Fluorophores emitting in the second near-infrared window (NIR-II, 900–1700nm) allow for high-resolution deep-tissue bioimaging owing to minimal tissue scattering. Although J-aggregation offers a promising approach to...Fluorophores emitting in the second near-infrared window (NIR-II, 900–1700nm) allow for high-resolution deep-tissue bioimaging owing to minimal tissue scattering. Although J-aggregation offers a promising approach to developing long-wavelength emitters, the scarcity of J-type backbones and reliable design principles limits their application in biological imaging. Here, we introduce a strategy for engineering high-brightness NIR-II J-aggregated fluorophores by incorporating electron-withdrawing substituents into a fused-ring backbone. These substituents modulate the electrostatic potential (ESP) distribution across the conjugated backbone, reducing both electrostatic repulsion and intermolecular distance, which promotes ordered J-aggregation. As a result, Y8 aggregate (Y8 nanoparticles) exhibits an outstanding fluorescence quantum yield of up to 12.9% and strong near-infrared absorption in aqueous solution for high-performance NIR-II fluorescence imaging in vivo. This work not only presents a novel J-type backbone but also advances the understanding of the structure–property relationship critical to designing NIR-II J-aggregates.展开更多
Background:Vestibular migraine(VM)is a common disorder characterized by recurrent dizziness or vertigo,often aggravated by cold exposure.This study aimed to identify differentially expressed circular RNAs(circRNAs)in ...Background:Vestibular migraine(VM)is a common disorder characterized by recurrent dizziness or vertigo,often aggravated by cold exposure.This study aimed to identify differentially expressed circular RNAs(circRNAs)in cold-region VM and explore the underlying molecular mechanisms.Methods:Peripheral blood samples from long-term residents of Heilongjiang Province profiled by circRNA microarray,and differentially expressed circRNAs were validated by quantitative reverse transcription polymerase chain reaction(qRT-PCR).A competing endogenous RNA(ceRNA)network and enriched pathways were inferred by bioinformatics.A VM-like mouse model was established using nitroglycerin(NTG)and kainic acid(KA)and confirmed by behavioral testing and western blot.The hsa_circ_0003201/miR-31-5p/triggering receptor expressed on myeloid cells 2(TREM2)axis and related pathways were examined in clinical samples and in the trigeminal nucleus caudalis(TNC)and vestibular nuclei(VN)of mice using qRT-PCR,enzyme-linked immunosorbent assay(ELISA),and western blot.CircRNA microarray profiling also compared expression patterns between VM and migraine patients.Results:Hsa_circ_0003201 was significantly upregulated in cold-region VM patients.Bioinformatic analyses revealed that hsa_circ_0003201 may regulate the miR-31-5p/TREM2 axis and be associated with phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)signaling,pyruvate metabolism,and transient receptor potential(TRP)pathways.Clinical validation confirmed increased hsa_circ_0003201 and TREM2 and decreased miR-31-5p.VM-like mice exhibited central sensitization and vestibular dysfunction,with increased TREM2,decreased miR-31-5p,and PI3K/AKT activation in the TNC and VN.Comparative circRNA analysis between VM and migraine patients indicated distinct expression patterns.Conclusion:Hsa_circ_0003201 shows potential as a diagnostic biomarker for cold-region VM,and the hsa_circ_0003201/miR-31-5p/TREM2 axis may contribute to pathogenesis through PI3K/AKT signaling,pyruvate metabolism,and TRP-related pathways.展开更多
Migraine is a common primary headache which seriously affects the quality of patients’life due to the high prevalence and disability rate.Recent years a large number of studies have found that temperature is directly...Migraine is a common primary headache which seriously affects the quality of patients’life due to the high prevalence and disability rate.Recent years a large number of studies have found that temperature is directly bound to migraine and migraine patients in cold regions have higher prevalence,different manifestations and poor response to the conventional therapy.We propose in this review article a new concept of migraine in cold regions on the basis of geography and summarize the research advances on the pathogenesis of migraine in cold regions to provide conceptual basis for the clinical diagnosis and treatment of this disease entity.展开更多
Objective:It aims to evaluate the diagnostic ability of CGRP and other blood indicators in vestibular migraine(VM)patients,and to explain the potential pathological effects of these biomarkers.The hypothesis of VM bei...Objective:It aims to evaluate the diagnostic ability of CGRP and other blood indicators in vestibular migraine(VM)patients,and to explain the potential pathological effects of these biomarkers.The hypothesis of VM being a variant of migraine was examined.Methods:A total of 32 VM patients,35 migraine patients,and 30 healthy control subjects(HC)were selected for this cross-sectional study.Detailed statistics on demographic data,clinical manifestations,calcitonin gene-related peptide(CGRP)and common clinical laboratory indicators were measured within 24 hours from the onset of the conditions.Receptor operating characteristic(ROC)curve and area under the curve(AUC)were analyzed for biomarkers.The risk factors of VM and migraine were determined through univariate and multivariate analyses.Results:Compared with HC,serum CGRP levels(p(VM)=0.012,p(Migraine)=0.028)increased and Mg^(2+)levels(p(VM)<0.001,p(Migraine)<0.001)deceased in VM patients and migraine patients.In multiple logistic regression,VM was correlated with CGRP[odds ratio(OR)=1.07;95%confidence interval(CI),1.02-1.12;P=0.01]and Mg^(2+)[odds ratio(OR)=0.03;95%CI,0.07-0.15;P<0.001].Migraine was correlated with CGRP[odds ratio(OR)=1.07;95%CI,1.02-1.12;P=0.01]and Mg^(2+)[odd ratio(OR=0.01;95%CI,0-0.02;P<0.001)].Mg^(2+)discriminated good differentiation between VM and migraine groups,with AUC of 0.649(95%CI,0.518 to 0.780).The optimal threshold for Mg^(2+)to diagnose VM was 0.805.Conclusions:This study demonstrated that CGRP and Mg^(2+)may be promising laboratory indicators to discriminate HC from VM/migraine,while Mg^(2+)may be uded as a discriminator between VM and migraine.展开更多
Emission quenching resulting from fluorophore aggregation has long been a significant challenge in optimizing emission-based technologies,such as fluorescence imaging and optoelectronic devices.Alleviating this quench...Emission quenching resulting from fluorophore aggregation has long been a significant challenge in optimizing emission-based technologies,such as fluorescence imaging and optoelectronic devices.Alleviating this quenching in aggregates is crucial,yet progress is impeded by the limited understanding of the nature and impact of aggregates on emission.Here,we elucidate the critical role of dimeric aggregate(dimer)in alleviating second near-infrared(NIR-II,900-1700 nm)emission quenching from ring-fused fluorophore 4F for superior fluorescence imaging.Spectral decomposition and molecular dynamics simulations demonstrate the predominance of dimer populations in 4F aggregates.Notably,dimers exhibit significantly weaker emission but intense intermolecular nonradiative(interNR)decay compared to monomers,as demonstrated by ultrafast spectra and quantum calculation.Therefore,the predominant population of dimers with weak emission and pronounced interNR feature underlies the emission quenching in 4F aggregates.This discovery guides the preparation of ultrabright NIR-II 4F nanofluorophore(4F NP3s)by decreasing dimer populations,which show 5-fold greater NIR-II brightness than indocyanine green,enabling superior resolution in visualizing blood vessels.This work offers valuable insights into aggregation-caused quenching,with broad implications extending far beyond NIR-II fluorescence imaging.展开更多
Photo-induced excited-state dynamics within organic materials fundamentally determine their photophysical properties for various applications,and thus understanding the primary excited-state dynamics behavior is of fu...Photo-induced excited-state dynamics within organic materials fundamentally determine their photophysical properties for various applications,and thus understanding the primary excited-state dynamics behavior is of fundamental and practical significance.Until recently,the excited-state dynamics of organic materials towards biophotonics have been rarely studied,although numerous endeavors have been devoted to the design of organic materials for biophotonics.Herein,various spectroscopy technologies including femtosecond transient absorption(fs-TA)spectroscopy clearly reveal a totally different excited state dynamics behavior within Bodipy monomer(2B-BDP dye)and aggregates(2B-BDP NPs),indicating strongly morphology dependent character.2B-BDP dye undergoes an ultrafast conversion from S1 to intramolecular charge transfer(ICT)state for subsequent photoluminescence(PL)and nonradiative(NR)decay,while 2B-BDP NPs show an accelerated excited-state deactivation mainly through S1→S0 NR decay.The potential bioapplications based on the corresponding excited state dynamics behavior are discussed together with experimental results.Interestingly,the accelerated NR decay in 2B-BDP NPs does not yield a stronger photoacoustic(PA)signal than that in 2B-BDP dye,which violates the conventional wisdom that faster NR decay would benefit the photothermal effects for better photoacoustic imaging(PAI).These insightful and fundamental observations of the excited-state dynamics may contribute an alternative approach at the molecular level towards the future design of functional Bodipy-based organic molecules with desirable performances.展开更多
基金support from the National Natural Science Foundation of China (Nos. 62175201 and 52373142)the Natural Science Foundation of Jiangsu Province of China (No. BK20220404)+1 种基金the Fundamental Research Funds for the Central Universitiesthe open research fund of State Key Laboratory of Organic Electronics and Information Displays.
文摘Fluorophores emitting in the second near-infrared window (NIR-II, 900–1700nm) allow for high-resolution deep-tissue bioimaging owing to minimal tissue scattering. Although J-aggregation offers a promising approach to developing long-wavelength emitters, the scarcity of J-type backbones and reliable design principles limits their application in biological imaging. Here, we introduce a strategy for engineering high-brightness NIR-II J-aggregated fluorophores by incorporating electron-withdrawing substituents into a fused-ring backbone. These substituents modulate the electrostatic potential (ESP) distribution across the conjugated backbone, reducing both electrostatic repulsion and intermolecular distance, which promotes ordered J-aggregation. As a result, Y8 aggregate (Y8 nanoparticles) exhibits an outstanding fluorescence quantum yield of up to 12.9% and strong near-infrared absorption in aqueous solution for high-performance NIR-II fluorescence imaging in vivo. This work not only presents a novel J-type backbone but also advances the understanding of the structure–property relationship critical to designing NIR-II J-aggregates.
基金supported by General Program of National Natural Science Foundation of China(No.82071549,82371483)Key Research&Development Program of Heilongjiang(No.2023ZX06C02)Youth Foundation of the first Affiliated Hospital of Harbin Medical University(No.2024YQ22).
文摘Background:Vestibular migraine(VM)is a common disorder characterized by recurrent dizziness or vertigo,often aggravated by cold exposure.This study aimed to identify differentially expressed circular RNAs(circRNAs)in cold-region VM and explore the underlying molecular mechanisms.Methods:Peripheral blood samples from long-term residents of Heilongjiang Province profiled by circRNA microarray,and differentially expressed circRNAs were validated by quantitative reverse transcription polymerase chain reaction(qRT-PCR).A competing endogenous RNA(ceRNA)network and enriched pathways were inferred by bioinformatics.A VM-like mouse model was established using nitroglycerin(NTG)and kainic acid(KA)and confirmed by behavioral testing and western blot.The hsa_circ_0003201/miR-31-5p/triggering receptor expressed on myeloid cells 2(TREM2)axis and related pathways were examined in clinical samples and in the trigeminal nucleus caudalis(TNC)and vestibular nuclei(VN)of mice using qRT-PCR,enzyme-linked immunosorbent assay(ELISA),and western blot.CircRNA microarray profiling also compared expression patterns between VM and migraine patients.Results:Hsa_circ_0003201 was significantly upregulated in cold-region VM patients.Bioinformatic analyses revealed that hsa_circ_0003201 may regulate the miR-31-5p/TREM2 axis and be associated with phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)signaling,pyruvate metabolism,and transient receptor potential(TRP)pathways.Clinical validation confirmed increased hsa_circ_0003201 and TREM2 and decreased miR-31-5p.VM-like mice exhibited central sensitization and vestibular dysfunction,with increased TREM2,decreased miR-31-5p,and PI3K/AKT activation in the TNC and VN.Comparative circRNA analysis between VM and migraine patients indicated distinct expression patterns.Conclusion:Hsa_circ_0003201 shows potential as a diagnostic biomarker for cold-region VM,and the hsa_circ_0003201/miR-31-5p/TREM2 axis may contribute to pathogenesis through PI3K/AKT signaling,pyruvate metabolism,and TRP-related pathways.
基金General Program of National Natural Science Foundation of China(82071549)Key Program of Natural Science Foundation of Heilongjiang Province(ZD2019H006)Key Program of Planning Subject for the 13th Five-Year Plan of Heilongjiang Province Education Sciences(GJB1319086).
文摘Migraine is a common primary headache which seriously affects the quality of patients’life due to the high prevalence and disability rate.Recent years a large number of studies have found that temperature is directly bound to migraine and migraine patients in cold regions have higher prevalence,different manifestations and poor response to the conventional therapy.We propose in this review article a new concept of migraine in cold regions on the basis of geography and summarize the research advances on the pathogenesis of migraine in cold regions to provide conceptual basis for the clinical diagnosis and treatment of this disease entity.
基金National Natural Science Foundation of China(No.82071549)Key Program of the Natural Science Fund in Heilongjiang Province(No.ZD2019H006)National Key Research&Development Program of China(No.2016YFC1307205).
文摘Objective:It aims to evaluate the diagnostic ability of CGRP and other blood indicators in vestibular migraine(VM)patients,and to explain the potential pathological effects of these biomarkers.The hypothesis of VM being a variant of migraine was examined.Methods:A total of 32 VM patients,35 migraine patients,and 30 healthy control subjects(HC)were selected for this cross-sectional study.Detailed statistics on demographic data,clinical manifestations,calcitonin gene-related peptide(CGRP)and common clinical laboratory indicators were measured within 24 hours from the onset of the conditions.Receptor operating characteristic(ROC)curve and area under the curve(AUC)were analyzed for biomarkers.The risk factors of VM and migraine were determined through univariate and multivariate analyses.Results:Compared with HC,serum CGRP levels(p(VM)=0.012,p(Migraine)=0.028)increased and Mg^(2+)levels(p(VM)<0.001,p(Migraine)<0.001)deceased in VM patients and migraine patients.In multiple logistic regression,VM was correlated with CGRP[odds ratio(OR)=1.07;95%confidence interval(CI),1.02-1.12;P=0.01]and Mg^(2+)[odds ratio(OR)=0.03;95%CI,0.07-0.15;P<0.001].Migraine was correlated with CGRP[odds ratio(OR)=1.07;95%CI,1.02-1.12;P=0.01]and Mg^(2+)[odd ratio(OR=0.01;95%CI,0-0.02;P<0.001)].Mg^(2+)discriminated good differentiation between VM and migraine groups,with AUC of 0.649(95%CI,0.518 to 0.780).The optimal threshold for Mg^(2+)to diagnose VM was 0.805.Conclusions:This study demonstrated that CGRP and Mg^(2+)may be promising laboratory indicators to discriminate HC from VM/migraine,while Mg^(2+)may be uded as a discriminator between VM and migraine.
基金support by the National Natural Science Foundation of China(No.62175201,62288102,and 52373142)the Fundamental Research Funds for the Central Universities,and the open research fund of State Key Laboratory of Organic Electronics and Information Displays.
文摘Emission quenching resulting from fluorophore aggregation has long been a significant challenge in optimizing emission-based technologies,such as fluorescence imaging and optoelectronic devices.Alleviating this quenching in aggregates is crucial,yet progress is impeded by the limited understanding of the nature and impact of aggregates on emission.Here,we elucidate the critical role of dimeric aggregate(dimer)in alleviating second near-infrared(NIR-II,900-1700 nm)emission quenching from ring-fused fluorophore 4F for superior fluorescence imaging.Spectral decomposition and molecular dynamics simulations demonstrate the predominance of dimer populations in 4F aggregates.Notably,dimers exhibit significantly weaker emission but intense intermolecular nonradiative(interNR)decay compared to monomers,as demonstrated by ultrafast spectra and quantum calculation.Therefore,the predominant population of dimers with weak emission and pronounced interNR feature underlies the emission quenching in 4F aggregates.This discovery guides the preparation of ultrabright NIR-II 4F nanofluorophore(4F NP3s)by decreasing dimer populations,which show 5-fold greater NIR-II brightness than indocyanine green,enabling superior resolution in visualizing blood vessels.This work offers valuable insights into aggregation-caused quenching,with broad implications extending far beyond NIR-II fluorescence imaging.
基金supported by the National Natural Science Foundation of China(61805118,21674048)the Natural Science Foundation of Jiangsu Province of China(BK20171020)Open Research Fund of Key Laboratory for Organic Electronics and Information Displays。
文摘Photo-induced excited-state dynamics within organic materials fundamentally determine their photophysical properties for various applications,and thus understanding the primary excited-state dynamics behavior is of fundamental and practical significance.Until recently,the excited-state dynamics of organic materials towards biophotonics have been rarely studied,although numerous endeavors have been devoted to the design of organic materials for biophotonics.Herein,various spectroscopy technologies including femtosecond transient absorption(fs-TA)spectroscopy clearly reveal a totally different excited state dynamics behavior within Bodipy monomer(2B-BDP dye)and aggregates(2B-BDP NPs),indicating strongly morphology dependent character.2B-BDP dye undergoes an ultrafast conversion from S1 to intramolecular charge transfer(ICT)state for subsequent photoluminescence(PL)and nonradiative(NR)decay,while 2B-BDP NPs show an accelerated excited-state deactivation mainly through S1→S0 NR decay.The potential bioapplications based on the corresponding excited state dynamics behavior are discussed together with experimental results.Interestingly,the accelerated NR decay in 2B-BDP NPs does not yield a stronger photoacoustic(PA)signal than that in 2B-BDP dye,which violates the conventional wisdom that faster NR decay would benefit the photothermal effects for better photoacoustic imaging(PAI).These insightful and fundamental observations of the excited-state dynamics may contribute an alternative approach at the molecular level towards the future design of functional Bodipy-based organic molecules with desirable performances.
