Objectives:Non-small cell lung cancer(NSCLC)remains a leading cause of cancer-related mortality,with limited understanding of lncRNA-driven mechanisms in tumor progression.This study aimed to identify differentially e...Objectives:Non-small cell lung cancer(NSCLC)remains a leading cause of cancer-related mortality,with limited understanding of lncRNA-driven mechanisms in tumor progression.This study aimed to identify differentially expressed lncRNAs in NSCLC tissues and elucidate the functional role of the significantly upregulated RP3-340N1.2 in promoting malignancy.Methods:RNA sequencing was used to screen dysregulated lncRNAs.RP3-340N1.2 was functionally characterized via gain/loss-of-function assays in NSCLC cells,assessing proliferation,migration,and macrophage polarization.Mechanisms of interleukin 6(IL-6)regulation were explored using cytokine profiling,Actinomycin D assays,and RNA Immunoprecipitation(RIP)assays to study RP3-340N1.2 interactions with zinc finger CCCH-type containing 12A(ZC3H12A)and IL-6 mRNA.Results:RP3-340N1.2 was upregulated in NSCLC tissues and cells.Functional assays demonstrated that RP3-340N1.2 knockdown suppressed NSCLC cell proliferation/migration and reduced macrophage polarization toward tumor-associated phenotypes.Mechanistically,RP3-340N1.2 knockdown promoted IL-6 mRNA degradation,as supported by reduced IL-6 levels and accelerated mRNA decay.Further RIP assays revealed that RP3-340N1.2 interacts with ZC3H12A,an RNA-binding protein previously reported to degrade IL-6 mRNA,and that RP3-340N1.2 knockdown enhanced ZC3H12A binding to IL-6 mRNA.Consequently,RP3-340N1.2 knockdown in carcinoma cells attenuated IL-6-mediated tumor-promoting effects,including tumor cell proliferation and migration.Importantly,these effectswere observed not only in a direct carcinoma cell culturing system but also when carcinoma cells were exposed to conditioned medium from co-culturing RP3-340N1.2-knockdown tumor cells andmacrophages.Conclusion:RP3-340N1.2 drivesNSCLC malignancy by stabilizing IL-6 mRNA;its inhibition offers a potential therapeutic strategy to disrupt tumor-promoting interactions.展开更多
Serial-parallel manipulators are of great interest to academic community in recent years,especially those composed of classical parallel mechanisms.There have been many studies around 2(3RPS)and 2(3SPR)S-PMs,but unfor...Serial-parallel manipulators are of great interest to academic community in recent years,especially those composed of classical parallel mechanisms.There have been many studies around 2(3RPS)and 2(3SPR)S-PMs,but unfortunately their inverse kinematics have not yet been resolved.This paper discovers that the unknown kinematic parameters of middle platform are responsible for the unresolvable of inverse kinematics,meanwhile the unknown kinematic parameters of middle platform also have huge coupling relationships.Therefore,to break through this challenges,the huge coupling relationships are decoupled layer by layer,the kinematic parameters of middle platform are solved by combining Sylvester's elimination method,and the inverse displacements of 2(3RPS)and 2(3SPR)S-PMs are obtained subsequently.This paper not only solves the inverse kinematics of classical 2(3RPS)and 2(3SPR)S-PMs,but also reveals the essence of the inverse kinematics of general(3-DOF)+(3-DOF)6-DOF S-PMs and proposes a corresponding solution.展开更多
基金supported by the National Natural Science Foundation of China(No.81702296).
文摘Objectives:Non-small cell lung cancer(NSCLC)remains a leading cause of cancer-related mortality,with limited understanding of lncRNA-driven mechanisms in tumor progression.This study aimed to identify differentially expressed lncRNAs in NSCLC tissues and elucidate the functional role of the significantly upregulated RP3-340N1.2 in promoting malignancy.Methods:RNA sequencing was used to screen dysregulated lncRNAs.RP3-340N1.2 was functionally characterized via gain/loss-of-function assays in NSCLC cells,assessing proliferation,migration,and macrophage polarization.Mechanisms of interleukin 6(IL-6)regulation were explored using cytokine profiling,Actinomycin D assays,and RNA Immunoprecipitation(RIP)assays to study RP3-340N1.2 interactions with zinc finger CCCH-type containing 12A(ZC3H12A)and IL-6 mRNA.Results:RP3-340N1.2 was upregulated in NSCLC tissues and cells.Functional assays demonstrated that RP3-340N1.2 knockdown suppressed NSCLC cell proliferation/migration and reduced macrophage polarization toward tumor-associated phenotypes.Mechanistically,RP3-340N1.2 knockdown promoted IL-6 mRNA degradation,as supported by reduced IL-6 levels and accelerated mRNA decay.Further RIP assays revealed that RP3-340N1.2 interacts with ZC3H12A,an RNA-binding protein previously reported to degrade IL-6 mRNA,and that RP3-340N1.2 knockdown enhanced ZC3H12A binding to IL-6 mRNA.Consequently,RP3-340N1.2 knockdown in carcinoma cells attenuated IL-6-mediated tumor-promoting effects,including tumor cell proliferation and migration.Importantly,these effectswere observed not only in a direct carcinoma cell culturing system but also when carcinoma cells were exposed to conditioned medium from co-culturing RP3-340N1.2-knockdown tumor cells andmacrophages.Conclusion:RP3-340N1.2 drivesNSCLC malignancy by stabilizing IL-6 mRNA;its inhibition offers a potential therapeutic strategy to disrupt tumor-promoting interactions.
基金Supported by National Natural Science Foundation of China(Grant No.52275033)National Natural Science Youth Foundation of China(Grant No.52205033)Hebei Provincial Natural Science Foundation of China(Grant No.E2021203019)。
文摘Serial-parallel manipulators are of great interest to academic community in recent years,especially those composed of classical parallel mechanisms.There have been many studies around 2(3RPS)and 2(3SPR)S-PMs,but unfortunately their inverse kinematics have not yet been resolved.This paper discovers that the unknown kinematic parameters of middle platform are responsible for the unresolvable of inverse kinematics,meanwhile the unknown kinematic parameters of middle platform also have huge coupling relationships.Therefore,to break through this challenges,the huge coupling relationships are decoupled layer by layer,the kinematic parameters of middle platform are solved by combining Sylvester's elimination method,and the inverse displacements of 2(3RPS)and 2(3SPR)S-PMs are obtained subsequently.This paper not only solves the inverse kinematics of classical 2(3RPS)and 2(3SPR)S-PMs,but also reveals the essence of the inverse kinematics of general(3-DOF)+(3-DOF)6-DOF S-PMs and proposes a corresponding solution.
