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.

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.

Influence of pore structure heterogeneity on channeling channels during hot water flooding in heavy oil reservoir based on CT scanning

Hot water flooding is an effective way to develop heavy oil reservoirs.However,local channeling channels may form,possibly leading to a low thermal utilization efficiency and high water cut in the reservoir.The pore structure heterogeneity is an important factor in forming these channels.This study proposes a method that mixes quartz sand with different particle sizes to prepare weakly heterogeneous and strongly heterogeneous models through which hot water flooding experiments are conducted.During the experiments,computer tomography(CT)scanning identifies the pore structure and micro remaining oil saturation distribution to analyze the influence of the pore structure heterogeneity on the channeling channels.The oil saturation reduction and average pore size are divided into three levels to quantitatively describe the relationship between the channeling channel distribution and pore structure heterogeneity.The zone where oil saturation reduction exceeds 20%is defined as a channeling channel.The scanning area is divided into 180 equally sized zones based on the CT scanning images,and threedimensional(3D)distributions of the channeling channels are developed.Four micro remaining oil distribution patterns are proposed,and the morphology characteristics of micro remaining oil inside and outside the channeling channels are analyzed.The results show that hot water flooding is more balanced in the weakly heterogeneous model,and the oil saturation decreases by more than 20%in most zones without narrow channeling channels forming.In the strongly heterogeneous model,hot water flooding is unbalanced,and three narrow channeling channels of different lengths form.In the weakly heterogeneous model,the oil saturation reduction is greater in zones with larger pores.The distribution range of the average pore size is larger in the strongly heterogeneous model.The network remaining oil inside the channeling channels is less than outside the channeling channels,and the hot water converts the network remaining oil into cluster,film,and droplet remaining oil.

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.

Dilation,discrimination and Uhlmann's theorem of link products of quantum channels

We establish the Stinespring dilation theorem of the link product of quantum channels in two different ways,discuss the discrimination of quantum channels,and show that the distinguishability can be improved by self-linking each quantum channel n times as n grows.We also find that the maximum value of Uhlmann's theorem can be achieved for diagonal channels.

Effective Capacity of URLLC over Parallel Fading Channels with Imperfect Channel State Information

This paper investigates the effective capacity of a point-to-point ultra-reliable low latency communication(URLLC)transmission over multiple parallel sub-channels at finite blocklength(FBL)with imperfect channel state information(CSI).Based on reasonable assumptions and approximations,we derive the effective capacity as a function of the pilot length,decoding error probability,transmit power and the sub-channel number.Then we reveal significant impact of the above parameters on the effective capacity.A closed-form lower bound of the effective capacity is derived and an alternating optimization based algorithm is proposed to find the optimal pilot length and decoding error probability.Simulation results validate our theoretical analysis and show that the closedform lower bound is very tight.In addition,through the simulations of the optimized effective capacity,insights for pilot length and decoding error probability optimization are provided to evaluate the optimal parameters in realistic systems.

Cooperative Covert Communication in Multi-Antenna Broadcast Channels

With the gradual popularization of 5G communications,the application of multi-antenna broadcasting technology has become widespread.Therefore,this study aims to investigate the wireless covert communication in the two-user cooperative multi-antenna broadcast channel.We focus on the issue that the deteriorated reliability and undetectability are mainly affected by the transmission power.To tackle this issue,we design a scheme based on beamforming to increase the reliability and undetectability of wireless covert communication in the multi-antenna broadcast channel.We first modeled and analyzed the cooperative multi-antenna broadcasting system,and put forward the target question.Then we use the SCA(successive convex approximation)algorithm to transform the target problem into a series of convex subproblems.Then the convex problems are solved and the covert channel capacity is calculated.In order to verify the effectiveness of the scheme,we conducted simulation verification.The simulation results show that the proposed beamforming scheme can effectively improve the reliability and undetectability of covert communication in multi-antenna broadcast channels.

A Deep Learning Based Broadcast Approach for Image Semantic Communication over Fading Channels

We consider an image semantic communication system in a time-varying fading Gaussian MIMO channel,with a finite number of channel states.A deep learning-aided broadcast approach scheme is proposed to benefit the adaptive semantic transmission in terms of different channel states.We combine the classic broadcast approach with the image transformer to implement this adaptive joint source and channel coding(JSCC)scheme.Specifically,we utilize the neural network(NN)to jointly optimize the hierarchical image compression and superposition code mapping within this scheme.The learned transformers and codebooks allow recovering of the image with an adaptive quality and low error rate at the receiver side,in each channel state.The simulation results exhibit our proposed scheme can dynamically adapt the coding to the current channel state and outperform some existing intelligent schemes with the fixed coding block.

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.

Cooperative activation of sodium channels for downgrading the energy efficiency in neuronal information processing

The Hodgkin–Huxley model assumes independent ion channel activation,although mutual interactions are common in biological systems.This raises the problem why neurons would favor independent over cooperative channel activation.In this study,we evaluate how cooperative activation of sodium channels affects the neuron’s information processing and energy consumption.Simulations of the stochastic Hodgkin–Huxley model with cooperative activation of sodium channels show that,while cooperative activation enhances neuronal information processing capacity,it greatly increases the neuron’s energy consumption.As a result,cooperative activation of sodium channel degrades the energy efficiency for neuronal information processing.This discovery improves our understanding of the design principles for neural systems,and may provide insights into future designs of the neuromorphic computing devices as well as systematic understanding of pathological mechanisms for neural diseases.

The variation in basal channels and basal melt rates of Pine Island Ice Shelf

In recent years,there has been a significant acceleration in the thinning,calving and retreat of the Pine Island Ice Shelf(PIIS).The basal channels,results of enhanced basal melting,have the potential to significantly impact the stability of the PIIS.In this study,we used a variety of remote sensing data,including Landsat,REMA DEM,ICESat-1 and ICESat-2 satellite altimetry observations,and Ice Bridge airborne measurements,to study the spatiotemporal changes in the basal channels from 2003 to 2020 and basal melt rate from 2010 to 2017 of the PIIS under the Eulerian framework.We found that the basal channels are highly developed in the PIIS,with a total length exceeding 450 km.Most of the basal channels are ocean-sourced or groundingline-sourced basal channels,caused by the rapid melting under the ice shelf or near the groundingline.A raised seabed prevented warm water intrusion into the eastern branch of the PIIS,resulting in a lower basal melt rate in that area.In contrast,a deepsea trough facilitates warm seawater into the mainstream and the western branch of the PIIS,resulting in a higher basal melt rate in the main-stream,and the surface elevation changes above the basal channels of the mainstream and western branch are more significant.The El Ni?o event in 2015–2016 possibly slowed down the basal melting of the PIIS by modulating wind field,surface sea temperature and depth seawater temperature.Ocean and atmospheric changes were driven by El Ni?o,which can further explain and confirm the changes in the basal melting of the PIIS.

Assessment of the Recent Hydromorphological Features of Nokoue Lake and Its Channels (South-East Benin)

Based on 2022 and 2023 hydrometric data and satellite images (Sentinel 2022, SPOT 2010), this study aims to present the Nokoué Lake and its channels’ re-cent hydromorphological characteristics. Integrating flow, tributary morphology, and topography data determined specific power values along the axes studied. The values obtained range from 2.69 to 12.92 W/m2 for Ouémé River and 2.46 to 10.99 W/m2 for Sô River. The resulting water erosion on banks and bottoms is of linear, areolar, or gully and claw types. Lake bathymetry varies from -0.5 to -2.6 m (low flow period) and -1 to -4 m;in the Ouémé, Sô, and Totchè rivers, it varies from -5 m to -7 m, reaching -10 m at the Cotonou channel entrance (flood period). Bathymetric profiles reveal varied “U”, “V” and “Intermediate” bottom morphologies, influenced by erosion/sedimentation processes and human activities. The flow facies identified are lentic in the northern tributaries and lotic in the Cotonou and Totchè canals. Spatial analysis identified nine (09) thematic classes. In 2022, the surface area of the water body has increased from 274 km2 at low water to 280 km2 at high water, whereas in 2010 (a recent year of exceptional flooding), the surface area was 270 km2 at low water and 277 km2 at high water. Significant changes in land use are observed between 2010 and 2022. The floodplain area decreased slightly, from 421 km2 in 2010 (year of exceptional flooding) to 419 km2 in 2022. The evolution of land use shows a progressive expansion of the urban environment to the detriment of the natural environment. In the medium to long term, this trend could threaten the hydromorphological balance and even the existence of this important lagoon ecosystem.

Temperature Drop of Molten Metals in Open Channels

The temperature drop of molten metal flowing in open channels is numerically determined. Rectangular, trapezoidal and triangular geometries are considered. The overall heat transfer coefficients for the bottom, side walls and free surface of the channel have been taken from the literature. For each geometry, the volumetric flow rate, mean residence time and temperature drop as a function of the channel inclination angle were determined. The rectangular and trapezoidal geometries present the smallest temperature drops, while the triangular geometry presents the greatest temperature drop. The factors that most affect this drop are the value of the free surface area of the channel, and the average residence time of the molten metal in the channel.

Differences of polygonal faults related to upper Miocene channels:a case study from the Beijiao sag of Qiongdongnan basin,South China Sea

Deep-water coarse-grained channels are embedded within a polygonal fault tier,and the polygonal faults(PFs)present non-polygonal geometries rather than classic polygonal geometry in plan view.However,PFs present differences when they encounter deep-water(coarse-grained vs.fine-grained)channels with different lithology,which has not been further studied to date.Three-dimensional(3D)seismic data and a drilling well from Beijiao sag of Qiongdongnanbasin,South China Sea were utilized to document the plan view and cross-sectional properties of the PFs and their differences and genetic mechanism were investigated.Results show that,first,PFs can be divided morphologically into channel-segmenting PFs and channel-bounding PFs in plan view.The former virtually cuts or segments the axes of channels in highand low-amplitudes,and the latter nearly parallels the boundaries of the channels.Both are approximately perpendicular to each other.Secondly,channel-bounding PFs that related to low-amplitude channels are much longer than those of high-amplitude ones;channel-segmenting PFs related to low-amplitude channels are slightly longer than the counterparts related to high-amplitude channels.Lastly,the magnitudes(e.g.,heights)of the PFs are proportional to the scales(e.g.,widths and heights)of low-amplitude channels,whereas the magnitudes of the PFs are inversely proportional to the scales of high amplitude channels.Coarse-grained(high amplitude)channels act as a mechanical barrier to the propagation of PFs,whereas fine-grained(low-amplitude)channels are beneficial to the propagation and nucleation of PFs.Additionally,the genetic mechanism of PFs is discussed and reckoned as combined geneses of gravitational spreading and overpressure hydrofracture.The differences of the PFs can be used to reasonably differentiate coarse-grained channels from fine-grained channels.This study provides new insights into understanding the different geometries of the PFs related to coarse-grained and fine-grained channels and their genetic mechanism.

Coupling ferromagnetic ordering electron transfer channels and surface reconstructed active species for spintronic electrocatalysis of water oxidation

Sluggish reaction kinetics of oxygen evolution reaction(OER), resulting from multistep proton-coupled electron transfer and spin constriction, limits overall efficiency for most reported catalysts. Herein, using modeled ZnFe_(2-x)Ni_xO_(4)(0 ≤ x ≤ 0.4) spinel oxides, we aim to develop better OER electrocatalyst through combining the construction of ferromagnetic(FM) ordering channels and generation of highly active reconstructed species. The number of symmetry-breaking Fe–O–Ni structure links to the formation of FM ordering electron transfer channels. Meanwhile, as the number of Ni^(3+)increases, more ligand holes are formed, beneficial for redirecting surface reconstruction. The electro-activated ZnFe_(1.6)Ni_(0.4)O_(4) shows the highest specific activity, which is 13 and 2.5 times higher than that of ZnFe_(2)O_(4) and unactivated ZnFe_(1.6)Ni_(0.4)O_(4), and even superior to the benchmark IrO_(2) under the overpotential of 350 mV. Applying external magnetic field can make electron spin more aligned, and the activity can be further improved to 39 times of ZnFe_(2)O_(4). We propose that intriguing FM exchange-field interaction at FM/paramagnetic interfaces can penetrate FM ordering channels into reconstructed oxyhydroxide layers, thereby activating oxyhydroxide layers as spin-filter to accelerate spin-selective electron transfer. This work provides a new guideline to develop highly efficient spintronic catalysts for water oxidation and other spin-forbidden reactions.

Multi-Sinusoidal Waveform Shaping for Integrated Data and Energy Transfer in Aging Channels

Integrated data and energy transfer(IDET)is capable of simultaneously delivering on-demand data and energy to low-power Internet of Everything(Io E)devices.We propose a multi-carrier IDET transceiver relying on superposition waveforms consisting of multi-sinusoidal signals for wireless energy transfer(WET)and orthogonal-frequency-divisionmultiplexing(OFDM)signals for wireless data transfer(WDT).The outdated channel state information(CSI)in aging channels is employed by the transmitter to shape IDET waveforms.With the constraints of transmission power and WDT requirement,the amplitudes and phases of the IDET waveform at the transmitter and the power splitter at the receiver are jointly optimised for maximising the average directcurrent(DC)among a limited number of transmission frames with the existence of carrier-frequencyoffset(CFO).For the amplitude optimisation,the original non-convex problem can be transformed into a reversed geometric programming problem,then it can be effectively solved with existing tools.As for the phase optimisation,the artificial bee colony(ABC)algorithm is invoked in order to deal with the nonconvexity.Iteration between the amplitude optimisation and phase optimisation yields our joint design.Numerical results demonstrate the advantage of our joint design for the IDET waveform shaping with the existence of the CFO and the outdated CSI.

An improved ISR-WV rumor propagation model based on multichannels with time delay and pulse vaccination

The rapid development of the Internet has broadened the channels of dissemination of information,it has also led to the rapid and widespread propagation of rumors,which can have a serious negative impact socially.In this paper,an improved ISR-WV rumor propagation model integrating multichannels is proposed by considering the system’s time delay,and the influence of different channels of propagation on the dynamic process is further analyzed.Moreover,the basic reproduction number R0,rumor-free equilibrium,and rumor-prevailing equilibrium,as well as their stability,are deduced.Then,an optimal control problem with pulse vaccination is designed.Finally,the validity of the model and theoretical results is verified by numerical simulations and a practical application.The results show that the rumor propagation threshold R0 is more sensitive to the rate of the propagation of the information base channel.The shorter the thinking timeτ_(1)required for the ignorant to react after obtaining the information,the larger the final scale of propagation.Under this condition,the time delayτ_(2)spent by a spreader in producing a video is negatively related to the final scale of the propagation;conversely,a longerτ_(1)implies that the person tends to more cognizant,which can suppress the spread of rumors.Under this condition,τ_(2)has little effect on the final scale of propagation.In addition,the results also prove that timely implementation of the pulse vaccination control strategy of popular science education can effectively control the propagation of rumors and reduce their negative impact.

Morphological evolution and flow conduction characteristics of fracture channels in fractured sandstone under cyclic loading and unloading

In coal mining,rock strata are fractured under cyclic loading and unloading to form fracture channels.Fracture channels are the main flow narrows for gas.Therefore,expounding the flow conductivity of fracture channels in rocks on fluids is significant for gas flow in rock strata.In this regard,graded incremental cyclic loading and unloading experiments were conducted on sandstones with different initial stress levels.Then,the three-dimensional models for fracture channels in sandstones were established.Finally,the fracture channel percentages were used to reflect the flow conductivity of fracture channels.The study revealed how the particle size distribution of fractured sandstone affects the formation and expansion of fracture channels.It was found that a smaller proportion of large blocks and a higher proportion of small blocks after sandstone fails contribute more to the formation of fracture channels.The proportion of fracture channels in fractured rock can indicate the flow conductivity of those channels.When the proportion of fracture channels varies gently,fluids flow evenly through those channels.However,if the proportion of fracture channels varies significantly,it can greatly affect the flow rate of fluids.The research results contribute to revealing the morphological evolution and flow conductivity of fracture channels in sandstone and then provide a theoretical basis for clarifying the gas flow pattern in the rock strata of coal mines.

Modulation Recognition with Frequency Offset and Phase Offset over Multipath Channels

Modulation recognition becomes unreliable at low signal-to-noise ratio(SNR)over fading channel.A novel method is proposed to recognize the digital modulated signals with frequency and phase offsets over multi-path fading channels in this paper.This method can overcome the effects of phase offset,Gaussian noise and multi-path fading.To achieve this,firstly,the characteristic parameters search is constructed based on the cyclostationarity of received signals,to overcome the phase offset,Gaussian white noise,and influence caused by multi-path fading.Then,the carrier frequency of the received signal is estimated,and the maximum characteristic parameter is searched around the integer multiple carriers and their vicinities.Finally,the modulation types of the received signal with frequency and phase offsets are classified using decision thresholds.Simulation results demonstrate that the performance of the proposed method is better than the traditional methods when SNR is over 5dB,and that the proposed method is robust to frequency and phase offsets over multipath channels.

Diabetes-induced changes in cardiac voltage-gated ion channels

Diabetes mellitus affects the heart through various mechanisms such as microvascular defects,metabolic abnormalities,autonomic dysfunction and incompatible immune response.Furthermore,it can also cause functional and structural changes in the myocardium by a disease known as diabetic cardiomyopathy(DCM)in the absence of coronary artery disease.As DCM progresses it causes electrical remodeling of the heart,left ventricular dysfunction and heart failure.Electrophysiological changes in the diabetic heart contribute significantly to the incidence of arrhythmias and sudden cardiac death in diabetes mellitus patients.In recent studies,significant changes in repolarizing K+currents,Na+currents and L-type Ca^(2+)currents along with impaired Ca^(2+ )homeostasis and defective contractile function have been identified in the diabetic heart.In addition,insulin levels and other trophic factors change significantly to maintain the ionic channel expression in diabetic patients.There are many diagnostic tools and management options for DCM,but it is difficult to detect its development and to effectively prevent its progress.In this review,diabetes-associated alterations in voltage-sensitive cardiac ion channels are comprehensively assessed to understand their potential role in the pathophysiology and pathogenesis of DCM.