自噬是一种广泛存在于真核细胞中的溶酶体依赖性分解代谢途径,涉及细胞分化、饥饿耐受和免疫防御等生物学功能。其中,异体自噬被定义为真核细胞特异性识别并清除胞内病原微生物的过程,是免疫细胞行使宿主防御的重要方式。然而,许多病原...自噬是一种广泛存在于真核细胞中的溶酶体依赖性分解代谢途径,涉及细胞分化、饥饿耐受和免疫防御等生物学功能。其中,异体自噬被定义为真核细胞特异性识别并清除胞内病原微生物的过程,是免疫细胞行使宿主防御的重要方式。然而,许多病原微生物已经“开发”了特殊的毒力因子(包括效应蛋白质和表面蛋白质等),衍生出多种逃避或劫持自噬作用的策略。研究表明,调控自噬的信号复杂,涉及到多种自噬相关蛋白质(autophagy related proteins,ATG proteins)的精细调控。现已证实,自噬的关键步骤经历了广泛的蛋白质翻译后修饰(post-translational modifications,PTMs),例如磷酸化/去磷酸化、泛素化/去泛素化等。这些修饰作用通过影响蛋白质的结构、稳定性、活性及其在细胞中的定位,赋予了宿主细胞自噬调控高度的动态性和可逆性。此外,研究发现,病原微生物的毒力因子能够劫持宿主细胞中ATG蛋白的蛋白质翻译后修饰,干扰自噬的信号传递,从而对抗异体自噬并促进其在宿主细胞中的存活。本文总结了常见的蛋白质翻译后修饰在异体自噬中的作用,并重点关注病原微生物利用宿主蛋白质翻译后修饰操纵异体自噬,进而促进自身存活的相关机制,为探索异体自噬干预策略和控制病原微生物感染提供参考。展开更多
In order to simultaneously measure the initiation toughness of pure mode Ⅰ and mode Ⅱ cracks in one specimen,a large-size double-cracked concave-convex plate(DCCP)specimen configuration was proposed.Impacting tests ...In order to simultaneously measure the initiation toughness of pure mode Ⅰ and mode Ⅱ cracks in one specimen,a large-size double-cracked concave-convex plate(DCCP)specimen configuration was proposed.Impacting tests were implemented in the drop plate impact device.Strain gauges were employed to measure impact loads and crack initiation time.The corresponding numerical model was established by using the dynamic finite difference program AUTODYN,and the experimental-numerical method and ABAQUS code were utilized to obtain the initial fracture toughness of the crack.Using experiments and numerical research,we concluded that the DCCP specimen is suitable for measuring the initial fracture toughness of pure mode Ⅰ and mode Ⅱ cracks at the same time;the dynamic initiation toughness increases with the increase of loading rate and the crack initiation time decreases with increasing loading rate;the initiation toughness of mode Ⅱ crack is 0.5 times that of mode Ⅰ crack when subjected to the same loading rate.For the pre-crack in the vicinity of the bottom of a sample,when its length increases from 20 to 100 mm,the dynamic initiation toughness of the pure mode Ⅰ crack gradually decreases,and the longer the lower crack length is,the easier the crack would initiate,but the dynamic initiation toughness of pure mode Ⅱ crack varies little.展开更多
乙型肝炎病毒(Hepatitis B Virus)是一种经体液传播的的DNA病毒,可引起急性和慢性肝炎。急性肝炎尚未有有效治疗药物,治疗目的是保持身体舒适和营养平衡。而慢性肝炎主要服用干扰素/核苷类似物等抗病毒治疗药物,以延缓肝硬化或原发性肝...乙型肝炎病毒(Hepatitis B Virus)是一种经体液传播的的DNA病毒,可引起急性和慢性肝炎。急性肝炎尚未有有效治疗药物,治疗目的是保持身体舒适和营养平衡。而慢性肝炎主要服用干扰素/核苷类似物等抗病毒治疗药物,以延缓肝硬化或原发性肝癌的发生发展。但这两类药物或疗效有限、副作用明显,或需长期服用,导致病毒耐药,总之都不能彻底治愈乙肝,因此急需新型抗病毒治疗药物的出现或辅助。文章旨在对当前已上市或正在研发中的药物进展进行综述,以便优化抗乙肝病毒治疗方案,推动抗乙肝病毒新药的研发。展开更多
低氧是大多数实体肿瘤的一个重要特征。它可以导致肿瘤向恶性方向发展,使肿瘤细胞具有更强的侵袭和转移能力,并对化学治疗和放射治疗产生抵抗。在这个过程之中,以低氧诱导因子(Hypoxia-inducible factors,HIFs)为代表的一系列低氧诱导...低氧是大多数实体肿瘤的一个重要特征。它可以导致肿瘤向恶性方向发展,使肿瘤细胞具有更强的侵袭和转移能力,并对化学治疗和放射治疗产生抵抗。在这个过程之中,以低氧诱导因子(Hypoxia-inducible factors,HIFs)为代表的一系列低氧诱导蛋白起主要调控作用,它们通过影响下游多种信号通路调节肿瘤细胞增殖、迁移、侵袭、血管生成、免疫应答、放/化疗抗性来促进或抑制肿瘤发生发展。随着对低氧诱导蛋白的深入研究,发现尽管大多数情况下低氧会促进肿瘤发生发展,但同时也存在着一小部分低氧诱导蛋白具有抑制肿瘤进展的作用。因此,对低氧诱导蛋白的研究在抗肿瘤药物开发以及肿瘤治疗方法的选择上具有重要意义。文章对HIFs以及两种新发现的低氧诱导蛋白—孕酮诱导的蜕膜蛋白(Decidual protein induced by progesterone,DEPP)和蛋白激酶A锚定蛋白(A-kinase anchor protein 4,AKAP4)在肿瘤发展和治疗中的功能加以整理总结,希望能够推动以低氧蛋白为靶点的抗肿瘤治疗在临床的应用。展开更多
Radix Adenophorae, a traditional Chinese medicine, has been reported to have a variety of biological functions. In the present study, a polysaccharide component, Radix Adenophorae Polysaccharide （RAPS）, was purified...Radix Adenophorae, a traditional Chinese medicine, has been reported to have a variety of biological functions. In the present study, a polysaccharide component, Radix Adenophorae Polysaccharide （RAPS）, was purified from Radix Adenophorae by decoloring with ADS-7 macroporous adsorption resin, DEAE-52 cellulose ion-exchange chromatography, and Sephacryl S-300HR gel chromatography, with the purity of 98.3% and a molecular weight of 1.8 × 104 Da. The cell viability assay and microscopic examination revealed that RAPS promoted the proliferation and activation of macrophages. At 400 μg·mL-1, RAPS stimulated RAW264.7 cell proliferation by 1.91-fold compared with the control. Meanwhile, RAPS significantly increased the secretion of pro-inflammatory cytokines （TNF-a and IL-6） in a dose-dependent manner in the supernatant of RAW264.7 cell culture as determined by ELISA. At 400 μg·mL-1, the production of TNF-a was 20.8-fold higher than that of the control. Simultaneously, the production of nitric oxide （NO） and the expression of inducible nitric oxide synthase （iNOS） were increased in RAW264.7 cells incubated with RAPS, as measured by Griess assay and Western blot analysis. The NO production of cells treated with RAPS （400 μg·mL-1） reached 15.8 μmol·L-L, which was 30.4-fold higher than that of the control （0.53 μmol·L-1）. These data suggested that RAPS may enhance the immune function and protect against exogenous pathogens by activating macrophages.展开更多
文摘自噬是一种广泛存在于真核细胞中的溶酶体依赖性分解代谢途径,涉及细胞分化、饥饿耐受和免疫防御等生物学功能。其中,异体自噬被定义为真核细胞特异性识别并清除胞内病原微生物的过程,是免疫细胞行使宿主防御的重要方式。然而,许多病原微生物已经“开发”了特殊的毒力因子(包括效应蛋白质和表面蛋白质等),衍生出多种逃避或劫持自噬作用的策略。研究表明,调控自噬的信号复杂,涉及到多种自噬相关蛋白质(autophagy related proteins,ATG proteins)的精细调控。现已证实,自噬的关键步骤经历了广泛的蛋白质翻译后修饰(post-translational modifications,PTMs),例如磷酸化/去磷酸化、泛素化/去泛素化等。这些修饰作用通过影响蛋白质的结构、稳定性、活性及其在细胞中的定位,赋予了宿主细胞自噬调控高度的动态性和可逆性。此外,研究发现,病原微生物的毒力因子能够劫持宿主细胞中ATG蛋白的蛋白质翻译后修饰,干扰自噬的信号传递,从而对抗异体自噬并促进其在宿主细胞中的存活。本文总结了常见的蛋白质翻译后修饰在异体自噬中的作用,并重点关注病原微生物利用宿主蛋白质翻译后修饰操纵异体自噬,进而促进自身存活的相关机制,为探索异体自噬干预策略和控制病原微生物感染提供参考。
基金Projects(U19A2098,1210021843)supported by the National Natural Science Foundation of ChinaProject(2021SCU12130)supported by Fundamental Research Funds for the Central Universities,China+1 种基金Project(2021YJ0511)supported by the Sichuan Science and Technology Program,ChinaProjects(DESEYU202205,DESE202005)supported by the Open Fund of Key Laboratory of Deep Earth Science and Engineering,China。
文摘In order to simultaneously measure the initiation toughness of pure mode Ⅰ and mode Ⅱ cracks in one specimen,a large-size double-cracked concave-convex plate(DCCP)specimen configuration was proposed.Impacting tests were implemented in the drop plate impact device.Strain gauges were employed to measure impact loads and crack initiation time.The corresponding numerical model was established by using the dynamic finite difference program AUTODYN,and the experimental-numerical method and ABAQUS code were utilized to obtain the initial fracture toughness of the crack.Using experiments and numerical research,we concluded that the DCCP specimen is suitable for measuring the initial fracture toughness of pure mode Ⅰ and mode Ⅱ cracks at the same time;the dynamic initiation toughness increases with the increase of loading rate and the crack initiation time decreases with increasing loading rate;the initiation toughness of mode Ⅱ crack is 0.5 times that of mode Ⅰ crack when subjected to the same loading rate.For the pre-crack in the vicinity of the bottom of a sample,when its length increases from 20 to 100 mm,the dynamic initiation toughness of the pure mode Ⅰ crack gradually decreases,and the longer the lower crack length is,the easier the crack would initiate,but the dynamic initiation toughness of pure mode Ⅱ crack varies little.
文摘乙型肝炎病毒(Hepatitis B Virus)是一种经体液传播的的DNA病毒,可引起急性和慢性肝炎。急性肝炎尚未有有效治疗药物,治疗目的是保持身体舒适和营养平衡。而慢性肝炎主要服用干扰素/核苷类似物等抗病毒治疗药物,以延缓肝硬化或原发性肝癌的发生发展。但这两类药物或疗效有限、副作用明显,或需长期服用,导致病毒耐药,总之都不能彻底治愈乙肝,因此急需新型抗病毒治疗药物的出现或辅助。文章旨在对当前已上市或正在研发中的药物进展进行综述,以便优化抗乙肝病毒治疗方案,推动抗乙肝病毒新药的研发。
文摘低氧是大多数实体肿瘤的一个重要特征。它可以导致肿瘤向恶性方向发展,使肿瘤细胞具有更强的侵袭和转移能力,并对化学治疗和放射治疗产生抵抗。在这个过程之中,以低氧诱导因子(Hypoxia-inducible factors,HIFs)为代表的一系列低氧诱导蛋白起主要调控作用,它们通过影响下游多种信号通路调节肿瘤细胞增殖、迁移、侵袭、血管生成、免疫应答、放/化疗抗性来促进或抑制肿瘤发生发展。随着对低氧诱导蛋白的深入研究,发现尽管大多数情况下低氧会促进肿瘤发生发展,但同时也存在着一小部分低氧诱导蛋白具有抑制肿瘤进展的作用。因此,对低氧诱导蛋白的研究在抗肿瘤药物开发以及肿瘤治疗方法的选择上具有重要意义。文章对HIFs以及两种新发现的低氧诱导蛋白—孕酮诱导的蜕膜蛋白(Decidual protein induced by progesterone,DEPP)和蛋白激酶A锚定蛋白(A-kinase anchor protein 4,AKAP4)在肿瘤发展和治疗中的功能加以整理总结,希望能够推动以低氧蛋白为靶点的抗肿瘤治疗在临床的应用。
基金supported by the National Science and Technology Major Project Foundation of China(No.2012ZX09102301-003)the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)
文摘Radix Adenophorae, a traditional Chinese medicine, has been reported to have a variety of biological functions. In the present study, a polysaccharide component, Radix Adenophorae Polysaccharide （RAPS）, was purified from Radix Adenophorae by decoloring with ADS-7 macroporous adsorption resin, DEAE-52 cellulose ion-exchange chromatography, and Sephacryl S-300HR gel chromatography, with the purity of 98.3% and a molecular weight of 1.8 × 104 Da. The cell viability assay and microscopic examination revealed that RAPS promoted the proliferation and activation of macrophages. At 400 μg·mL-1, RAPS stimulated RAW264.7 cell proliferation by 1.91-fold compared with the control. Meanwhile, RAPS significantly increased the secretion of pro-inflammatory cytokines （TNF-a and IL-6） in a dose-dependent manner in the supernatant of RAW264.7 cell culture as determined by ELISA. At 400 μg·mL-1, the production of TNF-a was 20.8-fold higher than that of the control. Simultaneously, the production of nitric oxide （NO） and the expression of inducible nitric oxide synthase （iNOS） were increased in RAW264.7 cells incubated with RAPS, as measured by Griess assay and Western blot analysis. The NO production of cells treated with RAPS （400 μg·mL-1） reached 15.8 μmol·L-L, which was 30.4-fold higher than that of the control （0.53 μmol·L-1）. These data suggested that RAPS may enhance the immune function and protect against exogenous pathogens by activating macrophages.
