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
Tumor-related PD-L2 expression is associated with the clinical efficacy of PD-1/PD-L1 blockade therapy.PD-L2-specific imaging can help selecting patients for appropriate immunotherapy.In this study,a PD-L2-targeting p...Tumor-related PD-L2 expression is associated with the clinical efficacy of PD-1/PD-L1 blockade therapy.PD-L2-specific imaging can help selecting patients for appropriate immunotherapy.In this study,a PD-L2-targeting peptide(PDP2)was screened by the one-bead one-compound combinatorial library approach.Using the retro-inverso D-peptide of PDP2(RD-PDP2)and PEGylation strategies,we developed a novel Tc-99m-labeled PD-L2-targeting peptide as a SPECT tracer(^(99m)Tc-PEG_(6)-RD-PDP2)for imaging of tumor PD-L2 expression.The radiolabeling yield of ^(99m)Tc-PEG_(6)-RD-PDP2 was greater than 95%by the standard HYNIC/tricine/TPPTS labeling procedure.^(99m)Tc-PEG_(6)-RD-PDP2 displayed high PD-L2-binding specificity both in vitro and in vivo.SPECT/CT imaging with^(99m)Tc-PEG_(6)-RD-PDP2 showed that the A549-PD-L2tumors were clearly visualized,whereas the signals in PD-L2-negative A549 tumors were much lower.In vivo blocking study suggested that the tumor uptake of^(99m)Tc-PEG_(6)-RD-PDP2 was PD-L2 specifically mediated.^(99m)Tc-PEG_(6)-RD-PDP2 is a promising SPECT probe for the non-invasive imaging of tumor PD-L2expression and has a great potential in guiding the anti-PD-1 or anti-PD-L1 immunotherapy of cancer.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
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
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
Herein,we utilized nucleic acids induced peptide co-assembly strategy to develop novel nucleic acids induced peptide-based AIE(NIP-AIE)nanoparticles.Strong fluorescent of AIE could be observed when a little amount of ...Herein,we utilized nucleic acids induced peptide co-assembly strategy to develop novel nucleic acids induced peptide-based AIE(NIP-AIE)nanoparticles.Strong fluorescent of AIE could be observed when a little amount of nucleic acids was added into the peptide solution,and the intensity could be regulated by the concentration of nucleic acids.This AIE nanoparticle with good biocompatibility could achieve fast cell imaging.It is also proved that the fluorescence intensity of AIE decreased with time,which indicates that the reducible cross-linkers of Wpc peptide by GSH and nanoparticles gradually disintegrate in cell.Based on the different of AIE fluorescence signals which regulated by the formation and disintegration of nanoparticles,this AIE system is expected to be used for real-time monitoring of drug release from peptide-based nano carriers in vivo or in vitro,and may provide a new platform for the construction of other organic AIE nanoparticles.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
A zinc sulfate open framework matrix,[Zn(SO_4)(DMSO)](1),was synthesized by solvothermal evaporationusing dimethyl sulfoxide(DMSO)as the solvent.A compositeP@1,which exhibits fluorescence and room tempera-ture phospho...A zinc sulfate open framework matrix,[Zn(SO_4)(DMSO)](1),was synthesized by solvothermal evaporationusing dimethyl sulfoxide(DMSO)as the solvent.A compositeP@1,which exhibits fluorescence and room tempera-ture phosphorescence(RTP)properties,was prepared by doping 2,6-naphthalic acid(P)into matrix1at a low con-centration.P@1emitted a green RTP that was visible to the naked eye and lasted for approximately 2 s.P@1exhib-ited selective phosphorescence enhancement response towards Pb^(2+),with a detection limit of 2.52μmol·L^(-1).Themain detection mechanism is the Pb—O coordination-induced phosphorescence enhancement in the system.Inter-estingly,P@1also functioned as a dual-channel probe for the rapid detection of Fe^(3+)ions through fluorescencequenching with a detection limit of 0.038μmol·L^(-1).The recognition mechanism may be attributed to the competi-tive energy absorption betweenP@1and Fe^(3+)ions.CCDC:2388502,1.展开更多
To address the lack of systematic studies on heavy metal fluorescent probes in typical buffer solutions,this study developed a Fe^(3+)and Cu^(2+)fluorescent probe,DHU‑NP‑4,based on a naphthalimide fluorophore.Comparat...To address the lack of systematic studies on heavy metal fluorescent probes in typical buffer solutions,this study developed a Fe^(3+)and Cu^(2+)fluorescent probe,DHU‑NP‑4,based on a naphthalimide fluorophore.Comparative analysis of the probe's performance in various buffer systems revealed that buffers with high organic content are unsuitable for evaluating such probes.Furthermore,the pH of the solvent system was found to significantly influence the probe's behavior.Under highly acidic conditions(pH≤2),DHU‑NP‑4 exhibited exceptional specificity for Fe^(3+),while in alkaline conditions,it demonstrated high specificity for Cu^(2+).Leveraging these properties,the probe enabled the quantitative detection of Fe^(3+)and Cu^(2+)in solution.展开更多
Rheumatoid arthritis(RA) is a chronic inflammatory disease with multi-system damage and autoimmune features.The main clinical manifestations of RA include joint pain,swelling,and stiffness,and RA may lead to joint def...Rheumatoid arthritis(RA) is a chronic inflammatory disease with multi-system damage and autoimmune features.The main clinical manifestations of RA include joint pain,swelling,and stiffness,and RA may lead to joint deformity and dysfunction in severe cases.The pathologic development of RA involves complex interactions of multiple biomarkers,and detecting a single biomarker may produce falsepositive results due to other confounding factors.Therefore,fluorescent probes that can detect multiple biomarkers simultaneously are crucial for precise RA diagnosis.Peroxynitrite(ONOO^(-)) and viscosity are inflammation-related factors in cells.In this study,we developed a dual responsive near-infrared fluorescent probe,YLS,for ONOO^(-) and viscosity.The probe features dual-channel turn-on fluorescence responses at 625 and 760 nm upon the presence of ONOO^(-) and viscosity,respectively.Supported by YLS,we found that during RA pathology,lymphocyte infiltration not only increases the concentration of proteins in the joint fluid resulting in elevated viscosity;at the same time,the overproduction of ONOO^(-) exacerbates oxidative stress and inflammatory responses.This multiparameter assay is expected to improve the diagnostic accuracy of the early stages of RA,thus providing a scientific basis for early intervention and personalized treatment.展开更多
Colorectal cancer(CRC)is one of the most prevalent malignant tumors worldwide,exhibiting high morbidity and mortality.Lack of efficient tools for early diagnosis and surgical resection guidance of CRC have been a seri...Colorectal cancer(CRC)is one of the most prevalent malignant tumors worldwide,exhibiting high morbidity and mortality.Lack of efficient tools for early diagnosis and surgical resection guidance of CRC have been a serious threat to the long-term survival rate of the CRC patients.Recent studies have shown that relative higher viscosity was presented in tumor cells compared to that in normal cells,leading to viscosity as a potential biomarker for CRC.Herein,we reported the development of a series of novel viscosity-sensitive and mitochondria-specific fluorescent probes(HTB,HTI,and HTP)for CRC detection.Among them,HTB showed high sensitivity,minimal background interference,low cytotoxicity,and significant viscous response capability,making it an ideal tool for distinguishing colorectal tumor cells from normal cells.Importantly,we have successfully utilized HTB to visualize in a CRC-cells-derived xenograft(CDX)model,enriching its medical imaging capacity,which laid a foundation for further clinical translational application.展开更多
In this study,a self-calibrating near-infrared fluorescence probe was designed and synthesized based on the dual-fluorophore strategy utilizing methylene blue and coumarin.The probe utilized methylene blue(emission sp...In this study,a self-calibrating near-infrared fluorescence probe was designed and synthesized based on the dual-fluorophore strategy utilizing methylene blue and coumarin.The probe utilized methylene blue(emission spectrum range:640-740 nm)and coumarin fluorophore(emission spectrum range:440-600 nm)as signal output units,thereby achieving effective spectral separation and highly selective detection of HClO.Under physiological pH conditions,HClO triggers an oxidation-cleavage reaction,releasing methylene blue and coumarin,which emit distinct red and green fluorescence,respectively.This dual-emission feature enabled rapid HClO detection with two-channel detection limits of 25.13 nmol·L^(-1)(green channel)and 31.55 nmol·L^(-1)(red channel).Furthermore,in cell imaging experiments,this probe demonstrated excellent cell membrane permeability and low cytotoxicity,successfully enabling the monitoring of both endogenous and exogenous HClO in living cells.By incorporating a twochannel self-calibration system,the probe effectively mitigated signal variations caused by instrumental or environmental interference,substantially improving detection sensitivity and reliability.展开更多
Herein,a luminescent europium-based metal-organic framework(Eu-MOF,[Eu_(3)(L)(HL)(NO_(3))_(2)(DMF)_(2)]·4DMF·5H_(2)O,H_(4)L=5,5′-(pyrazine-2,6-diyl)diisophthalic acid,DMF=N,N-dimethylformamide)was developed...Herein,a luminescent europium-based metal-organic framework(Eu-MOF,[Eu_(3)(L)(HL)(NO_(3))_(2)(DMF)_(2)]·4DMF·5H_(2)O,H_(4)L=5,5′-(pyrazine-2,6-diyl)diisophthalic acid,DMF=N,N-dimethylformamide)was developed for the dual-functional detection of environmental pollutants.This fluorescence-quenching-based sensor exhibited excep-tional sensitivity for both 2,4,6-trinitrophenol(TNP)and tetracycline(TC),achieving remarkably low detection lim-its of 1.96×10^(-6)and 1.71×10^(-7)mol·L^(-1),respectively.Notably,the system exhibited 99%fluorescence quenching ef-ficiency for TC,indicating ultra-efficient analyte recognition.The detection performance surpasses most reported lu-minescent MOF sensors,attributed to synergistic mechanisms of fluorescence resonance energy transfer(FRET)and photoinduced electron transfer(PET).CCDC:2446483.展开更多
This article provides a short review on the importance of the detailed analysis of a Langmuir probe I-V trace in a multi-Maxwellian plasma,and discuss proper procedures analyzing Langmuir probe I-V traces in bi-Maxwel...This article provides a short review on the importance of the detailed analysis of a Langmuir probe I-V trace in a multi-Maxwellian plasma,and discuss proper procedures analyzing Langmuir probe I-V traces in bi-Maxwellian and triple-Maxwellian Electron Energy Distribution Function(EEDF)plasmas.Discus⁃sion and demonstration of procedures include the treatment of the ion saturation current,electron saturation cur⁃rent,space-charge effects on the I-V trace,and most importantly how to properly isolate and fit for each electron group present in an I-V trace reflecting a mult-Maxwellian EEDF,as well as how having a multi-Maxwellian EEDF affects the procedures of treating the ion and electron saturation currents.Shortcomings of common improp⁃er procedures are discussed and demonstrated with simulated I-V traces to show how these procedures gives false measurements.展开更多
The abnormal metabolic activity of the tumor can increase the oxygen consumption in tumor cells,and the poor blood perfusion often happens in tumor regions as well,which are the main reasons that result in a hypoxic s...The abnormal metabolic activity of the tumor can increase the oxygen consumption in tumor cells,and the poor blood perfusion often happens in tumor regions as well,which are the main reasons that result in a hypoxic situation in the tumor.A fluorescence probe,AQD,with selective response toward hypoxia was designed for the detection of hypoxic tumor cells,which was obtained by the covalent connection of a large planar conjugated fluorophore with good fluorescence stability and a N,N-dimethylaniline moiety via the azo bond.The introduction of the azo bond in AQD caused significant fluorescence emission quenching,and the probe was reduced under hypoxic conditions to release the fluorophore via breaking the azo bond,resulting in the gradual recovery of fluorescence emission.Probe AQD exhibited a remarkable fluorescence response in hypoxic conditions,high selectivity,and good biocompatibility,which was successfully used for the imaging of hypoxic tumor cells and realized the detection of hypoxic A549 cells.展开更多
Using 2-dicyanomethylene-3-cyano-4,5,5-trimethyl-2,5-dihydrofuran(TCF)as a near-infrared fluorescent chromophore,we designed and synthesized a TCF-based fluorescent probe TCF-NS by introducing 2,4-dinitrophenyl ether ...Using 2-dicyanomethylene-3-cyano-4,5,5-trimethyl-2,5-dihydrofuran(TCF)as a near-infrared fluorescent chromophore,we designed and synthesized a TCF-based fluorescent probe TCF-NS by introducing 2,4-dinitrophenyl ether as the recognized site for H_(2)S.The probe TCF-NS displayed a rapid-response fluorescent against H_(2)S with high sensitivity and selection but had no significant fluorescence response to other biothiols.Furthermore,TCF-NS was applied to sense H_(2)S in living cells successfully with minimized cytotoxicity and a large Stokes shift.展开更多
Cutaneous squamous cell carcinoma(cSCC),the second most common skin cancer,requires early and accurate detection to optimize clinical management.Fluorescence imaging has emerged as a non-invasive and cost-effective to...Cutaneous squamous cell carcinoma(cSCC),the second most common skin cancer,requires early and accurate detection to optimize clinical management.Fluorescence imaging has emerged as a non-invasive and cost-effective tool with high sensitivity for tumor diagnosis;however,existing probes for cSCC are limited in achieving rapid and specific imaging.In this study,we introduce FC-1,a dualtandem activatable fluorescent probe designed for precise cSCC diagnosis by simultaneously targeting fibroblast activation proteinαand cathepsin C(CTSC).This dual-locked activation strategy effectively reduces nonspecific signals in normal tissues while enhancing diagnostic specificity.In vivo studies in SCC-7 xenografted mice demonstrated FC-1's ability to visualize subcutaneous tumors with high sensitivity and specificity.Moreover,FC-1 enabled clear differentiation between cSCC and keloids.The probe's dual-activation mechanism and robust performance underscore its potential as a clinically translatable tool for early cSCC detection and differential diagnosis.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
Icing detection is critically important for preventing safety accidents and economic losses,especially concerning ice formation from invalidated anti-icing fluids(water and ethylene glycol)under extreme conditions.Tra...Icing detection is critically important for preventing safety accidents and economic losses,especially concerning ice formation from invalidated anti-icing fluids(water and ethylene glycol)under extreme conditions.Traditional technologies like ultrasonics and capacitor-antenna face challenges with limited detection areas,lower accuracy,and susceptibility to electromagnetic interference.Here,we introduce a novel viscosity-ultrasensitive fluorescent probe 40,4‴-(2,2-diphenyle-thene-1,1-diyl)bis-(3,5-dicarboxylate)(TPE-2B4C)based on AIEgens for moni-toring ice formation of anti-icing fluids in low-temperature environments.TPE-2B4C,consisting of four sodium carboxylate groups and multiple freely rotating benzene rings,demonstrates outstanding solubility in anti-icing fluids and exhibits no fluorescent background signal even at low temperatures(<−20°C).Upon freezing,TPE-2B4C relocates from the water phase to higher viscosity ethylene glycol,causing restriction of benzene rings and a significantly increased green fluorescence signal.TPE-2B4C can successfully determine whether the anti-icing fluids are icing from−5 to−20°C with a high contrast ratio.Due to its simple setup,fast operation,and broad applicability,our new method is anticipated to be employed for rapid,real-time,and large-scale icing detection.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
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the National Natural Science Foundation of China(NSFC,Nos.92159201,81630045 and 81927802 to F.WangNo.81971676 to J.Shi+3 种基金No.32027801 to Z.Hu)National Key R&D Program of China(No.2017YFA0205600 to F.Wang)Emergency Key Program of Guangzhou Laboratory,(No.EKPG21–16 to F.Wang)Youth Innovation Promotion Association of Chinese Academy of Sciences(YIPACAS,No.2016090 to J.Shi)for financial support。
文摘Tumor-related PD-L2 expression is associated with the clinical efficacy of PD-1/PD-L1 blockade therapy.PD-L2-specific imaging can help selecting patients for appropriate immunotherapy.In this study,a PD-L2-targeting peptide(PDP2)was screened by the one-bead one-compound combinatorial library approach.Using the retro-inverso D-peptide of PDP2(RD-PDP2)and PEGylation strategies,we developed a novel Tc-99m-labeled PD-L2-targeting peptide as a SPECT tracer(^(99m)Tc-PEG_(6)-RD-PDP2)for imaging of tumor PD-L2 expression.The radiolabeling yield of ^(99m)Tc-PEG_(6)-RD-PDP2 was greater than 95%by the standard HYNIC/tricine/TPPTS labeling procedure.^(99m)Tc-PEG_(6)-RD-PDP2 displayed high PD-L2-binding specificity both in vitro and in vivo.SPECT/CT imaging with^(99m)Tc-PEG_(6)-RD-PDP2 showed that the A549-PD-L2tumors were clearly visualized,whereas the signals in PD-L2-negative A549 tumors were much lower.In vivo blocking study suggested that the tumor uptake of^(99m)Tc-PEG_(6)-RD-PDP2 was PD-L2 specifically mediated.^(99m)Tc-PEG_(6)-RD-PDP2 is a promising SPECT probe for the non-invasive imaging of tumor PD-L2expression and has a great potential in guiding the anti-PD-1 or anti-PD-L1 immunotherapy of cancer.
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financial support from the Natural Science Foundation of China(Nos.21778009,21977010 and 81701818)the Natural Science Foundation of Guangdong Province(No.2020A1515010522)+4 种基金the Guangdong Foundation for Basic and Applied Basic Research(No.2019A1515110365)the Shenzhen Science and Technology Innovation Committee(Nos.JCYJ20180507181527112,JCYJ201805081522131455 and JCYJ20170817172023838)the China Postdoctoral Science Foundation(No.2020M670054)financial support from Beijing National Laboratory of Molecular Science open grant(No.BNLMS20160112)Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions(No.2019SHIBS0004)。
文摘Herein,we utilized nucleic acids induced peptide co-assembly strategy to develop novel nucleic acids induced peptide-based AIE(NIP-AIE)nanoparticles.Strong fluorescent of AIE could be observed when a little amount of nucleic acids was added into the peptide solution,and the intensity could be regulated by the concentration of nucleic acids.This AIE nanoparticle with good biocompatibility could achieve fast cell imaging.It is also proved that the fluorescence intensity of AIE decreased with time,which indicates that the reducible cross-linkers of Wpc peptide by GSH and nanoparticles gradually disintegrate in cell.Based on the different of AIE fluorescence signals which regulated by the formation and disintegration of nanoparticles,this AIE system is expected to be used for real-time monitoring of drug release from peptide-based nano carriers in vivo or in vitro,and may provide a new platform for the construction of other organic AIE nanoparticles.
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.
文摘A zinc sulfate open framework matrix,[Zn(SO_4)(DMSO)](1),was synthesized by solvothermal evaporationusing dimethyl sulfoxide(DMSO)as the solvent.A compositeP@1,which exhibits fluorescence and room tempera-ture phosphorescence(RTP)properties,was prepared by doping 2,6-naphthalic acid(P)into matrix1at a low con-centration.P@1emitted a green RTP that was visible to the naked eye and lasted for approximately 2 s.P@1exhib-ited selective phosphorescence enhancement response towards Pb^(2+),with a detection limit of 2.52μmol·L^(-1).Themain detection mechanism is the Pb—O coordination-induced phosphorescence enhancement in the system.Inter-estingly,P@1also functioned as a dual-channel probe for the rapid detection of Fe^(3+)ions through fluorescencequenching with a detection limit of 0.038μmol·L^(-1).The recognition mechanism may be attributed to the competi-tive energy absorption betweenP@1and Fe^(3+)ions.CCDC:2388502,1.
文摘To address the lack of systematic studies on heavy metal fluorescent probes in typical buffer solutions,this study developed a Fe^(3+)and Cu^(2+)fluorescent probe,DHU‑NP‑4,based on a naphthalimide fluorophore.Comparative analysis of the probe's performance in various buffer systems revealed that buffers with high organic content are unsuitable for evaluating such probes.Furthermore,the pH of the solvent system was found to significantly influence the probe's behavior.Under highly acidic conditions(pH≤2),DHU‑NP‑4 exhibited exceptional specificity for Fe^(3+),while in alkaline conditions,it demonstrated high specificity for Cu^(2+).Leveraging these properties,the probe enabled the quantitative detection of Fe^(3+)and Cu^(2+)in solution.
基金the National Natural Science Foundation of China(Nos.22325703,22377071,U23A6009)Research Project Supported by Shanxi Scholarship Council of China(No.2022-002)+1 种基金the Shanxi Province Science Foundation(No.202203021221009)Shanxi Province Science and Technology activities for overseas people selected funding project(No.2024001)。
文摘Rheumatoid arthritis(RA) is a chronic inflammatory disease with multi-system damage and autoimmune features.The main clinical manifestations of RA include joint pain,swelling,and stiffness,and RA may lead to joint deformity and dysfunction in severe cases.The pathologic development of RA involves complex interactions of multiple biomarkers,and detecting a single biomarker may produce falsepositive results due to other confounding factors.Therefore,fluorescent probes that can detect multiple biomarkers simultaneously are crucial for precise RA diagnosis.Peroxynitrite(ONOO^(-)) and viscosity are inflammation-related factors in cells.In this study,we developed a dual responsive near-infrared fluorescent probe,YLS,for ONOO^(-) and viscosity.The probe features dual-channel turn-on fluorescence responses at 625 and 760 nm upon the presence of ONOO^(-) and viscosity,respectively.Supported by YLS,we found that during RA pathology,lymphocyte infiltration not only increases the concentration of proteins in the joint fluid resulting in elevated viscosity;at the same time,the overproduction of ONOO^(-) exacerbates oxidative stress and inflammatory responses.This multiparameter assay is expected to improve the diagnostic accuracy of the early stages of RA,thus providing a scientific basis for early intervention and personalized treatment.
基金supported by the National Natural Science Foundation of China(Nos.82272067,81974386,M-0696,and 82273486)Natural Science Foundation of Hunan Province(Nos.2022JJ80052,2024JJ6596)the Innovation Fund for Postgraduate Students of Central South University(No.2023ZZTS0841)。
文摘Colorectal cancer(CRC)is one of the most prevalent malignant tumors worldwide,exhibiting high morbidity and mortality.Lack of efficient tools for early diagnosis and surgical resection guidance of CRC have been a serious threat to the long-term survival rate of the CRC patients.Recent studies have shown that relative higher viscosity was presented in tumor cells compared to that in normal cells,leading to viscosity as a potential biomarker for CRC.Herein,we reported the development of a series of novel viscosity-sensitive and mitochondria-specific fluorescent probes(HTB,HTI,and HTP)for CRC detection.Among them,HTB showed high sensitivity,minimal background interference,low cytotoxicity,and significant viscous response capability,making it an ideal tool for distinguishing colorectal tumor cells from normal cells.Importantly,we have successfully utilized HTB to visualize in a CRC-cells-derived xenograft(CDX)model,enriching its medical imaging capacity,which laid a foundation for further clinical translational application.
文摘In this study,a self-calibrating near-infrared fluorescence probe was designed and synthesized based on the dual-fluorophore strategy utilizing methylene blue and coumarin.The probe utilized methylene blue(emission spectrum range:640-740 nm)and coumarin fluorophore(emission spectrum range:440-600 nm)as signal output units,thereby achieving effective spectral separation and highly selective detection of HClO.Under physiological pH conditions,HClO triggers an oxidation-cleavage reaction,releasing methylene blue and coumarin,which emit distinct red and green fluorescence,respectively.This dual-emission feature enabled rapid HClO detection with two-channel detection limits of 25.13 nmol·L^(-1)(green channel)and 31.55 nmol·L^(-1)(red channel).Furthermore,in cell imaging experiments,this probe demonstrated excellent cell membrane permeability and low cytotoxicity,successfully enabling the monitoring of both endogenous and exogenous HClO in living cells.By incorporating a twochannel self-calibration system,the probe effectively mitigated signal variations caused by instrumental or environmental interference,substantially improving detection sensitivity and reliability.
文摘Herein,a luminescent europium-based metal-organic framework(Eu-MOF,[Eu_(3)(L)(HL)(NO_(3))_(2)(DMF)_(2)]·4DMF·5H_(2)O,H_(4)L=5,5′-(pyrazine-2,6-diyl)diisophthalic acid,DMF=N,N-dimethylformamide)was developed for the dual-functional detection of environmental pollutants.This fluorescence-quenching-based sensor exhibited excep-tional sensitivity for both 2,4,6-trinitrophenol(TNP)and tetracycline(TC),achieving remarkably low detection lim-its of 1.96×10^(-6)and 1.71×10^(-7)mol·L^(-1),respectively.Notably,the system exhibited 99%fluorescence quenching ef-ficiency for TC,indicating ultra-efficient analyte recognition.The detection performance surpasses most reported lu-minescent MOF sensors,attributed to synergistic mechanisms of fluorescence resonance energy transfer(FRET)and photoinduced electron transfer(PET).CCDC:2446483.
文摘This article provides a short review on the importance of the detailed analysis of a Langmuir probe I-V trace in a multi-Maxwellian plasma,and discuss proper procedures analyzing Langmuir probe I-V traces in bi-Maxwellian and triple-Maxwellian Electron Energy Distribution Function(EEDF)plasmas.Discus⁃sion and demonstration of procedures include the treatment of the ion saturation current,electron saturation cur⁃rent,space-charge effects on the I-V trace,and most importantly how to properly isolate and fit for each electron group present in an I-V trace reflecting a mult-Maxwellian EEDF,as well as how having a multi-Maxwellian EEDF affects the procedures of treating the ion and electron saturation currents.Shortcomings of common improp⁃er procedures are discussed and demonstrated with simulated I-V traces to show how these procedures gives false measurements.
文摘The abnormal metabolic activity of the tumor can increase the oxygen consumption in tumor cells,and the poor blood perfusion often happens in tumor regions as well,which are the main reasons that result in a hypoxic situation in the tumor.A fluorescence probe,AQD,with selective response toward hypoxia was designed for the detection of hypoxic tumor cells,which was obtained by the covalent connection of a large planar conjugated fluorophore with good fluorescence stability and a N,N-dimethylaniline moiety via the azo bond.The introduction of the azo bond in AQD caused significant fluorescence emission quenching,and the probe was reduced under hypoxic conditions to release the fluorophore via breaking the azo bond,resulting in the gradual recovery of fluorescence emission.Probe AQD exhibited a remarkable fluorescence response in hypoxic conditions,high selectivity,and good biocompatibility,which was successfully used for the imaging of hypoxic tumor cells and realized the detection of hypoxic A549 cells.
基金financially supported by the Natural Science Foundation of Jiangsu Province(Grant No.BK20241181)the State Key Laboratory of AnalyticalChemistry for Life Science,School of Chemistry and Chemical Engineering,Nanjing University(Grant No.SKLACLS2419)。
文摘Using 2-dicyanomethylene-3-cyano-4,5,5-trimethyl-2,5-dihydrofuran(TCF)as a near-infrared fluorescent chromophore,we designed and synthesized a TCF-based fluorescent probe TCF-NS by introducing 2,4-dinitrophenyl ether as the recognized site for H_(2)S.The probe TCF-NS displayed a rapid-response fluorescent against H_(2)S with high sensitivity and selection but had no significant fluorescence response to other biothiols.Furthermore,TCF-NS was applied to sense H_(2)S in living cells successfully with minimized cytotoxicity and a large Stokes shift.
基金supported by the National Natural Science Foundation of China(No.22325401,22404049)Special Funds for the Construction of Innovative Provinces in Hunan Province(No.2021RC4021)the China Postdoctoral Science Foundation(No.2024 M750866).
文摘Cutaneous squamous cell carcinoma(cSCC),the second most common skin cancer,requires early and accurate detection to optimize clinical management.Fluorescence imaging has emerged as a non-invasive and cost-effective tool with high sensitivity for tumor diagnosis;however,existing probes for cSCC are limited in achieving rapid and specific imaging.In this study,we introduce FC-1,a dualtandem activatable fluorescent probe designed for precise cSCC diagnosis by simultaneously targeting fibroblast activation proteinαand cathepsin C(CTSC).This dual-locked activation strategy effectively reduces nonspecific signals in normal tissues while enhancing diagnostic specificity.In vivo studies in SCC-7 xenografted mice demonstrated FC-1's ability to visualize subcutaneous tumors with high sensitivity and specificity.Moreover,FC-1 enabled clear differentiation between cSCC and keloids.The probe's dual-activation mechanism and robust performance underscore its potential as a clinically translatable tool for early cSCC detection and differential diagnosis.
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support from the National Natural Science Foundation of China(9235630033,22105069)Shanghai Pujiang Program(20PJ1402900)+2 种基金Shanghai Natural Science Foundation(21ZR1418400)Innovation Program of Shanghai Municipal Education Commission(2023FGS01)Natural Science Foundation of Jiangsu Province(BK20231225).
文摘Icing detection is critically important for preventing safety accidents and economic losses,especially concerning ice formation from invalidated anti-icing fluids(water and ethylene glycol)under extreme conditions.Traditional technologies like ultrasonics and capacitor-antenna face challenges with limited detection areas,lower accuracy,and susceptibility to electromagnetic interference.Here,we introduce a novel viscosity-ultrasensitive fluorescent probe 40,4‴-(2,2-diphenyle-thene-1,1-diyl)bis-(3,5-dicarboxylate)(TPE-2B4C)based on AIEgens for moni-toring ice formation of anti-icing fluids in low-temperature environments.TPE-2B4C,consisting of four sodium carboxylate groups and multiple freely rotating benzene rings,demonstrates outstanding solubility in anti-icing fluids and exhibits no fluorescent background signal even at low temperatures(<−20°C).Upon freezing,TPE-2B4C relocates from the water phase to higher viscosity ethylene glycol,causing restriction of benzene rings and a significantly increased green fluorescence signal.TPE-2B4C can successfully determine whether the anti-icing fluids are icing from−5 to−20°C with a high contrast ratio.Due to its simple setup,fast operation,and broad applicability,our new method is anticipated to be employed for rapid,real-time,and large-scale icing detection.
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.
