神经元限制性沉默因子REST/NRSF参与调控癫痫作用及机制研究

目的探究神经元限制性沉默因子(REST/NRSF)参与调控癫痫作用及分子机制。方法采用免疫组织化学染色、免疫荧光、Western blot和qPCR检测癫痫患者病灶组织和海人藻酸(kainic acid,KA)癫痫小鼠海马脑区REST/NRSF表达水平的变化;采用病毒注射,脑电图记录和行为学方法检测在海马CA1区分别敲低或过表达REST/NRSF后对小鼠癫痫发作的影响。结果癫痫患者病灶REST/NRSF表达水平相对于脑外伤患者脑组织明显升高;KA模型组小鼠海马CA1区REST/NRSF蛋白和mRNA水平均明显升高,Kv7.2、Kv7.3钾通道mRNA表达水平明显下调;脑内注射NMDA兴奋海马脑区小鼠REST/NRSF表达水平明显上调;海马CA1区敲低REST/NRSF明显升高Kv7.2、Kv7.3钾通道mRNA表达水平,明显降低小鼠脑电图棘波、尖波发放频率以及癫痫发作等级;海马CA1区过表达REST/NRSF明显降低Kv7.2、Kv7.3钾通道mRNA表达水平,明显升高小鼠棘波、尖波发放频率,癫痫症状明显加重。结论小鼠海马脑区REST/NRSF通过转录调控Kv7.2、Kv7.3钾通道参与癫痫疾病发生发展。

Piezo1 channel exaggerates ferroptosis of nucleus pulposus cells by mediating mechanical stress-induced iron influx

To date,several molecules have been found to facilitate iron influx,while the types of iron influx channels remain to be elucidated.Here,Piezo1 channel was identified as a key iron transporter in response to mechanical stress.Piezo1-mediated iron overload disturbed iron metabolism and exaggerated ferroptosis in nucleus pulposus cells(NPCs).Importantly,Piezo1-induced iron influx was independent of the transferrin receptor(TFRC),a well-recognized iron gatekeeper.Furthermore,pharmacological inactivation of Piezo1 profoundly reduced iron accumulation,alleviated mitochondrial ROS,and suppressed ferroptotic alterations in stimulation of mechanical stress.Moreover,conditional knockout of Piezo1(Col2a1-CreERT Piezo1^(flox/flox))attenuated the mechanical injury-induced intervertebral disc degeneration(IVDD).Notably,the protective effect of Piezo1 deficiency in IVDD was dampened in Piezo1/Gpx4 conditional double knockout(cDKO)mice(Col2a1-CreERT Piezo1^(flox/flox)/Gpx4^(flox/flox)).These findings suggest that Piezo1 is a potential determinant of iron influx,indicating that the Piezo1-iron-ferroptosis axis might shed light on the treatment of mechanical stress-induced diseases.

Lithium-Ion Charged Polymer Channels Flattening Lithium Metal Anode

The concentration difference in the near-surface region of lithium metal is the main cause of lithium dendrite growth.Resolving this issue will be key to achieving high-performance lithium metal batteries(LMBs).Herein,we construct a lithium nitrate(LiNO_(3))-implanted electroactiveβphase polyvinylidene fluoride-co-hexafluoropropylene(PVDF-HFP)crystalline polymorph layer(PHL).The electronegatively charged polymer chains attain lithium ions on the surface to form lithium-ion charged channels.These channels act as reservoirs to sustainably release Li ions to recompense the ionic flux of electrolytes,decreasing the growth of lithium dendrites.The stretched molecular channels can also accelerate the transport of Li ions.The combined effects enable a high Coulombic efficiency of 97.0%for 250 cycles in lithium(Li)||copper(Cu)cell and a stable symmetric plating/stripping behavior over 2000 h at 3 mA cm^(-2)with ultrahigh Li utilization of 50%.Furthermore,the full cell coupled with PHL-Cu@Li anode and Li Fe PO_(4) cathode exhibits long-term cycle stability with high-capacity retention of 95.9%after 900 cycles.Impressively,the full cell paired with LiNi_(0.87)Co_(0.1)Mn_(0.03)O_(2)maintains a discharge capacity of 170.0 mAh g^(-1)with a capacity retention of 84.3%after 100 cycles even under harsh condition of ultralow N/P ratio of 0.83.This facile strategy will widen the potential application of LiNO_(3)in ester-based electrolyte for practical high-voltage LMBs.

Na^(+)/K^(+)-ATPase:ion pump,signal transducer,or cytoprotective protein,and novel biological functions

Na^(+)/K^(+)-ATPase is a transmembrane protein that has important roles in the maintenance of electrochemical gradients across cell membranes by transporting three Na^(+)out of and two K^(+)into cells.Additionally,Na^(+)/K^(+)-ATPase participates in Ca^(2+)-signaling transduction and neurotransmitter release by coordinating the ion concentration gradient across the cell membrane.Na^(+)/K^(+)-ATPase works synergistically with multiple ion channels in the cell membrane to form a dynamic network of ion homeostatic regulation and affects cellular communication by regulating chemical signals and the ion balance among different types of cells.Therefo re,it is not surprising that Na^(+)/K^(+)-ATPase dysfunction has emerged as a risk factor for a variety of neurological diseases.However,published studies have so far only elucidated the important roles of Na^(+)/K^(+)-ATPase dysfunction in disease development,and we are lacking detailed mechanisms to clarify how Na^(+)/K^(+)-ATPase affects cell function.Our recent studies revealed that membrane loss of Na^(+)/K^(+)-ATPase is a key mechanism in many neurological disorders,particularly stroke and Parkinson's disease.Stabilization of plasma membrane Na^(+)/K^(+)-ATPase with an antibody is a novel strategy to treat these diseases.For this reason,Na^(+)/K^(+)-ATPase acts not only as a simple ion pump but also as a sensor/regulator or cytoprotective protein,participating in signal transduction such as neuronal autophagy and apoptosis,and glial cell migration.Thus,the present review attempts to summarize the novel biological functions of Na^(+)/K^(+)-ATPase and Na^(+)/K^(+)-ATPase-related pathogenesis.The potential for novel strategies to treat Na^(+)/K^(+)-ATPase-related brain diseases will also be discussed.

Influence of variable viscosity and double diffusion on the convective stability of a nanofluid flow in an inclined porous channel

The influence of variable viscosity and double diffusion on the convective stability of a nanofluid flow in an inclined porous channel is investigated.The DarcyBrinkman model is used to characterize the fluid flow dynamics in porous materials.The analytical solutions are obtained for the unidirectional and completely developed flow.Based on a normal mode analysis,the generalized eigenvalue problem under a perturbed state is solved.The eigenvalue problem is then solved by the spectral method.Finally,the critical Rayleigh number with the corresponding wavenumber is evaluated at the assigned values of the other flow-governing parameters.The results show that increasing the Darcy number,the Lewis number,the Dufour parameter,or the Soret parameter increases the stability of the system,whereas increasing the inclination angle of the channel destabilizes the flow.Besides,the flow is the most unstable when the channel is vertically oriented.

Two-Staged Method for Ice Channel Identification Based on Image Segmentation and Corner Point Regression

Identification of the ice channel is the basic technology for developing intelligent ships in ice-covered waters,which is important to ensure the safety and economy of navigation.In the Arctic,merchant ships with low ice class often navigate in channels opened up by icebreakers.Navigation in the ice channel often depends on good maneuverability skills and abundant experience from the captain to a large extent.The ship may get stuck if steered into ice fields off the channel.Under this circumstance,it is very important to study how to identify the boundary lines of ice channels with a reliable method.In this paper,a two-staged ice channel identification method is developed based on image segmentation and corner point regression.The first stage employs the image segmentation method to extract channel regions.In the second stage,an intelligent corner regression network is proposed to extract the channel boundary lines from the channel region.A non-intelligent angle-based filtering and clustering method is proposed and compared with corner point regression network.The training and evaluation of the segmentation method and corner regression network are carried out on the synthetic and real ice channel dataset.The evaluation results show that the accuracy of the method using the corner point regression network in the second stage is achieved as high as 73.33%on the synthetic ice channel dataset and 70.66%on the real ice channel dataset,and the processing speed can reach up to 14.58frames per second.

Channel Correlation Based User Grouping Algorithm for Nonlinear Precoding Satellite Communication System

Low Earth Orbit(LEO)multibeam satellites will be widely used in the next generation of satellite communication systems,whose inter-beam interference will inevitably limit the performance of the whole system.Nonlinear precoding such as Tomlinson-Harashima precoding(THP)algorithm has been proved to be a promising technology to solve this problem,which has smaller noise amplification effect compared with linear precoding.However,the similarity of different user channels(defined as channel correlation)will degrade the performance of THP algorithm.In this paper,we qualitatively analyze the inter-beam interference in the whole process of LEO satellite over a specific coverage area,and the impact of channel correlation on Signal-to-Noise Ratio(SNR)of receivers when THP is applied.One user grouping algorithm is proposed based on the analysis of channel correlation,which could decrease the number of users with high channel correlation in each precoding group,thus improve the performance of THP.Furthermore,our algorithm is designed under the premise of co-frequency deployment and orthogonal frequency division multiplexing(OFDM),which leads to more users under severe inter-beam interference compared to the existing research on geostationary orbit satellites broadcasting systems.Simulation results show that the proposed user grouping algorithm possesses higher channel capacity and better bit error rate(BER)performance in high SNR conditions relative to existing works.

Deep learning for joint channel estimation and feedback in massive MIMO systems

The great potentials of massive Multiple-Input Multiple-Output(MIMO)in Frequency Division Duplex(FDD)mode can be fully exploited when the downlink Channel State Information(CSI)is available at base stations.However,the accurate CsI is difficult to obtain due to the large amount of feedback overhead caused by massive antennas.In this paper,we propose a deep learning based joint channel estimation and feedback framework,which comprehensively realizes the estimation,compression,and reconstruction of downlink channels in FDD massive MIMO systems.Two networks are constructed to perform estimation and feedback explicitly and implicitly.The explicit network adopts a multi-Signal-to-Noise-Ratios(SNRs)technique to obtain a single trained channel estimation subnet that works well with different SNRs and employs a deep residual network to reconstruct the channels,while the implicit network directly compresses pilots and sends them back to reduce network parameters.Quantization module is also designed to generate data-bearing bitstreams.Simulation results show that the two proposed networks exhibit excellent performance of reconstruction and are robust to different environments and quantization errors.

Cascaded ELM-Based Joint Frame Synchronization and Channel Estimation over Rician Fading Channel with Hardware Imperfections

Due to the interdependency of frame synchronization(FS)and channel estimation(CE),joint FS and CE(JFSCE)schemes are proposed to enhance their functionalities and therefore boost the overall performance of wireless communication systems.Although traditional JFSCE schemes alleviate the influence between FS and CE,they show deficiencies in dealing with hardware imperfection(HI)and deterministic line-of-sight(LOS)path.To tackle this challenge,we proposed a cascaded ELM-based JFSCE to alleviate the influence of HI in the scenario of the Rician fading channel.Specifically,the conventional JFSCE method is first employed to extract the initial features,and thus forms the non-Neural Network(NN)solutions for FS and CE,respectively.Then,the ELMbased networks,named FS-NET and CE-NET,are cascaded to capture the NN solutions of FS and CE.Simulation and analysis results show that,compared with the conventional JFSCE methods,the proposed cascaded ELM-based JFSCE significantly reduces the error probability of FS and the normalized mean square error(NMSE)of CE,even against the impacts of parameter variations.

Research progress on the water vapor channel within the Yarlung Zsangbo Grand Canyon, China

The Second Tibetan Plateau Scientific Expedition and Research Program tasked a research team with the“Investigation of the water vapor channel of the Yarlung Zsangbo Grand Canyon(INVC)”in the southeastern Tibetan Plateau(TP).This paper summarizes the scientific achievements obtained from the data collected by the INVC observation network and highlights the progress in investigating the development of heavy rainfall events associated with water vapor changes.The rain gauge network of the INVC can represent the impacts of the Yarlung Zsangbo Grand Canyon(YGC)topography on precipitation at the hourly scale.The microphysical characteristics of the precipitation in the YGC are different than those in the lowland area.The GPM-IMERG(Integrated MultisatellitE Retrievals for Global Precipitation Measurement)satellite precipitation data for the YGC region should be calibrated before they are used.The meridional water vapor flux through the YGC is more important than the zonal flux for the precipitation over the southeastern TP.The decreased precipitation around the YGC region is partly due to the decreased meridional water vapor flux passing through the YGC.High-resolution numerical models can benefit precipitation forecasting in this region by using a combination of specific schemes that capture the valley wind and water vapor flux along the valley floor.

Transient receptor potential channels as predictive marker and potential indicator of chemoresistance in colon cancer

Transient receptor potential(TRP)channels are strongly associated with colon cancer development and progression.This study leveraged a multivariate Cox regression model on publicly available datasets to construct a TRP channels-associated gene signature,with further validation of signature in real world samples from our hospital treated patient samples.Kaplan-Meier(K-M)survival analysis and receiver operating characteristic(ROC)curves were employed to evaluate this gene signature’s predictive accuracy and robustness in both training and testing cohorts,respectively.Additionally,the study utilized the CIBERSORT algorithm and single-sample gene set enrichment analysis to explore the signature’s immune infiltration landscape and underlying functional implications.The support vector machine algorithm was applied to evaluate the signature’s potential in predicting chemotherapy outcomes.The findings unveiled a novel three TRP channels-related gene signature(MCOLN1,TRPM5,and TRPV4)in colon adenocarcinoma(COAD).The ROC and K-M survival curves in the training dataset(AUC=0.761;p=1.58e-05)and testing dataset(AUC=0.699;p=0.004)showed the signature’s robust predictive capability for the overall survival of COAD patients.Analysis of the immune infiltration landscape associated with the signature revealed higher immune infiltration,especially an increased presence of M2 macrophages,in high-risk group patients compared to their low-risk counterparts.High-risk score patients also exhibited potential responsiveness to immune checkpoint inhibitor therapy,evident through increased CD86 and PD-1 expression profiles.Moreover,the TRPM5 gene within the signature was highly expressed in the chemoresistance group(p=0.00095)and associated with poor prognosis(p=0.036)in COAD patients,highlighting its role as a hub gene of chemoresistance.Ultimately,this signature emerged as an independent prognosis factor for COAD patients(p=6.48e-06)and expression of model gene are validated by public data and real-world patients.Overall,this bioinformatics study provides valuable insights into the prognostic implications and potential chemotherapy resistance mechanisms associated with TRPs-related genes in colon cancer.

Cooperative Anti-Jamming and Interference Mitigation for UAV Networks: A Local Altruistic Game Approach

To improve the anti-jamming and interference mitigation ability of the UAV-aided communication systems, this paper investigates the channel selection optimization problem in face of both internal mutual interference and external malicious jamming. A cooperative anti-jamming and interference mitigation method based on local altruistic is proposed to optimize UAVs’ channel selection. Specifically, a Stackelberg game is modeled to formulate the confrontation relationship between UAVs and the jammer. A local altruistic game is modeled with each UAV considering the utilities of both itself and other UAVs. A distributed cooperative anti-jamming and interference mitigation algorithm is proposed to obtain the Stackelberg equilibrium. Finally, the convergence of the proposed algorithm and the impact of the transmission power on the system loss value are analyzed, and the anti-jamming performance of the proposed algorithm can be improved by around 64% compared with the existing algorithms.

High-Precision Doppler Frequency Estimation Based Positioning Using OTFS Modulations by Red and Blue Frequency Shift Discriminator

Orthogonal Time Frequency and Space(OTFS) modulation is expected to provide high-speed and ultra-reliable communications for emerging mobile applications, including low-orbit satellite communications. Using the Doppler frequency for positioning is a promising research direction on communication and navigation integration. To tackle the high Doppler frequency and low signal-to-noise ratio(SNR) in satellite communication, this paper proposes a Red and Blue Frequency Shift Discriminator(RBFSD) based on the pseudo-noise(PN) sequence.The paper derives that the cross-correlation function on the Doppler domain exhibits the characteristic of a Sinc function. Therefore, it applies modulation onto the Delay-Doppler domain using PN sequence and adjusts Doppler frequency estimation by red-shifting or blue-shifting. Simulation results show that the performance of Doppler frequency estimation is close to the Cramér-Rao Lower Bound when the SNR is greater than -15dB. The proposed algorithm is about 1/D times less complex than the existing PN pilot sequence algorithm, where D is the resolution of the fractional Doppler.

Cav3.2 channel regulates cerebral ischemia/reperfusion injury:a promising target for intervention

Calcium influx into neurons triggers neuronal death during cerebral ischemia/reperfusion injury.Various calcium channels are involved in cerebral ischemia/reperfusion injury.Cav3.2 channel is a main subtype of T-type calcium channels.T-type calcium channel blockers,such as pimozide and mibefradil,have been shown to prevent cerebral ischemia/reperfusion injury-induced brain injury.However,the role of Cav3.2 channels in cerebral ischemia/reperfusion injury remains unclear.Here,in vitro and in vivo models of cerebral ischemia/reperfusion injury were established using middle cerebral artery occlusion in mice and high glucose hypoxia/reoxygenation exposure in primary hippocampal neurons.The results showed that Cav3.2 expression was significantly upregulated in injured hippocampal tissue and primary hippocampal neurons.We further established a Cav3.2 gene-knockout mouse model of cerebral ischemia/reperfusion injury.Cav3.2 knockout markedly reduced infarct volume and brain water content,and alleviated neurological dysfunction after cerebral ischemia/reperfusion injury.Additionally,Cav3.2 knockout attenuated cerebral ischemia/reperfusion injury-induced oxidative stress,inflammatory response,and neuronal apoptosis.In the hippocampus of Cav3.2-knockout mice,calcineurin overexpression offset the beneficial effect of Cav3.2 knockout after cerebral ischemia/reperfusion injury.These findings suggest that the neuroprotective function of Cav3.2 knockout is mediated by calcineurin/nuclear factor of activated T cells 3 signaling.Findings from this study suggest that Cav3.2 could be a promising target for treatment of cerebral ischemia/reperfusion injury.

Statistical Channel Modeling for Indoor VLC Communications Based on Channel Measurements

Visible light communication(VLC)has attracted much attention in the research of sixthgeneration(6G)systems.Furthermore,channel modeling is the foundation for designing efficient and robust VLC systems.In this paper,we present extensive VLC channel measurement campaigns in indoor environments,i.e.,an office and a corridor.Based on the measured data,the large-scale fading characteristics and multipath-related characteristics,including omnidirectional optical path loss(OPL),K-factor,power angular spectrum(PAS),angle spread(AS),and clustering characteristics,are analyzed and modeled through a statistical method.Based on the extracted statistics of the above-mentioned channel characteristics,we propose a statistical spatial channel model(SSCM)capable of modeling multipath in the spatial domain.Furthermore,the simulated statistics of the proposed model are compared with the measured statistics.For instance,in the office,the simulated path loss exponent(PLE)and the measured PLE are 1.96and 1.97,respectively.And,the simulated medians of AS and measured medians of AS are 25.94°and 24.84°,respectively.Generally,the fact that the simulated results fit well with measured results has demonstrated the accuracy of our SSCM.

A Correlation-Based Stochastic Model for Massive MIMO Channel

In this paper,the channel impulse response matrix(CIRM)can be expressed as a sum of couplings between the steering vectors at the base station(BS)and the eigenbases at the mobile station(MS).Nakagami distribution was used to describe the fading of the coupling between the steering vectors and the eigenbases.Extensive measurements were carried out to evaluate the performance of this proposed model.Furthermore,the physical implications of this model were illustrated and the capacities are analyzed.In addition,the azimuthal power spectrum(APS)of several models was analyzed.Finally,the channel hardening effect was simulated and discussed.Results showed that the proposed model provides a better fit to the measured results than the other CBSM,i.e.,Weichselberger model.Moreover,the proposed model can provide better tradeoff between accuracy and complexity in channel synthesis.This CIRM model can be used for massive MIMO design in the future communication system design.

Potassium and calcium channels in different nerve cells act as therapeutic targets in neurological disorders

The central nervous system, information integration center of the body, is mainly composed of neurons and glial cells. The neuron is one of the most basic and important structural and functional units of the central nervous system, with sensory stimulation and excitation conduction functions. Astrocytes and microglia belong to the glial cell family, which is the main source of cytokines and represents the main defense system of the central nervous system. Nerve cells undergo neurotransmission or gliotransmission, which regulates neuronal activity via the ion channels, receptors, or transporters expressed on nerve cell membranes. Ion channels, composed of large transmembrane proteins, play crucial roles in maintaining nerve cell homeostasis. These channels are also important for control of the membrane potential and in the secretion of neurotransmitters. A variety of cellular functions and life activities, including functional regulation of the central nervous system, the generation and conduction of nerve excitation, the occurrence of receptor potential, heart pulsation, smooth muscle peristalsis, skeletal muscle contraction, and hormone secretion, are closely related to ion channels associated with passive transmembrane transport. Two types of ion channels in the central nervous system, potassium channels and calcium channels, are closely related to various neurological disorders, including Alzheimer's disease, Parkinson's disease, and epilepsy. Accordingly, various drugs that can affect these ion channels have been explored deeply to provide new directions for the treatment of these neurological disorders. In this review, we focus on the functions of potassium and calcium ion channels in different nerve cells and their involvement in neurological disorders such as Parkinson's disease, Alzheimer's disease, depression, epilepsy, autism, and rare disorders. We also describe several clinical drugs that target potassium or calcium channels in nerve cells and could be used to treat these disorders. We concluded that there are few clinical drugs that can improve the pathology these diseases by acting on potassium or calcium ions. Although a few novel ion-channelspecific modulators have been discovered, meaningful therapies have largely not yet been realized. The lack of target-specific drugs, their requirement to cross the blood–brain barrier, and their exact underlying mechanisms all need further attention. This review aims to explain the urgent problems that need research progress and provide comprehensive information aiming to arouse the research community's interest in the development of ion channel-targeting drugs and the identification of new therapeutic targets for that can increase the cure rate of nervous system diseases and reduce the occurrence of adverse reactions in other systems.

Artificial Intelligence Based Multi-Scenario mmWave Channel Modeling for Intelligent High-Speed Train Communications

A large amount of mobile data from growing high-speed train(HST)users makes intelligent HST communications enter the era of big data.The corresponding artificial intelligence(AI)based HST channel modeling becomes a trend.This paper provides AI based channel characteristic prediction and scenario classification model for millimeter wave(mmWave)HST communications.Firstly,the ray tracing method verified by measurement data is applied to reconstruct four representative HST scenarios.By setting the positions of transmitter(Tx),receiver(Rx),and other parameters,the multi-scenarios wireless channel big data is acquired.Then,based on the obtained channel database,radial basis function neural network(RBF-NN)and back propagation neural network(BP-NN)are trained for channel characteristic prediction and scenario classification.Finally,the channel characteristic prediction and scenario classification capabilities of the network are evaluated by calculating the root mean square error(RMSE).The results show that RBF-NN can generally achieve better performance than BP-NN,and is more applicable to prediction of HST scenarios.

A Probing Model of Secret Key Generation Based on Channel Autocorrelation Function

Secret key generation(SKG)is a promising solution to the problem of wireless communications security.As the first step of SKG,channel probing affects it significantly.Although there have been some probing schemes,there is a lack of research on the optimization of the probing process.This study investigates how to optimize correlated parameters to maximize the SKG rate(SKGR)in the time-division duplex(TDD)mode.First,we build a probing model which includes the effects of transmitting power,the probing period,and the dimension of sample vectors.Based on the model,the analytical expression of the SKGR is given.Next,we formulate an optimization problem for maximizing the SKGR and give an algorithm to solve it.We conclude the SKGR monotonically increases as the transmitting power increases.Relevant mathematical proofs are given in this study.From the simulation results,increasing appropriately the probing period and the dimension of the sample vector could increase the SKGR dramatically compared to a yardstick,which indicates the importance of optimizing the parameters related to the channel probing phase.

Multi-User Semantic Fusion for Semantic Communications over Degraded Broadcast Channels

Degraded broadcast channels(DBC) are a typical multiuser communication scenario, Semantic communications over DBC still lack in-depth research. In this paper, we design a semantic communications approach based on multi-user semantic fusion for wireless image transmission over DBC. The transmitter extracts semantic features for two users separately and then effectively fuses them for broadcasting by leveraging semantic similarity. Unlike traditional allocation of time, power, or bandwidth, the semantic fusion scheme can dynamically control the weight of the semantic features of the two users to balance their performance. Considering the different channel state information(CSI) of both users over DBC,a DBC-Aware method is developed that embeds the CSI of both users into the joint source-channel coding encoder and fusion module to adapt to the channel.Experimental results show that the proposed system outperforms the traditional broadcasting schemes.