Fluorescent probes,with their superior optical properties and labeling versatility,have greatly advanced the visualization of intracellular molecules and subcellular structures.However,poor cytoplasmic delivery,caused...Fluorescent probes,with their superior optical properties and labeling versatility,have greatly advanced the visualization of intracellular molecules and subcellular structures.However,poor cytoplasmic delivery,caused by charge,size,or targeting groups,limits the effective use of many fluorescent probes in live cells.Recently,cell-penetrating peptides(CPPs)have emerged as efficient carriers,offering great potential for the cytoplasmic delivery of fluorescent probes in live cells.This review provides a comprehensive overview of CPPs as vehicles for probe delivery,outlining advances in their development,conjugation chemistries,and intracellular delivery mechanisms.Recent applications in live-cell imaging are highlighted and organized according to major CPP modification strategies,including sequence engineering,cyclization,hybrid design and enhancement by chemical reagents.Finally,the challenges that remain and the future outlook of this rapidly evolvingfield are discussed.展开更多
Objectives:The tumor microenvironment and epithelial-mesenchymal transition(EMT)are closely linked to the progression of differentiated thyroid cancer(DTC).However,the functional mechanisms of lysine-specific demethyl...Objectives:The tumor microenvironment and epithelial-mesenchymal transition(EMT)are closely linked to the progression of differentiated thyroid cancer(DTC).However,the functional mechanisms of lysine-specific demethylase 6B(KDM6B)in carcinogenesis remain incompletely understood.This study aims to clarify whether KDM6B affects DTC progression and EMT through the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of the rapamycin(PI3K/AKT/mTOR)pathway,providing a potential target for clinical treatment of DTC.Methods:Tissue samples from DTC patients(n=39)were collected,and KDM6B expression was determined through Reverse Transcription-Polymerase Chain Reaction(RT-PCR)and Western blot.Cell counting kit-8 assay,5-Ethynyl-2′-deoxyuridine staining,Transwell,Scratch-Wound,and other experiments were used to detect cell biological behavior;flow cytometry and enzyme-linked immunosorbent assay were used to investigate its effect on macrophage polarization.A subcutaneous tumor model was constructed in mice,and immunohistochemistry was used to detect nuclear proliferation antigen Ki-67,and a Western blot was used to validate protein expression.Results:KDM6B level was elevated in DTC tissues and cells compared to normal ones.Knocking down KDM6B inhibited DTC cell proliferation,reducedmigratory and invasive capabilities,suppressedM2macrophage polarization and EMTprocesses,while overexpression of KDM6B promoted the aforementioned biological behaviors.Knocking down KDM6B blocked the PI3K/AKT/mTOR pathway,while overexpression of KDM6B activated this pathway.PI3K agonists weakened the inhibitory impact of KDM6B knockdown on malignant biological characteristics;the opposite was true for PI3K inhibitors.Additionally,knocking down KDM6B inhibited tumor growth,decreased the Ki67 positivity rate,and inhibited the EMT process and M2 macrophage polarization in mice.Conclusion:KDM6B regulates the tumor microenvironment and EMT process via PI3K/AKT/mTOR pathway,thereby influencing DTC progression.展开更多
The development of super-resolution technology has made it possible to investigate the ultrastructure of intracellular organelles by fuorescence microscopy,which has greatly facilitated the development of life science...The development of super-resolution technology has made it possible to investigate the ultrastructure of intracellular organelles by fuorescence microscopy,which has greatly facilitated the development of life sciences and biomedicine.To realize super-resolution imaging of living cells,both advanced imaging systems and excellent fuorescent probes are required.Traditional fuorescent probes have good availability,but that is not the case for probes for live-cell super-resolution imaging.In this review,we frst introduce the principles of various super-resolution technologies and their probe requirements,then summarize the existing designs and delivery strategies of super-resolution probes for live-cell imaging,and fnally provide a brief conclusion and overview of the future.展开更多
Embedded phase-change random-access memory(ePCRAM)applications demand superior data retention in amorphous phase-change materials(PCMs).Traditional PCM design strategies have focused on enhancing the thermal stability...Embedded phase-change random-access memory(ePCRAM)applications demand superior data retention in amorphous phase-change materials(PCMs).Traditional PCM design strategies have focused on enhancing the thermal stability of the amorphous phase,often at the expense of the crystallization speed.While this approach supports reliable microchip operations,it compromises the ability to achieve rapid responses.To address this limitation,we modified ultrafast-crystallizing Sb thin films by incorporating Sc dopants,achieving the highest 10-year retention temperature(~175℃)among binary antimonide PCMs while maintaining a sub-10-ns SET operation speed.This reconciliation of two seemingly contradictory properties arises from the unique kinetic features of the 5-nm-thick Sc12Sb88 films,which exhibit an enlarged fragile-to-strong crossover in viscosity at medium supercooled temperature zones and an incompatible sublattice ordering behavior between the Sc and Sb atoms.By tailoring the crystallization kinetics of PCMs through strategic doping and nanoscale confinement,we provide new opportunities for developing robust yet swift ePCRAMs.展开更多
基金supported by the following grants:National Natural Science Foundation of China(Grant Nos.92354305 and 32271428),National Key R&D Program of China(Grant No.2022YFC3401100)Young Talent Program of Hubei Provincial Health Commission(WJ2025Q037)+1 种基金Interdisciplinary Research Program of HUST(Grant No.2023JCY5045)Director Fund of WNLO.
文摘Fluorescent probes,with their superior optical properties and labeling versatility,have greatly advanced the visualization of intracellular molecules and subcellular structures.However,poor cytoplasmic delivery,caused by charge,size,or targeting groups,limits the effective use of many fluorescent probes in live cells.Recently,cell-penetrating peptides(CPPs)have emerged as efficient carriers,offering great potential for the cytoplasmic delivery of fluorescent probes in live cells.This review provides a comprehensive overview of CPPs as vehicles for probe delivery,outlining advances in their development,conjugation chemistries,and intracellular delivery mechanisms.Recent applications in live-cell imaging are highlighted and organized according to major CPP modification strategies,including sequence engineering,cyclization,hybrid design and enhancement by chemical reagents.Finally,the challenges that remain and the future outlook of this rapidly evolvingfield are discussed.
基金funded by the Key Scientific Research Project Plan of colleges and universities in Henan Province(No.24B320007).
文摘Objectives:The tumor microenvironment and epithelial-mesenchymal transition(EMT)are closely linked to the progression of differentiated thyroid cancer(DTC).However,the functional mechanisms of lysine-specific demethylase 6B(KDM6B)in carcinogenesis remain incompletely understood.This study aims to clarify whether KDM6B affects DTC progression and EMT through the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of the rapamycin(PI3K/AKT/mTOR)pathway,providing a potential target for clinical treatment of DTC.Methods:Tissue samples from DTC patients(n=39)were collected,and KDM6B expression was determined through Reverse Transcription-Polymerase Chain Reaction(RT-PCR)and Western blot.Cell counting kit-8 assay,5-Ethynyl-2′-deoxyuridine staining,Transwell,Scratch-Wound,and other experiments were used to detect cell biological behavior;flow cytometry and enzyme-linked immunosorbent assay were used to investigate its effect on macrophage polarization.A subcutaneous tumor model was constructed in mice,and immunohistochemistry was used to detect nuclear proliferation antigen Ki-67,and a Western blot was used to validate protein expression.Results:KDM6B level was elevated in DTC tissues and cells compared to normal ones.Knocking down KDM6B inhibited DTC cell proliferation,reducedmigratory and invasive capabilities,suppressedM2macrophage polarization and EMTprocesses,while overexpression of KDM6B promoted the aforementioned biological behaviors.Knocking down KDM6B blocked the PI3K/AKT/mTOR pathway,while overexpression of KDM6B activated this pathway.PI3K agonists weakened the inhibitory impact of KDM6B knockdown on malignant biological characteristics;the opposite was true for PI3K inhibitors.Additionally,knocking down KDM6B inhibited tumor growth,decreased the Ki67 positivity rate,and inhibited the EMT process and M2 macrophage polarization in mice.Conclusion:KDM6B regulates the tumor microenvironment and EMT process via PI3K/AKT/mTOR pathway,thereby influencing DTC progression.
基金supported by the National Key Research and Development Program of China(No.2022YFC3401100)the National Natural Science Foundation of China(Grant Nos.32271428,92054110,and 32201132)China Postdoctoral Science Foundation funded project(Nos.BX20220125 and 2022M711257).
文摘The development of super-resolution technology has made it possible to investigate the ultrastructure of intracellular organelles by fuorescence microscopy,which has greatly facilitated the development of life sciences and biomedicine.To realize super-resolution imaging of living cells,both advanced imaging systems and excellent fuorescent probes are required.Traditional fuorescent probes have good availability,but that is not the case for probes for live-cell super-resolution imaging.In this review,we frst introduce the principles of various super-resolution technologies and their probe requirements,then summarize the existing designs and delivery strategies of super-resolution probes for live-cell imaging,and fnally provide a brief conclusion and overview of the future.
基金the National Natural Science Foundation of China(52032006)the Basic and Applied Basic Research Foundation of Guangdong(2020B1515120008)+1 种基金the Science and Technology Foundation of Shenzhen(ZDSYS20210623091813040)Shenzhen University 2035 Program for Excellent Research(00000203)。
文摘Embedded phase-change random-access memory(ePCRAM)applications demand superior data retention in amorphous phase-change materials(PCMs).Traditional PCM design strategies have focused on enhancing the thermal stability of the amorphous phase,often at the expense of the crystallization speed.While this approach supports reliable microchip operations,it compromises the ability to achieve rapid responses.To address this limitation,we modified ultrafast-crystallizing Sb thin films by incorporating Sc dopants,achieving the highest 10-year retention temperature(~175℃)among binary antimonide PCMs while maintaining a sub-10-ns SET operation speed.This reconciliation of two seemingly contradictory properties arises from the unique kinetic features of the 5-nm-thick Sc12Sb88 films,which exhibit an enlarged fragile-to-strong crossover in viscosity at medium supercooled temperature zones and an incompatible sublattice ordering behavior between the Sc and Sb atoms.By tailoring the crystallization kinetics of PCMs through strategic doping and nanoscale confinement,we provide new opportunities for developing robust yet swift ePCRAMs.
