Acute lung injury(ALI)is a severe disease caused by viral infection that triggers an uncontrolled inflammatory response.This study investigated the capacity of jasurolignoside(JO),a natural compound,to bind to Toll-li...Acute lung injury(ALI)is a severe disease caused by viral infection that triggers an uncontrolled inflammatory response.This study investigated the capacity of jasurolignoside(JO),a natural compound,to bind to Toll-like receptor 4(TLR4)and treat ALI.The anti-inflammatory properties of JO were evaluated in vitro through Western blotting,enzyme-linked immunosorbent assay(ELISA),immunofluorescence staining,and co-immunoprecipitation.The investigation utilized a lipopolysaccharide(LPS)-induced ALI animal model to examine the therapeutic efficacy and mechanism of JO in vivo.JO attenuated inflammatory symptoms in infected cells and tissues by modulating the NOD-like receptor family pyrin domain containing protein 3(NLRP3)inflammasome and the nuclear factorκB(NF-κB)/mitogen-activated protein kinase(MAPK)pathway.Molecular docking simulations revealed JO binding to TLR4 active sites,confirmed by cellular thermal shift assay.Surface plasmon resonance(SPR)demonstrated direct interaction between JO and TLR4 with a Kd value of 35.1μmol·L^(-1).Moreover,JO inhibited tumor necrosis factorα(TNF-α),interleukin-1β(IL-1β),and IL-6 secretion and reduced leukocyte,neutrophil,lymphocyte,and macrophage infiltration in ALI-affected mice.JO also enhanced lung function and reduced ALI-related mortality.Immunohistochemical staining demonstrated JO's ability to suppress TLR4 expression in ALI-affected mouse lung tissue.This study establishes that JO can bind to TLR4 and effectively treat ALI,indicating its potential as a therapeutic agent for clinical applications.展开更多
ISO 13679规定特殊螺纹油管的气密封试验需要在9次上卸扣后进行,且特殊螺纹接头的上扣性能直接影响到其服役时的密封性能与连接强度。为探索有限元方法动态模拟多次上卸扣试验的可行性,建立了某锥面-锥面密封型特殊螺纹油管接头上卸扣...ISO 13679规定特殊螺纹油管的气密封试验需要在9次上卸扣后进行,且特殊螺纹接头的上扣性能直接影响到其服役时的密封性能与连接强度。为探索有限元方法动态模拟多次上卸扣试验的可行性,建立了某锥面-锥面密封型特殊螺纹油管接头上卸扣的有限元模型,对该接头进行了9次上卸扣的全过程模拟,仿真分析了该接头的密封性能,并进行了实物试验验证。研究结果表明:特殊螺纹接头的气密封性能随着上卸扣次数的增加而降低,最终其密封指数降低为第1次上扣时的73%;密封面处的塑性应变是影响接头密封性能的重要原因;随着上扣次数的增加,特殊螺纹接头的密封接触长度呈现先减小后增大的趋势;在上卸扣过程中密封面过盈量的变化较为显著。通过与实物试验的对比,验证了该方法的可行性与准确性,为深入了解上卸扣试验对接头密封性能的影响提供了有效方法。展开更多
特发性肺纤维化(idiopathic pulmonary fibrosis,IPF)是一种原因不明的最常见的间质性肺疾病(interstitial lung disease,ILD),以最终导致肺间质纤维化为特征,确诊后的中位生存期为2年-4年。近年来,IPF相关的肺癌(lung cancer associate...特发性肺纤维化(idiopathic pulmonary fibrosis,IPF)是一种原因不明的最常见的间质性肺疾病(interstitial lung disease,ILD),以最终导致肺间质纤维化为特征,确诊后的中位生存期为2年-4年。近年来,IPF相关的肺癌(lung cancer associated with IPF,IPF-LC)的发病率越来越高,且预后较单纯的IPF差。研究发现,IPF可能与肺癌的发生发展密切相关。尽管IPF-LC的发生机制尚不清楚,但目前的研究表示这两种疾病在分子及细胞水平的致病过程存在相似之处。目前肺纤维化相关的肺癌的细胞分子机制的研究已经成为研究者的关注焦点。本文通过回顾相关文献,以IPF-LC的细胞和分子机制及治疗最新现状为重点进行综述,希望能够提高临床医生对IPF-LC的认识。展开更多
Tendon heterotopic ossification(HO)is characterized by bone formation inside tendon tissue,which severely debilitates people in their daily life.Current therapies fail to promote functional tissue repair largely due t...Tendon heterotopic ossification(HO)is characterized by bone formation inside tendon tissue,which severely debilitates people in their daily life.Current therapies fail to promote functional tissue repair largely due to our limited understanding of HO pathogenesis.Here,we investigate the pathological mechanism and propose a potential treatment method for HO.Immunofluorescence assays showed that the Mohawk(MKX)expression level was decreased in human tendon HO tissue,coinciding with spontaneous HO and the upregulated expression of osteochondrogenic and angiogenic genes in the tendons of Mkx^(−/−)mice.Single-cell RNA sequencing analyses of wild-type and Mkx^(−/−)tendons identified three cell types and revealed the excessive activation of osteochondrogenic genes during the tenogenesis of Mkx^(−/−)tendon cells.Single-cell analysis revealed that the gene expression program of angiogenesis,which is strongly associated with bone formation,was activated in all cell types during HO.Moreover,inhibition of angiogenesis by the small-molecule inhibitor BIBF1120 attenuated bone formation and angiogenesis in the Achilles tendons of both Mkx mutant mice and a rat traumatic model of HO.These findings provide new insights into the cellular mechanisms of tendon HO and highlight the inhibition of angiogenesis with BIBF1120 as a potential treatment strategy for HO.展开更多
Bambusa pervariabilis Dendrocalamopsis grandis blight is caused by a toxin from the fungus Arthrinium phaeospermum （corda） M. B. Ellis. We used shaking culture in a modified Fries culture medium and methanol extrac...Bambusa pervariabilis Dendrocalamopsis grandis blight is caused by a toxin from the fungus Arthrinium phaeospermum （corda） M. B. Ellis. We used shaking culture in a modified Fries culture medium and methanol extraction to isolate the toxin. The optimal developing solvent mixture （methanol： ethyl acetate： H20 at 7：1.5：3） was selected using thin layer chromatography and used as the eluent for toxin purification by silica gel column chromatography. Two toxic fractions were identi- fied in the bioassay. A flaxen oil substance, AP-I, showed higher toxicity than a toxic white powder, AP-II. The more toxic AP-I was determined to be dibutyl phthalate （C16H2204, molecular weight of 278） by mass spectrome- try, nuclear magnetic resonance, and infrared spectropho- tometry. Dibutyl phthalate might contribute to the pathogenesis of bamboo blight.展开更多
基金supported by the National Natural Science Foundation of China(No.82260799)Guangxi Science and Technology Base and Talent Project(No.AA23026010)+3 种基金Undergraduate Innovation and Entrepreneurship Training Program(No.S202110600120)Guangxi Overseas“100 Persons’Plan”Highlevel Expert,University of Chinese Medicine(No.2022BS008)Guangxi University Young and Middle-aged Teachers Research Basic Ability Improvement Project(No.2023KY0303)Jiangxi Province 2022 Annual Graduate Student Innovation Special Fund Project(No.YC2022-B189)。
文摘Acute lung injury(ALI)is a severe disease caused by viral infection that triggers an uncontrolled inflammatory response.This study investigated the capacity of jasurolignoside(JO),a natural compound,to bind to Toll-like receptor 4(TLR4)and treat ALI.The anti-inflammatory properties of JO were evaluated in vitro through Western blotting,enzyme-linked immunosorbent assay(ELISA),immunofluorescence staining,and co-immunoprecipitation.The investigation utilized a lipopolysaccharide(LPS)-induced ALI animal model to examine the therapeutic efficacy and mechanism of JO in vivo.JO attenuated inflammatory symptoms in infected cells and tissues by modulating the NOD-like receptor family pyrin domain containing protein 3(NLRP3)inflammasome and the nuclear factorκB(NF-κB)/mitogen-activated protein kinase(MAPK)pathway.Molecular docking simulations revealed JO binding to TLR4 active sites,confirmed by cellular thermal shift assay.Surface plasmon resonance(SPR)demonstrated direct interaction between JO and TLR4 with a Kd value of 35.1μmol·L^(-1).Moreover,JO inhibited tumor necrosis factorα(TNF-α),interleukin-1β(IL-1β),and IL-6 secretion and reduced leukocyte,neutrophil,lymphocyte,and macrophage infiltration in ALI-affected mice.JO also enhanced lung function and reduced ALI-related mortality.Immunohistochemical staining demonstrated JO's ability to suppress TLR4 expression in ALI-affected mouse lung tissue.This study establishes that JO can bind to TLR4 and effectively treat ALI,indicating its potential as a therapeutic agent for clinical applications.
文摘特发性肺纤维化(idiopathic pulmonary fibrosis,IPF)是一种原因不明的最常见的间质性肺疾病(interstitial lung disease,ILD),以最终导致肺间质纤维化为特征,确诊后的中位生存期为2年-4年。近年来,IPF相关的肺癌(lung cancer associated with IPF,IPF-LC)的发病率越来越高,且预后较单纯的IPF差。研究发现,IPF可能与肺癌的发生发展密切相关。尽管IPF-LC的发生机制尚不清楚,但目前的研究表示这两种疾病在分子及细胞水平的致病过程存在相似之处。目前肺纤维化相关的肺癌的细胞分子机制的研究已经成为研究者的关注焦点。本文通过回顾相关文献,以IPF-LC的细胞和分子机制及治疗最新现状为重点进行综述,希望能够提高临床医生对IPF-LC的认识。
基金supported by the National Key R&D Program of China(2017YFA0104900)the National Natural Science Foundation of China(31830029,81501937 and 81522029)the Fundamental Research Funds for the Central Universities(K20200099).
文摘Tendon heterotopic ossification(HO)is characterized by bone formation inside tendon tissue,which severely debilitates people in their daily life.Current therapies fail to promote functional tissue repair largely due to our limited understanding of HO pathogenesis.Here,we investigate the pathological mechanism and propose a potential treatment method for HO.Immunofluorescence assays showed that the Mohawk(MKX)expression level was decreased in human tendon HO tissue,coinciding with spontaneous HO and the upregulated expression of osteochondrogenic and angiogenic genes in the tendons of Mkx^(−/−)mice.Single-cell RNA sequencing analyses of wild-type and Mkx^(−/−)tendons identified three cell types and revealed the excessive activation of osteochondrogenic genes during the tenogenesis of Mkx^(−/−)tendon cells.Single-cell analysis revealed that the gene expression program of angiogenesis,which is strongly associated with bone formation,was activated in all cell types during HO.Moreover,inhibition of angiogenesis by the small-molecule inhibitor BIBF1120 attenuated bone formation and angiogenesis in the Achilles tendons of both Mkx mutant mice and a rat traumatic model of HO.These findings provide new insights into the cellular mechanisms of tendon HO and highlight the inhibition of angiogenesis with BIBF1120 as a potential treatment strategy for HO.
基金supported by the National Natural Science Foundation of China(31070578)the National Natural Science and Technology Resources Sharing Platform of China(2005DKA21207-13)
文摘Bambusa pervariabilis Dendrocalamopsis grandis blight is caused by a toxin from the fungus Arthrinium phaeospermum （corda） M. B. Ellis. We used shaking culture in a modified Fries culture medium and methanol extraction to isolate the toxin. The optimal developing solvent mixture （methanol： ethyl acetate： H20 at 7：1.5：3） was selected using thin layer chromatography and used as the eluent for toxin purification by silica gel column chromatography. Two toxic fractions were identi- fied in the bioassay. A flaxen oil substance, AP-I, showed higher toxicity than a toxic white powder, AP-II. The more toxic AP-I was determined to be dibutyl phthalate （C16H2204, molecular weight of 278） by mass spectrome- try, nuclear magnetic resonance, and infrared spectropho- tometry. Dibutyl phthalate might contribute to the pathogenesis of bamboo blight.
