The undercurrent research survey explores the roles of nonlocality and strain gradient size dependencies in nonlinear asymmetric buckling of shallow nanoscale arches having dissimilar end conditions through a numerica...The undercurrent research survey explores the roles of nonlocality and strain gradient size dependencies in nonlinear asymmetric buckling of shallow nanoscale arches having dissimilar end conditions through a numerical analysis.The arches,made from a functionally graded graphene nanofiller reinforced composite(FG-GNRC),are subjected to discretional radial concentrated loads along with converting of temperature.To account for the size dependencies,the exploration is carried out stemming from the nonlocal strain gradient theory(NSGT)in the sense of a quasi-2D parabolic shear flexible concept of curved beam.The material properties of the contemplated FG-GNRC sandwich are determined using the modified Halpin-Tsai micromechanics model.Subsequently,an extended isogeometric analysis(XIGA)is manipulated comprising insertion plus multiplication of knots to achieve the demanded lower continuity allocated to the integration between flexural and tangential reflexes.It is perceived that the both softening and stiffening concomitants assigned to the salient concentrated radial loads obtained by the developed NSGT-based XIGA diminish from the first upper limit to the second one,and then likewise from the first lower limit to the second one.Although,by becoming the upsurge in temperature higher,these softening and stiffening concomitants get more remarkable.展开更多
As the support mechanism of space-borne antennas,space deployable antenna mechanism belongs to complex multi-closed-loop coupling mechanism,configuration design and dynamic analysis are more difficult than general par...As the support mechanism of space-borne antennas,space deployable antenna mechanism belongs to complex multi-closed-loop coupling mechanism,configuration design and dynamic analysis are more difficult than general parallel mechanism.In this paper,an unequal-length scissors mechanism(ULSM)is proposed by changing the position of the internal rotational joint through a basic scissors mechanism.A scissors hoop-rib truss deployable antenna mechanism(SHRTDAM)is constructed by replacing the parabolic rib with the ULSM.Kinematic analysis of SHRTDAM is conducted,and the degree of freedom(DOF)of the whole antenna mechanism is analyzed based on screw theory,the result showed that it has only one DOF.Velocity and acceleration characteristics of SHRTDAM are obtained by the screw derivative and rotation transformation.Based on Lagrange equation,dynamic model of this mechanism is established,the torque required to drive the mechanism is simulated and verified by Adams and MATLAB software.In addition,a ground experiment prototype of 1.5-m diameter was fabricated and a deployment test is conducted,which demonstrated the mobility and deployment performance of the whole mechanism.The mechanism proposed in this paper can provide a good reference for the design and analysis of large aperture space deployable antennas.展开更多
OBJECTIVE Despite the status of cisplatin(DDP) as a classical chemotherapeutic agent in the treatment of cancer,the development of multidrug resistance often leads to a failure of DDP therapy.Traditional Chinese medic...OBJECTIVE Despite the status of cisplatin(DDP) as a classical chemotherapeutic agent in the treatment of cancer,the development of multidrug resistance often leads to a failure of DDP therapy.Traditional Chinese medicine(TCM) as adjuvant chemotherapy of cancer drugs in China has been widely used in cancer treatment.ZuoJin WAN(ZJW),a TCM formula,was proved reversing drug resistance in gastric cancer,but its exact mechanism was still unclear.METHODS CCK-8 assay was used to detect the cell viability.The levels of proteins and mRNA were evaluated using Western blot and q-PCR.Mitochondrial membrane potential was measured by flow cytometry.Depolymerisa.tion of F-actin and translocation of G-actin(gamma-actin) from the cytoplasm to the mitochondria was detected using an immuno fl uorescence assay.RESULTS phosphorylated coflin-1(p-coflin-1) was overexpressed in the DDP-resistant human gastric cancer cell lines SGC7901/DDP and BGC823/DDP,relative to the respective parent cell lines(SGC7901 and BGC823),and DDP induced the dephosphory.lation of p-coflin-1 in both parent lines but not in the DDP-resistant lines.However,ZJW could induce the dephosphorylation of pcoflin-1 and promote coflin-1 translocation from the cytoplasm into the mito.chondria in both SGC7901/DDP and BGC823/DDP cells.This mitochondrial translocation of coflin-1 was found to induce the conversion of flamentous actin to globular-actin,activate mitochondrial dam.age and calcium overloading,and induce the mitochondrial apoptosis pathway.These effects of ZJW on DDP-resistant human gastric cancer cell lines could be reversed via transfection with coflin-1-specifc siRNA,or treatment with a PP1 and PP2A inhibitor.CONCLUSION ZJW can be used as an inhibitor of chemoresistance in gastric cancer,which may partly be due to dephosphorylation of p-coflin-1 via the activation of PP1 and PP2A.展开更多
It is known that mechanical forces play critical roles in physiology and diseases but the underlying mechanisms remain largely unknown[1].Most studies on the role of forces focus on cell surface molecules and cytoplas...It is known that mechanical forces play critical roles in physiology and diseases but the underlying mechanisms remain largely unknown[1].Most studies on the role of forces focus on cell surface molecules and cytoplasmic proteins.However,increasing evidence suggests that nuclear mechanotransduction impacts nuclear activities and functions.Recently we have revealed that transgene dihydrofolate reductase(DHFR)gene expression is directly upregulated via cell surface forceinduced stretching of chromatin [2].Here we show that endogenous genes are also upregulated directly by force via integrins.We present evidence on an underlying mechanism of how gene transcription is regulated by force.We have developed a technique of elastic round microgels to quantify 3D tractions in vitro and in vivo[3].We report a synthetic small molecule(which has been stiffened structurally)that inhibits malignant tumor repopulating cell growth in a low-stiffness(force)microenvironment and cancer metastasis in mouse models without detectable toxicity[4].These findings suggest that direct nuclear mechanotransduction impacts mechanobiology and mechanomedicine at cellular and molecular levels.展开更多
All living cells in a human body are made of the same DNA molecule but cells in different tissues express different genes and proteins.How the transcription process is controlled and regulated is largely unknown.Speci...All living cells in a human body are made of the same DNA molecule but cells in different tissues express different genes and proteins.How the transcription process is controlled and regulated is largely unknown.Specifically,mechanical forces are increasingly recognized to play critical roles in cell and tissue functions.However,what controls force-induced gene transcription is elusive.Recently we have reported that a local surface force transfers from integrins to the cytoskeleton and the link of nucleoskeleton and the cytoskeleton(LINC)into the nucleus and deforms chromatin directly to induce rapid activation of transgene DHFR.Here we show that endogenous mechanoresponsive genes egr-1 and Cav1 are rapidly upregulated and their upregulation depends on stress angles relative to the cell long axis,suggesting direct impact of these genes by force.Demethylation of histone 3 at lysine 9(H3K9)trimethylation(H3K9me3)at nuclear interiors(euchromatin)is necessary for force-induced transcription upregulation.Our findings suggest that force-rapid upregulation of mechanoresponsive genes by force depends on H3K9me3 demethylation.展开更多
基金supported by projects VEGA 1/0307/23 and APVV-23-0204 of Scientific Grant Agency of the Ministry of Education,Research,Development and Youth of the Slovak Republic.
文摘The undercurrent research survey explores the roles of nonlocality and strain gradient size dependencies in nonlinear asymmetric buckling of shallow nanoscale arches having dissimilar end conditions through a numerical analysis.The arches,made from a functionally graded graphene nanofiller reinforced composite(FG-GNRC),are subjected to discretional radial concentrated loads along with converting of temperature.To account for the size dependencies,the exploration is carried out stemming from the nonlocal strain gradient theory(NSGT)in the sense of a quasi-2D parabolic shear flexible concept of curved beam.The material properties of the contemplated FG-GNRC sandwich are determined using the modified Halpin-Tsai micromechanics model.Subsequently,an extended isogeometric analysis(XIGA)is manipulated comprising insertion plus multiplication of knots to achieve the demanded lower continuity allocated to the integration between flexural and tangential reflexes.It is perceived that the both softening and stiffening concomitants assigned to the salient concentrated radial loads obtained by the developed NSGT-based XIGA diminish from the first upper limit to the second one,and then likewise from the first lower limit to the second one.Although,by becoming the upsurge in temperature higher,these softening and stiffening concomitants get more remarkable.
基金supported by the National Natural Science Foundation of China(Grant Nos.52105035 and 52075467)the Natural Science Foundation of Hebei Province of China(Grant No.E2021203109)+1 种基金the State Key Laboratory of Robotics and Systems(HIT)(Grant No.SKLRS-2021-KF-15)the Industrial Robot Control and Reliability Technology Innovation Center of Hebei Province(Grant No.JXKF2105).
文摘As the support mechanism of space-borne antennas,space deployable antenna mechanism belongs to complex multi-closed-loop coupling mechanism,configuration design and dynamic analysis are more difficult than general parallel mechanism.In this paper,an unequal-length scissors mechanism(ULSM)is proposed by changing the position of the internal rotational joint through a basic scissors mechanism.A scissors hoop-rib truss deployable antenna mechanism(SHRTDAM)is constructed by replacing the parabolic rib with the ULSM.Kinematic analysis of SHRTDAM is conducted,and the degree of freedom(DOF)of the whole antenna mechanism is analyzed based on screw theory,the result showed that it has only one DOF.Velocity and acceleration characteristics of SHRTDAM are obtained by the screw derivative and rotation transformation.Based on Lagrange equation,dynamic model of this mechanism is established,the torque required to drive the mechanism is simulated and verified by Adams and MATLAB software.In addition,a ground experiment prototype of 1.5-m diameter was fabricated and a deployment test is conducted,which demonstrated the mobility and deployment performance of the whole mechanism.The mechanism proposed in this paper can provide a good reference for the design and analysis of large aperture space deployable antennas.
基金supported by National Natural Science Foundation of China(81473481)Construct Program of the Key Discipline of State Administration of Traditional Chinese Medicine of People′s Republic of Chinathe Science Foundation for Shanghai Municipal Health and Family Planning Commission(20124065)
文摘OBJECTIVE Despite the status of cisplatin(DDP) as a classical chemotherapeutic agent in the treatment of cancer,the development of multidrug resistance often leads to a failure of DDP therapy.Traditional Chinese medicine(TCM) as adjuvant chemotherapy of cancer drugs in China has been widely used in cancer treatment.ZuoJin WAN(ZJW),a TCM formula,was proved reversing drug resistance in gastric cancer,but its exact mechanism was still unclear.METHODS CCK-8 assay was used to detect the cell viability.The levels of proteins and mRNA were evaluated using Western blot and q-PCR.Mitochondrial membrane potential was measured by flow cytometry.Depolymerisa.tion of F-actin and translocation of G-actin(gamma-actin) from the cytoplasm to the mitochondria was detected using an immuno fl uorescence assay.RESULTS phosphorylated coflin-1(p-coflin-1) was overexpressed in the DDP-resistant human gastric cancer cell lines SGC7901/DDP and BGC823/DDP,relative to the respective parent cell lines(SGC7901 and BGC823),and DDP induced the dephosphory.lation of p-coflin-1 in both parent lines but not in the DDP-resistant lines.However,ZJW could induce the dephosphorylation of pcoflin-1 and promote coflin-1 translocation from the cytoplasm into the mito.chondria in both SGC7901/DDP and BGC823/DDP cells.This mitochondrial translocation of coflin-1 was found to induce the conversion of flamentous actin to globular-actin,activate mitochondrial dam.age and calcium overloading,and induce the mitochondrial apoptosis pathway.These effects of ZJW on DDP-resistant human gastric cancer cell lines could be reversed via transfection with coflin-1-specifc siRNA,or treatment with a PP1 and PP2A inhibitor.CONCLUSION ZJW can be used as an inhibitor of chemoresistance in gastric cancer,which may partly be due to dephosphorylation of p-coflin-1 via the activation of PP1 and PP2A.
基金supported by funds from National Institutes of Health,USA and Huazhong University of Science and Technology,Wuhan,Chinathe support from Hoeft Professorship at University of Illinois at Urbana-Champaign
文摘It is known that mechanical forces play critical roles in physiology and diseases but the underlying mechanisms remain largely unknown[1].Most studies on the role of forces focus on cell surface molecules and cytoplasmic proteins.However,increasing evidence suggests that nuclear mechanotransduction impacts nuclear activities and functions.Recently we have revealed that transgene dihydrofolate reductase(DHFR)gene expression is directly upregulated via cell surface forceinduced stretching of chromatin [2].Here we show that endogenous genes are also upregulated directly by force via integrins.We present evidence on an underlying mechanism of how gene transcription is regulated by force.We have developed a technique of elastic round microgels to quantify 3D tractions in vitro and in vivo[3].We report a synthetic small molecule(which has been stiffened structurally)that inhibits malignant tumor repopulating cell growth in a low-stiffness(force)microenvironment and cancer metastasis in mouse models without detectable toxicity[4].These findings suggest that direct nuclear mechanotransduction impacts mechanobiology and mechanomedicine at cellular and molecular levels.
基金supported by the funds from Huazhong University of Science and Technology and US NIH grant GM 072744
文摘All living cells in a human body are made of the same DNA molecule but cells in different tissues express different genes and proteins.How the transcription process is controlled and regulated is largely unknown.Specifically,mechanical forces are increasingly recognized to play critical roles in cell and tissue functions.However,what controls force-induced gene transcription is elusive.Recently we have reported that a local surface force transfers from integrins to the cytoskeleton and the link of nucleoskeleton and the cytoskeleton(LINC)into the nucleus and deforms chromatin directly to induce rapid activation of transgene DHFR.Here we show that endogenous mechanoresponsive genes egr-1 and Cav1 are rapidly upregulated and their upregulation depends on stress angles relative to the cell long axis,suggesting direct impact of these genes by force.Demethylation of histone 3 at lysine 9(H3K9)trimethylation(H3K9me3)at nuclear interiors(euchromatin)is necessary for force-induced transcription upregulation.Our findings suggest that force-rapid upregulation of mechanoresponsive genes by force depends on H3K9me3 demethylation.
