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Background and Purpose Experimental Approach Key Results Conclusion and Implications Mutations in both KCNQ1 and KCNE1, which together form the cardiac IKs current, are associated with inherited conditions such as long and short QT syndromes. Mefenamic acid, a non‐steroidal anti‐inflammatory drug, is an IKs potentiator and may be utilised as an archetype to design therapeutically useful IKs agonists. However, here we show that mefenamic acid can also act as an IKs inhibitor, and our data reveal its dual effects on KCNQ1/KCNE1 channels.Effects of mefenamic acid on wild type (WT) and mutant KCNQ1/KCNE1 channels expressed in tsA201 cells were studied using whole cell patch clamp. Molecular dynamics simulations were used to determine trajectory clustering.Mefenamic acid inhibits WT IKs at high concentrations while preserving some attributes of current potentiation. Inhibitory actions of mefenamic acid are unmasked at lower drug concentrations by KCNE1 and KCNQ1 mutations in the mefenamic acid binding pocket, at the extracellular end of KCNE1 and in the KCNQ1 S6 helix. Mefenamic acid does not inhibit KCNQ1 in the absence of KCNE1 but inhibits IKs current in a concentration‐dependent manner in the mutant channels. Inhibition involves modulation of pore kinetics and/or voltage sensor domain‐pore coupling in WT and in the KCNE1 E43C mutant.This work highlights the importance of structural motifs at the extracellular inter‐subunit interface of KCNQ1 and KCNE1 channels, and their interactions, in determining the nature of drug effects on the IKs channel complex and has important implications for treating patients with specific long QT mutations. [ABSTRACT FROM AUTHOR]

Extracting lithium resources from seawater and brine can promote the development of the new energy materials industry. The electrochemical method is green and efficient. Iron phosphate (FePO4) crystal, with its 1D ion channel, holds significant potential as a primary lithium extraction electrode material. Li+ encounters a substantial concentration disadvantage in brines, and the co‐intercalation of Na+ diminishes Li+ selectivity. To address this issue, this work enhances the energy barrier for Na+ insertion through prelithiation strategies applied to the 1D channels of FePO4 crystal, thereby improving Li+ selectivity, and further investigating the prelithiation effect with particle size and morphology control. The results indicate that the Li(4C‐40%)FePO4// Activated carbon(AC) system enhances selectivity of lithium. The Li(4C‐40%)FePO4 with size diameter of 2500 nm demonstrates an energy consumption of 0.79 Wh mol−1 and a purity of 97.94% for lithium extraction at a unit lithium extraction of 5.93 mmol g−1 in simulated brine. Li(4C‐40%)FePO4‐nanoplates demonstrate the most optimal lithium extraction performance among the three morphologies due to their lamellar structure's short ion diffusion path in the [010] channel, favoring Li+ diffusion. The diffusion energy barriers of Li+ and Na+ are calculated using Density Functional Theory (DFT) before and after prelithiation, showing good agreement with experimental results. [ABSTRACT FROM AUTHOR]

In the current era of rapid development in the new energy vehicle industry, graphite (Gr) has gained significant attention as the primary anode material for commercial lithium‐ion batteries due to its exceptional reversibility in lithium‐ion insertion/extraction and abundant availability. In this study, a multifunctional ferroelectric Bi12TiO20@C (BIT@C) modified interlayer between Gr and polymer electrolyte (PE) is fabricated. This approach established a channel and homogeneous ion‐conducting network that facilitated lithium‐ion intercalation into Gr at the interface while suppressing erratic lithium precipitation, thereby stabilizing the structure of Gr. The uniform electric field generated by BIT intercalation enabled homogeneous intercalation/deintercalation of lithium ions, effectively preventing the structural collapse of the Gr anode. Assembled LIBs exhibited reduced polarization and enhanced electrochemical properties attributed to facile charge transfer at the interface. The results revealed that Gr│carbon‐BIT@C‐lithium bistrifluoromethane sulfonimide (LiTFSI)/silicon dioxide (SiO2)/poly allyl acetoacetate (PAAA)/poly(vinylidene fluoride‐hexafluoropropylene) (P(VDF‐HFP))/polyvinylidene fluoride (PVDF)│LiFePO4 (LFP) batteries achieved an initial discharge specific capacity of 120.4 mAh g−1 with stable performance over 1200 cycles at 2 C and room temperature (RT), maintaining a Coulombic efficiency of 99.5% after 1200 cycles. The ferroelectric‐modified interface addressed challenges associated with ion transport at the electrode‐electrolyte interface. [ABSTRACT FROM AUTHOR]

Electrospun is a unique technique for the fabrication of multiscale structured nanofibers (MSNFs), which can be used as functional units for improving the performance of lithium‐based batteries. This review systematically examines how MSNFs, including core–shell, hollow porous, multichannel, wire‐in‐tube, tube‐in‐tube, and hierarchical nanofibers, effectively improve battery performance as components in lithium‐based batteries. The application of aforementioned MSNFs and their chemical modification contributes to the development of lithium‐based batteries with high energy density and enhanced safety when used as electrodes, separators, and electrolytes. Specifically, MSNFs are used to derive electrodes and electrolytes that improve electron/ion transfer rates, increase the utilization ratio of active materials, suppress dendrite growth, and mitigate volume expansion, enabling fast and stable electrochemical reactions at the electrodes. Additionally, MSNFs‐derived separators, which feature more ion transport channels, exceptional mechanical properties, and the capability to inhibit thermal runaway, are also discussed. Finally, the challenges and prospective pathways for electrospun technology in the application of lithium‐based batteries are reviewed. [ABSTRACT FROM AUTHOR]

Chronic neuropathic pain is a debilitating pain syndrome caused by damage to the nervous system that is poorly served by current medications. Given these problems, clinical studies have pursued extracts of the plant Cannabis sativa as alternative treatments for this condition. The vast majority of these studies have examined cannabinoids which contain the psychoactive constituent delta‐9‐tetrahydrocannabinol (THC). While there have been some positive findings, meta‐analyses of this clinical work indicates that this effectiveness is limited and hampered by side‐effects. This review focuses on how recent preclinical studies have predicted the clinical limitations of THC‐containing cannabis extracts, and importantly, point to how they might be improved. This work highlights the importance of targeting channels and receptors other than cannabinoid CB1 receptors which mediate many of the side‐effects of cannabis. [ABSTRACT FROM AUTHOR]

Chronic pelvic pain (CPP) is the primary symptom of endometriosis patients, but adequate treatments are lacking. Modulation of ion channels expressed by sensory nerves innervating the viscera has shown promise for the treatment of irritable bowel syndrome and overactive bladder. However, similar approaches for endometriosis‐associated CPP remain underdeveloped. Here, we examined the role of the voltage‐gated sodium (NaV) channel NaV1.7 in (i) the sensitivity of vagina‐innervating sensory afferents and investigated whether (ii) NaV1.7 inhibition reduces nociceptive signals from the vagina and (iii) ameliorates endometriosis‐associated CPP. The mechanical responsiveness of vagina‐innervating sensory afferents was assessed with ex vivo single‐unit recording preparations. Pain evoked by vaginal distension (VD) was quantified by the visceromotor response (VMR) in vivo. In control mice, pharmacological activation of NaV1.7 with OD1 sensitised vagina‐innervating pelvic afferents to mechanical stimuli. Using a syngeneic mouse model of endometriosis, we established that endometriosis sensitised vagina‐innervating pelvic afferents to mechanical stimuli. The highly selective NaV1.7 inhibitor Tsp1a revealed that this afferent hypersensitivity occurred in a NaV1.7‐dependent manner. Moreover, in vivo intra‐vaginal treatment with Tsp1a reduced the exaggerated VMRs to VD which is characteristic of mice with endometriosis. Conversely, Tsp1a did not alter ex vivo afferent mechanosensitivity nor in vivo VMRs to VD in Sham control mice. Collectively, these findings suggest that NaV1.7 plays a crucial role in endometriosis‐induced vaginal hyperalgesia. Importantly, NaV1.7 inhibition selectively alleviated endometriosis‐associated CPP without the loss of normal sensation, suggesting that selective targeting of NaV1.7 could improve the quality of life of women with endometriosis. [ABSTRACT FROM AUTHOR]

Neuronal information processing depends on converting membrane depolarizations into compartmentalized biochemical signals that can modify neuronal activity and structure. However, our understanding of how neurons translate electrical signals into specific biochemical responses remains limited, especially in the soma where gene expression and ion channel function are crucial for neuronal activity. Here, I emphasize the importance of physically compartmentalizing action potential‐triggered biochemical reactions within the soma. Emerging evidence suggests that somatic endoplasmic reticulum–plasma membrane (ER‐PM) junctions are specialized organelles that coordinate electrical and biochemical signaling. The juxtaposition of ion channels and signaling proteins at a prominent subset of these sites enables compartmentalized calcium and cAMP‐dependent protein kinase (PKA) signaling. I explore the hypothesis that these PKA‐containing ER‐PM junctions serve as critical sites for translating membrane depolarizations into PKA signals and identify key gaps in knowledge of the assembly, regulation, and neurobiological functions of this somatic signaling system. [ABSTRACT FROM AUTHOR]

Objective: Developmental and epileptic encephalopathies (DEEs) can result from dominant, gain of function variants of neuronal ion channels. More than 450 de novo missense variants of the sodium channel gene SCN8A have been identified in individuals with DEE. Methods: We studied a mouse model carrying the patient Scn8a variant p.Asn1768Asp. An AAV‐PHP.eB virus carrying an allele‐specific single guide RNA (sgRNA) was administered by intracerebroventricular injection. Cas9 was provided by an inherited transgene. Results: Allele‐specific disruption of the reading frame of the pathogenic transcript generated out‐of‐frame indels in 1/4 to 1/3 of transcripts throughout the brain. This editing efficiency was sufficient to rescue lethality and seizures. Neuronal hyperexcitability was reduced in cells expressing the virus. Interpretation: The data demonstrate efficient allele‐specific editing of a dominant missense variant and support the feasibility of allele‐specific therapy for DEE epilepsy. ANN NEUROL 2024;96:958–969 [ABSTRACT FROM AUTHOR]

Millions of people worldwide are affected by neurodegenerative diseases and cognitive impairment, which includes dementia, while there are only symptomatic treatments available for this syndrome at present. However, several important prospective drug targets have been identified in recent years that can potentially arrest or even reverse the progression of neurodegenerative diseases. Their natural or synthetic ligands are currently in the experimental stage of drug development. In vitro and preclinical (e.g. using animal models) studies confirm their therapeutic potential, but clinical trials often fail or produce conflicting results. Here, we first review the complexity and typology of dementia, followed by the discussion of currently available treatments, and, finally, some novel molecular and cellular approaches to this problem. [ABSTRACT FROM AUTHOR]

Transient receptor potential canonical 3 (TRPC3) protein belongs to the TRP family of nonselective cation channels. Its activation occurs by signaling through a G protein‐coupled receptor (GPCR) and a phospholipase C‐dependent (PLC) pathway. Perturbations in the expression of TRPC3 are associated with a plethora of pathophysiological conditions responsible for disorders of the cardiovascular, immune, and central nervous systems. The recently solved cryo‐EM structure of TRPC3 provides detailed inputs about the underlying mechanistic aspects of the channel, which in turn enables more efficient ways of designing small‐molecule modulators. Pharmacologically targeting TRPC3 in animal models has demonstrated great efficacy in treating diseases including cancers, neurological disorders, and cardiovascular diseases. Despite extensive scientific evidence supporting some strong correlations between the expression and activity of TRPC3 and various pathophysiological conditions, therapeutic strategies based on its pharmacological modulations have not led to clinical trials. The development of small‐molecule TRPC3 modulators with high safety, sufficient brain penetration, and acceptable drug‐like profiles remains in progress. Determining the pathological mechanisms for TRPC3 involvement in human diseases and understanding the requirements for a drug‐like TRPC3 modulator will be valuable in advancing small‐molecule therapeutics to future clinical trials. In this review, we provide an overview of the origin and activation mechanism of TRPC3 channels, diseases associated with irregularities in their expression, and new development in small‐molecule modulators as potential therapeutic interventions for treating TRPC3 channelopathies. [ABSTRACT FROM AUTHOR]

Priority 1: critical WHO pathogen Acinetobacter baumannii depends on ATP synthesis and ATP:ADP homeostasis and its bifunctional F1FO‐ATP synthase. While synthesizing ATP, it regulates ATP cleavage by its inhibitory ε subunit to prevent wasteful ATP consumption. We determined cryo‐electron microscopy structures of the ATPase active A. baumannii F1‐αßγεΔ134–139 mutant in four distinct conformational states, revealing four transition states and structural transformation of the ε's C‐terminal domain, forming the switch of an ATP hydrolysis off‐ and an ATP synthesis on‐state based. These alterations go in concert with altered motions and interactions in the catalytic‐ and rotary subunits of this engine. These A. baumannii interacting sites provide novel pathogen‐specific targets for inhibitors, with the aim of ATP depletion and/or ATP synthesis and growth inhibition. Furthermore, the presented diversity to other bacterial F‐ATP synthases extends the view of structural elements regulating such a catalyst. [ABSTRACT FROM AUTHOR]

Calcium homeostasis modulators (CALHMs) are the most recently discovered members of the large‐pore channel family. They mediate the conductance of ions and larger molecules, such as ATP, and play critical roles in pathways related to Alzheimer's disease, neuroinflammation, neuromodulation, taste perception and innate immune responses. Since the inaugural report on CALHM1 in 2008, significant breakthroughs have revealed their biological roles, ion and ATP channel functions, and structures, positioning the field for further advancements. In this review, we discuss the overall progress and recent developments in understanding the biological roles, functions and molecular structures of CALHM proteins. [ABSTRACT FROM AUTHOR]

Reverse electrodialysis (RED) technology, relying on ion‐selective permeability membranes (ISPM), offers a direct means of harnessing osmotic energy from the salinity difference between seawater and freshwater. Critical technical challenges include limitations in ISPM's immobile charge carriers, transmembrane ionic internal resistance, and durability in water. Drawing inspiration from the subunit structure of the epithelial sodium channel (ENaC), an ISPM assembled using a supramolecular engineering strategy is introduced. This innovative approach enables the synergistic action of multiple molecular building blocks to mimic the distribution of ENaC subunit structures, strategically planning the placement of immobile charge carriers on nanofluidic channels. The design incorporates nano‐confined oxygen‐rich functionalized MXene (O‐MXene) and high‐strength polymer backbone aramid fibers to construct 3D nanofluidic channels with a high surface charge density. Enhanced by a bonding network of sodium carboxymethylcellulose, the ISPM achieved an exceptional output power density of 21.7 W m−2 and 46.0% energy conversion efficiency in a RED half‐cell system using natural seawater and river water, surpassing current technologies. This research not only advances RED technology but also provides biomimetic customization concepts for ISPM design across various applications, including flow batteries, fuel cells, and related fields. [ABSTRACT FROM AUTHOR]

Serotonin, a monoamine neurotransmitter, is important in both the central nervous system (CNS) and the peripheral nervous system. Malfunction of serotonin signaling leads to various disorders. We studied serotonin signaling from serotonergic neurons inside the ventral nerve cord of Drosophila melanogaster. Serotonergic neurons and stimulated release were visualized and achieved with mCherry and channelrhodopsin‐2 (an optogenetically transfected ion channel), respectively, and two electrochemical techniques quantified serotonin release and vesicular content. Mean vesicular serotonin content released during exocytosis from these neurons was 84 %, considerably higher than reported in previous studies regarding octopamine (4.5 %) and glutamate release (31 %). Serotonin content within all vesicles is uniformly changed when serotonin concentration is inhibited or enhanced. However, serotonin release exhibits two Gaussian distributions: higher frequency of small release events, and similar or slightly higher frequency of large events, resulting in differential release fractions ranging from partial (13–18 %) to full (100 %) release after treatment with agents to either enhance or diminish release. This is the first example of consistent full exocytotic release events we have observed in any system. We suggest one pool of vesicles can release significantly diverse fractions of transmitter load during exocytosis, a potentially novel pathway to regulate exocytosis and neuronal signaling. [ABSTRACT FROM AUTHOR]

Developing biodegradable electrodes is a significant step toward environmental sustainability and cost reduction in battery technology. This paper presents a new approach that utilizes metal‐organic framework (MOF)‐encapsulated silicon nanoparticles (SiNPs) as the active anode material within a cellulose‐based electrode. The electrode is free‐standing, flexible, biodegradable, and significantly reduces the strain experienced by SiNPs during volume expansion, resulting in improved capacity and cycle life stability of SiNPs. The high porosity of the electrode creates efficient lithium (Li+) ion transport channels and enhances electrolyte absorption, thus promoting effective contact between the electrolyte and active material. The outcome is rapid electrode kinetics and a highly reversible discharge capacity of 1744.6 mAh g−1 at 0.5 A g−1 versus Li/Li+ over 1000 cycles. Further, full cell tests are conducted that demonstrate a stable cycle performance exceeding 3400 cycles, with an initial discharge capacity retention of 80.5% at 0.5 A g−1. By employing cellulose and avoiding toxic organic solvents and binders, the proposed approach is promising for a substantial reduction of the production costs of Li‐ion batteries. The scalability of the proposed method further enhances its practical viability, offering intriguing economic implications for the future of battery technology. [ABSTRACT FROM AUTHOR]

Covalent organic framework (COF) membranes feature with well‐developed 1D in‐plane pores and parallelly arranged 2D interlayer gallery, presenting promising platform for precise separations. However, it remains a formidable challenge to construct and regulate membrane channels at angstrom scale. Herein, pH‐sensitive dopamine is taken advantage to elaborately engineer the spatial size of 1D/2D channels in COF membranes for the separations of alkali metal ions. Acid treatment allows monomolecular dopamine to segment 1D in‐plane pores of COF membrane, achieving ultramicroporous regulation from 1.25 nm to 0.71 nm, which enables high selectivity of 18.7 for K+/Li+ separation. Molecular dynamics simulations reveal the higher dehydration degree, weaker channel‐cation interaction and faster diffusion coefficient of K+ than Li+. For alkaline treatment, dopamine self‐polymerizes to form nanoparticles between COF layers, which enlarges the 2D interlayer channels from 0.33 nm to 0.45 nm in COF membrane, enabling high‐permeance ion/molecule separations. The water permeance increases 86.7% to 404 L m−2 h−1 bar−1, without the sacrifice of membrane sieving ability. Both cation separation and ion/molecule separation performances outperform the current state‐of‐the‐art membranes. This dopamine‐mediated channel engineering strategy may provide the new insights for the design of membrane channels in precise separations. [ABSTRACT FROM AUTHOR]

Solid‐state nanopore gating inspired by biological ion channels is gaining increasing traction due to a large range of applications in biosensing and drug delivery. Integration of stimuli‐responsive molecules such as poly(N‐isopropylacrylamide) (PNIPAM) inside nanopores can enable temperature‐dependent gating, which so far has only been demonstrated using external heaters. In this work, plasmonic resonators are combined inside the nanopore architecture with PNIPAM to enable optical gating of individual or multiple nanopores with micrometer resolution and a switching speed of a few milliseconds by thermo‐plasmonics effects. A temperature change of 40 kelvin per millisecond is achieved and demonstrates the efficacy of this method using nanopore ionic conductivity measurements that enable selective activation of individual nanopores in an array. Moreover, the selective gating of specific nanopores in an array can set distinct ionic conductance levels: low, medium, and high (i.e., “0,” “1,” and “2”), which can be exploited for logical gating with optical signal control. Such selective optical gating in nanopore arrays marks a breakthrough in nanofluidics, as it paves the way toward smart devices that offer multifunctional applications including biosensing, targeted drug delivery, and fluidic mixing. [ABSTRACT FROM AUTHOR]

Recently, research on polyoxometalates (POMs) has gained significant momentum. Owing to their properties as electronic sponges, POMs catalyst harbor substantial potential in lithium‐sulfur battery research. However, POMs undergo a transformation into reduced heteropoly blue (HPB) during electrochemical reactions, which then dissolve into the electrolyte, resulting in catalyst loss. In this research, we amalgamated 18‐crown‐6 (CR6) with K3PW12O40, (KPW), synthesized a novel POM‐based supramolecular compound, and integrated it with graphene oxide (GO) to fabricate a multi‐functional composite polypropylene (PP) separator KPW‐CR6/GO/PP. The crown ether array was employed to immobilize POM and construct ion transport channels, thereby enhancing the Li+ migration rate and capturing polysulfides. Subsequently, leveraging the stable structure and redox properties of POM, the polysulfide is catalyzed to transform and inhibit the shuttle effect, thereby protecting the Li anode. The lithium‐sulfur batteries with the Crown ether‐POM supramolecular compound separators, exhibit enhanced capacity and stability (1073.3 mAh g−1 at 1.0 C, and 81.5 % retention rate after 250 cycles). The battery (S loading: 3.2 mg cm−2) presents an initial specific discharge capacity of 543.4 mAh g−1 at 0.5 C, with 89.8 % of the capacity retained after 160 cycles. This underlines the practical application potential of Crown ether‐POM supramolecular materials in Li−S batteries. [ABSTRACT FROM AUTHOR]

Angstrom‐scale fluidic channels offer immense potential for applications in areas such as desalination, molecular sieving, biomolecular sequencing, and dialysis. Inspired by biological ion channels, nano‐ and angstrom (Å)‐scale channels are fabricated that mimic these molecular or atomic‐scale dimensions. At the Å‐scale, these channels exhibit unique phenomena, including selective ion transport, osmotic energy generation, fast water and gas flows, and neuromorphic ion memory. However, practical utilization of Å‐scale channels is often hindered by contamination, which can clog these nanochannels. In this context, a promising technique is introduced here for unclogging 2D channels, particularly those with sub‐nanometre dimensions (≈6.8 Å). The voltage‐cycling method emerges as an efficient and reliable solution for this challenge. The electric field effectively dislodges contaminants from the clogged Å‐scale channels, facilitating ion and molecular transport. This study provides practical guidelines for reviving clogged nano‐ and Å‐scale channels, thereby enhancing their applicability in various ion and molecular transport applications. [ABSTRACT FROM AUTHOR]

Background and Purposes Experimental Approach Key Results Conclusion and Implications Reduced inward rectifier potassium channel (Kir2.1) functioning is associated with heart failure and may cause Andersen‐Tawil Syndrome, among others characterized by ventricular arrhythmias. Most heart failure or Andersen–Tawil Syndrome patients are treated with β‐adrenoceptor antagonists (β‐blockers) or sodium channel blockers; however, these do not specifically address the inward rectifier current (IK1) nor aim to improve resting membrane potential stability. Consequently, additional pharmacotherapy for heart failure and Andersen–Tawil Syndrome treatment would be highly desirable. Acute propafenone treatment at low concentrations enhances IK1 current, but it also exerts many off‐target effects. Therefore, discovering and exploring new IK1‐channel openers is necessary.Effects of propafenone and 10 additional propafenone analogues were analysed. Currents were measured by single‐cell patch‐clamp electrophysiology. Kir2.1 protein expression levels were determined by western blot analysis and action potential characteristics were further validated in human‐induced pluripotent stem cells–derived cardiomyocytes (hiPSC‐CMCs). Molecular docking was performed to obtain detailed information on drug‐channel interactions.Analogues GPV0019, GPV0057 and GPV0576 strongly increased the outward component of IK1 while not affecting the Kir2.1 channel expression levels. GPV0057 did not block IKr at concentrations below 0.5 μmol L−1 nor NaV1.5 current below 1 μmol L−1. Moreover, hiPSC‐CMC action potential duration was also not affected by GPV0057 at 0.5 and 1 μmol L−1. Structure analysis indicates a mechanism by which GPV0057 might enhance Kir2.1 channel activation.GPV0057 has a strong efficiency towards increasing IK1, which makes it a good candidate to address IK1 deficiency‐associated diseases. [ABSTRACT FROM AUTHOR]

Multimeric membrane proteins are produced in the endoplasmic reticulum and transported to their target membranes which, for ion channels, is typically the plasma membrane. Despite the availability of many fully assembled channel structures, our understanding of assembly intermediates, multimer assembly mechanisms, and potential functions of non-standard assemblies is limited. We demonstrate that the pentameric ligand-gated serotonin 5-HT3A receptor (5-HT3AR) can assemble to tetrameric forms and report the structures of the tetramers in plasma membranes of cell-derived microvesicles and in membrane memetics using cryo-electron microscopy and tomography. The tetrameric structures have near-symmetric transmembrane domains, and asymmetric extracellular domains, and can bind serotonin molecules. Computer simulations, based on our cryo-EM structures, were used to decipher the assembly pathway of pentameric 5-HT3R and suggest a potential functional role for the tetrameric receptors. Synopsis: Serotonin-gated ion channels are typically found as pentamers in the plasma membrane, but how these structures assemble is not well understood. This work shows that on such receptor, 5-HT3AR, can also form stable tetramers, providing insights into the receptor's assembly pathway. The pentameric ligand-gated serotonin 5-HT3A receptor can assemble into stable near-C2 symmetric and asymmetric tetrameric forms. Tetramers are capable of binding serotonin which does not lead to the opening of the ion pore. Tetramers can be delivered to the cellular plasma membrane where they co-localize with pentamers of 5-HT3AR. Simulations suggest the assembly pathway of 5-HT3AR pentamers from lower oligomers via the tetrameric forms. Different assemblies of a serotonin-gated ion channel co-exist in the plasma membrane, informing about receptor assembly. [ABSTRACT FROM AUTHOR]

Fiber gel dye‐sensitized solar cells (FGDSCs) are recognized as an effective solution for high‐performance, durable and safe wearable power supply. However, poor and unstable interfaces between fiber electrodes and gel electrolytes are bottleneck problems that have restricted the photovoltaic performances of FGDSCs and their stabilities during deformations. Here, an FGDSC with stable interlaced interfaces is designed by incorporating polymerized gel electrolyte into the aligned channels in fiber electrodes and the gaps between photoanode and counter electrode in situ. The interlaced structure of gel electrolyte in FGDSC improves the interfacial stability and provided stable channels for rapid ion diffusions, offering efficient charge transports at interfaces. The resulting FGDSC thus produced a high power conversion efficiency of 7.95%, and it is further maintained by over 90% after bending for 5000 cycles. These FGDSCs can be integrated with fiber batteries as a self‐charging power system, demonstrating an effective power solution for wearables. [ABSTRACT FROM AUTHOR]

Micro energy storage devices (MESDs) have emerged as promising energy providers for micro applications due to their integrated performance. However, the limited cycle life and low power density of microbattery, and low energy density of microsupercapacitor have consistently impeded their broader practical implementation. Herein, to obtain a MESD with a long cycle life, excellent power density, and superior energy density, a novel micro battery‐supercapacitor hybrid (MBSH) device is fabricated. Two types of 3D microelectrodes are fabricated, namely, a nanowire network anode based on PEDOT‐TiON and a porous cathode based on Ni(OH)2. Benefiting from the unique hydrophobic characteristics of the PEDOT layer, high electrical conductivity of TiON, and high conductivity, and abundant ion diffusion channels of network microstructure, PEDOT‐TiON NW microelectrodes demonstrate exceptional cycling stability by retaining 70% of their capacity after 40 000 cycles. The achieved MBSH exhibits an extended voltage window ranging from 0 to 1.9 V, impressive power density of 77.5 mW cm−2, and a superior energy density of 55.6 µWh cm−2. Furthermore, it maintains a remarkable capacity retention rate of 71.6% even after undergoing 30 000 cycles. This innovative design paves the way for the developing of high‐performance microdevices with superior electrochemical properties. [ABSTRACT FROM AUTHOR]

In sharp contrast to numerous artificial potassium channels developed over the past decade, the study of artificial lithium‐transporting channels has remained limited. We demonstrate here the use of an interesting class of polymers with intrinsic microporosity (PIM) for constructing artificial lithium channels. These PIM‐derived lithium channels show exceptionally efficient (γLi+>40 pS) and highly selective transport of Li+ ions, with selectivity factors of>10 against both Na+ and K+. By simply adjusting the initial reaction temperature, we can tune the transport property in a way that PIMs synthesized at initial reaction temperatures of 60 °C and 80 °C exhibit improved transport efficiency and selectivity, respectively, in the dioleoyl phosphatidylcholine membrane. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to investigate whether flow fluid shear stress (FFSS)‐mediated signal transduction affects the function of Piezo1 ion channel in chondrocyte and to further explore the role of mechanical overloading in development of temporomandibular joint osteoarthritis (TMJ OA). Methods: Immunohistochemical staining was used to determine the expression of Piezo1 in TMJ OA tissue collected from rat unilateral anterior crossbite (UAC) models. Chondrocytes harvested from normal adult SD rats were treated with FFSS (0, 4, 8, 12 dyn/cm2) in vitro. Immunofluorescent staining, real‐time polymerase chain reaction, western blotting, flow cytometry and phalloidin assay were performed to detect the changes of cellular morphology as well as the expression of Piezo1 and certain pro‐inflammatory and degradative factors in chondrocyte. Results: Immunohistochemical analysis revealed that significantly increased Piezo1 expression was associated with UAC stimulation (p <.05). As applied FFSS escalated (4, 8 and 12 dyn/cm2), the expression levels of Piezo1, ADAMTS‐5, MMP‐13 and Col‐X gradually increased, compared with the non‐FFSS group (p <.05). Administering Piezo1 ion channel inhibitor to chondrocytes beforehand, it was observed that expression of ADAMTS‐5, MMP‐13 and Col‐X was substantially decreased following FFSS treatment (p <.05) and the effect of cytoskeletal thinning was counteracted. The activated Piezo1 ion channel enhanced intracellular Ca2+ excess in chondrocytes during abnormal mechanical stimulation and the increased intracellular Ca2+ thinned the cytoskeleton of F‐actin. Conclusions: Mechanical overloading activates Piezo1 ion channel to promote pro‐inflammation and degradation and to increase Ca2+ concentration in chondrocyte, which may eventually result in TMJ OA. [ABSTRACT FROM AUTHOR]

The sense of smell is still considered a fuzzy sensation. Softly wafting aromas can stimulate the appetite and trigger memories; however, there are many unexplored aspects of its underlying mechanisms, and not all of these have been elucidated. Although the final sense of smell takes place in the brain, it is greatly affected during the preliminary stage, when odorants are converted into electrical signals. After signal conversion through ion channels in olfactory cilia, action potentials are generated through other types of ion channels located in the cell body. Spike trains through axons transmit this information as digital signals to the brain, however, before odorants are converted into digital electric signals, such as an action potential, modification of the transduction signal has already occurred. This review focuses on the early stages of olfactory signaling. Modification of signal transduction mechanisms and their effect on the human sense of smell through three characteristics (signal amplification, olfactory adaptation, and olfactory masking) produced by olfactory cilia, which is the site of signal transduction are being addressed in this review. [ABSTRACT FROM AUTHOR]

Hypotension is one of the main characteristics of the systemic inflammation, basically caused by endothelial dysfunction. Studies have shown that the amino acid L‐kynurenine (KYN) causes vasodilation in mammals, leading to hypotensive shock. In hypotensive shock, when activated by the KYN, the voltage‐gated potassium channel encoded by the family KCNQ (Kv7) gene can cause vasodilation. Fructose‐1,6‐bisphosphate (FBP) it is being considered in studies an anti‐inflammatory, antioxidant, immunomodulator, and a modulator of some ion channels (Ca2+, Na+, and K+). We analyzed the effects of KYN and FBP on mean blood pressure (MBP), systolic and diastolic (DBP) blood pressure, and heart rate variability (HRV) in Wistar rats. Results demonstrated that the administration of KYN significant decreased MBP, DBP, and increased HRV. Importantly, the FBP treatment reversed the KYN effects on MBP, DBP, and HRV. Molecular Docking Simulations suggested that KYN and FBP present a very close estimated free energy of binding and the same position into structure of KCNQ4. Our results did demonstrate that FBP blunted the decrease in BP, provoked by KYN. Results raise new hypotheses for future and studies in the treatment of hypotension resulting from inflammation. [ABSTRACT FROM AUTHOR]

This review paper explores the critical role of vascular ion channels in the regulation of cerebral artery function and examines the impact of Alzheimer's disease (AD) on these processes. Vascular ion channels are fundamental in controlling vascular tone, blood flow, and endothelial function in cerebral arteries. Dysfunction of these channels can lead to impaired cerebral autoregulation, contributing to cerebrovascular pathologies. AD, characterized by the accumulation of amyloid beta (Aβ) plaques and neurofibrillary tangles, has been increasingly linked to vascular abnormalities, including altered vascular ion channel activity. Here, we briefly review the role of vascular ion channels in cerebral blood flow control and neurovascular coupling. We then examine the vascular defects in AD, the current understanding of how AD pathology affects vascular ion channel function, and how these changes may lead to compromised cerebral blood flow and neurodegenerative processes. Finally, we provide future perspectives and conclusions. Understanding this topic is important as ion channels may be potential therapeutic targets for improving cerebrovascular health and mitigating AD progression. [ABSTRACT FROM AUTHOR]

The atrioventricular node (AVN) is a crucial component of the cardiac conduction system. Despite its pivotal role in regulating the transmission of electrical signals between atria and ventricles, a comprehensive understanding of the cellular electrophysiological mechanisms governing AVN function has remained elusive. This paper presents a detailed computational model of mouse AVN cell action potential (AP). Our model builds upon previous work and introduces several key refinements, including accurate representation of membrane currents and exchangers, calcium handling, cellular compartmentalization, dynamic update of intracellular ion concentrations, and calcium buffering. We recalibrated and validated the model against existing and unpublished experimental data. In control conditions, our model reproduces the AVN AP experimental features, (e.g. rate = 175 bpm, experimental range [121, 191] bpm). Notably, our study sheds light on the contribution of L‐type calcium currents, through both Cav1.2 and Cav1.3 channels, in AVN cells. The model replicates several experimental observations, including the cessation of firing upon block of Cav1.3 or INa,r current. If block induces a reduction in beating rate of 11%. In summary, this work presents a comprehensive computational model of mouse AVN cell AP, offering a valuable tool for investigating pacemaking mechanisms and simulating the impact of ionic current blockades. By integrating calcium handling and refining formulation of ionic currents, our model advances understanding of this critical component of the cardiac conduction system, providing a platform for future developments in cardiac electrophysiology. Key points: This paper introduces a comprehensive computational model of mouse atrioventricular node (AVN) cell action potentials (APs).Our model is based on the electrophysiological data from isolated mouse AVN cells and exhibits an action potential and calcium transient that closely match the experimental records.By simulating the effects of blocking specific ionic currents, the model effectively predicts the roles of L‐type Cav1.2 and Cav1.3 channels, T‐type calcium channels, sodium currents (TTX‐sensitive and TTX‐resistant), and the funny current (If) in AVN pacemaking.The study also emphasizes the significance of other ionic currents, including IKr, Ito, IKur, in regulating AP characteristics and cycle length in AVN cells.The model faithfully reproduces the rate dependence of action potentials under pacing, opening the possibility of use in impulse propagation models.The population‐of‐models approach showed the robustness of this new AP model in simulating a wide spectrum of cellular pacemaking in AVN. [ABSTRACT FROM AUTHOR]

Mammalian olfactory sensory neurons (OSNs) generate an odorant‐induced response by sequentially activating two ion channels, which are in their ciliary membranes. First, a cationic, Ca2+‐permeable cyclic nucleotide‐gated channel is opened following odorant stimulation via a G protein‐coupled transduction cascade and an ensuing rise in cAMP. Second, the increase in ciliary Ca2+ opens the excitatory Ca2+‐activated Cl− channel TMEM16B, which carries most of the odorant‐induced receptor current. While the role of TMEM16B in amplifying the response has been well established, it is less understood how this secondary ion channel contributes to response kinetics and action potential generation during single as well as repeated stimulation and, on the other hand, which response properties the cyclic nucleotide‐gated (CNG) channel determines. We first demonstrate that basic membrane properties such as input resistance, resting potential and voltage‐gated currents remained unchanged in OSNs that lack TMEM16B. The CNG channel predominantly determines the response delay and adaptation during odorant exposure, while the absence of the Cl− channels shortens both the time the response requires to reach its maximum and the time to terminate after odorant stimulation. This faster response termination in Tmem16b knockout OSNs allows them, somewhat counterintuitively despite the large reduction in receptor current, to fire action potentials more reliably when stimulated repeatedly in rapid succession, a phenomenon that occurs both in isolated OSNs and in OSNs within epithelial slices. Thus, while the two olfactory ion channels act in concert to generate the overall response, each one controls specific aspects of the odorant‐induced response. Key points: Mammalian olfactory sensory neurons (OSNs) generate odorant‐induced responses by activating two ion channels sequentially in their ciliary membranes: a Na+, Ca2⁺‐permeable cyclic nucleotide‐gated (CNG) channel and the Ca2⁺‐activated Cl⁻ channel TMEM16B.The CNG channel controls response delay and adaptation during odorant exposure, while TMEM16B amplifies the response and influences the time required for the response to reach its peak and terminate.OSNs lacking TMEM16B display faster response termination, allowing them to fire action potentials more reliably during rapid repeated stimulation.The CNG and TMEM16B channels have distinct and complementary roles in shaping the kinetics and reliability of odorant‐induced responses in OSNs. [ABSTRACT FROM AUTHOR]

Many organs are designed to move: the heart pumps each second, the gastrointestinal tract squeezes and churns to digest food, and we contract and relax skeletal muscles to move our bodies. Sensory neurons of the peripheral nervous system detect signals from bodily tissues, including the forces generated by these movements, to control physiology. The processing of these internal signals is called interoception, but this is a broad term that includes a wide variety of both chemical and mechanical sensory processes. Mechanical senses are understudied, but rapid progress has been made in the last decade, thanks in part to the discovery of the mechanosensory PIEZO ion channels (Coste et al., 2010). The role of these mechanosensors within the interoceptive nervous system is the focus of this review. In defining the transduction molecules that govern mechanical interoception, we will have a better grasp of how these signals drive physiology. [ABSTRACT FROM AUTHOR]

Background information: The purinergic ligand‐gated ion channel 7 receptor (P2X7R) is an ATP‐gated ion channel that transmits extracellular signals and induces corresponding biological effects, transient receptor potential vanilloid type 1 (TRPV1) is a non‐selective cation channel that maintains normal physiological functions; numerous studies showed that P2X7R and TRPV1 are associated with inflammatory reactions. Results: The effect of P2X7R knockdown in satellite glial cells (SGCs) on neuronal TRPV1 expression under high glucose and high free fat (HGHF) environment was investigated. P2X7 short hairpin RNA (shRNA) was utilized to downregulate P2X7R in SGCs, and treated and untreated SGCs were co‐cultured with neuronal cell lines. The expression levels of inflammatory factors and signaling pathways in SGCs and neurons were measured using Western blot analysis, RT‐qPCR, immunofluorescence, and enzyme‐linked immunosorbent assays. Results suggested that P2X7 shRNA reduced the expression levels of P2X7R protein and mRNA in SGCs surrounding DRG neurons and downregulated the release of tumor necrosis factor‐alpha and interleukin‐1 beta via the Ca2+/p38 MAPK/NF‐κB pathway. Additionally, the downregulation of P2X7R might decrease TRPV1 expression in neurons via the Ca2+/PKC‐ɛ/p38 MAPK pathway.Conclusions: Reducing P2X7R expression in SCGs in an HGHF environment could decrease neuronal TRPV1 expression via the Ca2+/PKC‐ɛ/p38 MAPK pathway. [ABSTRACT FROM AUTHOR]

Potassium metal batteries (PMBs) are regarded as viable candidates for future electrochemical energy storage devices with potential high energy density and low cost. However, uncontrollable potassium dendrite growth and huge volume expansion severely inhibit the practical application of PMBs. Herein, inspired by the structure and functionalities of tree bark, an antimony (Sb) nano‐clusters decorated N‐doped interconnected carbon nanospheres/potassium composite electrode with biomimetic fast ionic channels is developed to realize the dendrite‐free potassium metal batteries. The composite electrode provides abundant nucleation sites and interconnected ion transport channels, facilitating rapid ion transport kinetics and highly reversible potassium plating/stripping behaviors. Consequently, the assembled symmetric cell exhibits an ultra‐long cycle life (1100 h at 1.0 mA cm−2/1.0 mAh cm−2) in carbonate electrolyte. Moreover, the K full cells demonstrate enhanced cycling stability (1500 cycles at 8 C) and rate capacity (117.27 mAh g−1 at 20 C). This novel biomimetic design of composite anode presents an effective and rational approach for achieving stable PMBs. [ABSTRACT FROM AUTHOR]

Introduction Methods Results Conclusions Arrhythmia occurs as a common heart vascular disease. Functional food is a rich source of natural compounds with significant pharmacological, The aim of this paper is to explore its effect on arrhythmia.By reviewing the literature and summarising the findings, we described the role of functional foods in the alleviation of cardiac arrhythmias from different perspectives.Our study shows that functional foods have anti‐arrhythmic effects through modulation of ion channels, oxidative stress, and Calmodulin‐dependent protein kinase II.We summarize the mechanism of arrhythmia inhibition by the active ingredients of medicinal diets in this review article, intending to provide research ideas for dietary therapy to regulate arrhythmia. [ABSTRACT FROM AUTHOR]

Solid‐state electrolytes (SSEs) based on metal‐organic frameworks (MOFs) are an ideal material for constructing high‐performance lithium metal batteries (LMBs). However, the low ion conductivity and poor interface contact (especially at low temperatures) still seriously hinder its further application. Herein, inspired by the Na+/K+ conduction in biology systems, a series (NH2, OH, NH‐(CH2)3‐SO3H)‐modified MIL‐53‐X as SSEs is reported. These functional groups are similar to anions suspended in biological ion channels, partially repelling anions while allowing cations to be effectively transported through pore channels. Subsequently, MIL‐53‐X with hierarchical pore structure (H‐MIL‐53‐X) is obtained by introducing lauric acid as a regulator, and then the effects of structural design and morphology control on its performance are explored. The conductivity of H‐MIL‐53‐NH‐SO3Li with multi‐level pore structure and modified by sulfonic acid groups reached 2.2 × 10−3 S cm−1 at 25 °C, lithium‐ion transference number of 0.78. Besides, the H‐MIL‐53‐NH‐SO3Li still has an excellent conductivity of 10−4 S cm−1 at −40 °C. Additionally, LiFePO4/Li batteries equipped with H‐MIL‐53‐NH‐SO3Li SSEs could operate stably for over 200 cycles at 0.1 C. The strategy of combining structural and morphological design of MOFs with biomimetic ion channels opens new avenues for the design of high‐performance SSEs. [ABSTRACT FROM AUTHOR]

It has long been an aspirational goal to create artificial channel structures that replicate the feat achieved by ion channel proteins. Biological ion channels occasionally demonstrate multiple conductance states (known as subconductance), remaining a challenging property to achieve in artificial channel molecules. We report a funnel‐shaped single‐molecule channel constructed by an electron‐deficient macrocycle and two electron‐deficient aromatic imide arms. Planar lipid bilayer measurements reveal distinct current recordings, including a closed state, two conducting states, and spontaneous transitions between the three states, resembling the events seen in biological ion channels. The transitions result from conformational changes induced by chloride transport in the channel molecule. Both opening states show a non‐linear and rectifying I–V relationship, indicating voltage‐dependent transport due to the asymmetrical channel structure. This work could enhance our understanding of ion permeation and channel opening mechanism. [ABSTRACT FROM AUTHOR]

Transient receptor potential vanilloid‐1 (TRPV1) is a capsaicin receptor that employs use‐dependent desensitization to protect highly evolved mammals from noxious heat damage in response to repeated or constant heat stimuli. However, the underlying structural factor or motif has not been precisely resolved. In this computational study, the graph theory‐based grid thermodynamic model was used to reveal how temperature‐dependent noncovalent interactions, as identified in the 3D structures of rat TRPV1, could develop a well‐organized fluidic grid‐like mesh network. This network features various topological grids constrained as thermosensitive rings that range in size from the biggest to the smallest, governing distinct structural and functional traits of the channel in response to different temperature degrees. After discovering that heat unfolding of three specific biggest grids, one in the closed state and two in the open state, respectively, causes the reversible activation at 43°C and thermal inactivation between 56°C and 61°C, a smaller random grid was also found to be responsible for irreversible inactivation and use‐dependent desensitization from the pre‐open closed state within the temperature range of 43°C–61°C. Thus, these two distinct inactivation pathways of TRPV1 may be involved in protecting those mammals against noxious heat damage. Key Points: A perturbation at the protein–water interface was accompanied by partial heat or cold unfolding of the membrane protein.A reversible or irreversible gating transition of an ion channel may result from a specific or random interaction between two active sites, respectively.Kinetically driven protein aggregation was not the cause of thermodynamically trapped irreversible inactivation, but rather a later stage of partial heat‐induced unfolding. [ABSTRACT FROM AUTHOR]

The cystic fibrosis transmembrane conductance regulator (CFTR) is a cyclic adenosine monophosphate (cAMP)‐regulated chloride and bicarbonate ion channel found in many human cells. Its unique biochemical characteristics and role as a member of the adenosine triphosphate (ATP)‐binding cassette transporters superfamily are pivotal for the transport of several substrates across cellular membranes. CFTR is known to interact, physically and functionally, with several other cellular proteins. Hence, its properties are essential for moving various substances across cell membranes and ensuring correct cell functioning. Genetic mutations or environmental factors may disrupt CFTR's function resulting in different possible phenotypes due to gene variations that affect not only CFTR's function, localization, and processing within cells, but also those of its interactors. This has been reported as an underlying cause of various diseases, including cystic fibrosis. The severe clinical implications of cystic fibrosis have driven intense research into the role of CFTR in lung function but its significance to fertility, particularly in men, has been comparatively understudied. However, ongoing and more recent research into CFTR and its interacting proteins in the testis or specific testicular cells is beginning to shed light on this field. Herein, we provide a comprehensive and up‐to‐date overview of the CFTR, its interactome, and its crucial role in male reproduction, highlighting recent discoveries and advancements in understanding the molecular mechanisms involved. The comprehension of these complex interactions may pave the way for potential therapeutic approaches to improve fertility of men suffering from alterations in the function of CFTR. [ABSTRACT FROM AUTHOR]

Organic electrochemical transistors (OECTs) are promising candidates for artificial synapses to achieve high‐performance synaptic characteristics. While most research has focused on modifying the properties of organic semiconductors for efficient ion doping, there is a lack of systematic investigation into the relationship between ion‐mediated mechanisms and synaptic performance. In this study, an effective strategy for enhancing electrochemical doping and de‐doping by utilizing different coulombic anions is proposed. The findings reveal that doped ions in the channel layer affect inter‐ion interactions, influencing the non‐volatile effects by improving the doping performance of the synaptic device. Moreover, electrochemical analysis indicates that ions in the channel layer are sequentially de‐doped, enabling high linearity and symmetry. The fabricated devices demonstrate high‐performance synaptic properties including a retention time of ≈102 s with ≈50% retention over peak current and near‐ideal long‐term potentiation/long‐term depression (LTP/LTD) through effective electrochemical doping and de‐doping. These results show that controlling both the properties of organic semiconductors and ion interactions in the electrolyte is crucial for OECTs, opening up various applications for neuromorphic computing. [ABSTRACT FROM AUTHOR]

δ‐MnO2 has been vigorously developed as an ideal cathode material for rechargeable aqueous zinc‐ion batteries (AZIBs) due to its spacious layer spacing suitable for ion storage. However, poor intrinsic conductivity, structural collapse, and sluggish reaction kinetics are major limitations restricting their battery performance. Doping engineering has been proven to be an effective strategy for modifying the structure, conductivity, and electronic properties of Mn‐based oxides. Here, a series of δ‐MnO2 hierarchical flowers with different cerium‐doped sites are proposed as high‐performance cathodes for AZIBs, revealing the effects of various Ce doping sites on the MnO2 layer‐by‐layer structure and battery performance. Chemical analysis and theoretical calculations indicate that δ‐MnO2 with both in‐layer and interlayer Ce doping (Cein/inter‐MnO2) allows for sufficient Zn2+ storage sites, higher conductivity, and enhanced reaction kinetics due to enlarged interlayer spacing, increased oxygen defects, and reduced Coulombic repulsion between zinc ions and manganese oxide hosts. As a result, Cein/inter‐MnO2 with extended ion transfer channels and sturdy structure delivers a superior capacity of 348.8 mAh g−1 at a current density of 300 mA g−1 over 100 cycles, and a high retention rate of ≈100% at a current density of 3000 mA g−1 over 2000 cycles. [ABSTRACT FROM AUTHOR]

Membranes with precise Li+/Na+ and Li+/K+ separations are imperative for lithium extraction from brine to address the lithium supply shortage. However, achieving this goal remains a daunting challenge due to the similar valence, chemical properties, and subtle atomic‐scale distinctions among these monovalent cations. Herein, inspired by the strict size‐sieving effect of biological ion channels, a membrane is presented based on nonporous crystalline materials featuring structurally rigid, dimensionally confined, and long‐range ordered ion channels that exclusively permeate naked Li+ but block Na+ and K+. This naked‐Li+‐sieving behavior not only enables unprecedented Li+/Na+ and Li+/K+ selectivities up to 2707.4 and 5109.8, respectively, even surpassing the state‐of‐the‐art membranes by at least two orders of magnitude, but also demonstrates impressive Li+/Mg2+ and Li+/Ca2+ separation capabilities. Moreover, this bioinspired membrane has to be utilized for creating a one‐step lithium extraction strategy from natural brines rich in Na+, K+, and Mg2+ without utilizing chemicals or creating solid waste, and it simultaneously produces hydrogen. This research has proposed a new type of ion‐sieving membrane and also provides an envisioning of the design paradigm and development of advanced membranes, ion separation, and lithium extraction. [ABSTRACT FROM AUTHOR]

Macrophages (MΦ) play pivotal roles in tissue homeostasis and repair. Their mechanical environment has been identified as a key modulator of various cell functions, and MΦ mechanosensitivity is likely to be critical – in particular in a rhythmically contracting organ such as the heart. Cultured MΦ, differentiated in vitro from bone marrow (MΦBM), form a popular research model. This study explores the activity of mechanosensitive ion channels (MSC) in murine MΦBM and compares it to MSC activity in MΦ enzymatically isolated from cardiac tissue (tissue‐resident MΦ; MΦTR). We show that MΦBM and MΦTR have stretch‐induced currents, indicating the presence of functional MSC in their plasma membrane. The current profiles in MΦBM and in MΦTR show characteristics of cation non‐selective MSC such as Piezo1 or transient receptor potential channels. While Piezo1 ion channel activity is detectable in the plasma membrane of MΦBM using the patch‐clamp technique, or by measuring cytosolic calcium concentration upon perfusion with the Piezo1 channel agonist Yoda1, no Piezo1 channel activity was observed in MΦTR. The selective transient receptor potential vanilloid 4 (TRPV4) channel agonist GSK1016790A induces calcium entry in MΦTR and in MΦBM. In MΦ isolated from left‐ventricular scar tissue 28 days after cryoablation, stretch‐induced current characteristics are not significantly different compared to non‐injured control tissue, even though scarred ventricular tissue is expected to be mechanically remodelled and to contain an altered composition of pre‐existing cardiac and circulation‐recruited MΦ. Our data suggest that the in vitro differentiation protocols used to obtain MΦBM generate cells that differ from MΦ recruited from the circulation during tissue repair in vivo. Further investigations are needed to explore MSC identity in lineage‐traced MΦ in scar tissue, and to compare mechanosensitivity of circulating monocytes with that of MΦBM. Key points: Bone marrow‐derived (MΦBM) and tissue resident (MΦTR) macrophages have stretch‐induced currents, indicating expression of functional mechanosensitive channels (MSC) in their plasma membrane.Stretch‐activated current profiles show characteristics of cation non‐selective MSC; and mRNA coding for MSC, including Piezo1 and TRPV4, is expressed in murine MΦBM and in MΦTR.Calcium entry upon pharmacological activation of TRPV4 confirms functionality of the channel in MΦTR and in MΦBM.Piezo1 ion channel activity is detected in the plasma membrane of MΦBM but not in MΦTR, suggesting that MΦBM may not be a good model to study the mechanotransduction of MΦTR.Stretch‐induced currents, Piezo1 mRNA expression and response to pharmacological activation are not significantly changed in cardiac MΦ 28 days after cryoinjury compared to sham operated mice. [ABSTRACT FROM AUTHOR]

Cardiac electrophysiology and mechanics are strongly interconnected. Their interaction is, among others, mediated by mechano‐electric feedback through stretch‐activated ion channels (SACs). The electrophysiological changes induced by SACs may contribute to arrhythmogenesis, but the precise SAC‐induced electrophysiological changes remain incompletely understood. Here, we provide a systematic characterization of stretch effects through three distinguished SACs on cardiac electrophysiology using computational modelling. We implemented potassium‐selective, calcium‐selective and non‐selective SACs in the Tomek–Rodriguez–O'Hara–Rudy model of human ventricular electrophysiology. The model was calibrated to experimental data from isolated cardiomyocytes undergoing stretch, considering inter‐species differences, and disease‐related remodelling of SACs. SAC‐mediated effects on the action potential (AP) were analysed by varying stretch amplitude, application timing and/or duration. Afterdepolarizations of different amplitudes were observed with transient 10‐ms stretch stimuli of 15–18% applied during phase 4, while stretch ≥18% during phase 4 elicited triggered APs. Longer stimuli shifted the threshold of AP trigger during phase 4 to lower amplitudes, while shorter stimuli increased it. Continuous stretch provoked electrophysiological remodelling. Furthermore, stretch shortened duration or changed morphology of a subsequent electrically evoked AP, and, if applied during a vulnerable time window with sufficient amplitude, prevented its occurrence because of stretch‐induced modulation of sodium and L‐type calcium channel gating. These effects were more pronounced with disease‐related SAC remodelling due to increased stretch sensitivity of diseased hearts. We showed that SACs may induce afterdepolarizations and triggered activities, and prevent subsequent AP generation or change its morphology. These effects depend on cardiomyocyte stretch characteristics and disease‐related SACs remodelling and may contribute to cardiac arrhythmogenesis. Key points: The interplay between cardiac electrophysiology and mechanics is mediated by mechano‐electric feedback through stretch‐activated ion channels (SACs). These channels may be pro‐arrhythmic, but their precise effect on electrophysiology remains unclear.Here we present a systematic in silico characterization of stretch effects through three SACs by implementing inter‐species differences as well as disease‐related remodelling of SACs in a novel computational model of human ventricular cardiomyocyte electrophysiology.Our simulations showed that, at the cellular level, SACs may provoke electrophysiological remodelling, afterdepolarizations, triggered activities, change the morphology or shorten subsequent electrically evoked action potentials. The model further suggests that a vulnerable window exists in which stretch prevents the following electrically triggered beat occurrence.The pro‐arrhythmic effects of stretch strongly depend on disease‐related SAC remodelling as well as on stretch characteristics, such as amplitude, time of application and duration. Our study helps in understanding the role of stretch in cardiac arrhythmogenesis and revealing the underlying cellular mechanisms. [ABSTRACT FROM AUTHOR]

Modeled after biological neurons, neuristors are emerging hardware that generate recurring voltage spikes in response to electrical stimulation. This type of excitability can enable transistor‐free spiking neural networks for efficient signal processing and computing. Yet, most neuristors consist of circuits containing numerous devices, thus complicating fabrication and increasing size, power usage, and cost. In contrast, it is shown that a single, 5nm‐thick lipid membrane functionalized with voltage‐activated peptides functions as a two‐terminal, ultra‐low power (fW‐pW) artificial neuristor in response to supplied current. Specifically, the biomolecular membrane generates stochastic voltage oscillations (10–150 mV) in response to direct currents (|5–40| pA), and is capable of generating two distinct types of action potentials fast (≈1–50 ms) and slow (≈1–2 s) spikes via distinct physical mechanisms. This discovery showcases the inherent multifunctionality and modularity of engineered biomembranes, and it contributes to an expanding suite of ionic and biomolecular devices designed with synapse and neuron functionalities for emerging computing architectures. [ABSTRACT FROM AUTHOR]

As the key component of various energy storage and conversion devices, proton exchange membranes (PEMs) have been attracting significant interest. However, their further development is limited by the high cost of perfluorosulfonic acid polymers and the poor stability of acid‐dopped non‐fluorinated polymers. Recently, a new group of PEMs has been developed by hybridizing polyoxometalates (POMs), a group of super acidic sub‐nanoscale metal oxide clusters, with polymers. POMs can serve simultaneously as both proton sponges and stabilizing agents, and their complexation with polymers can further improve polymers' mechanical performance and processability. Enormous efforts have been focused on studying supramolecular complexation or covalent grafting of POMs with various polymers to optimize PEMs in terms of cost, mechanical properties and stabilities. This concept summarizes recent advances in this emerging field and outlines the design strategies and application perspectives employed for using POM‐polymer hybrid materials as PEMs. [ABSTRACT FROM AUTHOR]

Cellulose‐based solid electrolyte possesses the characteristics of low cost, high strength, and sustainability, and has great potential in the field of solid‐state lithium metal batteries. However, the large hydrogen bonds between cellulose molecules make the molecular chains tightly arranged, and hinder the ion conduction, seriously limiting its further development. Herein, an ion‐conducting molecular grafting strategy is proposed for the fabrication of cellulose acetate quasi‐solid composite electrolyte (CLA‐CN‐LATP QCE) with a superior ionic conductivity of 1.25 × 10−3 S cm−1 at room temperature. Benefited from grafted functional molecules, the assembled symmetrical battery exhibits low polarization voltage and highly stable lithium stripping/plating cycling of more than 1200 h at 0.1 mA cm−2 current density. Moreover, it endows LFP|CLA‐CN‐LATP QCE|Li battery with excellent long‐cycle stability of 1500 cycles at 0.5 C and 25 °C and superior capacity retention of 92.1%. Importantly, this work provides an effective strategy for further opening the ion transport channel between cellulose molecular chains and improving the interface properties of electrolytes and electrodes. [ABSTRACT FROM AUTHOR]

This article explores the concept of paraptosis, a type of programmed cell death that is different from apoptosis and necrosis. It discusses the mechanisms of paraptosis and highlights the potential of natural products to induce paraptosis in cancer cells, offering an alternative to traditional cancer therapies. The article also mentions the potential of paraptosis in enhancing tumor immunogenicity and triggering immune responses against cancer cells. Clinical trials are being conducted to test the efficacy and safety of paraptosis in cancer treatment, although challenges such as the lack of rigorous clinical trials and difficulties in large-scale isolation and standardization of natural products exist. Overall, the article provides valuable insights into the field of paraptosis and its potential applications in cancer therapy. [Extracted from the article]

While natural channels respond to external stimuli to regulate ion concentration across cell membranes, creating a synthetic version remains challenging. Here, we present a photo‐responsive uncaging technique within an artificial ion channel system, which activates the ion transport process from a transport‐inactive o‐nitrobenzyl‐based caged system. From the comparative ion transport screening, 1 b emerged as the most active transporter. Interestingly, its bis(o‐nitrobenzyl) derivative, i.e., protransporter 1 b′ was inefficient in transporting ions. Detailed transport studies indicated that compound 1 b is an anion selective transporter with a prominent selectivity towards chloride ions by following the antiport mechanism. Compound 1 b′ did not form an ion channel, but after the o‐nitrobenzyl groups were photocleaved, it released 1 b, forming a transmembrane ion channel. The channel exhibited an average diameter of 6.5±0.2 Å and a permeability ratio of PCl-/PK+=7.3±1.5 ${{P}_{{Cl}^{-}}/{P}_{{K}^{+}}=7.3\pm 1.5}$ . The geometry‐optimization of protransporter 1 b′ indicated significant non‐planarity, corroborating its inefficient self‐assembly. In contrast, the crystal structure of 1 b demonstrates strong self‐assembly via the formation of an intermolecular H‐bond. Geometry optimization studies revealed the plausible self‐assembled channel model and the interactions between the channel and chloride ion. [ABSTRACT FROM AUTHOR]

The current application of gel electrolytes in energy storage fails to meet the demand for higher ion transport and excellent mechanical properties due to the low ionic conductivity and poor mechanical properties. Herein, a novel strategy is proposed to graft oligomer polyetheramine on the surface of MXene to achieve a transformation from solid MXene to MXene nanofluid avoiding oxidation and aggregation of MXene, and then it is introduced to gel electrolytes providing ion transport channels and mechanical properties. The synergistic effect on the core of MXene and the canopy of polyetheramine produce Lewis acid–base interactions on electrolyte ions, which not only promote electrolyte dissociation but also provides ion transport path‐way. The experiment and molecular dynamics simulations show that the ionic diffusion ability of electrolyte ions is enhanced, because the MXene and polyetheramine promote electrolyte dissociation and reduce the electrostatic interference between anions and cations. The specific capacity of the assembled supercapacitor is 114.28 F g−1 at 1 A g−1 current density, and the capacity retention rate is 91.30% after 3000 cycles. This work provides a new insight for fabricating high‐performance devices. [ABSTRACT FROM AUTHOR]

Exploring special anode materials with high capacity, stable structure, and extreme temperature feasibility remains a great challenge in secondary sodium based energy systems. Here, a bimetallic Cu‐Fe selenide nanosheet with refined nanostructure providing confined internal ion transport channels are reported, in which the structure improves the pseudocapacitance and reduces the charge transfer resistance for making a significant contribution to accelerating the reaction dynamics. The CuFeSe2 nanosheets have a high initial specific capacity of 480.4 mAh g−1 at 0.25 A g−1, showing impressively excellent rate performance and ultralong cycling life over 1000 cycles with 261.1 mAh g−1 at 2.5 A g−1. Meanwhile, it exhibits a good sodium storage performance at extreme temperatures from −20 °C to 50 °C, supporting at least 500 cycles. Besides, the CuFeSe2||Na3V2(PO4)3/C full cell delivers a high specific capacity of 168.5 mAh g−1 at 0.5 A g−1 and excellent feasibility for over 600 cycles long cycling. Additionally, the Na+ storage mechanisms are further revealed by ex situ X‐ray diffraction (XRD) and in situ transmission electron microscopy (TEM) techniques. A feasible channelized structural design strategy is provided that inspires new instruction into the development of novel materials with high structural stability and low volume expansion rate toward the application of other secondary batteries. [ABSTRACT FROM AUTHOR]