Although mesenchymal stem cell-derived exosomes(MSC-exos)have been shown to have therapeutic effects in experimental periodontitis,their drawbacks,such as low yield and limited efficacy,have hampered their clinical ap...Although mesenchymal stem cell-derived exosomes(MSC-exos)have been shown to have therapeutic effects in experimental periodontitis,their drawbacks,such as low yield and limited efficacy,have hampered their clinical application.These drawbacks can be largely reduced by replacing the traditional 2D culture system with a 3D system.However,the potential function of MSC-exos produced by 3D culture(3D-exos)in periodontitis remains elusive.This study showed that compared with MSC-exos generated via 2D culture(2D-exos),3D-exos showed enhanced anti-inflammatory effects in a ligature-induced model of periodontitis by restoring the reactive T helper 17(Th17)cell/Treg balance in inflamed periodontal tissues.Mechanistically,3D-exos exhibited greater enrichment of miR-1246,which can suppress the expression of Nfat5,a key factor that mediates Th17 cell polarization in a sequence-dependent manner.Furthermore,we found that recovery of the Th17 cell/Treg balance in the inflamed periodontium by the local injection of 3D-exos attenuated experimental colitis.Our study not only showed that by restoring the Th17 cell/Treg balance through the miR-1246/Nfat5 axis,the 3D culture system improved the function of MSC-exos in the treatment of periodontitis,but also it provided a basis for treating inflammatory bowel disease(IBD)by restoring immune responses in the inflamed periodontium.展开更多
High-entropy carbide ceramics(HECCs)commonly exhibit non-stoichiometric compositions and short-range order(SRO)arising from diverse elemental mixing.In this study,taking(TiZrHfNb)C as a representative HECC,we explore ...High-entropy carbide ceramics(HECCs)commonly exhibit non-stoichiometric compositions and short-range order(SRO)arising from diverse elemental mixing.In this study,taking(TiZrHfNb)C as a representative HECC,we explore the coupling effects of SRO and carbon non-stoichiometry based on density-functional theory(DFT)and machine learning(ML).DFT results indicate that carbon non-stoichiometry is favored in Ti and Nb environments due to enhanced local atomic relaxation and charge transfer,which contribute to improved d-d bonding interactions.DFT-based Monte Carlo(MC)simulations further reveal a clustering tendency of Ti and Nb elements that compete with carbon non-stoichiometry formation.These local features are effectively captured by ML models,enabling rapid assessment of the interplay among carbon deficiency,SRO,and their influences on the mechanical properties of HECCs.This work elucidates the microscopic local properties responsible for the macroscopic behavior,offering key insights for designing HECCs through careful element selection and local chemistry control.展开更多
Developing high-performance multicomponent ceramics,which are promising in solving challenges posed by emerging technologies,shows grand difficulties because of the immense compositional space and complex local distor...Developing high-performance multicomponent ceramics,which are promising in solving challenges posed by emerging technologies,shows grand difficulties because of the immense compositional space and complex local distortions.In this work,an accurate machine learning(ML)model built upon an ab initio database is developed to predict the mechanical properties and structural distortions of multicomponent transition metal carbides(MTMCs).展开更多
基金This work was supported by grants from the National Natural Science Foundation of China(Grant Nos.81873713,81700959 and 81873829)the International Cooperation Project of Science and Technology in Guangdong Province(Grant No.2016B050502008)the Natural Science Foundation of the Tibet Autonomous Region(XZ2019ZR-ZY64(Z)).
文摘Although mesenchymal stem cell-derived exosomes(MSC-exos)have been shown to have therapeutic effects in experimental periodontitis,their drawbacks,such as low yield and limited efficacy,have hampered their clinical application.These drawbacks can be largely reduced by replacing the traditional 2D culture system with a 3D system.However,the potential function of MSC-exos produced by 3D culture(3D-exos)in periodontitis remains elusive.This study showed that compared with MSC-exos generated via 2D culture(2D-exos),3D-exos showed enhanced anti-inflammatory effects in a ligature-induced model of periodontitis by restoring the reactive T helper 17(Th17)cell/Treg balance in inflamed periodontal tissues.Mechanistically,3D-exos exhibited greater enrichment of miR-1246,which can suppress the expression of Nfat5,a key factor that mediates Th17 cell polarization in a sequence-dependent manner.Furthermore,we found that recovery of the Th17 cell/Treg balance in the inflamed periodontium by the local injection of 3D-exos attenuated experimental colitis.Our study not only showed that by restoring the Th17 cell/Treg balance through the miR-1246/Nfat5 axis,the 3D culture system improved the function of MSC-exos in the treatment of periodontitis,but also it provided a basis for treating inflammatory bowel disease(IBD)by restoring immune responses in the inflamed periodontium.
基金supported by the Hong Kong Innovation and Technology Commission(No.MHP/098/21)the Research Grant Council of Hong Kong(No.11205224)+2 种基金Key Program of National Natural Science of Hunan province(2024JJ3011)Hunan Province’s Key Research and Development Project(2023GK2091)Hunan Province’s Major Scientific and technological breakthroughs“Revealing the List and Taking Command”Project(2023ZJ1050).The computational time provided by the CityU Burgundy Supercomputer is highly acknowledged.
文摘High-entropy carbide ceramics(HECCs)commonly exhibit non-stoichiometric compositions and short-range order(SRO)arising from diverse elemental mixing.In this study,taking(TiZrHfNb)C as a representative HECC,we explore the coupling effects of SRO and carbon non-stoichiometry based on density-functional theory(DFT)and machine learning(ML).DFT results indicate that carbon non-stoichiometry is favored in Ti and Nb environments due to enhanced local atomic relaxation and charge transfer,which contribute to improved d-d bonding interactions.DFT-based Monte Carlo(MC)simulations further reveal a clustering tendency of Ti and Nb elements that compete with carbon non-stoichiometry formation.These local features are effectively captured by ML models,enabling rapid assessment of the interplay among carbon deficiency,SRO,and their influences on the mechanical properties of HECCs.This work elucidates the microscopic local properties responsible for the macroscopic behavior,offering key insights for designing HECCs through careful element selection and local chemistry control.
基金supported by the National Key R&D Program of China(No.2022YFE0200900)the Research Grants Council of Hong Kong(No.11200421)the Hong Kong Innovation and Technology Commission(No.MHP/098/21).
文摘Developing high-performance multicomponent ceramics,which are promising in solving challenges posed by emerging technologies,shows grand difficulties because of the immense compositional space and complex local distortions.In this work,an accurate machine learning(ML)model built upon an ab initio database is developed to predict the mechanical properties and structural distortions of multicomponent transition metal carbides(MTMCs).
