The photocatalytic reduction of carbon dioxide(CO2)into high-value C2+hydrocarbons represents a sustainable pathway to alleviate energy shortages and reduce atmospheric CO2levels.In this study,a unique tandem...The photocatalytic reduction of carbon dioxide(CO2)into high-value C2+hydrocarbons represents a sustainable pathway to alleviate energy shortages and reduce atmospheric CO2levels.In this study,a unique tandem photocatalyst(CoTi-CN)is constructed by integrating bimetallic CoTi-MOF with metal-free half-metallic C(CN)3.This composite demonstrates markedly enhanced activity and selectivity in the photocatalytic CO2reduction to ethylene(C2H4),achieving a C2H4selectivity of 36.8%and a generation yield of 31.3μmol g-1over 5 h.Density functional theory(DFT)calculations combined with in situ diffuse reflectance infrared Fourier transform spectroscopy(DRIFTS)analysis reveal that C(CN)3acts as an efficient CO2to CO converter,while CoTi-MOF favors the adsorption and C-C coupling of*CO intermediates.The spatially decoupled CO generation and C-C coupling processes lead to optimized intermediate coverage and reduced energy barriers,resulting in superior selectivity toward multi-carbon products.This work opens new horizons for the design of tandem photocatalysts that combine half-metallic catalysts with bimetallic MOFs,achieving a significant enhancement in the activity and selectivity of photocatalytic C2H4production.展开更多
Activation of spinal cord neural stem cells(NSCs)and subsequent neurogenesis holds a promising alternative for spinal cord injury(SCI)repair.Our previous study demonstrated that complement C3a,derived from reactive as...Activation of spinal cord neural stem cells(NSCs)and subsequent neurogenesis holds a promising alternative for spinal cord injury(SCI)repair.Our previous study demonstrated that complement C3a,derived from reactive astrocytes,inhibits NSC proliferation by suppressing protein aggregate clearance through the deubiquitinating enzyme ubiquitin carboxy-terminal hydrolase L1(UCHL1)-proteasome system post-SCI.However,the potential molecular mechanism by which C3a modulates NSC activation via this pathway remains unclear.Here,we revealed that C3a/C3a receptor(C3aR)signaling activated NF-κB p65,which in turn inhibited Nrf2 activity and UCHL1 expression,resulting in diminished proteasome activity and the accumulation of protein aggregates,and ultimately impaired NSC activation.Both knockdown of NF-κB p65 and Nrf2 upregulation restored UCHL1 expression and proteasome activity in vitro,promoting NSC activation by enhancing protein aggregate clearance.Mechanistically,we found that NF-κB p65 regulated Nrf2 activity through a dual mechanism:(1)promoting Keap1-dependent ubiquitination and proteasome degradation of Nrf2;(2)inhibiting protein kinase C-mediated Nrf2 phosphorylation and nuclear translocation.Using the dual-luciferase reporter assay and chromatin immunoprecipitation(ChIP)analysis,we further identified UCHL1 as a direct transcriptional target of Nrf2.Importantly,in vivo experiments using SCI mice confirmed that either C3aR blockade,NF-κB p65 knockdown,or Nrf2 overexpression could rescue SCI-induced UCHL1 downregulation.Together,this study uncovers the C3a-NF-κB p65-Nrf2-UCHL1-proteasome axis as a critical regulator of NSC activation after SCI.This may provide novel molecular targets and intervention strategies for SCI repair.展开更多
Magnesium hydride serves as a promising solid-state hydrogen storage material owing to its high potential.However,its practical applications are constrained by the high enthalpy of hydrogen absorption and slow kinetic...Magnesium hydride serves as a promising solid-state hydrogen storage material owing to its high potential.However,its practical applications are constrained by the high enthalpy of hydrogen absorption and slow kinetics.In this study,we prepared a Ni/Ti3O5@graphene oxide(GO)dual-heterojunction composite material via solvent heating,electrostatic adsorption,and calcination to improve the hydrogen storage capabilities of MgH2.Adding Ni/Ti3O5@GO to MgH2 lowered the initial dehydrogenation temperature of MgH2 to 183℃;at a dehydrogenation temperature of 275℃,6.4 wt.%of H2 escaped from the MgH2 bulk.In addition,the hydrogen storage material absorbed 1.8 wt.%H2 at 30℃ for 30 min.The calculated activation energy of dehydrogenation was 48.221±0.141 kJ·mol-1,which was significantly lower than that of the ball-milled MgH2(112.63±1.44 kJ·mol-1).Mechanistic analysis results revealed that the heterojunction constructed from the multiphase compound system provided a large number of active sites and hydrogen diffusion routes,resulting in a synergistic catalytic effect that enhanced the hydrogen storage capacity of MgH2.In this work,we clarified the compositions of fuzzy interfaces in heterostructured materials by conducting ultraviolet photoelectron spectroscopy tests and identified key composite materials for the formation of heterojunctions.展开更多
The stereodivergent coupling via photoredoxransition metal catalysis has emerged as a powerful tool to construct diverse alkenes in both E and Z configurations.Despite well-established catalytic systems involving late...The stereodivergent coupling via photoredoxransition metal catalysis has emerged as a powerful tool to construct diverse alkenes in both E and Z configurations.Despite well-established catalytic systems involving late transition metals,the early transition metal catalyzed stereodivergent synthesis of alkenes still remains underdeveloped.Herein in this work,a stereodivergent reductive C(sp2)-C(sp3)coupling between cycloketone oximes and vinyl halides has been achieved by tunable photoredox/Ti dual catalysis,providing a facile access to a broad scope of cyano-substituted(fluoro)alkenes with high efficiency and controlled E/Z selectivity.Several products exhibited promising antifungal activities.展开更多
The selective cleavage of Cα-Cβbonds is of great significance to lignin valorization,and photocataly-sis offers an eco-friendly pathway to achieve this process.Here,graphitic carbon nitride(g-C3N4)modifi...The selective cleavage of Cα-Cβbonds is of great significance to lignin valorization,and photocataly-sis offers an eco-friendly pathway to achieve this process.Here,graphitic carbon nitride(g-C3N4)modified with hollow tubular In2O3was constructed via the calcination method for the photocatalytic cleavage of lignin Cα-Cβbonds.MIL-68(In)was used as the precursor of In2O3,imparting a unique hollow tubular structure and a relatively large specific surface area.The hollow tubular structure is helpful for light penetration and scattering,as well as rapid migration of the lignin substrate.The Z-scheme g-C3N4/In2O3heterojunction exhibited 92.1% conversion(corresponding benzaldehyde yield:82.4%)of the lignin model compound 2-phenoxy-1-phenylethanol(PP-ol),outperforming pure In2O3and g-C3N4by 40-and 2.3-fold,respectively,under 395 nm light illumination.By varying the illumination wavelength,the conversion and yields of the g-C3N4/In2O3composites were found to follow wavelength-dependent reactivities.Additionally,photogenerated holes are capable of converting PP-ol into benzoic acid,whereas1O2mainly converts PP-ol into benzaldehyde.This work could encourage the application of metal-organic frameworks in biomass conversion and provide insight into photocatalytic lignin valorization.展开更多
Objective:Aloin,the main active component in Aloe vera(L.)Burm.f.,has shown promising anti-tumor effects.This study investigated the impact of aloin in lung squamous cell carcinoma(LUSC)and explored its functional mec...Objective:Aloin,the main active component in Aloe vera(L.)Burm.f.,has shown promising anti-tumor effects.This study investigated the impact of aloin in lung squamous cell carcinoma(LUSC)and explored its functional mechanism.Methods:We analyzed the viability,migration,invasion,proliferation,and apoptosis of two LUSC cell lines after treatment with aloin.Target molecules of aloin and downstream target transcripts of nuclear receptor subfamily 3 group C member 2(NR3C2)were predicted by bioinformatics.The biological functions of NR3C2 and metallothionein 1M(MT1M)in the malignant properties of LUSC cells were determined.A co-culture system of LUSC cells with monocyte-derived macrophages was constructed.Mouse xenograft tumor models were generated to analyze the functions of aloin and NR3C2 in the tumorigenic activity of LUSC cells and macrophage polarization in vivo.Results:Aloin suppressed malignant properties of LUSC cells in vitro.However,these effects were negated by the silencing of NR3C2.NR3C2 was found to activate MT1M transcription by binding to its promoter.Additional upregulation of MT1M suppressed the malignant behavior of LUSC cells augmented by NR3C2 silencing.Analysis of the M1 and M2 markers/cytokines in the macrophages or the culture supernatant revealed that aloin treatment or MT1M overexpression in LUSC cells enhanced M1 polarization while suppressing M2 polarization of macrophages,whereas NR3C2 silencing led to reverse trends.Consistent findings were reproduced in vivo.Conclusion:This study demonstrated that aloin activates the NR3C2/MT1M axis to suppress the malignant behavior of LUSC cells and M2 macrophage polarization.Please cite this article as:Chen YN,Lu JY,Gao CF,Fang ZR,Zhou Y.Aloin blocks the malignant behavior of lung squamous cell carcinoma cells and M2 macrophage polarization by modulating the NR3C2/MT1M axis.展开更多
Cr2O3was used as grain inhibitor in Ti(C,N)-based cermets with vacuum sintering.The microstructure and mechanical and tribological properties of cermets with Cr2O3and Cr3C2were investigated.The resul...Cr2O3was used as grain inhibitor in Ti(C,N)-based cermets with vacuum sintering.The microstructure and mechanical and tribological properties of cermets with Cr2O3and Cr3C2were investigated.The results show that adding Cr2O3promotes a gray core/gray rim structure formation and finer size of Ti(C,N)hard phase.Compared with the cermet with an equal Cr3C2addition,the cermet with 0.6 wt.%Cr2O3exhibits 16.5%higher transverse rupture strength.This enhancement is likely due to the smaller lattice misfit at the coreim interface and more uniform Cr distribution in the binder.Additionally,at room temperature(25℃)and 800℃,Cr2O3-containing cermets demonstrate lower coefficients of friction and volume wear ratios than Cr3C2-containing cermets,with the wear ratio difference reaching an order of magnitude.Scanning electron microscopy and X-ray photoelectron spectroscopy results further confirm more oxidation wear in Cr2O3-containing cermets than in Cr3C2-containing cermets.展开更多
Background:Human adipose-derived stem cells(hADSCs)are seed cells with application prospects in cartilage repair.However,the mechanism of hADSC chondrogenic differentiation is still unclear.This study identifies a nov...Background:Human adipose-derived stem cells(hADSCs)are seed cells with application prospects in cartilage repair.However,the mechanism of hADSC chondrogenic differentiation is still unclear.This study identifies a novel circRNA,circNR3C2,which is significantly upregulated during the chondrogenic differentiation of hADSCs.Methods:To analyze their role in hADSC chondrogenic differentiation,hADSCs were separated and identified by flow cytometry.Thereafter,we conducted Alcian Blue staining to assess chondrogenic differentiation levels.Additionally,RT-qPCR was carried out to detect levels of the cartilage-related genes COL2,Aggrecan and SOX9.Moreover,overlapping target SOX9 and circNR3C2 miRNAs were detected by bioinformatics and luciferase analyses.Finally,the role of circNR3C2 was confirmed in vivo using animal models.Results:We confirmed that the cell surface receptors CD44,CD90 and CD105 were positively expressed on hADSCs,and their cartilage differentiation levels dramatically increased after 2 weeks.Expression of the cartilage-related genes COL2 and Aggrecan and circNR3C2 also markedly increased.CircNR3C2 overexpression enhanced cartilage differentiation of hADSCs,while up-regulating COL2,SOX9 and Aggrecan.Bioinformatics analysis identified hsa-miR-647 as the target miRNA of circ-NR3C2 and SOX9.Hsa-miR-647 overexpression in hADSCs can antagonize the effect of circNR3C2 on chondrogenic differentiation,and reverse its effect on regulating the expression of COL2,Aggrecan,and SOX9.We also showed that hADSCs overexpressing circNR3C2 promote cartilage repair in vivo.Conclusions:We show that circNR3C2 modulates SOX9 expression to promote hsamiR-647-mediated hADSC chondrogenic differentiation;targeting circNR3C2 may help to develop new treatments to manage cartilage-related disorders.展开更多
Pathological cardiac hypertrophy is an early and significant cardiac structural characteristic that contributes to the onset and progression of heart failure(HF).Its mainly structural feature is the abnormally enlarge...Pathological cardiac hypertrophy is an early and significant cardiac structural characteristic that contributes to the onset and progression of heart failure(HF).Its mainly structural feature is the abnormally enlarged cardiomyocyte.Effective intervention targets for abnormally enlarged cardiomyocyte remain to be identified.Previous studies have shown that the cellular shape and size can be regulated by the actin related protein 2/3(Arp2/3)complex,which is an actin-binding protein complex involved in the actin nucleation and assembly.However,the roles of the Arp2/3 complex in cardiomyocyte hypertrophy remain unknown.Here our study identifies its novel roles in the occurrence and development of cardiomyocyte hypertrophy.We found that mRNA levels of all subunits from the Arp2/3 complex are significantly upregulated(P<0.05)in the angiotensin Ⅱ(Ang Ⅱ)-induced neonatal rat primary and H9c2 cardiomyocyte hypertrophy.Further studies showed that siRNA-directed ARPC 2 silencing inhibits the reactivation of fetal genes and enlargement of cardiomyocyte area induced by Ang Ⅱ in neonatal rat primary cardiomyocytes(NRCMs)and H9c2 cells(P<0.05).In addition,the upstream activators of the Arp2/3 complex including SH3 protein interacting with Nck,90 kD(SPIN90)and Ras-related C3 botulinum toxin substrate 1(Rac1)/WASp family Verprolin-homologous protein-2(WAVE-2)are upregulated(P<0.05)in Ang Ⅱ-induced neonatal rat primary and H9c2 cardiomyocyte hypertrophy,indicating the excessive activation of the Arp2/3 complex.We further show that CK666,a specific Arp2/3 complex inhibitor,prevents the reactivation of fetal genes and the enlargement of cardiomyocyte area induced by Ang Ⅱ in NRCMs and H9c2 cells(P<0.05).Our results reveal that the Arp2/3 complex plays a crucial role in Ang Ⅱ-induced cardiomyocyte hypertrophy,which is beneficial to further studies about the molecular mechanisms by which the Arp2/3 complex regulates pathological cardiac hypertrophy.展开更多
基金supported by the National Natural Science Foundation of China(51303083)the National Natural Science Foundation of China for Excellent Young Scholars(51922050)+1 种基金the Natural Science Foundation of Jiangsu Province(BK20191293)the Fundamental Research Funds for the Central Universities(30920021123).
摘要The photocatalytic reduction of carbon dioxide(CO2)into high-value C2+hydrocarbons represents a sustainable pathway to alleviate energy shortages and reduce atmospheric CO2levels.In this study,a unique tandem photocatalyst(CoTi-CN)is constructed by integrating bimetallic CoTi-MOF with metal-free half-metallic C(CN)3.This composite demonstrates markedly enhanced activity and selectivity in the photocatalytic CO2reduction to ethylene(C2H4),achieving a C2H4selectivity of 36.8%and a generation yield of 31.3μmol g-1over 5 h.Density functional theory(DFT)calculations combined with in situ diffuse reflectance infrared Fourier transform spectroscopy(DRIFTS)analysis reveal that C(CN)3acts as an efficient CO2to CO converter,while CoTi-MOF favors the adsorption and C-C coupling of*CO intermediates.The spatially decoupled CO generation and C-C coupling processes lead to optimized intermediate coverage and reduced energy barriers,resulting in superior selectivity toward multi-carbon products.This work opens new horizons for the design of tandem photocatalysts that combine half-metallic catalysts with bimetallic MOFs,achieving a significant enhancement in the activity and selectivity of photocatalytic C2H4production.
基金supported by the National Natural Science Foundation of China(82071362 and 82270669)Key Project of the Regional Joint Fund of Guangdong Province(2023B1515120077)+3 种基金Basic Research Program of Shenzhen Science and Technology Innovation Commission(JCYJ20210324123001003 and JCYJ20220530144801003)Shenzhen Key Laboratory of Bone Tissue Repair and Translational Research(ZDSYS20230626091402006)the Innovation and Entrepreneurship Training Program for College Students,Sun Yat-sen University(20242150)the Leading Innovation and Entrepreneurship Team Program of Zhejiang Province,China(2023R01005).
摘要Activation of spinal cord neural stem cells(NSCs)and subsequent neurogenesis holds a promising alternative for spinal cord injury(SCI)repair.Our previous study demonstrated that complement C3a,derived from reactive astrocytes,inhibits NSC proliferation by suppressing protein aggregate clearance through the deubiquitinating enzyme ubiquitin carboxy-terminal hydrolase L1(UCHL1)-proteasome system post-SCI.However,the potential molecular mechanism by which C3a modulates NSC activation via this pathway remains unclear.Here,we revealed that C3a/C3a receptor(C3aR)signaling activated NF-κB p65,which in turn inhibited Nrf2 activity and UCHL1 expression,resulting in diminished proteasome activity and the accumulation of protein aggregates,and ultimately impaired NSC activation.Both knockdown of NF-κB p65 and Nrf2 upregulation restored UCHL1 expression and proteasome activity in vitro,promoting NSC activation by enhancing protein aggregate clearance.Mechanistically,we found that NF-κB p65 regulated Nrf2 activity through a dual mechanism:(1)promoting Keap1-dependent ubiquitination and proteasome degradation of Nrf2;(2)inhibiting protein kinase C-mediated Nrf2 phosphorylation and nuclear translocation.Using the dual-luciferase reporter assay and chromatin immunoprecipitation(ChIP)analysis,we further identified UCHL1 as a direct transcriptional target of Nrf2.Importantly,in vivo experiments using SCI mice confirmed that either C3aR blockade,NF-κB p65 knockdown,or Nrf2 overexpression could rescue SCI-induced UCHL1 downregulation.Together,this study uncovers the C3a-NF-κB p65-Nrf2-UCHL1-proteasome axis as a critical regulator of NSC activation after SCI.This may provide novel molecular targets and intervention strategies for SCI repair.
基金supported by the National Natural Science Foundation of China[grant number U24A2044]Science and Technology Major Program of Guangxi Province[grant number GUIKEAA24206007].
摘要Magnesium hydride serves as a promising solid-state hydrogen storage material owing to its high potential.However,its practical applications are constrained by the high enthalpy of hydrogen absorption and slow kinetics.In this study,we prepared a Ni/Ti3O5@graphene oxide(GO)dual-heterojunction composite material via solvent heating,electrostatic adsorption,and calcination to improve the hydrogen storage capabilities of MgH2.Adding Ni/Ti3O5@GO to MgH2 lowered the initial dehydrogenation temperature of MgH2 to 183℃;at a dehydrogenation temperature of 275℃,6.4 wt.%of H2 escaped from the MgH2 bulk.In addition,the hydrogen storage material absorbed 1.8 wt.%H2 at 30℃ for 30 min.The calculated activation energy of dehydrogenation was 48.221±0.141 kJ·mol-1,which was significantly lower than that of the ball-milled MgH2(112.63±1.44 kJ·mol-1).Mechanistic analysis results revealed that the heterojunction constructed from the multiphase compound system provided a large number of active sites and hydrogen diffusion routes,resulting in a synergistic catalytic effect that enhanced the hydrogen storage capacity of MgH2.In this work,we clarified the compositions of fuzzy interfaces in heterostructured materials by conducting ultraviolet photoelectron spectroscopy tests and identified key composite materials for the formation of heterojunctions.
基金the National Natural Science Foundation of China(Nos.22101135,22271293 and 21502096)the Natural Science Foundation of Jiangsu Province(Nos.BK20210381 and BK20150652)+3 种基金the Fundamental Research Funds for the Central Universities(Nos.KYQN2022058,KJQN201629,and XUEKEN2022032)the Strategic Priority Research Program of the Chinese Academy of Sciences(No.XDB0960000)CAS Project for Young Scientists in Basic Research(No.YSBR-050)the Chinese Academy of Sciences and the“333 High Level Talent Project”of Jiangsu Province for financial support。
摘要The stereodivergent coupling via photoredoxransition metal catalysis has emerged as a powerful tool to construct diverse alkenes in both E and Z configurations.Despite well-established catalytic systems involving late transition metals,the early transition metal catalyzed stereodivergent synthesis of alkenes still remains underdeveloped.Herein in this work,a stereodivergent reductive C(sp2)-C(sp3)coupling between cycloketone oximes and vinyl halides has been achieved by tunable photoredox/Ti dual catalysis,providing a facile access to a broad scope of cyano-substituted(fluoro)alkenes with high efficiency and controlled E/Z selectivity.Several products exhibited promising antifungal activities.
摘要The selective cleavage of Cα-Cβbonds is of great significance to lignin valorization,and photocataly-sis offers an eco-friendly pathway to achieve this process.Here,graphitic carbon nitride(g-C3N4)modified with hollow tubular In2O3was constructed via the calcination method for the photocatalytic cleavage of lignin Cα-Cβbonds.MIL-68(In)was used as the precursor of In2O3,imparting a unique hollow tubular structure and a relatively large specific surface area.The hollow tubular structure is helpful for light penetration and scattering,as well as rapid migration of the lignin substrate.The Z-scheme g-C3N4/In2O3heterojunction exhibited 92.1% conversion(corresponding benzaldehyde yield:82.4%)of the lignin model compound 2-phenoxy-1-phenylethanol(PP-ol),outperforming pure In2O3and g-C3N4by 40-and 2.3-fold,respectively,under 395 nm light illumination.By varying the illumination wavelength,the conversion and yields of the g-C3N4/In2O3composites were found to follow wavelength-dependent reactivities.Additionally,photogenerated holes are capable of converting PP-ol into benzoic acid,whereas1O2mainly converts PP-ol into benzaldehyde.This work could encourage the application of metal-organic frameworks in biomass conversion and provide insight into photocatalytic lignin valorization.
基金Financial support was provided by the Research Start-up Funding of Changzhou University(No.ZMF19020381)。
摘要Objective:Aloin,the main active component in Aloe vera(L.)Burm.f.,has shown promising anti-tumor effects.This study investigated the impact of aloin in lung squamous cell carcinoma(LUSC)and explored its functional mechanism.Methods:We analyzed the viability,migration,invasion,proliferation,and apoptosis of two LUSC cell lines after treatment with aloin.Target molecules of aloin and downstream target transcripts of nuclear receptor subfamily 3 group C member 2(NR3C2)were predicted by bioinformatics.The biological functions of NR3C2 and metallothionein 1M(MT1M)in the malignant properties of LUSC cells were determined.A co-culture system of LUSC cells with monocyte-derived macrophages was constructed.Mouse xenograft tumor models were generated to analyze the functions of aloin and NR3C2 in the tumorigenic activity of LUSC cells and macrophage polarization in vivo.Results:Aloin suppressed malignant properties of LUSC cells in vitro.However,these effects were negated by the silencing of NR3C2.NR3C2 was found to activate MT1M transcription by binding to its promoter.Additional upregulation of MT1M suppressed the malignant behavior of LUSC cells augmented by NR3C2 silencing.Analysis of the M1 and M2 markers/cytokines in the macrophages or the culture supernatant revealed that aloin treatment or MT1M overexpression in LUSC cells enhanced M1 polarization while suppressing M2 polarization of macrophages,whereas NR3C2 silencing led to reverse trends.Consistent findings were reproduced in vivo.Conclusion:This study demonstrated that aloin activates the NR3C2/MT1M axis to suppress the malignant behavior of LUSC cells and M2 macrophage polarization.Please cite this article as:Chen YN,Lu JY,Gao CF,Fang ZR,Zhou Y.Aloin blocks the malignant behavior of lung squamous cell carcinoma cells and M2 macrophage polarization by modulating the NR3C2/MT1M axis.
基金Natural Science Foundation of Ningxia,China(No.2023AAC03284)Fundamental Research Funds for the Central Universities Research Project of North Minzu University,China(No.2022XYZCL04)+1 种基金Project of Key Laboratory of Powders and Advanced CeramicsCo-founded by Ningxia and the State Ethnic Affairs Commission,China(No.2103)。
摘要Cr2O3was used as grain inhibitor in Ti(C,N)-based cermets with vacuum sintering.The microstructure and mechanical and tribological properties of cermets with Cr2O3and Cr3C2were investigated.The results show that adding Cr2O3promotes a gray core/gray rim structure formation and finer size of Ti(C,N)hard phase.Compared with the cermet with an equal Cr3C2addition,the cermet with 0.6 wt.%Cr2O3exhibits 16.5%higher transverse rupture strength.This enhancement is likely due to the smaller lattice misfit at the coreim interface and more uniform Cr distribution in the binder.Additionally,at room temperature(25℃)and 800℃,Cr2O3-containing cermets demonstrate lower coefficients of friction and volume wear ratios than Cr3C2-containing cermets,with the wear ratio difference reaching an order of magnitude.Scanning electron microscopy and X-ray photoelectron spectroscopy results further confirm more oxidation wear in Cr2O3-containing cermets than in Cr3C2-containing cermets.
基金supported by the Science and Technology Projects in Guangzhou(202201020566)Medical Joint Fund of Jinan University(YXJC2022005)+1 种基金Fundamental Research Funds for the Central Universities(21623319)Huadu District Basic and Applied Basic Research District and Hospital Joint Funding Program(23HDQYLH20).
摘要Background:Human adipose-derived stem cells(hADSCs)are seed cells with application prospects in cartilage repair.However,the mechanism of hADSC chondrogenic differentiation is still unclear.This study identifies a novel circRNA,circNR3C2,which is significantly upregulated during the chondrogenic differentiation of hADSCs.Methods:To analyze their role in hADSC chondrogenic differentiation,hADSCs were separated and identified by flow cytometry.Thereafter,we conducted Alcian Blue staining to assess chondrogenic differentiation levels.Additionally,RT-qPCR was carried out to detect levels of the cartilage-related genes COL2,Aggrecan and SOX9.Moreover,overlapping target SOX9 and circNR3C2 miRNAs were detected by bioinformatics and luciferase analyses.Finally,the role of circNR3C2 was confirmed in vivo using animal models.Results:We confirmed that the cell surface receptors CD44,CD90 and CD105 were positively expressed on hADSCs,and their cartilage differentiation levels dramatically increased after 2 weeks.Expression of the cartilage-related genes COL2 and Aggrecan and circNR3C2 also markedly increased.CircNR3C2 overexpression enhanced cartilage differentiation of hADSCs,while up-regulating COL2,SOX9 and Aggrecan.Bioinformatics analysis identified hsa-miR-647 as the target miRNA of circ-NR3C2 and SOX9.Hsa-miR-647 overexpression in hADSCs can antagonize the effect of circNR3C2 on chondrogenic differentiation,and reverse its effect on regulating the expression of COL2,Aggrecan,and SOX9.We also showed that hADSCs overexpressing circNR3C2 promote cartilage repair in vivo.Conclusions:We show that circNR3C2 modulates SOX9 expression to promote hsamiR-647-mediated hADSC chondrogenic differentiation;targeting circNR3C2 may help to develop new treatments to manage cartilage-related disorders.
摘要Pathological cardiac hypertrophy is an early and significant cardiac structural characteristic that contributes to the onset and progression of heart failure(HF).Its mainly structural feature is the abnormally enlarged cardiomyocyte.Effective intervention targets for abnormally enlarged cardiomyocyte remain to be identified.Previous studies have shown that the cellular shape and size can be regulated by the actin related protein 2/3(Arp2/3)complex,which is an actin-binding protein complex involved in the actin nucleation and assembly.However,the roles of the Arp2/3 complex in cardiomyocyte hypertrophy remain unknown.Here our study identifies its novel roles in the occurrence and development of cardiomyocyte hypertrophy.We found that mRNA levels of all subunits from the Arp2/3 complex are significantly upregulated(P<0.05)in the angiotensin Ⅱ(Ang Ⅱ)-induced neonatal rat primary and H9c2 cardiomyocyte hypertrophy.Further studies showed that siRNA-directed ARPC 2 silencing inhibits the reactivation of fetal genes and enlargement of cardiomyocyte area induced by Ang Ⅱ in neonatal rat primary cardiomyocytes(NRCMs)and H9c2 cells(P<0.05).In addition,the upstream activators of the Arp2/3 complex including SH3 protein interacting with Nck,90 kD(SPIN90)and Ras-related C3 botulinum toxin substrate 1(Rac1)/WASp family Verprolin-homologous protein-2(WAVE-2)are upregulated(P<0.05)in Ang Ⅱ-induced neonatal rat primary and H9c2 cardiomyocyte hypertrophy,indicating the excessive activation of the Arp2/3 complex.We further show that CK666,a specific Arp2/3 complex inhibitor,prevents the reactivation of fetal genes and the enlargement of cardiomyocyte area induced by Ang Ⅱ in NRCMs and H9c2 cells(P<0.05).Our results reveal that the Arp2/3 complex plays a crucial role in Ang Ⅱ-induced cardiomyocyte hypertrophy,which is beneficial to further studies about the molecular mechanisms by which the Arp2/3 complex regulates pathological cardiac hypertrophy.