OBJECTIVE Identification of novel autophagy inhibitors for the combinational treatment of non-small cell lung cancer(NSCLC).METHODS MTT assay and annexin V/PI staining assay were used to evaluate the cell proliferatio...OBJECTIVE Identification of novel autophagy inhibitors for the combinational treatment of non-small cell lung cancer(NSCLC).METHODS MTT assay and annexin V/PI staining assay were used to evaluate the cell proliferation and apoptosis,respectively.Immunofluorescence staining and cathepsin activity assay were used to detect autophagy.Small interfering RNA was performed to silence the genes and Western blot assay was used to evaluate the protein express levels.Xenograft experiments were applied for in vivo evaluation.RESULTS Cepharanthine,a natural compound,increased LC3-II expression and GFP-LC3 puncta formation in NSCLC NCI-H1975 cells.Numerous yellow puncta were observed in cepharanthine-treated cells with m RFP-EGFP-LC3 transfection.Co-staining of GFP-LC3 with LysoT racker red or LAMP1 antibody suggested that cepharanthine inhibits autophagosomes-lysosomes fusion.Moreover,cepharanthine attenuated the lysosomal cathepsins maturation.We also confirmed that dacomitinib induced cytoprotective autophagy.Combined treatment with cepharanthine increased the anti-cancer effects of dacomitinib in vitro and in vivo.Besides,cepharanthine could not enhance the anti-cancer effect of dacomitinib in autophagy deficient cells.CONCLUSION Cepharanthine might be further developed as a promising autophagic inhibitor,and combined treatment cepharanthine with dacomitinib could pose as an effective strategy for NSCLC treatment.展开更多
通过在橡胶基体中集成多种功能性橡胶颗粒(FRGs),构筑具有多相网络结构的阻尼橡胶材料.首先通过扫描电子显微镜(scanning electron microscopy,SEM)和原子力显微镜(atomic force microscopy,AFM)观察所制备集成材料的微观形貌,然后探究...通过在橡胶基体中集成多种功能性橡胶颗粒(FRGs),构筑具有多相网络结构的阻尼橡胶材料.首先通过扫描电子显微镜(scanning electron microscopy,SEM)和原子力显微镜(atomic force microscopy,AFM)观察所制备集成材料的微观形貌,然后探究了FRGs多种组合对橡胶样品的动态性能的影响.结果表明,基于FRGs集成的多组分样品呈典型的“海-岛”多相结构,在保持每种FRGs组分相对独立的黏弹特性的同时,通过有效的界面反应实现黏弹特性的集成.进一步地,通过调控FRGs的网络结构参数和相对含量实现了各组分损耗峰的有序组合,获得一种多相结构的宽温域阻尼橡胶材料,其在吸音降噪方面展现出较好的应用潜力.此外,该多相阻尼材料还兼具优异的力学性能和吸能减震能力.本文工作基于传统橡胶工业原料和共混工艺,提出了一种简单易行、可规模化生产的橡胶阻尼材料制备新策略,不涉及复杂合成与改性,为发展高性能橡胶阻尼材料提供了新思路.展开更多
Although bioinspired sacrificial bonds have been demonstrated to be efficient in improving the mechanical properties of polymer materials, the effect of binding energy of a specific dynamic bond on the ultimate mechan...Although bioinspired sacrificial bonds have been demonstrated to be efficient in improving the mechanical properties of polymer materials, the effect of binding energy of a specific dynamic bond on the ultimate mechanical performance of a polymer network with dual-crosslink remains unclear. In this contribution, diamine and sulfur curing package are introduced simultaneously into a sulfonated cis-1,4-polyisoprene to create dually-crosslinked cis-1,4-polyisoprene network with sulfonate-aminium ionic bonds as the sacrificial bonds. Three diamines （primary, secondary and tertiary） with the same spacer between the two nitrogen atoms are used to create the ionic bonds with different binding energies. Although the binding energy of ionic bond does not affect the glass transition temperature of cis-1,4-polyisoprene （IR）, it exerts definite influences on strain-induced crystallization and mechanical performance. The capabilities of diamine in dissipating energy, promoting strain-induced crystallization and enhancing the mechanical performance are in the same order of secondary diamine 〉 primary diamine 〉 tertiary diamine. The variations in mechanical performances are correlated to the binding energy of the ionic bond, which is determined by pKa values.展开更多
Recently,increasingly growing efforts have been devoted to incorporating dynamic covalent bonds into covalently crosslinked networks to address the persistent trade-offs between chemical crosslinking and malleability....Recently,increasingly growing efforts have been devoted to incorporating dynamic covalent bonds into covalently crosslinked networks to address the persistent trade-offs between chemical crosslinking and malleability.Herein,a series of dynamic aminal bond crosslinked polybutadiene rubbers(PAPB)are prepared by crosslinking aldehyde group-terminated polybutadiene rubber(APB)with piperazine.By varying the molecular weight of APB,the crosslinking density of PAPB is changed,which offers the platform to regulate the mechanical characteristics and dynamic properties.Specially,with the decrease of APB molecular weight,i.e.with the increase of crosslinking density,the modulus of PAPB gradually increases while the elongation at break conversely decreases,and the activation energy for network rearrangement initially decreases and then increases.The resultant PAPB exhibit vitrimer-like behaviors that can alter the network topologies at elevated temperatures without the loss of structural integrity through dissociative aminal exchange reactions,while the protic source can accelerate aminal dissociation and result in network dissolution even at room temperature.Due to the aminal exchange,PAPB are thermally malleable and can almost restore the original mechanical characteristics after recycling;besides,they are capable of healing at a relatively low crosslinking density.展开更多
基金supported by Science and Technology Development Fund,Macao S.A.R(FDCT)(024/2016/A1)Research Fund of University of Macao(MYRG2015-00091-ICMS-QRCM and MYRG2015-00101-ICMS-QRCM)
文摘OBJECTIVE Identification of novel autophagy inhibitors for the combinational treatment of non-small cell lung cancer(NSCLC).METHODS MTT assay and annexin V/PI staining assay were used to evaluate the cell proliferation and apoptosis,respectively.Immunofluorescence staining and cathepsin activity assay were used to detect autophagy.Small interfering RNA was performed to silence the genes and Western blot assay was used to evaluate the protein express levels.Xenograft experiments were applied for in vivo evaluation.RESULTS Cepharanthine,a natural compound,increased LC3-II expression and GFP-LC3 puncta formation in NSCLC NCI-H1975 cells.Numerous yellow puncta were observed in cepharanthine-treated cells with m RFP-EGFP-LC3 transfection.Co-staining of GFP-LC3 with LysoT racker red or LAMP1 antibody suggested that cepharanthine inhibits autophagosomes-lysosomes fusion.Moreover,cepharanthine attenuated the lysosomal cathepsins maturation.We also confirmed that dacomitinib induced cytoprotective autophagy.Combined treatment with cepharanthine increased the anti-cancer effects of dacomitinib in vitro and in vivo.Besides,cepharanthine could not enhance the anti-cancer effect of dacomitinib in autophagy deficient cells.CONCLUSION Cepharanthine might be further developed as a promising autophagic inhibitor,and combined treatment cepharanthine with dacomitinib could pose as an effective strategy for NSCLC treatment.
文摘通过在橡胶基体中集成多种功能性橡胶颗粒(FRGs),构筑具有多相网络结构的阻尼橡胶材料.首先通过扫描电子显微镜(scanning electron microscopy,SEM)和原子力显微镜(atomic force microscopy,AFM)观察所制备集成材料的微观形貌,然后探究了FRGs多种组合对橡胶样品的动态性能的影响.结果表明,基于FRGs集成的多组分样品呈典型的“海-岛”多相结构,在保持每种FRGs组分相对独立的黏弹特性的同时,通过有效的界面反应实现黏弹特性的集成.进一步地,通过调控FRGs的网络结构参数和相对含量实现了各组分损耗峰的有序组合,获得一种多相结构的宽温域阻尼橡胶材料,其在吸音降噪方面展现出较好的应用潜力.此外,该多相阻尼材料还兼具优异的力学性能和吸能减震能力.本文工作基于传统橡胶工业原料和共混工艺,提出了一种简单易行、可规模化生产的橡胶阻尼材料制备新策略,不涉及复杂合成与改性,为发展高性能橡胶阻尼材料提供了新思路.
基金financially supported by the National Basic Research Program of China(No.2015CB654700(2015CB654703))the National Natural Science Foundation of China(Nos.51673065,51703064,51473050 and 51333003)Fundamental Research Funds for the Central Universities(No.2017PY006)
文摘Although bioinspired sacrificial bonds have been demonstrated to be efficient in improving the mechanical properties of polymer materials, the effect of binding energy of a specific dynamic bond on the ultimate mechanical performance of a polymer network with dual-crosslink remains unclear. In this contribution, diamine and sulfur curing package are introduced simultaneously into a sulfonated cis-1,4-polyisoprene to create dually-crosslinked cis-1,4-polyisoprene network with sulfonate-aminium ionic bonds as the sacrificial bonds. Three diamines （primary, secondary and tertiary） with the same spacer between the two nitrogen atoms are used to create the ionic bonds with different binding energies. Although the binding energy of ionic bond does not affect the glass transition temperature of cis-1,4-polyisoprene （IR）, it exerts definite influences on strain-induced crystallization and mechanical performance. The capabilities of diamine in dissipating energy, promoting strain-induced crystallization and enhancing the mechanical performance are in the same order of secondary diamine 〉 primary diamine 〉 tertiary diamine. The variations in mechanical performances are correlated to the binding energy of the ionic bond, which is determined by pKa values.
基金supported by the National Science Fund for Distinguished Young Scholars(No.51825303)the National Natural Science Foundation of China(Nos.52073097 and 51790503).
文摘Recently,increasingly growing efforts have been devoted to incorporating dynamic covalent bonds into covalently crosslinked networks to address the persistent trade-offs between chemical crosslinking and malleability.Herein,a series of dynamic aminal bond crosslinked polybutadiene rubbers(PAPB)are prepared by crosslinking aldehyde group-terminated polybutadiene rubber(APB)with piperazine.By varying the molecular weight of APB,the crosslinking density of PAPB is changed,which offers the platform to regulate the mechanical characteristics and dynamic properties.Specially,with the decrease of APB molecular weight,i.e.with the increase of crosslinking density,the modulus of PAPB gradually increases while the elongation at break conversely decreases,and the activation energy for network rearrangement initially decreases and then increases.The resultant PAPB exhibit vitrimer-like behaviors that can alter the network topologies at elevated temperatures without the loss of structural integrity through dissociative aminal exchange reactions,while the protic source can accelerate aminal dissociation and result in network dissolution even at room temperature.Due to the aminal exchange,PAPB are thermally malleable and can almost restore the original mechanical characteristics after recycling;besides,they are capable of healing at a relatively low crosslinking density.
