Search Results (723)

In this study, we propose a bidirectional chemical sensor platform based on a reconfigurable ion-sensitive field-effect transistor (R-ISFET) architecture. The device incorporates Ni-silicide Schottky barrier source/drain (S/D) contacts, enabling ambipolar conduction and bidirectional turn-on behavior for both p-type and n-type configurations. Channel polarity is dynamically controlled via the program gate (PG), while the control gate (CG) suppresses leakage current, enhancing operational stability and energy efficiency. A dual-control-gate (DCG) structure enhances capacitive coupling, enabling sensitivity beyond the Nernst limit without external amplification. The extended-gate (EG) architecture physically separates the transistor and sensing regions, improving durability and long-term reliability. Electrical characteristics were evaluated through transfer and output curves, and carrier transport mechanisms were analyzed using band diagrams. Sensor performance—including sensitivity, hysteresis, and drift—was assessed under various pH conditions and external noise up to 5 V_pp (i.e., peak-to-peak voltage). The n-type configuration exhibited high mobility and fast response, while the p-type configuration demonstrated excellent noise immunity and low drift. Both modes showed consistent sensitivity trends, confirming the feasibility of complementary sensing. These results indicate that the proposed R-ISFET sensor enables selective mode switching for high sensitivity and robust operation, offering strong potential for next-generation biosensing and chemical detection. Full article

Since the initial use of biological ion channels to detect single-stranded genomic base pair differences, label-free and highly sensitive resistive pulse sensing (RPS) with nanopores has made remarkable progress in single-molecule analysis. By monitoring transient ionic current disruptions caused by molecules translocating through a nanopore, this technology offers detailed insights into the structure, charge, and dynamics of the analytes. In this work, the RPS platforms based on biological, solid-state, and other sensing pores, detailing their latest research progress and applications, are reviewed. Their core capability is the high-precision characterization of tiny particles, ions, and nucleotides, which are widely used in biomedicine, clinical diagnosis, and environmental monitoring. However, current RPS methods involve bottlenecks, including limited sensitivity (weak signals from sub-nanometer targets with low SNR), complex sample interference (high false positives from ionic strength, etc.), and field consistency (solid-state channel drift, short-lived bio-pores failing POCT needs). To overcome this, bio-solid-state fusion channels, in-well reactors, deep learning models, and transfer learning provide various options. Evolving into an intelligent sensing ecosystem, RPS is expected to become a universal platform linking basic research, precision medicine, and on-site rapid detection. Full article

The focal “hot spot” neuropathologies in COVID-19 infection are revealing footprints of a hidden underlying collapse of a novel ultrafast ultradian Piezo2 signaling system within the nervous system. Paradoxically, the same initiating pathophysiology may underpin the systemic findings in COVID-19 infection, namely the multiorgan SARS-CoV-2 infection-induced vascular pathologies and brain–body-wide systemic pro-inflammatory signaling, depending on the concentration and exposure to infecting SARS-CoV-2 viruses. This common initiating microdamage is suggested to be the primary damage or the acquired channelopathy of the Piezo2 ion channel, leading to a principal gateway to pathophysiology. This Piezo2 channelopathy-induced neural switch could not only explain the initiation of disrupted cell–cell interactions, metabolic failure, microglial dysfunction, mitochondrial injury, glutamatergic synapse loss, inflammation and neurological states with the central involvement of the hippocampus and the medulla, but also the initiating pathophysiology without SARS-CoV-2 viral intracellular entry into neurons as well. Therefore, the impairment of the proposed Piezo2-induced quantum mechanical free-energy-stimulated ultrafast proton-coupled tunneling seems to be the principal and critical underlying COVID-19 infection-induced primary damage along the brain axes, depending on the loci of SARS-CoV-2 viral infection and intracellular entry. Moreover, this initiating Piezo2 channelopathy may also explain resultant autonomic dysregulation involving the medulla, hippocampus and heart rate regulation, not to mention sleep disturbance with altered rapid eye movement sleep and cognitive deficit in the short term, and even as a consequence of long COVID. The current opinion piece aims to promote future angles of science and research in order to further elucidate the not entirely known initiating pathophysiology of SARS-CoV-2 infection. Full article

Diabetic sensorimotor polyneuropathy (DSPN) is the most prevalent complication of diabetes, affecting nearly half of all persons with diabetes. It is characterized by nerve degeneration, progressive sensory loss and pain, with increased risk of ulceration and amputation. Despite its high prevalence, disease-modifying treatments for DSPN do not exist. Mitochondrial dysfunction and Ca²⁺ dyshomeostasis are key contributors to the pathophysiology of DSPN, disrupting neuronal energy homeostasis and initiating axonal degeneration. Recent findings have demonstrated that antagonism of the muscarinic acetylcholine type 1 receptor (M₁R) promotes restoration of mitochondrial function and axon repair in various neuropathies, including DSPN, chemotherapy-induced peripheral neuropathy (CIPN) and HIV-associated neuropathy. Pirenzepine, a selective M₁R antagonist with a well-established safety profile, is currently under clinical investigation for its potential to reverse neuropathy. The transient receptor potential melastatin-3 (TRPM3) channel, a Ca²⁺-permeable ion channel, has recently emerged as a downstream effector of G protein-coupled receptor (GPCR) pathways, including M₁R. TRPM3 activation enhanced mitochondrial Ca²⁺ uptake and bioenergetics, promoting axonal sprouting. This review highlights mitochondrial and Ca²⁺ signaling imbalances in DSPN and presents M₁R antagonism and TRPM3 activation as promising neuro-regenerative strategies that shift treatment from symptom control to nerve restoration in diabetic and other peripheral neuropathies. Full article

Synthetic nanopores were recently demonstrated with memristive and nonlinear voltage-current behaviors, akin to ion channels in a cell membrane. Such ionic devices are considered a promising candidate for the development of brain-inspired neuromorphic computing techniques. In this work, we show the composite behavior of nanopore-array large memristors, formed with different membrane materials, pore sizes, electrolytes, and device arrangements. Anodic aluminum oxide (AAO) membranes with 5 nm and 20 nm diameter pores and track-etched polycarbonate (PCTE) membranes with 10 nm diameter pores are tested and shown to demonstrate memristive and nonlinear behaviors with approximately 10⁷–10¹⁰ pores in parallel when electrolyte concentration across the membranes is asymmetric. Ion diffusion through the large number of channels induces time-dependent electrolyte asymmetry that drives the system through different memristive states. The behaviors of series composite memristors with different configurations are also presented. In addition to helping understand fluidic devices and circuits for neuromorphic computing, the results also shed light on the development of field-assisted ion-selection-membrane filtration techniques as well as the investigations of large neurons and giant synapses. Further work is needed to de-embed parasitic components of the measurement setup to obtain intrinsic large memristor properties. Full article

The mechanism by which voltage-gated ion channels open and close has been the subject of intensive investigation for decades. For a large class of potassium channels and related sodium channels, the consensus has been that the gating current preceding the main ionic current is a large movement of positively charged segments of protein from voltage-sensing domains that are mechanically connected to the gate through linker sections of the protein, thus opening and closing the gate. We have pointed out that this mechanism is based on evidence that has alternate interpretations in which protons move. Very little literature considers the role of water and protons in gating, although water must be present, and there is evidence that protons can move in related channels. It is known that water has properties in confined spaces and at the surface of proteins different from those in bulk water. In addition, there is the possibility of quantum properties that are associated with mobile protons and the hydrogen bonds that must be present in the pore; these are likely to be of major importance in gating. In this review, we consider the evidence that indicates a central role for water and the mobility of protons, as well as alternate ways to interpret the evidence of the standard model in which a segment of protein moves. We discuss evidence that includes the importance of quantum effects and hydrogen bonding in confined spaces. K⁺ must be partially dehydrated as it passes the gate, and a possible mechanism for this is considered; added protons could prevent this mechanism from operating, thus closing the channel. The implications of certain mutations have been unclear, and we offer consistent interpretations for some that are of particular interest. Evidence for proton transport in response to voltage change includes a similarity in sequence to the H_v1 channel; this appears to be conserved in a number of K⁺ channels. We also consider evidence for a switch in -OH side chain orientation in certain key serines and threonines. Full article

Alkaline electrolytic water hydrogen generation, a key driver in the growth of hydrogen energy, heavily relies on high-efficiency and high-purity ion exchange membranes. In this study, three-dimensional (3D) wrinkled reduced graphene oxide (WG) nanosheets obtained through a simple thermal reduction process and two-dimensional (2D) graphene oxide act as building blocks, with ethylenediamine as a crosslinking stabilizer, to construct a unique 3D/2D 2 nm-tunneling structure between the GO and WG sheets through via an amide connection at a WG/GO ratio of 1:1. Here, the wrinkled graphene (WG) undergoes a transition from two-dimensional (2D) graphene oxide (GO) into three-dimensional (3D) through the adjustment of surface energy. By increasing the interlayer spacing and the number of ion fluid channels within the membranes, the E-W/G membrane has achieved the rapid passage of hydroxide ions (OH⁻) and simultaneous isolation of produced gas molecules. Moreover, the dense 2 nm nano-tunneling structure in the electrolytic water process enables the E-W/G membrane to attain current densities >99.9% and an extremely low gas crossover rate of hydrogen and oxygen. This result suggests that the as-prepared membrane effectively restricts the unwanted crossover of gases between the anode and cathode compartments, leading to improved efficiency and reduced gas leakage during electrolysis. By enhancing the purity of the hydrogen production industry and facilitating the energy transition, our strategy holds great potential for realizing the widespread utilization of hydrogen energy. Full article

Animal venoms are complex biochemical secretions rich in highly potent and selective bioactive molecules, including peptides, enzymes, and small organic compounds. Once associated primarily with toxicity, these venoms are now recognized as a promising source of therapeutic agents for a wide range of medical conditions. This review provides a comprehensive analysis of the pharmacological potential of venom-derived compounds, highlighting their mechanisms of action, such as ion channel modulation, receptor targeting, and enzyme inhibition. Successful venom-derived drugs like captopril and ziconotide exemplify the translational potential of this biological arsenal. We discuss therapeutic applications in cardiovascular diseases, chronic pain, cancer, thrombosis, and infectious diseases, as well as emerging peptide candidates in clinical development. Technological advancements in omics, structural biology, and synthetic peptide engineering have significantly enhanced the discovery and optimization of venom-based therapeutics. Despite challenges related to stability, immunogenicity, and ecological sustainability, the integration of AI-driven drug discovery and personalized medicine is expected to accelerate progress in this field. By synthesizing current findings and future directions, this review underscores the transformative potential of animal venoms in modern pharmacotherapy and drug development. We also discuss current therapeutic limitations and how venom-derived compounds may address unmet needs in specific disorders. Full article

Electrical restitution (ER) is a determinant of cardiac repolarization stability and can be measured as steady action potential (AP) duration (APD) at different pacing rates—the so-called dynamic restitution (ER_dyn) curve—or as APD changes after pre- or post-mature stimulations—the so-called standard restitution (ER_s1s2) curve. Short-term AP memory (M_s) has been described as the slope difference between the ER_dyn and ER_s1s2 curves, and represents the information stored in repolarization dynamics due to previous pacing conditions. Although previous studies have shown its dependence on ion currents and calcium cycling, a systematic picture of these features is lacking. By means of simulations with a human ventricular AP model, I show that APD restitution can be described under randomly changing pacing conditions (ER_rand) and M_s derived as the slope difference between ER_dyn and ER_rand. Thus measured, M_s values correlate with those measured using ER_s1s2. I investigate the effect on M_s of modulating the conductance of ion channels involved in AP repolarization, and of abolishing intracellular calcium transient. I show that M_s is chiefly determined by ER_dyn rather than ER_rand, and that interventions that shorten/prolong APD tend to decrease/increase M_s. Full article

Bestrophinopathies are a group of inherited retinal diseases caused by mutations in the BEST1 gene. The protein encoded by this gene, bestorphin-1 (hBest1), is a calcium-dependent transmembrane channel localized on the basolateral membrane of retinal pigment epithelial (RPE) cells. We have already demonstrated the surface behavior and organization of recombinant hBest1 and its interactions with membrane lipids such as 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), sphingomyelin (SM) and cholesterol (Chol) in models of biological membranes, which affect the hBest1 structure–function relationship. The main aim of our current investigation is to integrate pure hBest1 protein into lipid bilayer nanostructures. We synthesized and characterized various hBest1-containing nanostructures based on 1,2-Dipalmitoylphosphatidylcholine (DPPC), SM, glycerol monooleate (GMO) and Chol in different ratios and determined their cytotoxicity and incorporation into cell membranes and/or cells by immunofluorescence staining. Our results show that these newly designed nanoparticles are not cytotoxic and that their incorporation into MDCK II cell membranes (used as a model system) may provide a mechanism that could be applied to RPE cells expressing mutated hBest1 in order to restore their ion transport functions, affected by mutated and malfunctioning hBest1 molecules. Full article

Cardiomyocytes, similarly to cells in various tissues, are responsive to mechanical stress of all types, which is reflected in the significant alterations to their electrophysiological characteristics. This phenomenon, known as mechanoelectric feedback, is based on the work of mechanically gated channels (MGCs) and mechano-sensitive channels (MSCs). Since microgravity (MG) in space, as well as simulated microgravity (SMG), changes the morphological and physiological properties of the heart, it was assumed that this result would be associated with a change in the expression of genes encoding MGCs and MSCs, leading to a change in the synthesis of channel proteins and, ultimately, a change in channel currents during cell stretching. In isolated ventricular cardiomyocytes of rats exposed to SMG for 14 days, the amount of MGCs and MSCs gene transcripts was studied using the RNA sequencing method by normalizing the amount of “raw” reads using the Transcripts Per Kilobase Million (TPM) method. Changes in the level of channel protein, using the example of the MGCs TRPM7, were assessed by the Western blot method, and changes in membrane ion currents in the control and during cardiomyocyte stretching were assessed by the patch-clamp method in the whole-cell configuration. The data obtained demonstrate that SMG results in a multidirectional change in the expression of genes encoding various MGCs and MSCs. At the same time, a decrease in the TPM of the MGCs TRPM7 gene leads to a decrease in the amount of TRPM7 protein. The resulting redistribution in the synthesis of most channel proteins leads to a marked decrease in the sensitivity of the current through MGCs to cell stretching and, ultimately, to a change in the functioning of the heart. Full article

This study presents a quantitative electrophysiological method to directly measure the passive transport of ammonium ions through bacterial outer membrane porins. Using a zero-current reversal potential assay in planar lipid bilayers under defined bi-ionic gradients, this study evaluates the permeability of ammonium salts through two general diffusion porins: Omp-Pst2 from Providencia stuartii and OmpF from Escherichia coli. Under matched ionic conditions, Omp-Pst2 exhibited significantly higher ammonium flux—approximately 6000 ions per second per monomer at a 1 µM gradient—compared to ~4000 ions per second for OmpF. Importantly, the identity of the accompanying anion (chloride vs. sulfate) modulated both the ion selectivity and flux rate, highlighting the influence of counterion interactions on porin-mediated transport. These findings underscore how structural differences between porins—such as pore geometry and charge distribution—govern ion permeability. The method applied here provides a robust framework for quantifying nutrient flux at the single-channel level and offers novel insights into how Gram-negative bacteria may adapt their membrane transport mechanisms under nitrogen-limited conditions. This work not only enhances our understanding of outer membrane permeability to small ions like ammonium, but also has implications for antimicrobial strategy development and biotechnological applications in nitrogen assimilation. Full article

Redox regulation is crucial for the cardiac action potential, coordinating the sodium-driven depolarization, calcium-mediated plateau formation, and potassium-dependent repolarization processes required for proper heart function. Under physiological conditions, low-level reactive oxygen species (ROS), generated by mitochondria and membrane oxidases, adjust ion channel function and support excitation–contraction coupling. However, when ROS accumulate, they modify a variety of important channel proteins in cardiomyocytes, which commonly results in reducing potassium currents, enhancing sodium and calcium influx, and enhancing intracellular calcium release. These redox-driven alterations disrupt the cardiac rhythm, promote after-depolarizations, impair contractile force, and accelerate the development of heart diseases. Experimental models demonstrate that oxidizing agents reduce repolarizing currents, whereas reducing systems restore normal channel activity. Similarly, oxidative modifications of calcium-handling proteins amplify sarcoplasmic reticulum release and diastolic calcium leak. Understanding the precise redox-dependent modifications of cardiac ion channels would guide new possibilities for targeted therapies aimed at restoring electrophysiological homeostasis under oxidative stress, potentially alleviating myocardial infarction and cardiovascular dysfunction. Full article

The amyloid-beta 1-42 (Aβ1-42) oligomers are the most cytotoxic species of the amyloid family and play a key role in the pathology of Alzheimer’s Disease (AD). They have been shown to damage cellular membranes, but the exact mechanism is complex and not well understood. Multiple routes of membrane damage have been proposed, including the formation of pores and ion channels. In this work, we study the membrane damage induced by Aβ1-42 oligomers using black lipid membrane (BLM) electrophysiology and compare their action with gramicidin, known to form ion channels. Our data show that Aβ1-42 oligomers can induce a variety of damage in the lipid membranes composed of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), and cholesterol (CHOL), including small ion channels, similar to the gramicidin channels, with an average inner diameter smaller than 5 Å. These channels have a short retaining time in lipid membranes, suggesting that they are highly dynamic. Our studies provide new insights into the mechanism of membrane damage caused by Aβ1-42 oligomers and extend the current perception of the Aβ channelopathy hypothesis. It provides a more in-depth understanding of the molecular mechanism by which small Aβ oligomers induce cytotoxicity by interacting with lipid membranes in AD. Full article

Proton and heavy ion irradiation experiments were carried out on Cascode GaN HEMT devices. Results show that device degradation from heavy ion irradiation is more significant than from proton irradiation. Under proton irradiation, obvious device degradation occurred. Low-frequency noise testing revealed a notable increase in internal defect density, reducing channel carrier concentration and mobility, and causing electrical performance degradation. Under heavy ion irradiation, devices suffered from single-event burnout (SEB) and exhibited increased leakage current. Failure analysis of post-irradiation devices showed that those with leakage current increase had conductive channels without morphological changes, while burned out devices showed obvious damage between the gate and drain regions. SRIM simulation indicated that ionization energy loss-induced electron–hole pairs and displacement damage from nuclear energy loss were the main causes of degradation. Sentaurus TCAD simulation of heavy ion irradiated GaN HEMT devices confirmed the mechanisms of leakage current increase and SEB. Full article