Search Results (197)

Voltage-gated ion channels (VGICs) are traditionally associated with electrically excitable cells; however, increasing evidence indicates that they are also expressed in non-excitable cells, including vascular endothelial cells. This review aims to summarize the current knowledge on the expression, regulation, and functional role of VGICs in the vascular endothelium, and to highlight their potential contribution to endothelial signaling. We examined the molecular structure, biophysical properties, and functional roles of voltage-gated Na⁺ (Na_V), Ca²⁺ (Ca_V), and K⁺ (K_V) channels in vascular endothelial cells. Particular attention was given to studies investigating VGIC activity in native endothelium and to emerging mechanisms regulating their activation. Endothelial cells express multiple VGIC subtypes at low densities, which are insufficient to generate action potentials but can modulate membrane potential (V_M) and Ca²⁺-dependent signaling. The dynamic regulation of the endothelial V_M, through the interplay between hyperpolarizing and depolarizing conductances, emerges as a key determinant of VGIC availability and activation. VGICs contribute to essential endothelial functions, including angiogenesis, vasomotor responses, blood–brain barrier permeability, and inflammation. Dysregulated VGIC expression and/or activity may be implicated in several pathological conditions, such as atherosclerosis, calcific aortic stenosis, and tumor vascularization. VGICs represent an unexpected but functionally relevant component of endothelial signaling. Elucidating their role in native vascular beds and disease contexts may uncover novel mechanisms of endothelial regulation and identify new therapeutic targets in cardiovascular and cancer biology. Full article

With the continuous advancement of display technology and advanced integrated circuits, oxide thin-film transistors (TFTs) have become core devices due to their high mobility, low leakage current and excellent large-area uniformity. To achieve low power consumption, high performance and high reliability, the introduction of high-k gate insulating layers is crucial. Among the numerous high-k materials, hafnium oxide (HfO₂) has attracted significant attention due to its excellent dielectric properties and good compatibility with CMOS processes. In this paper, uniform and dense HfO₂ films were successfully fabricated using the sol–gel method to serve as insulating layers for TFT devices. Through experimental analysis, 400 °C was determined to be the optimal annealing temperature. At this temperature, the effects of replacing SiO₂ with HfO₂ as the insulating layer, as well as the impact of reducing film thickness, on TFT devices were investigated. Ultimately, at an annealing temperature of 400 °C, an 85 nm-thick HfO₂ film achieved the highest on/off current ratio (I_on/off = 1.11 × 10⁶), the lowest subthreshold swing (SS = 0.53 V/dec), the lowest threshold voltage (Vth = −1.1 V) and the lowest off-current ratio (I_off = 2.5 × 10⁻¹² A). It was confirmed that replacing SiO₂ with HfO₂ as the insulating layer is a viable approach for reducing the volume of TFT devices. Full article

Human endometrial mesenchymal stem/stromal cells (eMSCs) are widely used in laboratories and clinical applications to study various aspects of tissue engineering and regenerative medicine. Three-dimensional (3D) cultivated MSCs have a higher therapeutic efficacy compared to 2D culture. Ion channels are involved in maintaining many physiological cell functions, including proliferation, differentiation, apoptosis, and migration. This study describes the functional expression of voltage-gated sodium channels (NaV) in eMSCs and the role of these channels in cell migration. Using RT-PCR analysis and immunofluorescent microscopy, we identified the expression of almost all pore-forming alpha (NaV 1.1, 1.2, 1.4–1.9) and channel-modulating beta-NaV subunits (except beta2) in eMSCs. In the whole-cell patch-clamp configuration, channels activated by membrane depolarization of eMSC were detected. The channels were blocked by the selective NaV antagonist TTX in nanomolar concentrations. The NaV agonist veratridine at a concentration of less than 40 μM inhibited voltage-gated sodium currents, while 100 μM and above prevented channel inactivation. The wound healing assay showed that both TTX (10 μM) and veratridine (100 μM) reduced the migration properties (the wound healing rate) of eMSCs cultivated in 2D conditions compared to the control. An opposite effect by both agents was shown on the motility of eMSCs cultivated in 3D conditions, increasing the cell spreading rate from spheroids. Our data suggest that NaV channels are expressed in human eMSCs and play an important role in the regulation of stem cell migration; this regulatory mechanism significantly depends on the culture conditions of MSCs. Full article

Molybdenum disulfide (MoS₂) is a compelling candidate for visible-light detection due to its strong optical absorption and tunable bandgap, yet the development of high-performance MoS₂ photodetectors remains limited by challenges in scalable integration, low-voltage operation, and efficient photoresponse. Here, we report an ion-gel-assisted transfer strategy that enables the fabrication of large-area MoS₂/ion gel films that are suitable for low-power phototransistor applications. The transferred MoS₂/ion gel stack is laminated onto an indium-tin-zinc-oxide (ITZO) layer on a glass substrate to fabricate a MoS₂/ITZO heterojunction phototransistor, with the ion gel serving as an ultrathin, high-capacitance gate dielectric. The resulting phototransistor exhibits a field-effect mobility of 4.12 cm²/Vs, an on/off current ratio of 4.9 × 10⁵, and a subthreshold swing of 0.17 V/dec. Under 635, 520, and 405 nm illumination with a power density of 4.5 mW/cm², it achieves responsivities of 0.58, 1.82, and 5.56 A W⁻¹ and detectivities of 5.90 × 10⁹, 1.86 × 10¹⁰, and 5.68 × 10¹⁰ Jones, respectively. These findings demonstrate that the ion-gel-assisted transfer process offers a robust route to high-performance, low-voltage photodetection and provides a promising platform for next-generation optoelectronic technologies. Full article

This review provides a comprehensive overview of the modulatory actions of plant-derived constituents on membrane ion channels in various cell types. Among their diverse bioactivities, ion channel regulation—governing membrane excitability, signal transduction, and cellular homeostasis—has emerged as a critical mechanistic basis for their pharmacological effects. Twenty-four representative phytoconstituents are discussed and classified into five major categories based on their structural features: alkaloids, terpenoids, lignans and acetogenins, polyphenols, and other aromatic and conjugated compounds. Across these categories, the reviewed compounds exhibit distinct and often highly specific effects on the amplitude and gating kinetics of multiple ionic currents, including voltage-gated Na⁺ currents (I_Na), delayed-rectifier K⁺ currents (I_K(DR)), M-type K⁺ currents (I_K(M)), hyperpolarization-activated cation currents (I_h), erg-mediated K⁺ currents (I_K(erg)), inwardly rectifying K⁺ currents, and Ca²⁺-activated K⁺ currents (I_K(Ca)). Alkaloids predominantly suppress voltage-gated K⁺ currents, with notable exceptions such as aconitine, which alters the properties of both I_Na and I_K(DR), thereby contributing to its proarrhythmic toxicity. Terpenoids, including cannabidiol, croton diterpenoids, lutein, thymol, and triptolide, exert multifaceted effects on I_K(M), I_h, inwardly rectifying K⁺ currents, and Ca²⁺-activated K⁺ channels. Lignans and acetogenins, such as gomisin A, honokiol, sesamin, and squamocin, primarily modulate I_Na, I_h, and I_K(Ca), with several compounds demonstrating strong links between ion-channel modulation and anti-neoplastic or neuroprotective actions. Polyphenolic compounds, including curcumin, eugenol, resveratrol, gastrodigenin, gastrodin, and pterostilbene, display diverse ion-channel targeting profiles, influencing multiple Na⁺ and K⁺ channel subtypes. Other aromatic or conjugated compounds, such as isoplumbagin, plumbagin, and verteporfin, regulate I_K(erg) and I_K(Ca), potentially contributing to both therapeutic efficacy and adverse effects. Collectively, the compound-specific modulation of current amplitude and gating kinetics offers valuable mechanistic insight into the pharmacological and toxicological significance of plant-derived natural products, highlighting the functional role of ion channel evaluation in guiding their therapeutic development and ensuring safety assessment. Full article

Scorpion neurotoxins are small peptides that target ion channels and offer opportunities for novel therapeutic discovery. This study analyzed the functional effects of the venom and toxins from the Costa Rican endemic scorpion, Tityus championi. Initially, crude venom was tested on different isoforms of voltage-gated sodium channels. Our findings revealed that the venom contains toxins that affect mammalian Na_V1.6 and Na_V1.7, as well as the cockroach BgNa_V1 channel. Increased currents through Na_V1.6 and BgNa_V1 channels were associated with bigger window currents and inhibition of inactivation. Decreased Na_V1.7 currents were associated with smaller conductance. Crude venom and TCh3 toxin inhibited action potential generation in invertebrate neurons expressing Na_V1.7-like channels. In these neurons, Tch2 and Tch4 toxins shifted voltage sensitivity to more negative potentials, ultimately widening the window current but decreasing channel availability. Conversely, Tch3 behaved as an inhibitory toxin, closing window currents and decreasing channel availability. Structural modeling showed that Tch3 adopts an αββ fold and binds the S3–S4 loop of Domain II in human Na_V1.7. These data show the diverse effects of scorpion venoms on channels and neurons, characterize its principal toxins, and show that Tch3 has therapeutic potential for pain relief. Full article

Skeletal muscle differentiation is tightly regulated by membrane potential dynamics and voltage-dependent ion channel activity. Potassium (K⁺) and calcium (Ca²⁺) currents cooperate to orchestrate the transition of myoblasts into fusion-competent myotubes, and alterations in this process are associated with dystrophic phenotypes. Here, we investigated the electrophysiological remodeling accompanying C2C12 myogenesis and the modulatory effects of the polyphenol resveratrol (RES) on calcium voltage-gated channel subunit alpha 1 S (CACNA1S, Cav1.1, L-type) currents. Whole-cell patch-clamp recordings were performed in proliferating and differentiating C2C12 cells to characterize the temporal expression of K⁺ currents and voltage-dependent Ca²⁺ channels (VDCCs). During differentiation, three electrophysiological subpopulations were identified according to K⁺ current profiles: SK4+/EAG−/Kir−, SK4−/EAG+/Kir−, and SK4−/EAG+/Kir+. This sequence paralleled a progressive membrane hyperpolarization from −20 mV to −70 mV, consistent with the physiological maturation of myogenic cells. In C2C12 myocytes, nimodipine-sensitive L-type currents were the only Ca²⁺ conductance observed. Their activation threshold (~−30 mV) and half-activation voltage (V/2 ≈ −12 mV) indicated the co-expression of embryonic and adult Cav1.1 isoforms. Exposure to RES (30 µM, 48 h) produced a depolarizing shift in activation (ΔV/2 ≈ +9 mV) and a reduction in current amplitude across all voltages, consistent with a transition toward the adult splice variant of Cav1.1. These findings suggest that RES promotes electrophysiological maturation of skeletal muscle cells by modulating calcium channel expression and gating behavior. Given its known ability to correct splicing abnormalities in CACNA1S and related genes, resveratrol emerges as a promising pharmacological agent for restoring calcium homeostasis in neuromuscular disorders such as myotonic dystrophy type 1 (DM1). Full article

Accurate capacity prediction is paramount for ensuring the operational safety and reliability of lithium-ion battery management systems (BMS). Nevertheless, contemporary data-driven approaches often grapple with limited feature representation—frequently relying solely on aggregate charging duration or noise measures—which compromises the robustness of these approaches. To address these limitations, this study proposes a robust framework integrating multi-point voltage temporal sampling (MVTS) with an adaptive gated hybrid ensemble learning strategy. The MVTS method is first used to extract high-dimensional geometric features from the constant-current (CC) charging phase (3.9 V–4.15 V), effectively capturing subtle degradation patterns. Subsequently, an unsupervised isolation forest algorithm is incorporated for automated anomaly detection and rectification, thereby augmenting data stability prior to training. In the fusion stage, a heterogeneous hybrid model comprising eXtreme gradient boosting (XGBoost) and long short-term memory (LSTM) is constructed. An adaptive gating mechanism based on random forest (RF) is added to dynamically weight the base learners. To mitigate data leakage during the stacking process, this study employs an out-of-fold (OOF) training strategy based on leave-one-battery-out (LOBO) cross-validation to generate unbiased meta-features for the gating model. This mechanism dynamically modulates fusion weights contingent upon the multi-point voltage features and model discrepancies, thereby accommodating diverse aging stages and capacity degradation patterns. Experimental results from the NASA battery aging dataset demonstrate that the proposed framework significantly outperforms single-model baselines in terms of RMSE and ${\mathrm{R}}^2$, exhibiting superior adaptability and predictive precision. Full article

Serotonergic projections innervate both the dorsal and ventral cochlear nuclei; however, the electrophysiological consequences of serotonergic input in the ventral cochlear nucleus (VCN) remain incompletely understood. This study aimed to identify the serotonin receptor subtypes involved in serotonergic modulation of stellate cells in the mouse anteroventral cochlear nucleus (AVCN) and to determine the underlying ion channel mechanisms. Whole-cell patch-clamp recordings were performed in acute brain slices obtained from postnatal day 12–17 mice. Bath application of serotonin (25 µM) induced membrane depolarization (~5 mV) and increased action potential firing. Pharmacological experiments demonstrated that antagonists of 5-HT1A, 5-HT2A, and 5-HT2C receptors partially reversed the depolarization and reduced serotonin-induced inward currents, indicating that multiple receptor subtypes contribute to serotonergic excitation. Blockade of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels with extracellular Cs⁺ suppressed approximately 95% of the serotonin-induced depolarization and inward current, implicating HCN channel-mediated Ih as a principal ionic mechanism. Serotonin significantly increased Ih amplitude. Analysis of steady-state activation revealed no statistically significant shift in V0.5; however, under near-resting membrane potential conditions, serotonin significantly reduced the slope factor of the activation curve, consistent with altered voltage sensitivity of Ih gating. Immunohistochemical analysis confirmed the presence of 5-HT1A, 5-HT2A, and 5-HT2C receptors in the AVCN. Together, these findings indicate that serotonergic excitation of AVCN stellate cells is mediated by coordinated activation of multiple 5-HT receptor subtypes and primarily involves modulation of HCN-dependent subthreshold membrane dynamics. Full article

Dry eye disease (DED) is an ocular surface disorder characterized by tear film instability, inflammation, epithelial damage, and neurosensory abnormalities. Due to its multifactorial etiology and pathophysiology, conventional therapies that focus on lubrication and immunosuppression often fall short in addressing the neuropathic component of ocular pain experienced by a growing subset of patients. Recent developments in sensory neuroscience have highlighted the pivotal role of ion channels in mediating ocular surface homeostasis, pain signaling, and inflammation. This review examines the role of the following major ion channel families in the pathophysiology of DED and neuropathic ocular pain: transient receptor potential (TRP) channels, voltage-gated sodium (Nav) channels, and purinergic P2X receptors. The review details their anatomical distribution, molecular function, and responses to environmental stimuli such as heat, cold, osmolarity, and injury. Current treatments, such as artificial tears, anti-inflammatory drops, and systemic neuromodulators, are also reviewed in relation to their effects on ion channel modulation. Additionally, emerging therapies that directly target sensory transduction pathways are introduced. This review highlights the therapeutic potential of ion channel modulation in personalizing treatment for patients with ocular surface pain, particularly those with neuropathic features unresponsive to standard care. Full article

The state of health (SOH) estimation of lithium-ion batteries faces significant challenges under complex operating conditions due to transient disturbances and distribution shifts. This paper proposes a deep learning framework named Conformer-KAN, which integrates a convolution-augmented Transformer (Conformer) with a Kolmogorov–Arnold Network (KAN). The method first constructs a unified input representation by fusing multi-view features including voltage, current, temperature, and incremental capacity. It then employs a Conformer encoder that combines gated local convolution units (GLCU) and multi-head self-attention (MHSA) to achieve joint modeling of local and global features. In addition, learnable spline-based activation functions are introduced within the KAN structure to enhance the model’s capacity for capturing complex nonlinear degradation behaviors. Cross-battery and cross-condition evaluations conducted on two public datasets demonstrate that the proposed method achieves root mean square errors (RMSE) of 0.006 ± 0.001 and 0.003 ± 0.001, and coefficients of determination (R²) of 0.987 ± 0.003 and 0.994 ± 0.002, respectively. These results show that Conformer-KAN significantly outperforms existing mainstream approaches in both robustness and generalization performance. Full article

Fibroblast growth factor 12 (FGF12), a member of the intracellular fibroblast growth factor homologous factor (iFGF) subfamily, has been widely studied for its role in the modulation of voltage-gated ion channels. However, recent studies suggest that FGF12 possesses various cellular functions beyond ion channel regulation, particularly in cancer progression. Accumulating evidence indicates that the upregulation of FGF12 is associated with tumor survival, therapeutic resistance, and poor prognosis through signaling pathways independent of its canonical ion channel interactions. This review summarizes the current understanding of FGF12’s non-canonical functions, highlights its emerging roles in cellular regulation, and discusses its potential mechanism in oncogenic progression. Understanding these novel functions may provide a new aspect for therapeutic targeting of FGF12 in malignancies. Full article

Ion-Sensitive Field-Effect Transistors (ISFETs) have been extensively used to detect various biomolecules, as the intrinsic charge of these molecules can change the transistor’s current or threshold voltage. Recently, realizing ISFET biosensors with better performance has attracted much attention. This paper proposes a novel ISFET biosensor by using the advantage of Tunnel Field-Effect Transistor (TFET). The device characteristics and sensing performance are systematically investigated by Silvaco Atlas TCAD simulations. Due to the novel structural design, the proposed sensor achieves a maximum current sensitivity (S_IDSmax) of 99.99% and a threshold voltage sensitivity (S_VTH) of 124%. To provide optimization guidelines, this work further explored the effect of geometric dimensions and gate dielectric materials on device performance. The excellent performance of the proposed biosensor makes it a promising candidate for future low-power, high-sensitivity biodetection applications. Full article

Tunnel Field-Effect Transistors (TFETs) are being explored for ultra-low-power very-large-scale integrated circuits (VLSI) because their band-to-band tunnelling (BTBT) transport permits subthreshold swings (SS) below the 60 mV/dec thermionic limit at room temperature, along with significantly lower leakage than MOSFETs. This paper presents a systematic TCAD study of DG-TFETs that maps how four primary knobs–gate dielectric materials, silicon channel thickness, temperature variation, and different channel material shape key figures of merit: the ON current (I_ON), OFF current (I_OFF), threshold voltage (V_TH), SS, and the I_ON/I_OFF switching ratio. High-k gate enhances gate-to-channel coupling and boost tunnelling efficiency; rigorous body scaling enhances electrostatic control; and targeted source-proximal doping profiles elevate I_ON while minimizing leakage. We also measure the trade-offs between I_ON, SS, and I_OFF that occur when scaling is performed at the same time. This shows that careful coordination is needed instead of just tuning one parameter. This is a simulated work, and the physical models are calibrated to experimental TFET data and all parameters are checked against previously reported results. The device reaches SS = 31.4 mV/dec, V_TH = 0.46 V, I_ON = 5.91 × 10⁻⁵ A and an I_ON/I_OFF of about 4.5 × 10¹¹. This shows that it can switch quickly with little leakage. The design insights that come from this work provide useful advice regarding how to choose gate dielectric material, structures, and doping strategies to add DG-TFETs to the next generation of low-power semiconductor technologies. Full article

Oxidative stress-induced lipid peroxidation products (LPPs), particularly 4-hydroxy-nonenal (4-HNE) and 4-oxo-nonenal (4-ONE), have recently gained attention for their direct regulation of ion channels essential for pain signaling. In this study, we investigated how these two LPPs affect the electrophysiological properties of neurons, specifically voltage-gated sodium (Na_V) channels, thereby influencing sensory neuron excitability and pain pathways. Using human neuroblastoma (SH-SY5Y) and ND7/23 cells (a fusion cell line exhibiting partial sensory neuron properties), we measured changes in Na_V channel-mediated sodium currents following treatment with 4-HNE or 4-ONE. Whole-cell patch-clamp experiments showed that 4-ONE (10 µM) and 4-HNE (100 µM) did not significantly alter the peak sodium current amplitude in SH-SY5Y cells. However, in ND7/23 cells, both 4-HNE and 4-ONE induced a negative shift in Na_V channel activation voltage dependence, enabling sodium channel activation at lower membrane potentials. Furthermore, current-clamp recordings in primary mouse dorsal root ganglion neurons demonstrated that treatment with 4-ONE and 4-HNE reduced the current threshold required to elicit action potentials and significantly increased action potential firing frequency. These findings indicate that LPPs enhance pain sensitivity by modulating Na_V channels, which play a crucial role in pain transmission. In conclusion, 4-HNE and 4-ONE shift the voltage-dependent activation of sodium channels toward more negative potentials, thereby increasing the excitability of primary sensory neurons and amplifying pain signals. This study provides molecular insights into how oxidative stress-related lipid peroxidation contributes to sensory mechanisms and offers potential avenues for developing new treatments for oxidative stress- or inflammation-associated pain. Full article