Search Results (366)

Accurate estimation of the state of health (SOH) of lithium-ion batteries is crucial for the safe operation of electric vehicles and energy storage systems. However, most existing methods rely on complete charging curves or manual feature engineering, making them difficult to adapt to practical scenarios where only limited charging segments are available. To fully exploit degradation information from limited charging data, this paper proposes a dual-modal mixture of Kolmogorov–Arnold network (DM-MoKAN) for lithium-ion battery SOH estimation using only early-stage constant-current charging voltage data. The proposed method incorporates three synergistic modules: an image branch, a sequence branch, and a dual-modal fusion regression module. The image branch converts one-dimensional voltage sequences into two-dimensional Gramian Angular Difference Field (GADF) images and extracts spatial degradation features through a lightweight network integrating Ghost convolution and efficient channel attention (ECA). The sequence branch employs a patch-based Transformer encoder to directly model local patterns and long-range dependencies in the raw voltage sequence. The dual-modal fusion module concatenates features from both branches and feeds them into a MoKAN regression head composed of multiple KAN experts and a gating network for adaptive nonlinear mapping to SOH. Experimental results demonstrate that DM-MoKAN outperforms various baseline methods on both Oxford and NASA datasets, achieving average RMSE/MAE of 0.28%/0.19% and 0.89%/0.71%, respectively. Ablation experiments further verify the effective contributions of the dual-modal fusion strategy, ECA attention mechanism, and MoKAN regression head to estimation performance improvement. Full article

R-limonene has been integrated into various pest control practices as a repellent or an insecticide. However, how limonene induces aversion or mortality remains largely unknown. To elucidate the underlying mechanisms, we conducted behavioral, toxicological, and electrophysiological assays in Aedes aegypti, a primary vector of human diseases. To investigate whether limonene acts on voltage-gated sodium channels and/or the Rdl (Resistance to dieldrin) receptor, two major targets of neuroactive insecticides, we characterized the effect of limonene on Ae. aegypti sodium and Rdl channels expressed in Xenopus oocytes. Limonene significantly potentiated GABA-induced chloride currents through Rdl in a concentration-dependent manner but had no effect on sodium channels. For repellency, limonene evoked spatial repellency in wild-type mosquitoes; however, the spatial repellency by limonene was significantly reduced in knockout mutants of Orco^−/− (odorant receptor co-receptor) and TRPA1^−/− (Transient Receptor Protein, subfamily A and member 1). These results indicate that limonene likely targets the Rdl receptor for insecticidal activity and limonene spatial repellency requires both Orco and TRPA1 channels. Our results reveal the involvement of multiple ion channels and receptors in the mosquito nervous system for limonene’s insecticidal and/or spatial repellency actions, highlighting limonene’s potential as a multi-target neuroactive agent for pest control. Full article

Calcium (Ca²⁺) is a signal messenger for ion flow in and out of microbial, parasitic, and host defense cells. Manipulation of calcium ion signaling with ion blockers and calcineurin inhibitors may improve host defense while decreasing microbial/parasitic resistance to therapy. Ca²⁺ release from intracellular storage sites controls many host defense functions (cell integrity, movement, and growth). The transformation of phospholipids in the erythrocyte membrane is associated with changes in deformability. This type of lipid bilayer defense mechanism helps to prevent attack by Plasmodium. Patients with sickle cell disease (SS hemoglobin) do not have this protection and are extremely vulnerable to massive hemolysis from parasitic infestation. Patients with thalassemia major also lack parasite protection. Alteration of Ca²⁺ ion channels responsive to environmental stimuli (transient receptor potential) results in erythrocyte protection from Plasmodium. Similarly, calcineurin inhibitors (cyclosporine) reduce heart and brain inflammation injury with Trypanosoma and Taenia. Ca²⁺ channel blockers interfere with malarial life cycles. Several species of parasites are known to invade hepatocytes: Plasmodium, Echinococcus, Schistosoma, Taenia, and Toxoplasma. Ligand-specific membrane channel constituents (inositol triphosphate and sphingosine phospholipid) constitute membrane surface signal messengers. Plasmodium requires Ca²⁺ for energy to grow and to occupy red blood cells. A cascade of signals proceeds from Ca²⁺ to two proteins: calmodulin and calcineurin. Inhibitors of calmodulin were found to blunt the population growth of Plasmodium. An inhibitor of calcineurin (cyclosporine) was found to retard population growth of both Plasmodium and Schistosoma. Calcineurin also controls sensitivity and resistance to antibiotics. After exposure to cyclosporine, the liver directs Ca²⁺ ions into storage sites in the endoplasmic reticulum and mitochondria. Storage of large amounts of Ca²⁺ would be useful if pathogens began to occupy both red blood cells and liver cells. We present scientific evidence supporting the benefits of calcium channel blockers and calcineurin inhibitors to potentiate current antiparasitic therapies. Full article

Magnesium ions regulate synaptic and nonsynaptic neuronal excitability from intracellular (Mg²⁺_i) and extracellular (Mg²⁺_o) domains, modulating voltage- and ligand-gated ion channels. K+ inward rectifier (Kir) channel inward rectification arises from Mg²⁺_i blocking the pore and outward K⁺ current, while Mg²⁺_o targets external sites. Mg²⁺_i causes voltage-dependent Ca²⁺ voltage-gated (Ca_V) and Na⁺ voltage-gated (Na_V) channel block while phosphorylation modulates channel activity. Mg²⁺_o elicits direct voltage-dependent Ca_V channel block, and screens surface charge, and in Na_V channels reduces conduction and may cause depolarization by quantum tunneling across closed channels. Mg²⁺_i is an allosteric large conductance Ca²⁺-activated K⁺ (BK) channel activator, binding to low-affinity sites to alter Ca²⁺ and voltage sensitivity but reduces small conductance Ca²⁺-activated K⁺ (SK) channels’ outward K⁺ current and induces inward rectification. N-Methyl-D-aspartate receptor (NMDAR) channels are inhibited by Mg²⁺_i binding within the pore, while Mg²⁺_o stabilizes excitability through voltage-dependent block, Mg²⁺_o forms Mg-ATP complex modifying purinergic P2X receptor (P2XR) channel affinity and gating and directly blocks the pore. Mg²⁺_o reduces gamma-aminobutyric acid type A receptor (GABA_AR) channel Cl⁻ current amplitude and augments susceptibility to blockers. Mg²⁺_o and Mg²⁺_i block nicotinic acetylcholine receptor (nAChR) channels through voltage-dependent pore binding and surface charge screening, impeding current flow and altering gating. Full article

Organic electrochemical transistors (OECTs) are compelling artificial synapses because mixed ionic–electronic coupling and transport enables low-voltage, analog weight updates that mirror biological plasticity. Here, we engineered solid-state, polymer electrolyte-gated vertical OECTs (vOECTs) and elucidate how electrolyte molecular weight influences synaptic dynamics. Using Pg2T-T as the redox-active channel and pDADMAC polymer electrolytes spanning low- (~100 k), medium- (~300 k), and high- (~500 k) molecular weights, cyclic voltammetry reveals reversible Pg2T-T redox, while peak separation and current density systematically track ion transport kinetics. Increasing electrolyte molecular weight enlarges the transfer curve hysteresis (memory window ΔV_mem from ~0.15 V to ~0.50 V) but suppresses on-current, consistent with slower, more confining ion motion and stabilized partially doped states. Devices exhibit rich short- and long-term plasticity: paired-pulse facilitation (A₂/A₁ ≈ 1.75 at Δt = 50 ms), frequency-dependent EPSCs (low-pass accumulation), cumulative potentiation, and reversible LTP/LTD. A device-aware CrossSim framework built from continuous write/erase cycles (probabilistic LUT) supports Fashion-MNIST inference with high accuracy and bounded update errors (mean −0.02; asymmetry 0.198), validating that measured nonidealities remain algorithm-compatible. These results provide a materials-level handle on polymer–ion coupling to deterministically tailor temporal learning in compact, robust neuromorphic hardware. Full article

Scorpion venom toxins are important peptides being studied for their clinical significance. These peptides act by binding to ion channels in the membrane of nerve cells, causing the symptoms associated with scorpion stings (scorpionism). They principally affect the function of voltage-gated sodium channels (Nav) and are valuable for studying ion channels. Scorpions from the Buthidae family contain toxins that affect sodium channels and have a high affinity for mammalian channels. In this study, two sodium toxins isolated from the venom of the scorpion Centruroides hirsutipalpus, a member of the Buthidae family, were identified as belonging to the beta-type subfamily. These toxins were purified from whole venom using molecular exclusion, cationic-exchange, and reverse-phase chromatography techniques. Their molecular masses were determined using mass spectrometry, while their amino acid sequences were obtained by Edman degradation. A comparative analysis revealed that the sequences are identical to ChiNaBet60 and ChiNaBet50 toxins (now named Chirp7 and Chirp9, respectively) previously identified in the venom gland transcriptomics from C. hirsutipalpus. Furthermore, toxicity studies showed that these toxins were lethal to mammals. Electrophysiological analysis revealed that these peptides act as sodium channel–modulating toxins. In addition, interaction assays with antibodies were performed to analyze the structural determinants governing the binding mechanism. Full article

Toxins as channel probes, small guanidinium alkaloids, such as tetrodotoxin and saxitoxin, canonical pore occlusion in voltage-gated Na⁺ channels. Cystine-rich peptides from spiders, scorpions, cone snails, and sea anemones, which act as pore blockers or gating modifiers targeting voltage-sensing domains. Recent structural and electrophysiological studies have identified specific binding sites on ion channels, including the S5–S6 pore loops, outer vestibule and turret regions, and S3–S4 “paddle” motifs in NaV, Kv, and CaV channels. These discrete binding epitopes are recognized by different peptide toxins, enabling isoform- and state-specific modulation; for example, μ-conotoxins bind the NaV pore, whereas charybdotoxin and agitoxin target the Kv outer vestibule. Beyond mechanistic insights, peptide toxins inspire translational strategies, including emerging therapies for retinal degenerative diseases. Photopharmacology using chemical photoswitches allows reversible, light-controlled modulation of ion channels in retinal ganglion cells without genetic manipulation or cell transplantation. Although BENAQ was discovered by small-molecule screening rather than toxin-guided design, its ion channel control demonstrates the potential of toxin-based molecular determinants for engineering synthetic compounds. This review thus integrates structural, functional, and translational perspectives, emphasizing the versatility of animal-derived peptide toxins as molecular probes and as blueprints for precision ion channel modulation in health and disease. Full article

To enhance the electrical performance of MgZnO-TFTs, this study employed radio-frequency (RF) magnetron sputtering to fabricate MgZnO/ZTO thin films. Using these films as the channel layer, bottom-gate top-contact MgZnO/ZTO-TFT devices were constructed. The thin films were characterized using atomic force microscopy (AFM) and X-ray photoelectron spectroscopy (XPS). After optimization, the MgZnO/ZTO-TFT exhibited a high field-effect mobility of 16.80 cm²·V⁻¹·s⁻¹, high Ion/off of 7.63 × 10⁸, threshold voltage of −1.60 V, and subthreshold swing as low as 0.74 V·dec⁻¹. Bias stress stability tests were conducted under positive bias stress (PBS) and negative bias stress (NBS) conditions with a source-drain voltage of 20 V and gate bias stresses (VGS) of +10 V and −10 V, respectively, for a duration of 1000 s. The resulting threshold voltage shifts were only +0.58 V and −0.15 V, respectively, indicating excellent bias stability. These results suggest that the ZTO film, serving as the lower channel layer, effectively enhances carrier transport at the MgZnO/ZTO interface, thereby improving the field-effect mobility and on/off current ratio. Meanwhile, the MgZnO film as the upper channel layer adjusts the device’s threshold voltage and enhances its bias stability. Full article

Background/Objective: Acute and chronic pain affect millions of individuals, yet there are currently no molecular imaging tools to directly assess pain-related mechanisms in the central nervous system (CNS). The voltage-gated sodium channel Na_V1.8 plays a pivotal role in neuropathic pain by increasing the excitability of nociceptive neurons following nerve injury or inflammation. In this work, we aimed to develop a novel positron emission tomography (PET) imaging probe for Na_V1.8 to facilitate noninvasive quantification of this target in the CNS and thereby advance our understanding of pain neurobiology. Methods: We selected the compound suzetrigine, a U.S. FDA-approved, highly selective non-opioid Na_V1.8 inhibitor, as the first candidate for a Na_V1.8-targeted PET tracer. The compound was first assessed using in silico docking and CNS multiparameter optimization (MPO) analysis to evaluate target binding and predicted brain penetrability. Radiolabeling was accomplished by O-methylation with [¹¹C]methyl iodide to yield [¹¹C]suzetrigine without structural modification. The tracer was then evaluated using in vitro binding assays, including autoradiography and saturation binding on rat brain tissues, to determine binding parameters (K_D, B_max), and using in vivo PET imaging in rats to assess brain uptake, time–activity curves (TACs), and tracer behavior under baseline and pretreatment conditions. Pretreatment was performed with unlabeled suzetrigine, the P-glycoprotein (P-gp) inhibitor verapamil, and the heterologous Na_V1.8 inhibitor A-803467. Results: In silico docking demonstrated favorable binding of suzetrigine to the Na_V1.8 active site, and the calculated CNS MPO score (>3.5) suggested adequate brain penetration. Radiochemical synthesis of [¹¹C]suzetrigine via O-methylation yielded a high decay-corrected radiochemical yield (19.2 ± 2.7%, n = 3), excellent purity (>98%, n = 3), and moderate molar activity (62.9 ± 51.8 MBq/nmol, n = 3). Autoradiography on rat brain tissue confirmed saturable and selective binding of [¹¹C]suzetrigine to Na_V1.8. Saturation binding assays revealed a B_max = 93 fmol/mg and a K_D = 0.1 nM, supporting the imageability of Na_V1.8 in the brain using this tracer. In vivo PET imaging in rats demonstrated rapid and sufficient brain uptake but revealed unexpected tracer behavior: signal intensity markedly increased following pretreatment with either unlabeled suzetrigine or the P-gp inhibitor verapamil, and showed a slight increase after pretreatment with the heterologous Na_V1.8 inhibitor A-803467. Detailed analysis of PET images, TACs, and normalized area-under-curve (AUC) values indicated that these atypical uptake patterns were primarily attributable to P-gp-mediated effects, although additional factors may also contribute. Conclusions: [¹¹C]Suzetrigine exhibits high affinity, good brain uptake, and selective target engagement in vitro, supporting its potential as a first-in-class Na_V1.8-PET tracer. However, in vivo performance is confounded by P-gp-mediated efflux and possibly other mechanisms that limit accurate quantification of Na_V1.8 in the living brain. These findings underscore the critical role of efflux transporters in CNS radiotracer development and highlight the need for design strategies that mitigate P-gp interaction when targeting ion channels in the brain. Future studies will include imaging under constant P-gp inhibition, arterial blood sampling for radiometabolite analysis and full kinetic modeling, and evaluation in non-human primates to assess translational feasibility. Full article

Germanium (Ge) has long been regarded as a promising channel material, owing to its superior carrier mobility and highly tunable electronic band structure. The new generation of low-power electronics is approaching the formation of fully depleted (FD) transistors on Si-on-insulator (SOl) and Ge-on-insulator (GOl) substrates. In this work, we present a full process of a novel FDGOI transistor formed on a strained GOI with low defect density. This scalable and industry-compatible approach enables the formation of uniform 50 nm thick Ge layers by using spinning wet etch with ultrasmooth surfaces (RMS roughness = 0.262 nm) and a low etch-pit density of ~10⁵ cm⁻². Electrical measurements reveal excellent carrier transport properties, with back-gate (BG) transistors achieving mobilities of 550–600 cm²/V·s, while front-gate (FG) devices exhibit sharp switching behavior and steep subthreshold slopes, yielding I_ON/I_OFF ratios up to 10⁵. Temperature-dependent measurements further demonstrate a pronounced enhancement of device performance: the I_ON/I_OFF ratio increases to 106, the subthreshold swing (SS) decreases from 179 mV/dec at room temperature to 137 mV/dec at 120 K, and the threshold-voltage shift with temperature is as low as 1.87 mV/K across the range of 30–300 K. Such behavior highlights the potential of band-gap engineering for precise threshold-voltage control. Taken together, these results establish GOI as a CMOS-compatible material platform and provide a solid technological basis for the development of next-generation low-power transistors beyond conventional CMOS scaling. Full article

Spider-derived venoms are a rich source of cystine knot peptides with immense therapeutic potential. Many of these peptides exert unique biological activities through the modulation of ion channels, including of human voltage-gated sodium (Na_V1.1–Na_V1.9) channels. Na_V channel subtypes have diverse functions determined by their tissue and cellular distribution and biophysical properties, and are pathophysiology mediators in various diseases. Therefore, Na_Vs are central in studies of human biology. This work investigated the pharmacological properties of venom of the Thai theraphosid Ornithoctonus aureotibialis on Na_V channels. We discovered a predominant venom peptide named Oa1a and assessed its pharmacological properties across human Na_V channel subtypes. Synthetic forms of the peptide Oa1a showed preferential inhibition of Na_V1.1 and Na_V1.7, while recombinant Oa1a displayed a preference for inhibiting Na_V1.2, Na_V1.6, and Na_V1.7. Interestingly, all versions of Oa1a peptides exerted dual pharmacological effect by reducing the peak current and slowing fast inactivation of Na_V1.3, consistent with Oa1a having more than one binding site on Na_V channels. Such complex pharmacology was previously observed for a venom peptide in a Central American and Costa Rican tarantula, suggesting a conserved mechanism of action amongst these geographically distinct species. However, Oa1a lacked activity in the T-type channels observed in the tarantula peptide from Central America. Structure–function relationships investigated using molecular modelling showed that the dual pharmacology is driven by a conserved mechanism utilizing a mix of aromatic and charged residues, while the T-type activity appears to require additional charged residues in loop 2 and fewer positive charges in loop 4. Future structure–activity relationship studies of Oa1a will guide the development of pharmacological tools as well as next-generation drugs to treat Na_V channel dysfunction associated with neurological disorders. Full article

Calmodulin (CaM) plays a central role in cardiac excitation–contraction coupling by regulating ion channels, including the L-type calcium (Ca²⁺) channel Ca_v1.2 and the voltage-gated potassium (K⁺) channel K_v7.1. Mutations in CaM are linked to severe arrhythmogenic disorders such as Long QT syndrome (LQTS), yet the molecular mechanisms remain incompletely understood. Here, we investigate the structural and functional consequences of the arrhythmia-associated CaM variant D133H. Biophysical analysis revealed that D133H destabilises Ca²⁺ binding at the C-terminal lobe of CaM, altering its Ca²⁺-dependent conformational changes. Electrophysiological recordings demonstrated that CaM D133H impairs Ca²⁺-dependent inactivation (CDI) of Ca_v1.2, prolonging Ca²⁺ influx, while also reducing activation of K_v7.1, thereby limiting repolarising K⁺ currents. Together, these dual defects converge to prolong action potential duration, providing a mechanistic basis for arrhythmogenesis in LQTS. Our findings establish that CaM D133H perturbs both Ca²⁺ and K⁺ channel regulation, highlighting a shared pathway by which calmodulinopathy mutations disrupt cardiac excitability. Full article

Endometrial cancer is one of the most common malignancies of the female reproductive system, with incidence rising globally due to population ageing and life-style-related risk factors. Calcium (Ca²⁺) is a ubiquitous second messenger regulating diverse physiological processes, and its dysregulation has been increasingly implicated in carcinogenesis, including endometrial. Altered expression and function of Ca²⁺ channels, pumps, exchangers, and binding proteins disrupt the finely tuned balance of Ca²⁺ influx, efflux, and intracellular storage, leading to aberrant signalling that promotes tumour proliferation, migration, survival, and metastasis. This review summarises current knowledge on the molecular “Ca²⁺ toolkit” in the human uterus, highlighting the role of voltage-gated calcium channels (VGCCs), transient receptor potential (TRP) channels, store-operated calcium entry (SOCE) components, Na⁺/Ca²⁺ exchangers, purinergic receptors, P-type ATPases (SERCA, SPCA, PMCA), ryanodine (RyR) and inositol 1,4,5-trisphosphate (IP₃R) receptors, and mitochondrial Ca²⁺ uniporter (MCU) complexes in endometrial cancer progression. Multiple Ca²⁺-handling proteins, including CACNA1D, CACNA2D1, TRPV4, TRPV1, TRPM4, MCU, and RyR1, exhibit cancer-associated overexpression or functional changes, correlating with poor prognosis and aggressive disease features. Emerging evidence supports the therapeutic potential of targeting Ca²⁺ homeostasis using small-molecule inhibitors, ion channel modulators or gene-silencing strategies. These interventions may restore Ca²⁺ balance, induce apoptosis or autophagy, and suppress metastatic behaviour. While no clinical trials have yet explicitly focused on Ca²⁺ modulation in endometrial cancer, the diversity of dysregulated Ca²⁺ pathways offers a rich landscape for novel therapeutic strategies. Targeting key components of the Ca²⁺ signalling network holds promise for improving outcomes in endometrial cancer. Full article

Animal toxins contain various bioactive peptides and proteins which have evolved to interact in specific ways. As such, they are a good starting point for developing new drugs and vaccines. This paper examines three natural neurotoxins derived from the black mamba (Dendroaspis polylepis), which show significant pharmacological potential: mambalgins, fasciculins and dendrotoxins. All three may be of value in the treatment of pain, cancer and neurodegenerative disease. Mambalgins provide similar pain relief to opioids but without the risk of addiction; they act by selectively blocking acid-sensitive ion channels (ASICs), especially ASIC1a. Thanks to this inhibitory activity they also demonstrate selective activity against glioblastoma, melanoma and leukemia cells as innovative anticancer drugs. Fasciculins are very strong inhibitors of acetylcholinesterase (AChE) and hence offer promise in multi-target drugs and as treatments for treating Alzheimer’s disease. Dendrotoxins such as DTX-K and DTX-I are able to modulate neuronal excitability and synaptic transmission by blocking voltage-gated potassium channels (Kv1.1, Kv1.2, Kv1.6); both have been shown to be effective against cancer cells, and to influence the cardiovascular, immune, and digestive systems. Recent advances in recombinant biotechnology and protein engineering have allowed their safe production with increased therapeutic value. The review examines the translational potential of D. polylepis venom proteins and highlights the need for additional preclinical research on bioactive molecules of toxin origin. Full article

Understanding the functional modulation of ion channels by multiple activating substances is critical to grasping stimulus-specific gating mechanisms and possible synergistic or competitive interactions. This study investigates the activation of large-conductance, voltage- and Ca²⁺-activated potassium channels (BK) in the plasma membrane of human bronchial epithelial cells by Ca²⁺ and quercetin (Que), both individually and in combination. Patch-clamp recordings were analyzed using open state probability, dwell-time distributions, Shannon entropy, sample entropy, power spectral density (PSD), and empirical mode decomposition (EMD). Our results reveal concentration-dependent alterations in gating kinetics, particularly at a low concentration of quercetin ([Que] = 10 μM) compared with [Que] = 100 μM, where some Que-related effects are strongly attenuated in the presence of Ca²⁺. We also identify specific frequency bands where oscillatory components are most sensitive to the considered stimuli. Our findings highlight the complex reciprocal interplay between Ca²⁺ and Que in modulating BK channel function, and demonstrate the interpretative power of entropic and signal-decomposition approaches in characterizing stimulus-specific gating dynamics. Full article