Objectives Dysregulated osteoclast function contributes to skeletal diseases.However,the specific ubiquitination regulators of the osteoclastogenesis repressor MafB,particularly at the post-translational level,remain ...Objectives Dysregulated osteoclast function contributes to skeletal diseases.However,the specific ubiquitination regulators of the osteoclastogenesis repressor MafB,particularly at the post-translational level,remain undefined.This study aims to identify ubiquitin-specific proteases(USPs)that deubiquitinate MafB and enhance its stability.Methods We constructed a MafB-conjugated luciferase and overexpressed 40 individual USPs,measuring changes in luciferase activity.The identified USP was overexpressed in human CD14^(+) peripheral blood mononuclear cells(PBMCs)to evaluate its effect.Osteoclast differentiation was assessed through osteoclast marker Integrin alpha-V(CD51)staining and Western blot analysis.Co-immunoprecipitation(co-IP)was performed to assess the interplay.The influence on MafB ubiquitination and degradation was evaluated via immunoprecipitation and Western blot.Finally,MafB was knocked down in the USP-overexpressing PBMCs to analyze its effect on osteoclast differentiation.Results Overexpression of ubiquitin-specific protease 29(USP29)significantly increased MafB expression by approximately 75%(p<0.0001).Elevated USP29 levels strongly inhibited osteoclastic differentiation in CD14^(+) PBMCs(p<0.0001).USP29 was found to interact with MafB,markedly reducing its ubiquitination and subsequent degradation in PBMCs(p<0.001).Knocking down MafB in USP29-overexpressing PBMCs alleviated the inhibitory effect of USP29 on osteoclastogenesis.Conclusion USP29 acts as a potent stabilizer of MafB,inhibiting osteoclastogenesis in human CD14^(+) PBMCs,at least in part,by enhancing MafB stability.These findings expand our understanding of USP29’s role and the post-translational regulation of MafB.Furthermore,USP29 serves as a vital factor that controls osteoclast differentiation,and its regulatory function is at least partially mediated by deubiquitinating and stabilizing MafB.展开更多
The PICOSEC Micromegas(MM)is a precise timing gaseous detector based on a Cherenkov radiator coupled with a semi-transparent photocathode and an MM amplifying structure.It features a two-stage amplification process th...The PICOSEC Micromegas(MM)is a precise timing gaseous detector based on a Cherenkov radiator coupled with a semi-transparent photocathode and an MM amplifying structure.It features a two-stage amplification process that leads to a significant deterioration of non-uniformity when scaling up to larger areas.Since the performance of gaseous detectors is highly dependent on the choice of working gas,optimizing the gas mixture offers a promising solution to improve the uniformity performance.This paper addresses these challenges through a combined approach of simulation based on Garfield++and experimental studies.The simulation investigates the properties of different mixing fractions of gas mixtures and their impact on detector performance,including gain uniformity and time resolution.To verify the simulation results,experimental tests were conducted using a multi-channel PICOSEC MM prototype with different gas mixtures.The experimental results are consistent with the findings of the simulation,indicating that a higher concentration of neon significantly improves the detector’s gain uniformity.Furthermore,the influence of gas mixtures on time resolution was explored as a critical performance indicator.The study presented in this paper offers valuable insights for improving uniformity in large-area PICOSEC MM detectors and optimizing overall performance.展开更多
Traditional Chinese medicine(TCM)has a long history and is widely used to prevent and treat various diseases.With the development of modern technology,an increasing number of active ingredients—such as curcumin,berbe...Traditional Chinese medicine(TCM)has a long history and is widely used to prevent and treat various diseases.With the development of modern technology,an increasing number of active ingredients—such as curcumin,berberine,and baicalin—have been identified and validated within TCM.Concurrently,the emergence of nanotechnology has led to the discovery of numerous nanomedicines based on the self-assembly of active ingredients from TCM.Polymer materials can enhance the bioavailability of these active compounds and reduce their toxic side effects.Moreover,compared to synthetic polymers,natural polymer materials offer advantages such as non-toxicity and high biosafety when used in drug delivery systems.However,natural polymers tend to be unstable and are easily influenced by environmental factors such as temperature,humidity,and pH,which complicates quality control.Additionally,the cost of obtaining natural polymer materials remains high.This article summarizes and analyzes 232 pieces of the research studies on self-assembled polymer materials via noncovalent interactions,including hydrogen bonding,π-πinteractions,hydrophobic interactions,and electrostatic interactions.The review primarily focuses on the active ingredients derived from TCM and provides a concise overview of future directions for polymer materials,including controlled drug delivery,targeted disease treatment,clinical translation,and green synthesis methods.展开更多
The efficient utilization of photogenerated electrons and the effective activation of reactive molecules are among the major challenges in photocatalytic nitrogen reduction.Defect engineering can enhance the catalyst&...The efficient utilization of photogenerated electrons and the effective activation of reactive molecules are among the major challenges in photocatalytic nitrogen reduction.Defect engineering can enhance the catalyst's ability to adsorb and activate N_(2)and H_(2)O,while the ultrathin structure with maximized active crystal facets can maximize the enrichment of effective photogenerated electrons.This work employs a two-step synergistic method to fabricate ultrathin BiVO_(4)with oxygen vacancies and bismuth vacancies(2D-V_(Bi+O)-BVO,thickness<20 nm)for photocatalytic nitrogen reduction.Scanning electron microscopy,transmission electron microscopy(TEM),and atomic force microscopy characterization confirm the transformation of BiVO_(4)from bulk material(bulk-BVO,~1300 nm)to an ultrathin structure(~15 nm).TEM,X-ray photoelectron spectroscopy,electron paramagnetic resonance characterizations,and density functional theory(DFT)calculations verify the construction of oxygen and bismuth vacancies in the ultrathin BiVO_(4).Compared to bulk-BVO,the photocatalytic nitrogen fixation efficiency of 2D-V_(Bi+O)-BVO is increased by 4.7 times,with the highest activity reaching 158.73μmol·g^(-1)·h^(-1).N_(2)-temperature programmed desorption and DFT calculations demonstrate that the oxygen and bismuth vacancies in BiVO_(4),respectively,promote the adsorption/activation of N_(2)and H_(2)O,which is crucial for the overall nitrogen reduction reaction.Photo-deposition experiments prove that the(040)plane is the active surface for electrons.And the ultrathin structure maximizes the(040)facet of BiVO_(4),which is conducive to the high enrichment of electrons.Meanwhile,more active sites can be exposed for the activation of N_(2)and H_(2)O.In situ infrared spectroscopy confirms that N_(2)can be effectively adsorbed onto 2D-V_(Bi+O)-BVO,and the presence of NH_(2)-NH_(2)active species is consistent with the alternating reaction pathway.This study provides new insights into the development of green and efficient photocatalysts with dual vacancies and ultrathin structures.展开更多
The irregular porous structure,similar to human bone tissue,is more beneficial for bone ingrowth than the regular one.We proposed a new design method to create uniform and gradient irregular porous structures with por...The irregular porous structure,similar to human bone tissue,is more beneficial for bone ingrowth than the regular one.We proposed a new design method to create uniform and gradient irregular porous structures with porosities from 38 to 83%based on Voronoi tessellation.The models were fabricated using selective laser sintering,and micro-CT was used to assess their morphological features.Mechanical and fluid flow properties were evaluated through experiments and computational fluid dynamics simulations.Micro-CT scans confirmed that 3D printing can produce high-quality irregular structures.The Graded Irregular(GI)structure showed clear advantages in mechanical properties by reducing stress shielding and improving hydrodynamic performance with higher fluid flow velocity and lower permeability compared to the Uniform Irregular(UI)structure.Additionally,in vitro cell experiments indicated that the GI structure was better than the UI structure in promoting osteogenic differentiation,while in vivo animal studies showed that the GI structure was superior in terms of the ratio of Bone Volume to Total Volume(BV/TV)and Trabecular Number(Tb.N).Thus,the GI structure has greater application potential in bone tissue engineering.展开更多
文摘Objectives Dysregulated osteoclast function contributes to skeletal diseases.However,the specific ubiquitination regulators of the osteoclastogenesis repressor MafB,particularly at the post-translational level,remain undefined.This study aims to identify ubiquitin-specific proteases(USPs)that deubiquitinate MafB and enhance its stability.Methods We constructed a MafB-conjugated luciferase and overexpressed 40 individual USPs,measuring changes in luciferase activity.The identified USP was overexpressed in human CD14^(+) peripheral blood mononuclear cells(PBMCs)to evaluate its effect.Osteoclast differentiation was assessed through osteoclast marker Integrin alpha-V(CD51)staining and Western blot analysis.Co-immunoprecipitation(co-IP)was performed to assess the interplay.The influence on MafB ubiquitination and degradation was evaluated via immunoprecipitation and Western blot.Finally,MafB was knocked down in the USP-overexpressing PBMCs to analyze its effect on osteoclast differentiation.Results Overexpression of ubiquitin-specific protease 29(USP29)significantly increased MafB expression by approximately 75%(p<0.0001).Elevated USP29 levels strongly inhibited osteoclastic differentiation in CD14^(+) PBMCs(p<0.0001).USP29 was found to interact with MafB,markedly reducing its ubiquitination and subsequent degradation in PBMCs(p<0.001).Knocking down MafB in USP29-overexpressing PBMCs alleviated the inhibitory effect of USP29 on osteoclastogenesis.Conclusion USP29 acts as a potent stabilizer of MafB,inhibiting osteoclastogenesis in human CD14^(+) PBMCs,at least in part,by enhancing MafB stability.These findings expand our understanding of USP29’s role and the post-translational regulation of MafB.Furthermore,USP29 serves as a vital factor that controls osteoclast differentiation,and its regulatory function is at least partially mediated by deubiquitinating and stabilizing MafB.
基金supported by the National Natural Science Foundation of China(12125505).
文摘The PICOSEC Micromegas(MM)is a precise timing gaseous detector based on a Cherenkov radiator coupled with a semi-transparent photocathode and an MM amplifying structure.It features a two-stage amplification process that leads to a significant deterioration of non-uniformity when scaling up to larger areas.Since the performance of gaseous detectors is highly dependent on the choice of working gas,optimizing the gas mixture offers a promising solution to improve the uniformity performance.This paper addresses these challenges through a combined approach of simulation based on Garfield++and experimental studies.The simulation investigates the properties of different mixing fractions of gas mixtures and their impact on detector performance,including gain uniformity and time resolution.To verify the simulation results,experimental tests were conducted using a multi-channel PICOSEC MM prototype with different gas mixtures.The experimental results are consistent with the findings of the simulation,indicating that a higher concentration of neon significantly improves the detector’s gain uniformity.Furthermore,the influence of gas mixtures on time resolution was explored as a critical performance indicator.The study presented in this paper offers valuable insights for improving uniformity in large-area PICOSEC MM detectors and optimizing overall performance.
基金supported by the Department of Education of Anhui Province of China(Nos.2023AH050754 and KJ2019A0470)the Natural Science Foundation of Anhui Province of China(No.1608085MH227)+4 种基金the Anhui Provincial Quality Engineering Project for Education in the New Era-Research on the Reform of Graduate Education and Teaching(2023jyjxggyjY168)the Quality Engineering Project of the Anhui Provincial Department of Education in 2021(No.2021jyxm0824)the Research and Development Project Entrusted by the Enterprise:Research on Antioxidant Biological Activity of Quercetin(No.2022HZ049)the Quality Engineering Project of Anhui University of Chinese Medicine in 2021(No.2021zlgc042)the Anhui University of Chinese Medicine Annual Innovation Training Program for College Students(Nos.2017142,2017171).
文摘Traditional Chinese medicine(TCM)has a long history and is widely used to prevent and treat various diseases.With the development of modern technology,an increasing number of active ingredients—such as curcumin,berberine,and baicalin—have been identified and validated within TCM.Concurrently,the emergence of nanotechnology has led to the discovery of numerous nanomedicines based on the self-assembly of active ingredients from TCM.Polymer materials can enhance the bioavailability of these active compounds and reduce their toxic side effects.Moreover,compared to synthetic polymers,natural polymer materials offer advantages such as non-toxicity and high biosafety when used in drug delivery systems.However,natural polymers tend to be unstable and are easily influenced by environmental factors such as temperature,humidity,and pH,which complicates quality control.Additionally,the cost of obtaining natural polymer materials remains high.This article summarizes and analyzes 232 pieces of the research studies on self-assembled polymer materials via noncovalent interactions,including hydrogen bonding,π-πinteractions,hydrophobic interactions,and electrostatic interactions.The review primarily focuses on the active ingredients derived from TCM and provides a concise overview of future directions for polymer materials,including controlled drug delivery,targeted disease treatment,clinical translation,and green synthesis methods.
文摘The efficient utilization of photogenerated electrons and the effective activation of reactive molecules are among the major challenges in photocatalytic nitrogen reduction.Defect engineering can enhance the catalyst's ability to adsorb and activate N_(2)and H_(2)O,while the ultrathin structure with maximized active crystal facets can maximize the enrichment of effective photogenerated electrons.This work employs a two-step synergistic method to fabricate ultrathin BiVO_(4)with oxygen vacancies and bismuth vacancies(2D-V_(Bi+O)-BVO,thickness<20 nm)for photocatalytic nitrogen reduction.Scanning electron microscopy,transmission electron microscopy(TEM),and atomic force microscopy characterization confirm the transformation of BiVO_(4)from bulk material(bulk-BVO,~1300 nm)to an ultrathin structure(~15 nm).TEM,X-ray photoelectron spectroscopy,electron paramagnetic resonance characterizations,and density functional theory(DFT)calculations verify the construction of oxygen and bismuth vacancies in the ultrathin BiVO_(4).Compared to bulk-BVO,the photocatalytic nitrogen fixation efficiency of 2D-V_(Bi+O)-BVO is increased by 4.7 times,with the highest activity reaching 158.73μmol·g^(-1)·h^(-1).N_(2)-temperature programmed desorption and DFT calculations demonstrate that the oxygen and bismuth vacancies in BiVO_(4),respectively,promote the adsorption/activation of N_(2)and H_(2)O,which is crucial for the overall nitrogen reduction reaction.Photo-deposition experiments prove that the(040)plane is the active surface for electrons.And the ultrathin structure maximizes the(040)facet of BiVO_(4),which is conducive to the high enrichment of electrons.Meanwhile,more active sites can be exposed for the activation of N_(2)and H_(2)O.In situ infrared spectroscopy confirms that N_(2)can be effectively adsorbed onto 2D-V_(Bi+O)-BVO,and the presence of NH_(2)-NH_(2)active species is consistent with the alternating reaction pathway.This study provides new insights into the development of green and efficient photocatalysts with dual vacancies and ultrathin structures.
基金supported by Medical Science and Technology Research of Guangdong Province(NO.B2024033)Medical Science and Technology Research of Guangdong Province(NO.A2024352)+1 种基金National Demonstration Pilot Project for the Inheritance and Innovative Development of Traditional Chinese Medicine-Research Project on Traditional Chinese Medicine at Zhongshan Hospital of Traditional Chinese Medicine(NO.YN2024B002)China Postdoctoral Science Foundation(NO.2024M750668).
文摘The irregular porous structure,similar to human bone tissue,is more beneficial for bone ingrowth than the regular one.We proposed a new design method to create uniform and gradient irregular porous structures with porosities from 38 to 83%based on Voronoi tessellation.The models were fabricated using selective laser sintering,and micro-CT was used to assess their morphological features.Mechanical and fluid flow properties were evaluated through experiments and computational fluid dynamics simulations.Micro-CT scans confirmed that 3D printing can produce high-quality irregular structures.The Graded Irregular(GI)structure showed clear advantages in mechanical properties by reducing stress shielding and improving hydrodynamic performance with higher fluid flow velocity and lower permeability compared to the Uniform Irregular(UI)structure.Additionally,in vitro cell experiments indicated that the GI structure was better than the UI structure in promoting osteogenic differentiation,while in vivo animal studies showed that the GI structure was superior in terms of the ratio of Bone Volume to Total Volume(BV/TV)and Trabecular Number(Tb.N).Thus,the GI structure has greater application potential in bone tissue engineering.
