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Exploration (Beijing, China) Feb 2024Halide perovskite solar cells are characterized by a hysteresis between current-voltage (- curves recorded on the reverse and on the forward scan directions, and the...
Halide perovskite solar cells are characterized by a hysteresis between current-voltage (- curves recorded on the reverse and on the forward scan directions, and the suppression of this phenomenon has focused great attention. In the present work, it is shown that a special family of 3D perovskites, that are rendered lead -and iodide- deficient (d-HPs) by incorporating large organic cations, are characterized by a large hysteresis. The strategy of passivating defects by K, which has been successful in reducing the hysteresis of 3D perovskite perovskite solar cells, is inefficient with the d-HPs. By glow discharge optical emission spectroscopy (GD-OES), the existence of the classic iodide migration in these layers is unveiled, which is efficiently blocked by potassium cation insertion. However, it is also shown that it co-exists with the migration of the large organic cations characteristics of d-HPs which are not blocked by the alkali metal ion. The migration of those large cations is intrinsically linked to the special structure of the d-HP. It is suggested that it takes place through channels, present throughout the whole perovskite layer after the substitution of PbI units by the large cations, making this phenomenon intrinsic to the original structure of d-HPs.
PubMed: 38854492
DOI: 10.1002/EXP.20220156 -
BioRxiv : the Preprint Server For... May 2024Piezo1 is a mechanically activated ion channel that senses forces with short latency and high sensitivity. Piezos undergo large conformational changes, induce...
Piezo1 is a mechanically activated ion channel that senses forces with short latency and high sensitivity. Piezos undergo large conformational changes, induce far-reaching deformation onto the membrane, and modulate the function of two-pore potassium (K2P) channels. Taken together, this led us to hypothesize that Piezos may be able to signal their conformational state to other nearby proteins. Here, we use chemical control to acutely restrict Piezo1 conformational flexibility and show that Piezo1 conformational changes, but not ion permeation through it, are required for modulating the K2P channel TREK1. Super-resolution imaging and stochastic simulations further reveal that both channels do not co-localize, which implies that modulation is not mediated through direct binding interactions; however, at high Piezo1 densities, most TREK1 channels are within the predicted Piezo1 membrane footprint, suggesting the footprint may underlie conformational signaling. We speculate that physiological roles originally attributed to Piezo1 ionotropic function could, alternatively, involve conformational signaling.
PubMed: 38854150
DOI: 10.1101/2024.05.28.596257 -
Journal of Pharmacological and... Jun 2024Cardiovascular safety and the risk of developing the potentially fatal ventricular tachyarrhythmia, Torsades de Pointes (TdP), have long been major concerns of drug...
INTRODUCTION
Cardiovascular safety and the risk of developing the potentially fatal ventricular tachyarrhythmia, Torsades de Pointes (TdP), have long been major concerns of drug development. TdP is associated with a delayed ventricular repolarization represented by QT interval prolongation in the electrocardiogram (ECG), typically due to block of the potassium channel encoded by the human ether-a-go-go related gene (hERG). Importantly however, not all drugs that prolong the QT interval are torsadagenic and not all hERG blockers prolong the QT interval. Recent clinical reports suggest that partitioning the QT interval into early (J to T peak; JTp) and late repolarization (T peak to T end; TpTe) components may be valuable for distinguishing low-risk mixed ion channel blockers (hERG plus calcium and/or late sodium currents) from high-risk pure hERG channel blockers. This strategy, if true for nonclinical animal models, could be used to de-risk QT prolonging compounds earlier in the drug development process.
METHODS
To explore this, we investigated JTp and TpTe in ECG data collected from telemetered dogs and/or monkeys administered moxifloxacin or amiodarone at doses targeting relevant clinical exposures. An optimized placement of the Tpeak fiducial mark was utilized, and all intervals were corrected for heart rate (QTc, JTpc, TpTec).
RESULTS
Increases in QTc and JTpc intervals with administration of the pure hERG blocker moxifloxacin and an initial QTc and JTpc shortening followed by prolongation with the mixed ion channel blocker amiodarone were detected as expected, aligning with clinical data. However, anticipated increases in TpTec by both standard agents were not detected.
DISCUSSION
The inability to detect changes in TpTec reduces the utility of these subintervals for prediction of arrhythmias using continuous single‑lead ECGs collected from freely moving dogs and monkeys.
PubMed: 38852685
DOI: 10.1016/j.vascn.2024.107527 -
Neural Regeneration Research Jun 2024The central nervous system, information integration center of the body, is mainly composed of neurons and glial cells. The neuron is one of the most basic and important...
The central nervous system, information integration center of the body, is mainly composed of neurons and glial cells. The neuron is one of the most basic and important structural and functional units of the central nervous system, with sensory stimulation and excitation conduction functions. Astrocytes and microglia belong to the glial cell family, which is the main source of cytokines and represents the main defense system of the central nervous system. Nerve cells undergo neurotransmission or gliotransmission, which regulates neuronal activity via the ion channels, receptors, or transporters expressed on nerve cell membranes. Ion channels, composed of large transmembrane proteins, play crucial roles in maintaining nerve cell homeostasis. These channels are also important for control of the membrane potential and in the secretion of neurotransmitters. A variety of cellular functions and life activities, including functional regulation of the central nervous system, the generation and conduction of nerve excitation, the occurrence of receptor potential, heart pulsation, smooth muscle peristalsis, skeletal muscle contraction, and hormone secretion, are closely related to ion channels associated with passive transmembrane transport. Two types of ion channels in the central nervous system, potassium channels and calcium channels, are closely related to various neurological disorders, including Alzheimer's disease, Parkinson's disease, and epilepsy. Accordingly, various drugs that can affect these ion channels have been explored deeply to provide new directions for the treatment of these neurological disorders. In this review, we focus on the functions of potassium and calcium ion channels in different nerve cells and their involvement in neurological disorders such as Parkinson's disease, Alzheimer's disease, depression, epilepsy, autism, and rare disorders. We also describe several clinical drugs that target potassium or calcium channels in nerve cells and could be used to treat these disorders. We concluded that there are few clinical drugs that can improve the pathology these diseases by acting on potassium or calcium ions. Although a few novel ion-channel- specific modulators have been discovered, meaningful therapies have largely not yet been realized. The lack of target-specific drugs, their requirement to cross the blood-brain barrier, and their exact underlying mechanisms all need further attention. This review aims to explain the urgent problems that need research progress and provide comprehensive information aiming to arouse the research community's interest in the development of ion channel-targeting drugs and the identification of new therapeutic targets for that can increase the cure rate of nervous system diseases and reduce the occurrence of adverse reactions in other systems.
PubMed: 38845230
DOI: 10.4103/NRR.NRR-D-23-01766 -
Nature Jun 2024Membranes are widely used for separation processes in applications such as water desalination, batteries and dialysis, and are crucial in key sectors of our economy and...
Membranes are widely used for separation processes in applications such as water desalination, batteries and dialysis, and are crucial in key sectors of our economy and society. The majority of technologically exploited membranes are based on solid polymers and function as passive barriers, whose transport characteristics are governed by their chemical composition and nanostructure. Although such membranes are ubiquitous, it has proved challenging to maximize selectivity and permeability independently, leading to trade-offs between these pertinent characteristics. Self-assembled biological membranes, in which barrier and transport functions are decoupled, provide the inspiration to address this problem. Here we introduce a self-assembly strategy that uses the interface of an aqueous two-phase system to template and stabilize molecularly thin (approximately 35 nm) biomimetic block copolymer bilayers of scalable area that can exceed 10 cm without defects. These membranes are self-healing, and their barrier function against the passage of ions (specific resistance of approximately 1 MΩ cm) approaches that of phospholipid membranes. The fluidity of these membranes enables straightforward functionalization with molecular carriers that shuttle potassium ions down a concentration gradient with exquisite selectivity over sodium ions. This ion selectivity enables the generation of electric power from equimolar solutions of NaCl and KCl in devices that mimic the electric organ of electric rays.
PubMed: 38839964
DOI: 10.1038/s41586-024-07481-2 -
Scientific Reports Jun 2024Alternaria alternata fungus is a potent paclitaxel producer isolated from Corylus avellana. The major challenge is the lack of optimized media for endophytic fungi...
Alternaria alternata fungus is a potent paclitaxel producer isolated from Corylus avellana. The major challenge is the lack of optimized media for endophytic fungi productivity. In the effort to maximize the production of taxoids by A. alternata, several fermentation conditions, including pH (pH 4.0-7.0), different types and concentrations of carbon (fructose, glucose, sucrose, mannitol, sorbitol, and malt extract), and nitrogen (urea, ammonium nitrate, potassium nitrate, ammonium phosphate, and ammonium sulfate) were applied step by step. Based on the results, A. alternata in a medium containing sucrose 5% (w/v) and ammonium phosphate 2.5 mM at pH 6.0 showed a rapid and sustainable growth rate, the highest paclitaxel yield (94.8 µg gFW vs 2.8 µg gFW in controls), and the maximum content of amino acids. Additionally, the effect of pectin was evaluated on fungus, and mycelia harvested. Pectin significantly enhanced the growth and taxoid yield on day 21 (respectively 171% and 116% of their corresponding on day 7). The results were checked out by mathematical modeling as well. Accordingly, these findings suggest a low-cost, eco-friendly, and easy-to-produce approach with excellent biotechnological potential for the industrial manufacture of taxoids.
Topics: Alternaria; Fermentation; Pectins; Culture Media; Paclitaxel; Models, Theoretical; Hydrogen-Ion Concentration; Nitrogen
PubMed: 38839906
DOI: 10.1038/s41598-024-63681-w -
Nature Communications Jun 2024The exploration of post-Lithium (Li) metals, such as Sodium (Na), Potassium (K), Magnesium (Mg), Calcium (Ca), Aluminum (Al), and Zinc (Zn), for electrochemical energy... (Review)
Review
The exploration of post-Lithium (Li) metals, such as Sodium (Na), Potassium (K), Magnesium (Mg), Calcium (Ca), Aluminum (Al), and Zinc (Zn), for electrochemical energy storage has been driven by the limited availability of Li and the higher theoretical specific energies compared to the state-of-the-art Li-ion batteries. Post-Li metal||S batteries have emerged as a promising system for practical applications. Yet, the insufficient understanding of quantitative cell parameters and the mechanisms of sulfur electrocatalytic conversion hinder the advancement of these battery technologies. This perspective offers a comprehensive analysis of electrode parameters, including S mass loading, S content, electrolyte/S ratio, and negative/positive electrode capacity ratio, in establishing the specific energy (Wh kg) of post-Li metal||S batteries. Additionally, we critically evaluate the progress in investigating electrochemical sulfur conversion via homogeneous and heterogeneous electrocatalytic approaches in both non-aqueous Na/K/Mg/Ca/Al||S and aqueous Zn||S batteries. Lastly, we provide a critical outlook on potential research directions for designing practical post-Li metal||S batteries.
PubMed: 38839870
DOI: 10.1038/s41467-024-49164-6 -
The Journal of Biological Chemistry Jun 2024Hearing crucially depends on cochlear ion homeostasis as evident from deafness elicited by mutations in various genes encoding cation or anion channels and transporters....
Hearing crucially depends on cochlear ion homeostasis as evident from deafness elicited by mutations in various genes encoding cation or anion channels and transporters. Ablation of ClC‑K/barttin chloride channels causes deafness by interfering with the positive electrical potential of the endolymph, but roles of other anion channels in the inner ear have not been studied. Here we report the intracochlear distribution of all five LRRC8 subunits of VRAC, a volume-regulated anion channel that transports chloride, metabolites, and drugs such as the ototoxic anti-cancer drug cisplatin, and explore its physiological role by ablating its subunits. Sensory hair cells express all LRRC8 isoforms, whereas only LRRC8A, D and E were found in the potassium-secreting epithelium of the stria vascularis. Cochlear disruption of the essential LRRC8A subunit, or combined ablation of LRRC8D and E, resulted in cochlear degeneration and congenital deafness of Lrrc8a mice. It was associated with a progressive degeneration of the organ of Corti and its innervating spiral ganglion. Like disruption of ClC-K/barttin, loss of VRAC severely reduced the endocochlear potential. However, the mechanism underlying this reduction seems different. Disruption of VRAC, but not ClC-K/barttin, led to an almost complete loss of Kir4.1 (KCNJ10), a strial K channel crucial for the generation of the endocochlear potential. The strong downregulation of Kir4.1 might be secondary to a loss of VRAC-mediated transport of metabolites regulating inner ear redox potential such as glutathione. Our study extends the knowledge of the role of cochlear ion transport in hearing and ototoxicity.
PubMed: 38838775
DOI: 10.1016/j.jbc.2024.107436 -
Nature Communications Jun 2024Intracellular potassium (K) homeostasis is fundamental to cell viability. In addition to channels, K levels are maintained by various ion transporters. One major family...
Intracellular potassium (K) homeostasis is fundamental to cell viability. In addition to channels, K levels are maintained by various ion transporters. One major family is the proton-driven K efflux transporters, which in gram-negative bacteria is important for detoxification and in plants is critical for efficient photosynthesis and growth. Despite their importance, the structure and molecular basis for K-selectivity is poorly understood. Here, we report ~3.1 Å resolution cryo-EM structures of the Escherichia coli glutathione (GSH)-gated K efflux transporter KefC in complex with AMP, AMP/GSH and an ion-binding variant. KefC forms a homodimer similar to the inward-facing conformation of Na/H antiporter NapA. By structural assignment of a coordinated K ion, MD simulations, and SSM-based electrophysiology, we demonstrate how ion-binding in KefC is adapted for binding a dehydrated K ion. KefC harbors C-terminal regulator of K conductance (RCK) domains, as present in some bacterial K-ion channels. The domain-swapped helices in the RCK domains bind AMP and GSH and they inhibit transport by directly interacting with the ion-transporter module. Taken together, we propose that KefC is activated by detachment of the RCK domains and that ion selectivity exploits the biophysical properties likewise adapted by K-ion-channels.
Topics: Cryoelectron Microscopy; Escherichia coli; Escherichia coli Proteins; Glutathione; Molecular Dynamics Simulation; Potassium; Potassium-Hydrogen Antiporters; Protein Domains
PubMed: 38834573
DOI: 10.1038/s41467-024-49082-7 -
ELife Jun 2024Bacteria in biofilms secrete potassium ions to attract free swimming cells. However, the basis of chemotaxis to potassium remains poorly understood. Here, using a...
Bacteria in biofilms secrete potassium ions to attract free swimming cells. However, the basis of chemotaxis to potassium remains poorly understood. Here, using a microfluidic device, we found that can rapidly accumulate in regions of high potassium concentration on the order of millimoles. Using a bead assay, we measured the dynamic response of individual flagellar motors to stepwise changes in potassium concentration, finding that the response resulted from the chemotaxis signaling pathway. To characterize the chemotactic response to potassium, we measured the dose-response curve and adaptation kinetics via an Förster resonance energy transfer (FRET) assay, finding that the chemotaxis pathway exhibited a sensitive response and fast adaptation to potassium. We further found that the two major chemoreceptors Tar and Tsr respond differently to potassium. Tar receptors exhibit a biphasic response, whereas Tsr receptors respond to potassium as an attractant. These different responses were consistent with the responses of the two receptors to intracellular pH changes. The sensitive response and fast adaptation allow bacteria to sense and localize small changes in potassium concentration. The differential responses of Tar and Tsr receptors to potassium suggest that cells at different growth stages respond differently to potassium and may have different requirements for potassium.
Topics: Chemotaxis; Potassium; Escherichia coli; Escherichia coli Proteins; Fluorescence Resonance Energy Transfer; Signal Transduction; Receptors, Cell Surface
PubMed: 38832501
DOI: 10.7554/eLife.91452