In order to improve the low output accuracy caused by the elastic deformations of the branch chains,a finite element-based dynamic accuracy analysis method for parallel mechanisms is proposed in this paper.First,takin...In order to improve the low output accuracy caused by the elastic deformations of the branch chains,a finite element-based dynamic accuracy analysis method for parallel mechanisms is proposed in this paper.First,taking a 5-prismatic-spherical-spherical(PSS)/universal-prismatic-universal(UPU)parallel mechanism as an example,the error model is established by a closed vector chain method,while its influence on the dynamic accuracy of the parallel mechanism is analyzed through numerical simulation.According to the structural and error characteristics of the parallel mechanism,a vector calibration algorithm is proposed to reduce the position and pose errors along the whole motion trajectory.Then,considering the elastic deformation of the rod,the rigid-flexible coupling dynamic equations of each component are established by combining the finite element method with the Lagrange method.The elastodynamic model of the whole machine is obtained based on the constraint condition of each moving part,and the correctness of the model is verified by simulation.Moreover,the effect of component flexibility on the dimensionless root mean square error of the displacement,velocity and acceleration of the moving platform is investigated by using a Newmark method,and the mapping relationship of these dimensionless root mean square errors to dynamic accuracy is further studied.The research work provides a theoretical basis for the design of the parameter size of the prototype.展开更多
Relaxor ferroelectric ceramics have very high dielectric constant(e)but relatively low electrical breakdown strength(Eb),while glass-ceramics exhibit higher E,due to the more uniformly dispersed amorphous phases and s...Relaxor ferroelectric ceramics have very high dielectric constant(e)but relatively low electrical breakdown strength(Eb),while glass-ceramics exhibit higher E,due to the more uniformly dispersed amorphous phases and submicrocrystals/nanocrystals inside.How to effectively combine the advantages of both relaxor ferroelectric ceramics and glass-ceramics is of great significance for the development of new dielectric materials with high energy storage performance.In this work,we firstly prepared BaO-SrO-Bi_(2)O_(3)-Na_(2)0-TiO_(2)-Al_(2)O_(3)-SiO_(2)(abbreviated as GS)glass powders,and then fabricated(Ba_(0.3)Sr_(0.7))_(0.5)(Bi_(0.5)Na_(0.5))_(0.5)TiO_(3)+x wt%GS ceramic composites(abbreviated as BSo.sBNT-xGS,x=0,2,6,10,14,16,and 18).Submicrocrystals/nanocrystals with a similar composition to BSo.sBNT were crystalized from the glass,ensuring the formation of uniform core-shell structure in BSo.sBNT-xGS relaxor ferroelectric ceramic/glass-ceramic composites.When the addition amount of GS was 14 wt%,the composite possessed both high&r(>3200 at 1 kHz)and high E,(~170 kV/cm)at room temperature,and their recoverable energy storage density and efficiency were Wrec=2.1 J/cm’and n=65.2%,respectively.The BSo.sBNT-14GS composite also had several attractive properties such as good temperature,frequency,cycle stability,and fast charge-discharge speed.This work provides insights into the relaxor ceramic/glass-ceramic composites for pulsed power capacitors and sheds light on the utilization of the hybrid systems.展开更多
Cellular senescence provides a protective barrier against tumorigenesis in precancerous or normal tissues upon distinct stressors.However,the detailed mechanisms by which tumor cells evade premature senescence to mali...Cellular senescence provides a protective barrier against tumorigenesis in precancerous or normal tissues upon distinct stressors.However,the detailed mechanisms by which tumor cells evade premature senescence to malignant progression remain largely elusive.Here we reported that RBM4 adversely impacted cellular senescence to favor glutamine-dependent survival of esophageal squamous cell carcinoma(ESCC)cells by dictating the activity of LKB1,a critical governor of cancer metabolism.The level of RBM4 was specifically elevated in ESCC compared to normal tissues,and RBM4 overexpression promoted the malignant phenotype.RBM4 contributed to overcome H-RAS-or doxorubicin-induced senescence,while its depletion caused P27-dependent senescence and proliferation arrest by activating LKB1-AMPK-mTOR cascade.Mechanistically,RBM4 competitively bound LKB1 to disrupt the LKB1/STRAD/MO25 heterotrimeric complex,subsequently recruiting the E3 ligase TRIM26 to LKB1,promoting LKB1 ubiquitination and degradation in nucleus.Therefore,such molecular process leads to bypassing senescence and sustaining cell proliferation through the activation of glutamine metabolism.Clinically,the ESCC patients with high RBM4 and low LKB1 have significantly worse overall survival than those with low RBM4 and high LKB1.The RBM4 high/LKB1 low expression confers increased sensitivity of ESCC cells to glutaminase inhibitor CB-839,providing a novel insight into mechanisms underlying the glutamine-dependency to improve the efficacy of glutamine inhibitors in ESCC therapeutics.展开更多
Alternative splicing is a critical process to generate protein diversity.However,whether and how alternative splicing regulates autophagy remains largely elusive.Here we systematically identify the splicing factor SRS...Alternative splicing is a critical process to generate protein diversity.However,whether and how alternative splicing regulates autophagy remains largely elusive.Here we systematically identify the splicing factor SRSF1 as an autophagy suppressor.Specifically,SRSF1 inhibits autophagosome formation by reducing the accumulation of LC3-ⅡI and numbers of autophagosomes in different cell lines.Mechanistically,SRSF1 promotes the splicing of the long isoform of Bcl-x that interacts with Beclinl,thereby dissociating the Beclin1-PIK3C3 complex.In addition,SRSF1 also directly interacts with PIK3C3 to disrupt the interaction between Beclinl and PIK3C3.Consequently,the decrease of SRSF1 stabilizes the Beclinl and PIK3C3 complex and activates autophagy.Interestingly,SRSF1 can be degraded by starvation-and oxidative stresses-induced autophagy through interacting with LC3-Ⅱ,whereas reduced SRSF1 further promotes autophagy.This positive feedback is critical to inhibiting Gefitinib-resistant cancer cell progression both in vitro and in vivo.Consistently,the expression level of SRSF1 is inversely correlated to LC3 level in clinical cancer samples.Our study not only provides mechanistic insights of alternative splicing in autophagy regulation but also discovers a new regulatory role of SRSF1 in tumorigenesis,thereby offering a novel avenue for potential cancer therapeutics.展开更多
In this work,a novel fluorescent biosensor has been constructed for rapid detection of Cu(Ⅱ)via the interaction between the fluorophore groups on the surface of nitrogen-doped-carbon-dots(N-CDs)and·OH produced f...In this work,a novel fluorescent biosensor has been constructed for rapid detection of Cu(Ⅱ)via the interaction between the fluorophore groups on the surface of nitrogen-doped-carbon-dots(N-CDs)and·OH produced from the catalytic reaction between Cu(Ⅱ)and cysteine(Cys).Specifically,Cu(Ⅱ)can catalyze the oxidation of Cys to form cystine(Cys–Cys)and hydrogen peroxide(H_(2)O_(2)),and Cu(Ⅱ)can also catalyze the decomposition of H_(2)O_(2)to produce hydroxyl radicals(·OH)by the Fenton-like reaction.·OH can oxidize and destroy the surface structure of N-CDs,resulting in the fluorescence quenching of the N-CDs.Under the optimal experimental conditions,the linear range of Cu(Ⅱ)is determined to be 0.05–25μmol L_(-1,),and the limit of detection is 23 nmol L^(-1)with the limit of quantitation of 77 nmol L^(-1).Besides,some characterizations are provided to verify the proposed principle.The method has been successfully applied for the detection of Cu(Ⅱ)in human serum and environmental water with high sensitivity and higher selectivity.展开更多
基金Supported by the National Natural Science Foundation of China(Grant Nos.U21A20122,51975523 and 51905481)the Natural Science Foundation of Zhejiang Province(Grant No.LY22E050012)the Students in Zhejiang Province Science and technology Innovation Plan(Grant No.2020R403054).
文摘In order to improve the low output accuracy caused by the elastic deformations of the branch chains,a finite element-based dynamic accuracy analysis method for parallel mechanisms is proposed in this paper.First,taking a 5-prismatic-spherical-spherical(PSS)/universal-prismatic-universal(UPU)parallel mechanism as an example,the error model is established by a closed vector chain method,while its influence on the dynamic accuracy of the parallel mechanism is analyzed through numerical simulation.According to the structural and error characteristics of the parallel mechanism,a vector calibration algorithm is proposed to reduce the position and pose errors along the whole motion trajectory.Then,considering the elastic deformation of the rod,the rigid-flexible coupling dynamic equations of each component are established by combining the finite element method with the Lagrange method.The elastodynamic model of the whole machine is obtained based on the constraint condition of each moving part,and the correctness of the model is verified by simulation.Moreover,the effect of component flexibility on the dimensionless root mean square error of the displacement,velocity and acceleration of the moving platform is investigated by using a Newmark method,and the mapping relationship of these dimensionless root mean square errors to dynamic accuracy is further studied.The research work provides a theoretical basis for the design of the parameter size of the prototype.
基金supported by the National Natural Science Foundation of China(52267002)Natural Science Foundation of Jiangxi Province(20212ACB204010)+1 种基金Science&Technology Research Project of Jiangxi Provincial Education Department(GJJ211301)the Graduate Innovation Fund of Jiangxi Province(YC2021-S527).
文摘Relaxor ferroelectric ceramics have very high dielectric constant(e)but relatively low electrical breakdown strength(Eb),while glass-ceramics exhibit higher E,due to the more uniformly dispersed amorphous phases and submicrocrystals/nanocrystals inside.How to effectively combine the advantages of both relaxor ferroelectric ceramics and glass-ceramics is of great significance for the development of new dielectric materials with high energy storage performance.In this work,we firstly prepared BaO-SrO-Bi_(2)O_(3)-Na_(2)0-TiO_(2)-Al_(2)O_(3)-SiO_(2)(abbreviated as GS)glass powders,and then fabricated(Ba_(0.3)Sr_(0.7))_(0.5)(Bi_(0.5)Na_(0.5))_(0.5)TiO_(3)+x wt%GS ceramic composites(abbreviated as BSo.sBNT-xGS,x=0,2,6,10,14,16,and 18).Submicrocrystals/nanocrystals with a similar composition to BSo.sBNT were crystalized from the glass,ensuring the formation of uniform core-shell structure in BSo.sBNT-xGS relaxor ferroelectric ceramic/glass-ceramic composites.When the addition amount of GS was 14 wt%,the composite possessed both high&r(>3200 at 1 kHz)and high E,(~170 kV/cm)at room temperature,and their recoverable energy storage density and efficiency were Wrec=2.1 J/cm’and n=65.2%,respectively.The BSo.sBNT-14GS composite also had several attractive properties such as good temperature,frequency,cycle stability,and fast charge-discharge speed.This work provides insights into the relaxor ceramic/glass-ceramic composites for pulsed power capacitors and sheds light on the utilization of the hybrid systems.
基金supported by the National Natural Science Foundation of China (82225034,81830088 to Y.W.,82103148 to Y.Q.81872247 to W.Z.)+4 种基金the Department of Science and Technology of Liaoning Province (2021JH6/10500160 to Y.W.)the Basic Scientific Research Project of Education Department of Liaoning Province (LJKQZ2021104 to Y.Q.)the Science and Technology Innovation Talent Support Program of Dalian (2022RQ056 Y.Q.)the Science and Technology Innovation Foundation of Dalian (2022JJ11CG009 to Y.W.)Dalian High Level Talents Renovation Supporting Program (2019RQ097 to W.Z.).
文摘Cellular senescence provides a protective barrier against tumorigenesis in precancerous or normal tissues upon distinct stressors.However,the detailed mechanisms by which tumor cells evade premature senescence to malignant progression remain largely elusive.Here we reported that RBM4 adversely impacted cellular senescence to favor glutamine-dependent survival of esophageal squamous cell carcinoma(ESCC)cells by dictating the activity of LKB1,a critical governor of cancer metabolism.The level of RBM4 was specifically elevated in ESCC compared to normal tissues,and RBM4 overexpression promoted the malignant phenotype.RBM4 contributed to overcome H-RAS-or doxorubicin-induced senescence,while its depletion caused P27-dependent senescence and proliferation arrest by activating LKB1-AMPK-mTOR cascade.Mechanistically,RBM4 competitively bound LKB1 to disrupt the LKB1/STRAD/MO25 heterotrimeric complex,subsequently recruiting the E3 ligase TRIM26 to LKB1,promoting LKB1 ubiquitination and degradation in nucleus.Therefore,such molecular process leads to bypassing senescence and sustaining cell proliferation through the activation of glutamine metabolism.Clinically,the ESCC patients with high RBM4 and low LKB1 have significantly worse overall survival than those with low RBM4 and high LKB1.The RBM4 high/LKB1 low expression confers increased sensitivity of ESCC cells to glutaminase inhibitor CB-839,providing a novel insight into mechanisms underlying the glutamine-dependency to improve the efficacy of glutamine inhibitors in ESCC therapeutics.
基金This work was supported by the National Natural Science Foundation of China(81830088,81422038,91540110,and 31471235 to Y.W.,81872247 and 31400726 to W.Z.)the Department of Education of Liaoning Province(the"Liaoning Supports High Level Talents Innovation and Entrepreneurship Program"XLYC1802067 to Y.W.)+1 种基金the Department of Science and Technology of Dalian City(the HDalian Supports High Level Talents Innovation and Entrepreneurship Program" 2016RJ02 to Y.W.)the Newton Advanced Fellowship from the Academy of Medical Sciences in UK(JXR11831 to Y.W.).
文摘Alternative splicing is a critical process to generate protein diversity.However,whether and how alternative splicing regulates autophagy remains largely elusive.Here we systematically identify the splicing factor SRSF1 as an autophagy suppressor.Specifically,SRSF1 inhibits autophagosome formation by reducing the accumulation of LC3-ⅡI and numbers of autophagosomes in different cell lines.Mechanistically,SRSF1 promotes the splicing of the long isoform of Bcl-x that interacts with Beclinl,thereby dissociating the Beclin1-PIK3C3 complex.In addition,SRSF1 also directly interacts with PIK3C3 to disrupt the interaction between Beclinl and PIK3C3.Consequently,the decrease of SRSF1 stabilizes the Beclinl and PIK3C3 complex and activates autophagy.Interestingly,SRSF1 can be degraded by starvation-and oxidative stresses-induced autophagy through interacting with LC3-Ⅱ,whereas reduced SRSF1 further promotes autophagy.This positive feedback is critical to inhibiting Gefitinib-resistant cancer cell progression both in vitro and in vivo.Consistently,the expression level of SRSF1 is inversely correlated to LC3 level in clinical cancer samples.Our study not only provides mechanistic insights of alternative splicing in autophagy regulation but also discovers a new regulatory role of SRSF1 in tumorigenesis,thereby offering a novel avenue for potential cancer therapeutics.
基金financially supported by the National Natural Science Foundation of China(21775026,21904020,21974020)the Program for Changjiang Scholars and Innovative Research Team in University(IRT15R11)+2 种基金the cooperative project of production and study in the University of Fujian Province(2018Y4007)the Sciences Foundation of Fujian Province(2018J05018,2018J01685,2018J01682)“Thirteenth Five-Year Plan”Marine Economy Innovation and Development Demonstration Project(FZHJ19)
文摘In this work,a novel fluorescent biosensor has been constructed for rapid detection of Cu(Ⅱ)via the interaction between the fluorophore groups on the surface of nitrogen-doped-carbon-dots(N-CDs)and·OH produced from the catalytic reaction between Cu(Ⅱ)and cysteine(Cys).Specifically,Cu(Ⅱ)can catalyze the oxidation of Cys to form cystine(Cys–Cys)and hydrogen peroxide(H_(2)O_(2)),and Cu(Ⅱ)can also catalyze the decomposition of H_(2)O_(2)to produce hydroxyl radicals(·OH)by the Fenton-like reaction.·OH can oxidize and destroy the surface structure of N-CDs,resulting in the fluorescence quenching of the N-CDs.Under the optimal experimental conditions,the linear range of Cu(Ⅱ)is determined to be 0.05–25μmol L_(-1,),and the limit of detection is 23 nmol L^(-1)with the limit of quantitation of 77 nmol L^(-1).Besides,some characterizations are provided to verify the proposed principle.The method has been successfully applied for the detection of Cu(Ⅱ)in human serum and environmental water with high sensitivity and higher selectivity.