Mechanosensitive ion channels are essential for sensing and converting mechanical forces into electrical or chemical signals.These channels are widely distributed across bacteria,animals,and plants.In Arabidopsis thal...Mechanosensitive ion channels are essential for sensing and converting mechanical forces into electrical or chemical signals.These channels are widely distributed across bacteria,animals,and plants.In Arabidopsis thaliana,the OSCA family has been identified as mechanically activated ion channels that respond to osmotic stress by allowing calcium ions to enter the cell.This influx increases the cytoplasmic calcium concentration,triggering osmotic stress-induced signal transduction cascades in plants.In this study,we determined the structures of OSCA2.2 and OSCA3.1 via cryoelectron microscopy(cryo-EM).Both proteins form homodimers consisting of 11 transmembrane helices(TM1–11).The ion conduction pathway is formed by TM4–8.Despite belonging to the same family,OSCA2.2 and OSCA3.1 exhibit notable structural variations.Structural analysis revealed that both OSCA2.2 and OSCA3.1 exhibit a closed conformation.We also conducted functional studies on OSCA proteins via electrophysiological experiments and confirmed the role of key amino acids in the process of ion permeation.展开更多
Sexually reproducing animals require an orchestrated communication between spermatozoa and the egg to generate a new individual. Capacitation, a maturational complex phenomenon that occurs in the female reproductive t...Sexually reproducing animals require an orchestrated communication between spermatozoa and the egg to generate a new individual. Capacitation, a maturational complex phenomenon that occurs in the female reproductive tract, renders spermatozoa capable of binding and fusing with the oocyte, and it is a requirement for mammalian fertilization. Capacitation encompasses plasma membrane reorganization, ion permeability regulation, cholesterol loss and changes in the phosphorylation state of many proteins. Novel tools to study sperm ion channels, image intracellular ionic changes and proteins with better spatial and temporal resolution, are unraveling how modifications in sperm ion transport and phosphorylation states lead to capacitation. Recent evidence indicates that two parallel pathways regulate phosphorylation events leading to capacitation, one of them requiring activation of protein kinase A and the second one involving inactivation of ser/thr phosphatases. This review examines the involvement of ion transporters and phosphorylation signaling processes needed for spermatozoa to achieve capacitation. Understanding the molecular mechanisms leading to fertilization is central for societies to deal with rising male infertility rates, to develop safe male gamete-based contraceptives and to preserve biodiversity through better assisted fertilization strategies.展开更多
Diabetes mellitus affects the heart through various mechanisms such as microvascular defects,metabolic abnormalities,autonomic dysfunction and incompatible immune response.Furthermore,it can also cause functional and ...Diabetes mellitus affects the heart through various mechanisms such as microvascular defects,metabolic abnormalities,autonomic dysfunction and incompatible immune response.Furthermore,it can also cause functional and structural changes in the myocardium by a disease known as diabetic cardiomyopathy(DCM)in the absence of coronary artery disease.As DCM progresses it causes electrical remodeling of the heart,left ventricular dysfunction and heart failure.Electrophysiological changes in the diabetic heart contribute significantly to the incidence of arrhythmias and sudden cardiac death in diabetes mellitus patients.In recent studies,significant changes in repolarizing K+currents,Na+currents and L-type Ca^(2+)currents along with impaired Ca^(2+ )homeostasis and defective contractile function have been identified in the diabetic heart.In addition,insulin levels and other trophic factors change significantly to maintain the ionic channel expression in diabetic patients.There are many diagnostic tools and management options for DCM,but it is difficult to detect its development and to effectively prevent its progress.In this review,diabetes-associated alterations in voltage-sensitive cardiac ion channels are comprehensively assessed to understand their potential role in the pathophysiology and pathogenesis of DCM.展开更多
The locus coeruleus(LC) is one of the essential chemoregulatory and sleep–wake(S–W) modulating centers in the brain. LC neurons remain highly active during wakefulness, and some implicitly become silent during rapid...The locus coeruleus(LC) is one of the essential chemoregulatory and sleep–wake(S–W) modulating centers in the brain. LC neurons remain highly active during wakefulness, and some implicitly become silent during rapid eye movement(REM) sleep. LC neurons are also involved in CO_2-dependent modulation of the respiratory drive. Acid-sensing ion channels(ASICs) are highly expressed in some brainstem chemosensory breathing regulatory areas, but their localization and functions in the LC remain unknown. Mild hypercapnia increases the amount of non-REM(NREM) sleep and the number of REM sleep episodes, but whether ASICs in the LC modulate S–W is unclear. Here, we investigated the presence of ASICs in the LC and their role in S–W modulation and the state transition from NREM to REM sleep. Male Wistar rats were surgically prepared for chronic polysomnographic recordings and drug microinjections into the LC. The presence of ASIC-2 and ASIC-3 in the LC was immunohistochemically characterized.Microinjections of amiloride(an ASIC blocker) and APETx2(a blocker of ASIC-2 and-3) into the LC significantly decreased wakefulness and REM sleep, but significantly increased NREM sleep. Mild hypercapnia increased the amount of NREM and the number of REM episodes. However, APETx2 microinjection inhibited this increase in REM frequency. These results suggest that the ASICs of LC neurons modulate S–W, indicating that ASICs could play an important role in vigilance-state transition. A mild increase in CO_2 level during NREM sleep sensed by ASICs could be one of the determinants of state transition from NREM to REM sleep.展开更多
Activation of acid-sensing ion channels （ASICs） plays an important role in neuroinflammation. Macrophage recruitment to the sites of inflammation is an essential step in host defense. ASIC1 and ASIC3 have been repor...Activation of acid-sensing ion channels （ASICs） plays an important role in neuroinflammation. Macrophage recruitment to the sites of inflammation is an essential step in host defense. ASIC1 and ASIC3 have been reported to mediate the endocytosis and maturation of bone marrow derived macrophages. However, the expression and inflammation-related functions of ASICs in RAW 264.7 cells, another common macrophage, are still elusive. In the present study, we first demonstrated the presence of ASIC 1, ASIC2a and ASIC3 in RAW 264.7 macrophage cell line by using reverse transcriptase polymerase chain reaction （RT-PCR）, Western blotting and immunofluorescence experiments. The non-specific ASICs inhibitor amiloride and specific homomeric ASICla blocker PcTxl reduced the production of iNOS and COX-2 by LPS-induced activating RAW 264.7 cells. Furthermore, not only amiloride but also PcTxl inhibited the migration and LPS-induced apoptosis of RAW 264.7 cells. Taken together, our findings suggest that ASICs promote the inflammatory response and apoptosis of RAW 264.7 cells, and ASICs may serve as a potential novel target for immunological disease therapy.展开更多
OBJECTIVE:To investigate the impact of electro-acupuncture at the Neiguan(PC 6) acupoint on protein and RNA expression of acid-sensing ion channel 2(ASIC2) and ASIC3 in myocardial ischemia rats.METHODS:Fifty male Spra...OBJECTIVE:To investigate the impact of electro-acupuncture at the Neiguan(PC 6) acupoint on protein and RNA expression of acid-sensing ion channel 2(ASIC2) and ASIC3 in myocardial ischemia rats.METHODS:Fifty male Sprague-Dawley rats were used,weighing(230 ± 50) g.The rats were randomized into a normal group A,model group B,Neiguan(PC 6) group C,Lieque(LU 7) group D,and A-shi points group E.There were 10 rats in each group.Rats were continuously administered 85 mg/kg intravenous isoproterenol daily to establish the model.Successfully modeled rats in groups C,D,and E were given electro-acupuncture treatment.Each group of rats was sacrificed with chloral hydrate(1 mL/100 g) intraperitoneal injection.The left ventricular myocardium was extracted and placed at- 70 ℃ until use.Western blot analysis and real-time PCR were performed to assay protein and RNA expressions of ASIC2 and ASIC3,respectively.Fold changes in RNA expression were quantified with the 2~^(-△△Ct) method.Blood samples were drawn from the aorta abdominalis and tested for creatine kinase-MB(CK-MB) and lactate dehydrogenase(LDH) levels using enzyme-linked immunosorbent assay.RESULTS:Myocardial ischemia rats given electro-acupuncture at the Neiguan(PC 6) acupoint had significantly lower protein and RNA expression of ASIC2 and ASIC3,and CK-MB and LDH levels,compared with model rats(P < 0.01).CONCLUSION:Electro-acupuncture at the Neiguan(PC 6) acupoint can not only decrease the protein and RNA expression of ASIC2 and ASIC3,but also inhibit the opening of ASICs and reduce the cardiomyocyte damage in myocardial ischemia rats.展开更多
Capacitation and acrosome reaction are important prerequisites of the fertilization process. Capacitation is a highlycomplex phenomenon occurring in the female genital tract, rendering the spermatozoa capable of bindi...Capacitation and acrosome reaction are important prerequisites of the fertilization process. Capacitation is a highlycomplex phenomenon occurring in the female genital tract, rendering the spermatozoa capable of binding and fusionwith the oocyte. During capacitation various biochemical and biophysical changes occur in the spermatozoa and thespermatozoal membranes. Ions and ion channels also play important roles in governing the process of capacitation bychanging the fluxes of different ions which in turn controls various characteristics of capacitated spermatozoa. Alongwith the mobilization of ions the generation of free radicals and efflux of cholesterol also plays an important role in thecapacitation state of the spermatozoa. The generation of free radical and efflux of cholesterol change the mechano-dynamic properties of the membrane by oxidation of the polyunsaturated lipids and by generating the cholesterol freepatches. The process of capacitation renders the spermatozoa responsive to the inducers of the acrosome reaction. Theglycoprotein zona pellucida 3 (ZP3) of the egg coat zona pellucida is the potent physiological stimulator of the acro-some reaction; progesterone, a major compoent of the follicular fluid, is also an induce of the acrosome reaction.The inducers of the acrosome reaction cause the activation of the various ion-channels leading to high influxes of calci-um, sodium and bicarbonate. The efflux of cholesterol during the process of capacitation alters the permeablity of themembrane to the ions and generate areas which are prone to fusion and vesculation process during the acrosome reac-tion. Ths review focuses mainly on effects of the ion and ion-channels, free radicals, and membrane fluidity changesduring the process of capacitation and acrosome reaction. (Asian J Androl 1999 Sep; 1: 95-107)展开更多
Cancer has been one of the most serious public health issues in the world. Traditional medicines are widely used in adjunctive therapies in clinical cancer treatment in many countries. One of the unique traditional me...Cancer has been one of the most serious public health issues in the world. Traditional medicines are widely used in adjunctive therapies in clinical cancer treatment in many countries. One of the unique traditional medicine usages in tumor treatment is the high-dose application of traditional toxin medicine, including venom or body from toxin animals. Evidence has shown that they are very likely to have direct effects on cancer cells. One of the potential pharmacological effects of traditional toxin medicines is their regulation of ion channels in cancers. Many ion channels are found critical in cancers. This study suggested that ion channels were involved in the effect of traditional toxin medicine on cancers. However, so far, the study of the effect of traditional toxin medicine on ion channels in cancers is relatively lacking. This perspective article urged the study in this field because, given the fact that these traditional toxin traditional medicines have been widely used in cancer treatment, the identification of the effective components and pharmacological targets can improve their clinical application.展开更多
OBJECTIVE:To explore how Qingfei Zhisou oral liquid(清肺止嗽口服液,QFZS)adjusts body temperature bias and the interaction of inflammatory factors levels and metabolomic differences.METHODS:Dry yeast was subcutaneously...OBJECTIVE:To explore how Qingfei Zhisou oral liquid(清肺止嗽口服液,QFZS)adjusts body temperature bias and the interaction of inflammatory factors levels and metabolomic differences.METHODS:Dry yeast was subcutaneously injected at 10 mL/kg to establish the pyrexia model.We randomly divided 60 Sprague-Dawley rats into five groups:control,model,positive,low dose of QFZS and high dose of QFZS.Inflammatory proteins were evaluated by Western blotting and immunohistochemistry.For the examination of the endogenous metabolites,enzyme linked immunosorbent assay and ultra-high-performance liquid chromatography high-resolution mass spectrometry were employed.RESULTS:QFZS significantly reduced rats'body temperature within 6 h after dry yeast injection and reduced the secretion of the arginine vasopressin,cyclic adenosine monophosphate,prostaglandin E-2,tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),and interleukin-1βin serum.Meanwhile,we identified 41 metabolites between the model and QFZS groups,including arachidonic acid and lysophospholipids.QFZS restored normal arachidonic acid levels.Based on the differential metabolite enrichment analysis,QFZS's antiinflammatory and anti-pyrexia effects might be related to the inflammatory pathway regulated by transient receptor potential.Additionally,QFZS treatment reduced transient receptor potential melastatin 2 ion channel expression and affected TNF-α,heat shock protein 70,and cyclooxygenase-2 expression in the hypothalamus.CONCLUSION:QFZS exerts its regulatory effects on fever by regulating the metabolism of lysophospholipids and arachidonic acid and the regulation of inflammation via transient receptor potential ion channels channels.展开更多
MXene has given great promises to superca-pacitor electrode material due to its high conductivity and redox properties.However,the self-agglomeration of the MXene lamella will reduce its contact area with the elec-tro...MXene has given great promises to superca-pacitor electrode material due to its high conductivity and redox properties.However,the self-agglomeration of the MXene lamella will reduce its contact area with the elec-trolyte and generate a tortuous transportation pathway of the electrolyte ions,thereby reducing its capacitive per-formance and rate capability.In this work,we engineered the electrolyte ion channels by adjusting the MXene lamella size and inserting holey graphene(HG)nanosheets into the interlayer of the MXene flakes.The developed MXene/HG electrode can not only avoid the self-restack-ing of MXene but also provide unimpeded ion transport channels.As a result,the supercapacitive and rate perfor-mances of the small MXene lamella-based MXene/HG(S-MXene/HG)supercapacitor are prominently ameliorated.By adjusting the content of HG,the S-MXene/HG0.05 electrode exhibits excellent gravimetric capacitance of 446 F·g^(-1)and a rate capability of 77.5%.The S-MXene/HG0.05-based symmetric supercapacitor provides an impressive energy density of 14.84 Wh·kg^(-1)with excellent cyclic stability of 96%capacitance retention after 10,000 cycles.This demonstration of the engineering of the ion channels shows great potential in two-dimensional mate-rial-based supercapacitor electrodes.展开更多
Acidosis is a common characteristic of brain damage. Because studies have shown that permeable Ca2＋-acid-sensing ion channels can mediate the toxic effects of calcium ions, they have become new targets against pain a...Acidosis is a common characteristic of brain damage. Because studies have shown that permeable Ca2＋-acid-sensing ion channels can mediate the toxic effects of calcium ions, they have become new targets against pain and various intracranial diseases. However, the mechanism associated with expression of these channels remains unclear. This study sought to observe the expression characteristics of permeable Ca2＋-acid-sensing ion channels during different reperfusion inflows in rats after cerebral ischemia. The rat models were randomly divided into three groups： adaptive ischemia/reperfusion group, one-time ischemia/reperfusion group, and severe cerebral ischemic injury group. Western blot assays and immunofluorescence staining results exhibited that when compared with the one-time ischemia/reperfusion group, acid-sensing ion channel 3 and Bcl-x/I expression decreased in the adaptive ischemia/reperfusion group. Calmodulin expression was lowest in the adaptive ischemia/reperfusion group. Following adaptive reperfusion, common carotid artery flow was close to normal, and the pH value improved. Results verified that adaptive reperfusion following cerebral ischemia can suppress acid-sensing ion channel 3 expression, significantly reduce Ca2＋ influx, inhibit calcium overload, and diminish Ca2＋ toxicity. The effects of adaptive ischemia/reperfusion on suppressing cell apoptosis and relieving brain damage were better than that of one-time ischemia/reperfusion.展开更多
Ion channels are membrane proteins that are found in a number of viruses and which are of crucial physiological importance in the viral life cycle. They have one common feature in that their action mode involves a cha...Ion channels are membrane proteins that are found in a number of viruses and which are of crucial physiological importance in the viral life cycle. They have one common feature in that their action mode involves a change of electrochemical or proton gradient across the bilayer lipid membrane which modulates viral or cellular activity. We will discuss a group of viral channel proteins that belong to the viroproin family, and which participate in a number of viral functions including promoting the release of viral particles from cells. Blocking these channel-forming proteins may be ＂lethal＂, which can be a suitable and potential therapeutic strategy. In this review we discuss seven ion channels of viruses which can lead serious infections in human beings： M2 of influenza A, NB and BM2 of influenza B, CM2 of influenza C, Vpu of HIV-1, p7 of HCV and 2B of picomaviruses.展开更多
The reliable functioning of ion channels should be closely related to their structural stability. The selectivity filter in the KcsA potassium channel possesses four stable ion binding sites that can coordinate nearly...The reliable functioning of ion channels should be closely related to their structural stability. The selectivity filter in the KcsA potassium channel possesses four stable ion binding sites that can coordinate nearly fully dehydrated ions, whereas only two of such binding sites exist in the non-selective NaK channel, and none of them is found in the NavAb sodium channel. Here we show that the stability of the selectivity filters in these tetrameric cation channels is inversely correlated with the number of stable binding sites by extensive molecular dynamics simulations. While the presence of coordinated ions is crucial for the selectivity filters of the KcsA and NaK channels to stabilize the conformations in their crystal structures, the selectivity filter of the NavAb channel shows higher stability, independent of the presence of ions. We further show that the distinct repulsive electrostatic interactions between negatively charged oxygen atoms in the selectivity filter which form the stable binding sites are responsible for the different stability of these cation channels. The hydrogen bonding networks between residues in the selectivity filter and its adjacent pore helix also play an important role in maintaining stability. Together, these results provide important mechanistic insights into the structural stability of the selectivity filters in typical cation channels.展开更多
Biological ion channels are essential for ion and molecule transport,playing a critical role in maintaining cellular equilibrium and regulating vital physiological functions such as cell growth,hormone secretion,and n...Biological ion channels are essential for ion and molecule transport,playing a critical role in maintaining cellular equilibrium and regulating vital physiological functions such as cell growth,hormone secretion,and nerve-muscle interactions.Drawing inspiration from nature,researchers have crafted an array of supramolecular artificial ion channels(AICs)using both unimolecular and self-assembly approaches.Notably,AICs based on macrocyclic molecules,such as cyclodextrins,crown ethers,and pillararenes,offer distinct advantages,including biocompatibility,precise structural design,ease of customization,and simple preparation.This review spotlights recent progress in bioinspired AICs rooted in macrocycles and their applications in the realm of biomedicine.We commence with an overview of the significance of biological channels and the strategies employed for fashioning supramolecular artificial channels.Subsequently,we navigate through the intricate landscape of molecular design,structural modulation,and the ion transport prowess exhibited by macrocycle-based AICs.Furthermore,we explore the promising biomedical applications of these AICs,encompassing roles in antibacterial measures,anticancer interventions,biosensing technologies,and treatments for channelopathies.Finally,we address the persisting challenges and illuminate prospects within this field,with the ultimate aim of steering future innovations in the development of supramolecular AICs.展开更多
Ion channels play instrumental roles in regulating membrane potential and cross-membrane signal transduction,thus making them attractive targets for understanding various physiological processes and associated disease...Ion channels play instrumental roles in regulating membrane potential and cross-membrane signal transduction,thus making them attractive targets for understanding various physiological processes and associated diseases.Gaining a deeper understanding of their structural and functional properties has significant implications for developing therapeutic interventions.In recent years,nanobodies,single-domain antibody fragments derived from camelids,have emerged as powerful tools in ion channel and synthetic biology research.Their small size,high specificity,and ability to recognize difficult-to-reach epitopes offer advantages over conventional antibodies and biologics.Furthermore,their resemblance to the variable region of human IgG family III reduces immunogenicity concerns.Nanobodies have introduced new opportunities for exploring ion channel structure-function relationships and offer a promising alternative to conventional drugs,which often face challenges such as off-target effects and toxicity.This review highlights recent progress in applying nanobodies to interrogate and modulate ion channel activity,with an emphasis on their potential to overcome current technical and therapeutic limitations.展开更多
Throughout the annals of human civilization,the utilization of energy has been a cornerstone of our advancement.Particularly over the past few centuries,each technological revolution has catalyzed a leap in developmen...Throughout the annals of human civilization,the utilization of energy has been a cornerstone of our advancement.Particularly over the past few centuries,each technological revolution has catalyzed a leap in development,profoundly transforming society.However,with these advancements,energy consumption has surged.展开更多
Cardiac ion channels are critical transmembrane proteins that mediate almost all aspects of cardiac function including generation and propagation of cardiac action potential(AP)aswell asmaintenance of normal heart exc...Cardiac ion channels are critical transmembrane proteins that mediate almost all aspects of cardiac function including generation and propagation of cardiac action potential(AP)aswell asmaintenance of normal heart excitability and contraction.In addition,the pivotal role of cardiac ion channels in cardiac health and disease is underscored by the profound effects of their dysfunctional mutations on various arrhythmias.Hence,ion channels are vital targets for antiarrhythmic drugs.In this review,we first summarize the characteristics,structure of the various cardiac ion channels and their specific roles in cardiac electrophysiology.Subsequently,we highlight the implications of genetic mutations that disrupt ion channel function,which are associated with inherited cardiac arrhythmias.Finally,we address antiarrhythmic drugs acting on cardiac ion channels respectively,according to their therapeutic targets.In conclusion,this manuscript aims to review the physiology,pathophysiology and pharmacology of the most prominent ventricular NaV,CaV,KV,andKir ion channels.展开更多
Osmotic energy,existing between the seawater and river water,is a renewable energy source,which can be directly converted into electricity by ion-exchange membranes(IEM).In traditional IEMs,the ion transport channels ...Osmotic energy,existing between the seawater and river water,is a renewable energy source,which can be directly converted into electricity by ion-exchange membranes(IEM).In traditional IEMs,the ion transport channels are formed by nanophase separation of hydrophilic ion carriers and hydrophobic segments.It is difficult to realize high-density ion channels with controlled spatial arrangement and length scale of ion carriers.Herein,we construct high-density 1D ion wires as transmission channels.Through molecular design,hydrophilic imidazole groups and hydrophobic alkyl tails were introduced into the repeat units,which self-assembled into 1D ion transporting core and protecting shell along the main chains.The areal density of the ionic wire arrays is up to~10^(12)cm^(-2),which is the highest value.The ionic wires ensure both high ion flux transport and high selectivity,achieving an ultrahigh-power density of 40.5 W m^(-2)at a 500-fold salinity gradient.Besides,the ionic wire array membrane is well recyclable and antibacterial.The ionic wires provide novel concept for next generation of high-performance membranes.展开更多
Numerous pathological states of the nervous system involve alterations in neuronal excitability and synaptic dysfunction,which depend on the function of ion channels.Due to their critical involvement in health and dis...Numerous pathological states of the nervous system involve alterations in neuronal excitability and synaptic dysfunction,which depend on the function of ion channels.Due to their critical involvement in health and disease,the search for new compounds that modulate these proteins is still relevant.Traditional medicine has long been a rich source of neuroactive compounds.For example,the indigenous Mapuche people have used the leaves and bark of the Drimys winteri tree for centuries to treat various diseases.Consequently,several studies have investigated the biological effects of compounds in Drimys winteri,highlighting sesquiterpenes such asα-humulene,drimenin,polygodial,andα-,β-,γ-eudesmol.However,there is currently no literature review focusing on the ability of these sesquiterpenes to modulate ion channels.This review summarizes the current knowledge about neuroactive compounds found in Drimys winteri,with special emphasis on their direct actions on neuronal ion channels.Several Drimys winteri sesquiterpenes modulate a diverse array of neuronal ion channels,including transient receptor potential channels,gamma-aminobutyric acid A receptors,nicotinic acetylcholine receptors,and voltage-dependent Ca^(2+)and Na^(+)channels.Interestingly,the modulation of these molecular targets by Drimys winteri sesquiterpenes correlates with their therapeutic actions.The promiscuous pharmacological profile of Drimys winteri sesquiterpenes suggests they modulate multiple protein targets in vivo,making them potentially useful for treating complex,multifactorial diseases.Further studies at the molecular level may aid in developing multitargeted drugs with enhanced therapeutic effects.展开更多
Covalent organic frameworks(COFs)are an emerging class for solid-state electrolytes due to their ordered and customizable ion transport nanochannels.Although high ionic conductivity(σ_(Li+))and Li^(+) transference nu...Covalent organic frameworks(COFs)are an emerging class for solid-state electrolytes due to their ordered and customizable ion transport nanochannels.Although high ionic conductivity(σ_(Li+))and Li^(+) transference number(t_(Li+))are achieved;the high-arealcapacity solid-state lithium metal battery(LMB)still encountered challenges;which is mainly determined by homogeneous Li^(+) flux through channels and interfaces.Herein;we design a COF coupling anionic skeletons with branched ion-conductive chains(COF-S)as tailored fast ion-transport channels to achieve high-areal-capacity solid-state LMB.Then the dispersed COF-S-based electrolyte is further obtained by incorporating ethoxylated trimethylolpropane triacrylate(ETPTA)and Li FSI(ETPTA-COF-S)via in situ light solidification.In this way;the abundant SO_(3)-groups promote Li+adsorption and facilitate axial transport via 1D channels;thus enabling highσLi+of 1.29 m S cm^(-1)and tLi+of 0.83.The branched chains can tailor ion channels to suppress largesize anions transport;disperse and uniform Li+flux;thus leading to high average Coulombic efficiency(CE)up to 98.43%for 100 cycles(~800 h)at 0.5 m A cm^(-2)under the high areal capacity of 2 mAh cm^(-2).When paired with 2 m Ah cm^(-2)LiFePO_(4)(LFP)cathode and thin Li anode of 20μm;Li||ETPTA-COF-S||LFP exhibits superior cyclic stability for 80 cycles.展开更多
基金supported by the National Natural Science Foundation of China(32322041,W2412029,32321001,32471279)USTC Research Funds of the Double First-Class Initiative(YD9100002004,YD9100002020)+2 种基金Fundamental Research Funds for the Central Universities(WK9100000031)Research Funds of Center for Advanced Interdisciplinary Science and Biomedicine of IHM(QYPY20230034)the Natural Science Foundation of Anhui Province(2408085JX005).
文摘Mechanosensitive ion channels are essential for sensing and converting mechanical forces into electrical or chemical signals.These channels are widely distributed across bacteria,animals,and plants.In Arabidopsis thaliana,the OSCA family has been identified as mechanically activated ion channels that respond to osmotic stress by allowing calcium ions to enter the cell.This influx increases the cytoplasmic calcium concentration,triggering osmotic stress-induced signal transduction cascades in plants.In this study,we determined the structures of OSCA2.2 and OSCA3.1 via cryoelectron microscopy(cryo-EM).Both proteins form homodimers consisting of 11 transmembrane helices(TM1–11).The ion conduction pathway is formed by TM4–8.Despite belonging to the same family,OSCA2.2 and OSCA3.1 exhibit notable structural variations.Structural analysis revealed that both OSCA2.2 and OSCA3.1 exhibit a closed conformation.We also conducted functional studies on OSCA proteins via electrophysiological experiments and confirmed the role of key amino acids in the process of ion permeation.
文摘Sexually reproducing animals require an orchestrated communication between spermatozoa and the egg to generate a new individual. Capacitation, a maturational complex phenomenon that occurs in the female reproductive tract, renders spermatozoa capable of binding and fusing with the oocyte, and it is a requirement for mammalian fertilization. Capacitation encompasses plasma membrane reorganization, ion permeability regulation, cholesterol loss and changes in the phosphorylation state of many proteins. Novel tools to study sperm ion channels, image intracellular ionic changes and proteins with better spatial and temporal resolution, are unraveling how modifications in sperm ion transport and phosphorylation states lead to capacitation. Recent evidence indicates that two parallel pathways regulate phosphorylation events leading to capacitation, one of them requiring activation of protein kinase A and the second one involving inactivation of ser/thr phosphatases. This review examines the involvement of ion transporters and phosphorylation signaling processes needed for spermatozoa to achieve capacitation. Understanding the molecular mechanisms leading to fertilization is central for societies to deal with rising male infertility rates, to develop safe male gamete-based contraceptives and to preserve biodiversity through better assisted fertilization strategies.
文摘Diabetes mellitus affects the heart through various mechanisms such as microvascular defects,metabolic abnormalities,autonomic dysfunction and incompatible immune response.Furthermore,it can also cause functional and structural changes in the myocardium by a disease known as diabetic cardiomyopathy(DCM)in the absence of coronary artery disease.As DCM progresses it causes electrical remodeling of the heart,left ventricular dysfunction and heart failure.Electrophysiological changes in the diabetic heart contribute significantly to the incidence of arrhythmias and sudden cardiac death in diabetes mellitus patients.In recent studies,significant changes in repolarizing K+currents,Na+currents and L-type Ca^(2+)currents along with impaired Ca^(2+ )homeostasis and defective contractile function have been identified in the diabetic heart.In addition,insulin levels and other trophic factors change significantly to maintain the ionic channel expression in diabetic patients.There are many diagnostic tools and management options for DCM,but it is difficult to detect its development and to effectively prevent its progress.In this review,diabetes-associated alterations in voltage-sensitive cardiac ion channels are comprehensively assessed to understand their potential role in the pathophysiology and pathogenesis of DCM.
基金supported by the Department of Science and Technology-Cognitive Science Initiative project funded to Sushil K Jhasupport from Department of Biotechnology (DBT), Department of Science and Technology(PURSE), Universities for Potential of Excellence (UPOE Ⅱ) and University Grants Commission-Special Assistance Programme)JNU funds to Sushil K Jha。
文摘The locus coeruleus(LC) is one of the essential chemoregulatory and sleep–wake(S–W) modulating centers in the brain. LC neurons remain highly active during wakefulness, and some implicitly become silent during rapid eye movement(REM) sleep. LC neurons are also involved in CO_2-dependent modulation of the respiratory drive. Acid-sensing ion channels(ASICs) are highly expressed in some brainstem chemosensory breathing regulatory areas, but their localization and functions in the LC remain unknown. Mild hypercapnia increases the amount of non-REM(NREM) sleep and the number of REM sleep episodes, but whether ASICs in the LC modulate S–W is unclear. Here, we investigated the presence of ASICs in the LC and their role in S–W modulation and the state transition from NREM to REM sleep. Male Wistar rats were surgically prepared for chronic polysomnographic recordings and drug microinjections into the LC. The presence of ASIC-2 and ASIC-3 in the LC was immunohistochemically characterized.Microinjections of amiloride(an ASIC blocker) and APETx2(a blocker of ASIC-2 and-3) into the LC significantly decreased wakefulness and REM sleep, but significantly increased NREM sleep. Mild hypercapnia increased the amount of NREM and the number of REM episodes. However, APETx2 microinjection inhibited this increase in REM frequency. These results suggest that the ASICs of LC neurons modulate S–W, indicating that ASICs could play an important role in vigilance-state transition. A mild increase in CO_2 level during NREM sleep sensed by ASICs could be one of the determinants of state transition from NREM to REM sleep.
基金This work was supported by grants from the National Natural science Foundation of China （No. 81473199）, and the Fundamental Research Funds for the Central Universities （No, 015TS 125）.
文摘Activation of acid-sensing ion channels （ASICs） plays an important role in neuroinflammation. Macrophage recruitment to the sites of inflammation is an essential step in host defense. ASIC1 and ASIC3 have been reported to mediate the endocytosis and maturation of bone marrow derived macrophages. However, the expression and inflammation-related functions of ASICs in RAW 264.7 cells, another common macrophage, are still elusive. In the present study, we first demonstrated the presence of ASIC 1, ASIC2a and ASIC3 in RAW 264.7 macrophage cell line by using reverse transcriptase polymerase chain reaction （RT-PCR）, Western blotting and immunofluorescence experiments. The non-specific ASICs inhibitor amiloride and specific homomeric ASICla blocker PcTxl reduced the production of iNOS and COX-2 by LPS-induced activating RAW 264.7 cells. Furthermore, not only amiloride but also PcTxl inhibited the migration and LPS-induced apoptosis of RAW 264.7 cells. Taken together, our findings suggest that ASICs promote the inflammatory response and apoptosis of RAW 264.7 cells, and ASICs may serve as a potential novel target for immunological disease therapy.
基金Supported by National Essence Basic Research and Development 973 Program(the Effects of Meridian Specific Target Organ Response to Biological Basic Research,No.2012CB518503)
文摘OBJECTIVE:To investigate the impact of electro-acupuncture at the Neiguan(PC 6) acupoint on protein and RNA expression of acid-sensing ion channel 2(ASIC2) and ASIC3 in myocardial ischemia rats.METHODS:Fifty male Sprague-Dawley rats were used,weighing(230 ± 50) g.The rats were randomized into a normal group A,model group B,Neiguan(PC 6) group C,Lieque(LU 7) group D,and A-shi points group E.There were 10 rats in each group.Rats were continuously administered 85 mg/kg intravenous isoproterenol daily to establish the model.Successfully modeled rats in groups C,D,and E were given electro-acupuncture treatment.Each group of rats was sacrificed with chloral hydrate(1 mL/100 g) intraperitoneal injection.The left ventricular myocardium was extracted and placed at- 70 ℃ until use.Western blot analysis and real-time PCR were performed to assay protein and RNA expressions of ASIC2 and ASIC3,respectively.Fold changes in RNA expression were quantified with the 2~^(-△△Ct) method.Blood samples were drawn from the aorta abdominalis and tested for creatine kinase-MB(CK-MB) and lactate dehydrogenase(LDH) levels using enzyme-linked immunosorbent assay.RESULTS:Myocardial ischemia rats given electro-acupuncture at the Neiguan(PC 6) acupoint had significantly lower protein and RNA expression of ASIC2 and ASIC3,and CK-MB and LDH levels,compared with model rats(P < 0.01).CONCLUSION:Electro-acupuncture at the Neiguan(PC 6) acupoint can not only decrease the protein and RNA expression of ASIC2 and ASIC3,but also inhibit the opening of ASICs and reduce the cardiomyocyte damage in myocardial ischemia rats.
文摘Capacitation and acrosome reaction are important prerequisites of the fertilization process. Capacitation is a highlycomplex phenomenon occurring in the female genital tract, rendering the spermatozoa capable of binding and fusionwith the oocyte. During capacitation various biochemical and biophysical changes occur in the spermatozoa and thespermatozoal membranes. Ions and ion channels also play important roles in governing the process of capacitation bychanging the fluxes of different ions which in turn controls various characteristics of capacitated spermatozoa. Alongwith the mobilization of ions the generation of free radicals and efflux of cholesterol also plays an important role in thecapacitation state of the spermatozoa. The generation of free radical and efflux of cholesterol change the mechano-dynamic properties of the membrane by oxidation of the polyunsaturated lipids and by generating the cholesterol freepatches. The process of capacitation renders the spermatozoa responsive to the inducers of the acrosome reaction. Theglycoprotein zona pellucida 3 (ZP3) of the egg coat zona pellucida is the potent physiological stimulator of the acro-some reaction; progesterone, a major compoent of the follicular fluid, is also an induce of the acrosome reaction.The inducers of the acrosome reaction cause the activation of the various ion-channels leading to high influxes of calci-um, sodium and bicarbonate. The efflux of cholesterol during the process of capacitation alters the permeablity of themembrane to the ions and generate areas which are prone to fusion and vesculation process during the acrosome reac-tion. Ths review focuses mainly on effects of the ion and ion-channels, free radicals, and membrane fluidity changesduring the process of capacitation and acrosome reaction. (Asian J Androl 1999 Sep; 1: 95-107)
文摘Cancer has been one of the most serious public health issues in the world. Traditional medicines are widely used in adjunctive therapies in clinical cancer treatment in many countries. One of the unique traditional medicine usages in tumor treatment is the high-dose application of traditional toxin medicine, including venom or body from toxin animals. Evidence has shown that they are very likely to have direct effects on cancer cells. One of the potential pharmacological effects of traditional toxin medicines is their regulation of ion channels in cancers. Many ion channels are found critical in cancers. This study suggested that ion channels were involved in the effect of traditional toxin medicine on cancers. However, so far, the study of the effect of traditional toxin medicine on ion channels in cancers is relatively lacking. This perspective article urged the study in this field because, given the fact that these traditional toxin traditional medicines have been widely used in cancer treatment, the identification of the effective components and pharmacological targets can improve their clinical application.
基金Beijing Traditional Chinese Medicine Foundation for Science and Technology(JJ-2020-78):Research on the Protection of Intellectual Property Rights of Traditional Chinese MedicineScientific and Technological Innovation Project of China Academy of Chinese Medical Sciences(CI2021A00912):Basic and Translational Research on the Application of Traditional Chinese Medicine+1 种基金the Research Foundation of Major New Drug Creation,from the Ministry of Science and Technology of China(2018ZX09721003-009-022):Research on Key Technologies and Industrialization of Traditional Chinese Medicine Preparations for ChildrenNational Natural Science Foundation of China(82074060):Study on the Effect of Tanyu Tongzhi Fang in Maintaining Vascular Homeostasis in the Treatment of Atherosclerosis。
文摘OBJECTIVE:To explore how Qingfei Zhisou oral liquid(清肺止嗽口服液,QFZS)adjusts body temperature bias and the interaction of inflammatory factors levels and metabolomic differences.METHODS:Dry yeast was subcutaneously injected at 10 mL/kg to establish the pyrexia model.We randomly divided 60 Sprague-Dawley rats into five groups:control,model,positive,low dose of QFZS and high dose of QFZS.Inflammatory proteins were evaluated by Western blotting and immunohistochemistry.For the examination of the endogenous metabolites,enzyme linked immunosorbent assay and ultra-high-performance liquid chromatography high-resolution mass spectrometry were employed.RESULTS:QFZS significantly reduced rats'body temperature within 6 h after dry yeast injection and reduced the secretion of the arginine vasopressin,cyclic adenosine monophosphate,prostaglandin E-2,tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),and interleukin-1βin serum.Meanwhile,we identified 41 metabolites between the model and QFZS groups,including arachidonic acid and lysophospholipids.QFZS restored normal arachidonic acid levels.Based on the differential metabolite enrichment analysis,QFZS's antiinflammatory and anti-pyrexia effects might be related to the inflammatory pathway regulated by transient receptor potential.Additionally,QFZS treatment reduced transient receptor potential melastatin 2 ion channel expression and affected TNF-α,heat shock protein 70,and cyclooxygenase-2 expression in the hypothalamus.CONCLUSION:QFZS exerts its regulatory effects on fever by regulating the metabolism of lysophospholipids and arachidonic acid and the regulation of inflammation via transient receptor potential ion channels channels.
基金financially supported by the National Key R&D Program of China (No.2017YFA0304203)the National Natural Science Foundation of China (Nos.21805174 and 51902190)+5 种基金the Key Research and Development Program of Shanxi Province for International Cooperation (No.201803D421082)the Scientific and Technological Innovation Programs of Higher Education Institutions in Shanxi (Nos.2019L0013 and 2019L0018)Shanxi Scholarship Council of China (No.2021-004)the Program of Introducing Talents of Discipline to Universities (No.D18001)the Changjiang Scholars and Innovative Research Team at the University of Ministry of Education of China (No.IRT_17R70)the Fund for Shanxi “1331 Project”
文摘MXene has given great promises to superca-pacitor electrode material due to its high conductivity and redox properties.However,the self-agglomeration of the MXene lamella will reduce its contact area with the elec-trolyte and generate a tortuous transportation pathway of the electrolyte ions,thereby reducing its capacitive per-formance and rate capability.In this work,we engineered the electrolyte ion channels by adjusting the MXene lamella size and inserting holey graphene(HG)nanosheets into the interlayer of the MXene flakes.The developed MXene/HG electrode can not only avoid the self-restack-ing of MXene but also provide unimpeded ion transport channels.As a result,the supercapacitive and rate perfor-mances of the small MXene lamella-based MXene/HG(S-MXene/HG)supercapacitor are prominently ameliorated.By adjusting the content of HG,the S-MXene/HG0.05 electrode exhibits excellent gravimetric capacitance of 446 F·g^(-1)and a rate capability of 77.5%.The S-MXene/HG0.05-based symmetric supercapacitor provides an impressive energy density of 14.84 Wh·kg^(-1)with excellent cyclic stability of 96%capacitance retention after 10,000 cycles.This demonstration of the engineering of the ion channels shows great potential in two-dimensional mate-rial-based supercapacitor electrodes.
基金supported by the National Natural Science Foundation of China,No.30872665
文摘Acidosis is a common characteristic of brain damage. Because studies have shown that permeable Ca2＋-acid-sensing ion channels can mediate the toxic effects of calcium ions, they have become new targets against pain and various intracranial diseases. However, the mechanism associated with expression of these channels remains unclear. This study sought to observe the expression characteristics of permeable Ca2＋-acid-sensing ion channels during different reperfusion inflows in rats after cerebral ischemia. The rat models were randomly divided into three groups： adaptive ischemia/reperfusion group, one-time ischemia/reperfusion group, and severe cerebral ischemic injury group. Western blot assays and immunofluorescence staining results exhibited that when compared with the one-time ischemia/reperfusion group, acid-sensing ion channel 3 and Bcl-x/I expression decreased in the adaptive ischemia/reperfusion group. Calmodulin expression was lowest in the adaptive ischemia/reperfusion group. Following adaptive reperfusion, common carotid artery flow was close to normal, and the pH value improved. Results verified that adaptive reperfusion following cerebral ischemia can suppress acid-sensing ion channel 3 expression, significantly reduce Ca2＋ influx, inhibit calcium overload, and diminish Ca2＋ toxicity. The effects of adaptive ischemia/reperfusion on suppressing cell apoptosis and relieving brain damage were better than that of one-time ischemia/reperfusion.
文摘Ion channels are membrane proteins that are found in a number of viruses and which are of crucial physiological importance in the viral life cycle. They have one common feature in that their action mode involves a change of electrochemical or proton gradient across the bilayer lipid membrane which modulates viral or cellular activity. We will discuss a group of viral channel proteins that belong to the viroproin family, and which participate in a number of viral functions including promoting the release of viral particles from cells. Blocking these channel-forming proteins may be ＂lethal＂, which can be a suitable and potential therapeutic strategy. In this review we discuss seven ion channels of viruses which can lead serious infections in human beings： M2 of influenza A, NB and BM2 of influenza B, CM2 of influenza C, Vpu of HIV-1, p7 of HCV and 2B of picomaviruses.
文摘The reliable functioning of ion channels should be closely related to their structural stability. The selectivity filter in the KcsA potassium channel possesses four stable ion binding sites that can coordinate nearly fully dehydrated ions, whereas only two of such binding sites exist in the non-selective NaK channel, and none of them is found in the NavAb sodium channel. Here we show that the stability of the selectivity filters in these tetrameric cation channels is inversely correlated with the number of stable binding sites by extensive molecular dynamics simulations. While the presence of coordinated ions is crucial for the selectivity filters of the KcsA and NaK channels to stabilize the conformations in their crystal structures, the selectivity filter of the NavAb channel shows higher stability, independent of the presence of ions. We further show that the distinct repulsive electrostatic interactions between negatively charged oxygen atoms in the selectivity filter which form the stable binding sites are responsible for the different stability of these cation channels. The hydrogen bonding networks between residues in the selectivity filter and its adjacent pore helix also play an important role in maintaining stability. Together, these results provide important mechanistic insights into the structural stability of the selectivity filters in typical cation channels.
基金supported by the National Key Research and De-velopment Program of China(2022YFB3203801,2022YFB3203804,2022YFB3203800)the Shanghai Sailing Program(23YF1420100),the National Natural Science Foundation of China(32071374)+5 种基金the Program of Shanghai Academic Research Leader under the Science and Technology Innovation Action Plan(21XD1422100)Program of Shanghai Science and Technology Development(22TS1400700)CAS Interdisciplinary Innovation Team(JCTD-2020-08),start-up funds from Shanghai Jiao Tong University(22X010201631)the Zhejiang Provin-cial Natural Science Foundation of China(LR22C100001)the Inno-vative Research Team of High-level Local Universities in Shanghai(SHSMU-ZDCX20210900)Shanghai Municipal Science and Tech-nology Commission(21dz2210100).
文摘Biological ion channels are essential for ion and molecule transport,playing a critical role in maintaining cellular equilibrium and regulating vital physiological functions such as cell growth,hormone secretion,and nerve-muscle interactions.Drawing inspiration from nature,researchers have crafted an array of supramolecular artificial ion channels(AICs)using both unimolecular and self-assembly approaches.Notably,AICs based on macrocyclic molecules,such as cyclodextrins,crown ethers,and pillararenes,offer distinct advantages,including biocompatibility,precise structural design,ease of customization,and simple preparation.This review spotlights recent progress in bioinspired AICs rooted in macrocycles and their applications in the realm of biomedicine.We commence with an overview of the significance of biological channels and the strategies employed for fashioning supramolecular artificial channels.Subsequently,we navigate through the intricate landscape of molecular design,structural modulation,and the ion transport prowess exhibited by macrocycle-based AICs.Furthermore,we explore the promising biomedical applications of these AICs,encompassing roles in antibacterial measures,anticancer interventions,biosensing technologies,and treatments for channelopathies.Finally,we address the persisting challenges and illuminate prospects within this field,with the ultimate aim of steering future innovations in the development of supramolecular AICs.
基金support from the National Institutes of Health(R01GM144986,R01CA232017,and R21AI174606 to Y.Z.,as well as R35HL166557,R01DK132286,and R01CA240258 to Y.H.)the Leukemia&Lymphoma Society(to Y.Z.)the Welch Foundation(BE-1913-20220331 to Y.Z.).
文摘Ion channels play instrumental roles in regulating membrane potential and cross-membrane signal transduction,thus making them attractive targets for understanding various physiological processes and associated diseases.Gaining a deeper understanding of their structural and functional properties has significant implications for developing therapeutic interventions.In recent years,nanobodies,single-domain antibody fragments derived from camelids,have emerged as powerful tools in ion channel and synthetic biology research.Their small size,high specificity,and ability to recognize difficult-to-reach epitopes offer advantages over conventional antibodies and biologics.Furthermore,their resemblance to the variable region of human IgG family III reduces immunogenicity concerns.Nanobodies have introduced new opportunities for exploring ion channel structure-function relationships and offer a promising alternative to conventional drugs,which often face challenges such as off-target effects and toxicity.This review highlights recent progress in applying nanobodies to interrogate and modulate ion channel activity,with an emphasis on their potential to overcome current technical and therapeutic limitations.
文摘Throughout the annals of human civilization,the utilization of energy has been a cornerstone of our advancement.Particularly over the past few centuries,each technological revolution has catalyzed a leap in development,profoundly transforming society.However,with these advancements,energy consumption has surged.
文摘Cardiac ion channels are critical transmembrane proteins that mediate almost all aspects of cardiac function including generation and propagation of cardiac action potential(AP)aswell asmaintenance of normal heart excitability and contraction.In addition,the pivotal role of cardiac ion channels in cardiac health and disease is underscored by the profound effects of their dysfunctional mutations on various arrhythmias.Hence,ion channels are vital targets for antiarrhythmic drugs.In this review,we first summarize the characteristics,structure of the various cardiac ion channels and their specific roles in cardiac electrophysiology.Subsequently,we highlight the implications of genetic mutations that disrupt ion channel function,which are associated with inherited cardiac arrhythmias.Finally,we address antiarrhythmic drugs acting on cardiac ion channels respectively,according to their therapeutic targets.In conclusion,this manuscript aims to review the physiology,pathophysiology and pharmacology of the most prominent ventricular NaV,CaV,KV,andKir ion channels.
基金financially supported by the Key R&D Program of Shandong Province(2022SFGC0801)the National Natural Science Foundation of China(No.22005162 and 22175009)the Natural Science Foundation of Shandong Province(No.ZR2020QE093)。
文摘Osmotic energy,existing between the seawater and river water,is a renewable energy source,which can be directly converted into electricity by ion-exchange membranes(IEM).In traditional IEMs,the ion transport channels are formed by nanophase separation of hydrophilic ion carriers and hydrophobic segments.It is difficult to realize high-density ion channels with controlled spatial arrangement and length scale of ion carriers.Herein,we construct high-density 1D ion wires as transmission channels.Through molecular design,hydrophilic imidazole groups and hydrophobic alkyl tails were introduced into the repeat units,which self-assembled into 1D ion transporting core and protecting shell along the main chains.The areal density of the ionic wire arrays is up to~10^(12)cm^(-2),which is the highest value.The ionic wires ensure both high ion flux transport and high selectivity,achieving an ultrahigh-power density of 40.5 W m^(-2)at a 500-fold salinity gradient.Besides,the ionic wire array membrane is well recyclable and antibacterial.The ionic wires provide novel concept for next generation of high-performance membranes.
基金supported by ANID-FONDECYT 1200908(to JF),ANID-FONDECYT 1211082 and 1250856(to GEY)by the Millennium Nucleus for the Study of Pain NCN19_038(Mi Nu SPain)(to GEY)funded by the ANID scholarship 21201176。
文摘Numerous pathological states of the nervous system involve alterations in neuronal excitability and synaptic dysfunction,which depend on the function of ion channels.Due to their critical involvement in health and disease,the search for new compounds that modulate these proteins is still relevant.Traditional medicine has long been a rich source of neuroactive compounds.For example,the indigenous Mapuche people have used the leaves and bark of the Drimys winteri tree for centuries to treat various diseases.Consequently,several studies have investigated the biological effects of compounds in Drimys winteri,highlighting sesquiterpenes such asα-humulene,drimenin,polygodial,andα-,β-,γ-eudesmol.However,there is currently no literature review focusing on the ability of these sesquiterpenes to modulate ion channels.This review summarizes the current knowledge about neuroactive compounds found in Drimys winteri,with special emphasis on their direct actions on neuronal ion channels.Several Drimys winteri sesquiterpenes modulate a diverse array of neuronal ion channels,including transient receptor potential channels,gamma-aminobutyric acid A receptors,nicotinic acetylcholine receptors,and voltage-dependent Ca^(2+)and Na^(+)channels.Interestingly,the modulation of these molecular targets by Drimys winteri sesquiterpenes correlates with their therapeutic actions.The promiscuous pharmacological profile of Drimys winteri sesquiterpenes suggests they modulate multiple protein targets in vivo,making them potentially useful for treating complex,multifactorial diseases.Further studies at the molecular level may aid in developing multitargeted drugs with enhanced therapeutic effects.
基金supported by the National Natural Science Foundation of China(No.22209182,22425905 and 22279141)he Self-deployment Project Research Program of Haixi Institutes,Chinese Academy of Sciences(No.CXZX-2022-GH04)+3 种基金the Key Research Program of Frontier Sciences,CAS(No.ZDBS-LY-SLH028)National key Research&Development Program of China(2021YFA1501500)Fujian Science&Technology Innovation Laboratory for Optoelectronic Information of China(No.2021ZZ106)Science and Technology Service Network Initiative(KFJ-STS-QYZD-2021-09-003).
文摘Covalent organic frameworks(COFs)are an emerging class for solid-state electrolytes due to their ordered and customizable ion transport nanochannels.Although high ionic conductivity(σ_(Li+))and Li^(+) transference number(t_(Li+))are achieved;the high-arealcapacity solid-state lithium metal battery(LMB)still encountered challenges;which is mainly determined by homogeneous Li^(+) flux through channels and interfaces.Herein;we design a COF coupling anionic skeletons with branched ion-conductive chains(COF-S)as tailored fast ion-transport channels to achieve high-areal-capacity solid-state LMB.Then the dispersed COF-S-based electrolyte is further obtained by incorporating ethoxylated trimethylolpropane triacrylate(ETPTA)and Li FSI(ETPTA-COF-S)via in situ light solidification.In this way;the abundant SO_(3)-groups promote Li+adsorption and facilitate axial transport via 1D channels;thus enabling highσLi+of 1.29 m S cm^(-1)and tLi+of 0.83.The branched chains can tailor ion channels to suppress largesize anions transport;disperse and uniform Li+flux;thus leading to high average Coulombic efficiency(CE)up to 98.43%for 100 cycles(~800 h)at 0.5 m A cm^(-2)under the high areal capacity of 2 mAh cm^(-2).When paired with 2 m Ah cm^(-2)LiFePO_(4)(LFP)cathode and thin Li anode of 20μm;Li||ETPTA-COF-S||LFP exhibits superior cyclic stability for 80 cycles.
