Photocatalysis uses solar energy to convert nitrogen and water directly into ammonia,helping reduce dependence on fossil fuels and offering a way to integrate the nitrogen cycle into a clean energy network.Ohmic junct...Photocatalysis uses solar energy to convert nitrogen and water directly into ammonia,helping reduce dependence on fossil fuels and offering a way to integrate the nitrogen cycle into a clean energy network.Ohmic junctions between metals and semiconductors have demonstrated significant advantages in enhancing stability and reducing carrier recombination,but their application in photocatalytic nitrogen fixation is limited due to the difficulty of work function matching and the complexity of fabrication processes.In this study,density functional theory(DFT) calculations were used to confirm the work function matching between Bi and Bi_(2)Ti_(2)O_(7)(BTO),ensuring the formation of an Ohmic junction.A Bi-Bi_(2)Ti_(2)O_(7)(B-BTO) composite was successfully synthesized via a one-step hydrothermal method,using bismuth nitrate and titanium sulfate as precursors.Compared to pure BTO,the B-BTO heterojunction,driven by dual electron injection from both metal Bi and BTO,significantly increased the ammonia synthesis rate to 686.95 μmol g^(-1)h^(-1),making it the most active nitrogen fixation material among similar pyrochlorebased catalysts to date.The differential charge density calculations,photocurrent(i-t) measurements,and photoluminescence(PL) tests further validate the role of Ohmic contacts in enhancing charge transfer and prolonging carrier lifetimes.This research provides valuable insight into the application of Ohmic junctions in photocatalytic nitrogen fixation and contributes to advancements in this field.展开更多
Nociception is an important physiological process that detects harmful signals and results in pain perception. In this review, we discuss important experimental evidence involving some TRP ion channels as molecular se...Nociception is an important physiological process that detects harmful signals and results in pain perception. In this review, we discuss important experimental evidence involving some TRP ion channels as molecular sensors of chemical, thermal, and mechanical noxious stimuli to evoke the pain and itch sensations. Among them are the TRPA1 channel, members of the vanilloid subfamily （TRPV1, TRPV3, and TRPV4）, and finally members of the melastatin group （TRPM2, TRPM3, and TRPMS）. Given that pain and itch are pro-survival, evolutionarily-honed protective mechanisms, care has to be exercised when developing inhibitory/modulatory com- pounds targeting specific pain/itch-TRPs so that physio- logical protective mechanisms are not disabled to a degree that stimulus-mediated injury can occur. Such events have impeded the development of safe and effective TRPV1- modulating compounds and have diverted substantial resources. A beneficial outcome can be readily accom- plished via simple dosing strategies, and also by incorpo- rating medicinal chemistry design features during compound design and synthesis. Beyond clinical use, where compounds that target more than one channel might have a place and possibly have advantageous features, highly specific and high-potency compounds will be helpful in mechanistic discovery at the structure-function level.展开更多
During the last decade, transient receptor potential （TRP） channels emerge as key proteins in central mechanisms of the carcinogenesis such as cell proliferation, apoptosis and migration. Initial studies showed that...During the last decade, transient receptor potential （TRP） channels emerge as key proteins in central mechanisms of the carcinogenesis such as cell proliferation, apoptosis and migration. Initial studies showed that expression profile of some TRP channels, notably TRP melastatin 8 （TRPM8）, TRP vanilloid 6 （TRPV6）,TRP canonical （TRPC6） and TRPV2, is changing during the development and the progression of prostate cancer towards the hormone-refractory stages. The link between the change in expression levels and the functional role of these channels in prostate cancer is step by step being elucidated. These recent advances are here described and discussed.展开更多
Aphelinus asychis is an important aphid endoparasitoid.Under field and greenhouse conditions,high temperature is one of the factors limiting the application of A asychis for biological pest control.To explore the pote...Aphelinus asychis is an important aphid endoparasitoid.Under field and greenhouse conditions,high temperature is one of the factors limiting the application of A asychis for biological pest control.To explore the potential role of transient receptor potential(TRP)channels and heat shock proteins(HSPs)in this process,we identified 11 genes encoding TRP channels and nine genes encoding HSPs.Three proteins(AasyTRPA5,AasyPyrexia,AasyPainless)that belong to transient receptor potential ankyrin(TRPA)subfamily and nine HSPs are involved in the response to high temperature.We also investigated the survival of A asychis and the response of the identified TRP channels and HSPs to high temperature.The results showed that the maximum temperature that allowed A.asychis survival was approximately 41°C;females had higher survival rates than that of the males at 40 and 41°C.Short-term heat-shock resulted in increased expression of Amsysbsp in males,and Aasyhsp40,Aasyhsp68,Aasyhsp70-4,Aasyhsp70-5 and Aasyhsp90 were upregulated and then down regulated,whereas Aasyhsp70-3was upregulated at41°C.Moreover,Aasyhsp40and Aasyhsp90showed higherexpression levels in females,while Aasyshsp and Aasyhsp70-3 presented opposite expression patterns.At temperature above 35°C,expression of AasyPyrexia in females was significant higher than that in males,whereas AasyPainless mnd AasyTRPA5 presented higher expression in males at 40 and 41°C,respectively.Altogether,these results indicate that protect!on against thermal stress in A.asychis is coordinated by TRP channels and HSPs.These findings provide a basis for understanding the potential mechanism of A asychis in response to high temperatures.展开更多
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 n...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-channelspecific 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.展开更多
Objective: To examine the effects of Tribulus terrestris L.(T. terrestris) extract on the modulation of calcium channels to evaluate its use in topical agents for treatment of atopic dermatitis.Methods: The 70% methan...Objective: To examine the effects of Tribulus terrestris L.(T. terrestris) extract on the modulation of calcium channels to evaluate its use in topical agents for treatment of atopic dermatitis.Methods: The 70% methanol extract of T. terrestris was prepared. Human HEK293 T cells with over-expressed calcium release-activated calcium channel protein 1(Orai1),transient receptor potential vanilloid 1, or transient receptor potential vanilloid 3(TRPV3)were treated with T. terrestris extract. Modulation of ion channels was measured using a conventional whole-cell patch-clamp technique.Results: T. terrestris extract(100 mg/m L) significantly inhibited Orai1 activity in Orai1-stromal interaction molecule 1 co-overexpressed HEK293 T cells. In addition, T. terrestris extract significantly increased the TRPV3 activity compared with 2-Aminoethyl diphenylborinate(100 mmol/L), which induces the full activation of TRPV3.Conclusions: Our results suggest that T. terrestris extract may have a therapeutic potential for recovery of abnormal skin barrier pathologies in atopic dermatitis through modulating the activities of calcium ion channels, Orai1 and TRPV3. This is the first study to report the modulatory effect of a medicinal plant on the function of ion channels in skin barrier.展开更多
This study numerically examines the heat and mass transfer characteristics of two ternary nanofluids via converging and diverg-ing channels.Furthermore,the study aims to assess two ternary nanofluids combinations to d...This study numerically examines the heat and mass transfer characteristics of two ternary nanofluids via converging and diverg-ing channels.Furthermore,the study aims to assess two ternary nanofluids combinations to determine which configuration can provide better heat and mass transfer and lower entropy production,while ensuring cost efficiency.This work bridges the gap be-tween academic research and industrial feasibility by incorporating cost analysis,entropy generation,and thermal efficiency.To compare the velocity,temperature,and concentration profiles,we examine two ternary nanofluids,i.e.,TiO_(2)+SiO_(2)+Al_(2)O_(3)/H_(2)O and TiO_(2)+SiO_(2)+Cu/H_(2)O,while considering the shape of nanoparticles.The velocity slip and Soret/Dufour effects are taken into consideration.Furthermore,regression analysis for Nusselt and Sherwood numbers of the model is carried out.The Runge-Kutta fourth-order method with shooting technique is employed to acquire the numerical solution of the governed system of ordinary differential equations.The flow pattern attributes of ternary nanofluids are meticulously examined and simulated with the fluc-tuation of flow-dominating parameters.Additionally,the influence of these parameters is demonstrated in the flow,temperature,and concentration fields.For variation in Eckert and Dufour numbers,TiO_(2)+SiO_(2)+Al_(2)O_(3)/H_(2)O has a higher temperature than TiO_(2)+SiO_(2)+Cu/H_(2)O.The results obtained indicate that the ternary nanofluid TiO_(2)+SiO_(2)+Al_(2)O_(3)/H_(2)O has a higher heat transfer rate,lesser entropy generation,greater mass transfer rate,and lower cost than that of TiO_(2)+SiO_(2)+Cu/H_(2)O ternary nanofluid.展开更多
Constructing silicon(Si)-based composite electrodes that possess high energy density,long cycle life,and fast charging capability simultaneously is critical for the development of high performance lithium-ion batterie...Constructing silicon(Si)-based composite electrodes that possess high energy density,long cycle life,and fast charging capability simultaneously is critical for the development of high performance lithium-ion batteries for mitigating range anxiety and slow charging issues in new energy vehicles.Herein,a thick silicon/carbon composite electrode with vertically aligned channels in the thickness direction(VC-SC)is constructed by employing a bubble formation method.Both experimental characterizations and theoretical simulations confirm that the obtained vertical channel structure can effectively address the problem of sluggish ion transport caused by high tortuosity in conventional thick electrodes,conspicuously enhance reaction kinetics,reduce polarization and side reactions,mitigate stress,increase the utilization of active materials,and promote cycling stability of the thick electrode.Consequently,when paired with LiNi_(0.6)Co_(0.2)Mn_(0.2)O_(2)(NCM622),the VC-SC||NCM622 pouch type full cell(~6.0 mAh cm^(-2))exhibits significantly improved rate performance and capacity retention compared with the SC||NCM622 full cell with the conventional silicon/carbon composite electrode without channels(SC)as the anode.The assembled VC-SC||NCM622 pouch full cell with a high energy density of 490.3 Wh kg^(-1)also reveals a remarkable fast charging capability at a high current density of 2.0 mA cm^(-2),with a capacity retention of 72.0%after 500 cycles.展开更多
Transient receptor potential(TRP)channels are a class of ion channel proteins that are closely related to thermosensation in insects.They are involved in detecting the ambient temperature and play vital roles in insec...Transient receptor potential(TRP)channels are a class of ion channel proteins that are closely related to thermosensation in insects.They are involved in detecting the ambient temperature and play vital roles in insect survival and reproduction.In this study,we identifed and cloned two variants of the TRPA subfamily gene in Myzus persicae,MperTRPA1(A)and MperTRPA1(B),and analyzed their tissue expression by real-time quantitative PCR.Subsequently,these two variants of MperTRPA1 were expressed in the Xenopus oocyte system,and their functions were investigated using the two-electrode voltage clamp technique.The role of the MperTRPA1 gene in temperature adaptation of M.persicae was further determined by RNA interference and a behavioral choice assay to evaluate responses to temperature gradients.The results showed that the MperTRPA1 gene is widely expressed in tissues of M.persicae,with MperTRPA1(A)highly expressed in the mouthparts and MperTRPA1(B)mainly expressed in the antennae.The functional characterization results showed that both variants of MperTRPA1 could be activated and were not desensitized when the temperature increased from 20 to 45℃.The current value and thermal sensitivity(coeffcient Q_(10)value)of MperTRPA1(B)were signifcantly higher than those of MperTRPA1(A).When the MperTRPA1 gene was knocked down,the behavioral preference of M.persicae for the optimal temperature was reduced and tended to be at a higher temperature,showing a shift in the temperature adaptation range compared to both the wild type and ds GFP-treated M.persicae.In summary,our results elucidated the molecular mechanism of adaptive temperature perception in M.persicae mediated by the thermal sensor MperTRPA1.展开更多
AIM： To investigate the characteristics of slow electrical waves and the presence of transient receptor potential melastatin-type 7 （TRPM7） in the human gastrointestinal （GI） tract. METHODS： Conventional microel...AIM： To investigate the characteristics of slow electrical waves and the presence of transient receptor potential melastatin-type 7 （TRPM7） in the human gastrointestinal （GI） tract. METHODS： Conventional microelectrode techniques were used to record intracellular electrical responses from human GI smooth muscle tissue. Immunohistochemistry was used to identify TRPM7 channels in interstitial cells of Cajat （ICCs）. RESULTS： The human GI tract generated slow electrical waves and had ICCs which functioned as pacemak er cells. Flufenamic acid, a nonselective cation channel blocker, and 2-APB （2-aminoethoxydiphenyl borate） and La3＋, TRPM7 channel blockers, inhibited the slowwaves. Also, TRPM7 channels were expressed in ICCs in human tissue. CONCLUSION： These results suggest that the human GI tract generates slow waves and that TRPM7 channels expressed in the ICCs may be involved in the gen- eration of the slow waves.展开更多
AIM： To explore the possibility of using the Noninvasive Micro-test Technique （NMT） to investigate the role of Transient Receptor Potential Canonical 1 （TRPC1） in regulating Ca^2＋ influxes in HL-7702 cells, a no...AIM： To explore the possibility of using the Noninvasive Micro-test Technique （NMT） to investigate the role of Transient Receptor Potential Canonical 1 （TRPC1） in regulating Ca^2＋ influxes in HL-7702 cells, a normal human liver cell line.METHODS： Net Ca^2＋ fluxes were measured with NMT, a technology that can obtain dynamic information of specific/selective ionic/molecular activities on material surfaces, non-invasively. The expression levels of TRPCl were increased by liposomal transfection, whose effectiveness was evaluated by Western-blotting and single cell reverse transcription-polymerase chain reaction.RESULTS： Ca^2＋ influxes could be elicited by adding 1 mmol/L CaCl2 to the test solution of HL-7702 cells. They were enhanced by addition of 20 μmol/L noradrenalin and inhibited by 100 μmol/L LaCl3 （a non-selective Ca^2＋ channel blocker）; 5 μmol/L nifedipine did not induce any change. Overexpression of TRPCl caused increased Ca^2＋ influx. Five micromoles per liter nifedipine did not inhibit this elevation, whereas 100 μmol/L LaCI3 did.CONCLUSION： In HL-7702 cells, there is a type of TRPCl-dependent Ca^2＋ channel, which could be detected v/a NMT and inhibited by La^3＋.展开更多
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
Reliable channel data helps characterize the limitations and performance boundaries of communication technologies accurately.However,channel measurement is highly costly and time-consuming,and taking actual measuremen...Reliable channel data helps characterize the limitations and performance boundaries of communication technologies accurately.However,channel measurement is highly costly and time-consuming,and taking actual measurement as the only channel data source may reduce efficiency because of the constraints of high testing difficulty and limited data volume.Although existing standard channel models can generate channel data,their authenticity and diversity cannot be guaranteed.To address this,we use deep learning methods to learn the attributes of limited measured data and propose a generative model based on generative adversarial networks to rapidly synthesize data.A software simulation platform is also established to verify that the proposed model can generate data that are statistically similar to the measured data while maintaining necessary randomness.The proposed algorithm and platform can be applied to channel data enhancement and serve channel modeling and algorithm evaluation applications with urgent needs for data.展开更多
This research study focuses on addressing the limitations of current neuropathic pain(NP)treatments by developing a novel dual-target modulator,E0199,targeting both Na_(V)1.7,Na_(V)1.8,and Na_(V)1.9 and K_(V)7 channel...This research study focuses on addressing the limitations of current neuropathic pain(NP)treatments by developing a novel dual-target modulator,E0199,targeting both Na_(V)1.7,Na_(V)1.8,and Na_(V)1.9 and K_(V)7 channels,a crucial regulator in controlling NP symptoms.The objective of the study was to synthesize a compound capable of modulating these channels to alleviate NP.Through an experimental design involving both in vitro and in vivo methods,E0199 was tested for its efficacy on ion channels and its therapeutic potential in a chronic constriction injury(CCI)mouse model.The results demonstrated that E0199 significantly inhibited Na_(V)1.7,Na_(V)1.8,and Na_(V)1.9 channels with a particularly low half maximal inhibitory concentration(IC50)for Na_(V)1.9 by promoting sodium channel inactivation,and also effectively increased K_(V)7.2/7.3,K_(V)7.2,and K_(V)7.5 channels,excluding K_(V)7.1 by promoting potassium channel activation.This dual action significantly reduced the excitability of dorsal root ganglion neurons and alleviated pain hypersensitivity in mice at low doses,indicating a potent analgesic effect without affecting heart and skeletal muscle ion channels critically.The safety of E0199 was supported by neurobehavioral evaluations.Conclusively,E0199 represents a ground-breaking approach in NP treatment,showcasing the potential of dual-target small-molecule compounds in providing a more effective and safe therapeutic option for NP.This study introduces a promising direction for the future development of NP therapeutics.展开更多
Efficient selective adsorption and separation using porous frameworks are critical in many industrial processes,where adsorption energy and dynamic diffusion rate are predominant factors governing selectivity.They are...Efficient selective adsorption and separation using porous frameworks are critical in many industrial processes,where adsorption energy and dynamic diffusion rate are predominant factors governing selectivity.They are highly susceptible to framework charge,which plays a significant role in selective adsorption.Currently,ionic porous frameworks can be divided into two types.One of them is composed of a charged backbone and counter ions.The framework with zwitterionic channels is another type.It is composed of regular and alternating arrangements of cationic and anionic building units.Herein,we report a hydrogen-bonded ionic framework(HIF)of{(CN_(3)H_(6))_(2)[Ti(μ_(2)-O)(SO_(4))_(2)]}_nwith 1D channel exhibits unique adsorption selectivity for Ar against N_(2)and CO_(2).Density functional theory(DFT)results suggest that CO_(2)cannot be adsorbed by HIF at the experimental temperature due to a positive adsorption free energy.In addition,due to a relatively large diffusion barrier at 77 K,N_(2)molecules hardly diffuse in HIF channels,while Ar has a negligible diffusion barrier.The unique net positively-charged space in the channel is the key to the unusual phenomena,based on DFT simulations and structural analysis.The findings in this work proposes the new adsorption mechanism and provides unique perspective for special separation applications,such as isotope and noble gasses separations.展开更多
Patch-clamp technique serve as a powerful tool for precisely measuring and characterizing ion channel currents,offering critical molecular-level insights essential for drug screening and optimization.By enabling a dee...Patch-clamp technique serve as a powerful tool for precisely measuring and characterizing ion channel currents,offering critical molecular-level insights essential for drug screening and optimization.By enabling a deeper understanding of ion channel behavior,these techniques significantly accelerate the process of drug discovery and development.In recent years,automated patch-clamp technique has undergone substantial advancements,surpassing traditional manual methods with its high throughput,improved data consistency,and automation.However,fully harnessing these advantages requires meticulous optimization of experimental conditions tailored to specific targets.Without such refinement,the high cost of consumables and operational expenses could severely hinder the widespread adoption of this technique.This study focused on the TRPV1 channel,detailing the establishment of an automated patch-clamp detection system for TRPV1 currents,optimization of experimental parameters,and a comparative evaluation of the results against manual patch-clamp techniques.展开更多
The robustness of reference-frame-independent measurement-device-independent quantum key distribution(RFIMDI-QKD)against detection system vulnerabilities and its tolerance to reference frame drifts make it an ideal ch...The robustness of reference-frame-independent measurement-device-independent quantum key distribution(RFIMDI-QKD)against detection system vulnerabilities and its tolerance to reference frame drifts make it an ideal choice for hybrid channels.However,the impact of atmospheric turbulence on transmittance fluctuations remains a significant challenge for enhancing the performance of RFI-MDI-QKD.In this paper,we apply prefixed-threshold real-time selection and advantage distillation techniques to RFI-MDI-QKD in a hybrid channels scenario.Then,we analytically derive formulas for secret key rate in hybrid channels.Simulation results show that our modified scheme has apparent advances in both maximum tolerant loss and secure key rate compared to the fiber-only channel.Specifically,the result demonstrates that the maximum transmission distance can be improved by 15 km and 28 km when N=10^(12)and 10^(11).Our work not only provides a more robust key distribution protocol but also establishes a solid theoretical foundation for enhancing the performance of RFI-MDI-QKD in hybrid channels.展开更多
基金supported by the Natural Science Foundation of China (NSFC,No.52372212)。
文摘Photocatalysis uses solar energy to convert nitrogen and water directly into ammonia,helping reduce dependence on fossil fuels and offering a way to integrate the nitrogen cycle into a clean energy network.Ohmic junctions between metals and semiconductors have demonstrated significant advantages in enhancing stability and reducing carrier recombination,but their application in photocatalytic nitrogen fixation is limited due to the difficulty of work function matching and the complexity of fabrication processes.In this study,density functional theory(DFT) calculations were used to confirm the work function matching between Bi and Bi_(2)Ti_(2)O_(7)(BTO),ensuring the formation of an Ohmic junction.A Bi-Bi_(2)Ti_(2)O_(7)(B-BTO) composite was successfully synthesized via a one-step hydrothermal method,using bismuth nitrate and titanium sulfate as precursors.Compared to pure BTO,the B-BTO heterojunction,driven by dual electron injection from both metal Bi and BTO,significantly increased the ammonia synthesis rate to 686.95 μmol g^(-1)h^(-1),making it the most active nitrogen fixation material among similar pyrochlorebased catalysts to date.The differential charge density calculations,photocurrent(i-t) measurements,and photoluminescence(PL) tests further validate the role of Ohmic contacts in enhancing charge transfer and prolonging carrier lifetimes.This research provides valuable insight into the application of Ohmic junctions in photocatalytic nitrogen fixation and contributes to advancements in this field.
基金supported by the National Institutes of Health,USA(DE018549,UL1TR001117,P30AR066527,and AR48182 to WL,AR48182-S1 to WL as co-investigatorF33DE024668 and K12DE022793 to YC)+1 种基金the US Department of Defense(W81XWH-13-1-0299 to WL)the Harrington Discovery Institute,Cleveland OH(to WL)
文摘Nociception is an important physiological process that detects harmful signals and results in pain perception. In this review, we discuss important experimental evidence involving some TRP ion channels as molecular sensors of chemical, thermal, and mechanical noxious stimuli to evoke the pain and itch sensations. Among them are the TRPA1 channel, members of the vanilloid subfamily （TRPV1, TRPV3, and TRPV4）, and finally members of the melastatin group （TRPM2, TRPM3, and TRPMS）. Given that pain and itch are pro-survival, evolutionarily-honed protective mechanisms, care has to be exercised when developing inhibitory/modulatory com- pounds targeting specific pain/itch-TRPs so that physio- logical protective mechanisms are not disabled to a degree that stimulus-mediated injury can occur. Such events have impeded the development of safe and effective TRPV1- modulating compounds and have diverted substantial resources. A beneficial outcome can be readily accom- plished via simple dosing strategies, and also by incorpo- rating medicinal chemistry design features during compound design and synthesis. Beyond clinical use, where compounds that target more than one channel might have a place and possibly have advantageous features, highly specific and high-potency compounds will be helpful in mechanistic discovery at the structure-function level.
文摘During the last decade, transient receptor potential （TRP） channels emerge as key proteins in central mechanisms of the carcinogenesis such as cell proliferation, apoptosis and migration. Initial studies showed that expression profile of some TRP channels, notably TRP melastatin 8 （TRPM8）, TRP vanilloid 6 （TRPV6）,TRP canonical （TRPC6） and TRPV2, is changing during the development and the progression of prostate cancer towards the hormone-refractory stages. The link between the change in expression levels and the functional role of these channels in prostate cancer is step by step being elucidated. These recent advances are here described and discussed.
基金This work was supported by the National Key Basic Research Program of China(973 Program2013CB127600).We are grateful to all staff and students in the Entomology Department,College of Plant Protection,Yunnan Agricultural University,China and the Key Laboratory of Applied Entomology,Northwest A&F University,China for their assistance.
文摘Aphelinus asychis is an important aphid endoparasitoid.Under field and greenhouse conditions,high temperature is one of the factors limiting the application of A asychis for biological pest control.To explore the potential role of transient receptor potential(TRP)channels and heat shock proteins(HSPs)in this process,we identified 11 genes encoding TRP channels and nine genes encoding HSPs.Three proteins(AasyTRPA5,AasyPyrexia,AasyPainless)that belong to transient receptor potential ankyrin(TRPA)subfamily and nine HSPs are involved in the response to high temperature.We also investigated the survival of A asychis and the response of the identified TRP channels and HSPs to high temperature.The results showed that the maximum temperature that allowed A.asychis survival was approximately 41°C;females had higher survival rates than that of the males at 40 and 41°C.Short-term heat-shock resulted in increased expression of Amsysbsp in males,and Aasyhsp40,Aasyhsp68,Aasyhsp70-4,Aasyhsp70-5 and Aasyhsp90 were upregulated and then down regulated,whereas Aasyhsp70-3was upregulated at41°C.Moreover,Aasyhsp40and Aasyhsp90showed higherexpression levels in females,while Aasyshsp and Aasyhsp70-3 presented opposite expression patterns.At temperature above 35°C,expression of AasyPyrexia in females was significant higher than that in males,whereas AasyPainless mnd AasyTRPA5 presented higher expression in males at 40 and 41°C,respectively.Altogether,these results indicate that protect!on against thermal stress in A.asychis is coordinated by TRP channels and HSPs.These findings provide a basis for understanding the potential mechanism of A asychis in response to high temperatures.
基金supported by the National Natural Science Foundation of China,Nos.81901098(to TC),82201668(to HL)Fujian Provincial Health Technology Project,No.2021QNA072(to HL)。
文摘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-channelspecific 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.
基金Supported by the Convergence of Conventional Medicine and Traditional Koran Medicine R&D Program funded by the Ministry of Health&Welfare through the Korean Health Industry Development Institute(Grant No.HI15C0256)
文摘Objective: To examine the effects of Tribulus terrestris L.(T. terrestris) extract on the modulation of calcium channels to evaluate its use in topical agents for treatment of atopic dermatitis.Methods: The 70% methanol extract of T. terrestris was prepared. Human HEK293 T cells with over-expressed calcium release-activated calcium channel protein 1(Orai1),transient receptor potential vanilloid 1, or transient receptor potential vanilloid 3(TRPV3)were treated with T. terrestris extract. Modulation of ion channels was measured using a conventional whole-cell patch-clamp technique.Results: T. terrestris extract(100 mg/m L) significantly inhibited Orai1 activity in Orai1-stromal interaction molecule 1 co-overexpressed HEK293 T cells. In addition, T. terrestris extract significantly increased the TRPV3 activity compared with 2-Aminoethyl diphenylborinate(100 mmol/L), which induces the full activation of TRPV3.Conclusions: Our results suggest that T. terrestris extract may have a therapeutic potential for recovery of abnormal skin barrier pathologies in atopic dermatitis through modulating the activities of calcium ion channels, Orai1 and TRPV3. This is the first study to report the modulatory effect of a medicinal plant on the function of ion channels in skin barrier.
基金supported by DST-FIST(Government of India)(Grant No.SR/FIST/MS-1/2017/13)and Seed Money Project(Grant No.DoRDC/733).
文摘This study numerically examines the heat and mass transfer characteristics of two ternary nanofluids via converging and diverg-ing channels.Furthermore,the study aims to assess two ternary nanofluids combinations to determine which configuration can provide better heat and mass transfer and lower entropy production,while ensuring cost efficiency.This work bridges the gap be-tween academic research and industrial feasibility by incorporating cost analysis,entropy generation,and thermal efficiency.To compare the velocity,temperature,and concentration profiles,we examine two ternary nanofluids,i.e.,TiO_(2)+SiO_(2)+Al_(2)O_(3)/H_(2)O and TiO_(2)+SiO_(2)+Cu/H_(2)O,while considering the shape of nanoparticles.The velocity slip and Soret/Dufour effects are taken into consideration.Furthermore,regression analysis for Nusselt and Sherwood numbers of the model is carried out.The Runge-Kutta fourth-order method with shooting technique is employed to acquire the numerical solution of the governed system of ordinary differential equations.The flow pattern attributes of ternary nanofluids are meticulously examined and simulated with the fluc-tuation of flow-dominating parameters.Additionally,the influence of these parameters is demonstrated in the flow,temperature,and concentration fields.For variation in Eckert and Dufour numbers,TiO_(2)+SiO_(2)+Al_(2)O_(3)/H_(2)O has a higher temperature than TiO_(2)+SiO_(2)+Cu/H_(2)O.The results obtained indicate that the ternary nanofluid TiO_(2)+SiO_(2)+Al_(2)O_(3)/H_(2)O has a higher heat transfer rate,lesser entropy generation,greater mass transfer rate,and lower cost than that of TiO_(2)+SiO_(2)+Cu/H_(2)O ternary nanofluid.
基金National Key R&D Program of China,Grant/Award Number:2023YFB2503900National Natural Science Foundation of China,Grant/Award Number:12172143Shenzhen Science and Technology Program,Grant/Award Numbers:JCYJ20220818100418040,JCYJ20220530160816038。
文摘Constructing silicon(Si)-based composite electrodes that possess high energy density,long cycle life,and fast charging capability simultaneously is critical for the development of high performance lithium-ion batteries for mitigating range anxiety and slow charging issues in new energy vehicles.Herein,a thick silicon/carbon composite electrode with vertically aligned channels in the thickness direction(VC-SC)is constructed by employing a bubble formation method.Both experimental characterizations and theoretical simulations confirm that the obtained vertical channel structure can effectively address the problem of sluggish ion transport caused by high tortuosity in conventional thick electrodes,conspicuously enhance reaction kinetics,reduce polarization and side reactions,mitigate stress,increase the utilization of active materials,and promote cycling stability of the thick electrode.Consequently,when paired with LiNi_(0.6)Co_(0.2)Mn_(0.2)O_(2)(NCM622),the VC-SC||NCM622 pouch type full cell(~6.0 mAh cm^(-2))exhibits significantly improved rate performance and capacity retention compared with the SC||NCM622 full cell with the conventional silicon/carbon composite electrode without channels(SC)as the anode.The assembled VC-SC||NCM622 pouch full cell with a high energy density of 490.3 Wh kg^(-1)also reveals a remarkable fast charging capability at a high current density of 2.0 mA cm^(-2),with a capacity retention of 72.0%after 500 cycles.
基金funded by the National Natural Science Foundation of China(32472553 and 31872039)the Major Special Projects for Green Pest Control,China(110202201017(LS-01))+1 种基金the Shenzhen Science and Technology Program,China(KQTD20180411143628272)the Agricultural Science and Technology Innovation Program of Chinese Academy of Agricultural Sciences。
文摘Transient receptor potential(TRP)channels are a class of ion channel proteins that are closely related to thermosensation in insects.They are involved in detecting the ambient temperature and play vital roles in insect survival and reproduction.In this study,we identifed and cloned two variants of the TRPA subfamily gene in Myzus persicae,MperTRPA1(A)and MperTRPA1(B),and analyzed their tissue expression by real-time quantitative PCR.Subsequently,these two variants of MperTRPA1 were expressed in the Xenopus oocyte system,and their functions were investigated using the two-electrode voltage clamp technique.The role of the MperTRPA1 gene in temperature adaptation of M.persicae was further determined by RNA interference and a behavioral choice assay to evaluate responses to temperature gradients.The results showed that the MperTRPA1 gene is widely expressed in tissues of M.persicae,with MperTRPA1(A)highly expressed in the mouthparts and MperTRPA1(B)mainly expressed in the antennae.The functional characterization results showed that both variants of MperTRPA1 could be activated and were not desensitized when the temperature increased from 20 to 45℃.The current value and thermal sensitivity(coeffcient Q_(10)value)of MperTRPA1(B)were signifcantly higher than those of MperTRPA1(A).When the MperTRPA1 gene was knocked down,the behavioral preference of M.persicae for the optimal temperature was reduced and tended to be at a higher temperature,showing a shift in the temperature adaptation range compared to both the wild type and ds GFP-treated M.persicae.In summary,our results elucidated the molecular mechanism of adaptive temperature perception in M.persicae mediated by the thermal sensor MperTRPA1.
基金Supported by The Creative Research Initiative Center for Bio-Artificial Muscle of the Ministry of Education,Science and Technology (MEST) in Korea
文摘AIM： To investigate the characteristics of slow electrical waves and the presence of transient receptor potential melastatin-type 7 （TRPM7） in the human gastrointestinal （GI） tract. METHODS： Conventional microelectrode techniques were used to record intracellular electrical responses from human GI smooth muscle tissue. Immunohistochemistry was used to identify TRPM7 channels in interstitial cells of Cajat （ICCs）. RESULTS： The human GI tract generated slow electrical waves and had ICCs which functioned as pacemak er cells. Flufenamic acid, a nonselective cation channel blocker, and 2-APB （2-aminoethoxydiphenyl borate） and La3＋, TRPM7 channel blockers, inhibited the slowwaves. Also, TRPM7 channels were expressed in ICCs in human tissue. CONCLUSION： These results suggest that the human GI tract generates slow waves and that TRPM7 channels expressed in the ICCs may be involved in the gen- eration of the slow waves.
基金Supported by The National Natural Science Foundation of China,No.30270532 and No.30670774Tsinghua-Yue-Yuen Medical Science Foundation,No.20240000531 and No.20240000547
文摘AIM： To explore the possibility of using the Noninvasive Micro-test Technique （NMT） to investigate the role of Transient Receptor Potential Canonical 1 （TRPC1） in regulating Ca^2＋ influxes in HL-7702 cells, a normal human liver cell line.METHODS： Net Ca^2＋ fluxes were measured with NMT, a technology that can obtain dynamic information of specific/selective ionic/molecular activities on material surfaces, non-invasively. The expression levels of TRPCl were increased by liposomal transfection, whose effectiveness was evaluated by Western-blotting and single cell reverse transcription-polymerase chain reaction.RESULTS： Ca^2＋ influxes could be elicited by adding 1 mmol/L CaCl2 to the test solution of HL-7702 cells. They were enhanced by addition of 20 μmol/L noradrenalin and inhibited by 100 μmol/L LaCl3 （a non-selective Ca^2＋ channel blocker）; 5 μmol/L nifedipine did not induce any change. Overexpression of TRPCl caused increased Ca^2＋ influx. Five micromoles per liter nifedipine did not inhibit this elevation, whereas 100 μmol/L LaCI3 did.CONCLUSION： In HL-7702 cells, there is a type of TRPCl-dependent Ca^2＋ channel, which could be detected v/a NMT and inhibited by La^3＋.
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.
基金supported by the National Key R&D Program of China under Grant No.2023YFB2904802National Natural Science Foundation of China under Grant Nos.62301022,62221001,62431003,and 62101507+1 种基金Young Elite Scientists Sponsorship Program by CAST under Grant No.2022QNRC001Program for Science&Technology R&D Plan Joint Fund of Henan Province under Grant No.225200810112。
文摘Reliable channel data helps characterize the limitations and performance boundaries of communication technologies accurately.However,channel measurement is highly costly and time-consuming,and taking actual measurement as the only channel data source may reduce efficiency because of the constraints of high testing difficulty and limited data volume.Although existing standard channel models can generate channel data,their authenticity and diversity cannot be guaranteed.To address this,we use deep learning methods to learn the attributes of limited measured data and propose a generative model based on generative adversarial networks to rapidly synthesize data.A software simulation platform is also established to verify that the proposed model can generate data that are statistically similar to the measured data while maintaining necessary randomness.The proposed algorithm and platform can be applied to channel data enhancement and serve channel modeling and algorithm evaluation applications with urgent needs for data.
基金funded by the Key Project from the Hebei Provincial Department of Science and Technology,China(Grant No.:21372601D)the Foundation Postdoctoral Mobile Station of Basic Medical Sciences,Hebei Medical University,China(Grant No.:20123120019)+4 种基金the Natural Science Foundation of Hebei Province,China(Grant No.:H2021206352)the Science and Technology Research Project of Colleges and Universities in Hebei Province,China(Grant No.:QN2023197)Hebei Medical University,Science and Technology,China(Grant No.:CYQD2023014)Hebei Provincial Department of Human Resources and Social Security,China(Grant No.:B2023003034)the Consultative Foundation from Hebei Province,China(Grant No.:2020TXZH01).
文摘This research study focuses on addressing the limitations of current neuropathic pain(NP)treatments by developing a novel dual-target modulator,E0199,targeting both Na_(V)1.7,Na_(V)1.8,and Na_(V)1.9 and K_(V)7 channels,a crucial regulator in controlling NP symptoms.The objective of the study was to synthesize a compound capable of modulating these channels to alleviate NP.Through an experimental design involving both in vitro and in vivo methods,E0199 was tested for its efficacy on ion channels and its therapeutic potential in a chronic constriction injury(CCI)mouse model.The results demonstrated that E0199 significantly inhibited Na_(V)1.7,Na_(V)1.8,and Na_(V)1.9 channels with a particularly low half maximal inhibitory concentration(IC50)for Na_(V)1.9 by promoting sodium channel inactivation,and also effectively increased K_(V)7.2/7.3,K_(V)7.2,and K_(V)7.5 channels,excluding K_(V)7.1 by promoting potassium channel activation.This dual action significantly reduced the excitability of dorsal root ganglion neurons and alleviated pain hypersensitivity in mice at low doses,indicating a potent analgesic effect without affecting heart and skeletal muscle ion channels critically.The safety of E0199 was supported by neurobehavioral evaluations.Conclusively,E0199 represents a ground-breaking approach in NP treatment,showcasing the potential of dual-target small-molecule compounds in providing a more effective and safe therapeutic option for NP.This study introduces a promising direction for the future development of NP therapeutics.
基金support from the Chinese Academy of Sciences and University of Science and Technology of China,National Key Research and Development Program of China(No.2021YFA1500402)National Natural Science Foundation of China(Nos.21571167,51502282 and 22075266)Fundamental Research Funds for the Central Universities(Nos.WK2060190053 and WK2060190100)。
文摘Efficient selective adsorption and separation using porous frameworks are critical in many industrial processes,where adsorption energy and dynamic diffusion rate are predominant factors governing selectivity.They are highly susceptible to framework charge,which plays a significant role in selective adsorption.Currently,ionic porous frameworks can be divided into two types.One of them is composed of a charged backbone and counter ions.The framework with zwitterionic channels is another type.It is composed of regular and alternating arrangements of cationic and anionic building units.Herein,we report a hydrogen-bonded ionic framework(HIF)of{(CN_(3)H_(6))_(2)[Ti(μ_(2)-O)(SO_(4))_(2)]}_nwith 1D channel exhibits unique adsorption selectivity for Ar against N_(2)and CO_(2).Density functional theory(DFT)results suggest that CO_(2)cannot be adsorbed by HIF at the experimental temperature due to a positive adsorption free energy.In addition,due to a relatively large diffusion barrier at 77 K,N_(2)molecules hardly diffuse in HIF channels,while Ar has a negligible diffusion barrier.The unique net positively-charged space in the channel is the key to the unusual phenomena,based on DFT simulations and structural analysis.The findings in this work proposes the new adsorption mechanism and provides unique perspective for special separation applications,such as isotope and noble gasses separations.
基金The National Natural Science Foundation of China(Grant No.32000674).
文摘Patch-clamp technique serve as a powerful tool for precisely measuring and characterizing ion channel currents,offering critical molecular-level insights essential for drug screening and optimization.By enabling a deeper understanding of ion channel behavior,these techniques significantly accelerate the process of drug discovery and development.In recent years,automated patch-clamp technique has undergone substantial advancements,surpassing traditional manual methods with its high throughput,improved data consistency,and automation.However,fully harnessing these advantages requires meticulous optimization of experimental conditions tailored to specific targets.Without such refinement,the high cost of consumables and operational expenses could severely hinder the widespread adoption of this technique.This study focused on the TRPV1 channel,detailing the establishment of an automated patch-clamp detection system for TRPV1 currents,optimization of experimental parameters,and a comparative evaluation of the results against manual patch-clamp techniques.
基金supported by the National Natural Science Foundation of China(Grant Nos.61505261,62101597,61605248,and 61675235)the National Key Research and Development Program of China(Grant No.2020YFA0309702)the Natural Science Foundation of Henan Province(Grant Nos.202300410534 and 202300410534)。
文摘The robustness of reference-frame-independent measurement-device-independent quantum key distribution(RFIMDI-QKD)against detection system vulnerabilities and its tolerance to reference frame drifts make it an ideal choice for hybrid channels.However,the impact of atmospheric turbulence on transmittance fluctuations remains a significant challenge for enhancing the performance of RFI-MDI-QKD.In this paper,we apply prefixed-threshold real-time selection and advantage distillation techniques to RFI-MDI-QKD in a hybrid channels scenario.Then,we analytically derive formulas for secret key rate in hybrid channels.Simulation results show that our modified scheme has apparent advances in both maximum tolerant loss and secure key rate compared to the fiber-only channel.Specifically,the result demonstrates that the maximum transmission distance can be improved by 15 km and 28 km when N=10^(12)and 10^(11).Our work not only provides a more robust key distribution protocol but also establishes a solid theoretical foundation for enhancing the performance of RFI-MDI-QKD in hybrid channels.
