The volumetric imaging of two-photon microscopy expands the focal depth and improves the throughput,which has unparalleled superiority for three-dimension samples,especially in neuroscience.However,emerging in volumet...The volumetric imaging of two-photon microscopy expands the focal depth and improves the throughput,which has unparalleled superiority for three-dimension samples,especially in neuroscience.However,emerging in volumetric imaging is still largely customized,which limits the integration with commercial two-photon systems.Here,we analyzed the key parameters that modulate the focal depth and lateral resolution of polarized annular imaging and proposed a volumetric imaging module that can be directly integrated into commercial two-photon systems using conventional optical elements.This design incorporates the beam diameter adjustment settings of commercial two-photon systems,allowing flexibility to adjust the depth of focus while maintaining the same lateral resolution.Further,the depth range and lateral resolution of the design were verified,and the imaging throughput was demonstrated by an increase in the number of imaging neurons in the awake mouse cerebral cortex.展开更多
As a second messenger in signal transduction,calcium ion plays a very important role in neuronal information processing and integrating.Limited by the imaging technique,it is difficult to simultaneously perform deep t...As a second messenger in signal transduction,calcium ion plays a very important role in neuronal information processing and integrating.Limited by the imaging technique,it is difficult to simultaneously perform deep tissue imaging and measure intracellular free calcium concentration([Ca^(2+)]i)in different compartments of neurons in brain slice noncollinearly.By means of random access two-photon microscopy,which provides high optical penetration into tissues and low photo damage,we successfully measured[Ca^(2+)]i of different parts of pyramidal neurons in neocortical layer V in rat brain slices with high spatial and temporal resolution.Combining the patch clamp technique,we stimulated the soma with depolarizing current and explored the dynamics of calcium in pyramidal neurons.展开更多
Background:Pathological scars are a disorder that can lead to various cosmetic,psychological,and functional problems,and no effective assessment methods are currently available.Assessment and treatment of pathological...Background:Pathological scars are a disorder that can lead to various cosmetic,psychological,and functional problems,and no effective assessment methods are currently available.Assessment and treatment of pathological scars are based on cutaneous manifestations.A two-photon microscope(TPM)with the potential for real-time non-invasive assessment may help determine the under-surface pathophysiological conditions in vivo.This study used a portable handheld TPM to image epidermal cells and dermal collagen structures in pathological scars and normal skin in vivo to evaluate the effectiveness of treatment in scar patients.Methods:Fifteen patients with pathological scars and three healthy controls were recruited.Imaging was performed using a portable handheld TPM.Five indexes were extracted from two dimensional(2D)and three dimensional(3D)perspectives,including collagen depth,dermo-epidermal junction(DEJ)contour ratio,thickness,orientation,and occupation(proportion of collagen fibers in the field of view)of collagen.Two depth-dependent indexes were computed through the 3D second harmonic generation image and three morphology-related indexes from the 2D images.We assessed index differences between scar and normal skin and changes before and after treatment.Results:Pathological scars and normal skin differed markedly regarding the epidermal morphological structure and the spectral characteristics of collagen fibers.Five indexes were employed to distinguish between normal skin and scar tissue.Statistically significant differences were found in average depth(t=9.917,P<0.001),thickness(t=4.037,P<0.001),occupation(t=2.169,P<0.050),orientation of collagen(t=3.669,P<0.001),and the DEJ contour ratio(t=5.105,P<0.001).Conclusions:Use of portable handheld TPM can distinguish collagen from skin tissues;thus,it is more suitable for scar imaging than reflectance confocal microscopy.Thus,a TPM may be an auxiliary tool for scar treatment selection and assessing treatment efficacy.展开更多
During the continuous casting process of high-Mn high-Al steels,various types of gases such as Ar need to escape through the top of the mold.In which,the behavior of bubbles traversing the liquid slag serves as a rest...During the continuous casting process of high-Mn high-Al steels,various types of gases such as Ar need to escape through the top of the mold.In which,the behavior of bubbles traversing the liquid slag serves as a restrictive link,closely associated with viscosity and the thickness of liquid slag.In contrast to two-dimensional surface observation,three-dimensional(3D)analysis method can offer a more intuitive,accurate,and comprehensive information.Therefore,this study employs a 3D X-ray microscope(3D-XRM)to obtained spatial distribution and 3D morphological characteristics of residual bubbles in mold flux under different basicity of liquid slag,different temperatures,and different holding times.The results indicate that as basicity of slag increases from 0.52 to 1.03,temperature increases from 1423 to 1573 K,the viscosity of slag decreases,the floating rate of bubbles increases.In addition,when holding time increases from 10 to 30 s,the bubbles floating distance increases,and the volume fraction and average equivalent sphere diameter of the bubbles solidified in the mold flux gradually decreases.In one word,increasing the basicity,temperature,and holding time leading to an increase in the removal rate of bubbles especially for the large.These findings of bubbles escape behavior provide valuable insights into optimizing low basicity mold flux for high-Mn high-Al steels.展开更多
Background:Glioblastoma(GBM)is a highly aggressive brain tumor characterized by aberrant angiogenesis and an immunosuppressive microenvironment.Pericytes are aberrantly recruited but their spatiotemporal roles and mol...Background:Glioblastoma(GBM)is a highly aggressive brain tumor characterized by aberrant angiogenesis and an immunosuppressive microenvironment.Pericytes are aberrantly recruited but their spatiotemporal roles and molecular changes remain unclear.This study investigated platelet-derived growth factor receptor beta-positive(Pdgfrb+)pericyte dynamics and reprogramming in GBM vasculature.Methods:We generated GL261-Luc and GL261-CFP glioblastoma cells via lentiviral transduction and established two transgenic models.(1)For pericyte labeling,Ai14 reporter mice was crossed with PDGFRβ-P2A-CreERT2mice for td Tomato-specific lineage tracing(PT mice).(2)For conditional ablation,we generated inducible Pdgfrb-expressing cell ablation models(PT mice was crossed with ROSA-DTA mice).An intravital imaging platform(FITC-dextran/CFP/td Tomato+two-photon microscopy)tracked pericytes,vessels,and tumor cells,while FACSsorted Pdgfrb+cells from GBM and normal brain were analyzed by LC-MS/MS proteomics.Results:Cre-mediated ablation of Pdgfrb-expressing cells revealed stage-dependent effects on GBM growth:early ablation inhibited progression while late ablation promoted it.Pericytes undergo dual spatial reorganization in GBM:regional enrichment with pre-sprouting accumulation at the tumor-brain interface,and focal positioning with preferential localization at vascular branch points.Concurrently,GBM vasculature displayed simplified branching,dilation,and pericyte remodeling(shorter processes,higher density).Proteomics revealed 1426 altered proteins,with upregulated proliferation pathways(e.g.,matrix metallopeptidase 14[Mmp14],lysyl oxidase like 2[Loxl2])and downregulated homeostasis functions(e.g.,transforming growth factor beta 1[Tgfb1]),validated by scRNA-seq in human GBM.Conclusions:This study demonstrates that during early GBM progression,pericytes actively drive tumor angiogenesis through molecular reprogramming toward proliferative and pro-angiogenic phenotypes,with the integrated imaging-proteomics framework revealing potential therapeutic targets for disrupting pericyte-mediated vascular remodeling.展开更多
In comparison with conventional experimental teaching methods,the implementation of the Motic digital microscope mutual system in the experimental teaching of medicinal botany has been demonstrated to be a highly effi...In comparison with conventional experimental teaching methods,the implementation of the Motic digital microscope mutual system in the experimental teaching of medicinal botany has been demonstrated to be a highly efficacious approach to enhance the teaching level of experimental courses in medicinal botany.The implementation of a digital microscope mutual system in experimental teaching not only enhances students practical skills in laboratory operations but also increases classroom efficiency.Furthermore,it supports personalized development among students while fostering innovative thinking,independent learning capabilities,and analysis and problem-solving skills.Additionally,this approach contributes to the enhancement of students scientific literacy.展开更多
To investigate the nucleation behavior during the single-phased metallic solidification process,the commercial ultrapure ferritic stainless steels with no(Initial steel)and various melt treatments(R1,MR1,Y2,MY1,and M1...To investigate the nucleation behavior during the single-phased metallic solidification process,the commercial ultrapure ferritic stainless steels with no(Initial steel)and various melt treatments(R1,MR1,Y2,MY1,and M1 steels)were used to carry out the differential scanning colorimetry(DSC)and high-temperature confocal laser scanning microscope(HT-CLSM)experiments.Based on the results of DSC experiments,the equilibrium solidification process as well as the relationship among the critical undercooling degree(△T_(c)^(DSC)),latent heat of fusion/crystallization(△H_(f)/△H_(c)),equiaxed grain ratio(ER),and average grain size(△_(ave)^(ingot))was revealed.ER is increased with the decreasing△T_(c)^(DSC)and increasing△H_(f)/△H_(c);however,△_(ave)^(ingot)is decreased with them.Referring to the results of HT-CLSM experiments,the average sizes of micro-/macrostructures(d_(ave)/D_(ave)/)are decreased with the increasing cooling rate,as well as the difference between and apparent critical undercooling degree(△T_(c)^(CLSM))was revealed.The heterogeneous nucleation of the crystal nuclei occurs only if△T_(c)^(CLSM)>△T_(c)^(DSC).Combining with the interfacial wetting-lattice mismatch heterogeneous nucleation model,the dynamic mechanism of the metallic solidification was revealed.The as-cast grains of the melt-treated samples were obviously refined,owing to the much higher actual heterogeneous nucleation rates(I_(heter.,i))obtained through melt treatments,and the heterogeneous nucleation rates(I_(heter.,ij))for all samples are increased with the cooling rates,firmly confirming that the as-cast grains of each sample could be refined by the increasing cooling rates.展开更多
With the support by the National Natural Science Foundation of China,a study by the research groups led by Prof.Cheng Heping(Peace)(程和平)from the State Key Laboratory of Membrane Biology,Institute of Molecular Medic...With the support by the National Natural Science Foundation of China,a study by the research groups led by Prof.Cheng Heping(Peace)(程和平)from the State Key Laboratory of Membrane Biology,Institute of Molecular Medicine,Peking-Tsinghua Center for Life Sciences,Beijing Key Laboratory展开更多
Light-sheet fluorescence microscopy(LSFM)has been widely used to image the three-dimensional(3D)structures and functions of various millimeter-size bio-specimen such as zebrafish.However,the sample adsorption and scat...Light-sheet fluorescence microscopy(LSFM)has been widely used to image the three-dimensional(3D)structures and functions of various millimeter-size bio-specimen such as zebrafish.However,the sample adsorption and scattering cause shading of the light-sheet illumination,preventing the even 3D image of thick samples.Herein,we report a continuous-rotational light-sheet microscope(CR-LSM)that enables simultaneous 3D bright-field and fluorescence imaging.With a high-accuracy rotational stage,CR-LSM records the outline projections and the fluorescent images of the sample at multiple rotation angles.Then,3D morphology and fluorescent structure were reconstructed with a developed algorithm.Using CR-LSM,zebrafish’s whole-fish contour and blood vessel structures were obtained simultaneously.展开更多
The construction of advanced laboratories for precision instruments, such as electron microscopes, involves unique challenges that are influenced by the specific environmental conditions required for optimal functiona...The construction of advanced laboratories for precision instruments, such as electron microscopes, involves unique challenges that are influenced by the specific environmental conditions required for optimal functionality. These include mitigating interference from magnetic fields and vibrations, which are critical for maintaining the precision and accuracy of the instruments used. This study aims to offer enhanced project management strategies and detailed construction solutions that address the environmental and technical needs specific to electron microscopy labs, thereby facilitating effective lab operations and extending the lifecycle of high-end precision instruments. Case studies of existing laboratory constructions, onsite investigations, and comprehensive reviews of the technical and environmental requirements provide the basis for a best practice for constructing sophisticated electron microscopy labs. The approach integrates both pre-construction planning and post-construction adjustments to create optimal operational environments. The findings suggest that successful lab constructions are those that incorporate thorough onsite assessments, strategic location choices, and the use of advanced construction materials and techniques specifically designed to counteract environmental challenges like magnetic and vibration interferences. Actionable guidelines for both planning and executing the construction of electron microscope labs highlighted in this tutorial are intended as an important resource to troubleshoot or upgrade existing lab facilities and to consult in preparation of future lab construction projects.展开更多
The high-temperature dissolution behavior of primary carbides in samples taken from GCr15 continuous-casting bloom was observed in-situ by confocal laser scanning microscopy.Equations were fitted to the dissolution ki...The high-temperature dissolution behavior of primary carbides in samples taken from GCr15 continuous-casting bloom was observed in-situ by confocal laser scanning microscopy.Equations were fitted to the dissolution kinetics of primary carbides during either heating or soaking.Dissolution of carbides proceeded in three stages(fast→slow→faster)as either temperature or holding time was increased.During the heating process and during the first and third stages of the soaking process,the original size of the carbides determined the steepness of the slope,but during the middle(“slow”)stage of the soaking process,the slope remained zero.The initial size of the carbides varied greatly,but their final dissolution temperature fell within the narrow range of 1210-1235℃,and the holding time remained within 50 min.Fractal analysis was used to study the morphological characteristics of small and medium-sized carbides during the dissolution process.According to changes in the fractal dimension before and after soaking,the carbides tended to evolve towards a more regular morphology.展开更多
Two-photon dissociation of BeH^(+)ions is studied by detecting the fluorescence changes of Be^(+)-BeH^(+)bi-component Coulomb crystal in a linear Paul trap.BeH^(+)ions generated by an exothermic reaction between elect...Two-photon dissociation of BeH^(+)ions is studied by detecting the fluorescence changes of Be^(+)-BeH^(+)bi-component Coulomb crystal in a linear Paul trap.BeH^(+)ions generated by an exothermic reaction between electronically excited Be^(+)ions and residual H_(2) in the vacuum chamber are photon-dissociated with two photons scanning over the range of 201 nm to 208 nm.Our experiment provides a novel method to maintain the number of Be^(+)ions stable in a Coulomb crystal with a middle ultraviolet band dissociation laser.This two-photon dissociation method extends the wavelength range of the dissociation laser for BeH^(+)compared to the one-photon dissociation,and the method can be utilized to all alkaline earth atomic ions which require suppression of the reaction with residual H_(2) gas in vacuum.展开更多
Hypochlorous acid(HClO)is a critical biomolecule in living organisms,playing an essential role in numerous physiological or pathological processes.Abnormal levels of HClO in the body may lead to a series of diseases,f...Hypochlorous acid(HClO)is a critical biomolecule in living organisms,playing an essential role in numerous physiological or pathological processes.Abnormal levels of HClO in the body may lead to a series of diseases,for instance,inflammation and cancer.Thus,accurate measurement of HClO levels should be more beneficial for understanding its role in diseases and gaining a deeper insight into the pathogenesis of diseases.In this work,we designed a near-infrared two-photon fluorescent probe(HDM-Cl-HClO)for detecting fluctuations in HClO levels in inflammatory and tumor-bearing mice.Notably,the probe can respond to HClO within 5 s and trigger a brilliant red fluorescence at 660 nm.It exhibits high specificity and sensitivity for HClO.The superior spectral capability of the probe has enabled the detection of HClO levels in cells and zebrafish,as well as achieved the detection of HClO in inflammatory and tumor mice.This work not only provides a novel strategy and tool for HClO imaging in living systems,but also holds great potential for the diagnosis of inflammation and cancer.展开更多
The hybrid CO_(2) thermal technique has achieved considerable success globally in extracting residual heavy oil from reserves following a long-term steam stimulation process.Using microscopic visualization experiments...The hybrid CO_(2) thermal technique has achieved considerable success globally in extracting residual heavy oil from reserves following a long-term steam stimulation process.Using microscopic visualization experiments and molecular dynamics(MD)simulations,this study investigates the microscopic enhanced oil recovery(EOR)mechanisms underlying residual oil removal using hybrid CO_(2) thermal systems.Based on the experimental models for the occurrence of heavy oil,this study evaluates the performance of hybrid CO_(2) thermal systems under various conditions using MD simulations.The results demonstrate that introducing CO_(2) molecules into heavy oil can effectively penetrate and decompose dense aggregates that are originally formed on hydrophobic surfaces.A stable miscible hybrid CO_(2) thermal system,with a high effective distribution ratio of CO_(2),proficiently reduces the interaction energies between heavy oil and rock surfaces,as well as within heavy oil.A visualization analysis of the interactions reveals that strong van der Waals(vdW)attractions occur between CO_(2) and heavy oil molecules,effectively promoting the decomposition and swelling of heavy oil.This unlocks the residual oil on the hydrophobic surfaces.Considering the impacts of temperature and CO_(2) concentration,an optimal gas-to-steam injection ratio(here,the CO_(2):steam ratio)ranging between 1:6 and 1:9 is recommended.This study examines the microscopic mechanisms underlying the hybrid CO_(2) thermal technique at a molecular scale,providing a significant theoretical guide for its expanded application in EOR.展开更多
Four benzocoumarin-based two-photon fluorescent probes(BH1-BH4)are proposed for ra-tiometric detection of hypochlorous acid(HClO)and their two-photon sensing perfor-mance are evaluated by means of time-dependent densi...Four benzocoumarin-based two-photon fluorescent probes(BH1-BH4)are proposed for ra-tiometric detection of hypochlorous acid(HClO)and their two-photon sensing perfor-mance are evaluated by means of time-dependent density func-tional theory and quadratic re-sponse theory.The effects of benzene-fused position on Stokes shift,fluorescence quantum yield and two-photon absorption are discussed comprehensively.The results show that fusing a benzene ring in coumarin can enhance Stokes shift efficiently.The benzene-fused position has important effects on these photophysical properties.The benzo[g]coumarins(BH1)and benzo[f]coumarins(BH2)derivatives have larger Stokes shifts in comparison with benzo[h]coumarins(BH3)and dihydrophenazine(BH4)derivatives.The two-photon absorp-tion of benzo[f]coumarins(BH2)derivative is much smaller than those of other benzo-coumarins derivatives.The large Stokes shift and increased two-photon action cross section can be achieved simultaneously in the dihydrophenazine(BH4)derivative.Therefore,the de-signed BH4 is expected to have superior performance for the ratiometric detection of HClO.To explore the reasons behind these effects,the intramolecular charge transfer degrees are il-lustrated quantitatively by plotting the hole-electron isosurface map,and the relation be-tween charge transfer and Stokes shift is revealed.A two-state model analysis is employed to understand two-photon absorption ability.Moreover,the fluorescence near-quenching mecha-nism of the product molecules B1 and B3 is explained by analyzing reorganization energy and Huang-Rhys factor,as well as related normal mode.Our research could contribute to the effi-cient design of ratiometric two-photon fluorescent probes with large Stokes shift and signifi-cant two-photon action cross section.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
SnS,a well-known van der Waals chalcogenide,is susceptible to oxidation in high-temperature or highhumidity environments,significantly impacting its functional performance and device stability.Conversely,oxidation can...SnS,a well-known van der Waals chalcogenide,is susceptible to oxidation in high-temperature or highhumidity environments,significantly impacting its functional performance and device stability.Conversely,oxidation can be used as an effective strategy for surface engineering,allowing for structure modulation or design,property tuning and application exploration.However,there is currently a gap in understanding the relationship between the oxidation behavior of SnS,the structure of its oxidized surface,and the dependence on oxidation temperature.In this study,we systematically investigated the evolution of SnS surfaces under thermal oxidation using electron microscopy.The microstructure evolution(e.g.,surface structures,phases,defects,and interface)of SnS during high-temperature oxidation has been fully characterized and studied based on cross-sectional samples.Various surface heterostructures were constructed,including SnO_(2)/SnS,SnO_(2)/SnS_(2)/SnS,and SnO_(2)/Sn_(2)S_(3)/SnS,offering significant potential for the surface functionalization of SnS-based systems.Accordingly,oxidation mechanisms at different stages were elucidated based on the detailed and clear picture of microstructures.This research not only deepens our understanding of the fundamental science of SnS oxidation but also provides valuable insights for preventing and developing surface oxidation engineering in SnS and other van der Waals chalcogenides/materials.展开更多
Manipulating and braiding Majorana zero modes(MZM)are a critical step toward realizing topological quantum computing.The primary challenge is controlling the vortex,which hosts the MZM,within a superconducting film in...Manipulating and braiding Majorana zero modes(MZM)are a critical step toward realizing topological quantum computing.The primary challenge is controlling the vortex,which hosts the MZM,within a superconducting film in a spatially precise manner.To address this,we developed a magnetic force-based vortex control technology using the STM system with a self-designed four-electrode piezo-scanner tube and investigated vortex manipulation on the NbSe_(2) superconducting film.We employed ferromagnetic tips to control the movement of vortex array induced by the tip's remanent magnetism.A magnetic core solenoid device was integrated into the STM system and a strong magnetic tip demagnetization technique was developed,providing a viable technical solution for further enabling single vortex manipulation.展开更多
Embedding optical fiber sensors into composite materials offers the advantage of real-time structural monitoring.However,there is an order-of-magnitude difference in diameter between optical fibers and reinforcing fib...Embedding optical fiber sensors into composite materials offers the advantage of real-time structural monitoring.However,there is an order-of-magnitude difference in diameter between optical fibers and reinforcing fibers,and the detailed mechanism of how embedded optical fibers affect the micromechanical behavior and damage failure processes within composite materials remains unclear.This paper presents a micromechanical simulation analysis of composite materials embedded with optical fibers.By constructing representative volume elements(RVEs)with randomly distributed reinforcing fibers,the optical fiber,the matrix,and the interface phase,the micromechanical behavior and damage evolution under transverse tensile and compressive loads are explored.The study finds that the presence of embedded optical fibers significantly influences the initiation and propagation of microscopic damage within the composites.Under transverse tension,the fiber-matrix interface cracks first,followed by plastic cracking in the matrix surrounding the fibers,forming micro-cracks.Eventually,these cracks connect with the debonded areas at the fiber-matrix interface to form a dominant crack that spans the entire model.Under transverse compression,plastic cracking first occurs in the resin surrounding the optical fibers,connecting with the interface debonding areas between the optical fibers and the matrix to form two parallel shear bands.Additionally,it is observed that the strength of the interface between the optical fiber and the matrix critically affects the simulation results.The simulated damage morphologies align closely with those observed using scanning electron microscopy(SEM).These findings offer theoretical insights that can inform the design and fabrication of smart composite materials with embedded optical fiber sensors for advanced structural health monitoring.展开更多
The complexity of cancer therapy has led to the emergence of combination therapy as a promising approach to enhance treatment efficacy and safety.The integration of glutathione(GSH)-activatable two-photon photodynamic...The complexity of cancer therapy has led to the emergence of combination therapy as a promising approach to enhance treatment efficacy and safety.The integration of glutathione(GSH)-activatable two-photon photodynamic therapy(TP-PDT)and chemodynamic therapy(CDT)offers the possibility to advance precision and efficacy in anti-cancer treatments.In this study,a GSH-activatable photosensitizer(PS),namely copper-elsinochrome(CuEC),is synthesized and utilized for combination second nearinfrared(NIR-II)TP-PDT/CDT.The Cu^(2+)acts as a“lock”,suppressing the fluorescence and^(1)O_(2)generation ability of EC in a normal physiological environment(“OFF”state).However,the overexpressed GSH in the tumor microenvironment acts as the“key”,resulting in the release of EC(“ON”state)and Cu^(+)(reduced by GSH).The released EC can be utilized for fluorescence imaging and TP-PDT under NIR-II(λ=1000 nm)two-photon excitation,while Cu+can generate highly toxic hydroxyl radicals(•OH)via Fenton-like reaction for CDT.Additionally,this process consumes GSH and diminishes the tumor’s antioxidant capacity,thereby augmenting the efficacy of combination therapy.The CuEC achieves significant tumor cell ablation in both 2D monolayer cells and 3D multicellular tumor spheres through the combination of NIR-II TP-PDT and CDT.展开更多
基金supported by STI2030-Major Projects (2021ZD0201001 to H.G.)the National Natural Science Foundation of China (61890951 and 31871027 to W.Z.)+2 种基金Fundamental Research Funds for the Central Universities (HUST:2019KFYXMBZ011,2019KFYXMBZ039,2018KFYXMPT018,2019KFYXMBZ009 to H.G.)CAMS Innovation Fund for Medical Sciences (CIFMS,2019-I2M-5-014 to H.G.)the director fund of the WNLO.
文摘The volumetric imaging of two-photon microscopy expands the focal depth and improves the throughput,which has unparalleled superiority for three-dimension samples,especially in neuroscience.However,emerging in volumetric imaging is still largely customized,which limits the integration with commercial two-photon systems.Here,we analyzed the key parameters that modulate the focal depth and lateral resolution of polarized annular imaging and proposed a volumetric imaging module that can be directly integrated into commercial two-photon systems using conventional optical elements.This design incorporates the beam diameter adjustment settings of commercial two-photon systems,allowing flexibility to adjust the depth of focus while maintaining the same lateral resolution.Further,the depth range and lateral resolution of the design were verified,and the imaging throughput was demonstrated by an increase in the number of imaging neurons in the awake mouse cerebral cortex.
文摘As a second messenger in signal transduction,calcium ion plays a very important role in neuronal information processing and integrating.Limited by the imaging technique,it is difficult to simultaneously perform deep tissue imaging and measure intracellular free calcium concentration([Ca^(2+)]i)in different compartments of neurons in brain slice noncollinearly.By means of random access two-photon microscopy,which provides high optical penetration into tissues and low photo damage,we successfully measured[Ca^(2+)]i of different parts of pyramidal neurons in neocortical layer V in rat brain slices with high spatial and temporal resolution.Combining the patch clamp technique,we stimulated the soma with depolarizing current and explored the dynamics of calcium in pyramidal neurons.
基金supported by grants from Beijing Municipal Science and Technology Commission Medicine Collaborative Science and Technology Innovation Research Project(No.Z191100007719001)To Establish a Database and Study the Imaging Features of Common Skin Diseases based on Two-photon Imaging Technology(No.SK2021090379-1)
文摘Background:Pathological scars are a disorder that can lead to various cosmetic,psychological,and functional problems,and no effective assessment methods are currently available.Assessment and treatment of pathological scars are based on cutaneous manifestations.A two-photon microscope(TPM)with the potential for real-time non-invasive assessment may help determine the under-surface pathophysiological conditions in vivo.This study used a portable handheld TPM to image epidermal cells and dermal collagen structures in pathological scars and normal skin in vivo to evaluate the effectiveness of treatment in scar patients.Methods:Fifteen patients with pathological scars and three healthy controls were recruited.Imaging was performed using a portable handheld TPM.Five indexes were extracted from two dimensional(2D)and three dimensional(3D)perspectives,including collagen depth,dermo-epidermal junction(DEJ)contour ratio,thickness,orientation,and occupation(proportion of collagen fibers in the field of view)of collagen.Two depth-dependent indexes were computed through the 3D second harmonic generation image and three morphology-related indexes from the 2D images.We assessed index differences between scar and normal skin and changes before and after treatment.Results:Pathological scars and normal skin differed markedly regarding the epidermal morphological structure and the spectral characteristics of collagen fibers.Five indexes were employed to distinguish between normal skin and scar tissue.Statistically significant differences were found in average depth(t=9.917,P<0.001),thickness(t=4.037,P<0.001),occupation(t=2.169,P<0.050),orientation of collagen(t=3.669,P<0.001),and the DEJ contour ratio(t=5.105,P<0.001).Conclusions:Use of portable handheld TPM can distinguish collagen from skin tissues;thus,it is more suitable for scar imaging than reflectance confocal microscopy.Thus,a TPM may be an auxiliary tool for scar treatment selection and assessing treatment efficacy.
基金financially supported by the National Natural Science Foundation of China(Nos.52274315 and 52374320)the Fundamental Research Funds for the Central Universities(Nos.FRF-TP-22-011A1 and FRF-DF22-16)。
文摘During the continuous casting process of high-Mn high-Al steels,various types of gases such as Ar need to escape through the top of the mold.In which,the behavior of bubbles traversing the liquid slag serves as a restrictive link,closely associated with viscosity and the thickness of liquid slag.In contrast to two-dimensional surface observation,three-dimensional(3D)analysis method can offer a more intuitive,accurate,and comprehensive information.Therefore,this study employs a 3D X-ray microscope(3D-XRM)to obtained spatial distribution and 3D morphological characteristics of residual bubbles in mold flux under different basicity of liquid slag,different temperatures,and different holding times.The results indicate that as basicity of slag increases from 0.52 to 1.03,temperature increases from 1423 to 1573 K,the viscosity of slag decreases,the floating rate of bubbles increases.In addition,when holding time increases from 10 to 30 s,the bubbles floating distance increases,and the volume fraction and average equivalent sphere diameter of the bubbles solidified in the mold flux gradually decreases.In one word,increasing the basicity,temperature,and holding time leading to an increase in the removal rate of bubbles especially for the large.These findings of bubbles escape behavior provide valuable insights into optimizing low basicity mold flux for high-Mn high-Al steels.
基金The National Key Research and Development Program of China,Grant/Award Number:2022YFF0710700Nonprofit Central Research Institute Fund of Chinese Academy of Medical Sciences,Grant/Award Number:2023-PT180-01。
文摘Background:Glioblastoma(GBM)is a highly aggressive brain tumor characterized by aberrant angiogenesis and an immunosuppressive microenvironment.Pericytes are aberrantly recruited but their spatiotemporal roles and molecular changes remain unclear.This study investigated platelet-derived growth factor receptor beta-positive(Pdgfrb+)pericyte dynamics and reprogramming in GBM vasculature.Methods:We generated GL261-Luc and GL261-CFP glioblastoma cells via lentiviral transduction and established two transgenic models.(1)For pericyte labeling,Ai14 reporter mice was crossed with PDGFRβ-P2A-CreERT2mice for td Tomato-specific lineage tracing(PT mice).(2)For conditional ablation,we generated inducible Pdgfrb-expressing cell ablation models(PT mice was crossed with ROSA-DTA mice).An intravital imaging platform(FITC-dextran/CFP/td Tomato+two-photon microscopy)tracked pericytes,vessels,and tumor cells,while FACSsorted Pdgfrb+cells from GBM and normal brain were analyzed by LC-MS/MS proteomics.Results:Cre-mediated ablation of Pdgfrb-expressing cells revealed stage-dependent effects on GBM growth:early ablation inhibited progression while late ablation promoted it.Pericytes undergo dual spatial reorganization in GBM:regional enrichment with pre-sprouting accumulation at the tumor-brain interface,and focal positioning with preferential localization at vascular branch points.Concurrently,GBM vasculature displayed simplified branching,dilation,and pericyte remodeling(shorter processes,higher density).Proteomics revealed 1426 altered proteins,with upregulated proliferation pathways(e.g.,matrix metallopeptidase 14[Mmp14],lysyl oxidase like 2[Loxl2])and downregulated homeostasis functions(e.g.,transforming growth factor beta 1[Tgfb1]),validated by scRNA-seq in human GBM.Conclusions:This study demonstrates that during early GBM progression,pericytes actively drive tumor angiogenesis through molecular reprogramming toward proliferative and pro-angiogenic phenotypes,with the integrated imaging-proteomics framework revealing potential therapeutic targets for disrupting pericyte-mediated vascular remodeling.
基金Supported by Major Project of School-level Teaching Reform and Research of Guangxi University of Chinese Medicine(2022A006)。
文摘In comparison with conventional experimental teaching methods,the implementation of the Motic digital microscope mutual system in the experimental teaching of medicinal botany has been demonstrated to be a highly efficacious approach to enhance the teaching level of experimental courses in medicinal botany.The implementation of a digital microscope mutual system in experimental teaching not only enhances students practical skills in laboratory operations but also increases classroom efficiency.Furthermore,it supports personalized development among students while fostering innovative thinking,independent learning capabilities,and analysis and problem-solving skills.Additionally,this approach contributes to the enhancement of students scientific literacy.
基金supported by the National Natural Science Foundation of China(Grant Nos.52274339,52174321,52074186,and 52104337)Natural Science Foundation of Jiangsu Province(Grant No.BK20231317)China Baowu Low-Carbon Metallurgy Innovation Fund(Grant No.BWLCF202108).
文摘To investigate the nucleation behavior during the single-phased metallic solidification process,the commercial ultrapure ferritic stainless steels with no(Initial steel)and various melt treatments(R1,MR1,Y2,MY1,and M1 steels)were used to carry out the differential scanning colorimetry(DSC)and high-temperature confocal laser scanning microscope(HT-CLSM)experiments.Based on the results of DSC experiments,the equilibrium solidification process as well as the relationship among the critical undercooling degree(△T_(c)^(DSC)),latent heat of fusion/crystallization(△H_(f)/△H_(c)),equiaxed grain ratio(ER),and average grain size(△_(ave)^(ingot))was revealed.ER is increased with the decreasing△T_(c)^(DSC)and increasing△H_(f)/△H_(c);however,△_(ave)^(ingot)is decreased with them.Referring to the results of HT-CLSM experiments,the average sizes of micro-/macrostructures(d_(ave)/D_(ave)/)are decreased with the increasing cooling rate,as well as the difference between and apparent critical undercooling degree(△T_(c)^(CLSM))was revealed.The heterogeneous nucleation of the crystal nuclei occurs only if△T_(c)^(CLSM)>△T_(c)^(DSC).Combining with the interfacial wetting-lattice mismatch heterogeneous nucleation model,the dynamic mechanism of the metallic solidification was revealed.The as-cast grains of the melt-treated samples were obviously refined,owing to the much higher actual heterogeneous nucleation rates(I_(heter.,i))obtained through melt treatments,and the heterogeneous nucleation rates(I_(heter.,ij))for all samples are increased with the cooling rates,firmly confirming that the as-cast grains of each sample could be refined by the increasing cooling rates.
文摘With the support by the National Natural Science Foundation of China,a study by the research groups led by Prof.Cheng Heping(Peace)(程和平)from the State Key Laboratory of Membrane Biology,Institute of Molecular Medicine,Peking-Tsinghua Center for Life Sciences,Beijing Key Laboratory
基金the National Natural Science Foundation of China(62205368)the Key Research and Development Program of Jiangsu Province(BE2020664).
文摘Light-sheet fluorescence microscopy(LSFM)has been widely used to image the three-dimensional(3D)structures and functions of various millimeter-size bio-specimen such as zebrafish.However,the sample adsorption and scattering cause shading of the light-sheet illumination,preventing the even 3D image of thick samples.Herein,we report a continuous-rotational light-sheet microscope(CR-LSM)that enables simultaneous 3D bright-field and fluorescence imaging.With a high-accuracy rotational stage,CR-LSM records the outline projections and the fluorescent images of the sample at multiple rotation angles.Then,3D morphology and fluorescent structure were reconstructed with a developed algorithm.Using CR-LSM,zebrafish’s whole-fish contour and blood vessel structures were obtained simultaneously.
文摘The construction of advanced laboratories for precision instruments, such as electron microscopes, involves unique challenges that are influenced by the specific environmental conditions required for optimal functionality. These include mitigating interference from magnetic fields and vibrations, which are critical for maintaining the precision and accuracy of the instruments used. This study aims to offer enhanced project management strategies and detailed construction solutions that address the environmental and technical needs specific to electron microscopy labs, thereby facilitating effective lab operations and extending the lifecycle of high-end precision instruments. Case studies of existing laboratory constructions, onsite investigations, and comprehensive reviews of the technical and environmental requirements provide the basis for a best practice for constructing sophisticated electron microscopy labs. The approach integrates both pre-construction planning and post-construction adjustments to create optimal operational environments. The findings suggest that successful lab constructions are those that incorporate thorough onsite assessments, strategic location choices, and the use of advanced construction materials and techniques specifically designed to counteract environmental challenges like magnetic and vibration interferences. Actionable guidelines for both planning and executing the construction of electron microscope labs highlighted in this tutorial are intended as an important resource to troubleshoot or upgrade existing lab facilities and to consult in preparation of future lab construction projects.
基金supported by Independent Research Project of State Key Laboratory of Advanced Special Steel,Shanghai Key Laboratory of Advanced Ferrometallurgy,Shanghai University(SKLASS-2023-Z13)the Science and Technology Commission of Shanghai Municipality(No.19DZ2270200)+1 种基金A portion of the work was performed at US National High Magnetic Field Laboratory,which is supported by the National Science Foundation(Cooperative Agreement No.DMR-1157490 and DMR-1644779)the State of Florida.Thanks also to Mary Tyler for editing.
文摘The high-temperature dissolution behavior of primary carbides in samples taken from GCr15 continuous-casting bloom was observed in-situ by confocal laser scanning microscopy.Equations were fitted to the dissolution kinetics of primary carbides during either heating or soaking.Dissolution of carbides proceeded in three stages(fast→slow→faster)as either temperature or holding time was increased.During the heating process and during the first and third stages of the soaking process,the original size of the carbides determined the steepness of the slope,but during the middle(“slow”)stage of the soaking process,the slope remained zero.The initial size of the carbides varied greatly,but their final dissolution temperature fell within the narrow range of 1210-1235℃,and the holding time remained within 50 min.Fractal analysis was used to study the morphological characteristics of small and medium-sized carbides during the dissolution process.According to changes in the fractal dimension before and after soaking,the carbides tended to evolve towards a more regular morphology.
基金Project supported by the National Key Research and Development Program of China(Grant No.2021YFA1402103)the National Natural Science Foundation of China(Grant No.12393825)。
文摘Two-photon dissociation of BeH^(+)ions is studied by detecting the fluorescence changes of Be^(+)-BeH^(+)bi-component Coulomb crystal in a linear Paul trap.BeH^(+)ions generated by an exothermic reaction between electronically excited Be^(+)ions and residual H_(2) in the vacuum chamber are photon-dissociated with two photons scanning over the range of 201 nm to 208 nm.Our experiment provides a novel method to maintain the number of Be^(+)ions stable in a Coulomb crystal with a middle ultraviolet band dissociation laser.This two-photon dissociation method extends the wavelength range of the dissociation laser for BeH^(+)compared to the one-photon dissociation,and the method can be utilized to all alkaline earth atomic ions which require suppression of the reaction with residual H_(2) gas in vacuum.
基金National Natural Science Foundation of China(No.22264013)Hainan Province Clinical Medical Center(No.2021)Hainan Province Science and Technology Special Fund(No.ZDYF2024SHFZ104).
文摘Hypochlorous acid(HClO)is a critical biomolecule in living organisms,playing an essential role in numerous physiological or pathological processes.Abnormal levels of HClO in the body may lead to a series of diseases,for instance,inflammation and cancer.Thus,accurate measurement of HClO levels should be more beneficial for understanding its role in diseases and gaining a deeper insight into the pathogenesis of diseases.In this work,we designed a near-infrared two-photon fluorescent probe(HDM-Cl-HClO)for detecting fluctuations in HClO levels in inflammatory and tumor-bearing mice.Notably,the probe can respond to HClO within 5 s and trigger a brilliant red fluorescence at 660 nm.It exhibits high specificity and sensitivity for HClO.The superior spectral capability of the probe has enabled the detection of HClO levels in cells and zebrafish,as well as achieved the detection of HClO in inflammatory and tumor mice.This work not only provides a novel strategy and tool for HClO imaging in living systems,but also holds great potential for the diagnosis of inflammation and cancer.
基金financially supported by the National Natural Science Foundation of China(No.U20B6003)the China Scholarship Council(No.202306440015)a project of the China Petroleum&Chemical Corporation(No.P22174)。
文摘The hybrid CO_(2) thermal technique has achieved considerable success globally in extracting residual heavy oil from reserves following a long-term steam stimulation process.Using microscopic visualization experiments and molecular dynamics(MD)simulations,this study investigates the microscopic enhanced oil recovery(EOR)mechanisms underlying residual oil removal using hybrid CO_(2) thermal systems.Based on the experimental models for the occurrence of heavy oil,this study evaluates the performance of hybrid CO_(2) thermal systems under various conditions using MD simulations.The results demonstrate that introducing CO_(2) molecules into heavy oil can effectively penetrate and decompose dense aggregates that are originally formed on hydrophobic surfaces.A stable miscible hybrid CO_(2) thermal system,with a high effective distribution ratio of CO_(2),proficiently reduces the interaction energies between heavy oil and rock surfaces,as well as within heavy oil.A visualization analysis of the interactions reveals that strong van der Waals(vdW)attractions occur between CO_(2) and heavy oil molecules,effectively promoting the decomposition and swelling of heavy oil.This unlocks the residual oil on the hydrophobic surfaces.Considering the impacts of temperature and CO_(2) concentration,an optimal gas-to-steam injection ratio(here,the CO_(2):steam ratio)ranging between 1:6 and 1:9 is recommended.This study examines the microscopic mechanisms underlying the hybrid CO_(2) thermal technique at a molecular scale,providing a significant theoretical guide for its expanded application in EOR.
基金supported by the Shandong Provincial Natural Science Foundation,China(No.ZR2020MA078)。
文摘Four benzocoumarin-based two-photon fluorescent probes(BH1-BH4)are proposed for ra-tiometric detection of hypochlorous acid(HClO)and their two-photon sensing perfor-mance are evaluated by means of time-dependent density func-tional theory and quadratic re-sponse theory.The effects of benzene-fused position on Stokes shift,fluorescence quantum yield and two-photon absorption are discussed comprehensively.The results show that fusing a benzene ring in coumarin can enhance Stokes shift efficiently.The benzene-fused position has important effects on these photophysical properties.The benzo[g]coumarins(BH1)and benzo[f]coumarins(BH2)derivatives have larger Stokes shifts in comparison with benzo[h]coumarins(BH3)and dihydrophenazine(BH4)derivatives.The two-photon absorp-tion of benzo[f]coumarins(BH2)derivative is much smaller than those of other benzo-coumarins derivatives.The large Stokes shift and increased two-photon action cross section can be achieved simultaneously in the dihydrophenazine(BH4)derivative.Therefore,the de-signed BH4 is expected to have superior performance for the ratiometric detection of HClO.To explore the reasons behind these effects,the intramolecular charge transfer degrees are il-lustrated quantitatively by plotting the hole-electron isosurface map,and the relation be-tween charge transfer and Stokes shift is revealed.A two-state model analysis is employed to understand two-photon absorption ability.Moreover,the fluorescence near-quenching mecha-nism of the product molecules B1 and B3 is explained by analyzing reorganization energy and Huang-Rhys factor,as well as related normal mode.Our research could contribute to the effi-cient design of ratiometric two-photon fluorescent probes with large Stokes shift and signifi-cant two-photon action cross section.
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financially supported by the National Natural Science Foundation of China(Nos.11904039,52125103,52071041,U21A2054 and 12104071)。
文摘SnS,a well-known van der Waals chalcogenide,is susceptible to oxidation in high-temperature or highhumidity environments,significantly impacting its functional performance and device stability.Conversely,oxidation can be used as an effective strategy for surface engineering,allowing for structure modulation or design,property tuning and application exploration.However,there is currently a gap in understanding the relationship between the oxidation behavior of SnS,the structure of its oxidized surface,and the dependence on oxidation temperature.In this study,we systematically investigated the evolution of SnS surfaces under thermal oxidation using electron microscopy.The microstructure evolution(e.g.,surface structures,phases,defects,and interface)of SnS during high-temperature oxidation has been fully characterized and studied based on cross-sectional samples.Various surface heterostructures were constructed,including SnO_(2)/SnS,SnO_(2)/SnS_(2)/SnS,and SnO_(2)/Sn_(2)S_(3)/SnS,offering significant potential for the surface functionalization of SnS-based systems.Accordingly,oxidation mechanisms at different stages were elucidated based on the detailed and clear picture of microstructures.This research not only deepens our understanding of the fundamental science of SnS oxidation but also provides valuable insights for preventing and developing surface oxidation engineering in SnS and other van der Waals chalcogenides/materials.
基金Project supported by the National Key Research&Development Program of China(Grant Nos.2019YFA0308600 and 2020YFA0309000)the National Natural Science Foundation of China(Grant Nos.92365302,92065201,22325203,92265105,12074247,12174252,52102336)+2 种基金the Strategic Priority Research Program of Chinese Academy of Sciences(Grant No.XDB28000000)the Science and Technology Commission of Shanghai Municipality(Grant Nos.2019SHZDZX01,19JC1412701,20QA1405100,24LZ1401000,LZPY2024-04)financial support from the Innovation Program for Quantum Science and Technology(Grant No.2021ZD0302500)。
文摘Manipulating and braiding Majorana zero modes(MZM)are a critical step toward realizing topological quantum computing.The primary challenge is controlling the vortex,which hosts the MZM,within a superconducting film in a spatially precise manner.To address this,we developed a magnetic force-based vortex control technology using the STM system with a self-designed four-electrode piezo-scanner tube and investigated vortex manipulation on the NbSe_(2) superconducting film.We employed ferromagnetic tips to control the movement of vortex array induced by the tip's remanent magnetism.A magnetic core solenoid device was integrated into the STM system and a strong magnetic tip demagnetization technique was developed,providing a viable technical solution for further enabling single vortex manipulation.
基金funded by the National Key Research and Development Program of China(Grant No.2022YFB3402500)the National Natural Science Foundation of China(Grant No.12372129).
文摘Embedding optical fiber sensors into composite materials offers the advantage of real-time structural monitoring.However,there is an order-of-magnitude difference in diameter between optical fibers and reinforcing fibers,and the detailed mechanism of how embedded optical fibers affect the micromechanical behavior and damage failure processes within composite materials remains unclear.This paper presents a micromechanical simulation analysis of composite materials embedded with optical fibers.By constructing representative volume elements(RVEs)with randomly distributed reinforcing fibers,the optical fiber,the matrix,and the interface phase,the micromechanical behavior and damage evolution under transverse tensile and compressive loads are explored.The study finds that the presence of embedded optical fibers significantly influences the initiation and propagation of microscopic damage within the composites.Under transverse tension,the fiber-matrix interface cracks first,followed by plastic cracking in the matrix surrounding the fibers,forming micro-cracks.Eventually,these cracks connect with the debonded areas at the fiber-matrix interface to form a dominant crack that spans the entire model.Under transverse compression,plastic cracking first occurs in the resin surrounding the optical fibers,connecting with the interface debonding areas between the optical fibers and the matrix to form two parallel shear bands.Additionally,it is observed that the strength of the interface between the optical fiber and the matrix critically affects the simulation results.The simulated damage morphologies align closely with those observed using scanning electron microscopy(SEM).These findings offer theoretical insights that can inform the design and fabrication of smart composite materials with embedded optical fiber sensors for advanced structural health monitoring.
基金supported by the project of the National Key Research and Development Program of China(No.2022YFA1207600)the National Natural Science Foundation of China(Nos.62005294,62375272)TIPC Director’s Fund.
文摘The complexity of cancer therapy has led to the emergence of combination therapy as a promising approach to enhance treatment efficacy and safety.The integration of glutathione(GSH)-activatable two-photon photodynamic therapy(TP-PDT)and chemodynamic therapy(CDT)offers the possibility to advance precision and efficacy in anti-cancer treatments.In this study,a GSH-activatable photosensitizer(PS),namely copper-elsinochrome(CuEC),is synthesized and utilized for combination second nearinfrared(NIR-II)TP-PDT/CDT.The Cu^(2+)acts as a“lock”,suppressing the fluorescence and^(1)O_(2)generation ability of EC in a normal physiological environment(“OFF”state).However,the overexpressed GSH in the tumor microenvironment acts as the“key”,resulting in the release of EC(“ON”state)and Cu^(+)(reduced by GSH).The released EC can be utilized for fluorescence imaging and TP-PDT under NIR-II(λ=1000 nm)two-photon excitation,while Cu+can generate highly toxic hydroxyl radicals(•OH)via Fenton-like reaction for CDT.Additionally,this process consumes GSH and diminishes the tumor’s antioxidant capacity,thereby augmenting the efficacy of combination therapy.The CuEC achieves significant tumor cell ablation in both 2D monolayer cells and 3D multicellular tumor spheres through the combination of NIR-II TP-PDT and CDT.
