Cemented paste backfill(CPB)is a technology that achieves safe mining by filling the goaf with waste rocks,tailings,and other materials.It is an inevitable choice to deal with the development of deep and highly diffic...Cemented paste backfill(CPB)is a technology that achieves safe mining by filling the goaf with waste rocks,tailings,and other materials.It is an inevitable choice to deal with the development of deep and highly difficult mines and meet the requirements of environmental protection and safety regulations.It promotes the development of a circular economy in mines through the development of lowgrade resources and the resource utilization of waste,and extends the service life of mines.The mass concentration of solid content(abbreviated as“concentration”)is a critical parameter for CPB.However,discrepancies often arise between the on-site measurements and the pre-designed values due to factors such as groundwater inflow and segregation within the goaf,which cannot be evaluated after the solidification of CPB.This paper innovatively provides an in-situ non-destructive approach to identify the real concentration of CPB after curing for certain days using hyperspectral imaging(HSI)technology.Initially,the spectral variation patterns under different concentration conditions were investigated through hyperspectral scanning experiments on CPB samples.The results demonstrate that as the CPB concentration increases from 61wt%to 73wt%,the overall spectral reflectance gradually increases,with two distinct absorption peaks observed at 1407 and 1917 nm.Notably,the reflectance at 1407 nm exhibited a strong linear relationship with the concentration.Subsequently,the K-nearest neighbors(KNN)and support vector machine(SVM)algorithms were employed to classify and identify different concentrations.The study revealed that,with the KNN algorithm,the highest accuracy was achieved when K(number of nearest neighbors)was 1,although this resulted in overfitting.When K=3,the model displayed the optimal balance between accuracy and stability,with an accuracy of 95.03%.In the SVM algorithm,the highest accuracy of 98.24%was attained with parameters C(regularization parameter)=200 and Gamma(kernel coefficient)=10.A comparative analysis of precision,accuracy,and recall further highlighted that the SVM provided superior stability and precision for identifying CPB concentration.Thus,HSI technology offers an effective solution for the in-situ,non-destructive monitoring of CPB concentration,presenting a promising approach for optimizing and controlling CPB characteristic parameters.展开更多
We present a prototype for hybrid Compton and positron emission tomography(PET)imaging aimed at enhancing data utilization and enabling concurrent imaging of multiple radiopharmaceuticals.The prototype comprises two d...We present a prototype for hybrid Compton and positron emission tomography(PET)imaging aimed at enhancing data utilization and enabling concurrent imaging of multiple radiopharmaceuticals.The prototype comprises two detectors that utilize LYSO-SiPM and were available in our laboratory.One detector consists of a 50×50 array of LYSO crystals,each measuring 0.9mm×0.9mm×10mm with 1 mm pitches,whereas the other detector comprises a 25×25 array of LYSO crystals,each measuring 1.9mm×1.9mm×10mm with 2 mm pitches.These detectors are mounted on a rotational stage,which enables them to function as either a Compton camera or a PET detector pair.The 64-channel signals from the SiPMs of each detector are processed through a capacitive multiplexing circuit to yield four position-weighted outputs.Distinct energy windows were used to discriminate Compton events from PET events.Energy resolution and energy-channel relationships were calibrated via multiple sources.The measured average energy resolutions(full widths at half maximum,FWHMs)for the detectors at 511 keV were 17.5%and 15.2%,respectively.The initial experimental results indicate an angular resolution(FWHM)of 8.6◦for the system in Compton imaging mode.A V-shaped tube injected with 18 F solution was clearly reconstructed,which further verified the imaging capabilities of the system in Compton imaging mode.The results of simulation and experimental imaging studies show that the system can detect tumors as small as 1 mm in diameter when working in PET imaging mode.Mouse bone PET imaging was successfully conducted,with the results matching well with the corresponding CT images.This technology holds great potential for advancing the development of physiological function modalities.展开更多
Aqueous zinc metal batteries(AZMBs)face significant challenges in achieving reversibility and cycling stability,primarily due to hydrogen evolution reactions(HER)and zinc dendrite growth.In this study,by employing car...Aqueous zinc metal batteries(AZMBs)face significant challenges in achieving reversibility and cycling stability,primarily due to hydrogen evolution reactions(HER)and zinc dendrite growth.In this study,by employing carefully designed cells that approximate the structural characteristics of practical batteries,we revisit this widely held view through in-operando X-ray radiography to examine zinc dendrite formation and HER under nearpractical operating conditions.While conventional understanding emphasizes the severity of these processes,our findings suggest that zinc dendrites and HER are noticeably less pronounced in dense,real-operation configurations compared to modified cells,possibly due to a more uniform electric field and the suppression of triple-phase boundaries.This study indicates that other components,such as degradation at the cathode current collector interface and configuration mismatches within the full cell,may also represent important barriers to the practical application of AZMBs,particularly during the early stages of electrodeposition.展开更多
Synaptic pruning is a crucial process in synaptic refinement,eliminating unstable synaptic connections in neural circuits.This process is triggered and regulated primarily by spontaneous neural activity and experience...Synaptic pruning is a crucial process in synaptic refinement,eliminating unstable synaptic connections in neural circuits.This process is triggered and regulated primarily by spontaneous neural activity and experience-dependent mechanisms.The pruning process involves multiple molecular signals and a series of regulatory activities governing the“eat me”and“don't eat me”states.Under physiological conditions,the interaction between glial cells and neurons results in the clearance of unnecessary synapses,maintaining normal neural circuit functionality via synaptic pruning.Alterations in genetic and environmental factors can lead to imbalanced synaptic pruning,thus promoting the occurrence and development of autism spectrum disorder,schizophrenia,Alzheimer's disease,and other neurological disorders.In this review,we investigated the molecular mechanisms responsible for synaptic pruning during neural development.We focus on how synaptic pruning can regulate neural circuits and its association with neurological disorders.Furthermore,we discuss the application of emerging optical and imaging technologies to observe synaptic structure and function,as well as their potential for clinical translation.Our aim was to enhance our understanding of synaptic pruning during neural development,including the molecular basis underlying the regulation of synaptic function and the dynamic changes in synaptic density,and to investigate the potential role of these mechanisms in the pathophysiology of neurological diseases,thus providing a theoretical foundation for the treatment of neurological disorders.展开更多
Mesenchymal stromal cell transplantation is an effective and promising approach for treating various systemic and diffuse diseases.However,the biological characteristics of transplanted mesenchymal stromal cells in hu...Mesenchymal stromal cell transplantation is an effective and promising approach for treating various systemic and diffuse diseases.However,the biological characteristics of transplanted mesenchymal stromal cells in humans remain unclear,including cell viability,distribution,migration,and fate.Conventional cell tracing methods cannot be used in the clinic.The use of superparamagnetic iron oxide nanoparticles as contrast agents allows for the observation of transplanted cells using magnetic resonance imaging.In 2016,the National Medical Products Administration of China approved a new superparamagnetic iron oxide nanoparticle,Ruicun,for use as a contrast agent in clinical trials.In the present study,an acute hemi-transection spinal cord injury model was established in beagle dogs.The injury was then treated by transplantation of Ruicun-labeled mesenchymal stromal cells.The results indicated that Ruicunlabeled mesenchymal stromal cells repaired damaged spinal cord fibers and partially restored neurological function in animals with acute spinal cord injury.T2*-weighted imaging revealed low signal areas on both sides of the injured spinal cord.The results of quantitative susceptibility mapping with ultrashort echo time sequences indicated that Ruicun-labeled mesenchymal stromal cells persisted stably within the injured spinal cord for over 4 weeks.These findings suggest that magnetic resonance imaging has the potential to effectively track the migration of Ruicun-labeled mesenchymal stromal cells and assess their ability to repair spinal cord injury.展开更多
Freezing of gait is a significant and debilitating motor symptom often observed in individuals with Parkinson's disease.Resting-state functional magnetic resonance imaging,along with its multi-level feature indice...Freezing of gait is a significant and debilitating motor symptom often observed in individuals with Parkinson's disease.Resting-state functional magnetic resonance imaging,along with its multi-level feature indices,has provided a fresh perspective and valuable insight into the study of freezing of gait in Parkinson's disease.It has been revealed that Parkinson's disease is accompanied by widespread irregularities in inherent brain network activity.However,the effective integration of the multi-level indices of resting-state functional magnetic resonance imaging into clinical settings for the diagnosis of freezing of gait in Parkinson's disease remains a challenge.Although previous studies have demonstrated that radiomics can extract optimal features as biomarkers to identify or predict diseases,a knowledge gap still exists in the field of freezing of gait in Parkinson's disease.This cross-sectional study aimed to evaluate the ability of radiomics features based on multi-level indices of resting-state functional magnetic resonance imaging,along with clinical features,to distinguish between Parkinson's disease patients with and without freezing of gait.We recruited 28 patients with Parkinson's disease who had freezing of gait(15 men and 13 women,average age 63 years)and 30 patients with Parkinson's disease who had no freezing of gait(16 men and 14 women,average age 64 years).Magnetic resonance imaging scans were obtained using a 3.0T scanner to extract the mean amplitude of low-frequency fluctuations,mean regional homogeneity,and degree centrality.Neurological and clinical characteristics were also evaluated.We used the least absolute shrinkage and selection operator algorithm to extract features and established feedforward neural network models based solely on resting-state functional magnetic resonance imaging indicators.We then performed predictive analysis of three distinct groups based on resting-state functional magnetic resonance imaging indicators indicators combined with clinical features.Subsequently,we conducted 100 additional five-fold cross-validations to determine the most effective model for each classification task and evaluated the performance of the model using the area under the receiver operating characteristic curve.The results showed that when differentiating patients with Parkinson's disease who had freezing of gait from those who did not have freezing of gait,or from healthy controls,the models using only the mean regional homogeneity values achieved the highest area under the receiver operating characteristic curve values of 0.750(with an accuracy of 70.9%)and 0.759(with an accuracy of 65.3%),respectively.When classifying patients with Parkinson's disease who had freezing of gait from those who had no freezing of gait,the model using the mean amplitude of low-frequency fluctuation values combined with two clinical features achieved the highest area under the receiver operating characteristic curve of 0.847(with an accuracy of 74.3%).The most significant features for patients with Parkinson's disease who had freezing of gait were amplitude of low-frequency fluctuation alterations in the left parahippocampal gyrus and two clinical characteristics:Montreal Cognitive Assessment and Hamilton Depression Scale scores.Our findings suggest that radiomics features derived from resting-state functional magnetic resonance imaging indices and clinical information can serve as valuable indices for the identification of freezing of gait in Parkinson's disease.展开更多
Over the past decade,a growing number of studies have reported transcription factor-based in situ reprogramming that can directly conve rt endogenous glial cells into functional neurons as an alternative approach for ...Over the past decade,a growing number of studies have reported transcription factor-based in situ reprogramming that can directly conve rt endogenous glial cells into functional neurons as an alternative approach for n euro regeneration in the adult mammalian central ne rvous system.Howeve r,many questions remain regarding how a terminally differentiated glial cell can transform into a delicate neuron that forms part of the intricate brain circuitry.In addition,concerns have recently been raised around the absence of astrocyte-to-neuron conversion in astrocytic lineage-tra cing mice.In this study,we employed repetitive two-photon imaging to continuously capture the in situ astrocyte-to-neuron conversion process following ecto pic expression of the neural transcription factor NeuroD1 in both prolife rating reactive astrocytes and lineage-tra ced astrocytes in the mouse cortex.Time-lapse imaging over several wee ks revealed the ste p-by-step transition from a typical astrocyte with numero us short,tapered branches to a typical neuro n with a few long neurites and dynamic growth cones that actively explored the local environment.In addition,these lineage-converting cells were able to migrate ra dially or to ngentially to relocate to suitable positions.Furthermore,two-photon Ca2+imaging and patch-clamp recordings confirmed that the newly generated neuro ns exhibited synchronous calcium signals,repetitive action potentials,and spontaneous synaptic responses,suggesting that they had made functional synaptic connections within local neural circuits.In conclusion,we directly visualized the step-by-step lineage conversion process from astrocytes to functional neurons in vivo and unambiguously demonstrated that adult mammalian brains are highly plastic with respect to their potential for neuro regeneration and neural circuit reconstruction.展开更多
Herein,a reversible pH fluorescent sensor was developed using caffeic acid as the precursor by one-step solvothermal synthesis method.The carbon dots-based sensor(CA-CDs)exhibited pH-dependent increase in fluorescence...Herein,a reversible pH fluorescent sensor was developed using caffeic acid as the precursor by one-step solvothermal synthesis method.The carbon dots-based sensor(CA-CDs)exhibited pH-dependent increase in fluorescence intensity and showed linear relationship in the range of pH 6.60 and 8.00.Notably,the fluorescence sensor has a reversible response to pH change.Finally,the CA-CDs has been successfully applied for two-photon imaging of the pH in liver and kidney of diabetic mice.Imaging results showed that the pH value in kidney of diabetic mice was lower than that of the normal mice,while the pH value in liver of diabetic mice was almost the same as that of the normal mice.The present study provides a simple analytical method for pH detection suitable for in vivo.展开更多
Applying the fluorescent carbon dots as smart materials in anticancer therapy is of great interest.However,carbon dots for multimodal synergistic anticancer therapy,especially for the triple modality,is rarely reporte...Applying the fluorescent carbon dots as smart materials in anticancer therapy is of great interest.However,carbon dots for multimodal synergistic anticancer therapy,especially for the triple modality,is rarely reported.Herein,we successfully synthesized OCDs by citric acid and(1R,2S)-2-amino-1,2-diphenylethan-1-ol,which show aggregation-induced emission property and two-photon fluorescence imaging.Meanwhile,OCDs are ideal photosensitizers for photothermal therapy under 808 nm and TypeⅠphotodynamic therapy with white light.Hydroxyl radicals,generated by TypeⅠphotodynamic therapy based on OCDs can transform protumoral M2 macrophages into antitumoral M1 macrophages,which exhibited immunotherapy ability.The synergism trimodal of OCDs results in potent anticancer efficacy,showing great potential in cancer therapy.展开更多
The wavelength dependence of photoelectron angular distributions （PADs） of two-photon detachment of Cu^- has been directly studied by using the photoelectron map imaging. Results show that for the laser field intens...The wavelength dependence of photoelectron angular distributions （PADs） of two-photon detachment of Cu^- has been directly studied by using the photoelectron map imaging. Results show that for the laser field intensity of 6.0×10^10W/cm^2, PADs exhibit dramatic change with the external field wavelength. Comparison between the experimental observation and the lowest-order perturbation theory prediction indicates that the pattern of PADs can be explained by the interference of the s and d partial waves in the final state. Relative contri- butions of s and d partial waves in the two-photon detachment at different laser wavelengths are obtained.展开更多
Near-infrared(NIR) nanoparticles(NPs) based on fluorescence resonance energy transfer(FRET) were prepared by coencapsulation of a red aggregation-induced emission(AIE) molecule, 2-(4-bromophenyl)-3-(4-(4-(diphenylamin...Near-infrared(NIR) nanoparticles(NPs) based on fluorescence resonance energy transfer(FRET) were prepared by coencapsulation of a red aggregation-induced emission(AIE) molecule, 2-(4-bromophenyl)-3-(4-(4-(diphenylamino)styryl)phenyl)fumaronitrile(TB), and a commercial NIR fluorescence dye, silicon 2,3-naphthalocyanine bis(trihexylsilyloxide)(NIR775) with an amphiphilic polymer poly(styrene-co-maleic anhydride)(PSMA). The surface of the NPs, PSMA@TB/NIR775, was modified with poly(ethylene glycol)(PEG) to increase the in vivo biocompatibility of the NPs. The PSMA@TB/NIR775 NPs showed a strong NIR(780 nm) narrow emission and excellent two-photon absorption property. Moreover, the NPs exhibited good monodispersity, stability, and low cytotoxicity.Under the excitation of a 1040 nm femtosecond(fs) laser, the emission peaks at 680 nm of TB and 780 nm of NIR775 excited by FRET were obtained. We utilized PSMA@TB/NIR775 NPs as fluorescent contrast agents for two-photon excited NIR microscopic imaging, and good NIR imaging effect of mouse brain vasculature was obtained with the imaging depth of about 150 μm. The FRET strategy by coencapsulating AIE molecule and NIR dye will be helpful in preparing more narrow emission NIR probes for deep-tissue biological imaging.展开更多
Apoptosis is very important for the maintenance of cellular homeostasis and is closely related to the occurrence and treatment of many diseases.Mitochondria in cells play a crucial role in programmed cell death and re...Apoptosis is very important for the maintenance of cellular homeostasis and is closely related to the occurrence and treatment of many diseases.Mitochondria in cells play a crucial role in programmed cell death and redox processes.Nicotinamide adenine dinucleotide(NAD(P)H)is the primary producer of energy in mitochondria,changing NAD(P)H can directly reflect the physiological state of mitochondria.Therefore,NAD(P)H can be used to evaluate metabolic response.In this paper,we propose a noninvasive detection method that uses two-photon fluorescence lifetime imaging microscopy(TP-FLIM)to characterize apoptosis by observing the binding kinetics of cellular endogenous NAD(P)H.The result shows that the average fluorescence lifetime of NAD(P)H and the fluorescence lifetime of protein-bound NAD(P)H will be affected by the changing pH,serum content,and oxygen concentration in the cell culture environment,and by the treatment with reagents such as H2O2 and paclitaxel.Taxol(PTX).This noninvasive detection method realized the dynamic detection of cellular endogenous substances and the assessment of apoptosis.展开更多
PAHPN. a naphthalimide-based mitotracker with reasonable two-photon excitation emission activity and polarity-sensitive fluorescence properties has been efficiently synthesized and studied in twophoton, co-localizatio...PAHPN. a naphthalimide-based mitotracker with reasonable two-photon excitation emission activity and polarity-sensitive fluorescence properties has been efficiently synthesized and studied in twophoton, co-localization, and FLIM imaging.展开更多
The application of fluorescent probes for in vivo retinal imaging is of great importance,which could provide direct and crucial imaging evidence for a better understanding of common eye diseases.Herein,a group of brig...The application of fluorescent probes for in vivo retinal imaging is of great importance,which could provide direct and crucial imaging evidence for a better understanding of common eye diseases.Herein,a group of bright organic luminogens with typical electron-donating(D)and electron-accepting(A)structures(abbreviated as LDs-BDM,LDs-BTM,and LDs-BHM)was synthesized through a simple single-step reaction.They were found to be efficient solid-state emitters with high fluorescence quantum yields of above 70%(e.g.,83.7%for LDs-BTM).Their light-emission properties could be tuned by the modulation ofπ-conjugation effect with methoxy groups at different substituent positions.Their resulting fluorescent nanoparticles(NPs)were demonstrated as specific lipid droplets(LDs)targeting probes with high brightness,good biocompatibility,and satisfactory photostability.LDs-BTM NPs with a large two-photon absorption cross section(σ2=249 GM)were further utilized as ultrabright two-photon fluorescence(2PF)nanoprobes for in vivo retina imaging of live zebrafish by NIR excitation at an ultralow concentration(0.5μmol/L).Integrated histological structures at the tissue level and corresponding fine details at the cellular level of the embryonic retina of live zebrafish were clearly demonstrated.This is the first report of using ultrabright LDs-targeting nanoprobes to accurately measure fine details in the retina with 2PF microscopic technique.These good results are anticipated to open up a new avenue in the development of efficient 2PF emitters for non-invasive bioimaging of living animals.展开更多
Direct,in situ selective detection of intracellular formaldehyde(FA)is of great significance for understanding its function in FA-related diseases.Herein,red carbon dots(RCD)are reported as label-free two-photon fluor...Direct,in situ selective detection of intracellular formaldehyde(FA)is of great significance for understanding its function in FA-related diseases.Herein,red carbon dots(RCD)are reported as label-free two-photon fluorescent nanoprobes for detecting and imaging of FA.Upon addition of FA,the-NH2 groups of RCD could quickly and specially react with aldehydes to form Schiff base and then the strong fluorescence of RCD with blue-shift emission is recovery due to the destruction of the hydrogen bond interaction between RCD and water.In addition,the nanoprobes exhibit outsta nding photo stability,rapid response(<1 min),high sensitivity(~9.9μmol/L)and excellent selectivity toward FA over other aldehyde group compounds.Notably,owing to the good cell-membrane permeability and biocompatibility,as well as the large two-photon absorption cross-section,the as-prepared RCD can be used as label-free nanoprobes for selectively detecting and imaging FA in living cells and zebrafishes through one-photon and two-photon excitation.Moreover,RCD could stain the tissue of zebrafishes at depths interval of up to 240μm under two-photon excitation.This research implied that RCD are promising tools for directly and in situ imaging FA in vivo,thus providing critical insights into FA-related pathophysiological processes.展开更多
Alzheimer's disease(AD)is a neurodegenerative disease characterized by a progressive decline in cognitive functions.Given that AD undermines the quality of life for millions and has an extended asymptomatic period...Alzheimer's disease(AD)is a neurodegenerative disease characterized by a progressive decline in cognitive functions.Given that AD undermines the quality of life for millions and has an extended asymptomatic period,exploring the full AD pathogenesis and seeking the optimal therapeutic solution have become critical and imperative.This allows researchers to intervene,delay,and potentially prevent AD progression.Several clinical imaging methods are utilized routinely to diagnose and monitor AD,such as magnetic resonance imaging(MRI),functional magnetic resonance imaging(fMRI),positron emission tomography(PET),and single photon emission computed tomography(SPECT).Nevertheless,due to their intrinsic drawbacks and restrictions,such as radiation concerns,high cost,long acquisition time,and low spatial resolution,their applications in AD research are limited,especially at the cellular and molecular levels.In contrast,optical microscopic imaging methods overcome these limitations,offering researchers a variety of approaches with distinct advantages to explore AD pathology on diverse models.In this review,we provide a comprehensive overview of commonly utilized optical microscopic imaging techniques in AD research and introduce their contributions to image amyloid beta(Aβ)species.These techniques include fluorescence microscopy(FM),confocal microscopy(CM),two-photon fluorescence microscopy(TPFM),super-resolution microscopy(SRM),expansion microscopy(ExM),and light-sheet fluorescence microscopy(LSFM).In addition,we introduce some related topics,such as the development of near-infrared(NIR)Aβprobes,the Aβplaque hypothesis,and Aβoligomer hypothesis,and the roles of microglia and astrocytes in AD progression.We believe optical microscopic imaging methods continue to play an indispensable role in deciphering the full pathogenesis of AD and advancing therapeutic strategies.展开更多
A two-photon fluorescent probe TPZn was developed for specific ratiometric imaging Zn2＋ in living cells and tissues. Significant ratiometric fluorescence change was based on photoinduced electron transfer and intramo...A two-photon fluorescent probe TPZn was developed for specific ratiometric imaging Zn2＋ in living cells and tissues. Significant ratiometric fluorescence change was based on photoinduced electron transfer and intramolecular charge transfer. The synthetic method of TPZn was simple. It was successfully used to selectively image Zn2＋ based on the higher binding affinity for Zn2＋ than for Cd2＋. TPZn was easily loaded into the living cell and tissues with high membrane permeability in a complex biological environment. TPZn could clearly visualize endogenous Zn2＋ by TP ratiometric imaging in hippocampal slices at a depth of 120 μm. Thus, TPZn is a useful tool to image of Zn2＋ in living cells and tissues without interference from Cd2＋.展开更多
Optical imaging systems have greatly extended human visual capabilities,enabling the observation and understanding of diverse phenomena.Imaging technologies span a broad spectrum of wavelengths from x-ray to radio fre...Optical imaging systems have greatly extended human visual capabilities,enabling the observation and understanding of diverse phenomena.Imaging technologies span a broad spectrum of wavelengths from x-ray to radio frequencies and impact research activities and our daily lives.Traditional glass lenses are fabricated through a series of complex processes,while polymers offer versatility and ease of production.However,modern applications often require complex lens assemblies,driving the need for miniaturization and advanced designs with micro-and nanoscale features to surpass the capabilities of traditional fabrication methods.Three-dimensional(3D)printing,or additive manufacturing,presents a solution to these challenges with benefits of rapid prototyping,customized geometries,and efficient production,particularly suited for miniaturized optical imaging devices.Various 3D printing methods have demonstrated advantages over traditional counterparts,yet challenges remain in achieving nanoscale resolutions.Two-photon polymerization lithography(TPL),a nanoscale 3D printing technique,enables the fabrication of intricate structures beyond the optical diffraction limit via the nonlinear process of two-photon absorption within liquid resin.It offers unprecedented abilities,e.g.alignment-free fabrication,micro-and nanoscale capabilities,and rapid prototyping of almost arbitrary complex 3D nanostructures.In this review,we emphasize the importance of the criteria for optical performance evaluation of imaging devices,discuss material properties relevant to TPL,fabrication techniques,and highlight the application of TPL in optical imaging.As the first panoramic review on this topic,it will equip researchers with foundational knowledge and recent advancements of TPL for imaging optics,promoting a deeper understanding of the field.By leveraging on its high-resolution capability,extensive material range,and true 3D processing,alongside advances in materials,fabrication,and design,we envisage disruptive solutions to current challenges and a promising incorporation of TPL in future optical imaging applications.展开更多
A new two-photon fluorescent probe, ADNO, for nitric oxide （NO） based on intramolecular photoinduced electron transfer （PET） mechanism d/splays a rapid response to NO with a remarkable fluorescent enhancement in P...A new two-photon fluorescent probe, ADNO, for nitric oxide （NO） based on intramolecular photoinduced electron transfer （PET） mechanism d/splays a rapid response to NO with a remarkable fluorescent enhancement in PBS buffer. The excellent chemoselectivity of ADNO for NO over other ROS/RNS （reactive oxygen species or nitrogen species） and common metal ions was observed. Moreover, ADNO has been successfully applied in fluorescence imaging of NO of living cells using both one-photon microscopy （OPM） and two-~hoton microscopy （TPM）,展开更多
Monitoring neuronal activity in vivo is critical to understanding the physiological or pathological functions of the brain.Two-photon Ca^(2+)imaging in vivo using a cranial window and specific neuronal labeling enable...Monitoring neuronal activity in vivo is critical to understanding the physiological or pathological functions of the brain.Two-photon Ca^(2+)imaging in vivo using a cranial window and specific neuronal labeling enables realtime,in situ,and long-term imaging of the living brain.Here,we constructed a recombinant rabies virus containing the Ca^(2+)indicator GCaMP6 s along with the fluorescent protein DsRed2 as a baseline reference to ensure GCaMP6 s signal reliability.This functional tracer was applied to retrogradely label specific V1-thalamus circuits and detect spontaneous Ca^(2+)activity in the dendrites of V1 corticothalamic neurons by in vivo two-photon Ca^(2+)imaging.Notably,we were able to record single-spine spontaneous Ca2+activity in specific circuits.Distinct spontaneous Ca^(2+)dynamics in dendrites of V1 corticothalamic neurons were found for different V1-thalamus circuits.Our method can be applied to monitor Ca^(2+)dynamics in specific input circuits in vivo,and contribute to functional studies of defined neural circuits and the dissection of functional circuit connections.展开更多
基金funded by the National Natural Science Foundation of China(Nos.52474165 and 52522404)。
文摘Cemented paste backfill(CPB)is a technology that achieves safe mining by filling the goaf with waste rocks,tailings,and other materials.It is an inevitable choice to deal with the development of deep and highly difficult mines and meet the requirements of environmental protection and safety regulations.It promotes the development of a circular economy in mines through the development of lowgrade resources and the resource utilization of waste,and extends the service life of mines.The mass concentration of solid content(abbreviated as“concentration”)is a critical parameter for CPB.However,discrepancies often arise between the on-site measurements and the pre-designed values due to factors such as groundwater inflow and segregation within the goaf,which cannot be evaluated after the solidification of CPB.This paper innovatively provides an in-situ non-destructive approach to identify the real concentration of CPB after curing for certain days using hyperspectral imaging(HSI)technology.Initially,the spectral variation patterns under different concentration conditions were investigated through hyperspectral scanning experiments on CPB samples.The results demonstrate that as the CPB concentration increases from 61wt%to 73wt%,the overall spectral reflectance gradually increases,with two distinct absorption peaks observed at 1407 and 1917 nm.Notably,the reflectance at 1407 nm exhibited a strong linear relationship with the concentration.Subsequently,the K-nearest neighbors(KNN)and support vector machine(SVM)algorithms were employed to classify and identify different concentrations.The study revealed that,with the KNN algorithm,the highest accuracy was achieved when K(number of nearest neighbors)was 1,although this resulted in overfitting.When K=3,the model displayed the optimal balance between accuracy and stability,with an accuracy of 95.03%.In the SVM algorithm,the highest accuracy of 98.24%was attained with parameters C(regularization parameter)=200 and Gamma(kernel coefficient)=10.A comparative analysis of precision,accuracy,and recall further highlighted that the SVM provided superior stability and precision for identifying CPB concentration.Thus,HSI technology offers an effective solution for the in-situ,non-destructive monitoring of CPB concentration,presenting a promising approach for optimizing and controlling CPB characteristic parameters.
基金supported by the National Natural Science Foundation of China(No.12105018)the Beijing Nova Program(Nos.Z211100002121129 and 20230484413)the Beijing Normal University Start-up Grant(No.312232104).
文摘We present a prototype for hybrid Compton and positron emission tomography(PET)imaging aimed at enhancing data utilization and enabling concurrent imaging of multiple radiopharmaceuticals.The prototype comprises two detectors that utilize LYSO-SiPM and were available in our laboratory.One detector consists of a 50×50 array of LYSO crystals,each measuring 0.9mm×0.9mm×10mm with 1 mm pitches,whereas the other detector comprises a 25×25 array of LYSO crystals,each measuring 1.9mm×1.9mm×10mm with 2 mm pitches.These detectors are mounted on a rotational stage,which enables them to function as either a Compton camera or a PET detector pair.The 64-channel signals from the SiPMs of each detector are processed through a capacitive multiplexing circuit to yield four position-weighted outputs.Distinct energy windows were used to discriminate Compton events from PET events.Energy resolution and energy-channel relationships were calibrated via multiple sources.The measured average energy resolutions(full widths at half maximum,FWHMs)for the detectors at 511 keV were 17.5%and 15.2%,respectively.The initial experimental results indicate an angular resolution(FWHM)of 8.6◦for the system in Compton imaging mode.A V-shaped tube injected with 18 F solution was clearly reconstructed,which further verified the imaging capabilities of the system in Compton imaging mode.The results of simulation and experimental imaging studies show that the system can detect tumors as small as 1 mm in diameter when working in PET imaging mode.Mouse bone PET imaging was successfully conducted,with the results matching well with the corresponding CT images.This technology holds great potential for advancing the development of physiological function modalities.
基金the fundamental Research Funds for the central Universities(x2wjD2240360)for the funding supportMeanwhile,Engineering and Physical Sciences Research Council(EPSRC,EP/V027433/3)+2 种基金UK Research and Innovation(UKRI)under the UK government’s Horizon Europe funding(101077226,EP/Y008707/1)Faraday Institution(EP/S003053/1)Degradation project(FIRG001),Royal Society(IEC\NSFC\233361),QUB Agility Fund and Wright Technology and Research Centre(W-Tech,R5240MEE)Funding from UK aid from the UK Government through the Faraday Institution and the Transforming Energy Access Programme(Grant number FIRG050-Device engineering of Zn-based hybrid micro-flow batteries and by-product H2 collection for Emerging Economies)。
文摘Aqueous zinc metal batteries(AZMBs)face significant challenges in achieving reversibility and cycling stability,primarily due to hydrogen evolution reactions(HER)and zinc dendrite growth.In this study,by employing carefully designed cells that approximate the structural characteristics of practical batteries,we revisit this widely held view through in-operando X-ray radiography to examine zinc dendrite formation and HER under nearpractical operating conditions.While conventional understanding emphasizes the severity of these processes,our findings suggest that zinc dendrites and HER are noticeably less pronounced in dense,real-operation configurations compared to modified cells,possibly due to a more uniform electric field and the suppression of triple-phase boundaries.This study indicates that other components,such as degradation at the cathode current collector interface and configuration mismatches within the full cell,may also represent important barriers to the practical application of AZMBs,particularly during the early stages of electrodeposition.
基金supported by the National Natural Science Foundation of China,No.31760290,82160688the Key Development Areas Project of Ganzhou Science and Technology,No.2022B-SF9554(all to XL)。
文摘Synaptic pruning is a crucial process in synaptic refinement,eliminating unstable synaptic connections in neural circuits.This process is triggered and regulated primarily by spontaneous neural activity and experience-dependent mechanisms.The pruning process involves multiple molecular signals and a series of regulatory activities governing the“eat me”and“don't eat me”states.Under physiological conditions,the interaction between glial cells and neurons results in the clearance of unnecessary synapses,maintaining normal neural circuit functionality via synaptic pruning.Alterations in genetic and environmental factors can lead to imbalanced synaptic pruning,thus promoting the occurrence and development of autism spectrum disorder,schizophrenia,Alzheimer's disease,and other neurological disorders.In this review,we investigated the molecular mechanisms responsible for synaptic pruning during neural development.We focus on how synaptic pruning can regulate neural circuits and its association with neurological disorders.Furthermore,we discuss the application of emerging optical and imaging technologies to observe synaptic structure and function,as well as their potential for clinical translation.Our aim was to enhance our understanding of synaptic pruning during neural development,including the molecular basis underlying the regulation of synaptic function and the dynamic changes in synaptic density,and to investigate the potential role of these mechanisms in the pathophysiology of neurological diseases,thus providing a theoretical foundation for the treatment of neurological disorders.
基金supported by the National Key R&D Program of China,Nos.2017YFA0104302(to NG and XM)and 2017YFA0104304(to BW and ZZ)
文摘Mesenchymal stromal cell transplantation is an effective and promising approach for treating various systemic and diffuse diseases.However,the biological characteristics of transplanted mesenchymal stromal cells in humans remain unclear,including cell viability,distribution,migration,and fate.Conventional cell tracing methods cannot be used in the clinic.The use of superparamagnetic iron oxide nanoparticles as contrast agents allows for the observation of transplanted cells using magnetic resonance imaging.In 2016,the National Medical Products Administration of China approved a new superparamagnetic iron oxide nanoparticle,Ruicun,for use as a contrast agent in clinical trials.In the present study,an acute hemi-transection spinal cord injury model was established in beagle dogs.The injury was then treated by transplantation of Ruicun-labeled mesenchymal stromal cells.The results indicated that Ruicunlabeled mesenchymal stromal cells repaired damaged spinal cord fibers and partially restored neurological function in animals with acute spinal cord injury.T2*-weighted imaging revealed low signal areas on both sides of the injured spinal cord.The results of quantitative susceptibility mapping with ultrashort echo time sequences indicated that Ruicun-labeled mesenchymal stromal cells persisted stably within the injured spinal cord for over 4 weeks.These findings suggest that magnetic resonance imaging has the potential to effectively track the migration of Ruicun-labeled mesenchymal stromal cells and assess their ability to repair spinal cord injury.
基金supported by the National Natural Science Foundation of China,No.82071909(to GF)the Natural Science Foundation of Liaoning Province,No.2023-MS-07(to HL)。
文摘Freezing of gait is a significant and debilitating motor symptom often observed in individuals with Parkinson's disease.Resting-state functional magnetic resonance imaging,along with its multi-level feature indices,has provided a fresh perspective and valuable insight into the study of freezing of gait in Parkinson's disease.It has been revealed that Parkinson's disease is accompanied by widespread irregularities in inherent brain network activity.However,the effective integration of the multi-level indices of resting-state functional magnetic resonance imaging into clinical settings for the diagnosis of freezing of gait in Parkinson's disease remains a challenge.Although previous studies have demonstrated that radiomics can extract optimal features as biomarkers to identify or predict diseases,a knowledge gap still exists in the field of freezing of gait in Parkinson's disease.This cross-sectional study aimed to evaluate the ability of radiomics features based on multi-level indices of resting-state functional magnetic resonance imaging,along with clinical features,to distinguish between Parkinson's disease patients with and without freezing of gait.We recruited 28 patients with Parkinson's disease who had freezing of gait(15 men and 13 women,average age 63 years)and 30 patients with Parkinson's disease who had no freezing of gait(16 men and 14 women,average age 64 years).Magnetic resonance imaging scans were obtained using a 3.0T scanner to extract the mean amplitude of low-frequency fluctuations,mean regional homogeneity,and degree centrality.Neurological and clinical characteristics were also evaluated.We used the least absolute shrinkage and selection operator algorithm to extract features and established feedforward neural network models based solely on resting-state functional magnetic resonance imaging indicators.We then performed predictive analysis of three distinct groups based on resting-state functional magnetic resonance imaging indicators indicators combined with clinical features.Subsequently,we conducted 100 additional five-fold cross-validations to determine the most effective model for each classification task and evaluated the performance of the model using the area under the receiver operating characteristic curve.The results showed that when differentiating patients with Parkinson's disease who had freezing of gait from those who did not have freezing of gait,or from healthy controls,the models using only the mean regional homogeneity values achieved the highest area under the receiver operating characteristic curve values of 0.750(with an accuracy of 70.9%)and 0.759(with an accuracy of 65.3%),respectively.When classifying patients with Parkinson's disease who had freezing of gait from those who had no freezing of gait,the model using the mean amplitude of low-frequency fluctuation values combined with two clinical features achieved the highest area under the receiver operating characteristic curve of 0.847(with an accuracy of 74.3%).The most significant features for patients with Parkinson's disease who had freezing of gait were amplitude of low-frequency fluctuation alterations in the left parahippocampal gyrus and two clinical characteristics:Montreal Cognitive Assessment and Hamilton Depression Scale scores.Our findings suggest that radiomics features derived from resting-state functional magnetic resonance imaging indices and clinical information can serve as valuable indices for the identification of freezing of gait in Parkinson's disease.
基金supported by the National Natural Science Foundation of China,No.31970906(to WLei)the Natural Science Foundation of Guangdong Province,No.2020A1515011079(to WLei)+4 种基金Key Technologies R&D Program of Guangdong Province,No.2018B030332001(to GC)Science and Technology Projects of Guangzhou,No.202206060002(to GC)the Youth Science Program of the National Natural Science Foundation of China,No.32100793(to ZX)the Pearl River Innovation and Entrepreneurship Team,No.2021ZT09 Y552Yi-Liang Liu Endowment Fund from Jinan University Education Development Foundation。
文摘Over the past decade,a growing number of studies have reported transcription factor-based in situ reprogramming that can directly conve rt endogenous glial cells into functional neurons as an alternative approach for n euro regeneration in the adult mammalian central ne rvous system.Howeve r,many questions remain regarding how a terminally differentiated glial cell can transform into a delicate neuron that forms part of the intricate brain circuitry.In addition,concerns have recently been raised around the absence of astrocyte-to-neuron conversion in astrocytic lineage-tra cing mice.In this study,we employed repetitive two-photon imaging to continuously capture the in situ astrocyte-to-neuron conversion process following ecto pic expression of the neural transcription factor NeuroD1 in both prolife rating reactive astrocytes and lineage-tra ced astrocytes in the mouse cortex.Time-lapse imaging over several wee ks revealed the ste p-by-step transition from a typical astrocyte with numero us short,tapered branches to a typical neuro n with a few long neurites and dynamic growth cones that actively explored the local environment.In addition,these lineage-converting cells were able to migrate ra dially or to ngentially to relocate to suitable positions.Furthermore,two-photon Ca2+imaging and patch-clamp recordings confirmed that the newly generated neuro ns exhibited synchronous calcium signals,repetitive action potentials,and spontaneous synaptic responses,suggesting that they had made functional synaptic connections within local neural circuits.In conclusion,we directly visualized the step-by-step lineage conversion process from astrocytes to functional neurons in vivo and unambiguously demonstrated that adult mammalian brains are highly plastic with respect to their potential for neuro regeneration and neural circuit reconstruction.
基金supported by National Natural Science Foundation of China(Grant Nos.21927811,22076106 and 21874084)National Key R&D Program of China(Grant No.2019YFA0210100)Natural Science Foundation of Shandong Province(Grant No.ZR2019JQ07).
文摘Herein,a reversible pH fluorescent sensor was developed using caffeic acid as the precursor by one-step solvothermal synthesis method.The carbon dots-based sensor(CA-CDs)exhibited pH-dependent increase in fluorescence intensity and showed linear relationship in the range of pH 6.60 and 8.00.Notably,the fluorescence sensor has a reversible response to pH change.Finally,the CA-CDs has been successfully applied for two-photon imaging of the pH in liver and kidney of diabetic mice.Imaging results showed that the pH value in kidney of diabetic mice was lower than that of the normal mice,while the pH value in liver of diabetic mice was almost the same as that of the normal mice.The present study provides a simple analytical method for pH detection suitable for in vivo.
基金financially supported by the National Natural Science Foundation of China(Nos.21905021,U21A20308)Sichuan Science and Technology Support Program(Nos.2022NSFSC1269,2023NSF1977,2023NSFSC0637,2022ZYD0048,2021ZDYF3218,2021YFG0291,2021YFH0132)Sichuan Students’Platform for innovation and entrepreneurship training program(No.202210623013)。
文摘Applying the fluorescent carbon dots as smart materials in anticancer therapy is of great interest.However,carbon dots for multimodal synergistic anticancer therapy,especially for the triple modality,is rarely reported.Herein,we successfully synthesized OCDs by citric acid and(1R,2S)-2-amino-1,2-diphenylethan-1-ol,which show aggregation-induced emission property and two-photon fluorescence imaging.Meanwhile,OCDs are ideal photosensitizers for photothermal therapy under 808 nm and TypeⅠphotodynamic therapy with white light.Hydroxyl radicals,generated by TypeⅠphotodynamic therapy based on OCDs can transform protumoral M2 macrophages into antitumoral M1 macrophages,which exhibited immunotherapy ability.The synergism trimodal of OCDs results in potent anticancer efficacy,showing great potential in cancer therapy.
基金ACKNOWLEDGMENTS This work was supported by the National Natural Science Foundation of China （No.21073188）.
文摘The wavelength dependence of photoelectron angular distributions （PADs） of two-photon detachment of Cu^- has been directly studied by using the photoelectron map imaging. Results show that for the laser field intensity of 6.0×10^10W/cm^2, PADs exhibit dramatic change with the external field wavelength. Comparison between the experimental observation and the lowest-order perturbation theory prediction indicates that the pattern of PADs can be explained by the interference of the s and d partial waves in the final state. Relative contri- butions of s and d partial waves in the two-photon detachment at different laser wavelengths are obtained.
基金financially supported by the National Natural Science Foundation of China (Nos. 21835001, 51773080, 21674041, 51573068, and 21221063)Program for Changbaishan Scholars of Jilin Province, Jilin Province (No. 20160101305JC)the "Talents Cultivation Program" of Jilin University
文摘Near-infrared(NIR) nanoparticles(NPs) based on fluorescence resonance energy transfer(FRET) were prepared by coencapsulation of a red aggregation-induced emission(AIE) molecule, 2-(4-bromophenyl)-3-(4-(4-(diphenylamino)styryl)phenyl)fumaronitrile(TB), and a commercial NIR fluorescence dye, silicon 2,3-naphthalocyanine bis(trihexylsilyloxide)(NIR775) with an amphiphilic polymer poly(styrene-co-maleic anhydride)(PSMA). The surface of the NPs, PSMA@TB/NIR775, was modified with poly(ethylene glycol)(PEG) to increase the in vivo biocompatibility of the NPs. The PSMA@TB/NIR775 NPs showed a strong NIR(780 nm) narrow emission and excellent two-photon absorption property. Moreover, the NPs exhibited good monodispersity, stability, and low cytotoxicity.Under the excitation of a 1040 nm femtosecond(fs) laser, the emission peaks at 680 nm of TB and 780 nm of NIR775 excited by FRET were obtained. We utilized PSMA@TB/NIR775 NPs as fluorescent contrast agents for two-photon excited NIR microscopic imaging, and good NIR imaging effect of mouse brain vasculature was obtained with the imaging depth of about 150 μm. The FRET strategy by coencapsulating AIE molecule and NIR dye will be helpful in preparing more narrow emission NIR probes for deep-tissue biological imaging.
基金supported in part by the National Key R&D Program of China(2017YFA0700402)National Natural Science Foundation of China(61961136005/61935012/62175163/61835009)+1 种基金Shenzhen Key projects(JCYJ20200109105404067)Shenzhen International Cooperation Project(GJHZ 20190822095420249).
文摘Apoptosis is very important for the maintenance of cellular homeostasis and is closely related to the occurrence and treatment of many diseases.Mitochondria in cells play a crucial role in programmed cell death and redox processes.Nicotinamide adenine dinucleotide(NAD(P)H)is the primary producer of energy in mitochondria,changing NAD(P)H can directly reflect the physiological state of mitochondria.Therefore,NAD(P)H can be used to evaluate metabolic response.In this paper,we propose a noninvasive detection method that uses two-photon fluorescence lifetime imaging microscopy(TP-FLIM)to characterize apoptosis by observing the binding kinetics of cellular endogenous NAD(P)H.The result shows that the average fluorescence lifetime of NAD(P)H and the fluorescence lifetime of protein-bound NAD(P)H will be affected by the changing pH,serum content,and oxygen concentration in the cell culture environment,and by the treatment with reagents such as H2O2 and paclitaxel.Taxol(PTX).This noninvasive detection method realized the dynamic detection of cellular endogenous substances and the assessment of apoptosis.
基金National Natural Science Foundation of China(Nos.21174022,21376038)National Basic Research Program of China(No.2013CB733702)+1 种基金Key Project of the Education Department of Sichuan Province(No.12ZA087)Specialized Research Fund for the Doctoral Program of Higher Education(No.20110041110009)
文摘PAHPN. a naphthalimide-based mitotracker with reasonable two-photon excitation emission activity and polarity-sensitive fluorescence properties has been efficiently synthesized and studied in twophoton, co-localization, and FLIM imaging.
基金the National Natural Science Foundation of China(Nos.81902356,82072581,21971265 and 82272842)Programs for Medical Science and Technology Research Project of Henan Province Health Commission(Nos.2018020025,SB201901029)+2 种基金Henan Province Young and Middle-Aged Health Science and Technology Innovation Talent Project(No.YXKC2022032)Shenzhen Key Laboratory of Functional Aggregate Materials(No.ZDSYS20211021111400001)Provincial Science and Technology R&D Program Joint Fund of the Department of Science and Technology of Henan Province(superior discipline cultivation category)Key Project(No.222301420018)。
文摘The application of fluorescent probes for in vivo retinal imaging is of great importance,which could provide direct and crucial imaging evidence for a better understanding of common eye diseases.Herein,a group of bright organic luminogens with typical electron-donating(D)and electron-accepting(A)structures(abbreviated as LDs-BDM,LDs-BTM,and LDs-BHM)was synthesized through a simple single-step reaction.They were found to be efficient solid-state emitters with high fluorescence quantum yields of above 70%(e.g.,83.7%for LDs-BTM).Their light-emission properties could be tuned by the modulation ofπ-conjugation effect with methoxy groups at different substituent positions.Their resulting fluorescent nanoparticles(NPs)were demonstrated as specific lipid droplets(LDs)targeting probes with high brightness,good biocompatibility,and satisfactory photostability.LDs-BTM NPs with a large two-photon absorption cross section(σ2=249 GM)were further utilized as ultrabright two-photon fluorescence(2PF)nanoprobes for in vivo retina imaging of live zebrafish by NIR excitation at an ultralow concentration(0.5μmol/L).Integrated histological structures at the tissue level and corresponding fine details at the cellular level of the embryonic retina of live zebrafish were clearly demonstrated.This is the first report of using ultrabright LDs-targeting nanoprobes to accurately measure fine details in the retina with 2PF microscopic technique.These good results are anticipated to open up a new avenue in the development of efficient 2PF emitters for non-invasive bioimaging of living animals.
基金financial support of the present work by the National Natural Science Foundation of China(Nos.51773056,51603067,21705040)Natural Science Foundationof Hunan Province,China(No.2018JJ3143)+3 种基金China Postdoctoral Science Foundation(Nos.2017M622571,2017M622568 and 2018T110824)Open Project Program of State Key Laboratory of Chemo/Biosensing and Chemometrics(No.2016019)Open Fund of the State Key Laboratory of Luminescent Materials and Devices(South China University of Technology)(No.2019-skllmd-09)Natural Science Foundation of Guangdong Province(No.2017A030313299)。
文摘Direct,in situ selective detection of intracellular formaldehyde(FA)is of great significance for understanding its function in FA-related diseases.Herein,red carbon dots(RCD)are reported as label-free two-photon fluorescent nanoprobes for detecting and imaging of FA.Upon addition of FA,the-NH2 groups of RCD could quickly and specially react with aldehydes to form Schiff base and then the strong fluorescence of RCD with blue-shift emission is recovery due to the destruction of the hydrogen bond interaction between RCD and water.In addition,the nanoprobes exhibit outsta nding photo stability,rapid response(<1 min),high sensitivity(~9.9μmol/L)and excellent selectivity toward FA over other aldehyde group compounds.Notably,owing to the good cell-membrane permeability and biocompatibility,as well as the large two-photon absorption cross-section,the as-prepared RCD can be used as label-free nanoprobes for selectively detecting and imaging FA in living cells and zebrafishes through one-photon and two-photon excitation.Moreover,RCD could stain the tissue of zebrafishes at depths interval of up to 240μm under two-photon excitation.This research implied that RCD are promising tools for directly and in situ imaging FA in vivo,thus providing critical insights into FA-related pathophysiological processes.
基金supported by NIH(R01AG055413),(R01AG085562),(R21AG059134),(R21AG078749),and(S10OD028609)awards(C.R.).NIH Office of the Director,National Institute on Aging.
文摘Alzheimer's disease(AD)is a neurodegenerative disease characterized by a progressive decline in cognitive functions.Given that AD undermines the quality of life for millions and has an extended asymptomatic period,exploring the full AD pathogenesis and seeking the optimal therapeutic solution have become critical and imperative.This allows researchers to intervene,delay,and potentially prevent AD progression.Several clinical imaging methods are utilized routinely to diagnose and monitor AD,such as magnetic resonance imaging(MRI),functional magnetic resonance imaging(fMRI),positron emission tomography(PET),and single photon emission computed tomography(SPECT).Nevertheless,due to their intrinsic drawbacks and restrictions,such as radiation concerns,high cost,long acquisition time,and low spatial resolution,their applications in AD research are limited,especially at the cellular and molecular levels.In contrast,optical microscopic imaging methods overcome these limitations,offering researchers a variety of approaches with distinct advantages to explore AD pathology on diverse models.In this review,we provide a comprehensive overview of commonly utilized optical microscopic imaging techniques in AD research and introduce their contributions to image amyloid beta(Aβ)species.These techniques include fluorescence microscopy(FM),confocal microscopy(CM),two-photon fluorescence microscopy(TPFM),super-resolution microscopy(SRM),expansion microscopy(ExM),and light-sheet fluorescence microscopy(LSFM).In addition,we introduce some related topics,such as the development of near-infrared(NIR)Aβprobes,the Aβplaque hypothesis,and Aβoligomer hypothesis,and the roles of microglia and astrocytes in AD progression.We believe optical microscopic imaging methods continue to play an indispensable role in deciphering the full pathogenesis of AD and advancing therapeutic strategies.
基金supported by the Introduction Research Item of Northwest University for Nationalities(No.xbmuyjrc201110)the Fundamental Research Funds for the Central Universities(Nos.zyz2012062 and 31920130024)the Young and Middle-Aged Scientists Research Fund of Northwest University for Nationalities(No.12XB34)
文摘A two-photon fluorescent probe TPZn was developed for specific ratiometric imaging Zn2＋ in living cells and tissues. Significant ratiometric fluorescence change was based on photoinduced electron transfer and intramolecular charge transfer. The synthetic method of TPZn was simple. It was successfully used to selectively image Zn2＋ based on the higher binding affinity for Zn2＋ than for Cd2＋. TPZn was easily loaded into the living cell and tissues with high membrane permeability in a complex biological environment. TPZn could clearly visualize endogenous Zn2＋ by TP ratiometric imaging in hippocampal slices at a depth of 120 μm. Thus, TPZn is a useful tool to image of Zn2＋ in living cells and tissues without interference from Cd2＋.
基金support from the National Research Foundation (NRF) Singapore, under its Competitive Research Programme Award NRF-CRP20-20170004 and NRF Investigatorship Award NRF-NRFI06-20200005MTC Programmatic Grant M21J9b0085, as well as the Lite-On Project RS-INDUS-00090+5 种基金support from Australian Research Council (DE220101085, DP220102152)grants from German Research Foundation (SCHM2655/15-1, SCHM2655/21-1)Lee-Lucas Chair in Physics and funding by the Australian Research Council DP220102152financial support from the National Natural Science Foundation of China (Grant No. 62275078)Natural Science Foundation of Hunan Province of China (Grant No. 2022JJ20020)Shenzhen Science and Technology Program (Grant No. JCYJ20220530160405013)
文摘Optical imaging systems have greatly extended human visual capabilities,enabling the observation and understanding of diverse phenomena.Imaging technologies span a broad spectrum of wavelengths from x-ray to radio frequencies and impact research activities and our daily lives.Traditional glass lenses are fabricated through a series of complex processes,while polymers offer versatility and ease of production.However,modern applications often require complex lens assemblies,driving the need for miniaturization and advanced designs with micro-and nanoscale features to surpass the capabilities of traditional fabrication methods.Three-dimensional(3D)printing,or additive manufacturing,presents a solution to these challenges with benefits of rapid prototyping,customized geometries,and efficient production,particularly suited for miniaturized optical imaging devices.Various 3D printing methods have demonstrated advantages over traditional counterparts,yet challenges remain in achieving nanoscale resolutions.Two-photon polymerization lithography(TPL),a nanoscale 3D printing technique,enables the fabrication of intricate structures beyond the optical diffraction limit via the nonlinear process of two-photon absorption within liquid resin.It offers unprecedented abilities,e.g.alignment-free fabrication,micro-and nanoscale capabilities,and rapid prototyping of almost arbitrary complex 3D nanostructures.In this review,we emphasize the importance of the criteria for optical performance evaluation of imaging devices,discuss material properties relevant to TPL,fabrication techniques,and highlight the application of TPL in optical imaging.As the first panoramic review on this topic,it will equip researchers with foundational knowledge and recent advancements of TPL for imaging optics,promoting a deeper understanding of the field.By leveraging on its high-resolution capability,extensive material range,and true 3D processing,alongside advances in materials,fabrication,and design,we envisage disruptive solutions to current challenges and a promising incorporation of TPL in future optical imaging applications.
基金the National Natural Science Foundation of China(Nos.21102148 and 21125205)National Basic Research Program of China(No.2011CB935800)the State Key Laboratory of Fine Chemicals,Department of Chemical Engineering,Dalian University of Technology for financial supports
文摘A new two-photon fluorescent probe, ADNO, for nitric oxide （NO） based on intramolecular photoinduced electron transfer （PET） mechanism d/splays a rapid response to NO with a remarkable fluorescent enhancement in PBS buffer. The excellent chemoselectivity of ADNO for NO over other ROS/RNS （reactive oxygen species or nitrogen species） and common metal ions was observed. Moreover, ADNO has been successfully applied in fluorescence imaging of NO of living cells using both one-photon microscopy （OPM） and two-~hoton microscopy （TPM）,
基金supported by the National Natural Science Foundation of China(31700934 and 31371106)。
文摘Monitoring neuronal activity in vivo is critical to understanding the physiological or pathological functions of the brain.Two-photon Ca^(2+)imaging in vivo using a cranial window and specific neuronal labeling enables realtime,in situ,and long-term imaging of the living brain.Here,we constructed a recombinant rabies virus containing the Ca^(2+)indicator GCaMP6 s along with the fluorescent protein DsRed2 as a baseline reference to ensure GCaMP6 s signal reliability.This functional tracer was applied to retrogradely label specific V1-thalamus circuits and detect spontaneous Ca^(2+)activity in the dendrites of V1 corticothalamic neurons by in vivo two-photon Ca^(2+)imaging.Notably,we were able to record single-spine spontaneous Ca2+activity in specific circuits.Distinct spontaneous Ca^(2+)dynamics in dendrites of V1 corticothalamic neurons were found for different V1-thalamus circuits.Our method can be applied to monitor Ca^(2+)dynamics in specific input circuits in vivo,and contribute to functional studies of defined neural circuits and the dissection of functional circuit connections.
