The exploration of magnetism in two-dimensional layered materials has attracted extensive research interest.For the monoclinic phase Crl_(3) with interlayer antiferromagnetism,finding a static and robust way of realiz...The exploration of magnetism in two-dimensional layered materials has attracted extensive research interest.For the monoclinic phase Crl_(3) with interlayer antiferromagnetism,finding a static and robust way of realizing the intrinsic interlayer ferromagnetic coupling is desirable.In this work,we study the electronic structure and magnetic properties of the nonmag-netic element(e.g.,O,S,Se,N,P,As,and C)doped bi-and triple-layer Crl_(3) systems via first-principles calculations.Our results demonstrate that O,P,S,As,and Se doped Crls bilayer can realize interlayer ferromagnetism.Further analysis shows that the interlayer ferromagnetic coupling in the doped few-layer Crls is closely related to the formation of localized spin-polarized state around the doped elements.Further study presents that,for As-doped tri-layer Crl_(3),it can realize interlayer ferromagnetic coupling.This work proves that nonmagnetic element doping can realize the interlayer ferromagnetically-coupled few-layer Crl_(3) while maintaining its semiconducting characteristics without introducing additional carriers.展开更多
High-entropy alloys(HEAs)are a promising solution for large-scale hydrogen storage(H-storage)and are therefore receiving increasing attention from the materials science community.In this study,we systematically invest...High-entropy alloys(HEAs)are a promising solution for large-scale hydrogen storage(H-storage)and are therefore receiving increasing attention from the materials science community.In this study,we systematically investigated the microstructures and H-storage properties of V_(35)Ti_(35)Cr_(10) Fe_(10)M_(10)(M=Mn,Co,Sc,or Ni)HEAs prepared by arcmelting.The cast HEAs were found to be nanocrystalline.The crystal lattice parameters and hydrogen absorption energies of the alloys were calculated using density functional theory(DFT)calculations.The alloys can be fully activated in just one cycle of hydrogen absorption/desorption under mild conditions,after which they reach hydrogen absorption saturation in approximately 100 s at ambient temperature.The hydrogenation kinetics of the HEAs are approximately five times higher than that of conventional solid-solution alloys with a body-centered cubic(BCC)structure.By performing in-situ hydriding differential scanning calorimetry in combination with DFT calculations,we revealed that the alloys are more susceptible to hydrogenation than traditional BCC structural alloys.The H-storage capacity of V_(35)Ti_(35)Cr_(10) Fe_(10)M_(10) alloys at ambient temperature was higher than that of HEAs reported in the literature.Quasi-in-situ X-ray diffraction characterization of the HEAs’hydrogenation revealed a phase transition process from a BCC to facecentered cubic,passing through a pseudo-BCC structure.Our work introduces a new perspective for designing alloys with ultrafast hydrogen absorption kinetics and high capacity for large-scale,room-temperature-applicable H-storage.展开更多
Focal adhesion complexes function as the mediators of cell-extracellular matrix interactions to sense and transmit the extracellular signals.Previous studies have demonstrated that cardiomyocyte focal adhesions can be...Focal adhesion complexes function as the mediators of cell-extracellular matrix interactions to sense and transmit the extracellular signals.Previous studies have demonstrated that cardiomyocyte focal adhesions can be modulated by surface topographic features.However,the response of focal adhesions to dynamic surface topographic changes remains underexplored.To study this dynamic responsiveness of focal adhesions,we utilized a shape memory polymer-based substrate that can produce a flat-to-wrinkle surface transition triggered by an increase of temperature.Using this dynamic culture system,we analyzed three proteins(paxillin,vinculin and zyxin)from different layers of the focal adhesion complex in response to dynamic extracellular topographic change.Hence,we quantified the dynamic profile of cardiomyocyte focal adhesion in a time-dependent manner,which provides new understanding of dynamic cardiac mechanobiology.展开更多
Various c-mesenchymal-to-epithelial transition(c-MET) inhibitors are effective in the treatment of non-small cell lung cancer;however, the inevitable drug resistance remains a challenge, limiting their clinical effica...Various c-mesenchymal-to-epithelial transition(c-MET) inhibitors are effective in the treatment of non-small cell lung cancer;however, the inevitable drug resistance remains a challenge, limiting their clinical efficacy. Therefore, novel strategies targeting c-MET are urgently required. Herein, through rational structure optimization, we obtained novel exceptionally potent and orally active c-MET proteolysis targeting chimeras(PROTACs) namely D10 and D15 based on thalidomide and tepotinib. D10 and D15 inhibited cell growth with low nanomolar IC_(50) values and achieved picomolar DC_(50) values and>99% of maximum degradation(D_(max)) in EBC-1 and Hs746T cells. Mechanistically, D10 and D15dramatically induced cell apoptosis, G1 cell cycle arrest and inhibited cell migration and invasion.Notably, intraperitoneal administration of D10 and D15 significantly inhibited tumor growth in the EBC-1 xenograft model and oral administration of D15 induced approximately complete tumor suppression in the Hs746T xenograft model with well-tolerated dose-schedules. Furthermore, D10 and D15 exerted significant anti-tumor effect in cells with c-MET^(Y1230H) and c-MET^(D1228N) mutations, which are resistant to tepotinib in clinic. These findings demonstrated that D10 and D15 could serve as candidates for the treatment of tumors with MET alterations.展开更多
基金supported by the National Natural Science Foundation of China(Nos.11974098 and 11974327)the Natural Science Foundation of Hebei Province(No.A2023205017)+2 种基金the Science Foundation of Hebei Normal University(No.2019B16)the Fundamental Research Funds for the Central Universities(Nos.WK2030020032 and WK2340000082)Anhui Initiative in Quantum Information Technologies.
文摘The exploration of magnetism in two-dimensional layered materials has attracted extensive research interest.For the monoclinic phase Crl_(3) with interlayer antiferromagnetism,finding a static and robust way of realizing the intrinsic interlayer ferromagnetic coupling is desirable.In this work,we study the electronic structure and magnetic properties of the nonmag-netic element(e.g.,O,S,Se,N,P,As,and C)doped bi-and triple-layer Crl_(3) systems via first-principles calculations.Our results demonstrate that O,P,S,As,and Se doped Crls bilayer can realize interlayer ferromagnetism.Further analysis shows that the interlayer ferromagnetic coupling in the doped few-layer Crls is closely related to the formation of localized spin-polarized state around the doped elements.Further study presents that,for As-doped tri-layer Crl_(3),it can realize interlayer ferromagnetic coupling.This work proves that nonmagnetic element doping can realize the interlayer ferromagnetically-coupled few-layer Crl_(3) while maintaining its semiconducting characteristics without introducing additional carriers.
基金supported by the Natural Science Foundation of Inner Mongolia,China(grant nos.2022MS05011,2020LH01006,and 2022FX02)the National Natural Science Foundation of China(grant nos.52261041 and 51961032)+1 种基金the Major Science and Technology Project of Inner Mongolia(grant no.2021ZD0029)the Fundamental Research Funds for Inner Mongolia University of Science&Technology(grant no.2023QNJS119).
文摘High-entropy alloys(HEAs)are a promising solution for large-scale hydrogen storage(H-storage)and are therefore receiving increasing attention from the materials science community.In this study,we systematically investigated the microstructures and H-storage properties of V_(35)Ti_(35)Cr_(10) Fe_(10)M_(10)(M=Mn,Co,Sc,or Ni)HEAs prepared by arcmelting.The cast HEAs were found to be nanocrystalline.The crystal lattice parameters and hydrogen absorption energies of the alloys were calculated using density functional theory(DFT)calculations.The alloys can be fully activated in just one cycle of hydrogen absorption/desorption under mild conditions,after which they reach hydrogen absorption saturation in approximately 100 s at ambient temperature.The hydrogenation kinetics of the HEAs are approximately five times higher than that of conventional solid-solution alloys with a body-centered cubic(BCC)structure.By performing in-situ hydriding differential scanning calorimetry in combination with DFT calculations,we revealed that the alloys are more susceptible to hydrogenation than traditional BCC structural alloys.The H-storage capacity of V_(35)Ti_(35)Cr_(10) Fe_(10)M_(10) alloys at ambient temperature was higher than that of HEAs reported in the literature.Quasi-in-situ X-ray diffraction characterization of the HEAs’hydrogenation revealed a phase transition process from a BCC to facecentered cubic,passing through a pseudo-BCC structure.Our work introduces a new perspective for designing alloys with ultrafast hydrogen absorption kinetics and high capacity for large-scale,room-temperature-applicable H-storage.
基金supported by the NIH NICHD[R01HD101130]NSF[CBET-1804875,CBET-1943798 and CMMI-2130192]+3 种基金NSF[DMR-1609523 and CMMI-2022421]Syracuse University intramural CUSE GrantGerber GrantBioInspired Institute Seed Grant.
文摘Focal adhesion complexes function as the mediators of cell-extracellular matrix interactions to sense and transmit the extracellular signals.Previous studies have demonstrated that cardiomyocyte focal adhesions can be modulated by surface topographic features.However,the response of focal adhesions to dynamic surface topographic changes remains underexplored.To study this dynamic responsiveness of focal adhesions,we utilized a shape memory polymer-based substrate that can produce a flat-to-wrinkle surface transition triggered by an increase of temperature.Using this dynamic culture system,we analyzed three proteins(paxillin,vinculin and zyxin)from different layers of the focal adhesion complex in response to dynamic extracellular topographic change.Hence,we quantified the dynamic profile of cardiomyocyte focal adhesion in a time-dependent manner,which provides new understanding of dynamic cardiac mechanobiology.
基金supported by Major New Drugs Innovation and Development (2018ZX09J18102-002, China)。
文摘Various c-mesenchymal-to-epithelial transition(c-MET) inhibitors are effective in the treatment of non-small cell lung cancer;however, the inevitable drug resistance remains a challenge, limiting their clinical efficacy. Therefore, novel strategies targeting c-MET are urgently required. Herein, through rational structure optimization, we obtained novel exceptionally potent and orally active c-MET proteolysis targeting chimeras(PROTACs) namely D10 and D15 based on thalidomide and tepotinib. D10 and D15 inhibited cell growth with low nanomolar IC_(50) values and achieved picomolar DC_(50) values and>99% of maximum degradation(D_(max)) in EBC-1 and Hs746T cells. Mechanistically, D10 and D15dramatically induced cell apoptosis, G1 cell cycle arrest and inhibited cell migration and invasion.Notably, intraperitoneal administration of D10 and D15 significantly inhibited tumor growth in the EBC-1 xenograft model and oral administration of D15 induced approximately complete tumor suppression in the Hs746T xenograft model with well-tolerated dose-schedules. Furthermore, D10 and D15 exerted significant anti-tumor effect in cells with c-MET^(Y1230H) and c-MET^(D1228N) mutations, which are resistant to tepotinib in clinic. These findings demonstrated that D10 and D15 could serve as candidates for the treatment of tumors with MET alterations.
