hypoxicischemic brain injury;however,the therapeutic efficacy of bone marrow-derived mesenchymal stem cells largely depends on the number of cells that are successfully transferred to the target.Magnet-targeted drug d...hypoxicischemic brain injury;however,the therapeutic efficacy of bone marrow-derived mesenchymal stem cells largely depends on the number of cells that are successfully transferred to the target.Magnet-targeted drug delivery systems can use a specific magnetic field to attract the drug to the target site,increasing the drug concentration.In this study,we found that the double-labeling using superparamagnetic iron oxide nanoparticle and poly-L-lysine(SPIO-PLL)of bone marrow-derived mesenchymal stem cells had no effect on cell survival but decreased cell proliferation 48 hours after labeling.Rat models of hypoxic-ischemic brain injury were established by ligating the left common carotid artery.One day after modeling,intraventricular and caudal vein injections of 1×105 SPIO-PLL-labeled bone marrow-derived mesenchymal stem cells were performed.Twenty-four hours after the intraventricular injection,magnets were fixed to the left side of the rats’heads for 2 hours.Intravoxel incoherent motion magnetic resonance imaging revealed that the perfusion fraction and the diffusion coefficient of rat brain tissue were significantly increased in rats treated with SPIO-PLL-labeled cells through intraventricular injection combined with magnetic guidance,compared with those treated with SPIO-PLL-labeled cells through intraventricular or tail vein injections without magnetic guidance.Hematoxylin-eosin and terminal deoxynucleotidyl transferase dUTP nick-end labeling(TUNEL)staining revealed that in rats treated with SPIO-PLL-labeled cells through intraventricular injection under magnetic guidance,cerebral edema was alleviated,and apoptosis was decreased.These findings suggest that targeted magnetic guidance can be used to improve the therapeutic efficacy of bone marrow-derived mesenchymal stem cell transplantation for hypoxic-ischemic brain injury.This study was approved by the Animal Care and Use Committee of The Second Hospital of Dalian Medical University,China(approval No.2016-060)on March 2,2016.展开更多
Cellular collective motion in confluent epithelial monolayers is involved in many processes such as embryo development,carcinoma invasion,and wound healing.The development of new chemical strategies to achieve largesc...Cellular collective motion in confluent epithelial monolayers is involved in many processes such as embryo development,carcinoma invasion,and wound healing.The development of new chemical strategies to achieve largescale control of cells’collective motion is essential for biomedical applications.Here a series of DNA nanostructures with different dimensions were synthesized and their influences on cells’collective migration and packing behaviors in epithelial monolayers were investigated.We found that the framed DNA nanoassemblies effectively reduced the cells’speed by increasing the rigidity of cells,while the lipid-DNA micelles had a more pronounced effect on cells’projection area and shape factor.These DNA nanostructures all significantly enhanced the dependence of cells’speed on their shape factor.Our results indicate that cells’mobility in monolayers can be manipulated by chemical intercellular interactions without any genetic intervention.This may provide a new chemical strategy for tissue engineering and tumor therapy.展开更多
The motion of small bacteria consists of two phases:relatively long runs alternate with intermittent stops,back-ups,or tumbles,depending on the species.In polar monotrichous bacteria,the flagellum is anchored at the c...The motion of small bacteria consists of two phases:relatively long runs alternate with intermittent stops,back-ups,or tumbles,depending on the species.In polar monotrichous bacteria,the flagellum is anchored at the cell pole inherited from the parent generation(old pole) and is surrounded by a chemoreceptor cluster.During forward swimming,the leading pole is always the pole recently formed in cell division(new pole).The flagella of the peritrichous bacterium Escherichia coli often form a bundle behind the old pole.Its cell orientation and receptor positioning during runs generally mimic that of monotrichous bacteria.When encountering a solid surface,peritrichous bacteria exhibit a circular motion with the leading pole dipping downward.Some polar monotrichous bacteria also perform circular motion near solid boundaries,but during back-ups.In this case,the leading pole points upward.Very little is known about behavior near milieu-air interfaces.Biophysical simulations have revealed some of the mechanisms underlying these phenomena,but leave many questions unanswered.Combining biophysics with molecular techniques will certainly advance our understanding of bacterial locomotion.展开更多
BACKGROUND Motion sickness(MS)is a disease that occurs during unbalanced movement,characterized by gastrointestinal symptoms and autonomic nervous system activation.Current clinical treatments for MS are limited.Recen...BACKGROUND Motion sickness(MS)is a disease that occurs during unbalanced movement,characterized by gastrointestinal symptoms and autonomic nervous system activation.Current clinical treatments for MS are limited.Recent evidence indicates that the levels of pro-inflammatory cytokines increase during MS and are associated with an inner ear immune imbalance.In the present study,mesenchymal stem cells(MSCs)have been shown to exert strong immunosuppressive effects.AIM To explore whether umbilical cord-derived mesenchymal stem cells(UC-MSCs)can prevent the occurrence of MS,and the underlying mechanism regulated by MSCs in a mouse model of MS.METHODS A total of 144(equal numbers of males and females)5wkold BALB/c mice were randomly divided into five groups:Normal group(n=16),MS group(n=32),MSCs group(n=32),MS+MSCs group(n=32),and MS+AS101/MSCs group(n=32).The MSCs group(n=32),MS+MSCs group(n=32),and MS+AS101/MSCs group(n=32)were preventively transplanted with UC-MSCs or AS101-treated UC-MSCs(1×106 cells/mouse).Mice in the MS(n=32),MS+MSCs,and MS+AS101/MSCs groups were subjected to rotation on a centrifuge for 10 min at 8×g/min for MS model establishment on days 3,5,8,and 10 after UC-MSCs injection.The Morris water maze(MWM)test was used to observe the symptom of dizziness.Enzyme-linked immunosorbent assay(ELISA)and reverse transcription-quantitative polymerase chain reaction(RT-qPCR)were used to detect the levels of inflammatory cytokines in mice peripheral blood and the petrous part of the temporal bone samples.Western blot analysis was performed to analyze the JAK2/STAT3 signaling pathway in the cochlear tissues.Histological examination was performed by hematoxylin and eosin(HE)staining for conventional morphological evaluation in the petrous part of temporal bone samples.RESULTS The MWM test demonstrated that UC-MSCs improved the symptoms of MS.The MS+MSCs group was faster than the MS group on days 3 and 5(P=0.036 and P=0.002,respectively).ELISA and RT-qPCR showed that the serum and mRNA levels of interleukin-10(IL展开更多
A novel robust controller is proposed in this study to realize the precise motion control of a cell puncture mechanism(CPM)driven by piezoelectric ceramics(PEAs).The entire dynamic model of CPM is constructed based on...A novel robust controller is proposed in this study to realize the precise motion control of a cell puncture mechanism(CPM)driven by piezoelectric ceramics(PEAs).The entire dynamic model of CPM is constructed based on the Bouc–Wen model,and the nonlinear part of the dynamic model is optimized locally to facilitate the construction of a robust controller.A model-based,nonlinear robust controller is constructed using time-delay estimation(TDE)and fractional-order nonsingular terminal sliding mode(FONTSM).The proposed controller does not require prior knowledge of unknown disturbances due to its real-time online estimation and compensation of unknown terms by using the TDE technology.The controller also has finite-time convergence and high-precision trajectory tracking capabilities due to FONTSM manifold and fast terminal sliding mode-type reaching law.The stability of the closed-loop system is proved by Lyapunov stability theory.Computer simulation and hardware-in-loop simulation experiments of CPM verify that the proposed controller outperforms traditional terminal sliding mode controllers,such as the integer-order or model-free controller.The proposed controller can also continuously output without chattering and has high control accuracy.Zebrafish embryo is used as a verification target to complete the cell puncture experiment.From the engineering application perspective,the proposed control strategy can be effectively applied in a PEA-driven CPM.展开更多
Deformation of two-dimensional red blood cell in linear shear flow is simulated using the immersed boundary method,in which the cell is modeled as a force source instead of a real body.The effect of three constitutive...Deformation of two-dimensional red blood cell in linear shear flow is simulated using the immersed boundary method,in which the cell is modeled as a force source instead of a real body.The effect of three constitutive laws,i.e.Hookean,Neo-Hookean and Skalak elasticity,on the deformation is studied by simulating the cell movement in two linear shear flows.The results show that the effect of the constitutive laws gets more obvious as the shear rate increases.Both the aspect ratio and the inclination of the steady shapes get bigger, and the differences between the periods of the cell tank-treading motion become larger.For the same shear flow, the period with Hookean elasticity is less than the period with Neo-Hookean elasticity and bigger than the period with Skalak elasticity.展开更多
文摘hypoxicischemic brain injury;however,the therapeutic efficacy of bone marrow-derived mesenchymal stem cells largely depends on the number of cells that are successfully transferred to the target.Magnet-targeted drug delivery systems can use a specific magnetic field to attract the drug to the target site,increasing the drug concentration.In this study,we found that the double-labeling using superparamagnetic iron oxide nanoparticle and poly-L-lysine(SPIO-PLL)of bone marrow-derived mesenchymal stem cells had no effect on cell survival but decreased cell proliferation 48 hours after labeling.Rat models of hypoxic-ischemic brain injury were established by ligating the left common carotid artery.One day after modeling,intraventricular and caudal vein injections of 1×105 SPIO-PLL-labeled bone marrow-derived mesenchymal stem cells were performed.Twenty-four hours after the intraventricular injection,magnets were fixed to the left side of the rats’heads for 2 hours.Intravoxel incoherent motion magnetic resonance imaging revealed that the perfusion fraction and the diffusion coefficient of rat brain tissue were significantly increased in rats treated with SPIO-PLL-labeled cells through intraventricular injection combined with magnetic guidance,compared with those treated with SPIO-PLL-labeled cells through intraventricular or tail vein injections without magnetic guidance.Hematoxylin-eosin and terminal deoxynucleotidyl transferase dUTP nick-end labeling(TUNEL)staining revealed that in rats treated with SPIO-PLL-labeled cells through intraventricular injection under magnetic guidance,cerebral edema was alleviated,and apoptosis was decreased.These findings suggest that targeted magnetic guidance can be used to improve the therapeutic efficacy of bone marrow-derived mesenchymal stem cell transplantation for hypoxic-ischemic brain injury.This study was approved by the Animal Care and Use Committee of The Second Hospital of Dalian Medical University,China(approval No.2016-060)on March 2,2016.
基金the National Key Research and Development Program of China(2020YFA0908200,2018YFA0902600,2020YFA0712102,and 2020YFA0712102)the National Natural Science Foundation of China(12074407,11774394,22125701,21834007,and 21907088)+1 种基金the Strategic Priority Research Program of Chinese Academy of Sciences(XDB33000000)the Youth Innovation Promotion Association of CAS(2020228,2021007).
文摘Cellular collective motion in confluent epithelial monolayers is involved in many processes such as embryo development,carcinoma invasion,and wound healing.The development of new chemical strategies to achieve largescale control of cells’collective motion is essential for biomedical applications.Here a series of DNA nanostructures with different dimensions were synthesized and their influences on cells’collective migration and packing behaviors in epithelial monolayers were investigated.We found that the framed DNA nanoassemblies effectively reduced the cells’speed by increasing the rigidity of cells,while the lipid-DNA micelles had a more pronounced effect on cells’projection area and shape factor.These DNA nanostructures all significantly enhanced the dependence of cells’speed on their shape factor.Our results indicate that cells’mobility in monolayers can be manipulated by chemical intercellular interactions without any genetic intervention.This may provide a new chemical strategy for tissue engineering and tumor therapy.
文摘The motion of small bacteria consists of two phases:relatively long runs alternate with intermittent stops,back-ups,or tumbles,depending on the species.In polar monotrichous bacteria,the flagellum is anchored at the cell pole inherited from the parent generation(old pole) and is surrounded by a chemoreceptor cluster.During forward swimming,the leading pole is always the pole recently formed in cell division(new pole).The flagella of the peritrichous bacterium Escherichia coli often form a bundle behind the old pole.Its cell orientation and receptor positioning during runs generally mimic that of monotrichous bacteria.When encountering a solid surface,peritrichous bacteria exhibit a circular motion with the leading pole dipping downward.Some polar monotrichous bacteria also perform circular motion near solid boundaries,but during back-ups.In this case,the leading pole points upward.Very little is known about behavior near milieu-air interfaces.Biophysical simulations have revealed some of the mechanisms underlying these phenomena,but leave many questions unanswered.Combining biophysics with molecular techniques will certainly advance our understanding of bacterial locomotion.
基金Supported by Department of Science&Technology of Shandong Province,No.ZR2018MH012Quancheng Industrial Leader Project,No.2017018Ji'nan Science and Technology Development Foundation,No.201704066.
文摘BACKGROUND Motion sickness(MS)is a disease that occurs during unbalanced movement,characterized by gastrointestinal symptoms and autonomic nervous system activation.Current clinical treatments for MS are limited.Recent evidence indicates that the levels of pro-inflammatory cytokines increase during MS and are associated with an inner ear immune imbalance.In the present study,mesenchymal stem cells(MSCs)have been shown to exert strong immunosuppressive effects.AIM To explore whether umbilical cord-derived mesenchymal stem cells(UC-MSCs)can prevent the occurrence of MS,and the underlying mechanism regulated by MSCs in a mouse model of MS.METHODS A total of 144(equal numbers of males and females)5wkold BALB/c mice were randomly divided into five groups:Normal group(n=16),MS group(n=32),MSCs group(n=32),MS+MSCs group(n=32),and MS+AS101/MSCs group(n=32).The MSCs group(n=32),MS+MSCs group(n=32),and MS+AS101/MSCs group(n=32)were preventively transplanted with UC-MSCs or AS101-treated UC-MSCs(1×106 cells/mouse).Mice in the MS(n=32),MS+MSCs,and MS+AS101/MSCs groups were subjected to rotation on a centrifuge for 10 min at 8×g/min for MS model establishment on days 3,5,8,and 10 after UC-MSCs injection.The Morris water maze(MWM)test was used to observe the symptom of dizziness.Enzyme-linked immunosorbent assay(ELISA)and reverse transcription-quantitative polymerase chain reaction(RT-qPCR)were used to detect the levels of inflammatory cytokines in mice peripheral blood and the petrous part of the temporal bone samples.Western blot analysis was performed to analyze the JAK2/STAT3 signaling pathway in the cochlear tissues.Histological examination was performed by hematoxylin and eosin(HE)staining for conventional morphological evaluation in the petrous part of temporal bone samples.RESULTS The MWM test demonstrated that UC-MSCs improved the symptoms of MS.The MS+MSCs group was faster than the MS group on days 3 and 5(P=0.036 and P=0.002,respectively).ELISA and RT-qPCR showed that the serum and mRNA levels of interleukin-10(IL
文摘A novel robust controller is proposed in this study to realize the precise motion control of a cell puncture mechanism(CPM)driven by piezoelectric ceramics(PEAs).The entire dynamic model of CPM is constructed based on the Bouc–Wen model,and the nonlinear part of the dynamic model is optimized locally to facilitate the construction of a robust controller.A model-based,nonlinear robust controller is constructed using time-delay estimation(TDE)and fractional-order nonsingular terminal sliding mode(FONTSM).The proposed controller does not require prior knowledge of unknown disturbances due to its real-time online estimation and compensation of unknown terms by using the TDE technology.The controller also has finite-time convergence and high-precision trajectory tracking capabilities due to FONTSM manifold and fast terminal sliding mode-type reaching law.The stability of the closed-loop system is proved by Lyapunov stability theory.Computer simulation and hardware-in-loop simulation experiments of CPM verify that the proposed controller outperforms traditional terminal sliding mode controllers,such as the integer-order or model-free controller.The proposed controller can also continuously output without chattering and has high control accuracy.Zebrafish embryo is used as a verification target to complete the cell puncture experiment.From the engineering application perspective,the proposed control strategy can be effectively applied in a PEA-driven CPM.
基金the National Natural Science Foundation of China(No.10472070)the Shanghai Leading Academic Discipline Project(No.B206)
文摘Deformation of two-dimensional red blood cell in linear shear flow is simulated using the immersed boundary method,in which the cell is modeled as a force source instead of a real body.The effect of three constitutive laws,i.e.Hookean,Neo-Hookean and Skalak elasticity,on the deformation is studied by simulating the cell movement in two linear shear flows.The results show that the effect of the constitutive laws gets more obvious as the shear rate increases.Both the aspect ratio and the inclination of the steady shapes get bigger, and the differences between the periods of the cell tank-treading motion become larger.For the same shear flow, the period with Hookean elasticity is less than the period with Neo-Hookean elasticity and bigger than the period with Skalak elasticity.
