Evaluation of genetic response of mesenchymal stem cells to nanosecond pulsed electric fields by whole transcriptome sequencing

BACKGROUND Mesenchymal stem cells(MSCs)modulated by various exogenous signals have been applied extensively in regenerative medicine research.Notably,nanosecond pulsed electric fields(nsPEFs),characterized by short duration and high strength,significantly influence cell phenotypes and regulate MSCs differentiation via multiple pathways.Consequently,we used transcriptomics to study changes in messenger RNA(mRNA),long noncoding RNA(lncRNA),microRNA(miRNA),and circular RNA expression during nsPEFs application.AIM To explore gene expression profiles and potential transcriptional regulatory mechanisms in MSCs pretreated with nsPEFs.METHODS The impact of nsPEFs on the MSCs transcriptome was investigated through whole transcriptome sequencing.MSCs were pretreated with 5-pulse nsPEFs(100 ns at 10 kV/cm,1 Hz),followed by total RNA isolation.Each transcript was normalized by fragments per kilobase per million.Fold change and difference significance were applied to screen the differentially expressed genes(DEGs).Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed to elucidate gene functions,complemented by quantitative polymerase chain reaction verification.RESULTS In total,263 DEGs were discovered,with 92 upregulated and 171 downregulated.DEGs were predominantly enriched in epithelial cell proliferation,osteoblast differentiation,mesenchymal cell differentiation,nuclear division,and wound healing.Regarding cellular components,DEGs are primarily involved in condensed chromosome,chromosomal region,actin cytoskeleton,and kinetochore.From aspect of molecular functions,DEGs are mainly involved in glycosaminoglycan binding,integrin binding,nuclear steroid receptor activity,cytoskeletal motor activity,and steroid binding.Quantitative real-time polymerase chain reaction confirmed targeted transcript regulation.CONCLUSION Our systematic investigation of the wide-ranging transcriptional pattern modulated by nsPEFs revealed the differential expression of 263 mRNAs,2 miRNAs,and 65 lncRNAs.Our study demonstrates that nsPEFs may affect stem cells through several signaling pathways,which are involved in vesicular transport,calcium ion transport,cytoskeleton,and cell differentiation.

Effect of applied electric fields on supralinear dendritic integration of interneuron

Evidences show that electric fields(EFs)induced by the magnetic stimulation could modulates brain activities by regulating the excitability of GABAergic interneuron.However,it is still unclear how and why the EF-induced polarization affects the interneuron response as the interneuron receives NMDA synaptic inputs.Considering the key role of NMDA receptor-mediated supralinear dendritic integration in neuronal computations,we suppose that the applied EFs could functionally modulate interneurons’response via regulating dendritic integration.At first,we build a simplified multi-dendritic circuit model with inhomogeneous extracellular potentials,which characterizes the relationship among EF-induced spatial polarizations,dendritic integration,and somatic output.By performing model-based singular perturbation analysis,it is found that the equilibrium point of fast subsystem can be used to asymptotically depict the subthreshold input–output(sI/O)relationship of dendritic integration.It predicted that EF-induced strong depolarizations on the distal dendrites reduce the dendritic saturation output by reducing driving force of synaptic input,and it shifts the steep change of sI/O curve left by reducing stimulation threshold of triggering NMDA spike.Also,the EF modulation prefers the global dendritic integration with asymmetric scatter distribution of NMDA synapses.Furthermore,we identify the respective contribution of EF-regulated dendritic integration and EF-induced somatic polarization to an action potential generation and find that they have an antagonistic effect on AP generation due to the varied NMDA spike threshold under EF stimulation.

Oscillation of Dzyaloshinskii–Moriya interaction driven by weak electric fields

Dzyaloshinskii–Moriya interaction(DMI) is under extensive investigation considering its crucial status in chiral magnetic orders, such as Néel-type domain wall(DW) and skyrmions. It has been reported that the interfacial DMI originating from Rashba spin–orbit coupling(SOC) can be linearly tuned with strong external electric fields. In this work, we experimentally demonstrate that the strength of DMI exhibits rapid fluctuations, ranging from 10% to 30% of its original value, as a function of applied electric fields in Pt/Co/MgO heterostructures within the small field regime(< 10-2V/nm). Brillouin light scattering(BLS) experiments have been performed to measure DMI, and first-principles calculations show agreement with this observation, which can be explained by the variation in orbital hybridization at the Co/MgO interface in response to the weak electric fields. Our results on voltage control of DMI(VCDMI) suggest that research related to the voltage control of magnetic anisotropy for spin–orbit torque or the motion control of skyrmions might also have to consider the role of the external electric field on DMI as small voltages are generally used for the magnetoresistance detection.

Structure and stability of nitrogen hydrate in a single-walled carbon nanotube under external electric fields

The effects of an external electric field on the structure and stability of the nitrogen hydrate confined in a single-walled carbon nanotube(CNT)were studied by using molecular dynamics(MD)simulations.It was found that the structure of the nitrogen hydrate,the occupancy and distribution of the nitrogen molecules inside the nanotube depend sensitively on the direction of the external electric field.A parallel electric field can destabilize the nitrogen hydrate and cause the release of nitrogen molecules from the ice nanotube of the hydrate.While a vertical electric field can redistribute the nitrogen molecules from the core to the shell of the hydrate.The occupancy of the nitrogen molecules of the hydrate follows a sigmoid-like function as the direction of the electric field changes.Our findings may aid in the development of methods to control gas release and encapsulation by using electric fields.

Tumor ablation with nanosecond pulsed electric fields

Liver cancer is one of the most malignant cancers. It is reported that 600 000 patients died from liver cancer every year. [1,2] Hepatocellular carcinoma (HCC) is a particular problem because symptoms are not evident until the disease has progressed and hepatitis B, which is prominent specific regions of Asia, is a common precursor of the disease. There are many liver cancer

Design and Experiments of the High Voltage Pulsed Electric Fields Sterilization System

This experiment designed the pulsed electric fields （PEF） of high intensity of 100 kV· cm^-1 sterilization system. Fluorescent pseudomonas as target cell was operated 180 s in the PEF. By observing the difference of the bacteria before and after the disposal by TEM, it is found that the cell walls of the treated bacteria were broken. Irreversible perforations were formed on the cell membrane. The cell inclusions and cell fragments were leaked. The cell died as a result. The results showed that the PEF sterilization system designed can be used for liquid food sterilization experiments.

Molecular dynamics simulation of the response of bi-disperse polyelectrolyte brushes to external electric fields

Langevin dynamics simulations have been performed to investigate the response of bi-disperse and strong polyacid chains grafted on an electrode to electric fields generated by opposite surface charges on the polyelectrolyte （PE）-grafted electrode and a second parallel electrode. Simulation results clearly show that, under a negative external electric field, the longer grafted PE chains are more strongly stretched than the shorter ones in terms of the relative change in their respective brush heights. Whereas under a positive external electric field, the grafted shorter chains collapse more significantly than the longer ones. It was found that, under a positive external electric field, the magnitude of the total electric force acting on one shorter PE chain is larger than that on one longer PE chain, or vice versa. The effects of smeared and discrete charge distributions of grafted PE chains on the response of PE brushes to external electric fields were also examined.

Quantum Theory of Mesoscopic Fractional Electric Fields in a Cavity of Viscous Medium

With conjecture of fractional charge quantization (quantum dipole/multiple moments), Fourier transform stretching, twisting and twigging of an electron quanta and waver strings of electron quanta, the mathematical expressions for mesoscopic fractional electron fields in a cavity of viscous medium and the associated quantum dielectric susceptibility are developed. Agreement of this approach is experimentally evidenced on barite and Fanja site molecular sieves. These findings are in conformity with experimental results of 2012 Physics Nobel prize winning scientists, Serge Haroche and David J. Wineland especially for cavity quantum electro-dynamics electron and its associated mesoscopic electric fields. The mover electron quanta strings lead to warping of space and time following the behaviour of quantum electron dynamics.

Si_2O_2 molecule:structure of ground state and the excited properties under different external electric fields

Geometry and vibrational frequencies of the ground state of Si2O2 molecule are studied using density function theory （DFT） at the level of cc-pvtz and 6-311-k＋G^＊＊. It is found that the optimizing value by B31yp/cc-pvtz is closer to the experimental data. The excited properties under different external electric fields are also investigated by the time-dependent-DFT method. Transitions from the ground state of Si2O2 molecule to the first singlet state under different external electric fields can take place more easily. The corresponding absorption spectral line is about 360 nm in wavelength and the excitation energy is about 3.4 eV.

Electric fields inside and outside an anisotropic dielectric sphere

Analytical expressions of electric fields inside and outside an anisotropic dielectric sphere are presented by transforming an anisotropic medium into an isotropic one based on the multi-scale transformation of electromagnetic theory. The theoretical expressions are consistent with those in the literature. The inside electric field, the outside electric field and the angle between their directions are derived in detail. Numerical simulations show that the direction of the outside field influences the magnitude of the inside field, while the dielectric constant tensor greatly affects its direction.

Spiking patterns of a hippocampus model in electric fields

We develop a model of CA3 neurons embedded in a resistive array to mimic the effects of electric fields from a new perspective. Effects of DC and sinusoidal electric fields on firing patterns in CA3 neurons are investigated in this study. The firing patterns can be switched from no firing pattern to burst or from burst to fast periodic firing pattern with the increase of DC electric field intensity. It is also found that the firing activities are sensitive to the frequency and amplitude of the sinusoidal electric field. Different phase-locking states and chaotic firing regions are observed in the parameter space of frequency and amplitude. These findings are qualitatively in accordance with the results of relevant experimental and numerical studies. It is implied that the external or endogenous electric field can modulate the neural code in the brain. Furthermore, it is helpful to develop control strategies based on electric fields to control neural diseases such as epilepsy.

Action potential-simulated weak electric fields can directly initiate myelination

BACKGROUND： Myelination is a process whereby glial cells identify, adhere, wrap and enclose axons to form a spiral myelin sheath. OBJECTIVE： To investigate the effects of action potential-simulated weak electric fields on myelination in the central nervous system. DESIGN AND SETTING： This single-sample observation study was performed at the 324 Hospital of Chinese PLA. MATERIALS： Two 5 μm carbon fibers were provided by the Institute of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences. One Sprague Dawley rat, aged 1 day, was used. METHODS： Cerebral cortex was harvested from the rat to prepare a suspension [（1 2）× 10^5/mL] containing neurons and glial cells. To simulate the axon, carbon fibers were placed at the bottom of the neuron-glial cell coculture dish, and were electrified with a single phase square wave current, 1×10^-2, 1×10^-3, 1×10^-4, and 1×10^-5 seconds, 1 Hz, 40 mV, and 10 μA, 30 minutes each, once a day for 10 consecutive days to simulate weak negative electric fields during action potential conduction. MAIN OUTCOME MEASURES： Glial cell growth and wrapping of carbon fibers were observed by phase contrast microscopy and immunohistochemistry. RESULTS： On culture day 7, cell groups were found to adhere to negative carbon fibers in the 1 × 10^-3 seconds square wave group. Cell membrane-like substances grew out of cell groups, wrapped the carbon fibers, and stretched to the ends of carbon fibers. Only some small and round cells close to negative carbon fibers were found on culture day 12. In the 1 × 10^-4 and 1 × 10^-3 seconds square wave groups, the negative carbon fibers were wrapped by oligodendrocytes or their progenitor cells. CONCLUSION： The local negative electric field which is generated by action potentials at 1×（10^-4-10^-3） seconds, 40 mV can directly initiate and participate in myelination in the central nervous system.

Effects of resonant magnetic perturbations on radial electric fields in DIII-D tokamak

Gyrokinetic simulations of DIII-D tokamak equilibrium find that resonant magnetic perturbation(RMP)drives a neoclassical non-ambipolar electron particle flux,which causes a rapid change of equilibrium radial electric fields consistent with experimental observations during the suppression of the edge localized mode(ELM).The simulation results provide a support for the conjecture that RMP-induced changes of radial electric fields lead to the enhanced turbulent transport at the pedestal top during the ELM suppression(Taimourzadeh et al 2019 Nucl.Fusion59046005).Furthermore,gyrokinetic simulations of collisionless damping of zonal flows show that resonant responses to the RMP decrease the residual level of the zonal flows and damp the geodesic acoustic mode.

SPONTANEOUS POLARIZATION AND THE DISTRIBUTION OF INTERNAL STRESS AND ELECTRIC FIELDS AROUND A TRIPLE POINT

In this article, distributions of internal stress and internal electric fields around a triple point of ferroelectric polycrystals generated by the spontaneous deformation and spontaneous polarization were investigated. It was found that when all three grains consist of a single domain, the internal stresses and the internal electric fields do not vanish. Though it may be determined according to the principle of energy, the spontaneous configuration will not be unique without involving other conditions due to the symmetry of the crystal structure.

Chemical Analysis of NO_x Removal Under Different Reduced Electric Fields

This work presents a chemical kinetic analysis of different species involved in nitrogen-oxygen mixed gas induced by stationary corona discharge at room temperature and atmospheric pressure.This study takes into account twenty different chemical species participating in one hundred and seventy selected chemical reactions.The reaction rate coefficients are taken from the literature,and the density is analyzed by the continuity equation without the diffusion term.A large number of investigations considered the removal of NOx showing the effects of N,O and O3 radicals.The aim of the present simulation is to complete these studies by analysing various plasma species under different reduced electric fields in the range of 100-200 Td（1 Td=10-21 V·m^2）.In particular,we analyze the time evolution of depopulation（10^-9-10^-3s）of NOx.We have found that the depopulation rate of NO and NO2 is substantially affected by the rise of reduced electric field as it grows from 100 Td to 200 Td.This allows us to ascertain the important role played by the reduced electric field.

Investigation of electric fields inside and outside a magnetised cold plasma sphere

Based on the scales transformation of electromagnetic theory, the analytical expressions of electric fields inside and outside a magnetised cold plasma sphere are presented by reforming the spherical electromagnetic parameter. The obtained results are in good agreement with that in the literature. The angle between the direction of inside field and that of outside field is derived. In S wave band, calculations for the effects induced by parameters of the inner field are established. Simulations show that the angle between incident field and the outside magnetic field influences the inner field remarkably. The inner field will increase as the electron density increases. The inner field varies with frequency nonlinearly. There is an angle between the inner field and the incident field, it changes nonlinearly with the frequency.

Liquid crystal model of vesicle deformation in alternating electric fields

Considering the effects of osmotic pressure, elastic bending, Maxwell pressure, surface tension, as well as flexo-electric and dielectric properties of phospholipid membrane, the shape equation for sphere vesicle in alternation （AC） electric field is derived based on the liquid crystal model by minimizing the free energy due to coupled mechanical and AC electrical fields. Besides the effect of elastic bending, the influence of osmotic pressure and surface tension on the frequency dependent behavior of vesicle membrane in AC electric field is also discussed. Our theoretical results for membrane deformation are consistent with corresponding experiments. The present model provides the possibility to further disclose the frequency-depended behavior of biological cells in the coupled AC electric and different mechanical fields.

Effective response in nonlinear spherical coated composites under external AC and DC electric fields

By using the perturbation method, effective nonlinear direct current （DC） and alternating current （AC） responses of nonlinear composites with spherical coated inclusions randomly embedded in a host medium are studied under the action of an external electric field Ea = E0 ＋ E1 sinωt ＋ E3 sin 3ωt with different amplitudes and frequencies. The local potentials of composites at all harmonics are given in the inclusion particles and the host regions. All effective nonlinear responses to composites and the relationship between the effective nonlinear responses at all harmonics are also deduced for the spherical coated inclusions in a dilute limit.

CALCULATION AND EXPERIMENTAL INVESTIGATION OF ELECTRIC FIELDS INDUCED BY ELECTRODES IN ELECTROSTATIC CHARGED POWDER SPRAYING TECHNIQUE

Electric fields induced by ring and pin electrodes in electrostatic charged powder sprayingtechnique are analysed. The fundamental formulae to deseribe these fields have been built up. Theseformulae could be used to design electrostatic charged podwer spraying system. The chargingeffectiveness of ring and pin electrode is experimentally investigated and compared each other. Theperformance of ring electrode is better than that of pin electrode.

Electrotaxis of alveolar epithelial cells in direct-current electric fields

Purpose:This study aims to elucidate the electrotaxis response of alveolar epithelial cells(AECs)in direct-current electric fields(EFs),explore the impact of EFs on the cell fate of AECs,and lay the foundation for future exploitation of EFs for the treatment of acute lung injury.Methods:AECs were extracted from rat lung tissues using magnetic-activated cell sorting.To elucidate the electrotaxis responses of AECs,different voltages of EFs(0,50,100,and 200 mV/mm)were applied to two types of AECs,respectively.Cell migrations were recorded and trajectories were pooled to better demonstrate cellular activities through graphs.Cell directionality was calculated as the cosine value of the angle formed by the EF vector and cell migration.To further demonstrate the impact of EFs on the pulmonary tissue,the human bronchial epithelial cells transformed with Ad12-SV402B(BEAS-2B cells)were obtained and experimented under the same conditions as AECs.To determine the influence on cell fate,cells underwent electric stimulation were collected to perform Western blot analysis.Results:The successful separation and culturing of AECs were confirmed through immunofluorescence staining.Compared with the control,AECs in EFs demonstrated a significant directionality in a voltage-dependent way.In general,type I alveolar epithelial cells migrated faster than type II alveolar epithelial cells,and under EFs,these two types of cells exhibited different response threshold.For type II alveolar epithelial cells,only EFs at 200 mV/mm resulted a significant difference to the velocity,whereas for,EFs at both 100 mV/mm and 200 mV/mm gave rise to a significant difference.Western blotting suggested that EFs led to an increased expression of a AKT and myeloid leukemia 1 and a decreased expression of Bcl-2-associated X protein and Bcl-2-like protein 11.Conclusion:EFs could guide and accelerate the directional migration of AECs and exert antiapoptotic effects,which indicated that EFs are important biophysical signals in the re-epithelialization of alveolar epithelium in lung injury.