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.

Screening of Extracellular Binding Proteins of Rice Receptor-like Kinase CR4 by the Yeast Two-hybrid

[Objective] The research aimed to find the extracellular binding proteins of CR4.[Method] The extracellular domain of OsCR4 was as the bait protein,and the yeast two-hybrid was used to screen cDNA library of seedling which was cultivated 14 d.[Result] A lot of proteins which included a peroxide B（D26484）,a methionine thioredoxin reductase（ABF96078）and an unknown function protein were gained.[Conclusion] It provided the theory basis for studying the signal transduction mechanism of CR4.

Cloning and Hybrid Identification of Banana Receptor-like Protein Kinase Gene

[Objective] This study aimed to clone and identify the banana fruit receptor-like protein kinase gene.[Method] The cDNA phage libraries of banana fruit were adopted as the experimental materials to screen positive phage libraries of banana receptor-like protein kinase gene;cloning and sequence analysis of the gene were conducted,and the banana receptor-like protein kinase gene was identified by using in situ hybridization method.[Result] In this study,a 1 698 bp long banana receptor-like protein kinase gene was cloned from banana fruit,encoding 563 amino acids.Southern hybridization result confirmed that the banana receptor-like protein kinase gene was a multiple-copy gene from banana genome.[Conclusion] The study laid the foundation for further investigating the functions of banana receptor-like protein kinase gene in fruit.

The wheat receptor-like cytoplasmic kinase TaRLCK1B is required for host immune response to the necrotrophic pathogen Rhizoctonia cerealis

Receptor-like cytoplasmic kinases(RLCKs)represent a large family of proteins in plants.In Arabidopsis and rice,several RLCKs in subfamily VII(RLCKs-VII)have been implicated in pathogen-associated molecular pattern-triggered immunity and basal resistance against bacterial and fungal pathogens.However,little is known about roles of RLCKs-VII of the important crop common wheat(Triticum aestivum)in immune responses.Here,we isolated a RLCK-VII-encoding gene from wheat,designated as TaRLCK1B,and investigated its role in host immune response to infection of a necrotrophic fungus Rhizoctonia cerealis that is a major pathogen of sharp eyespot,a destructive disease of wheat.RNA-sequencing and RT-qPCR analyses showed that transcriptional level of TaRLCK1B was significantly higher in sharp eyespot-resistant wheat cultivars than in susceptible wheat cultivars.The gene transcription was rapidly and markedly elevated in the resistant wheat cultivars by R.cerealis infection.The TaRLCK1B protein was closely related to OsRLCK176,a rice resistance-related RLCKs-VII,with 84.03%identity.Virus-induced gene silencing plus wheat response to R.cerealis assay results indicated that silencing of TaRLCK1 impaired resistance to R.cerealis.Meantime,silencing of TaRLCK1 significantly elevated both the content of H2 O2(a major kind of reactive oxygen species,ROS)and the transcriptional level of the ROS-generating enzyme-encoding gene RBOH,but repressed the expression of the ROS-scavenging enzyme-encoding gene CAT1 at 18 hours after inoculation(hai)with R.cerealis.Taken together,these data suggested that TaRLCK1B was required for the early immune response of wheat to R.cerealis through modulating ROS signaling in wheat.

Role of cytokine receptor-like factor 1 in hepatic stellate cells and fibrosis

AIM: To elucidate the role of cytokine receptor-like factor 1 (CRLF1) in hepatic stellate cells and liver fibrosis.

Receptor-like kinase OsASLRK regulates methylglyoxal response and content in rice

Receptor-like kinases(RLKs) are essential for plant abiotic stress responses. Methylglyoxal(MG) is a cellular metabolite that is often considered to be a stress signal molecule. However, limited information is available about the relationship between RLKs and MG. Here, we addressed the function of a receptor-like kinase, Os ASLRK, in the MG response and content in rice. A typical MG-responsive element(AAAAAAAA) exists in the promoter region of the OsASLRK gene. RTqPCR analysis indicated that the transcript level of OsASLRK was significantly increased by exogenous MG in a time-and dosage-dependent fashion. GUS staining also confirmed that the expression of Os ASLRK in rice root was enhanced by exogenous MG treatment. Genetic analysis suggested that the Osaslrk mutant displays increased sensitivity to MG and it showed higher endogenous MG content under exogenous MG treatments, while OsASLRK-overexpressing rice plants showed the opposite phenotypes. Diaminobenzidine(DAB) staining, scavenging enzyme activities and GSH content assays indicate that OsASLRK regulates MG sensitivity and content via the elevation of antioxidative enzyme activities and alleviation of membrane damage. Therefore, our results provide new evidence illustrating the roles that receptor-like kinase Os ASLRK plays in MG regulation in rice.

Cloning and Characterization of a Somatic Embryogenesis Receptor-Like Kinase Gene in Cotton (Gossypium hirsutum)

A novel gene, GhSERK1, was identified in cotton. It encoded a protein belonging to the somatic embryogenesis receptor- like kinase （SERK） family. The genomic sequence of GhSERK1 was 6 920 bp in length, containing a predicted transcriptional start site （TSS）. Its full-length cDNA was 2 502 bp, encoding a protein of 627 amino acids. Sequence analysis of GhSERK1 revealed high levels of similarity to other reported SERKs, as well as a conserved intron/exon structure that was unique to members of the SERK family. Expression analysis showed that GhSERK1 mRNA was present in all organs of cotton plants and at different developmental stages, but its transcripts were most abundant in reproductive organs. Compared with that of the male-fertile line, the level of GhSERK1 mRNA was lower in the anther of the male-sterile cotton line, in which the pollen development was defected. Taken together, these findings illustrated that the GhSERK1 play a critical role during the anther formation, and may also have a broad role in other aspects of plant development.

Down-regulation of transforming growth factor β1/activin receptor-like kinase 1 pathway gene expression by herbal compound 861 is related to deactivation of LX-2 cells

AIM: To investigate the effect of herbal compound 861 (Cpd861) on the transforming growth factor-β1 (TGFβ1)/ activin receptor-like kinase 1 (ALK1, type Ⅰ receptor) signaling-pathway-related gene expression in the LX-2 cell line, and the inhibitory mechanism of Cpd861 on the activation of LX-2 cells. METHODS: LX-2 cells were treated with TGFβ1 (5 ng/mL) Cpd861 (0.1 mg/mL), TGFβ1 (5 ng/mL) plus Cpd861 (5 ng/mL) for 24 h to investigate the effect of Cpd861 on the TGFβ1/ALK1 pathway. Real-time PCR was performed to examine the expression of α-SMA (α-smooth muscle actin), ALK1, Id1 (inhibitor of differentiation 1). Western blotting was carried out to measure the levels of α-SMA and phosphorylated Smad1, and immunocytochemical analysis for the expression of α-SMA. RESULTS: In LX-2 cells, TGFβ1/ALK1-pathway-related gene expression could be stimulated by TGFβ1, which led to excessive activation of the cells. Cpd861 decreased the activation of LX-2 cells by reducing the expression of α-SMA mRNA and protein expression. This effect was related to inhibition of the above TGFβ1/ALK1-pathway- related expression of genes such as Id1 and ALK1, and phosphorylation of Smad1 in LX-2 cells, even with TGFβ1 co-treatment for 24 h. CONCLUSION: Cpd861 can restrain the activation of LX-2 cells by inhibiting the TGFβ1/ALK1/Smad1 pathway.

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.

Molecular cloning and transcriptional analysis of a NPY receptor-like in common Chinese cuttlefish Sepiella japonica

Neuropeptide Y(NPY) has a pivotal role in the regulation of many physiological processes. In this study, the gene encoding a NPY receptor-like from the common Chinese cuttlefish Sepiella japonica( SjNPYR-like) was identified and characterized. The full-length SjNPYR-like cDNA was cloned containing a 492-bp of 5′ untranslated region(UTR), 1 182 bp open reading frame(ORF) encoding a protein of 393 amino acid residues, and 228 bp of 3′ UTR. The putative protein was predicted to have a molecular weight of 45.54 kDa and an isoelectric point(pI) of 8.13. By informatic analyses, SjNPYR-like was identified as belonging to the class A G protein coupled receptor(GPCR) family(the rhodopsin-type). The amino acid sequence contained 12 potential phosphorylation sites and five predicted N-linked glycosylation sites. Multiple sequence alignment and 3D structure modeling were conducted to clarify SjNPYR bioinformatics characteristics. Phylogenetic analysis identifies it as an NPYR with identity of 33% to Lymnaea stagnalis NPFR. Transmembrane properties of SjNPYR-like were demonstrated in vitro using HEK293 cells and the p EGFP-N1 plasmid. Relative quantifi cation of SjNPYR-like mRNA level confi rmed a high level expression and broad distribution of SjNPYR-like in various tissues of female S. japonica. In addition, the transcriptional profile of SjNPYR-like in the brain, liver, and ovary during gonadal development was analyzed. The results provide basic understanding on the molecular characteristics of SjNPYR-like and its potentially physical functions.

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.

Functional expression of opioid receptor-like receptorand its endogenous specific agonist nociceptin/orphanin FQ during mouse embryogenesis

Expression of opioid receptor-like receptor (ORL1)and its endogenous peptide agonist nociceptin/orphaninFo (N/OFQ) during mouse embryogenesis have been investigated. Transcripts of ORL1 and N/OFQ were detected by RT-PCR in mouse brain of day 8 embryo (E8)and the expression continued afterwards. Northern blotanalysis revealed abundant expression of ORL1 at postnatal day 1 (P1) and N/OFQ at E17 and P1 in the brain butnone was detected in other embryonic tissues. The presence of functional ORL1 in mouse embryonic brain wasalso confirmed by specific binding of [3H] N/OFQ (kd=1.3±0.5 nM and Bmax = 72±9 fmol/mg protein) as wellas by N/OFQ-stimulated G protein activation.

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.

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.