A refined reciprocating probe system was installed on the midplane of HL-2A tokamak. The system is developed in collaboration with the Institute of Scientific Instrument, Chinese Academy of Science in Shenyang.The sys...A refined reciprocating probe system was installed on the midplane of HL-2A tokamak. The system is developed in collaboration with the Institute of Scientific Instrument, Chinese Academy of Science in Shenyang.The system has been used to measure edge density, temperature, potential and their fluctuation profiles with 8 cm scan from scrapeoff layer to plasma boundary. The velocity of the reciprocating stroke is designed by 1 m ·s^-1.展开更多
A fast radial scanning probe system was constructed for the Keda Torus eXperiment(KTX)to measure the profiles of boundary plasma parameters such as floating potential,electron density,temperature,transport fluxes,etc....A fast radial scanning probe system was constructed for the Keda Torus eXperiment(KTX)to measure the profiles of boundary plasma parameters such as floating potential,electron density,temperature,transport fluxes,etc.The scanning probe system is driven by slow and fast motion mechanisms,corresponding to the stand-by movement of a stepping motor and the fast scanning movement of a high-torque servo-motor,respectively.In fast scanning,the scanner drives the probe radially up to 20 cm at a maximum velocity of 4.0 m s-1.A noncontact magnetic grating ruler with a high spatial resolution of 5μm is used for the displacement measurement.New scanning probe can reach the center of plasmas rapidly.The comparison of plasma floating potential profiles obtained by a fixed radial rake probe and the single scanning probe suggests that the high-speed scanning probe system is reliable for measuring edge plasma parameter profiles on the KTX device.展开更多
A multi-voltage probe array system is designed to measure the coupling resistance of an ion cyclotron resonance frequency antenna. In the process of the antenna coupling resistance data extraction, the minimization al...A multi-voltage probe array system is designed to measure the coupling resistance of an ion cyclotron resonance frequency antenna. In the process of the antenna coupling resistance data extraction, the minimization algorithm, the original Levenberg–Marquardt algorithm, is replaced by the Broyden–Fletcher–Goldfarb–Shanno algorithm to achieve more stable and accurate results. Moreover, a simple model of the multi-voltage probe array was applied to simulate the performance of the Kalman filter, and to optimize the distance and position of the probes and probe number to mitigate the influence of the system noise on the rebuilt results. During the EAST experiment in 2019, a four-voltage probe array was applied to measure the coupling resistance of line 6 during high confined mode discharge. The measurement results by the multivoltage probe array system and the voltage/current probe pair show a good agreement.展开更多
Enzyme assisted DNA probes are powerful tools in molecular diagnostics for their simplicity,rapidity,and low detection limit.However,cost of probes,difficulty in optimization and disturbance of secondary structure hin...Enzyme assisted DNA probes are powerful tools in molecular diagnostics for their simplicity,rapidity,and low detection limit.However,cost of probes,difficulty in optimization and disturbance of secondary structure hindered the wider application of enzyme assisted DNA probes.To solve the problems,we designed a new system named shared-probe system.By introducing two unlabeled single stranded DNA named Sh1 and Sh2 as the bridge between probe and the substrate,the same sequence of dually labeled probe with stable performance was shared for different mutations,thus sparing the expense and time cost on designing,synthesizing and optimizing corresponding probes.Besides,the hybridization between Sh1 and the substrate could overcome secondary structures,which guaranteed the detection of different substrates.The performance and generality of the design were tested by low abundance detection in synthetic single DNA samples and the limit of detection was 0.05%for PTENR130 Q,EGFR-L858 R and 0.02%for BRCA1-NM007294.3.In genomic DNA samples,the limit of detection of 0.1%can be achieved for EGFR-L858 R,demonstrating the potential of clinical application in our design.展开更多
In order to obtain creditable data an applicable method to optimize parameters of the Langmuir probes and circuits in a stationary laboratory device is investigated and an experimental criterion of the probe dimension...In order to obtain creditable data an applicable method to optimize parameters of the Langmuir probes and circuits in a stationary laboratory device is investigated and an experimental criterion of the probe dimension is developed. To obtain the electron temperature and density the Electron Energy Distribution Function （EEDF） approach with less computing time and more accurate results is applied, instead of the conventional slope approach. Moreover the influence of the vessel wall materials on the plasma density is discussed briefly, indicating that the dielectric wall is helpful to enhancing the electron density.展开更多
A newly designed divertor Langmuir probe diagnostic system has been installed in a rare closed divertor of the HL-2A tokamak and steadily operated for the study of divertor physics involved edge-localized mode mitigat...A newly designed divertor Langmuir probe diagnostic system has been installed in a rare closed divertor of the HL-2A tokamak and steadily operated for the study of divertor physics involved edge-localized mode mitigation,detachment and redistribution of heat flux,etc.Two sets of probe arrays including 274 probe tips were placed at two ports(approximately 180°separated toroidally),and the spatial and temporal resolutions of this measurement system could reach6 mm and 1μs,respectively.A novel design of the ceramic isolation ring can ensure reliable electrical insulation property between the graphite tip and the copper substrate plate where plasma impurities and the dust are deposited into the gaps for a long experimental time.Meanwhile,the condition monitoring and mode conversion between single and triple probe of the probe system could be conveniently implemented via a remote-control station.The preliminary experimental result shows that the divertor Langmuir probe system is capable of measuring the high spatiotemporal parameters involved the plasma density,electron temperature,particle flux as well as heat flux during the ELMy H-mode discharges.展开更多
Schizophrenia(SCZ) is a severe mental disorder with an unclear pathogenesis.Increasing evidence suggests that oxidative stress(OS) may contribute to the neuropathological processes underlying SCZ.Biothiols,key endogen...Schizophrenia(SCZ) is a severe mental disorder with an unclear pathogenesis.Increasing evidence suggests that oxidative stress(OS) may contribute to the neuropathological processes underlying SCZ.Biothiols,key endogenous antioxidants,have been proposed as potential biomarkers for the disease.However,due to the presence of the blood-brain barrier(BBB),fluorescent probes are rarely used to image biothiols in the brain of SCZ models.In this study,a series of fluorescent probes for biothiols were developed using dicyanoisophorone derivatives as fluorophores known for their excellent optical properties,and carboxylic esters as recognition units.A parallel synthesis and rapid screening strategy was employed to construct and optimize these probes.By introducing trifluoromethyl and benzothiazole groups into the fluorophore,the emission wavelength was successfully shifted into the near-infrared region.Additionally,various trifluoromethyl-substituted aromatic and nitrogen heterocyclic compounds were incorporated to optimize the carboxylic esters,thereby improving the probes' reactivity and lipophilicity.Systematic evaluation of the physicochemical characteristics,and optical performance led to the identification of DCIBT-11 as the most promising candidate.DCI-BT-11 demonstrated excellent BBB permeability and a good response to biothiols both in vitro and in vivo.Notably,DCI-BT-11 was used for the first time to visualize biothiol flux and assess the therapeutic effects of the antioxidant N-acetylcysteine(NAC) in the brains of SCZ mouse models,offering new insights into the role of OS in the pathogenesis and treatment of SCZ.展开更多
Ferroptosis has exhibited great potential in therapies and intracellular reducing agents of sulfur species(RSSs) in the thiol-dependent redox systems are crucial in ferroptosis.This makes the simultaneous detection of...Ferroptosis has exhibited great potential in therapies and intracellular reducing agents of sulfur species(RSSs) in the thiol-dependent redox systems are crucial in ferroptosis.This makes the simultaneous detection of multiple RSSs significant for evaluating ferroptosis therapy.However,the traditional techniques,including fluorescent(FL) imaging and electrospray ionization-based mass spectrometry(MS) detection,cannot achieve the discrimination of different RSSs.Herein,simultaneous MS detection of multiple RSSs,including cysteine(Cys),homocysteine(Hcy),glutathione(GSH) and hydrogen sulfide(H_(2)S),was obtained upon enhancing ionization efficiency by a fluorescent probe(NBD-O-1).Based on the interaction between NBD-O-1 and RSSs,the complex of RSSs with a fragment of NBD-O-1 can be generated,which can be easily ionized for MS detection in the negative mode.Therefore,the intracellular RSSs can be well detected upon the incubation of He La cells with the probe of NBD-O-1,exhibiting the total RSS levels by the FL imaging and further providing expression of each RSS by enhanced MS detection.Furthermore,the RSSs during ferroptosis in He La cells have been evaluated using the present strategy,demonstrating the potential for ferroptosis examinations.This work has made an unconventional application of a fluorescent probe to enhance the detection of multiple RSSs by MS,providing significant molecular information for addressing the ferroptosis mechanism.展开更多
Cell-selective fluorescent probes have emerged as essential tools for live-cell imaging,enabling the differentiation of specific cell types within complex biological systems.Unlike traditional antibody-based methods t...Cell-selective fluorescent probes have emerged as essential tools for live-cell imaging,enabling the differentiation of specific cell types within complex biological systems.Unlike traditional antibody-based methods that target extracellular proteins,small-molecule probes can access intracellular environments and exploit diverse biochemical features for selective retention or activation.This perspective categorizes the mechanisms of cell selectivity into five principal strategies:Protein-oriented,carbohydrate-oriented,lipid-oriented,gating-oriented,and metabolism-oriented live-cell distinctions.Each class capitalizes on a unique cellular trait ranging from protein expression and membrane composition to transporter activity and metabolic enzyme presence.We discuss representative examples of each mechanism,outline a decision-tree workflow for elucidating a new probe's mode of action,and highlight how understanding these mechanisms is critical for both basic biological research and therapeutic probe design.Looking ahead,the development of such mechanism-informed cell-specific probes holds promise for advancing precision cell targeting in biomedical applications.展开更多
The study of target proteins is crucial for understanding molecular interactions and developing analytical platforms,therapeutic agents and functional tools.Herein,we present a novel nanoplatform activated by near-inf...The study of target proteins is crucial for understanding molecular interactions and developing analytical platforms,therapeutic agents and functional tools.Herein,we present a novel nanoplatform activated by near-infrared(NIR) light for triple-modal proteins study,which enabling target protein labeling,enrichment and visualization.Azido-naphthalimide-coated upconversion nanoparticles(UCNPs) serve as NIR light-responsive nanoplatforms,showing promising applications in studying interactions between various bioactive molecules and proteins in living systems.Under NIR light irradiation,azido-naphthalimides are activated by ultraviolet(UV) and blue light emitted from UCNPs and the resulting amino-naphthalimides intermediate not only crosslink nearby target proteins but also enable imaging performance.We demonstrate that this nanoplatform is capable of selective protein labeling and imaging in complex protein environments,achieving specific labeling and imaging of both intracellular and extracellular proteins in mammalian cells as well as bacteria.Furthermore,in vivo protein labeling has been achieved using this novel NIR light-activatable nanoplatform.This technique will open new avenues for discoveries and mechanistic interrogation in chemical biology.展开更多
The detection of amino acid enantiomers holds significant importance in biomedical,chemical,food,and other fields.Traditional chiral recognition methods using fluorescent probes primarily rely on fluorescence intensit...The detection of amino acid enantiomers holds significant importance in biomedical,chemical,food,and other fields.Traditional chiral recognition methods using fluorescent probes primarily rely on fluorescence intensity changes,which can compromise accuracy and repeatability.In this study,we report a novel fluorescent probe(R)-Z1 that achieves effective enantioselective recognition of chiral amino acids in water by altering emission wavelengths(>60 nm).This water-soluble probe(R)-Z1 exhibits cyan or yellow-green luminescence upon interaction with amino acid enantiomers,enabling reliable chiral detection of 14 natural amino acids.It also allows for the determination of enantiomeric excess through monitoring changes in luminescent color.Additionally,a logic operation with two inputs and three outputs was constructed based on these optical properties.Notably,amino acid enantiomers were successfully detected via dual-channel analysis at both the food and cellular levels.This study provides a new dynamic luminescence-based tool for the accurate sensing and detection of amino acid enantiomers.展开更多
To address the challenge of low survival rates and limited data collection efficiency in current virtual probe deployments,which results from anomaly detection mechanisms in location-based service(LBS)applications,thi...To address the challenge of low survival rates and limited data collection efficiency in current virtual probe deployments,which results from anomaly detection mechanisms in location-based service(LBS)applications,this paper proposes a novel virtual probe deployment method based on user behavioral feature analysis.The core idea is to circumvent LBS anomaly detection by mimicking real-user behavior patterns.First,we design an automated data extraction algorithm that recognizes graphical user interface(GUI)elements to collect spatio-temporal behavior data.Then,by analyzing the automatically collected user data,we identify normal users’spatio-temporal patterns and extract their features such as high-activity time windows and spatial clustering characteristics.Subsequently,an antidetection scheduling strategy is developed,integrating spatial clustering optimization,load-balanced allocation,and time window control to generate probe scheduling schemes.Additionally,a self-correction mechanism based on an exponential backoff strategy is implemented to rectify anomalous behaviors andmaintain system stability.Experiments in real-world environments demonstrate that the proposed method significantly outperforms baseline methods in terms of both probe ban rate and task completion rate,while maintaining high time efficiency.This study provides a more reliable and clandestine solution for geosocial data collection and lays the foundation for building more robust virtual probe systems.展开更多
Sulfur dioxide(SO_(2)) and its derivatives have been recognized as harmful environmental pollutants.However,they are often produced during the processing of traditional Chinese medicines,potentially compromising the q...Sulfur dioxide(SO_(2)) and its derivatives have been recognized as harmful environmental pollutants.However,they are often produced during the processing of traditional Chinese medicines,potentially compromising the quality of these medicinal materials and contributing to various health issues.Due to a lack of effective monitoring and imaging tools,the physiological effects of excessive SO_(2) residues in traditional Chinese medicine remain unclear.Therefore,developing a rapid and effective tool for detecting SO_(2) is crucial for understanding its metabolic pathways and effects in vivo.In this study,we developed a near infrared(NIR) and ratiometric fluorescent probe,NIR-RS,which exhibits high sensitivity,selectivity,and rapid response for SO_(2) detection.Notably,NIR-RS accurately quantifies SO_(2) contents in Pinelliae rhizoma(P.rhizoma) samples,with recovery rates from 98.46 % to 102.40 %,and relative standard deviations(RSDs)< 5.0 %.For bioimaging applications,NIR-RS has low cytotoxicity and good mitochondrial-targeting ability,making it suitable for imaging exogenous and endogenous SO_(2) in mitochondria.Additionally,NIR-RS was successfully applied to image SO_(2) content of P.rhizoma samples within cells,revealing that high SO_(2) residue elevated mitochondria adenosine triphosphate(ATP) content,these findings reveal that P.rhizoma with excessive SO_(2) can affect the organism's growth mechanisms through alterations in ATP pathways.In vivo,SO_(2) was found to predominantly accumulate in the liver following gavage with P.rhizoma solution,with accumulation levels increasing in proportion to SO_(2) residue concentration.High SO_(2) concentrations in P.rhizoma can cause pulmonary fibrosis and gastric mucosal damage.This work provides a valuable tool for regulating SO_(2) content in P.rhizoma and may help researcher better understand the metabolism of SO_(2) derivatives and explore their physiological roles in biological systems.展开更多
Fast reciprocating probe systems （ FRPS ） are widely used in some tokamaks, such as JT- 60 U, TEXT and DIlI-D. The parameters with high temporal-spatial resolution are measured for boundary plasmas using these syste...Fast reciprocating probe systems （ FRPS ） are widely used in some tokamaks, such as JT- 60 U, TEXT and DIlI-D. The parameters with high temporal-spatial resolution are measured for boundary plasmas using these systems. The FRPS on HL-2A is developed, which is composed of transmission bar, digital grating displacement system, electromagnetic valves, stepping motor and so on. The high-pressure gas from the electromagnetic valves controlled by trigger signals provides the power to drive the transmission bar forward or backward. Reciprocating distance is 8 cm with the maximum speed of 1.5 m·s^-1.展开更多
AIM:To review applications of confocal laser endomicroscopy(CLE) in pancreatobiliary lesions and studies that assessed training and interpretation of images. METHODS: A computerized literature search was performed usi...AIM:To review applications of confocal laser endomicroscopy(CLE) in pancreatobiliary lesions and studies that assessed training and interpretation of images. METHODS: A computerized literature search was performed using OVID MEDLINE, EMBASE, Cochrane library, and the ISI Web of Knowledge from 1980 to October 2014. We also searched abstracts from major meetings that included the Digestive Disease Week, Canadian Digestive Disease Week and the United European Gastroenterology Week using a combination of controlled vocabulary and text words related to p CLE, confocal, endomicroscopy, probe-based confocal laser endomicroscopy, and bile duct to identify reports of trials. In addition, recursive searches and crossreferencing was performed, and manual searches of articles identified after the initial search was also completed. We included fully published articles and those in abstract form. Given the relatively recent introduction of CLE we included randomized trials and cohort studies.R E S U LT S : In the evaluation of indeterminate pancreatobiliary strictures CLE with ERCP compared to ERCP alone can increase the detection of cancerous strictures with a sensitivity of(98% vs 45%) andhas a negative predictive value(97% vs 69%), but decreased the specificity(67% vs 100%) and the positive predictive value(71% vs 100%) when compared to index pathology. Modifications in the classification systems in indeterminate biliary strictures have increased the specificity of p CLE from 67% to 73%. In pancreatic cystic lesions there is a need to develop similar systems to interpret and characterize lesions based on CLE images obtained. The presence of superficial vascular network predicts serous cystadenomas accurately. Also training in acquiring and interpretation of images is feasible in those without any prior knowledge in CLE in a relatively simple manner and computer-aided diagnosis software is a promising innovation. CONCLUSION: The role of p CLE in the evaluation of pancreatobiliary disorders might be better suited for those with an intermediate and low probability.展开更多
Mercury ions are highly toxic and can accumulate along food chains in water,soil,crops and animals.Effective detection of mercury ions in various media is of great significance for maintaining the ecological environme...Mercury ions are highly toxic and can accumulate along food chains in water,soil,crops and animals.Effective detection of mercury ions in various media is of great significance for maintaining the ecological environment and protecting people's health.In this work,a mercury ions specific fluorescent probe was developed by a simple one-step reaction of commercial substrates of 4-chloro-7-nitro-2,1,3-benzoxadiazole and 1-(2-aminoethyl)-4-methylpiperazine.Investigation on sensing behavior showed that this probe had high sensitivity and selectivity towards mercury ions.Furthermore,this probe could be used as a tool to track the level of mercury ions in living system.In living cells,the probe with green emission emitted a bright red fluorescence when it was bound to mercury ions.In Arabidopsis thaliana,similar red emission could be detected from the root tip and stalk when A.thaliana was grown in culture medium containing mercury ions.The imaging in zebrafish showed that mercury ions were mainly concentrated in the stomach and head of zebrafish.Especially,this probe could be applied in quantitative analysis of mercury ions in tap water,green tea,sea shrimp and soil.This work provided a practical tool for the detection of mercury ions in living systems and quantitative analysis in real samples.展开更多
Carboxylesterase 1(CES1), one of the most abundant serine hydrolases in mammals, has drawn much attentions in recent years, owing to this enzyme involves in many physiological processes via hydrolysis of both endogeno...Carboxylesterase 1(CES1), one of the most abundant serine hydrolases in mammals, has drawn much attentions in recent years, owing to this enzyme involves in many physiological processes via hydrolysis of both endogenous esters and xenobiotic esters. Herein, to real-time monitor the activities of CES1 in various biological systems, a practical and iso form-specific fluorescent probe was developed on the basis of the substrate preference of CES1, as well as the structural and optical properties of BODIPY dyes. After screening of a panel of BODIPY ester derivatives, probe 1 displayed the best combination of specificity,sensitivity, enzymatic kinetics and applicability for monitoring CES1 activities in real samples. This probe was successfully used to detect CESl activities in several biological systems including tissue preparations,living cells, tissue slices and zebrafish. Furthermore, the biomedical applications of probe 1 for screening of CES1 inhibitors were also demonstrated using tissue preparations or living cells as enzyme sources. In summary, a practical and broadly applicable tool for real-time monitoring CES1 in biological systems was developed and well-characterized, which held great promise for further investigations on CES1-associated drug discovery, clinical practice and fundamental research.展开更多
Thiophenol(PhSH)is an important raw material for organic synthesis,while its high toxicity to organisms makes it an environmental pollutant.Therefore,it is crucial to accurately detect PhSH and explore its metabolic p...Thiophenol(PhSH)is an important raw material for organic synthesis,while its high toxicity to organisms makes it an environmental pollutant.Therefore,it is crucial to accurately detect PhSH and explore its metabolic process in the living system.Herein,a near-infrared(NIR)fluorescent probe TEM-FB was developed for sensing PhSH with a turn-on fluorescent signal at 719nm and a large Stokes shift(198 nm)based on generating the intramolecular charge transfer(ICT)process.TEM-FB shows high specificity and significant sensitivity towards PhSH(detection limit:10 nmol/L)via the aromatic nucleophilic substitution mechanism.Furthermore,it was successfully applied to image PhSH in multiple cell lines and in zebrafish.Notably,we revealed the oxidative stress process caused by PhSH and demonstrated that the hydrogen peroxide(H_(2)O_(2))in cells would alleviate the poisonousness from exogenous PhSH for the first time.This work provides a promising bioimaging tool for monitoring PhSH in living systems and visualizing the process of oxidative stress induced by PhSH.展开更多
A new vision coordinate measuring system--single camera 3 D coordinate measuring system based on optical probe imaging is presented. A new idea in vision coordinate measurement is proposed. A linear model is deduced w...A new vision coordinate measuring system--single camera 3 D coordinate measuring system based on optical probe imaging is presented. A new idea in vision coordinate measurement is proposed. A linear model is deduced which can distinguish six freedom degrees of optical probe to realize coordinate measurement of the object surface. The effects of some factors on the resolution of the system are analyzed. The simulating experiments have shown that the system model is available.展开更多
In this paper, we discuss and analyze theoretically probeabsorption-amplification response in a four-level coherent atomic system with vacuum-inducedcoherence via changing the sign of the parameter f, with f denoting ...In this paper, we discuss and analyze theoretically probeabsorption-amplification response in a four-level coherent atomic system with vacuum-inducedcoherence via changing the sign of the parameter f, with f denoting the ratio of a pair of dipolemoments associated with a doublet of closely upper hypernne sublevels. We find that the amplitude ofthe probe amplification for the case f = -1 can be about one order of magnitude larger than thatachievable for the case f = 1. In addition, with respect to the case f = -1 the probe amplificationcan be maintained all the time with weak incoherent pumping for a wide range of the probe detuning.展开更多
文摘A refined reciprocating probe system was installed on the midplane of HL-2A tokamak. The system is developed in collaboration with the Institute of Scientific Instrument, Chinese Academy of Science in Shenyang.The system has been used to measure edge density, temperature, potential and their fluctuation profiles with 8 cm scan from scrapeoff layer to plasma boundary. The velocity of the reciprocating stroke is designed by 1 m ·s^-1.
基金supported by the National Magnetic Confinement Fusion Science Program of China(No.2017YFE0301700)National Natural Science Foundation of China(No.11635008).
文摘A fast radial scanning probe system was constructed for the Keda Torus eXperiment(KTX)to measure the profiles of boundary plasma parameters such as floating potential,electron density,temperature,transport fluxes,etc.The scanning probe system is driven by slow and fast motion mechanisms,corresponding to the stand-by movement of a stepping motor and the fast scanning movement of a high-torque servo-motor,respectively.In fast scanning,the scanner drives the probe radially up to 20 cm at a maximum velocity of 4.0 m s-1.A noncontact magnetic grating ruler with a high spatial resolution of 5μm is used for the displacement measurement.New scanning probe can reach the center of plasmas rapidly.The comparison of plasma floating potential profiles obtained by a fixed radial rake probe and the single scanning probe suggests that the high-speed scanning probe system is reliable for measuring edge plasma parameter profiles on the KTX device.
基金China Fusion Engineering Experimental Reactor General Integration and Engineering Design (No. 2017YFE0300503)National Natural Science Foundation of China (No. 11775258)the Comprehensive Research Facility for Fusion Technology Program of China (No. 2018-000052-73-01-001228)。
文摘A multi-voltage probe array system is designed to measure the coupling resistance of an ion cyclotron resonance frequency antenna. In the process of the antenna coupling resistance data extraction, the minimization algorithm, the original Levenberg–Marquardt algorithm, is replaced by the Broyden–Fletcher–Goldfarb–Shanno algorithm to achieve more stable and accurate results. Moreover, a simple model of the multi-voltage probe array was applied to simulate the performance of the Kalman filter, and to optimize the distance and position of the probes and probe number to mitigate the influence of the system noise on the rebuilt results. During the EAST experiment in 2019, a four-voltage probe array was applied to measure the coupling resistance of line 6 during high confined mode discharge. The measurement results by the multivoltage probe array system and the voltage/current probe pair show a good agreement.
基金the National Natural Science Foundation of China(Nos.21705053 and 81871732)the Natural Science Foundation of Hubei Province(No.2017CFB117)+1 种基金Hubei Province Health and Family Planning Scientific Research Project(No.J2017Q017)Wuhan Youth Science and Technology Plan(No.2017050304010293)。
文摘Enzyme assisted DNA probes are powerful tools in molecular diagnostics for their simplicity,rapidity,and low detection limit.However,cost of probes,difficulty in optimization and disturbance of secondary structure hindered the wider application of enzyme assisted DNA probes.To solve the problems,we designed a new system named shared-probe system.By introducing two unlabeled single stranded DNA named Sh1 and Sh2 as the bridge between probe and the substrate,the same sequence of dually labeled probe with stable performance was shared for different mutations,thus sparing the expense and time cost on designing,synthesizing and optimizing corresponding probes.Besides,the hybridization between Sh1 and the substrate could overcome secondary structures,which guaranteed the detection of different substrates.The performance and generality of the design were tested by low abundance detection in synthetic single DNA samples and the limit of detection was 0.05%for PTENR130 Q,EGFR-L858 R and 0.02%for BRCA1-NM007294.3.In genomic DNA samples,the limit of detection of 0.1%can be achieved for EGFR-L858 R,demonstrating the potential of clinical application in our design.
文摘In order to obtain creditable data an applicable method to optimize parameters of the Langmuir probes and circuits in a stationary laboratory device is investigated and an experimental criterion of the probe dimension is developed. To obtain the electron temperature and density the Electron Energy Distribution Function （EEDF） approach with less computing time and more accurate results is applied, instead of the conventional slope approach. Moreover the influence of the vessel wall materials on the plasma density is discussed briefly, indicating that the dielectric wall is helpful to enhancing the electron density.
基金partially supported by National Natural Science Foundation of China(Nos.11875017,11875020,12175186 and 11905052)the National Magnetic Confinement Fusion Science Program of China(Nos.2019YFE03030002,2017YFE0301203 and 2018YFE0310100)the Sichuan Outstanding Youth Science Foundation(No.2020JDJQ0019)。
文摘A newly designed divertor Langmuir probe diagnostic system has been installed in a rare closed divertor of the HL-2A tokamak and steadily operated for the study of divertor physics involved edge-localized mode mitigation,detachment and redistribution of heat flux,etc.Two sets of probe arrays including 274 probe tips were placed at two ports(approximately 180°separated toroidally),and the spatial and temporal resolutions of this measurement system could reach6 mm and 1μs,respectively.A novel design of the ceramic isolation ring can ensure reliable electrical insulation property between the graphite tip and the copper substrate plate where plasma impurities and the dust are deposited into the gaps for a long experimental time.Meanwhile,the condition monitoring and mode conversion between single and triple probe of the probe system could be conveniently implemented via a remote-control station.The preliminary experimental result shows that the divertor Langmuir probe system is capable of measuring the high spatiotemporal parameters involved the plasma density,electron temperature,particle flux as well as heat flux during the ELMy H-mode discharges.
基金supported by the National Natural Science Foundation of China (Nos.22177025,21807021,22177026)the Science Fund for Creative Research Groups of the Natural Science Foundation of Hebei Province (No.B2021201038)+1 种基金the Foundation of Hebei University (No.050001-513300201004)the Director’s Foundation of the Key Laboratory of Medicinal Chemistry and Molecular Diagnosis,Ministry of Education,Hebei University (No.MCMDZR2024003)。
文摘Schizophrenia(SCZ) is a severe mental disorder with an unclear pathogenesis.Increasing evidence suggests that oxidative stress(OS) may contribute to the neuropathological processes underlying SCZ.Biothiols,key endogenous antioxidants,have been proposed as potential biomarkers for the disease.However,due to the presence of the blood-brain barrier(BBB),fluorescent probes are rarely used to image biothiols in the brain of SCZ models.In this study,a series of fluorescent probes for biothiols were developed using dicyanoisophorone derivatives as fluorophores known for their excellent optical properties,and carboxylic esters as recognition units.A parallel synthesis and rapid screening strategy was employed to construct and optimize these probes.By introducing trifluoromethyl and benzothiazole groups into the fluorophore,the emission wavelength was successfully shifted into the near-infrared region.Additionally,various trifluoromethyl-substituted aromatic and nitrogen heterocyclic compounds were incorporated to optimize the carboxylic esters,thereby improving the probes' reactivity and lipophilicity.Systematic evaluation of the physicochemical characteristics,and optical performance led to the identification of DCIBT-11 as the most promising candidate.DCI-BT-11 demonstrated excellent BBB permeability and a good response to biothiols both in vitro and in vivo.Notably,DCI-BT-11 was used for the first time to visualize biothiol flux and assess the therapeutic effects of the antioxidant N-acetylcysteine(NAC) in the brains of SCZ mouse models,offering new insights into the role of OS in the pathogenesis and treatment of SCZ.
基金supported by the National Key Research and Development Program of China (No.2024YFA1509600)National Natural Science Foundation of China (Nos.22474010 and 22274012)the Fundamental Research Funds for the Central Universities (No.2233300007)。
文摘Ferroptosis has exhibited great potential in therapies and intracellular reducing agents of sulfur species(RSSs) in the thiol-dependent redox systems are crucial in ferroptosis.This makes the simultaneous detection of multiple RSSs significant for evaluating ferroptosis therapy.However,the traditional techniques,including fluorescent(FL) imaging and electrospray ionization-based mass spectrometry(MS) detection,cannot achieve the discrimination of different RSSs.Herein,simultaneous MS detection of multiple RSSs,including cysteine(Cys),homocysteine(Hcy),glutathione(GSH) and hydrogen sulfide(H_(2)S),was obtained upon enhancing ionization efficiency by a fluorescent probe(NBD-O-1).Based on the interaction between NBD-O-1 and RSSs,the complex of RSSs with a fragment of NBD-O-1 can be generated,which can be easily ionized for MS detection in the negative mode.Therefore,the intracellular RSSs can be well detected upon the incubation of He La cells with the probe of NBD-O-1,exhibiting the total RSS levels by the FL imaging and further providing expression of each RSS by enhanced MS detection.Furthermore,the RSSs during ferroptosis in He La cells have been evaluated using the present strategy,demonstrating the potential for ferroptosis examinations.This work has made an unconventional application of a fluorescent probe to enhance the detection of multiple RSSs by MS,providing significant molecular information for addressing the ferroptosis mechanism.
基金supported by the Starting growth Technological R&D Program(TIPS Program,RS-2024-00468327)funded by the Ministry of SMEs and Startups(MSS,Korea)in 2024 and National Research Foundation of Korea(NRF)grant funded by the Korea government(MSIT)(Nos.2023R1A2C300453411 and RS2024-00411069),Glocal University 30 project(Molecular Imaging Center,POSTECH).
文摘Cell-selective fluorescent probes have emerged as essential tools for live-cell imaging,enabling the differentiation of specific cell types within complex biological systems.Unlike traditional antibody-based methods that target extracellular proteins,small-molecule probes can access intracellular environments and exploit diverse biochemical features for selective retention or activation.This perspective categorizes the mechanisms of cell selectivity into five principal strategies:Protein-oriented,carbohydrate-oriented,lipid-oriented,gating-oriented,and metabolism-oriented live-cell distinctions.Each class capitalizes on a unique cellular trait ranging from protein expression and membrane composition to transporter activity and metabolic enzyme presence.We discuss representative examples of each mechanism,outline a decision-tree workflow for elucidating a new probe's mode of action,and highlight how understanding these mechanisms is critical for both basic biological research and therapeutic probe design.Looking ahead,the development of such mechanism-informed cell-specific probes holds promise for advancing precision cell targeting in biomedical applications.
基金supported by the National Natural Science Foundation of China (No.22007008)the LiaoNing Revitalization Talents Program (No.XLYC1907021)the Fundamental Research Funds for the Central Universities (Nos.DUT23YG120,DUT19RC(3)009)。
文摘The study of target proteins is crucial for understanding molecular interactions and developing analytical platforms,therapeutic agents and functional tools.Herein,we present a novel nanoplatform activated by near-infrared(NIR) light for triple-modal proteins study,which enabling target protein labeling,enrichment and visualization.Azido-naphthalimide-coated upconversion nanoparticles(UCNPs) serve as NIR light-responsive nanoplatforms,showing promising applications in studying interactions between various bioactive molecules and proteins in living systems.Under NIR light irradiation,azido-naphthalimides are activated by ultraviolet(UV) and blue light emitted from UCNPs and the resulting amino-naphthalimides intermediate not only crosslink nearby target proteins but also enable imaging performance.We demonstrate that this nanoplatform is capable of selective protein labeling and imaging in complex protein environments,achieving specific labeling and imaging of both intracellular and extracellular proteins in mammalian cells as well as bacteria.Furthermore,in vivo protein labeling has been achieved using this novel NIR light-activatable nanoplatform.This technique will open new avenues for discoveries and mechanistic interrogation in chemical biology.
基金the financial support from the National Natural Science Foundation of China(Nos.22377097,22307036,22074114)Natural Science Foundation of Hubei Province of China(Nos.2020CFB623,2021CFB556)Engineering Research Center of Phosphorus Resources Development and Utilization of Ministry of Education(No.LCX202305)。
文摘The detection of amino acid enantiomers holds significant importance in biomedical,chemical,food,and other fields.Traditional chiral recognition methods using fluorescent probes primarily rely on fluorescence intensity changes,which can compromise accuracy and repeatability.In this study,we report a novel fluorescent probe(R)-Z1 that achieves effective enantioselective recognition of chiral amino acids in water by altering emission wavelengths(>60 nm).This water-soluble probe(R)-Z1 exhibits cyan or yellow-green luminescence upon interaction with amino acid enantiomers,enabling reliable chiral detection of 14 natural amino acids.It also allows for the determination of enantiomeric excess through monitoring changes in luminescent color.Additionally,a logic operation with two inputs and three outputs was constructed based on these optical properties.Notably,amino acid enantiomers were successfully detected via dual-channel analysis at both the food and cellular levels.This study provides a new dynamic luminescence-based tool for the accurate sensing and detection of amino acid enantiomers.
基金supported by theNationalNatural Science Foundation of China(No.U23A20305)National Key Research and Development Program of China(No.2022YFB3102900)+1 种基金Innovation Scientists and Technicians Troop Construction Projects of Henan Province,China(No.254000510007)Key Research and Development Project of Henan Province(No.221111321200).
文摘To address the challenge of low survival rates and limited data collection efficiency in current virtual probe deployments,which results from anomaly detection mechanisms in location-based service(LBS)applications,this paper proposes a novel virtual probe deployment method based on user behavioral feature analysis.The core idea is to circumvent LBS anomaly detection by mimicking real-user behavior patterns.First,we design an automated data extraction algorithm that recognizes graphical user interface(GUI)elements to collect spatio-temporal behavior data.Then,by analyzing the automatically collected user data,we identify normal users’spatio-temporal patterns and extract their features such as high-activity time windows and spatial clustering characteristics.Subsequently,an antidetection scheduling strategy is developed,integrating spatial clustering optimization,load-balanced allocation,and time window control to generate probe scheduling schemes.Additionally,a self-correction mechanism based on an exponential backoff strategy is implemented to rectify anomalous behaviors andmaintain system stability.Experiments in real-world environments demonstrate that the proposed method significantly outperforms baseline methods in terms of both probe ban rate and task completion rate,while maintaining high time efficiency.This study provides a more reliable and clandestine solution for geosocial data collection and lays the foundation for building more robust virtual probe systems.
基金supported by the Natural Science Foundation of Hubei Province (Nos.2023AFB376 and 2024AFD287)National Key Research and Development Program (No.2023YFC3503804)the National Natural Science Foundation of China (No.22077044)。
文摘Sulfur dioxide(SO_(2)) and its derivatives have been recognized as harmful environmental pollutants.However,they are often produced during the processing of traditional Chinese medicines,potentially compromising the quality of these medicinal materials and contributing to various health issues.Due to a lack of effective monitoring and imaging tools,the physiological effects of excessive SO_(2) residues in traditional Chinese medicine remain unclear.Therefore,developing a rapid and effective tool for detecting SO_(2) is crucial for understanding its metabolic pathways and effects in vivo.In this study,we developed a near infrared(NIR) and ratiometric fluorescent probe,NIR-RS,which exhibits high sensitivity,selectivity,and rapid response for SO_(2) detection.Notably,NIR-RS accurately quantifies SO_(2) contents in Pinelliae rhizoma(P.rhizoma) samples,with recovery rates from 98.46 % to 102.40 %,and relative standard deviations(RSDs)< 5.0 %.For bioimaging applications,NIR-RS has low cytotoxicity and good mitochondrial-targeting ability,making it suitable for imaging exogenous and endogenous SO_(2) in mitochondria.Additionally,NIR-RS was successfully applied to image SO_(2) content of P.rhizoma samples within cells,revealing that high SO_(2) residue elevated mitochondria adenosine triphosphate(ATP) content,these findings reveal that P.rhizoma with excessive SO_(2) can affect the organism's growth mechanisms through alterations in ATP pathways.In vivo,SO_(2) was found to predominantly accumulate in the liver following gavage with P.rhizoma solution,with accumulation levels increasing in proportion to SO_(2) residue concentration.High SO_(2) concentrations in P.rhizoma can cause pulmonary fibrosis and gastric mucosal damage.This work provides a valuable tool for regulating SO_(2) content in P.rhizoma and may help researcher better understand the metabolism of SO_(2) derivatives and explore their physiological roles in biological systems.
文摘Fast reciprocating probe systems （ FRPS ） are widely used in some tokamaks, such as JT- 60 U, TEXT and DIlI-D. The parameters with high temporal-spatial resolution are measured for boundary plasmas using these systems. The FRPS on HL-2A is developed, which is composed of transmission bar, digital grating displacement system, electromagnetic valves, stepping motor and so on. The high-pressure gas from the electromagnetic valves controlled by trigger signals provides the power to drive the transmission bar forward or backward. Reciprocating distance is 8 cm with the maximum speed of 1.5 m·s^-1.
基金Supported by Deanship of Scientific Research at King Saud University through the Research Group Project number RGPVPP-279
文摘AIM:To review applications of confocal laser endomicroscopy(CLE) in pancreatobiliary lesions and studies that assessed training and interpretation of images. METHODS: A computerized literature search was performed using OVID MEDLINE, EMBASE, Cochrane library, and the ISI Web of Knowledge from 1980 to October 2014. We also searched abstracts from major meetings that included the Digestive Disease Week, Canadian Digestive Disease Week and the United European Gastroenterology Week using a combination of controlled vocabulary and text words related to p CLE, confocal, endomicroscopy, probe-based confocal laser endomicroscopy, and bile duct to identify reports of trials. In addition, recursive searches and crossreferencing was performed, and manual searches of articles identified after the initial search was also completed. We included fully published articles and those in abstract form. Given the relatively recent introduction of CLE we included randomized trials and cohort studies.R E S U LT S : In the evaluation of indeterminate pancreatobiliary strictures CLE with ERCP compared to ERCP alone can increase the detection of cancerous strictures with a sensitivity of(98% vs 45%) andhas a negative predictive value(97% vs 69%), but decreased the specificity(67% vs 100%) and the positive predictive value(71% vs 100%) when compared to index pathology. Modifications in the classification systems in indeterminate biliary strictures have increased the specificity of p CLE from 67% to 73%. In pancreatic cystic lesions there is a need to develop similar systems to interpret and characterize lesions based on CLE images obtained. The presence of superficial vascular network predicts serous cystadenomas accurately. Also training in acquiring and interpretation of images is feasible in those without any prior knowledge in CLE in a relatively simple manner and computer-aided diagnosis software is a promising innovation. CONCLUSION: The role of p CLE in the evaluation of pancreatobiliary disorders might be better suited for those with an intermediate and low probability.
文摘Mercury ions are highly toxic and can accumulate along food chains in water,soil,crops and animals.Effective detection of mercury ions in various media is of great significance for maintaining the ecological environment and protecting people's health.In this work,a mercury ions specific fluorescent probe was developed by a simple one-step reaction of commercial substrates of 4-chloro-7-nitro-2,1,3-benzoxadiazole and 1-(2-aminoethyl)-4-methylpiperazine.Investigation on sensing behavior showed that this probe had high sensitivity and selectivity towards mercury ions.Furthermore,this probe could be used as a tool to track the level of mercury ions in living system.In living cells,the probe with green emission emitted a bright red fluorescence when it was bound to mercury ions.In Arabidopsis thaliana,similar red emission could be detected from the root tip and stalk when A.thaliana was grown in culture medium containing mercury ions.The imaging in zebrafish showed that mercury ions were mainly concentrated in the stomach and head of zebrafish.Especially,this probe could be applied in quantitative analysis of mercury ions in tap water,green tea,sea shrimp and soil.This work provided a practical tool for the detection of mercury ions in living systems and quantitative analysis in real samples.
基金supported by the National Natural Science Foundation of China(Nos. 21572029, 31600641,81703604, 81773687, 81672961 and 81573501)the National Key Research and Development Program of China (Nos. 2017YFC1700200 and 2017YFC1702000)+2 种基金Program of Shanghai Academic/Technology Research Leader(No. 18XD1403600)Shuguang Program (No. 18SG40)supported by Shanghai Education Development Foundation and Shanghai Municipal Education Commission and the Innovative Entrepreneurship Program of High-level Talents in Dalian (Nos. 2016RQ025 and 2017RQ121)
文摘Carboxylesterase 1(CES1), one of the most abundant serine hydrolases in mammals, has drawn much attentions in recent years, owing to this enzyme involves in many physiological processes via hydrolysis of both endogenous esters and xenobiotic esters. Herein, to real-time monitor the activities of CES1 in various biological systems, a practical and iso form-specific fluorescent probe was developed on the basis of the substrate preference of CES1, as well as the structural and optical properties of BODIPY dyes. After screening of a panel of BODIPY ester derivatives, probe 1 displayed the best combination of specificity,sensitivity, enzymatic kinetics and applicability for monitoring CES1 activities in real samples. This probe was successfully used to detect CESl activities in several biological systems including tissue preparations,living cells, tissue slices and zebrafish. Furthermore, the biomedical applications of probe 1 for screening of CES1 inhibitors were also demonstrated using tissue preparations or living cells as enzyme sources. In summary, a practical and broadly applicable tool for real-time monitoring CES1 in biological systems was developed and well-characterized, which held great promise for further investigations on CES1-associated drug discovery, clinical practice and fundamental research.
基金supported by the National Natural Science Foundation of China(Nos.22077099 and 22171223)the Technology Innovation Leading Program of Shaanxi(No.2020TG-031)+3 种基金the Innovation Capability Support Program of Shaanxi(Nos.2023-CXTD-75 and 2022KJXX-32)the Natural Science Basic Research Program of Shaanxi(No.2023-JC-YB-141)Young Talent Fund of Association for Science and Technology in Shaanxi,China(No.SWYY202206)the Natural Science Basic Research Plan in Shaanxi Province of China(Nos.2022JQ-151 and 2022JQ-125).
文摘Thiophenol(PhSH)is an important raw material for organic synthesis,while its high toxicity to organisms makes it an environmental pollutant.Therefore,it is crucial to accurately detect PhSH and explore its metabolic process in the living system.Herein,a near-infrared(NIR)fluorescent probe TEM-FB was developed for sensing PhSH with a turn-on fluorescent signal at 719nm and a large Stokes shift(198 nm)based on generating the intramolecular charge transfer(ICT)process.TEM-FB shows high specificity and significant sensitivity towards PhSH(detection limit:10 nmol/L)via the aromatic nucleophilic substitution mechanism.Furthermore,it was successfully applied to image PhSH in multiple cell lines and in zebrafish.Notably,we revealed the oxidative stress process caused by PhSH and demonstrated that the hydrogen peroxide(H_(2)O_(2))in cells would alleviate the poisonousness from exogenous PhSH for the first time.This work provides a promising bioimaging tool for monitoring PhSH in living systems and visualizing the process of oxidative stress induced by PhSH.
文摘A new vision coordinate measuring system--single camera 3 D coordinate measuring system based on optical probe imaging is presented. A new idea in vision coordinate measurement is proposed. A linear model is deduced which can distinguish six freedom degrees of optical probe to realize coordinate measurement of the object surface. The effects of some factors on the resolution of the system are analyzed. The simulating experiments have shown that the system model is available.
文摘In this paper, we discuss and analyze theoretically probeabsorption-amplification response in a four-level coherent atomic system with vacuum-inducedcoherence via changing the sign of the parameter f, with f denoting the ratio of a pair of dipolemoments associated with a doublet of closely upper hypernne sublevels. We find that the amplitude ofthe probe amplification for the case f = -1 can be about one order of magnitude larger than thatachievable for the case f = 1. In addition, with respect to the case f = -1 the probe amplificationcan be maintained all the time with weak incoherent pumping for a wide range of the probe detuning.
