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
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
Correlation between tunable optical properties and push-pull structural characters has attracted extensive attention in material science and nonlinear optics.Here,several indacenodithiophene(IDT)derivatives denoted as...Correlation between tunable optical properties and push-pull structural characters has attracted extensive attention in material science and nonlinear optics.Here,several indacenodithiophene(IDT)derivatives denoted as IDT-2NA,NA-IDT-CN,and IDT-2CN with different terminal substituents are investigated comparatively to demonstrate their intrinsic structure-property relationships.Interestingly,the IDT core acts diverse roles as acceptor(A)and donor(D)in the obtained three derivatives.Symmetric IDT-2NA with a D-A-D architecture shows an absorption maximum around 459 nm in THF.Contrary to the symmetric analog IDT-2CN with a reverse A-D-A feature,NA-IDT-CN with a different D-D'-A motif characterizes an obvious solvent polarity effect.Theo-retical calculation and electrostatic potential results confirm the terminal substituents with different electronic conjugation play vital roles in affecting the resultant photophysical properties.Utilizing the femtosecond open-aperture Z-scan technique,significant two-photon absorption(2PA)capabilities are obtained ranging from 540 to 900 nm.The 2PA cross section(δ_(2pA) )maximum about 5390 GM of centrosymmetric IDT-2CN exhibits at 600 nm.Distinct excited-state dynamics with the help of femtosecond transition absorption supports the effective intramolecular charge transfer which accounts for enhancing theδ_(2pA) values.Their potential optical power limiting applications based on the 2PA mechanism were further evaluated.The limiting thresholds were found to be 2.793.35 mJ/cm^(2) for the three IDT derivatives with a sequence of IDT-2CN<IDT-2NA<NA-IDT-CN.The distinct structural motifs and effective 2PA capabilities in the current work may provide reliable insights into the push-pull IDT chromophores for advanced nonlinear optical applications.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
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
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
Two-photon fluorescence microscopy,based on the principles of two-photon excited fluorescence and second harmonic generation,enables real-time non-invasive in vivo imaging of skin and cells,providing a means to assess...Two-photon fluorescence microscopy,based on the principles of two-photon excited fluorescence and second harmonic generation,enables real-time non-invasive in vivo imaging of skin and cells,providing a means to assess human health status.In this paper,a miniaturized two-photon imaging system is designed and fabricated to withstand extreme vibration and shock environments.The mechanical stability of the optical and structural components of the miniaturized probe is evaluated under random vibration and shock vibration tests using finite element simulation methods and ray tracing techniques.During the environmental testing,the maximum stress on the probe is 11.5 MPa,which is well below the threshold for structural failure.The largest structural displacement occurs at the collimator,where random vibrations produce an offset of 10.9μm.This offset is analyzed by using geometric optics and point spread functions.Under the maximum collimator offset,the theoretical resolution,as calculated by the point spread function,shifted from 463.28 nm to 463.48 nm.Additionally,a lateral offset of 127 nm is observed at the center position,which does not significantly impact the imaging performance.Finally,environmental and imaging performance tests are conducted.The system’s measured resolution after the environmental tests is 530 nm,consistent with its resolution prior to testing.Imaging tests are also performed on the skin’s stratum corneum,granular layer,spinous layer,and basal cell layer,revealing clear cellular structural information.These results confirm the device’s potential for applications in extreme shock and vibration environments.展开更多
Carbazole-core multi-branched chromophores 9-ethyl- 3, 6-bis （ 2- { 4- [ 5- （4-tert-butyl-phenyl） - [ 1, 3, 4 ] oxadiazol-2-yl ] - phenyl }-vinyl） -carbazole（3） and 9-ethyl-3-（ 2- {4-[ 5-（4-tert-butyl- phenyl...Carbazole-core multi-branched chromophores 9-ethyl- 3, 6-bis （ 2- { 4- [ 5- （4-tert-butyl-phenyl） - [ 1, 3, 4 ] oxadiazol-2-yl ] - phenyl }-vinyl） -carbazole（3） and 9-ethyl-3-（ 2- {4-[ 5-（4-tert-butyl- phenyl） -[ 1, 3, 4 ] oxadiazol-2-yl ] -phenyl }-vinyl ） -carbazole （ 2 ） are synthesized through Wittig reaction and characterized by nuclear magnetic resonance（NMR）and infrared（IR）. The two- photon absorption properties of chromophores are investigated. These chromophores exhibit large two-photon absorption crosssections and strong blue two-photon excited fluorescence. The cooperative enhancement of two-photon absorption（TPA） in the multi-branched structures is observed. This enhancement is partly attributed to the electronic coupling between the branches. The electronic push-pull structures in the arm and their cooperative effects help the extended charge transfer for TPA.展开更多
Two new bithiophene derivatives named as 5, 5-bis(p-N,N-dimethylaminostyryl)-2, 2 -bithiophene (BMSBT), and 5, 5-bis(p-N,N-diethylaminostyryl)-2, 2-bithiophene (BESBT) have been synthesized. Both compounds can emit s...Two new bithiophene derivatives named as 5, 5-bis(p-N,N-dimethylaminostyryl)-2, 2 -bithiophene (BMSBT), and 5, 5-bis(p-N,N-diethylaminostyryl)-2, 2-bithiophene (BESBT) have been synthesized. Both compounds can emit strong single-photon excited fluorescence (SPEF) and two-photon excited fluorescence (TPEF) with the emission peaks around ~560 nm and with the lifetime of ~1ns.展开更多
Efficient Ti-catalyzed reductive coupling methodology was first employed to synthesize the symmetrical bis-donor stilbene, trans-4, 4'-bis[diphenyl amino] stilbene (BDPAS). X-ray diffraction analyses reveal that t...Efficient Ti-catalyzed reductive coupling methodology was first employed to synthesize the symmetrical bis-donor stilbene, trans-4, 4'-bis[diphenyl amino] stilbene (BDPAS). X-ray diffraction analyses reveal that this new crystal belongs to the triclinic crystal system of centro-symmetric P-1 space group. The DBPAS solution, with the linear transmission at wavelength of greater than or equal to 450 nm, possesses large two-photon absorption cross section as high as 39.4x10(-48) cm(4).s/photon resulting in strong two-photon induced blue fluorescence of 460 nm, pumped by 740 nm laser irradiation.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
Two new s-triazine derivatives, which belong to linear dipolar type and triangle octupolar type respectively, have been synthesized. The structure of the dipolar compound has been determined by X-ray diffraction. The ...Two new s-triazine derivatives, which belong to linear dipolar type and triangle octupolar type respectively, have been synthesized. The structure of the dipolar compound has been determined by X-ray diffraction. The two-photon absorption cross-section σ, and the two-photon excited fluorescence (TPEF) intensities are increased significantly from dipolar compound to octupolar compound.展开更多
Two new compounds involving a thiophene moiety named as 2,5-bis[4-(N,N- diphenyl- amino)styryl]thiophene (BPST) and 2,5-bis[4-(N,N-diethylamino)styryl]thiophene (BEST) have been synthesized. The two-photon absorptio...Two new compounds involving a thiophene moiety named as 2,5-bis[4-(N,N- diphenyl- amino)styryl]thiophene (BPST) and 2,5-bis[4-(N,N-diethylamino)styryl]thiophene (BEST) have been synthesized. The two-photon absorption cross section of BPST was measured as large as 256 × 10-50 cm4·s/photon, when it was excited by 800 nm femtosecond laser.展开更多
By observing two-photon response and anisotropy of the light-induced voltage in Al-Si Schottky barrier potential,it is certified from the experimental and theoretical analysis that the built-in electric field generate...By observing two-photon response and anisotropy of the light-induced voltage in Al-Si Schottky barrier potential,it is certified from the experimental and theoretical analysis that the built-in electric field generated by the Schottky barrier potential will induce the phenomena of optical rectification in Si photodiode.Thus,it is deduced that there must be double-frequency absorption caused by phase-mismatch in the mechanism of two-photon response of Si photodiode.If the intensity of the built-in electric field is strong enough,the double-frequency absorption will be the main factor of the two-photon response,which is different from the conventional opinion that the two-photon response is just the two-photon absorption.展开更多
A surface femtosecond two-photon photoemission （2PPE） spectrometer devoted to the study of ultrafast excited electron dynamics and photochemical kinetics on metal and metal oxide surfaces has been constructed. Low e...A surface femtosecond two-photon photoemission （2PPE） spectrometer devoted to the study of ultrafast excited electron dynamics and photochemical kinetics on metal and metal oxide surfaces has been constructed. Low energy photoelectrons are measured using a hemispherical electron energy analyzer with an imaging detector that allows us to detect the energy and the angular distributions of the photoelectrons simultaneously. A Mach-Zehnder interferom- eter was built for the time-resolved 2PPE （TR-2PPE） measurement to study ultrafast surface excited electron dynamics, which was demonstrated on the Cu（111） surface. A scheme for measuring time-dependent 2PPE （TD-2PPE） spectra has also been developed for studies of surface photochemistry. This technique has been applied to a preliminary study on the photochemical kinetics on ethanol/TiO2（110）. We have also shown that the ultrafast dynamics of photoinduced surface excited resonances can be investigated in a reliable way by combining the TR-2PPE and TD-2PPE techniques.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
The isotope effects of XF （X=H, D） on the population transfer process via two-photon resonance excitation are investigated by solving the time-dependent SchrSdinger equation. The vibrational levels v=0 and 2 of the ...The isotope effects of XF （X=H, D） on the population transfer process via two-photon resonance excitation are investigated by solving the time-dependent SchrSdinger equation. The vibrational levels v=0 and 2 of the ground electronic state are taken to be the initial and target states, respectively, for the two molecular systems. The influences of the field peak amplitude and pulse duration on the population transfer process are discussed in detail. The pulse duration is required to be longer than 860 fs for the DF molecule to achieve a relatively high transfer probability （more than 80%）, while the one for the HF molecule is just required to be longer than 460 fs. Moreover, the intermediate level v=1 and the higher level v=3 may play more important roles in the two-photon resonance process for the DF molecule, compared to the roles in the process for the HF molecule.展开更多
The analytic response theory at density functional theory level is applied to investigate onephoton and two-photon absorption properties of a series of recently synthesized pyrene-core derivatives. The theoretical res...The analytic response theory at density functional theory level is applied to investigate onephoton and two-photon absorption properties of a series of recently synthesized pyrene-core derivatives. The theoretical results show that there are a few charge-transfer states for each compound in the lower energy region. The one-photon absorption properties of the five investigated compounds are highly consistent with those given by experimental measurements. The two-photon absorption intensities of the compounds are greatly enhanced with the increments of the molecular sizes, in which the two-photon absorption cross section of the four-branched compound is about 5.6 times of that of the mono-branched molecule. Fhrthermore, it is shown that the two-photon absorption properties are sensitive to the geometrical arrangements.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
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
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the National Natural Science Foundation of China(22172097)the Shaanxi Provincial Sci-ence Fund for Distinguished Young Scholars(2025JC-JCQN-044)+1 种基金the National Key Research and Development Program of China(2022YFA1205502)the 111 Project(B14041).
文摘Correlation between tunable optical properties and push-pull structural characters has attracted extensive attention in material science and nonlinear optics.Here,several indacenodithiophene(IDT)derivatives denoted as IDT-2NA,NA-IDT-CN,and IDT-2CN with different terminal substituents are investigated comparatively to demonstrate their intrinsic structure-property relationships.Interestingly,the IDT core acts diverse roles as acceptor(A)and donor(D)in the obtained three derivatives.Symmetric IDT-2NA with a D-A-D architecture shows an absorption maximum around 459 nm in THF.Contrary to the symmetric analog IDT-2CN with a reverse A-D-A feature,NA-IDT-CN with a different D-D'-A motif characterizes an obvious solvent polarity effect.Theo-retical calculation and electrostatic potential results confirm the terminal substituents with different electronic conjugation play vital roles in affecting the resultant photophysical properties.Utilizing the femtosecond open-aperture Z-scan technique,significant two-photon absorption(2PA)capabilities are obtained ranging from 540 to 900 nm.The 2PA cross section(δ_(2pA) )maximum about 5390 GM of centrosymmetric IDT-2CN exhibits at 600 nm.Distinct excited-state dynamics with the help of femtosecond transition absorption supports the effective intramolecular charge transfer which accounts for enhancing theδ_(2pA) values.Their potential optical power limiting applications based on the 2PA mechanism were further evaluated.The limiting thresholds were found to be 2.793.35 mJ/cm^(2) for the three IDT derivatives with a sequence of IDT-2CN<IDT-2NA<NA-IDT-CN.The distinct structural motifs and effective 2PA capabilities in the current work may provide reliable insights into the push-pull IDT chromophores for advanced nonlinear optical applications.
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 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.
基金supported by the National Natural Science Foundation of China(62475008,62305186).
文摘Two-photon fluorescence microscopy,based on the principles of two-photon excited fluorescence and second harmonic generation,enables real-time non-invasive in vivo imaging of skin and cells,providing a means to assess human health status.In this paper,a miniaturized two-photon imaging system is designed and fabricated to withstand extreme vibration and shock environments.The mechanical stability of the optical and structural components of the miniaturized probe is evaluated under random vibration and shock vibration tests using finite element simulation methods and ray tracing techniques.During the environmental testing,the maximum stress on the probe is 11.5 MPa,which is well below the threshold for structural failure.The largest structural displacement occurs at the collimator,where random vibrations produce an offset of 10.9μm.This offset is analyzed by using geometric optics and point spread functions.Under the maximum collimator offset,the theoretical resolution,as calculated by the point spread function,shifted from 463.28 nm to 463.48 nm.Additionally,a lateral offset of 127 nm is observed at the center position,which does not significantly impact the imaging performance.Finally,environmental and imaging performance tests are conducted.The system’s measured resolution after the environmental tests is 530 nm,consistent with its resolution prior to testing.Imaging tests are also performed on the skin’s stratum corneum,granular layer,spinous layer,and basal cell layer,revealing clear cellular structural information.These results confirm the device’s potential for applications in extreme shock and vibration environments.
基金The National Natural Science Foundation of China(No.60678042)the Natural Science Foundation of Jiangsu Province(No.BK2006553)the Pre-Research Project of the National Natural Science Foundation supported by Southeast University(No.9207041399)
文摘Carbazole-core multi-branched chromophores 9-ethyl- 3, 6-bis （ 2- { 4- [ 5- （4-tert-butyl-phenyl） - [ 1, 3, 4 ] oxadiazol-2-yl ] - phenyl }-vinyl） -carbazole（3） and 9-ethyl-3-（ 2- {4-[ 5-（4-tert-butyl- phenyl） -[ 1, 3, 4 ] oxadiazol-2-yl ] -phenyl }-vinyl ） -carbazole （ 2 ） are synthesized through Wittig reaction and characterized by nuclear magnetic resonance（NMR）and infrared（IR）. The two- photon absorption properties of chromophores are investigated. These chromophores exhibit large two-photon absorption crosssections and strong blue two-photon excited fluorescence. The cooperative enhancement of two-photon absorption（TPA） in the multi-branched structures is observed. This enhancement is partly attributed to the electronic coupling between the branches. The electronic push-pull structures in the arm and their cooperative effects help the extended charge transfer for TPA.
基金This work is supported by the National Natural Science Foundation of China(No.20172034)grant for State Key Program of China.
文摘Two new bithiophene derivatives named as 5, 5-bis(p-N,N-dimethylaminostyryl)-2, 2 -bithiophene (BMSBT), and 5, 5-bis(p-N,N-diethylaminostyryl)-2, 2-bithiophene (BESBT) have been synthesized. Both compounds can emit strong single-photon excited fluorescence (SPEF) and two-photon excited fluorescence (TPEF) with the emission peaks around ~560 nm and with the lifetime of ~1ns.
文摘Efficient Ti-catalyzed reductive coupling methodology was first employed to synthesize the symmetrical bis-donor stilbene, trans-4, 4'-bis[diphenyl amino] stilbene (BDPAS). X-ray diffraction analyses reveal that this new crystal belongs to the triclinic crystal system of centro-symmetric P-1 space group. The DBPAS solution, with the linear transmission at wavelength of greater than or equal to 450 nm, possesses large two-photon absorption cross section as high as 39.4x10(-48) cm(4).s/photon resulting in strong two-photon induced blue fluorescence of 460 nm, pumped by 740 nm laser irradiation.
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supported by the National Natural Science Foundation of China(No.20172034,20472044)the Ph.D.Programs Foundation of Ministry of Education of China
文摘Two new s-triazine derivatives, which belong to linear dipolar type and triangle octupolar type respectively, have been synthesized. The structure of the dipolar compound has been determined by X-ray diffraction. The two-photon absorption cross-section σ, and the two-photon excited fluorescence (TPEF) intensities are increased significantly from dipolar compound to octupolar compound.
基金supported by the National Natural Science Foundation of China(No.20172034)the Ph.D.programs Foundation of Ministry of Education of China
文摘Two new compounds involving a thiophene moiety named as 2,5-bis[4-(N,N- diphenyl- amino)styryl]thiophene (BPST) and 2,5-bis[4-(N,N-diethylamino)styryl]thiophene (BEST) have been synthesized. The two-photon absorption cross section of BPST was measured as large as 256 × 10-50 cm4·s/photon, when it was excited by 800 nm femtosecond laser.
文摘By observing two-photon response and anisotropy of the light-induced voltage in Al-Si Schottky barrier potential,it is certified from the experimental and theoretical analysis that the built-in electric field generated by the Schottky barrier potential will induce the phenomena of optical rectification in Si photodiode.Thus,it is deduced that there must be double-frequency absorption caused by phase-mismatch in the mechanism of two-photon response of Si photodiode.If the intensity of the built-in electric field is strong enough,the double-frequency absorption will be the main factor of the two-photon response,which is different from the conventional opinion that the two-photon response is just the two-photon absorption.
文摘A surface femtosecond two-photon photoemission （2PPE） spectrometer devoted to the study of ultrafast excited electron dynamics and photochemical kinetics on metal and metal oxide surfaces has been constructed. Low energy photoelectrons are measured using a hemispherical electron energy analyzer with an imaging detector that allows us to detect the energy and the angular distributions of the photoelectrons simultaneously. A Mach-Zehnder interferom- eter was built for the time-resolved 2PPE （TR-2PPE） measurement to study ultrafast surface excited electron dynamics, which was demonstrated on the Cu（111） surface. A scheme for measuring time-dependent 2PPE （TD-2PPE） spectra has also been developed for studies of surface photochemistry. This technique has been applied to a preliminary study on the photochemical kinetics on ethanol/TiO2（110）. We have also shown that the ultrafast dynamics of photoinduced surface excited resonances can be investigated in a reliable way by combining the TR-2PPE and TD-2PPE techniques.
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.
文摘The isotope effects of XF （X=H, D） on the population transfer process via two-photon resonance excitation are investigated by solving the time-dependent SchrSdinger equation. The vibrational levels v=0 and 2 of the ground electronic state are taken to be the initial and target states, respectively, for the two molecular systems. The influences of the field peak amplitude and pulse duration on the population transfer process are discussed in detail. The pulse duration is required to be longer than 860 fs for the DF molecule to achieve a relatively high transfer probability （more than 80%）, while the one for the HF molecule is just required to be longer than 460 fs. Moreover, the intermediate level v=1 and the higher level v=3 may play more important roles in the two-photon resonance process for the DF molecule, compared to the roles in the process for the HF molecule.
文摘The analytic response theory at density functional theory level is applied to investigate onephoton and two-photon absorption properties of a series of recently synthesized pyrene-core derivatives. The theoretical results show that there are a few charge-transfer states for each compound in the lower energy region. The one-photon absorption properties of the five investigated compounds are highly consistent with those given by experimental measurements. The two-photon absorption intensities of the compounds are greatly enhanced with the increments of the molecular sizes, in which the two-photon absorption cross section of the four-branched compound is about 5.6 times of that of the mono-branched molecule. Fhrthermore, it is shown that the two-photon absorption properties are sensitive to the geometrical arrangements.
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.
