Lanthanide(Ln^(3+))-doped luminescent nanocrystals(NCs)with excitation and emission in the second near-infrared biological window(NIRII,1000-1700 nm)have attracted considerable attention in the fields of deep-tissue b...Lanthanide(Ln^(3+))-doped luminescent nanocrystals(NCs)with excitation and emission in the second near-infrared biological window(NIRII,1000-1700 nm)have attracted considerable attention in the fields of deep-tissue bioimaging and non-invasive biodetection,owing to their superior advantages including good photochemical stability,sharp emission peaks,large penetration depth,and high signal-to-noise ratio[1].Conventionally,Yb3t-and Nd3t-sensitized NCs have been utilized as NIR-II luminescent nanoprobes for in vivo bioimaging upon excitation with 980 and 808 nm diode laser,respectively[2].展开更多
Traditional pulse Doppler radar estimates the Doppler frequency by taking advantage of Doppler modulation over different pulses and usually it requires a few pulses to estimate the Dop- pler frequency. In this paper, ...Traditional pulse Doppler radar estimates the Doppler frequency by taking advantage of Doppler modulation over different pulses and usually it requires a few pulses to estimate the Dop- pler frequency. In this paper, a novel range-Doppler imaging algorithm based on single pulse with orthogonal frequency division multiplexing （OFDM） radar is proposed, where the OFDM pulse is composed of phase coded symbols. The Doppler frequency is estimated using one single pulse by utilizing Doppler modulation over different symbols, which remarkably increases the data update rate. Besides, it is shown that the range and Doppler estimations are completely independent and the well-known range-Doppler coupling effect does not exist. The effects of target movement on the performances of the proposed algorithm are also discussed and the results show that the algo- rithm is not sensitive to velocity. Performances of the proposed algorithm as well as comparisons with other range-Doppler algorithms are demonstrated via simulation experiments.展开更多
Single-walled carbon nanotubes(SWNTs)with five different C13/C12 isotope compositions and well-separated Raman peaks have been synthesized and conjugated to five targeting ligands in order to impart molecular specific...Single-walled carbon nanotubes(SWNTs)with five different C13/C12 isotope compositions and well-separated Raman peaks have been synthesized and conjugated to five targeting ligands in order to impart molecular specificity.Multiplexed Raman imaging of live cells has been carried out by highly specific staining of cells with a five-color mixture of SWNTs.Ex vivo multiplexed Raman imaging of tumor samples uncovers a surprising up-regulation of epidermal growth factor receptor(EGFR)on LS174T colon cancer cells from cell culture to in vivo tumor growth.This is the first time five-color multiplexed molecular imaging has been performed in the near-infrared(NIR)region under a single laser excitation.Near zero interfering background of imaging is achieved due to the sharp Raman peaks unique to nanotubes over the low,smooth autofluorescence background of biological species.展开更多
The precise and rapid monitoring of multiple organ dysfunction is crucial in drug discovery.Traditional methods,such as pathological analysis,are often time-consuming and inefficient.Here,we developed a multiplexed ne...The precise and rapid monitoring of multiple organ dysfunction is crucial in drug discovery.Traditional methods,such as pathological analysis,are often time-consuming and inefficient.Here,we developed a multiplexed near-infrared window two(NIR-II)fluorescent bioimaging method that allows for real-time,rapid,and quantitative assessment of multiple organ dysfunctions.Given that existing probes did not fully meet requirements,we synthesized a range of NIR-II hemicyanine dyes(HDs)with varying absorption and emission wavelengths.By modifying these dyes,we achieved high spatial and temporal resolution imaging of the liver,kidneys,stomach,and intestines.This method was further applied to investigate disorders induced by cisplatin,a drug known to cause gastric emptying issues along with liver and kidney injuries.By monitoring the metabolic rate of the dyes in these organs,we accurately quantified multi-organ dysfunction,which was also confirmed by gold-standard pathological analysis.Additionally,we evaluated the effects of five aristolochic acids(AAs)on multiple organ dysfunction.For the first time,we identified that AA-I and AA-II could cause gastric emptying disorders,which was further validated through transcriptomics analysis.Our study introduces a novel approach for the simultaneous monitoring of multi-organ dysfunction,which may significantly enhance the evaluation of drug side effects.展开更多
Single-shot ultrafast multidimensional optical imaging(UMOI)combines ultrahigh temporal resolution with multidimensional imaging capabilities in a snapshot,making it an essential tool for real-time detection and analy...Single-shot ultrafast multidimensional optical imaging(UMOI)combines ultrahigh temporal resolution with multidimensional imaging capabilities in a snapshot,making it an essential tool for real-time detection and analysis of ultrafast scenes.However,current single-shot UMOI techniques cannot simultaneously capture the spatial-temporal-spectral complex amplitude information,hampering it from complete analyses of ultrafast scenes.To address this issue,we propose a single-shot spatial-temporal-spectral complex amplitude imaging(STS-CAI)technique using wavelength and time multiplexing.By employing precise modulation of a broadband pulse via an encoding plate in coherent diffraction imaging and spatial-temporal shearing through a wide-open-slit streak camera,dual-mode multiplexing image reconstruction of wavelength and time is achieved,which significantly enhances the efficiency of information acquisition.Experimentally,a custom-built STS-CAI apparatus precisely measures the spatiotemporal characteristics of picosecond spatiotemporally chirped and spatial vortex pulses,respectively.STS-CAI demonstrates both ultrahigh temporal resolution and robust phase sensitivity.Prospectively,this technique is valuable for spatiotemporal coupling measurements of large-aperture ultrashort pulses and offers promising applications in both fundamental research and applied sciences.展开更多
Combining bright-feld and edge-enhanced imaging affords an effective avenue for extracting complex morphological information from objects,which is particularly beneficial for biological imaging.Multiplexing metalenses...Combining bright-feld and edge-enhanced imaging affords an effective avenue for extracting complex morphological information from objects,which is particularly beneficial for biological imaging.Multiplexing metalenses present promising candidates for achieving this functionality.However,current multiplexing meta-lenses lack spectral modulation,and crosstalk between different wavelengths hampers the imaging quality,especilly for biological samples requiring precise wavelength specificity.Here,we experimentally demonstrate the nonlocal Huygens'meta-lens for high-quality-factor spin-multiplexing imaging.Quasi-bound states in the continuum(q-BlCs)are excited to provide a high quality factor of 90 and incident-angle dependence.The generalized Kerker condition,driven by Fano-like interactions between q-BIC and in-plane Mie resonances,breaks the radiation symmetry,resulting in a transmission peak with a geometric phase for polarization-converted light,while unconverted light exhibits a transmission dip without a geometric phase.Enhanced polarization conversion efficiency of 65%is achieved,accompanied by a minimal unconverted value,surpassing the theoretical limit of traditional thin nonlocal metasurfaces.Leveraging these effects,the output polarization-converted state exhibits an efficient wavelengthselective focusing phase profle.The unconverted counterpart serves as an effective spatial frequency filter based on incident-angular dispersion,passing high-frequency edge details.Bright-field imaging and edge detection are thus presented under two output spin states.This work provides a versatile framework for nonlocal metasurfaces,boosting biomedical imaging and sensing applications.展开更多
Aim:Therapeutic agents suppressing bone remodeling have been clinically approved to delay metastatic progression and skeletal-related events in patients with bone metastasis.However,therapeutic agents including zoledr...Aim:Therapeutic agents suppressing bone remodeling have been clinically approved to delay metastatic progression and skeletal-related events in patients with bone metastasis.However,therapeutic agents including zoledronic acid(ZA)are insufficient to regress established bone metastasis.Therefore,new treatment strategies are desired,and unraveling the status of cancer cells during bone metastatic progression will help develop therapeutic strategies.Methods:We developed a unique multiplexed reporter system for bioluminescent imaging(MRS-BLI)using three luciferase reporter genes.This system allows for the noninvasive and quantitative monitoring of tumor growth and activities of nuclear factor-kappa B(NF-κB)and hypoxia-inducible factor(HIF),which are the key transcriptional factors in response to inflammation and hypoxia,respectively.PC-3/MRS-BLI,a human prostate cancer cell line that stably retains the MRS-BLI reporter genes,was applied to the caudal-artery injection model of bone metastasis to observe the status of cancer cells during bone metastasis development and ZA treatment(<1 month).Results:MRS-BLI reveals key events during the bone metastasis development:NF-κB and HIF are activated in cancer cells after migration to the bone marrow and are transiently reduced,followed by rapid activation before proliferation begins.ZA treatment suppresses the growth of metastasized cancer cells by suppressing NF-κB and HIF activities that may be indirectly induced by osteoclast activation.Conclusion:By visualizing the NF-κB and HIF activities of PC-3/MRS-BLI in bone,MRS-BLI has enabled new discoveries regarding the regulation of bone metastases.Further analysis of the progression of bone metastases using MRS-BLI may provide important information for developing new therapeutic strategies.展开更多
Driven by the needs of precision medicine,current imaging techniques are under continuous development to offer more accurate and comprehensive information beyond traditional macroscopic anatomical images.Multispectral...Driven by the needs of precision medicine,current imaging techniques are under continuous development to offer more accurate and comprehensive information beyond traditional macroscopic anatomical images.Multispectral color-coded(multicolor)^(19)F magnetic resonance imaging(MRI)is receiving increasing attention owing to its capability for visualizing quantitative and multiplexed molecular information during various biological processes.The chemical design and preparation of^(19)F probes lie at the core of multicolor^(19)F MRI since their performance dominates the accomplishment of this technique.Herein,the working principles of multicolor^(19)F MRI are briefly introduced.Recent progress on multicolor^(19)F MRI probes for simultaneous in vivo visualization of multiple biological targets is summarized.Finally,current challenges and potential solutions in this fast-developing field are discussed.展开更多
Label-free cell classification is advantageous for supplying pristine cells for further use or examination,yet existing techniques frequently fall short in terms of specificity and speed.In this study,we address these...Label-free cell classification is advantageous for supplying pristine cells for further use or examination,yet existing techniques frequently fall short in terms of specificity and speed.In this study,we address these limitations through the development of a novel machine learning framework,Multiplex Image Machine Learning(MIML).This architecture uniquely combines label-free cell images with biomechanical property data,harnessing the vast,often underutilized biophysical information intrinsic to each cell.By integrating both types of data,our model offers a holistic understanding of cellular properties,utilizing cell biomechanical information typically discarded in traditional machine learning models.This approach has led to a remarkable 98.3%accuracy in cell classification,a substantial improvement over models that rely solely on image data.MIML has been proven effective in classifying white blood cells and tumor cells,with potential for broader application due to its inherent flexibility and transfer learning capability.It is particularly effective for cells with similar morphology but distinct biomechanical properties.This innovative approach has significant implications across various fields,from advancing disease diagnostics to understanding cellular behavior.展开更多
基金supported by the National Natural Science Foundation of China(Nos.12474418,U22A20398,and 22135008).
文摘Lanthanide(Ln^(3+))-doped luminescent nanocrystals(NCs)with excitation and emission in the second near-infrared biological window(NIRII,1000-1700 nm)have attracted considerable attention in the fields of deep-tissue bioimaging and non-invasive biodetection,owing to their superior advantages including good photochemical stability,sharp emission peaks,large penetration depth,and high signal-to-noise ratio[1].Conventionally,Yb3t-and Nd3t-sensitized NCs have been utilized as NIR-II luminescent nanoprobes for in vivo bioimaging upon excitation with 980 and 808 nm diode laser,respectively[2].
基金supported by the National Natural Science Foundation of China(No.61401475)
文摘Traditional pulse Doppler radar estimates the Doppler frequency by taking advantage of Doppler modulation over different pulses and usually it requires a few pulses to estimate the Dop- pler frequency. In this paper, a novel range-Doppler imaging algorithm based on single pulse with orthogonal frequency division multiplexing （OFDM） radar is proposed, where the OFDM pulse is composed of phase coded symbols. The Doppler frequency is estimated using one single pulse by utilizing Doppler modulation over different symbols, which remarkably increases the data update rate. Besides, it is shown that the range and Doppler estimations are completely independent and the well-known range-Doppler coupling effect does not exist. The effects of target movement on the performances of the proposed algorithm are also discussed and the results show that the algo- rithm is not sensitive to velocity. Performances of the proposed algorithm as well as comparisons with other range-Doppler algorithms are demonstrated via simulation experiments.
基金This work was supported partially by CCNE-TR at Stanford University,NIH-NCI R01 CA135109-02,and Ensysce Biosciences Inc.
文摘Single-walled carbon nanotubes(SWNTs)with five different C13/C12 isotope compositions and well-separated Raman peaks have been synthesized and conjugated to five targeting ligands in order to impart molecular specificity.Multiplexed Raman imaging of live cells has been carried out by highly specific staining of cells with a five-color mixture of SWNTs.Ex vivo multiplexed Raman imaging of tumor samples uncovers a surprising up-regulation of epidermal growth factor receptor(EGFR)on LS174T colon cancer cells from cell culture to in vivo tumor growth.This is the first time five-color multiplexed molecular imaging has been performed in the near-infrared(NIR)region under a single laser excitation.Near zero interfering background of imaging is achieved due to the sharp Raman peaks unique to nanotubes over the low,smooth autofluorescence background of biological species.
基金supported by the Science and Technology Commission of Shanghai Municipality(No.YDZX20233100004032001,China)the Strategic Priority Research Program of the Chinese Academy of Sciences(No.XDB1040000,China)+3 种基金the National Natural Science Foundation of China(Nos.32141005 and 82071976,China)the National Key Research and Development Program of China(No.2023YFA1800804)Science and Technology Innovation Key R&D Program of Chongqing(No.CSTB2023TIAD-STX0006,China)the National Science and Technology Innovation 2030 Major Project of China(No.2021ZD0203900).
文摘The precise and rapid monitoring of multiple organ dysfunction is crucial in drug discovery.Traditional methods,such as pathological analysis,are often time-consuming and inefficient.Here,we developed a multiplexed near-infrared window two(NIR-II)fluorescent bioimaging method that allows for real-time,rapid,and quantitative assessment of multiple organ dysfunctions.Given that existing probes did not fully meet requirements,we synthesized a range of NIR-II hemicyanine dyes(HDs)with varying absorption and emission wavelengths.By modifying these dyes,we achieved high spatial and temporal resolution imaging of the liver,kidneys,stomach,and intestines.This method was further applied to investigate disorders induced by cisplatin,a drug known to cause gastric emptying issues along with liver and kidney injuries.By monitoring the metabolic rate of the dyes in these organs,we accurately quantified multi-organ dysfunction,which was also confirmed by gold-standard pathological analysis.Additionally,we evaluated the effects of five aristolochic acids(AAs)on multiple organ dysfunction.For the first time,we identified that AA-I and AA-II could cause gastric emptying disorders,which was further validated through transcriptomics analysis.Our study introduces a novel approach for the simultaneous monitoring of multi-organ dysfunction,which may significantly enhance the evaluation of drug side effects.
基金supported by the National Natural Science Foundation of China(Grant Nos.12074121,12274139,and 12325408)the China Postdoctoral Science Foundation(Grant Nos.2023M743252 and 2024T170846)+1 种基金the Fundamental Research Funds for the Central Universities(Grant No.YZY24014)the Key Research and Development Program of Zhejiang Province(Grant No.2024SSYS0014).
文摘Single-shot ultrafast multidimensional optical imaging(UMOI)combines ultrahigh temporal resolution with multidimensional imaging capabilities in a snapshot,making it an essential tool for real-time detection and analysis of ultrafast scenes.However,current single-shot UMOI techniques cannot simultaneously capture the spatial-temporal-spectral complex amplitude information,hampering it from complete analyses of ultrafast scenes.To address this issue,we propose a single-shot spatial-temporal-spectral complex amplitude imaging(STS-CAI)technique using wavelength and time multiplexing.By employing precise modulation of a broadband pulse via an encoding plate in coherent diffraction imaging and spatial-temporal shearing through a wide-open-slit streak camera,dual-mode multiplexing image reconstruction of wavelength and time is achieved,which significantly enhances the efficiency of information acquisition.Experimentally,a custom-built STS-CAI apparatus precisely measures the spatiotemporal characteristics of picosecond spatiotemporally chirped and spatial vortex pulses,respectively.STS-CAI demonstrates both ultrahigh temporal resolution and robust phase sensitivity.Prospectively,this technique is valuable for spatiotemporal coupling measurements of large-aperture ultrashort pulses and offers promising applications in both fundamental research and applied sciences.
基金supported by the University Grants Committee/Research Grants Council of the Hong Kong Special Administrative Region,China[Project No.AoE/P-502/20,CRF Project:C5031-22G,GRF Project:CityU15303521,CityU11305223,CityU11300224]City University of Hong Kong[Project No.9380131 and 7005867]+3 种基金National Natural Science Foundation of China[Grant No.62375232]S.X.acknowledges financial support from National Natural Science Foundation of China(Grant Nos.62125501,and 6233000076)Fundamental Research Funds for the Central Universities(Grant No.2022FRRK030004)Shenzhen Fundamental Research Projects(Grant Nos.JCYJ20220818102218040).
文摘Combining bright-feld and edge-enhanced imaging affords an effective avenue for extracting complex morphological information from objects,which is particularly beneficial for biological imaging.Multiplexing metalenses present promising candidates for achieving this functionality.However,current multiplexing meta-lenses lack spectral modulation,and crosstalk between different wavelengths hampers the imaging quality,especilly for biological samples requiring precise wavelength specificity.Here,we experimentally demonstrate the nonlocal Huygens'meta-lens for high-quality-factor spin-multiplexing imaging.Quasi-bound states in the continuum(q-BlCs)are excited to provide a high quality factor of 90 and incident-angle dependence.The generalized Kerker condition,driven by Fano-like interactions between q-BIC and in-plane Mie resonances,breaks the radiation symmetry,resulting in a transmission peak with a geometric phase for polarization-converted light,while unconverted light exhibits a transmission dip without a geometric phase.Enhanced polarization conversion efficiency of 65%is achieved,accompanied by a minimal unconverted value,surpassing the theoretical limit of traditional thin nonlocal metasurfaces.Leveraging these effects,the output polarization-converted state exhibits an efficient wavelengthselective focusing phase profle.The unconverted counterpart serves as an effective spatial frequency filter based on incident-angular dispersion,passing high-frequency edge details.Bright-field imaging and edge detection are thus presented under two output spin states.This work provides a versatile framework for nonlocal metasurfaces,boosting biomedical imaging and sensing applications.
基金supported by a Grant-in-Aid for Scientific Research on Innovative Areas“Integrative Research on Cancer Microenvironment Networks from the Ministry of Education”,Culture,Sports,Science and Technology of Japan(S.K-K),Grant-in-Aid for Young Scientist(B)(T.Ku)and Princess Takamatsu Cancer Research Fund(T.Ku).
文摘Aim:Therapeutic agents suppressing bone remodeling have been clinically approved to delay metastatic progression and skeletal-related events in patients with bone metastasis.However,therapeutic agents including zoledronic acid(ZA)are insufficient to regress established bone metastasis.Therefore,new treatment strategies are desired,and unraveling the status of cancer cells during bone metastatic progression will help develop therapeutic strategies.Methods:We developed a unique multiplexed reporter system for bioluminescent imaging(MRS-BLI)using three luciferase reporter genes.This system allows for the noninvasive and quantitative monitoring of tumor growth and activities of nuclear factor-kappa B(NF-κB)and hypoxia-inducible factor(HIF),which are the key transcriptional factors in response to inflammation and hypoxia,respectively.PC-3/MRS-BLI,a human prostate cancer cell line that stably retains the MRS-BLI reporter genes,was applied to the caudal-artery injection model of bone metastasis to observe the status of cancer cells during bone metastasis development and ZA treatment(<1 month).Results:MRS-BLI reveals key events during the bone metastasis development:NF-κB and HIF are activated in cancer cells after migration to the bone marrow and are transiently reduced,followed by rapid activation before proliferation begins.ZA treatment suppresses the growth of metastasized cancer cells by suppressing NF-κB and HIF activities that may be indirectly induced by osteoclast activation.Conclusion:By visualizing the NF-κB and HIF activities of PC-3/MRS-BLI in bone,MRS-BLI has enabled new discoveries regarding the regulation of bone metastases.Further analysis of the progression of bone metastases using MRS-BLI may provide important information for developing new therapeutic strategies.
基金The authors thank the financial support from the National Natural Science Foundation of China(22125702,22077107,and 92059109)the Natural Science Foundation of Fujian Province of China(2020J02001)the Youth Innovation Funding Program of Xiamen City(3502Z20206051).
文摘Driven by the needs of precision medicine,current imaging techniques are under continuous development to offer more accurate and comprehensive information beyond traditional macroscopic anatomical images.Multispectral color-coded(multicolor)^(19)F magnetic resonance imaging(MRI)is receiving increasing attention owing to its capability for visualizing quantitative and multiplexed molecular information during various biological processes.The chemical design and preparation of^(19)F probes lie at the core of multicolor^(19)F MRI since their performance dominates the accomplishment of this technique.Herein,the working principles of multicolor^(19)F MRI are briefly introduced.Recent progress on multicolor^(19)F MRI probes for simultaneous in vivo visualization of multiple biological targets is summarized.Finally,current challenges and potential solutions in this fast-developing field are discussed.
文摘Label-free cell classification is advantageous for supplying pristine cells for further use or examination,yet existing techniques frequently fall short in terms of specificity and speed.In this study,we address these limitations through the development of a novel machine learning framework,Multiplex Image Machine Learning(MIML).This architecture uniquely combines label-free cell images with biomechanical property data,harnessing the vast,often underutilized biophysical information intrinsic to each cell.By integrating both types of data,our model offers a holistic understanding of cellular properties,utilizing cell biomechanical information typically discarded in traditional machine learning models.This approach has led to a remarkable 98.3%accuracy in cell classification,a substantial improvement over models that rely solely on image data.MIML has been proven effective in classifying white blood cells and tumor cells,with potential for broader application due to its inherent flexibility and transfer learning capability.It is particularly effective for cells with similar morphology but distinct biomechanical properties.This innovative approach has significant implications across various fields,from advancing disease diagnostics to understanding cellular behavior.
