Ischemia–reperfusion injury is a common pathophysiological mechanism in retinal degeneration.PANoptosis is a newly defined integral form of regulated cell death that combines the key features of pyroptosis,apoptosis,...Ischemia–reperfusion injury is a common pathophysiological mechanism in retinal degeneration.PANoptosis is a newly defined integral form of regulated cell death that combines the key features of pyroptosis,apoptosis,and necroptosis.Oligomerization of mitochondrial voltage-dependent anion channel 1 is an important pathological event in regulating cell death in retinal ischemia–reperfusion injury.However,its role in PANoptosis remains largely unknown.In this study,we demonstrated that voltage-dependent anion channel 1 oligomerization-mediated mitochondrial dysfunction was associated with PANoptosis in retinal ischemia–reperfusion injury.Inhibition of voltage-dependent anion channel 1 oligomerization suppressed mitochondrial dysfunction and PANoptosis in retinal cells subjected to ischemia–reperfusion injury.Mechanistically,mitochondria-derived reactive oxygen species played a central role in the voltagedependent anion channel 1-mediated regulation of PANoptosis by promoting PANoptosome assembly.Moreover,inhibiting voltage-dependent anion channel 1 oligomerization protected against PANoptosis in the retinas of rats subjected to ischemia–reperfusion injury.Overall,our findings reveal the critical role of voltage-dependent anion channel 1 oligomerization in regulating PANoptosis in retinal ischemia–reperfusion injury,highlighting voltage-dependent anion channel 1 as a promising therapeutic target.展开更多
Voltage-dependent anion channel 1（VDAC1） is thought to contribute to the progression of tumor development. However, whether VDAC1 contributes to bone cancer pain remains unknown. In this study, we found that the exp...Voltage-dependent anion channel 1（VDAC1） is thought to contribute to the progression of tumor development. However, whether VDAC1 contributes to bone cancer pain remains unknown. In this study, we found that the expression of VDAC1 was upregulated in the L2–5 segments of the spinal dorsal horn at 2 and 3 weeks after injection of tumor cells into the tibial cavity. Intrathecal injection of a VDAC1 inhibitor significantly reversed the pain hypersensitivity and reduced the over-expression of Toll-like receptor 4（TLR4）. Intrathecal injection of minocycline, an inhibitor of microglia, also attenuated the pain hypersensitivity of rat models of bone cancer pain.These results suggest that VDAC1 plays a significant role in the development of complicated cancer pain, possibly by regulating the expression of TLR4.展开更多
The roles of voltage-dependent K^＋ channels during activation and damage in alveolar macrophages （AMs） exposed to different silica particles were examined. Rat AMs were collected by means of bronchoalveolar lavage,...The roles of voltage-dependent K^＋ channels during activation and damage in alveolar macrophages （AMs） exposed to different silica particles were examined. Rat AMs were collected by means of bronchoalveolar lavage, and were adjusted to 5× 10^5/mL. After AMs were exposed to different concentrations （0, 25, 50, 100, 200 μg/mL） of quartz particles and 100 μg/mL amorphous silica particles for 24 h, the voltage-depended K^＋ current in AMs was measured by using patch clamp technique. Meanwhile the leakage of lactate dehydrogenase （LDH） and the viability of AMs were detected respectively. Patch clamp studies demonstrated that AMs possessed outward delayed and inward rectifying K^＋ current. Exposure to quartz particles increased the outward delayed K^＋ current but it had no effect on inward rectifier K^＋ current in AMs. Neither of the two K^＋ channels in AMs was affected by amorphous silica particles. Cytotoxicity test showed that both silica particles could damage AM membrane and result in significant leakage of LDH （P〈0.05）. MTT studies, however, showed that only quartz particles reduced viability of AMs （P〈0.05）. It is concluded that quartz parti- cles can activate the outward delayed K^＋ channel in AMs, which may act as an activating signal in AMs to initiate an inflammatory response during damage and necrosis in AMs induced by exposure to quartz particle. K^＋ channels do not contribute to the membrane damage of AMs.展开更多
Recently, the efficiency of CdTe thin film solar cell has been improved by using new type of window layer Mg_(x)Zn_(1-x)O(MZO). However, it is hard to achieve such a high efficiency as expected. In this report a compa...Recently, the efficiency of CdTe thin film solar cell has been improved by using new type of window layer Mg_(x)Zn_(1-x)O(MZO). However, it is hard to achieve such a high efficiency as expected. In this report a comparative study is carried out between the MZO/CdTe and CdS/CdTe solar cells to investigate the factors affecting the device performance of MZO/CdTe solar cells. The efficiency loss quantified by voltage-dependent photocurrent collection efficiency(ηC(V′)) is 3.89% for MZO/CdTe and 1.53% for CdS/CdTe solar cells. The higher efficiency loss for the MZO/CdTe solar cell is induced by more severe carrier recombination at the MZO/CdTe p-n junction interface and in CdTe bulk region than that for the CdS/CdTe solar cell. Activation energy(Ea) of the reverse saturation current of the MZO/CdTe and CdS/CdTe solar cells are found to be 1.08 e V and 1.36 e V, respectively. These values indicate that for the CdS/CdTe solar cell the carrier recombination is dominated by bulk Shockley-Read-Hall(SRH) recombination and for the MZO/CdTe solar cell the carrier recombination is dominated by the p-n junction interface recombination. It is found that the tunneling-enhanced interface recombination is also involved in carrier recombination in the MZO/CdTe solar cell. This work demonstrates the poor device performance of the MZO/CdTe solar cell is induced by more severe interface and bulk recombination than that of the CdS/CdTe solar cell.展开更多
The types of the voltage-dependent calcium channels （VDCCs） in human ejaculatory sperm and the effects of calcium channel blocker （CCB） on human sperm motility parameters in vitro were investigated. The human sper...The types of the voltage-dependent calcium channels （VDCCs） in human ejaculatory sperm and the effects of calcium channel blocker （CCB） on human sperm motility parameters in vitro were investigated. The human sperm motility parameters in vitro in response to the pharmacological agents nifedipine （NIF, inhibitor of L-type VDCC） and ω-conotoxin （GVIA, inhibitor of N-type VDCC） were compared and analyzed statistically. The results showed that NIF （1, 5, 10 μmol/L） could not only significantly affect human sperm＇s shape but also spermatozoa motility after incubated at least 10 rain in vitro （P〈0.001）. GVIA （0.1, 0.5 and 1 μmol/L） could just only significantly affect human sperm＇s progressive motility （a %＋b %） after incubated for 20 min in vitro （P〈0.01）, but they both could not significantly affect spermic abnormality rate. It is suggested that L-type VDCC, non L-type VDCCs and isoform of L-type VDCC exist in the cell membrane of human sperm solely or together, and they participate in the spermic physiological processes especially the spermic motility.展开更多
The effect of thyrosine kinase, calmodulin and voltage-dependent Ca 2+ channel on the proliferation of hepatoma cells induced by EGF was studied. Hepatoma cell line SMMC7721 was cultured in RPMI1640 serum-free me...The effect of thyrosine kinase, calmodulin and voltage-dependent Ca 2+ channel on the proliferation of hepatoma cells induced by EGF was studied. Hepatoma cell line SMMC7721 was cultured in RPMI1640 serum-free medium. DNA synthesis rate of hepatoma cells was measured by 3H-TdR incorporation. 10 -9 mol/L EGF could significantly stimulate the proliferation of hepatoma cells (P<0.05), and this effect might be significantly inhibited by tyrosine kinase inhibitor (P<0.001). Calmodulin inhibitor W-7 had no effect on the basic phase of cultured hepatoma cells (P> 0.05), but it had very significantly inhibitory effect on the proliferation of hepatoma cells induced by EGF (P<0.001). Voltage-dependent Ca 2+ channel inhibitor Varapamil had no inhibition on the proliferation of hepatoma cells induced by EGF (P>0.05). It had no effect on the basic phase of cultured hepatoma cells (P>0.05). It is suggested that tyrosine kinase and Ca 2+-calmodulin-dependent pathway may play a critical role on the proliferation of heptoma cells induced by EGF, and voltage-dependent Ca 2+ channel is independent of the effect of EGF.展开更多
OBJECTIVE Stroke has become the top ten leading cause of death in China.Isch⁃emic stroke accounts for 85%of stroke cases,and insufficiency of cerebral blood supply caused by atherosclerosis is one of the important cau...OBJECTIVE Stroke has become the top ten leading cause of death in China.Isch⁃emic stroke accounts for 85%of stroke cases,and insufficiency of cerebral blood supply caused by atherosclerosis is one of the important causes of ischemic stroke.Therefore,it is of posi⁃tive significance to study the molecular mecha⁃nism of stroke injury caused by hypoperfusion in the search for drug targets.Voltage-dependent potassium channels are a family of potassium channels widely expressed in the central ner⁃vous system.However,their roles in neurogene⁃sis after stroke insults have not been clearly illus⁃trated.The purpose of this experiment is to explore the expression changes of different sub⁃families of voltage-dependent potassium chan⁃nels after the occurrence of ischemic stroke and their influence on neuroregeneration,to study the molecular mechanism of stroke injury caused by hypoperfusion,and to find potential targets for drug therapy of ischemic stroke.METHODS C57BL/6 mice aged 7-8 weeks and C17.2 cells were used in vivo and in vitro in the experiment.The mice in the experimental group were suf⁃fered from bilateral common carotid artery occlu⁃sion(BCCO)for 1 h and reperfusion for 7 d.In the control group,bilateral carotid artery was dis⁃sected without occlusion.Behavioral assay of suspension test were performed to assess the motor deficits of the mice.In this assay,the time of the first drop(latency),the number of drops within one minute(frequency),and the final scores were recorded as the results of athletic ability.A lower score indicated more severe motor damage of the mice.TTC staining was used to observe the cerebral infarction areas caused by ligation of bilateral common carotid arteries.After seven days,mice were sacrificed and brain tissue protein samples were collected for real-time quantitative PCR(RT-PCR)and Western blotting test to detect the changes of potassium channel subfamily expression levels in different brain regions.Neuronal injuries in all brain regions were detected using Nissl staining methods 7 d following model establishment.To detect the effects and the underlying mechanism of the related potassium channel on neurogene⁃sis,recombinant plasmids of the potassium chan⁃nels were transfected in cultured C17.2 neural stem cells.Afterwards,oxygen glucose depriva⁃tion experiments were performed.RESULTS Behavioral tests showed that BCCO can cause impaired motor performance.TTC staining showed that cerebral infarction existed in the stri⁃atum region,and the motor function decline caused by the injury in this region was consistent with the behavioral experiment results which veri⁃fied the effectiveness of our surgical operation.Nissl staining revealed a large amount of neuronal cell necrosis in the cortex and striatum regions,and dense neuronal cells in the lateral ventricular limbic region,suggesting that neurogenesis may have occurred in this region.The results of real-time quantitative RT-PCR showed that among the detected potassium channels distributed in the measured nervous system,the expression of voltage-dependent potassium channel Kv4.2 decreased significantly in all brain regions after stroke,suggesting that it may be involved in the pathological process of stroke.Immunohisto⁃chemical staining showed that there was neuro⁃genesis in the subgranular zone(SGZ)and sub⁃ventricular zone(SVZ)of the mice,and Kv4.2 expression was significantly changed in the regions,suggesting that it may be involved in the regulation of neuro regeneration after stroke.The transfected Kv4.2 plasmid enhanced the dif⁃ferentiation of the C17.2 neural stem cells to neu⁃rons and astrocytes under normoxia and the oxy⁃gen-glucose deprivation,suggesting that Kv4.2 may induce the differentiation of neural stem cells after stroke.Kv4.2 could induce the neural stem cells to differentiate into neurons in vitro and in vivo,and Western blotting assay showed that Kv4.2 could up-regulate the expression level of ERK1/2,p-ERK1/2,p-STAT3,NGF,p-TtkA,and BDNF.Moreover,the calcium ions and CAMKⅡwas also increased by Kv4.2 in vitro.CONCLUSION BCCO insults can induce the expressions of the potassium channels in the brains,among which the expression of Kv4.2 is down-regulated in the cerebral cortex,hippocam⁃pus and striatum.In vitro experiments confirmed that Kv4.2 can induce the differentiation of C17.2 neural stem cells into neurons and astrocytes under the condition of normoxia and oxygen-glucose deprivation.We concluded that Kv4.2 possibly promoted neurogenesis through ERK1/2/STAT3,NGF/TrkA,and Ca2+/CAMKⅡsignal pathways after stroke.Regulating the physiologi⁃cal functions of Kv4.2 channel might contribute to the rehabilitation of neuronal damage after stroke.展开更多
Increasing distributed generators(DGs)and flexible loads(FLs)enable distribution systems to provide both active and reactive power reserves(P-Q reserves)in supporting the frequency and voltage regulations of transmiss...Increasing distributed generators(DGs)and flexible loads(FLs)enable distribution systems to provide both active and reactive power reserves(P-Q reserves)in supporting the frequency and voltage regulations of transmission systems.However,such requirements at the interface between the transmission system operator(TSO)and distribution system operator(DSO)affect the distribution system operation security,considering the uncertainties of DGs and FLs.To exploit the reserve potential of distribution systems,this paper investigates the voltagedependent P-Q reserve capacity(V-PQRC)of such types of distribution systems.V-PQRC reflects the feasible space of PQ reserves that the DSO can provide to the TSO taking the voltage deviation limit at TSO-DSO interface into consideration,while ensuring the distribution system operation security under uncertainties of DGs and FLs.An evaluation method for VPQRC at the TSO-DSO interface is proposed.To improve the robust performance of the evaluation method,the DG uncertainty is captured by a generalized ambiguity set and the FL uncertainty is addressed by designing a constrained sliding mode controller(CSMC).Three objectives are considered in the evaluation,i.e.,P reserve capacity,Q reserve capacity,and the voltage deviation limit at the TSO-DSO interface.Then,a multiobjective optimization model integrating the generalized robust chance-constrained optimization and CSMC(GRCC-CSMC)is established for V-PQRC evaluation to obtain the Pareto optimal reserve schemes.Finally,a non-approximated selecting(NAS)method is proposed to build up a simplified V-PQRC linear model,which can be convenient to apply in the transmissiondistribution system coordination.Simulation results reveal that the V-PQRC evaluation method can achieve a good performance of accuracy and robustness against uncertainties.展开更多
The voltage-dependent anion channel （VDAC） plays an essential role in the permeability of mltochondrial membrane. In the present study, we isolated a novel VDAC gene （brvdac） based on the assembly of expressed seq...The voltage-dependent anion channel （VDAC） plays an essential role in the permeability of mltochondrial membrane. In the present study, we isolated a novel VDAC gene （brvdac） based on the assembly of expressed sequence tag sequences from Brassica rapa L. and explored its differential expression patterns In growth, tissues, abiotlc stress, and stress recovery. Results of a tissue-specific expression study in young seedlings Indicated that, of all tissues tested, brvdac expression was the highest in the leaves. Under cold, drought, and salt stresses, brvdac expression showed a transient Increase, and then returned to normal levels when the stress was removed. When plants were exposed to heat shock, there was no Increase in brvdac expression, whereas during recovery a quick and considerable increase in expression was observed. These observations indicate that dissimilar modulations of brvdactranscription may occur when plant cells encounter heat shock and the other three types of stress. In addition, phylogenetic analysis Implied that an earlier duplication of vdac probably occurred before the divergence between monocotyledons and dicotyledons.展开更多
In this study,we present an in-depth exploration of charge transport phenomena and variable photo-switching characteristics in a novel double-perovskite-based three-terminal device.The Cs_(2)AgBiBr_(6) thin film(TF)wa...In this study,we present an in-depth exploration of charge transport phenomena and variable photo-switching characteristics in a novel double-perovskite-based three-terminal device.The Cs_(2)AgBiBr_(6) thin film(TF)was synthesized through a three-step thermal evaporation process followed by precise open-air annealing,ensuring superior film quality as confirmed by structural and morphological characterizations.Photoluminescence spectroscopy revealed distinct emissions at 2.28 and 2.07 eV,indicative of both direct and indirect electronic transitions.Our device exhibited space-charge limited current(SCLC)behaviour beyond 0.35 V,aligning with the relationship Current(I)∝Voltage(V)^(m),where the exponent m transitioned from≤1 to>1.Detailed analysis of Schottky parameters within the trap-filled limit(TFL)regime was conducted,accounting for variations in temperature and optical power.Significantly,the self-powered photodetector demonstrated outstanding performance under illumination.The sensitivity of the device was finely tunable via the applied bias voltages at the third terminal.Notably,an optimal bias voltage of±100μV yielded maximum responsivity(R)of 0.48 A/W and an impressive detectivity(D*)of 1.07×10^(9) Jones,highlighting the potential of this double-perovskite-based device for advanced optoelectronic applications.展开更多
The growth plate(GP)is a crucial tissue involved in skeleton development via endochondral ossification(EO).The bone organoid is a potential research model capable of simulating the physiological function,spatial struc...The growth plate(GP)is a crucial tissue involved in skeleton development via endochondral ossification(EO).The bone organoid is a potential research model capable of simulating the physiological function,spatial structure,and intercellular communication of native GPs.However,mimicking the EO process remains a key challenge for bone organoid research.To simulate this orderly mineralization process,we designed an in vitro sh Ca_(v)3.3 ATDC5-loaded gelatin methacryloyl(Gel MA)hydrogel model and evaluated its bioprintability for future organoid construction.In this paper,we report the first demonstration that the T-type voltage-dependent calcium channel(T-VDCC)subtype Ca_(v)3.3 is dominantly expressed in chondrocytes and is negatively correlated with the hypertrophic differentiation of chondrocytes during the EO process.Furthermore,Ca_(v)3.3 knockdown chondrocytes loaded with the Gel MA hydrogel successfully captured the EO process and provide a bioink capable of constructing layered and orderly mineralized GP organoids in the future.The results of this study could therefore provide a potential target for regulating the EO process and a novel strategy for simulating it in bone organoids.展开更多
AIM:To investigate the effect of hydrogen sulfide(H2S)on smooth muscle motility in the gastric fundus.METHODS:The expression of cystathionineβ-synthase(CBS)and cystathionineγ-lyase(CSE)in cultured smooth muscle cell...AIM:To investigate the effect of hydrogen sulfide(H2S)on smooth muscle motility in the gastric fundus.METHODS:The expression of cystathionineβ-synthase(CBS)and cystathionineγ-lyase(CSE)in cultured smooth muscle cells from the gastric fundus was examined by the immunocytochemistry technique.The tension of the gastric fundus smooth muscle was recorded by an isometric force transducer under the condition of isometric contraction with each end of the smooth muscle strip tied with a silk thread.Intracellular recording was used to identify whether hydrogen sulfide affects the resting membrane potential of the gastric fundus in vitro.Cells were freshly separated from the gastric fundus of mice using a variety of enzyme digestion methods and whole-cell patch-clamp technique was used to find the effects of hydrogen sulfide on voltage-dependent potassium channel and calcium channel.Calcium imaging with fura-3AM loading was used to investigate the mechanism by which hydrogen sulfide regulates gastric fundus motility in cultured smooth muscle cells.RESULTS:We found that both CBS and CSE were expressed in the cul tured smooth muscle cel ls from the gastric fundus and that H2S increased the smooth muscle tension of the gastric fundus in mice at low concentrations.In addition,nicardipine and aminooxyacetic acid(AOAA),a CBS inhibitor,reduced the tension,whereas Nω-nitro-L-arginine methyl ester,a nonspecific nitric oxide synthase,increased the tension.The AOAA-induced relaxation was significantly recovered by H2S,and the Na HS-induced increase in tonic contraction was blocked by 5 mmol/L4-aminopyridine and 1μmol/L nicardipine.Na HS significantly depolarized the membrane potential and inhibited the voltage-dependent potassium currents.Moreover,Na HS increased L-type Ca2+currents and caused an elevation in intracellular calcium([Ca2+]i).CONCLUSION:These findings suggest that H2S may be an excitatory modulator in the gastric fundus in mice.The excitatory effect is mediated by voltagedependent potassium and L-type calcium channels.展开更多
Wuzi-Yanzong-Wan(WZYZW)is a classic prescription for male infertility.Our previous investigation has demon-strated that it can inhibit sperm apoplosis via afecting mitochondria,but the underlying mechanisms are unclea...Wuzi-Yanzong-Wan(WZYZW)is a classic prescription for male infertility.Our previous investigation has demon-strated that it can inhibit sperm apoplosis via afecting mitochondria,but the underlying mechanisms are unclear.The purpose of the present study was to explore the actions of WZYZW on mitochondrial permeability transition pore(mPTP)in mouse spermatocyte cell line(GC-2 cells)opened by atractyloside(ATR).At first,WZYZW-mediated serum was prepared from rats following oral adminis-tration of WZYZW for 7 days.GC-2 cells were divided into control group,model group,positive group,as well as 5%,10%,15%WZYZW-medicated serum group.Cyclosporine A(CsA)was used as a positive control.50 μmol·L^(-1) ATR was added afer drugs in-cubation.Cell viability was asessed using CCK-8.Apoptosis was detected using flow cytometry and TUNEL method.The opening of mPTP and mitochondrial membrane potential(MMP)were dected by Calcein AM and JC-1 fuorescent probe respectively.The mRNA and protein levels of voltage-dependent anion channel I(VDACI),cyelophilin D(CypD),adenine nucleide translocator(ANT),cytochrome C(Cyt C),caspase 3,9 were dected by RT-PCR(real time quantity PCR)and Western blotting respectively.The results demonstrated that mPTP of GC-2 cells was opened alpter 24 hours of ATR treatment,resulting in decreased MMP and increased apoptosis.Pre-protection with WZYZ-medicated serum and CsA inhibited the opening of mPTP of GC-2 cells induced by ATR associ ated with increased MMP and decreased apoptosis.Morcover,the results of RT-qPCR and WB suggested that WZYZW-medicated serum could significantly reduce the mRNA and protein levels of VDACI and CypD,Caspase-3,9 and CylC,as well as a increased ra-tio of BclBax.However,ANT was not significantly ffected.Therefore,these findings indicated that WZYZW inhibited mitochondri-al mediated apoptosis by atenuating the opening of mPTP in GC-2 cells.WZYZW-medicated serum inhibited the expressions of VDACI and CypD and increased the expression of Bcl-2,which afected the opening of mPTP and exerted protective and anti-apop-totic ffects on GC-2 cell induced by ATR.展开更多
Voltage-gated potassium channels comprise 12 subtypes （Kv1-Kv12）. Kv2.1, which is expressed in most mammalian central neurons, provides the majority of delayed-rectifier K＋ current in cortical and hippocampal pyram...Voltage-gated potassium channels comprise 12 subtypes （Kv1-Kv12）. Kv2.1, which is expressed in most mammalian central neurons, provides the majority of delayed-rectifier K＋ current in cortical and hippocampal pyramidal neurons, and plays an especially prominent role in repolarizing membrane potential, as well as in facilitation of exocytosis. Kv2.1-encoded K＋ efflux is essential for neuronal apoptosis programming. The human form of the Kv2.1 potassium channel contains large intracellular regions. The cytoplasmic C-terminal plays a key role in modulating Kv2.1 gating. The present manuscript summarized Kv2.1 structure and modulation in neurons and analyzed the roles of the cytoplasmic C-terminal.展开更多
AIM： To induce the pancreatic duct cells into endocrine cells with a new natural protocol for electrophysiological study. METHODS： The pancreatic duct cells of neonatal rats were isolated, cultured and induced into ...AIM： To induce the pancreatic duct cells into endocrine cells with a new natural protocol for electrophysiological study. METHODS： The pancreatic duct cells of neonatal rats were isolated, cultured and induced into endocrine ceils with 15% fetal bovine serum for a period of 20 d. During this period, insulin secretion, MTT value, and morphological change of neonatal and adult pancreatic islet cells were comparatively investigated. Pancreatic β-cells were identified by morphological and electrophysiological characteristics, while ATP sensitive potassium channels （KATP）, voltage-dependent potassium channels （Kv）, and voltage-dependent calcium channels （KcA） in β-cells were identified by patch clamp technique. RESULTS： After incubation with fetal bovine serum, the neonatal duct cells budded out, changed from duct-like cells into islet clusters. In the first 4 d, MTT value and insulin secretion increased slowly （MTT value from 0.024 ±0.003 to 3.028±0.003, insulin secretion from 2.6±0.6 to 3.1±0.8 mIU/L）. Then MTT value and insulin secretion increased quickly from d 5 to d 10 （MTT value from 0.028 ±0.003 to 0.052±0.008, insulin secretion from 3.1±0.8 to 18.3±2.6 mIU/L）, then reached high plateau （MTT value 〉0.052±0.008, insulin secretion 〉18.3±2.6 mIU/L）. In contrast, for the isolated adult pancreatic islet cells, both insulin release and MTT value were stable in the first 4 d （MTT value from 0.029±0.01 to 0.031±0.011, insulin secretion from 13.9±3.1 to 14.3±3.3 mIU/L）, but afterwards they reduced gradually （MTT value 〈0.031 ±0.011, insulin secretion 〈8.2±1.5 mIU/L）, and the pancreatic islet cells became dispersed, broken or atrophied correspondingly. The differentiated neonatal cells were identified as pancreatic islet cells by dithizone staining method, and pancreatic β-cells were further identified by both morphological features and electrophysiological characteristics, i.e. the existence of recording currents from KATP, Kv, and KCA. CONCLUSION： Islet cells differentiated from neonatal pancreatic duct cells with the new natural protocol are more advantageous in performing patch clamp study over the isolated adult pancreatic islet cells.展开更多
Activation of cannabinoid receptor type 1 on presynaptic neurons is postulated to suppress neu- ~ ~ ~ 2＋ ~ ~ 2＋ rotransmlsslon by decreasing Ca reflux through high voltage-gated Ca channels. However, recent studies...Activation of cannabinoid receptor type 1 on presynaptic neurons is postulated to suppress neu- ~ ~ ~ 2＋ ~ ~ 2＋ rotransmlsslon by decreasing Ca reflux through high voltage-gated Ca channels. However, recent studies suggest that cannabinoids which activate cannabinoid receptor type 1 can increase neurotransmitter release by enhancing Ca2＋ influx in vitro. The aim of the present study was to investigate the modulation of intracellular Ca2＋ concentration by the cannabinoid receptor type 1 agonist anandamide, and its underlying mechanisms. Using whole cell voltage-damp and calcium imaging in cultured trigeminal ganglion neurons, we found that anandamide directly caused Ca2＋ influx in a dose-dependent manner, which then triggered an increase of intracellular Ca2＋ concentration. The cyclic adenosine and guanosine monophosphate-dependent protein kinase systems, but not the protein kinase C system, were involved in the increased intracellular Ca2＋concentration by anandamide. This result showed that anandamide increased intracellu- lar Ca2＋ concentration and inhibited high voltage-gated Ca2＋ channels through different signal transduction pathways.展开更多
Parkinson's disease(PD)is a neurodegenerative disorder due to gradual loss of dopaminergic neurons in the substantia nigra in the midbrain,however the pathogenesis is unclear.There is a correlation between the exc...Parkinson's disease(PD)is a neurodegenerative disorder due to gradual loss of dopaminergic neurons in the substantia nigra in the midbrain,however the pathogenesis is unclear.There is a correlation between the excitability of striatal neurons and PD.Ion channels are important to maintain membrane potential and regulate excitability of neurons,while ionic mechanisms for modulation of neurons excitability are not fully understood.This article reviews the relationship between ion channels and excitability of striatal neurons in PD and ion channel changes in the pathogenesis of PD.In order to find new targets to treatment PD by intervening ion channels.展开更多
Croton zambezicus Muell.Arg.(Euphorbiaceae)(Syn.C.amabilis Muell.Arg.,C.gratissimus Burch.)is a shrub or small tree reaching 10 m in height.The leaf decoction is used in Benin as anti-hypertensive,anti-microbial(urina...Croton zambezicus Muell.Arg.(Euphorbiaceae)(Syn.C.amabilis Muell.Arg.,C.gratissimus Burch.)is a shrub or small tree reaching 10 m in height.The leaf decoction is used in Benin as anti-hypertensive,anti-microbial(urinary infections)and to treat fever associated with malaria.We analysed the in vitro and in vivo vasorelaxant activity展开更多
Arabidopsis sepals coordinate flower opening in the morning as ambient temperature rises;however,the underlying molecular mechanisms are poorly understood. Mutation of one heat shock proteinencoding gene, HSP70-16, im...Arabidopsis sepals coordinate flower opening in the morning as ambient temperature rises;however,the underlying molecular mechanisms are poorly understood. Mutation of one heat shock proteinencoding gene, HSP70-16, impaired sepal heat stress responses (HSR), disrupting lipid metabolism,especially sepal cuticular lipids, leading to abnormal flower opening. To further explore, to what extent,lipids play roles in this process, in this study, we compared lipidomic changes in sepals of hsp70-16 andvdac3 (mutant of a voltage-dependent anion channel, VDAC3, an HSP70-16 interactor) grown underboth normal (22 C) and mild heat stress (27 C, mild HS) temperatures. Under normal temperature,neither hsp70-16 nor vdac3 sepals showed significant changes in total lipids;however, vdac3 but nothsp70-16 sepals exhibited significant reductions in the ratios of all detected 11 lipid classes, except themonogalactosyldiacylglycerols (MGDGs). Under mild HS temperature, hsp70-16 but not vdac3 sepalsshowed dramatic reduction in total lipids. In addition, vdac3 sepals exhibited a significant accumulationof plastidic lipids, especially sulfoquinovosyldiacylglycerols (SQDGs) and phosphatidylglycerols (PGs),whereas hsp70-16 sepals had a significant accumulation of triacylglycerols (TAGs) and simultaneousdramatic reductions in SQDGs and phospholipids (PLs), such as phosphatidylcholines (PCs), phosphatidylethanolamines (PEs), and phosphatidylserines (PSs). These findings revealed that the impact ofmild HS on sepal lipidome is influenced by genetic factors, and further, that HSP70-16 and VDAC3differently affect sepal lipidomic responses to mild HS. Our studies provide a lipidomic insight intofunctions of HSP and VDAC proteins in the plant’s HSR, in the context of floral development.展开更多
Pollution caused by toxic nitrobenzene has been a widespread environmental concern. Selective reduction of nitrobenzene to aniline is beneficial to further efficient and cost-effective biologic treatment. Electro- che...Pollution caused by toxic nitrobenzene has been a widespread environmental concern. Selective reduction of nitrobenzene to aniline is beneficial to further efficient and cost-effective biologic treatment. Electro- chemical reduction is a promising method and Cu-based catalysts have been found to be an efficient cathode material for this purpose. In this work, Cu catalysts with different morphologies were fabricated on Ti plate using a facile electrodepositon method via tuning the applied voltage. The dendritic nano-structured Cu catalysts obtained at high applied voltages exhibited an excellent efficiency and selectivity toward the reduction of nitro- benzene to aniline. Effects of the working potential and initial nitrobenzene concentration on the selective reduction of nitrobenzene to aniline using the Cu/Ti electrode were investigated. A high rate constant of 0.0251 mini and 97.1% aniline selectivity were achieved. The fabri- cated nano-structured Cu catalysts also exhibited good stability. This work provides a facile way to prepare highly efficient, cost-effective, and stable nano-sWuctured electro- catalysts for pollutant reduction.展开更多
基金supported by the National Natural Science Foundation of China,Nos.82172196(to KX),82372507(to KX)the Natural Science Foundation of Hunan Province,China,No.2023JJ40804(to QZ)the Key Laboratory of Emergency and Trauma(Hainan Medical University)of the Ministry of Education,China,No.KLET-202210(to QZ)。
文摘Ischemia–reperfusion injury is a common pathophysiological mechanism in retinal degeneration.PANoptosis is a newly defined integral form of regulated cell death that combines the key features of pyroptosis,apoptosis,and necroptosis.Oligomerization of mitochondrial voltage-dependent anion channel 1 is an important pathological event in regulating cell death in retinal ischemia–reperfusion injury.However,its role in PANoptosis remains largely unknown.In this study,we demonstrated that voltage-dependent anion channel 1 oligomerization-mediated mitochondrial dysfunction was associated with PANoptosis in retinal ischemia–reperfusion injury.Inhibition of voltage-dependent anion channel 1 oligomerization suppressed mitochondrial dysfunction and PANoptosis in retinal cells subjected to ischemia–reperfusion injury.Mechanistically,mitochondria-derived reactive oxygen species played a central role in the voltagedependent anion channel 1-mediated regulation of PANoptosis by promoting PANoptosome assembly.Moreover,inhibiting voltage-dependent anion channel 1 oligomerization protected against PANoptosis in the retinas of rats subjected to ischemia–reperfusion injury.Overall,our findings reveal the critical role of voltage-dependent anion channel 1 oligomerization in regulating PANoptosis in retinal ischemia–reperfusion injury,highlighting voltage-dependent anion channel 1 as a promising therapeutic target.
基金supported by grants from the National Key Research and Development Program of China (2016YFC1302200)the National Natural Science Foundation of China (31730040, 81070884, and 81471137)+2 种基金the Suzhou Health Planning Commission’s Key Clinical Diagnosis and Treatment Program (LCZX201606)the Priority Academic Program Development of Jiangsu Higher Education Institutions of Chinasubject to the Preponderant Clinic Discipline Group Project funding from the Second Affiliated Hospital of Soochow University (XKQ2015008)
文摘Voltage-dependent anion channel 1（VDAC1） is thought to contribute to the progression of tumor development. However, whether VDAC1 contributes to bone cancer pain remains unknown. In this study, we found that the expression of VDAC1 was upregulated in the L2–5 segments of the spinal dorsal horn at 2 and 3 weeks after injection of tumor cells into the tibial cavity. Intrathecal injection of a VDAC1 inhibitor significantly reversed the pain hypersensitivity and reduced the over-expression of Toll-like receptor 4（TLR4）. Intrathecal injection of minocycline, an inhibitor of microglia, also attenuated the pain hypersensitivity of rat models of bone cancer pain.These results suggest that VDAC1 plays a significant role in the development of complicated cancer pain, possibly by regulating the expression of TLR4.
基金supported by a grant from the National Natural Sciences Foundation of China (No. 30671743)
文摘The roles of voltage-dependent K^＋ channels during activation and damage in alveolar macrophages （AMs） exposed to different silica particles were examined. Rat AMs were collected by means of bronchoalveolar lavage, and were adjusted to 5× 10^5/mL. After AMs were exposed to different concentrations （0, 25, 50, 100, 200 μg/mL） of quartz particles and 100 μg/mL amorphous silica particles for 24 h, the voltage-depended K^＋ current in AMs was measured by using patch clamp technique. Meanwhile the leakage of lactate dehydrogenase （LDH） and the viability of AMs were detected respectively. Patch clamp studies demonstrated that AMs possessed outward delayed and inward rectifying K^＋ current. Exposure to quartz particles increased the outward delayed K^＋ current but it had no effect on inward rectifier K^＋ current in AMs. Neither of the two K^＋ channels in AMs was affected by amorphous silica particles. Cytotoxicity test showed that both silica particles could damage AM membrane and result in significant leakage of LDH （P〈0.05）. MTT studies, however, showed that only quartz particles reduced viability of AMs （P〈0.05）. It is concluded that quartz parti- cles can activate the outward delayed K^＋ channel in AMs, which may act as an activating signal in AMs to initiate an inflammatory response during damage and necrosis in AMs induced by exposure to quartz particle. K^＋ channels do not contribute to the membrane damage of AMs.
基金Project supported by the National Natural Science Foundation of China (Grant Nos. 61774140 and 61474103)。
文摘Recently, the efficiency of CdTe thin film solar cell has been improved by using new type of window layer Mg_(x)Zn_(1-x)O(MZO). However, it is hard to achieve such a high efficiency as expected. In this report a comparative study is carried out between the MZO/CdTe and CdS/CdTe solar cells to investigate the factors affecting the device performance of MZO/CdTe solar cells. The efficiency loss quantified by voltage-dependent photocurrent collection efficiency(ηC(V′)) is 3.89% for MZO/CdTe and 1.53% for CdS/CdTe solar cells. The higher efficiency loss for the MZO/CdTe solar cell is induced by more severe carrier recombination at the MZO/CdTe p-n junction interface and in CdTe bulk region than that for the CdS/CdTe solar cell. Activation energy(Ea) of the reverse saturation current of the MZO/CdTe and CdS/CdTe solar cells are found to be 1.08 e V and 1.36 e V, respectively. These values indicate that for the CdS/CdTe solar cell the carrier recombination is dominated by bulk Shockley-Read-Hall(SRH) recombination and for the MZO/CdTe solar cell the carrier recombination is dominated by the p-n junction interface recombination. It is found that the tunneling-enhanced interface recombination is also involved in carrier recombination in the MZO/CdTe solar cell. This work demonstrates the poor device performance of the MZO/CdTe solar cell is induced by more severe interface and bulk recombination than that of the CdS/CdTe solar cell.
文摘The types of the voltage-dependent calcium channels （VDCCs） in human ejaculatory sperm and the effects of calcium channel blocker （CCB） on human sperm motility parameters in vitro were investigated. The human sperm motility parameters in vitro in response to the pharmacological agents nifedipine （NIF, inhibitor of L-type VDCC） and ω-conotoxin （GVIA, inhibitor of N-type VDCC） were compared and analyzed statistically. The results showed that NIF （1, 5, 10 μmol/L） could not only significantly affect human sperm＇s shape but also spermatozoa motility after incubated at least 10 rain in vitro （P〈0.001）. GVIA （0.1, 0.5 and 1 μmol/L） could just only significantly affect human sperm＇s progressive motility （a %＋b %） after incubated for 20 min in vitro （P〈0.01）, but they both could not significantly affect spermic abnormality rate. It is suggested that L-type VDCC, non L-type VDCCs and isoform of L-type VDCC exist in the cell membrane of human sperm solely or together, and they participate in the spermic physiological processes especially the spermic motility.
文摘The effect of thyrosine kinase, calmodulin and voltage-dependent Ca 2+ channel on the proliferation of hepatoma cells induced by EGF was studied. Hepatoma cell line SMMC7721 was cultured in RPMI1640 serum-free medium. DNA synthesis rate of hepatoma cells was measured by 3H-TdR incorporation. 10 -9 mol/L EGF could significantly stimulate the proliferation of hepatoma cells (P<0.05), and this effect might be significantly inhibited by tyrosine kinase inhibitor (P<0.001). Calmodulin inhibitor W-7 had no effect on the basic phase of cultured hepatoma cells (P> 0.05), but it had very significantly inhibitory effect on the proliferation of hepatoma cells induced by EGF (P<0.001). Voltage-dependent Ca 2+ channel inhibitor Varapamil had no inhibition on the proliferation of hepatoma cells induced by EGF (P>0.05). It had no effect on the basic phase of cultured hepatoma cells (P>0.05). It is suggested that tyrosine kinase and Ca 2+-calmodulin-dependent pathway may play a critical role on the proliferation of heptoma cells induced by EGF, and voltage-dependent Ca 2+ channel is independent of the effect of EGF.
文摘OBJECTIVE Stroke has become the top ten leading cause of death in China.Isch⁃emic stroke accounts for 85%of stroke cases,and insufficiency of cerebral blood supply caused by atherosclerosis is one of the important causes of ischemic stroke.Therefore,it is of posi⁃tive significance to study the molecular mecha⁃nism of stroke injury caused by hypoperfusion in the search for drug targets.Voltage-dependent potassium channels are a family of potassium channels widely expressed in the central ner⁃vous system.However,their roles in neurogene⁃sis after stroke insults have not been clearly illus⁃trated.The purpose of this experiment is to explore the expression changes of different sub⁃families of voltage-dependent potassium chan⁃nels after the occurrence of ischemic stroke and their influence on neuroregeneration,to study the molecular mechanism of stroke injury caused by hypoperfusion,and to find potential targets for drug therapy of ischemic stroke.METHODS C57BL/6 mice aged 7-8 weeks and C17.2 cells were used in vivo and in vitro in the experiment.The mice in the experimental group were suf⁃fered from bilateral common carotid artery occlu⁃sion(BCCO)for 1 h and reperfusion for 7 d.In the control group,bilateral carotid artery was dis⁃sected without occlusion.Behavioral assay of suspension test were performed to assess the motor deficits of the mice.In this assay,the time of the first drop(latency),the number of drops within one minute(frequency),and the final scores were recorded as the results of athletic ability.A lower score indicated more severe motor damage of the mice.TTC staining was used to observe the cerebral infarction areas caused by ligation of bilateral common carotid arteries.After seven days,mice were sacrificed and brain tissue protein samples were collected for real-time quantitative PCR(RT-PCR)and Western blotting test to detect the changes of potassium channel subfamily expression levels in different brain regions.Neuronal injuries in all brain regions were detected using Nissl staining methods 7 d following model establishment.To detect the effects and the underlying mechanism of the related potassium channel on neurogene⁃sis,recombinant plasmids of the potassium chan⁃nels were transfected in cultured C17.2 neural stem cells.Afterwards,oxygen glucose depriva⁃tion experiments were performed.RESULTS Behavioral tests showed that BCCO can cause impaired motor performance.TTC staining showed that cerebral infarction existed in the stri⁃atum region,and the motor function decline caused by the injury in this region was consistent with the behavioral experiment results which veri⁃fied the effectiveness of our surgical operation.Nissl staining revealed a large amount of neuronal cell necrosis in the cortex and striatum regions,and dense neuronal cells in the lateral ventricular limbic region,suggesting that neurogenesis may have occurred in this region.The results of real-time quantitative RT-PCR showed that among the detected potassium channels distributed in the measured nervous system,the expression of voltage-dependent potassium channel Kv4.2 decreased significantly in all brain regions after stroke,suggesting that it may be involved in the pathological process of stroke.Immunohisto⁃chemical staining showed that there was neuro⁃genesis in the subgranular zone(SGZ)and sub⁃ventricular zone(SVZ)of the mice,and Kv4.2 expression was significantly changed in the regions,suggesting that it may be involved in the regulation of neuro regeneration after stroke.The transfected Kv4.2 plasmid enhanced the dif⁃ferentiation of the C17.2 neural stem cells to neu⁃rons and astrocytes under normoxia and the oxy⁃gen-glucose deprivation,suggesting that Kv4.2 may induce the differentiation of neural stem cells after stroke.Kv4.2 could induce the neural stem cells to differentiate into neurons in vitro and in vivo,and Western blotting assay showed that Kv4.2 could up-regulate the expression level of ERK1/2,p-ERK1/2,p-STAT3,NGF,p-TtkA,and BDNF.Moreover,the calcium ions and CAMKⅡwas also increased by Kv4.2 in vitro.CONCLUSION BCCO insults can induce the expressions of the potassium channels in the brains,among which the expression of Kv4.2 is down-regulated in the cerebral cortex,hippocam⁃pus and striatum.In vitro experiments confirmed that Kv4.2 can induce the differentiation of C17.2 neural stem cells into neurons and astrocytes under the condition of normoxia and oxygen-glucose deprivation.We concluded that Kv4.2 possibly promoted neurogenesis through ERK1/2/STAT3,NGF/TrkA,and Ca2+/CAMKⅡsignal pathways after stroke.Regulating the physiologi⁃cal functions of Kv4.2 channel might contribute to the rehabilitation of neuronal damage after stroke.
基金supported by the National Key R&D Program of China(2020YFB0905900)Science and Technology Project of SGCC(State Grid Corporation of China):The key Technologies for Electric Internet of Things(SGTJDK00DWJS2100042).
文摘Increasing distributed generators(DGs)and flexible loads(FLs)enable distribution systems to provide both active and reactive power reserves(P-Q reserves)in supporting the frequency and voltage regulations of transmission systems.However,such requirements at the interface between the transmission system operator(TSO)and distribution system operator(DSO)affect the distribution system operation security,considering the uncertainties of DGs and FLs.To exploit the reserve potential of distribution systems,this paper investigates the voltagedependent P-Q reserve capacity(V-PQRC)of such types of distribution systems.V-PQRC reflects the feasible space of PQ reserves that the DSO can provide to the TSO taking the voltage deviation limit at TSO-DSO interface into consideration,while ensuring the distribution system operation security under uncertainties of DGs and FLs.An evaluation method for VPQRC at the TSO-DSO interface is proposed.To improve the robust performance of the evaluation method,the DG uncertainty is captured by a generalized ambiguity set and the FL uncertainty is addressed by designing a constrained sliding mode controller(CSMC).Three objectives are considered in the evaluation,i.e.,P reserve capacity,Q reserve capacity,and the voltage deviation limit at the TSO-DSO interface.Then,a multiobjective optimization model integrating the generalized robust chance-constrained optimization and CSMC(GRCC-CSMC)is established for V-PQRC evaluation to obtain the Pareto optimal reserve schemes.Finally,a non-approximated selecting(NAS)method is proposed to build up a simplified V-PQRC linear model,which can be convenient to apply in the transmissiondistribution system coordination.Simulation results reveal that the V-PQRC evaluation method can achieve a good performance of accuracy and robustness against uncertainties.
文摘The voltage-dependent anion channel （VDAC） plays an essential role in the permeability of mltochondrial membrane. In the present study, we isolated a novel VDAC gene （brvdac） based on the assembly of expressed sequence tag sequences from Brassica rapa L. and explored its differential expression patterns In growth, tissues, abiotlc stress, and stress recovery. Results of a tissue-specific expression study in young seedlings Indicated that, of all tissues tested, brvdac expression was the highest in the leaves. Under cold, drought, and salt stresses, brvdac expression showed a transient Increase, and then returned to normal levels when the stress was removed. When plants were exposed to heat shock, there was no Increase in brvdac expression, whereas during recovery a quick and considerable increase in expression was observed. These observations indicate that dissimilar modulations of brvdactranscription may occur when plant cells encounter heat shock and the other three types of stress. In addition, phylogenetic analysis Implied that an earlier duplication of vdac probably occurred before the divergence between monocotyledons and dicotyledons.
基金Research Board(SERB),a statutory entity of the Department of Science and Technology(DST),Ministry of Science and Technology,India(File No:CRG/2021/000255)provided financial support to one of the authors.
文摘In this study,we present an in-depth exploration of charge transport phenomena and variable photo-switching characteristics in a novel double-perovskite-based three-terminal device.The Cs_(2)AgBiBr_(6) thin film(TF)was synthesized through a three-step thermal evaporation process followed by precise open-air annealing,ensuring superior film quality as confirmed by structural and morphological characterizations.Photoluminescence spectroscopy revealed distinct emissions at 2.28 and 2.07 eV,indicative of both direct and indirect electronic transitions.Our device exhibited space-charge limited current(SCLC)behaviour beyond 0.35 V,aligning with the relationship Current(I)∝Voltage(V)^(m),where the exponent m transitioned from≤1 to>1.Detailed analysis of Schottky parameters within the trap-filled limit(TFL)regime was conducted,accounting for variations in temperature and optical power.Significantly,the self-powered photodetector demonstrated outstanding performance under illumination.The sensitivity of the device was finely tunable via the applied bias voltages at the third terminal.Notably,an optimal bias voltage of±100μV yielded maximum responsivity(R)of 0.48 A/W and an impressive detectivity(D*)of 1.07×10^(9) Jones,highlighting the potential of this double-perovskite-based device for advanced optoelectronic applications.
基金supported by the National Natural Science Foundation of China(No.31800784)the Chongqing Key Laboratory of Precision Medicine in Joint Surgery(No.425Z2138)+2 种基金the Chongqing Excellent Scientist Project(No.425Z2W21)the Chongqing Natural Science Foundation General Project(No.cstc2021jcyjmsxm X0135)the Chongqing Postdoctoral Research Project Special Fund(No.2021XM3033)。
文摘The growth plate(GP)is a crucial tissue involved in skeleton development via endochondral ossification(EO).The bone organoid is a potential research model capable of simulating the physiological function,spatial structure,and intercellular communication of native GPs.However,mimicking the EO process remains a key challenge for bone organoid research.To simulate this orderly mineralization process,we designed an in vitro sh Ca_(v)3.3 ATDC5-loaded gelatin methacryloyl(Gel MA)hydrogel model and evaluated its bioprintability for future organoid construction.In this paper,we report the first demonstration that the T-type voltage-dependent calcium channel(T-VDCC)subtype Ca_(v)3.3 is dominantly expressed in chondrocytes and is negatively correlated with the hypertrophic differentiation of chondrocytes during the EO process.Furthermore,Ca_(v)3.3 knockdown chondrocytes loaded with the Gel MA hydrogel successfully captured the EO process and provide a bioink capable of constructing layered and orderly mineralized GP organoids in the future.The results of this study could therefore provide a potential target for regulating the EO process and a novel strategy for simulating it in bone organoids.
基金Supported by National Natural Science Foundation of China,No.31171107,No.31071011 and No.31271236
文摘AIM:To investigate the effect of hydrogen sulfide(H2S)on smooth muscle motility in the gastric fundus.METHODS:The expression of cystathionineβ-synthase(CBS)and cystathionineγ-lyase(CSE)in cultured smooth muscle cells from the gastric fundus was examined by the immunocytochemistry technique.The tension of the gastric fundus smooth muscle was recorded by an isometric force transducer under the condition of isometric contraction with each end of the smooth muscle strip tied with a silk thread.Intracellular recording was used to identify whether hydrogen sulfide affects the resting membrane potential of the gastric fundus in vitro.Cells were freshly separated from the gastric fundus of mice using a variety of enzyme digestion methods and whole-cell patch-clamp technique was used to find the effects of hydrogen sulfide on voltage-dependent potassium channel and calcium channel.Calcium imaging with fura-3AM loading was used to investigate the mechanism by which hydrogen sulfide regulates gastric fundus motility in cultured smooth muscle cells.RESULTS:We found that both CBS and CSE were expressed in the cul tured smooth muscle cel ls from the gastric fundus and that H2S increased the smooth muscle tension of the gastric fundus in mice at low concentrations.In addition,nicardipine and aminooxyacetic acid(AOAA),a CBS inhibitor,reduced the tension,whereas Nω-nitro-L-arginine methyl ester,a nonspecific nitric oxide synthase,increased the tension.The AOAA-induced relaxation was significantly recovered by H2S,and the Na HS-induced increase in tonic contraction was blocked by 5 mmol/L4-aminopyridine and 1μmol/L nicardipine.Na HS significantly depolarized the membrane potential and inhibited the voltage-dependent potassium currents.Moreover,Na HS increased L-type Ca2+currents and caused an elevation in intracellular calcium([Ca2+]i).CONCLUSION:These findings suggest that H2S may be an excitatory modulator in the gastric fundus in mice.The excitatory effect is mediated by voltagedependent potassium and L-type calcium channels.
基金This work was supported by the National Natural Science Foundation of China(No.81473674)and Natural Science Foundation of Anhui Provincial Department of Education(No.KJ2020A0386).
文摘Wuzi-Yanzong-Wan(WZYZW)is a classic prescription for male infertility.Our previous investigation has demon-strated that it can inhibit sperm apoplosis via afecting mitochondria,but the underlying mechanisms are unclear.The purpose of the present study was to explore the actions of WZYZW on mitochondrial permeability transition pore(mPTP)in mouse spermatocyte cell line(GC-2 cells)opened by atractyloside(ATR).At first,WZYZW-mediated serum was prepared from rats following oral adminis-tration of WZYZW for 7 days.GC-2 cells were divided into control group,model group,positive group,as well as 5%,10%,15%WZYZW-medicated serum group.Cyclosporine A(CsA)was used as a positive control.50 μmol·L^(-1) ATR was added afer drugs in-cubation.Cell viability was asessed using CCK-8.Apoptosis was detected using flow cytometry and TUNEL method.The opening of mPTP and mitochondrial membrane potential(MMP)were dected by Calcein AM and JC-1 fuorescent probe respectively.The mRNA and protein levels of voltage-dependent anion channel I(VDACI),cyelophilin D(CypD),adenine nucleide translocator(ANT),cytochrome C(Cyt C),caspase 3,9 were dected by RT-PCR(real time quantity PCR)and Western blotting respectively.The results demonstrated that mPTP of GC-2 cells was opened alpter 24 hours of ATR treatment,resulting in decreased MMP and increased apoptosis.Pre-protection with WZYZ-medicated serum and CsA inhibited the opening of mPTP of GC-2 cells induced by ATR associ ated with increased MMP and decreased apoptosis.Morcover,the results of RT-qPCR and WB suggested that WZYZW-medicated serum could significantly reduce the mRNA and protein levels of VDACI and CypD,Caspase-3,9 and CylC,as well as a increased ra-tio of BclBax.However,ANT was not significantly ffected.Therefore,these findings indicated that WZYZW inhibited mitochondri-al mediated apoptosis by atenuating the opening of mPTP in GC-2 cells.WZYZW-medicated serum inhibited the expressions of VDACI and CypD and increased the expression of Bcl-2,which afected the opening of mPTP and exerted protective and anti-apop-totic ffects on GC-2 cell induced by ATR.
基金the Department of International Cooperation, Hebei Province Science and Technology Research Council, China, No. 09396427D
文摘Voltage-gated potassium channels comprise 12 subtypes （Kv1-Kv12）. Kv2.1, which is expressed in most mammalian central neurons, provides the majority of delayed-rectifier K＋ current in cortical and hippocampal pyramidal neurons, and plays an especially prominent role in repolarizing membrane potential, as well as in facilitation of exocytosis. Kv2.1-encoded K＋ efflux is essential for neuronal apoptosis programming. The human form of the Kv2.1 potassium channel contains large intracellular regions. The cytoplasmic C-terminal plays a key role in modulating Kv2.1 gating. The present manuscript summarized Kv2.1 structure and modulation in neurons and analyzed the roles of the cytoplasmic C-terminal.
基金Supported by the National Natural Science Foundation of China,No. 30472254
文摘AIM： To induce the pancreatic duct cells into endocrine cells with a new natural protocol for electrophysiological study. METHODS： The pancreatic duct cells of neonatal rats were isolated, cultured and induced into endocrine ceils with 15% fetal bovine serum for a period of 20 d. During this period, insulin secretion, MTT value, and morphological change of neonatal and adult pancreatic islet cells were comparatively investigated. Pancreatic β-cells were identified by morphological and electrophysiological characteristics, while ATP sensitive potassium channels （KATP）, voltage-dependent potassium channels （Kv）, and voltage-dependent calcium channels （KcA） in β-cells were identified by patch clamp technique. RESULTS： After incubation with fetal bovine serum, the neonatal duct cells budded out, changed from duct-like cells into islet clusters. In the first 4 d, MTT value and insulin secretion increased slowly （MTT value from 0.024 ±0.003 to 3.028±0.003, insulin secretion from 2.6±0.6 to 3.1±0.8 mIU/L）. Then MTT value and insulin secretion increased quickly from d 5 to d 10 （MTT value from 0.028 ±0.003 to 0.052±0.008, insulin secretion from 3.1±0.8 to 18.3±2.6 mIU/L）, then reached high plateau （MTT value 〉0.052±0.008, insulin secretion 〉18.3±2.6 mIU/L）. In contrast, for the isolated adult pancreatic islet cells, both insulin release and MTT value were stable in the first 4 d （MTT value from 0.029±0.01 to 0.031±0.011, insulin secretion from 13.9±3.1 to 14.3±3.3 mIU/L）, but afterwards they reduced gradually （MTT value 〈0.031 ±0.011, insulin secretion 〈8.2±1.5 mIU/L）, and the pancreatic islet cells became dispersed, broken or atrophied correspondingly. The differentiated neonatal cells were identified as pancreatic islet cells by dithizone staining method, and pancreatic β-cells were further identified by both morphological features and electrophysiological characteristics, i.e. the existence of recording currents from KATP, Kv, and KCA. CONCLUSION： Islet cells differentiated from neonatal pancreatic duct cells with the new natural protocol are more advantageous in performing patch clamp study over the isolated adult pancreatic islet cells.
基金supported by NIH,grant No.GM-63577NNSF,grant No.30571537,No.30271500+1 种基金the National Natural Science Foundation of China,No.30271500,30571537 and 813702462010 National Clinical Key Disciplines Construction Grant from the Ministry of Health of the People’s Republic of China
文摘Activation of cannabinoid receptor type 1 on presynaptic neurons is postulated to suppress neu- ~ ~ ~ 2＋ ~ ~ 2＋ rotransmlsslon by decreasing Ca reflux through high voltage-gated Ca channels. However, recent studies suggest that cannabinoids which activate cannabinoid receptor type 1 can increase neurotransmitter release by enhancing Ca2＋ influx in vitro. The aim of the present study was to investigate the modulation of intracellular Ca2＋ concentration by the cannabinoid receptor type 1 agonist anandamide, and its underlying mechanisms. Using whole cell voltage-damp and calcium imaging in cultured trigeminal ganglion neurons, we found that anandamide directly caused Ca2＋ influx in a dose-dependent manner, which then triggered an increase of intracellular Ca2＋ concentration. The cyclic adenosine and guanosine monophosphate-dependent protein kinase systems, but not the protein kinase C system, were involved in the increased intracellular Ca2＋concentration by anandamide. This result showed that anandamide increased intracellu- lar Ca2＋ concentration and inhibited high voltage-gated Ca2＋ channels through different signal transduction pathways.
基金General Project of National Natural Science Foundation(No.81860243)。
文摘Parkinson's disease(PD)is a neurodegenerative disorder due to gradual loss of dopaminergic neurons in the substantia nigra in the midbrain,however the pathogenesis is unclear.There is a correlation between the excitability of striatal neurons and PD.Ion channels are important to maintain membrane potential and regulate excitability of neurons,while ionic mechanisms for modulation of neurons excitability are not fully understood.This article reviews the relationship between ion channels and excitability of striatal neurons in PD and ion channel changes in the pathogenesis of PD.In order to find new targets to treatment PD by intervening ion channels.
文摘Croton zambezicus Muell.Arg.(Euphorbiaceae)(Syn.C.amabilis Muell.Arg.,C.gratissimus Burch.)is a shrub or small tree reaching 10 m in height.The leaf decoction is used in Benin as anti-hypertensive,anti-microbial(urinary infections)and to treat fever associated with malaria.We analysed the in vitro and in vivo vasorelaxant activity
基金supported by National Natural Sciences Foundation of China(31671511 and 31971907)the SJTU JiRLMDS Joint Research Fund(MDS-JF-2019B02)the Programme of Introducing Talents of Discipline to Universities(111 Project,B14016).
文摘Arabidopsis sepals coordinate flower opening in the morning as ambient temperature rises;however,the underlying molecular mechanisms are poorly understood. Mutation of one heat shock proteinencoding gene, HSP70-16, impaired sepal heat stress responses (HSR), disrupting lipid metabolism,especially sepal cuticular lipids, leading to abnormal flower opening. To further explore, to what extent,lipids play roles in this process, in this study, we compared lipidomic changes in sepals of hsp70-16 andvdac3 (mutant of a voltage-dependent anion channel, VDAC3, an HSP70-16 interactor) grown underboth normal (22 C) and mild heat stress (27 C, mild HS) temperatures. Under normal temperature,neither hsp70-16 nor vdac3 sepals showed significant changes in total lipids;however, vdac3 but nothsp70-16 sepals exhibited significant reductions in the ratios of all detected 11 lipid classes, except themonogalactosyldiacylglycerols (MGDGs). Under mild HS temperature, hsp70-16 but not vdac3 sepalsshowed dramatic reduction in total lipids. In addition, vdac3 sepals exhibited a significant accumulationof plastidic lipids, especially sulfoquinovosyldiacylglycerols (SQDGs) and phosphatidylglycerols (PGs),whereas hsp70-16 sepals had a significant accumulation of triacylglycerols (TAGs) and simultaneousdramatic reductions in SQDGs and phospholipids (PLs), such as phosphatidylcholines (PCs), phosphatidylethanolamines (PEs), and phosphatidylserines (PSs). These findings revealed that the impact ofmild HS on sepal lipidome is influenced by genetic factors, and further, that HSP70-16 and VDAC3differently affect sepal lipidomic responses to mild HS. Our studies provide a lipidomic insight intofunctions of HSP and VDAC proteins in the plant’s HSR, in the context of floral development.
文摘Pollution caused by toxic nitrobenzene has been a widespread environmental concern. Selective reduction of nitrobenzene to aniline is beneficial to further efficient and cost-effective biologic treatment. Electro- chemical reduction is a promising method and Cu-based catalysts have been found to be an efficient cathode material for this purpose. In this work, Cu catalysts with different morphologies were fabricated on Ti plate using a facile electrodepositon method via tuning the applied voltage. The dendritic nano-structured Cu catalysts obtained at high applied voltages exhibited an excellent efficiency and selectivity toward the reduction of nitro- benzene to aniline. Effects of the working potential and initial nitrobenzene concentration on the selective reduction of nitrobenzene to aniline using the Cu/Ti electrode were investigated. A high rate constant of 0.0251 mini and 97.1% aniline selectivity were achieved. The fabri- cated nano-structured Cu catalysts also exhibited good stability. This work provides a facile way to prepare highly efficient, cost-effective, and stable nano-sWuctured electro- catalysts for pollutant reduction.
