV),nutritional status,body composition and biochemical parameters were assessed at baseline and on days 3,5,7,9,11,and 14.RESULTS A total of 19 patients were enrolled,9 patients in the peptide-based formula group and 10 patients in the standard formula group.During the study period,there were no differences of the average GRV,body weight,body composition,nutritional status and biochemical parameters in the patients receiving peptide-based formula,compared to the standard regimen.However,participants in the standard formula lost their body weight,body mass index(BMI)and skeletal muscle mass significantly.While body weight,BMI and muscle mass were maintained in the peptide-based formula,from baseline to day 14.Moreover,the participants in the peptide-based formula tended to reach their caloric target faster than the standard formula.CONCLUSION The study emphasizes the importance of early nutritional support in the SICU and showed the efficacy and safety of a high-protein,peptide-based formula in meeting caloric and protein intake targets while maintaining body weight and muscle mass.展开更多
基金partially supported by grants from the National Natural Science Foundation of China(NSFC Nos. 21708012,81773674, 81573383,21390402, 81725009, 21788102, 81425015)111 Project (No. B17019)+6 种基金NKR&DPC (No. 2016YFA00900)NSFHP(Nos. 2017CFB151, 2017CFA024, 2017CFB711, 2016ACA126)ABRPSTCS (No. SYG201521)NSFJP (No. BK20160387)Shenzhen Science and Technology Research Grant (No. JCYJ20170303170809222)self-determined research funds of CCNU from the colleges, basic research and operation of MOE for the Central Universities (No. 23020205170469)Wuhan Morning Light Plan of Youth Science and Technology (No. 201705304010321)
文摘Peptide-based probes play prominent roles in biomedical research due to their promising properties such as high biocompatibility,fast excretion, favorable pharmacokinetics as well as easy and robust preparation. Considering the translation of imaging probes into clinical applications, peptide-based probes remain to be the most desirable and optimal candidates. This review summarized the development of peptide-based probes with promising imaging modalities and highlighted the successful applications for in vivo biomedical imaging.
基金supported by the National Natural Science Foundation of China (Nos. 82173674 and 82204195)。
文摘Peptide-based therapies have attracted considerable interest in the treatment of cancer, diabetes, bacterial infections, and neurodegenerative diseases due to their promising therapeutic properties and enhanced safety profiles. This review provides a comprehensive overview of the major trends in peptide drug discovery and development, emphasizing preclinical strategies aimed at improving peptide stability, specificity, and pharmacokinetic properties. It assesses the current applications and challenges of peptide-based drugs in these diseases, illustrating the pharmaceutical areas where peptide-based drugs demonstrate significant potential. Furthermore, this review analyzes the obstacles that must be overcome in the future,aiming to provide valuable insights and references for the continued advancement of peptidebased drugs.
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.
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(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 (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the National Natural Science Foundation of China(22137003 and 21922406)Natural Science Foundation of Jiangsu Province(BK20200301 and BK20190055)the Fundamental Research Funds for the Central Universities(020514380251)are acknowledged.
文摘Fluorogenic probes with"off-on"fluorescence signals have emerged as powerful tools for biosensing and bioimaging of biomolecules in living systems.Conventional single-target probes,however,often suffer from false-positive signals due to non-specific activation in non-target tissues or the diffusion of activated fluorescent products.To address these limitations,dual-targeted fluorogenic probes(DTFPs)have been developed,which simultaneously target two biomarkers to enhance detection specificity and minimize false-positive outcomes.DTFPs are designed to activate or retain fluorescence only when both biomarkers are present within a targeted region,enabling precise in vivo imaging of pathological conditions such as tumors and inflammation.This review highlights recent advances in DTFP development,focusing on their design principles,activation mechanisms,and applications in biosensing and bioimaging.We also discuss current challenges and future directions for DTFP research,aiming to inspire the design of next-generation probes with improved accuracy and specificity.By providing a comprehensive overview of DTFPs,this review seeks to advance their potential for transformative applications in biomedical imaging and diagnostics.
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.
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.
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 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.
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financial support provided by National Natural Science Foundation of China(Nos.21775005,41430641 and 41140032)the Start-Up Fund of Qingdao University of Science and Technology(No.12030430010883)。
文摘As a hydrolase,chymotrypsin(CHT)is involved in many physiological activities,and its abnormal activity is closely related to diabetes,pancreatic fibrosis,chronic pancreatitis and pancreatic cancer.In this work,an innovative long-wavelength emission fluorescent probe TCF-CHT was designed and synthesized for the high specificity detection of CHT,which utilized TCF-OH and a mimetic peptide substrate 4-bromobutyryl as chromogenic group and recognition group,respectively.TCF-CHT exhibited excellent selectivity and eye-catching sensitivity(8.91 ng/m L)towards CHT,“off-on”long-wavelength emission at 670 nm and large Stokes shift(140 nm).Furthermore,the successful fulfillment and perfect performance in imaging endogenous CHT in complex organisms(P815 cells,HepG2 cells,zebrafish and tumor-bearing mice)verified its potential as a powerful tool for the recognition of CHT in complicated biological environments.
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partially supported by grants from the National Natural Science Foundation of China(Nos.81773674,21473041 and 81573383)Project First-Class Disciplines Development Supported by Chengdu University of Traditional Chinese Medicine(No.CZYJC1903)+4 种基金Natural Science Foundation of Hubei Province(Nos.2017CFA024,2016ACA126 and 2017CFB711)the Applied Basic Research Program of Wuhan Municipal Bureau of Science and Technology(No.2019020701011429)Shenzhen Science and Technology Research Grant(No.JCYJ20190808152019182)Tibet Autonomous Region Science and Technology Plan Project Key Project(No.XZ201901-GB-11)the Fundamental Research Funds for the Central Universities,and Health Commission of Hubei Province Scientific Research Project(Nos.WJ2019M177 and WJ2019M178)。
文摘Fluorescence imaging in the second near-infrared window(NIR-Ⅱ,1000-1700 nm)is a promising modality for real-time imaging of cancer and image-guided surgery with superior in vivo optical properties.So far,very few NIR-Ⅱfluorophores have been reported for in vivo biomedical imaging of chemically-induced spontaneous breast carcinoma.Herein,a NIR-Ⅱfluorescent probe CH1055-F3 with the nucleolin-targeted tumor-homing peptide F3 was demonstrated to prefe rentially accumulate in 4 T1 tumors.More importantly,CH1055-F3 exhibited specific NIR-Ⅱsignals with high spatial and temporal resolution,strong tumor uptake,and remarkable NIR-Ⅱimage-guided surgery in dimethylbenzanthracene(DMBA)-induced spontaneous breast tumor rats.This report presents the first tumor-homing peptide-based NIR-Ⅱprobe to diagnose transplantable and spontaneous breast tumors by the active targeting.
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.
文摘BACKGROUND Malnutrition is common in critically ill patients,and it is associated with an increased risk of complications.Early enteral nutrition with adequate caloric and protein intake is critical nevertheless it is difficult to achieve.Peptide-based formulas have been shown to be beneficial in patients with feeding intolerance.However,there are limited studies showing the efficacy and safety of high-protein peptide-based formula in critically ill surgical patients.AIM To determine the effects of a high-protein peptide formulation on gastrointestinal tolerance,nutritional status,biochemical changes,and adverse events in patients in the surgery intensive care unit(SICU)compared to an isocaloric isonitrogenous standard polymeric formulation.METHODS This study was a multi-center double-blind,randomized controlled trial.We enrolled adult patients in the surgical intensive care unit,age≥15 years and expected to receive enteral feeding for at least 5-14 d post-operation.They were randomly assigned to receive either the high-protein peptide-based formula or the isocaloric isonitrogenous standard formula for 14 d.Gastric residual volume(GRV),nutritional status,body composition and biochemical parameters were assessed at baseline and on days 3,5,7,9,11,and 14.RESULTS A total of 19 patients were enrolled,9 patients in the peptide-based formula group and 10 patients in the standard formula group.During the study period,there were no differences of the average GRV,body weight,body composition,nutritional status and biochemical parameters in the patients receiving peptide-based formula,compared to the standard regimen.However,participants in the standard formula lost their body weight,body mass index(BMI)and skeletal muscle mass significantly.While body weight,BMI and muscle mass were maintained in the peptide-based formula,from baseline to day 14.Moreover,the participants in the peptide-based formula tended to reach their caloric target faster than the standard formula.CONCLUSION The study emphasizes the importance of early nutritional support in the SICU and showed the efficacy and safety of a high-protein,peptide-based formula in meeting caloric and protein intake targets while maintaining body weight and muscle mass.