Objective:Ovarian cancer(OC)ranks among the leading causes of mortality among the female cancers worldwide.Numerous studies have explored the development and progression of OC at multiple genetic regulatory levels.How...Objective:Ovarian cancer(OC)ranks among the leading causes of mortality among the female cancers worldwide.Numerous studies have explored the development and progression of OC at multiple genetic regulatory levels.However,relatively few studies have explored the impact of post-translational modifications(PTM)on OC progression,which is essential for uncovering new therapeutic targets.This study aimed to systematically identify the key PTM types involved in OCprogression,and to explore and evaluate their translational potential as therapeutic targets.Methods:First,we utilized multiple general PTM antibodies to compare gross PTM levels between normal ovarian and OC tissues from clinical females.After identifying lactylation as the PTM with the most significant differences,we selected representative samples for label-free mass spectrometry to identify specific lactylation sites.Next,we transfected A2780(OC)cells with either wild-type(WT)or mutant(K192A[Q])poly(ADP-ribose)polymerase 1(PARP1)conjugated to enhanced green fluorescent protein(EGFP)with a StrepⅡpeptide tag and assessed various cellular indexes related to cell proliferation(clonogenicity assay),migration(scratch wound healing assay),and reactive oxygen species levels.Results:Pan-lactylation was significantly upregulated in clinical OC samples,with PARP1 lactylation at K192 being one of the most common modifications.The growth and migration of A2780 cells were markedly suppressed by overexpressing PARP1-WT but not mutant PARP1.Overexpressing PARP1 significantly downregulated the phosphorylation of extracellular signal-regulated kinases 1/2(ERK1/2).Conclusion:This study uncovered a novel PTM of PARP1 in OC,lactylation,and demonstrated that lactylation at K192 is crucial in regulating OC cell growth and migration via the ERK1/2 pathway.Further investigations are required to elucidate the broader functional implications of PARP1 lactylation and its therapeutic potential.展开更多
During the storage of composite propellants, the migration of plasticizers and other unbonded additives at the interfaces of liner adhesives has garnered significant attention in understanding liner failure mechanisms...During the storage of composite propellants, the migration of plasticizers and other unbonded additives at the interfaces of liner adhesives has garnered significant attention in understanding liner failure mechanisms, aging processes, and safety performance. However, there is currently no non-destructive and quantitative detection method for migration of plasticizers in propellant liner. In this study, we developed a HTPB sensing liner by incorporating conductive fillers-namely carbon black(CB), carbon nanotubes(CNTs), and graphene nanoplatelets(GNP)-into the HTPB matrix. The synergistic interaction between CNTs and GNP facilitates the formation of a tunneling conductive network that imparts electrical conductivity to the HTPB liner. To elucidate the functional relationship between conductivity and nitroglycerin(NG) migration, we applied the HTPB sensing liner onto double base propellant surfaces and measured both the conductivity of the sensing layer and NG migration during a 71°C accelerated aging experiment. The results shows that when CNTs/GNP content reaches 3wt%, there is an exponential correlation between conductivity and NG migration with a fitting degree of 0.9652;the average response sensitivity of ΔR/R0 relative to NG migration is calculated as 41.69, with an average deviation of merely5.67% between NG migrations derived from conductivity fittings compared to those obtained via TGA testing results. Overall, this sensing liner exhibits excellent capabilities for detecting NG migration nondestructively and quantitatively while offering a novel approach for assessing interfacial component migrations as well as debonding defects in propellants-a promising avenue for future self-monitoring strategies regarding propellant integrity.展开更多
The detection of hypersonic targets usually confronts range migration(RM)issue before coherent integration(CI).The traditional methods aiming at correcting RM to obtain CI mainly considers the narrow-band radar condit...The detection of hypersonic targets usually confronts range migration(RM)issue before coherent integration(CI).The traditional methods aiming at correcting RM to obtain CI mainly considers the narrow-band radar condition.However,with the increasing requirement of far-range detection,the time bandwidth product,which is corresponding to radar’s mean power,should be promoted in actual application.Thus,the echo signal generates the scale effect(SE)at large time bandwidth product situation,influencing the intra and inter pulse integration performance.To eliminate SE and correct RM,this paper proposes an effective algorithm,i.e.,scaled location rotation transform(ScLRT).The ScLRT can remove SE to obtain the matching pulse compression(PC)as well as correct RM to complete CI via the location rotation transform,being implemented by seeking the actual rotation angle.Compared to the traditional coherent detection algorithms,Sc LRT can address the SE problem to achieve better detection/estimation capabilities.At last,this paper gives several simulations to assess the viability of ScLRT.展开更多
文摘Objective:Ovarian cancer(OC)ranks among the leading causes of mortality among the female cancers worldwide.Numerous studies have explored the development and progression of OC at multiple genetic regulatory levels.However,relatively few studies have explored the impact of post-translational modifications(PTM)on OC progression,which is essential for uncovering new therapeutic targets.This study aimed to systematically identify the key PTM types involved in OCprogression,and to explore and evaluate their translational potential as therapeutic targets.Methods:First,we utilized multiple general PTM antibodies to compare gross PTM levels between normal ovarian and OC tissues from clinical females.After identifying lactylation as the PTM with the most significant differences,we selected representative samples for label-free mass spectrometry to identify specific lactylation sites.Next,we transfected A2780(OC)cells with either wild-type(WT)or mutant(K192A[Q])poly(ADP-ribose)polymerase 1(PARP1)conjugated to enhanced green fluorescent protein(EGFP)with a StrepⅡpeptide tag and assessed various cellular indexes related to cell proliferation(clonogenicity assay),migration(scratch wound healing assay),and reactive oxygen species levels.Results:Pan-lactylation was significantly upregulated in clinical OC samples,with PARP1 lactylation at K192 being one of the most common modifications.The growth and migration of A2780 cells were markedly suppressed by overexpressing PARP1-WT but not mutant PARP1.Overexpressing PARP1 significantly downregulated the phosphorylation of extracellular signal-regulated kinases 1/2(ERK1/2).Conclusion:This study uncovered a novel PTM of PARP1 in OC,lactylation,and demonstrated that lactylation at K192 is crucial in regulating OC cell growth and migration via the ERK1/2 pathway.Further investigations are required to elucidate the broader functional implications of PARP1 lactylation and its therapeutic potential.
基金funded by Zhijian Laboratory Open Fund,Rocket Force University of Engineering(Grant No.2023-ZJSYS-KF01-03).
文摘During the storage of composite propellants, the migration of plasticizers and other unbonded additives at the interfaces of liner adhesives has garnered significant attention in understanding liner failure mechanisms, aging processes, and safety performance. However, there is currently no non-destructive and quantitative detection method for migration of plasticizers in propellant liner. In this study, we developed a HTPB sensing liner by incorporating conductive fillers-namely carbon black(CB), carbon nanotubes(CNTs), and graphene nanoplatelets(GNP)-into the HTPB matrix. The synergistic interaction between CNTs and GNP facilitates the formation of a tunneling conductive network that imparts electrical conductivity to the HTPB liner. To elucidate the functional relationship between conductivity and nitroglycerin(NG) migration, we applied the HTPB sensing liner onto double base propellant surfaces and measured both the conductivity of the sensing layer and NG migration during a 71°C accelerated aging experiment. The results shows that when CNTs/GNP content reaches 3wt%, there is an exponential correlation between conductivity and NG migration with a fitting degree of 0.9652;the average response sensitivity of ΔR/R0 relative to NG migration is calculated as 41.69, with an average deviation of merely5.67% between NG migrations derived from conductivity fittings compared to those obtained via TGA testing results. Overall, this sensing liner exhibits excellent capabilities for detecting NG migration nondestructively and quantitatively while offering a novel approach for assessing interfacial component migrations as well as debonding defects in propellants-a promising avenue for future self-monitoring strategies regarding propellant integrity.
基金supported by the National Natural Science Foundation of China(62101099)the Chinese Postdoctoral Science Foundation(2021M690558,2022T150100,2018M633352,2019T120825)+3 种基金the Young Elite Scientist Sponsorship Program(YESS20200082)the Aeronautical Science Foundation of China(2022Z017080001)the Open Foundation of Science and Technology on Electronic Information Control Laboratorythe Natural Science Foundation of Sichuan Province(2023NSFSC1386)。
文摘The detection of hypersonic targets usually confronts range migration(RM)issue before coherent integration(CI).The traditional methods aiming at correcting RM to obtain CI mainly considers the narrow-band radar condition.However,with the increasing requirement of far-range detection,the time bandwidth product,which is corresponding to radar’s mean power,should be promoted in actual application.Thus,the echo signal generates the scale effect(SE)at large time bandwidth product situation,influencing the intra and inter pulse integration performance.To eliminate SE and correct RM,this paper proposes an effective algorithm,i.e.,scaled location rotation transform(ScLRT).The ScLRT can remove SE to obtain the matching pulse compression(PC)as well as correct RM to complete CI via the location rotation transform,being implemented by seeking the actual rotation angle.Compared to the traditional coherent detection algorithms,Sc LRT can address the SE problem to achieve better detection/estimation capabilities.At last,this paper gives several simulations to assess the viability of ScLRT.
