A novel synthesis of C2-spiroindoline derivatives based on the cascade reaction of 2-aryl-3H-indoles with cyclo- propanols is presented. The formation of product involves Rh(III)-catalyzed aryl C(sp2)—H bond alkylati...A novel synthesis of C2-spiroindoline derivatives based on the cascade reaction of 2-aryl-3H-indoles with cyclo- propanols is presented. The formation of product involves Rh(III)-catalyzed aryl C(sp2)—H bond alkylation of 2-aryl- 3H-indole, which is followed by intramolecular spiroannulation. In this tandem process, cyclopropanol acts as not only an alkylating agent but also a masked nucleophile to take part in the construction of the spirocyclic scaffold. Meanwhile, air acts as an economical and sustainable oxidant to promote the regeneration of the active catalyst. By using this method, hybrid compounds containing the central scaffolds of some clinical drugs were prepared effectively. In general, this newly developed method has advantages such as easily obtainable substrates, concise synthetic procedure, excellent atom-economy, good compatibility with diverse functional groups and ready scalability.展开更多
目的:通过对C3H10T1/2细胞分化为成熟棕色脂肪细胞的培养、诱导分化及鉴定,深入探讨棕色脂肪细胞的生物学特性,为人类棕色脂肪细胞的相关研究提供实验参考与理论依据。方法:C3H10T1/2细胞经细胞接种、培养及诱导分化处理,利用光学显微...目的:通过对C3H10T1/2细胞分化为成熟棕色脂肪细胞的培养、诱导分化及鉴定,深入探讨棕色脂肪细胞的生物学特性,为人类棕色脂肪细胞的相关研究提供实验参考与理论依据。方法:C3H10T1/2细胞经细胞接种、培养及诱导分化处理,利用光学显微镜观察细胞形态变化,并通过油红O染色、免疫荧光法、线粒体探针法以及线粒体电镜技术对分化细胞进行鉴定分析。结果:未分化的C3H10T1/2细胞形态多样,具有突触伸展特征;分化后的细胞逐渐变为圆形或椭圆形,形成环形脂滴;未分化组细胞形态无明显变化。油红O染色显示,未分化组细胞基本无染色,而分化组中约90%的细胞红染,脂滴分布于细胞核周围,吸光度值显著升高(P<0.05)。分化组解偶联蛋白1(uncoupling protein 1,UCP1)、过氧化物酶体增殖激活受体γ(peroxisome proliferator-activated receptorγ,PPARγ)辅激活因子1α(PPARγco-activator-1α,PGC-1α)、PPARγ和转录因子PRDM16的相对荧光强度和蛋白表达量显著高于未分化组(P<0.05),且线粒体活性增强。结论:本研究成功诱导C3H10T1/2细胞分化为成熟棕色脂肪细胞,结合细胞形态观察、关键蛋白表达检测及线粒体功能分析进行综合评估,证实了细胞的有效分化及成熟棕色脂肪细胞的功能特性。展开更多
Light-driven CO_(2) reduction reaction(CO_(2)RR)to value-added ethylene(C2H4)holds significant promise for addressing energy and environmental challenges.While the high energy barriers for*CO intermediates hydrogenati...Light-driven CO_(2) reduction reaction(CO_(2)RR)to value-added ethylene(C2H4)holds significant promise for addressing energy and environmental challenges.While the high energy barriers for*CO intermediates hydrogenation and C–C coupling limit the C_(2)H_(4)generation.Herein,CuxP/g-C_(3)N_(4) heterojunction prepared by an in-situ phosphating technique,achieved collaborative photocatalytic CO_(2) and H2O,producing CO and C_(2)H_(4)as the main products.Notably,the selectivity of C_(2)H_(4)produced by CuxP/g-C_(3)N_(4) attained to 64.25%,which was 9.85 times that of CuxP(6.52%).Detailed time-resolution photoluminescence spectra,femtosecond transient absorption spectroscopy tests and density functional theory(DFT)calculation validate the ultra-fast interfacial electron transfer mechanism in CuxP/g-C_(3)N_(4) heterojunction.Successive*H on P sites caused by adsorbed H2O splitting with moderate hydrogenation ability enables the multi-step hydrogenation during CO_(2)RR process over CuxP/g-C_(3)N_(4).With the aid of mediated asymmetric Cu and P dual sites by g-C_(3)N_(4) nanosheet,the produced*CHO shows an energetically favorable for C–C coupling.The coupling formed*CHOCHO further accepts photoexcited efficient e–and*H to deeply produce C_(2)H_(4)according to the C^(2+)intermediates,which has been detected by in-situ diffuse reflectance infrared Fourier transform spectroscopy and interpreted by DFT calculation.The novel insight mechanism offers an essential understanding for the development of CuxP-based heterojunctions for photocatalytic CO_(2) to C^(2+)value-added fuels.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
Cr_(2)O_(3)was used as grain inhibitor in Ti(C,N)-based cermets with vacuum sintering.The microstructure and mechanical and tribological properties of cermets with Cr_(2)O_(3)and Cr_(3)C_(2)were investigated.The resul...Cr_(2)O_(3)was used as grain inhibitor in Ti(C,N)-based cermets with vacuum sintering.The microstructure and mechanical and tribological properties of cermets with Cr_(2)O_(3)and Cr_(3)C_(2)were investigated.The results show that adding Cr_(2)O_(3)promotes a gray core/gray rim structure formation and finer size of Ti(C,N)hard phase.Compared with the cermet with an equal Cr_(3)C_(2)addition,the cermet with 0.6 wt.%Cr_(2)O_(3)exhibits 16.5%higher transverse rupture strength.This enhancement is likely due to the smaller lattice misfit at the core/rim interface and more uniform Cr distribution in the binder.Additionally,at room temperature(25℃)and 800℃,Cr_(2)O_(3)-containing cermets demonstrate lower coefficients of friction and volume wear ratios than Cr_(3)C_(2)-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 Cr_(2)O_(3)-containing cermets than in Cr_(3)C_(2)-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
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
文摘A novel synthesis of C2-spiroindoline derivatives based on the cascade reaction of 2-aryl-3H-indoles with cyclo- propanols is presented. The formation of product involves Rh(III)-catalyzed aryl C(sp2)—H bond alkylation of 2-aryl- 3H-indole, which is followed by intramolecular spiroannulation. In this tandem process, cyclopropanol acts as not only an alkylating agent but also a masked nucleophile to take part in the construction of the spirocyclic scaffold. Meanwhile, air acts as an economical and sustainable oxidant to promote the regeneration of the active catalyst. By using this method, hybrid compounds containing the central scaffolds of some clinical drugs were prepared effectively. In general, this newly developed method has advantages such as easily obtainable substrates, concise synthetic procedure, excellent atom-economy, good compatibility with diverse functional groups and ready scalability.
文摘目的:通过对C3H10T1/2细胞分化为成熟棕色脂肪细胞的培养、诱导分化及鉴定,深入探讨棕色脂肪细胞的生物学特性,为人类棕色脂肪细胞的相关研究提供实验参考与理论依据。方法:C3H10T1/2细胞经细胞接种、培养及诱导分化处理,利用光学显微镜观察细胞形态变化,并通过油红O染色、免疫荧光法、线粒体探针法以及线粒体电镜技术对分化细胞进行鉴定分析。结果:未分化的C3H10T1/2细胞形态多样,具有突触伸展特征;分化后的细胞逐渐变为圆形或椭圆形,形成环形脂滴;未分化组细胞形态无明显变化。油红O染色显示,未分化组细胞基本无染色,而分化组中约90%的细胞红染,脂滴分布于细胞核周围,吸光度值显著升高(P<0.05)。分化组解偶联蛋白1(uncoupling protein 1,UCP1)、过氧化物酶体增殖激活受体γ(peroxisome proliferator-activated receptorγ,PPARγ)辅激活因子1α(PPARγco-activator-1α,PGC-1α)、PPARγ和转录因子PRDM16的相对荧光强度和蛋白表达量显著高于未分化组(P<0.05),且线粒体活性增强。结论:本研究成功诱导C3H10T1/2细胞分化为成熟棕色脂肪细胞,结合细胞形态观察、关键蛋白表达检测及线粒体功能分析进行综合评估,证实了细胞的有效分化及成熟棕色脂肪细胞的功能特性。
文摘Light-driven CO_(2) reduction reaction(CO_(2)RR)to value-added ethylene(C2H4)holds significant promise for addressing energy and environmental challenges.While the high energy barriers for*CO intermediates hydrogenation and C–C coupling limit the C_(2)H_(4)generation.Herein,CuxP/g-C_(3)N_(4) heterojunction prepared by an in-situ phosphating technique,achieved collaborative photocatalytic CO_(2) and H2O,producing CO and C_(2)H_(4)as the main products.Notably,the selectivity of C_(2)H_(4)produced by CuxP/g-C_(3)N_(4) attained to 64.25%,which was 9.85 times that of CuxP(6.52%).Detailed time-resolution photoluminescence spectra,femtosecond transient absorption spectroscopy tests and density functional theory(DFT)calculation validate the ultra-fast interfacial electron transfer mechanism in CuxP/g-C_(3)N_(4) heterojunction.Successive*H on P sites caused by adsorbed H2O splitting with moderate hydrogenation ability enables the multi-step hydrogenation during CO_(2)RR process over CuxP/g-C_(3)N_(4).With the aid of mediated asymmetric Cu and P dual sites by g-C_(3)N_(4) nanosheet,the produced*CHO shows an energetically favorable for C–C coupling.The coupling formed*CHOCHO further accepts photoexcited efficient e–and*H to deeply produce C_(2)H_(4)according to the C^(2+)intermediates,which has been detected by in-situ diffuse reflectance infrared Fourier transform spectroscopy and interpreted by DFT calculation.The novel insight mechanism offers an essential understanding for the development of CuxP-based heterojunctions for photocatalytic CO_(2) to C^(2+)value-added fuels.
文摘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.
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)。
文摘Cr_(2)O_(3)was used as grain inhibitor in Ti(C,N)-based cermets with vacuum sintering.The microstructure and mechanical and tribological properties of cermets with Cr_(2)O_(3)and Cr_(3)C_(2)were investigated.The results show that adding Cr_(2)O_(3)promotes a gray core/gray rim structure formation and finer size of Ti(C,N)hard phase.Compared with the cermet with an equal Cr_(3)C_(2)addition,the cermet with 0.6 wt.%Cr_(2)O_(3)exhibits 16.5%higher transverse rupture strength.This enhancement is likely due to the smaller lattice misfit at the core/rim interface and more uniform Cr distribution in the binder.Additionally,at room temperature(25℃)and 800℃,Cr_(2)O_(3)-containing cermets demonstrate lower coefficients of friction and volume wear ratios than Cr_(3)C_(2)-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 Cr_(2)O_(3)-containing cermets than in Cr_(3)C_(2)-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).
文摘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.
基金Financial support was provided by the Research Start-up Funding of Changzhou University(No.ZMF19020381)。
文摘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.
