Complement C3 plays a critical role in periodontitis.However,its source,role and underlying mechanisms remain unclear.In our study,by analyzing single-cell sequencing data from mouse model of periodontitis,we identifi...Complement C3 plays a critical role in periodontitis.However,its source,role and underlying mechanisms remain unclear.In our study,by analyzing single-cell sequencing data from mouse model of periodontitis,we identified that C3 is primarily derived from periodontal fibroblasts.Subsequently,we demonstrated that C3a has a detrimental effect in ligature-induced periodontitis.C3ar−/−mice exhibited significantly less destruction of periodontal support tissues compared to wild-type mice,characterized by mild gingival tissue damage and reduced alveolar bone loss.This reduction was associated with decreased production of proinflammatory mediators and reduced osteoclast infiltration in the periodontal tissues.Mechanistic studies suggested that C3a could promote macrophage polarization and osteoclast differentiation.Finally,by analyzing single-cell sequencing data from the periodontal tissues of patients with periodontitis,we found that the results observed in mice were consistent with human data.Therefore,our findings clearly demonstrate the destructive role of fibroblast-derived C3 in ligature-induced periodontitis,driven by macrophage M1 polarization and osteoclast differentiation.These data strongly support the feasibility of C3a-targeted interventions for the treatment of human periodontitis.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
M23C6 chromium-rich carbides are common grain-boundary precipitations in Cr-containing steel.The presence of grain-boundary carbides often leads to intergranular brittleness and decreases mechanical properties.This st...M23C6 chromium-rich carbides are common grain-boundary precipitations in Cr-containing steel.The presence of grain-boundary carbides often leads to intergranular brittleness and decreases mechanical properties.This study proposes a deformation and aging technique to obtain a high-volume-fraction dispersion distribution of the hard nano-M23C6 phase by changing the nucleation sites from grain boundaries to deformation coherent twin boundaries produced during cold deformation.The M23C6 precipitation-strengthened austenitic stainless steel has a strength of up to 1.4 GPa but maintains favorable plasticity(>11%).This study provides a novel approach for the control of intergranular brittleness in metallic materials.展开更多
随着全球化进程的深入推进,中小企业在日益激烈的竞争环境中正面临双重的挑战:如何在国内市场中稳固其地位,同时积极拓展国际市场。C2M(Consumer to Manufacturer,从消费者到制造商)个性化定制模式为这些企业提供了一个独特的策略,使其...随着全球化进程的深入推进,中小企业在日益激烈的竞争环境中正面临双重的挑战:如何在国内市场中稳固其地位,同时积极拓展国际市场。C2M(Consumer to Manufacturer,从消费者到制造商)个性化定制模式为这些企业提供了一个独特的策略,使其能够更好地适应市场的快速变化,满足消费者的个性化需求。本研究深入探讨了适应国内经济大循环和国际经济大循环中的C2M个性化定制创新路径,并通过关键要素分析了这些路径的实施策略及其效益。结果表明,通过有效整合国内外资源并采用C2M模式,中小企业不仅可以提高其产品的市场竞争力,而且还能够实现在两个市场的同步增长,避免过度依赖任何一个市场。展开更多
基金supported by the National Key R&D Program of China(No.2022YFC2504200)the National Natural Science Foundation of China(Nos.82370936,81920108012,82471032).
文摘Complement C3 plays a critical role in periodontitis.However,its source,role and underlying mechanisms remain unclear.In our study,by analyzing single-cell sequencing data from mouse model of periodontitis,we identified that C3 is primarily derived from periodontal fibroblasts.Subsequently,we demonstrated that C3a has a detrimental effect in ligature-induced periodontitis.C3ar−/−mice exhibited significantly less destruction of periodontal support tissues compared to wild-type mice,characterized by mild gingival tissue damage and reduced alveolar bone loss.This reduction was associated with decreased production of proinflammatory mediators and reduced osteoclast infiltration in the periodontal tissues.Mechanistic studies suggested that C3a could promote macrophage polarization and osteoclast differentiation.Finally,by analyzing single-cell sequencing data from the periodontal tissues of patients with periodontitis,we found that the results observed in mice were consistent with human data.Therefore,our findings clearly demonstrate the destructive role of fibroblast-derived C3 in ligature-induced periodontitis,driven by macrophage M1 polarization and osteoclast differentiation.These data strongly support the feasibility of C3a-targeted interventions for the treatment of human periodontitis.
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.
基金supported by the National Natural Science Foundation of China(No.52250130).
文摘M23C6 chromium-rich carbides are common grain-boundary precipitations in Cr-containing steel.The presence of grain-boundary carbides often leads to intergranular brittleness and decreases mechanical properties.This study proposes a deformation and aging technique to obtain a high-volume-fraction dispersion distribution of the hard nano-M23C6 phase by changing the nucleation sites from grain boundaries to deformation coherent twin boundaries produced during cold deformation.The M23C6 precipitation-strengthened austenitic stainless steel has a strength of up to 1.4 GPa but maintains favorable plasticity(>11%).This study provides a novel approach for the control of intergranular brittleness in metallic materials.
文摘随着全球化进程的深入推进,中小企业在日益激烈的竞争环境中正面临双重的挑战:如何在国内市场中稳固其地位,同时积极拓展国际市场。C2M(Consumer to Manufacturer,从消费者到制造商)个性化定制模式为这些企业提供了一个独特的策略,使其能够更好地适应市场的快速变化,满足消费者的个性化需求。本研究深入探讨了适应国内经济大循环和国际经济大循环中的C2M个性化定制创新路径,并通过关键要素分析了这些路径的实施策略及其效益。结果表明,通过有效整合国内外资源并采用C2M模式,中小企业不仅可以提高其产品的市场竞争力,而且还能够实现在两个市场的同步增长,避免过度依赖任何一个市场。
