Although p21-activated kinase 2(PAK2)is an essential serine/threonine protein kinase,its role in the progression of lung squamous cell carcinoma(LUSC)has yet to be fully understood.We analyzed PAK2 mRNA levels,DNA cop...Although p21-activated kinase 2(PAK2)is an essential serine/threonine protein kinase,its role in the progression of lung squamous cell carcinoma(LUSC)has yet to be fully understood.We analyzed PAK2 mRNA levels,DNA copy numbers,and protein levels by quantitative reverse transcription-PCR and immunohistochemical staining in both human LUSC tissues and adjacent normal tissues.Then,we performed colony formation assays,cell counting kit-8 assays,Matrigel invasion assays,wound healing assays,and xenograft models in nude mice to investigate the functions of PAK2 in LUSC progression.We demonstrated that PAK2 mRNA levels,DNA copy numbers,and protein levels were upregulated in human LUSC tissues,compared with adjacent normal tissues.Additionally,higher PAK2 expression was associated with poorer prognosis in LUSC patients.In the in vitro study,we found that PAK2 promoted cell growth,migration,invasion,epithelialmesenchymal transition,and cell morphology regulation in LUSC cells.Mechanistically,PAK2 promoted tumor cell proliferation,migration,and invasion by regulating actin dynamics through the LIMK1/cofilin signaling pathway.Our findings indicate that the PAK2/LIMK1/cofilin signaling pathway may serve as a potential clinical marker and therapeutic target for LUSC.展开更多
p21活化蛋白激酶(p21-activated protein kinase,PAK)是一类高度保守的丝氨酸/苏氨酸蛋白家族,是Rho家族小GTP酶的效应蛋白,参与多种信号通路传导。PAK4是PAK家族中最有代表性的成员,通过磷酸化下游底物,调控细胞骨架重组、细胞增殖和...p21活化蛋白激酶(p21-activated protein kinase,PAK)是一类高度保守的丝氨酸/苏氨酸蛋白家族,是Rho家族小GTP酶的效应蛋白,参与多种信号通路传导。PAK4是PAK家族中最有代表性的成员,通过磷酸化下游底物,调控细胞骨架重组、细胞增殖和细胞周期进展等。PAK4过表达见于胰腺癌、胃癌和卵巢癌等多种肿瘤,参与肿瘤发生和肿瘤迁移等过程。研究PAK4的结构、作用机制对于揭示细胞周期调控和肿瘤生物学行为有重要价值。本文阐述和归纳了PAK4的结构、激活过程及其在细胞骨架、细胞周期进展中的生物学作用,并综述了PAK4调控妇科肿瘤发生发展以及PAK4抑制剂的最新研究进展。展开更多
Melatonin(MT)is a low molecular weight compound with multiple biological functions in plants.It is known to delay leaf senescence in various species.However,no data are available on the MT signaling pathway in posthar...Melatonin(MT)is a low molecular weight compound with multiple biological functions in plants.It is known to delay leaf senescence in various species.However,no data are available on the MT signaling pathway in postharvest vegetables.This study demonstrates that MT increases cGMP concentration and the expression of the cGMP synthesis gene BcGC1 in pak choi.The c GMP inhibitor LY83583 destroys effect of MT delaying the leaf senescence.LY83583 also prevents MT treatment from reducing the expression of chlorophyll metabolism-related genes(BcNYC1,BcNOL,BcPPH1/2,BcSGR1/2,and BcPAO)and senescence genes(BcSAG12 and BcSAG21).It also inhibits MT from reducing the activity of the key chlorophyll catabolism enzymes Mg-dechelatase,pheophytinase,and pheide a oxygenase.Thus,the ability of MT to maintain high levels of chlorophyll metabolites is also destroyed.The Arabidopsis c GMP synthetic gene mutant atgc1 was used to confirm that delayed leaf senescence caused by MT is mediated,at least in part,by the second messenger c GMP.展开更多
Igor Pak对立方体进行改造,构造出了表面和立方体等距同构的一个非凸多面体且围出更大的体积,本文将此构造方法称之为“Pak折叠”,在其启发下,本文将Pak折叠思想运用于对正六面体以外的正多面体的改造:(1) 正四面体、(2) 正八面体、(3)...Igor Pak对立方体进行改造,构造出了表面和立方体等距同构的一个非凸多面体且围出更大的体积,本文将此构造方法称之为“Pak折叠”,在其启发下,本文将Pak折叠思想运用于对正六面体以外的正多面体的改造:(1) 正四面体、(2) 正八面体、(3) 正十二面体、(4) 正二十面体,我们进行了类似的改造,详细计算了经过改造后所围体积,最终给出相应体积关于参数的渐近展开公式,从而发现决定体积增减的决定性原因。我们推测,对于其他凸多面体,都可能有类似于Pak折叠的通用改造方法,但是由于非正多面体的复杂性,该问题有待进一步解决证明。由于这样的改造在不改变表面积的情况下,会增加体积,而且改造后的形状可能适用于一些特殊需要,由此我们也指出一些潜在的实际应用并计算了改造的有效范围。Igor Pak transformed the cube and constructed a non-convex polyhedron with anisometric surface and a larger volume. This construction method is named “Pak bending” in this paper. Inspired by it, we study the application of the idea of Pak bending to the transformation of regular polyhedron other than regular hexahedron: (1) Regular tetrahedron, (2) Regular octahedron, (3) Regular dodecahedron, (4) Regular icosahedron. We carry out similar transformations, and calculate in detail the volume after transformation. Finally, we give the formula of the corresponding volume with asymptotic expansion of the parameter, and find the decisive factor that determines the change of volume. We speculate that for other convex polyhedron, there may be a general transformation method similar to Pak bending, but due to the complexity of non-regular polyhedron, this problem needs to be further solved and proved. Since such a transformation increases volume without changing surface area, and the modified shape may be suitable for some special needs, we also indicate some potential practical applications and calculate the effective range of the transformation.展开更多
基金National Natural Science Foundation of China(Grant No.32300615)Nanjing Medical Science and Technique Development Foundation(Grant No.JQX19010)。
文摘Although p21-activated kinase 2(PAK2)is an essential serine/threonine protein kinase,its role in the progression of lung squamous cell carcinoma(LUSC)has yet to be fully understood.We analyzed PAK2 mRNA levels,DNA copy numbers,and protein levels by quantitative reverse transcription-PCR and immunohistochemical staining in both human LUSC tissues and adjacent normal tissues.Then,we performed colony formation assays,cell counting kit-8 assays,Matrigel invasion assays,wound healing assays,and xenograft models in nude mice to investigate the functions of PAK2 in LUSC progression.We demonstrated that PAK2 mRNA levels,DNA copy numbers,and protein levels were upregulated in human LUSC tissues,compared with adjacent normal tissues.Additionally,higher PAK2 expression was associated with poorer prognosis in LUSC patients.In the in vitro study,we found that PAK2 promoted cell growth,migration,invasion,epithelialmesenchymal transition,and cell morphology regulation in LUSC cells.Mechanistically,PAK2 promoted tumor cell proliferation,migration,and invasion by regulating actin dynamics through the LIMK1/cofilin signaling pathway.Our findings indicate that the PAK2/LIMK1/cofilin signaling pathway may serve as a potential clinical marker and therapeutic target for LUSC.
文摘p21活化蛋白激酶(p21-activated protein kinase,PAK)是一类高度保守的丝氨酸/苏氨酸蛋白家族,是Rho家族小GTP酶的效应蛋白,参与多种信号通路传导。PAK4是PAK家族中最有代表性的成员,通过磷酸化下游底物,调控细胞骨架重组、细胞增殖和细胞周期进展等。PAK4过表达见于胰腺癌、胃癌和卵巢癌等多种肿瘤,参与肿瘤发生和肿瘤迁移等过程。研究PAK4的结构、作用机制对于揭示细胞周期调控和肿瘤生物学行为有重要价值。本文阐述和归纳了PAK4的结构、激活过程及其在细胞骨架、细胞周期进展中的生物学作用,并综述了PAK4调控妇科肿瘤发生发展以及PAK4抑制剂的最新研究进展。
基金supported by the National Natural Science Foundation of China(Grant No.32001451)Jiangsu Agriculture Science and Technology Innovation Fund[Grant No.CX(20)1008]。
文摘Melatonin(MT)is a low molecular weight compound with multiple biological functions in plants.It is known to delay leaf senescence in various species.However,no data are available on the MT signaling pathway in postharvest vegetables.This study demonstrates that MT increases cGMP concentration and the expression of the cGMP synthesis gene BcGC1 in pak choi.The c GMP inhibitor LY83583 destroys effect of MT delaying the leaf senescence.LY83583 also prevents MT treatment from reducing the expression of chlorophyll metabolism-related genes(BcNYC1,BcNOL,BcPPH1/2,BcSGR1/2,and BcPAO)and senescence genes(BcSAG12 and BcSAG21).It also inhibits MT from reducing the activity of the key chlorophyll catabolism enzymes Mg-dechelatase,pheophytinase,and pheide a oxygenase.Thus,the ability of MT to maintain high levels of chlorophyll metabolites is also destroyed.The Arabidopsis c GMP synthetic gene mutant atgc1 was used to confirm that delayed leaf senescence caused by MT is mediated,at least in part,by the second messenger c GMP.
文摘Igor Pak对立方体进行改造,构造出了表面和立方体等距同构的一个非凸多面体且围出更大的体积,本文将此构造方法称之为“Pak折叠”,在其启发下,本文将Pak折叠思想运用于对正六面体以外的正多面体的改造:(1) 正四面体、(2) 正八面体、(3) 正十二面体、(4) 正二十面体,我们进行了类似的改造,详细计算了经过改造后所围体积,最终给出相应体积关于参数的渐近展开公式,从而发现决定体积增减的决定性原因。我们推测,对于其他凸多面体,都可能有类似于Pak折叠的通用改造方法,但是由于非正多面体的复杂性,该问题有待进一步解决证明。由于这样的改造在不改变表面积的情况下,会增加体积,而且改造后的形状可能适用于一些特殊需要,由此我们也指出一些潜在的实际应用并计算了改造的有效范围。Igor Pak transformed the cube and constructed a non-convex polyhedron with anisometric surface and a larger volume. This construction method is named “Pak bending” in this paper. Inspired by it, we study the application of the idea of Pak bending to the transformation of regular polyhedron other than regular hexahedron: (1) Regular tetrahedron, (2) Regular octahedron, (3) Regular dodecahedron, (4) Regular icosahedron. We carry out similar transformations, and calculate in detail the volume after transformation. Finally, we give the formula of the corresponding volume with asymptotic expansion of the parameter, and find the decisive factor that determines the change of volume. We speculate that for other convex polyhedron, there may be a general transformation method similar to Pak bending, but due to the complexity of non-regular polyhedron, this problem needs to be further solved and proved. Since such a transformation increases volume without changing surface area, and the modified shape may be suitable for some special needs, we also indicate some potential practical applications and calculate the effective range of the transformation.
