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.

A Ventral Diverterless High Offset S-shaped Inlet at Transonic Speeds

An investigation on the ventral diverterless high offset S-shaped inlet is carried out at Mach numbers from 0.600 to 1.534, angles of attack from -4° to 9.4°, and yaw angles from 0° to 8°. Results indicate： （1） a large region of low total pressure exists at the lower part of the inlet exit caused by the counter-rotating vortices in the S-shaped duct; （2） the performances of the inlet at Mach number 1.000 reach almost the highest, so the propulsion system could work efficiently in terms of aerodynamics; （3） the total pressure recovery increases slowly at first and then remains unvaried as the Mach number rises from 0.6 to 1.0, however, it does in an opposite manner in the conventional diverter-equipped S-shaped inlet; （4） the performances of the inlet are generally insensitive to angles of attack from -4° to 9.4° and yaw angles from 0° to 8° at Mach number 0.850, and angles of attack from -2° to 6° and yaw angles from 0° to 5° at Mach number 1.534.

Numerical Investigation of Electrohydrodynamic (EHD) Flow Control in an S-Shaped Duct

An electrohydrodynamic （EHD） method, which is based on glow discharge plasma, is presented for flow control in an S-shaped duct. The research subject is an expanding channel with a constant width and a rectangular cross section. An equivalent divergence angle and basic function are introduced to build the three-dimensional model. Subsequently, the plasma physical models are simplified as the effects of electrical body force and work （done by the force） on the fluid near the wall. With the aid of FLUENT software, the source terms of momentum and energy are added to the Navier-Stokes equation. Finally, the original performance of three models （A, B and C） is studied, in which model A demonstrates better performance. Then EHD control based on model A is discussed. The results show that the EHD method is an effective way of reducing flow loss and improving uniformity at the duct exit. The innovation in this study is the assessment of the EHD control effect on the flow in an S-shaped duct. Both the parametric modeling of the S-shaped duct and the simplified models of plasma provide valuable information for future research on aircraft inlet ducts.

Incorporating S-shaped testing-effort functions into NHPP software reliability model with imperfect debugging

Testing-effort（TE） and imperfect debugging（ID） in the reliability modeling process may further improve the fitting and prediction results of software reliability growth models（SRGMs）. For describing the S-shaped varying trend of TE increasing rate more accurately, first, two S-shaped testing-effort functions（TEFs）, i.e.,delayed S-shaped TEF（DS-TEF） and inflected S-shaped TEF（IS-TEF）, are proposed. Then these two TEFs are incorporated into various types（exponential-type, delayed S-shaped and inflected S-shaped） of non-homogeneous Poisson process（NHPP）SRGMs with two forms of ID respectively for obtaining a series of new NHPP SRGMs which consider S-shaped TEFs as well as ID. Finally these new SRGMs and several comparison NHPP SRGMs are applied into four real failure data-sets respectively for investigating the fitting and prediction power of these new SRGMs.The experimental results show that：（i） the proposed IS-TEF is more suitable and flexible for describing the consumption of TE than the previous TEFs;（ii） incorporating TEFs into the inflected S-shaped NHPP SRGM may be more effective and appropriate compared with the exponential-type and the delayed S-shaped NHPP SRGMs;（iii） the inflected S-shaped NHPP SRGM considering both IS-TEF and ID yields the most accurate fitting and prediction results than the other comparison NHPP SRGMs.

Modeling behaviors of a coal pillar rib using the progressive S-shaped yield criterion

Spalling of pillar ribs has been a major hazard in the mining industry for decades.In the absence of rib support guidelines,accidents have continued to occur in recent years.Developing effective support guidelines requires a complete understanding of complex pillar damage mechanisms.Continuum models represent a convenient tool for analyzing this problem,but the behavior of such models is dependent of the choice of the constitutive model.In this study,a recently proposed constitutive model was used to simulate the rib fracturing process in a longwall chain pillar at West Cliff mine.After calibration,the model was able to capture the rib displacement profiles for multiple locations of the longwall face and the stress evolution 4 m into the pillar.The rib bolts in the model were found to be yielding over 60% of their length under the headgate loading condition.The model also predicted a steady damage accumulation in the rib for certain face locations,which is consistent with the description of the rib at the site.Damage was localized along the upper part of the pillar and underscored the role that the dirt band played in controlling rib deterioration at the site.The ability of the numerical model to replicate field measurements provides confidence in the capabilities of the new constitutive model.Finally,the need of using multi-point calibration is highlighted by comparing the results of the calibrated model to an alternative model calibrated to a smaller amount of data.

Analysis and Simulation of S-shaped Waveguide in Silicon-on-insulator

The simulation and analysis of S-shaped waveguide bend are presented.Bend radius larger than 30 mm assures less than 0.5 dB radiation loss for a 4-μm-wide silicon-on-insulator waveguide bend with 2-μm etch depth.Intersection angle greater than 20° provides negligible crosstalk (<-30 dB) and very low insertion loss.Any reduction in bend radius and intersection angle is at the cost of the degradation of characteristics of bent waveguide and intersecting waveguide, respectively.

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.

The Channel Branches & Network Vessels on the Tianhui Lacquered Meridian Figurine——Taking the Heart-Regulated Channel as an Example

Along with the surge of unearthed medical literature and cultural relics in recent years,a network of channels in the system of medical conduit vessels(meridians) during the early Western Han dynasty has become much clearer gradually.In it,the increasing number of channel branches,network vessels and needle insertion holes(acupoints) is an important feature of the development of channel medicine during the Western Han dynasty.This is not only a reflection of the expanding requirements of the theoretical system of the main trunk channels and other vessels,but also an inevitable result of the continuous enrichment and accumulation of clinical experience.This article integrates the information about channel branches,network vessels,inscriptions,dots and further relics on the Tianhui(天回) Lacquered Meridian Figurine to compare the unearthed literature of the channel genre with the transmitted classical literature about acupuncture.The “Heart-Regulated Channel” in Medical Manuscripts on Bamboo Slips from Tianhui(《天回医简》) serves as an example to explain the occurrence,development and changes of the channel branches and network vessels in the early system of medical channels.

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.

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.

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.

Enhancement of Characteristics of Antenna Arrays Employing S-Shaped Resonators

This paper illustrates a simple kind of tri-band printed G-shaped monopole antenna for Multiple-Input-Multiple-Output (MIMO) systems. The proposed antenna is used to achieve three operating frequencies, 2.45 GHz, 5.2 GHz and 8.2 GHz for wireless communications. To improve the isolation between the two radiating elements, we use left-handed materials composed of only S-shaped resonators to get negative refractive index at the three operating frequencies. When one layer of S-shaped resonators is employed, the antenna correlation, the diversity gain and the bandwidth are also enhanced. The simulated results are presented and evaluated with and without left-handed materials.

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.

Shaping ability of thermomechanically treated files in simulated S-shaped root canals

Aim: the aim of this study was to investigate the shaping ability of thermomechanically treated files manufactured by twisting(Twisted files)and compare it to conventional rotary system (K3, Sybron Endo, Orange, CA) in S-shaped canals, including formation of ledges, zipping, elbow, outer widening, danger zone, perforation and file deformation. Materials & Methods: Forty S-Shaped canals in resin blocks were randomly divided into 2 groups of 20 each. Pre-instrumentation images of the canals were taken via a digital camera and superimposed on images taken after preparation with TF and K3 systems to apical size of 25/06 and 30/06. Canal aberrations were measured from the superimposed image at five levels using AutoCAD system. Fisher exact test and Mann Whitney test were used for analysis of the data. Results: the incidence of zipping, elbow and apical transportation was significantly lower in the TF group (P = 0.04). Generally the incidence of aberration increased when the apical size increased to 30/0.06 regardless of the file system. Significant file deformation was evident in the TF after single use (P ? 0.001). Conclusion: Under the conditions of this study, TF manufactured by new technique performed better than K3 systems when used up to size 25/06 in simulated S-shaped canals. Clinical significance: The flexibility of thermomechanically treated files is beneficial in canals with multiple curvatures;however, attention should be paid to the instrument taper and final apical size of the preparation.

Identification of transient receptor potential channel genes and functional characterization of TRPA1 in Spodoptera frugiperda

Spodoptera frugiperda is a highly destructive pest that has become a global problem due to its robust reproductive and migratory capabilities.Transient receptor potential(TRP)channels,which constitute a vast ion channel family,play pivotal roles in sensing the external environment and maintaining internal homeostasis in insects.TRP channels have been widely investigated for their critical roles in regulating various insect behaviors in recent years.In this study,we identified 15 TRP gene loci encoding 26 transcripts in the genome of S.frugiperda and analyzed their expression profiles at different developmental stages.The results revealed that S.frugiperda possesses four TRPC genes,six TRPA genes,one TRPM gene,two TRPV genes,one TRPN gene,and one TRPML gene,while a canonical TRPP is absent.Moreover,the SfruTRPA1 was functionally characterized using the Xenopus oocyte expression system.The results showed that SfruTRPA1 is activated by temperature increases from 20 to 45℃,and there is no significant desensitization after repeated stimuli within the same temperature range.Additionally,SfruTRPA1 is activated by certain natural chemicals,including allyl isothiocyanate(AITC)and cinnamaldehyde(CA).These findings provide valuable insights to the TRP genes in S.frugiperda.

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.

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.

Analysis of the generation mechanism of the S-shaped J–V curves of MoS_(2)/Si-based solar cells

Amorphous–microcrystalline MoS_(2)thin films are fabricated using the sol-gel method to produce MoS_(2)/Si-based solar cells. The generation mechanisms of the S-shaped current density–voltage(J–V) curves of the solar cells are analyzed. To improve the performance of the solar cells and address the problem of the S-shaped J–V curve, a MoS_(2)film and a p^(+) layer are introduced into the front and back interfaces of the solar cell, respectively, which leads to the formation of a p–n junction between the p-Si and the MoS_(2)film as well as ohmic contacts between the MoS_(2)film and the ITO, improving the S-shaped J–V curve. As a result of the high doping characteristics and the high work function of the p^(+) layer, a high–low junction is formed between the p;and p layers along with ohmic contacts between the p;layer and the Ag electrode. Consequently,the S-shaped J–V curve is eliminated, and a significantly higher current density is achieved at a high voltage. The device exhibits ideal p–n junction rectification characteristics and achieves a high power-conversion efficiency(CE) of 7.55%. The findings of this study may improve the application of MoS_(2)thin films in silicon-based solar cells, which are expected to be widely used in various silicon-based electronic and optical devices.

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.