Objective:Osimertinib(OSI)therapy,a cornerstone in treating non-small cell lung cancer(NSCLC),has been severely limited by rapidly developing acquired resistance.Inhibition of bypass activation using a combination str...Objective:Osimertinib(OSI)therapy,a cornerstone in treating non-small cell lung cancer(NSCLC),has been severely limited by rapidly developing acquired resistance.Inhibition of bypass activation using a combination strategy holds promise in overcoming this resistance.Biguanides,with excellent anti-tumor effects,have recently attracted much attention for this potential.The current study investigated whether novel biguanide compounds developed by our team could overcome OSI resistance and the underlying mechanisms were explored.Methods:A comprehensive screening assay using OSI-resistant cells identified the optimal combination of biguanide compounds with OSI.Proteomics,co-immunoprecipitation mass spectrometry,RNA sequencing,and homologous recombination assays were used to elucidate the molecular mechanisms underlying combination therapy.NSCLC tumor tissues,especially OSI-resistant tissues,obtained from our clinic were used to assess the correlations between key proteins and OSI resistance.Results:SMK-010,a highly potent biguanide compound,effectively overcame OSI resistance in vitro and in vivo.Mechanistical studies showed that BMI1/FGFR1 pathway activation is responsible for OSI resistance.Specifically,silencing BMI1 promoted NEDD4-mediated FGFR1 ubiquitination and proteasomal degradation,whereas SMK-010 treatment induced FGFR1 lysosomal degradation.This reduction in FGFR1 levels impaired homologous recombination,increased DNA damage,and surmounted OSI resistance.Analysis of clinical samples revealed overexpression of BMI1 and FGFR1 in NSCLC tissues and represented potential biomarkers for OSI resistance.Conclusions:These findings highlight the crucial role of the BMI1/FGFR1 axis in OSI resistance and provide a rational basis for the future clinical application of the biguanide,SMK-010,in combination with OSI.展开更多
Herein,a simple and effective outer-surface interactions assisted supramolecular hierarchical assembly has been first exploited to uniformly distribute tungstosilicic acid(TSA)inside the porous structure of cucurbit[1...Herein,a simple and effective outer-surface interactions assisted supramolecular hierarchical assembly has been first exploited to uniformly distribute tungstosilicic acid(TSA)inside the porous structure of cucurbit[10]uril-based single-layer 2D supramolecular-organic-frameworks(Q[10]-SOFs)in water.Importantly,the 2D Q[10]-SOFs can further serve as light harvesting antenna,achieving fast energy transfer to the embedded redox-active TSA upon photoexcitation,resulting in efficient visible light-driven selective oxidation of benzyl alcohols into the corresponding aldehydes in high yield at room temperature.Further studies revealed that the integrated of 2D Q[10]-SOFs and TSA played a key role in the catalytic process,due to the presence of a novel stepwise electron transfer route in the single-layer hybrid 2D structures.展开更多
Effective electromagnetic wave absorption is now possible thanks to the design of the dielectric-magnetic double loss mechanism and the rich heterogeneous structure.In this study,hollow carbon spheres with rich hetero...Effective electromagnetic wave absorption is now possible thanks to the design of the dielectric-magnetic double loss mechanism and the rich heterogeneous structure.In this study,hollow carbon spheres with rich heterostructures were synthesized using an easy and effective in situ growing approach.In addition to improving impedance matching,the hollow structure also reduces material density and weight.By modifying the load,this system can alter the dielectric characteristics of MXene,which in turn affects the sample’s ability to absorb electromagnetic waves.MXene and the carbon material create a thick conductive network during the whole electromagnetic wave absorption process,creating the ideal environment for conduction loss.The sample’s ability to attenuate electromagnetic waves is further improved by the interfacial polarization that the rich heterogeneous structure can produce.Co-magnetic nanoparticle nanoparticles are the main source of magnetic loss.The MXene@Co/C-100–800(MCC-100–800)exhibits excellent electromagnetic wave absorption performance under the synergy of multiple loss mechanisms,with the maximum effective absorption bandwidth(EAB_(max))reaching 7.20 GHz and the minimum reflection loss(RL_(min))being–53.99 dB at 2.10 mm.Finally,this work is guided by the coating engineering of MXene and provides new ideas for the rational design of heterostructures of nanomaterials.展开更多
Design of multi-functional microwave absorption materials with strong dissipation ability is a practical approach to address the current issue of electromagnetic radiation pollution.Herein,based on the ex-change bias ...Design of multi-functional microwave absorption materials with strong dissipation ability is a practical approach to address the current issue of electromagnetic radiation pollution.Herein,based on the ex-change bias interaction between ferromagnetic and anti-ferromagnetic interfaces,a series of absorbers composed of the porous biochar loaded with ferromagnetic/anti-ferromagnetic NiCO_(2)O_(4)/CoO were suc-cessfully prepared via a fairly simple process of one-step calcination.By regulating the calcination tem-perature,the pore size and porosity of porous carbon,morphology of loaded NPs as well as the elec-tromagnetic response property and impedance matching characteristic in such composites can be mod-ulated.The porous biochar/NiCO_(2)O_(4)/CoO composite prepared under 350 ℃ possesses a remarkable elec-tromagnetic absorption reflection loss(RL)of-48.41 dB at 9.12 GHz with 2.5 mm thickness,and the effective absorption bandwidth(EAB)of 4.32 GHz with 2.2 mm thickness is located at X band,this is owing to the strong coupling effect of multiple dielectric polarizations,magnetic resonances,and eddy current consumption under matched impedance.In addition,the microwave absorbing patch prepared with this composite exhibits a well-hydrophobic property for self-cleaning function,and the large exten-sibility with substantial breaking strength endows its practical usage as a flexible absorber.展开更多
Subtle microstructure design and an appropriate multicomponent strategy are essential for advanced electromagnetic absorbing(EMA)materials with a wide effective absorption bandwidth(EAB)and intense absorption.However,...Subtle microstructure design and an appropriate multicomponent strategy are essential for advanced electromagnetic absorbing(EMA)materials with a wide effective absorption bandwidth(EAB)and intense absorption.However,sophisticated environments restrict the range of applications for EMA materials.Herein,three hollow spherical bifunctional CoSx/MnS/C nanocomposites with different crystal structures were constructed via cation exchange and subsequent vulcanization.The manganese sulfide and carbon generated during vulcanization exhibit a narrow band gap and enhanced conductivity,thereby facilitating conductive loss.The presence of cobalt sulfide facilitates the improvement of magnetic loss.More importantly,there is a potential difference between different phases at the heterogeneous interface,resulting in a region of space charge,which is conducive to interfacial polarization.The 3D hollow structure and heterogeneous dielectric/magnetic interfaces benefit the predominant EMA performance by forming perfect impedance matching,interface polarization,conduction loss,and magnetic loss effects.Specifically,an optimal reflection loss(RL)of-51.31 dB at 10.72 GHz and an effective EAB of 5.92 GHz at 2.1 mm can be achieved for Co_(1-x) S/MnS/C nanocomposite.Moreover,the nanocomposites maintained promising self-anticorrosion properties in simulated seawater environments.Transition metal sulfides with superior self-anticorrosion properties provide a pathway to efficient wave-absorbing materials in complicated environments.展开更多
基金supported by grants from the National Natural Science Foundation of China(Grant Nos.82172653 and 82472728)the Key Project of Developmental Biology and Breeding from Hunan Province(Grant No.2022XKQ0205)+1 种基金the Research Team for Reproduction Health and Translational Medicine of Hunan Normal University(Grant No.2023JC101)the Natural Science Foundation of Hunan Province(Grant No.2025JJ80150).
文摘Objective:Osimertinib(OSI)therapy,a cornerstone in treating non-small cell lung cancer(NSCLC),has been severely limited by rapidly developing acquired resistance.Inhibition of bypass activation using a combination strategy holds promise in overcoming this resistance.Biguanides,with excellent anti-tumor effects,have recently attracted much attention for this potential.The current study investigated whether novel biguanide compounds developed by our team could overcome OSI resistance and the underlying mechanisms were explored.Methods:A comprehensive screening assay using OSI-resistant cells identified the optimal combination of biguanide compounds with OSI.Proteomics,co-immunoprecipitation mass spectrometry,RNA sequencing,and homologous recombination assays were used to elucidate the molecular mechanisms underlying combination therapy.NSCLC tumor tissues,especially OSI-resistant tissues,obtained from our clinic were used to assess the correlations between key proteins and OSI resistance.Results:SMK-010,a highly potent biguanide compound,effectively overcame OSI resistance in vitro and in vivo.Mechanistical studies showed that BMI1/FGFR1 pathway activation is responsible for OSI resistance.Specifically,silencing BMI1 promoted NEDD4-mediated FGFR1 ubiquitination and proteasomal degradation,whereas SMK-010 treatment induced FGFR1 lysosomal degradation.This reduction in FGFR1 levels impaired homologous recombination,increased DNA damage,and surmounted OSI resistance.Analysis of clinical samples revealed overexpression of BMI1 and FGFR1 in NSCLC tissues and represented potential biomarkers for OSI resistance.Conclusions:These findings highlight the crucial role of the BMI1/FGFR1 axis in OSI resistance and provide a rational basis for the future clinical application of the biguanide,SMK-010,in combination with OSI.
基金supported by the National Natural Science Foundation of China(No.22271090)。
文摘Herein,a simple and effective outer-surface interactions assisted supramolecular hierarchical assembly has been first exploited to uniformly distribute tungstosilicic acid(TSA)inside the porous structure of cucurbit[10]uril-based single-layer 2D supramolecular-organic-frameworks(Q[10]-SOFs)in water.Importantly,the 2D Q[10]-SOFs can further serve as light harvesting antenna,achieving fast energy transfer to the embedded redox-active TSA upon photoexcitation,resulting in efficient visible light-driven selective oxidation of benzyl alcohols into the corresponding aldehydes in high yield at room temperature.Further studies revealed that the integrated of 2D Q[10]-SOFs and TSA played a key role in the catalytic process,due to the presence of a novel stepwise electron transfer route in the single-layer hybrid 2D structures.
基金financially supported by the National Natural Sci-ence Foundation of China(Nos.52377026 and 52301192)the Tais-han Scholars and Young Experts Program of Shandong Province(No.tsqn202103057)+1 种基金the Qingchuang Talents Induction Program of Shandong Higher Education Institution(Research and Inno-vation Team of Structural-Functional Polymer Composites)the Special Financial of Shandong Province(Structural Design of High-efficiency Electromagnetic Wave-absorbing Composite Mate-rials and the Construction of Shandong Provincial Talent Teams).
文摘Effective electromagnetic wave absorption is now possible thanks to the design of the dielectric-magnetic double loss mechanism and the rich heterogeneous structure.In this study,hollow carbon spheres with rich heterostructures were synthesized using an easy and effective in situ growing approach.In addition to improving impedance matching,the hollow structure also reduces material density and weight.By modifying the load,this system can alter the dielectric characteristics of MXene,which in turn affects the sample’s ability to absorb electromagnetic waves.MXene and the carbon material create a thick conductive network during the whole electromagnetic wave absorption process,creating the ideal environment for conduction loss.The sample’s ability to attenuate electromagnetic waves is further improved by the interfacial polarization that the rich heterogeneous structure can produce.Co-magnetic nanoparticle nanoparticles are the main source of magnetic loss.The MXene@Co/C-100–800(MCC-100–800)exhibits excellent electromagnetic wave absorption performance under the synergy of multiple loss mechanisms,with the maximum effective absorption bandwidth(EAB_(max))reaching 7.20 GHz and the minimum reflection loss(RL_(min))being–53.99 dB at 2.10 mm.Finally,this work is guided by the coating engineering of MXene and provides new ideas for the rational design of heterostructures of nanomaterials.
基金Surface Project of Local Development in Science and Technology Guided by Central Government(No.2021ZYD0041)National Natural Science Foundation of China(Nos.52377026 and 52301192)+2 种基金Natural Science Foundation of Shandong Province(No.ZR2019YQ24)Shandong Taishan Scholars Young Expert Program(No.tsqn202103057)Qingchuang Talents Induction Program of Shandong Higher Education Institution(Research and Innovation Team of Structural-Functional Polymer Composites).
文摘Design of multi-functional microwave absorption materials with strong dissipation ability is a practical approach to address the current issue of electromagnetic radiation pollution.Herein,based on the ex-change bias interaction between ferromagnetic and anti-ferromagnetic interfaces,a series of absorbers composed of the porous biochar loaded with ferromagnetic/anti-ferromagnetic NiCO_(2)O_(4)/CoO were suc-cessfully prepared via a fairly simple process of one-step calcination.By regulating the calcination tem-perature,the pore size and porosity of porous carbon,morphology of loaded NPs as well as the elec-tromagnetic response property and impedance matching characteristic in such composites can be mod-ulated.The porous biochar/NiCO_(2)O_(4)/CoO composite prepared under 350 ℃ possesses a remarkable elec-tromagnetic absorption reflection loss(RL)of-48.41 dB at 9.12 GHz with 2.5 mm thickness,and the effective absorption bandwidth(EAB)of 4.32 GHz with 2.2 mm thickness is located at X band,this is owing to the strong coupling effect of multiple dielectric polarizations,magnetic resonances,and eddy current consumption under matched impedance.In addition,the microwave absorbing patch prepared with this composite exhibits a well-hydrophobic property for self-cleaning function,and the large exten-sibility with substantial breaking strength endows its practical usage as a flexible absorber.
基金financially supported by the National Natu-ral Science Foundation of China(Nos.52377026 and 52301192)the Natural Science Foundation of Shandong Province(No.ZR2019YQ24)+3 种基金the Taishan Scholars and Young Experts Program of Shandong Province(No.tsqn202103057)the Qingchuang Talents Induction Program of Shandong Higher Education Institution(Re-search and Innovation Team of Structural-Functional Polymer Com-posites)the Special Financial of Shandong Province(Structural De-sign of High-efficiency Electromagnetic Wave-absorbing Composite Materials and Construction of Shandong Provincial Talent Teams)the“Sanqin Scholars”Innovation Teams Project of Shaanxi Province(Clean Energy Materials and High-Performance Devices Innovation Team of Shaanxi Dongling Smelting Co.,Ltd.).
文摘Subtle microstructure design and an appropriate multicomponent strategy are essential for advanced electromagnetic absorbing(EMA)materials with a wide effective absorption bandwidth(EAB)and intense absorption.However,sophisticated environments restrict the range of applications for EMA materials.Herein,three hollow spherical bifunctional CoSx/MnS/C nanocomposites with different crystal structures were constructed via cation exchange and subsequent vulcanization.The manganese sulfide and carbon generated during vulcanization exhibit a narrow band gap and enhanced conductivity,thereby facilitating conductive loss.The presence of cobalt sulfide facilitates the improvement of magnetic loss.More importantly,there is a potential difference between different phases at the heterogeneous interface,resulting in a region of space charge,which is conducive to interfacial polarization.The 3D hollow structure and heterogeneous dielectric/magnetic interfaces benefit the predominant EMA performance by forming perfect impedance matching,interface polarization,conduction loss,and magnetic loss effects.Specifically,an optimal reflection loss(RL)of-51.31 dB at 10.72 GHz and an effective EAB of 5.92 GHz at 2.1 mm can be achieved for Co_(1-x) S/MnS/C nanocomposite.Moreover,the nanocomposites maintained promising self-anticorrosion properties in simulated seawater environments.Transition metal sulfides with superior self-anticorrosion properties provide a pathway to efficient wave-absorbing materials in complicated environments.
