The family of voltage-gated （Shaker-like） potassium channels in plants includes both inward-rectifying （Kin） channels that allow plant cells to accumulate K＋ and outward-rectifying （Kout） channels that mediate ...The family of voltage-gated （Shaker-like） potassium channels in plants includes both inward-rectifying （Kin） channels that allow plant cells to accumulate K＋ and outward-rectifying （Kout） channels that mediate K＋ efflux. Despite their dose structural similarities, Kin and Kout channels differ in their gating sensitivity towards voltage and the extracellular K＋ concentration. We have carried out a systematic program of domain swapping between the Kout channel SKOR and the Kin channel KAT1 to examine the impacts on gating of the pore regions, the S4, S5, and the S6 helices. We found that, in particular, the N-terminal part of the S5 played a critical role in KAT1 and SKOR gating. Our findings were supported by molecular dynamics of KAT1 and SKOR homology models. In silico analysis revealed that during channel opening and closing, displacement of certain residues, especially in the S5 and S6 segments, is more pronounced in KAT1 than in SKOR. From our analysis of the S4-S6 region, we conclude that gating （and K＋-sensing in SKOR） depend on a number of structural elements that are dispersed over this -145-residue sequence and that these place additional constraints on configurational rearrangement of the channels during gating.展开更多
Canonical transient receptor potential 4(TRPC4) forms non-selective cation channels that contribute to phospholipase C-dependent Ca2+ entry into cells following stimulation of G protein coupled receptors and receptor ...Canonical transient receptor potential 4(TRPC4) forms non-selective cation channels that contribute to phospholipase C-dependent Ca2+ entry into cells following stimulation of G protein coupled receptors and receptor tyrosine kinases.Moreover,the channels are regulated by pertussis toxin-sensitive Gi/o proteins,lipids,and various other signaling mechanisms.TRPC4-containing channels participate in the regulation of a variety of physiological functions,including excitability of both gastrointestinal smooth muscles and brain neurons.This review is to present recent advances in the understanding of physiology and development of small molecular modulators of TRPC4 channels.展开更多
OBJECTIVE:To determine the effect of Wenyang Huazhuo Fang(WHF),a Traditional Chinese Medicine decoction,on renal function in a rat model of doxorubicin-induced nephropathy,and to elucidate the underlying mechanism.MET...OBJECTIVE:To determine the effect of Wenyang Huazhuo Fang(WHF),a Traditional Chinese Medicine decoction,on renal function in a rat model of doxorubicin-induced nephropathy,and to elucidate the underlying mechanism.METHODS:Sprague-Dawley rats were randomly divided into six groups:control,doxorubicin-nephropathy,and prednisone-treated(6.45 mg·kg^-1·d^-1)doxorubicin nephropathy groups,as well as high-(7.26 g·kg^-1·d^-1),medium-(2.42 g·kg-1·d-),and low-dose(0.81 g·kg^-1·d^-1)WHF-treated doxorubicin-nephropathy groups.The nephropathy rat model was established by two tail vein injections of doxorubicin,followed by prednisone or WHF treatment for 8 weeks.Body weights were monitored and urinary protein was measured every 2 weeks.After the end of the treatment period,the rats were euthanized.Serum biochemical indicators were determined and renal morphological alterations were assessed using histological staining.The expression of transient receptor potential cation channel subfamily C member 6(TRPC6),stromal interaction molecule 1(STIM1),and calcium release-activated calcium channel protein 1(Orai1)was detected using western blotting,and their mRNA levels were examined using quantitative real-time reverse transcription-polymerase chain reaction.RESULTS:WHF treatment was found to significantly ameliorate weight loss,proteinuria,hypoalbuminemia,and dyslipidemia in doxorubicin-nephropathy rats.The protein and mRNA levels of TRPC6,STIM1,and Orai1 were partially,but significantly suppressed by prednisone or WHF treatment.CONCLUSION:Treatment with WHF significantly ameliorates renal injury in a rat model of doxorubicin-induced nephropathy,which could be at least partially related to repression of the TRPC6 pathway.展开更多
To investigate the mechanisms of microwave induced pacemaker cell injuries, Wistar rats and the primary pacemaker cells of newborn Wistar rats were exposed to microwave at average power density of 50 mW/cm2. Slower sp...To investigate the mechanisms of microwave induced pacemaker cell injuries, Wistar rats and the primary pacemaker cells of newborn Wistar rats were exposed to microwave at average power density of 50 mW/cm2. Slower spontaneous beating rate, intercellular Ca2＋ aggregation and cell membrane perforation were detected immediately after the exposure. Moreover, hyperpolarizationactivated cyclic nucleotide-gated cation channel 4 （HCN4） was down-regulated immediately after the exposure and up-regulated at 12 h after the exposure. In the sinoatrial node （SAN） of the rats,展开更多
OBJECTIVE:To study the effect and underlying mechanisms of Chinese medicine Yanghe decoction(阳和汤)on pain relief in a rat model of bone metastasis of breast cancer induced by michigan cancer foundation-7(MCF-7).METH...OBJECTIVE:To study the effect and underlying mechanisms of Chinese medicine Yanghe decoction(阳和汤)on pain relief in a rat model of bone metastasis of breast cancer induced by michigan cancer foundation-7(MCF-7).METHODS:Bone pain was induced in the tibia of rats injected with MCF-7 cells.The Chinese herbal remedy was used to decoct Yanghe decoction for the treatment of bone pain rats.The behavior study was carried out to evaluate the paw mechanical withdraw threshold and thermal withdraw latency.Liquid chromatography-mass spectrometry,Western blotting,quantitative real-time polymerase chain reaction,enzyme-linked immunosorbent assay(ELISA),immunohistochemical(IHC)staining were performed for analysis.RESULTS:Yanghe decoction could improve the defensive behavior similar to the transient receptor potential ankyrin 1(TRPA1)inhibitor.In morphology study,Yanghe decoction could attenuate the cellular growth as well as inflammatory infiltration in the metastasis group.Furthermore,Yanghe decoction downregulated the TRPA1 expression on the dorsal root ganglion from the metastatic rats at both transcriptional and protein level.Yanghe decoction alleviated the inflammation in metastatic tissues by hematoxylin-eosin and IHC analysis,and Yanghe decoction also reduced the inflammatory cytokines production in the serum including tumor necrosis factor-αand interleukin-6,interleukin-1 beta by ELISA.As the cytochromec oxidase subunit II/prostaglandin E2(PGE2)is required for cancer development,Yanghe decoction reduced the expression of PGE2 in the tissue and serum.CONCLUSION:Taken together,Yanghe decoction protected the rats from breast cancer bone metastasis through TRPA1 signaling mediated neuropathic pain and additional immune modulation in tumor microenvironment.展开更多
Recently, single carrier block transmission(SCBT) has received much attention in high-rate phase-coherent underwater acoustic communication.However,minimum-mean-square-error(MMSE) linear FDE may suffer performance los...Recently, single carrier block transmission(SCBT) has received much attention in high-rate phase-coherent underwater acoustic communication.However,minimum-mean-square-error(MMSE) linear FDE may suffer performance loss in the severely time dispersive underwater acoustic channel. To combat the channel distortion, a novel multi-channel receiver with maximum ratio combining and a low complex T/4 fractional iterative frequency domain equalization(FDE) is investigated to improve diversity gain and the bit error rate(BER) performance. The proposed method has been verified by the real data from a lake underwater acoustic communication test in November 2011. At 1.8 km, the useful data rates are around 1500 and 3000 bits/s for BPSK and QPSK respectively. The results show the improvements of system performance. Compared with MMSE FDE system, the output SNR improvement is 6.9 d B, and the BER is from 10-3 to no error bits for BPSK. The output SNR improvement is 5.3 d B, and the BER is from 1.91×10-2 to 2.2×10-4for QPSK.展开更多
Transient receptor potential(TRP)channels are widely found throughout the animal kingdom.By serving as cellular sensors for a wide spectrum of physical and chemical stimuli,they play crucial physiological roles rangin...Transient receptor potential(TRP)channels are widely found throughout the animal kingdom.By serving as cellular sensors for a wide spectrum of physical and chemical stimuli,they play crucial physiological roles ranging from sensory transduction to cell cycle modulation.TRP channels are tetrameric protein complexes.While most TRP subunits can form functional homomeric channels,heteromerization of TRP channel subunits of either the same subfamily or different subfamilies has been widely observed.Heteromeric TRP channels exhibit many novel properties compared to their homomeric counterparts,indicating that co-assembly of TRP channel subunits has an important contribution to the diversity of TRP channel functions.展开更多
A water flow simulation device capable of adjusting flow velocity was designed in flow velocity range of 0–30 cm/s,with which an indoor experiment was conducted to simulate the movement and adhesive behaviors of diff...A water flow simulation device capable of adjusting flow velocity was designed in flow velocity range of 0–30 cm/s,with which an indoor experiment was conducted to simulate the movement and adhesive behaviors of different-sized Apostichopus japonicus under different flow velocities.Observation showed that,in slow flow(~5 cm/s),A.japonicus moved more distance than in still water,and hardly moved in the riptide(~30 cm/s);and the adhesive capacity of A.japonicus was related to the flow velocity and attachment time.A.japonicus were able to attach to the bottom after any attachment time in the slow flow,after 10 s in the medium flow(~15 cm/s),and after 60 s in the riptide(~30 cm/s).In addition,larger A.japonicus were stronger with adhesive ability than smaller ones.The transcriptome data showed that the expression of transient receptor potential cation channel subfamily A,member 1(TRPA1)in the tube feet was increased significantly in a flowing water,but those in the tentacles and tube feet were not significantly changed.Fluorescence in-situ hybridization results showed that TRPA1 was expressed around the watervascular of tentacles,tube feet,body wall,and spines.Therefore,tube feet were important for sea cucumbers to keep themselves stable in relatively swift flow with adhesion ability.展开更多
Aim： To investigate the distribution of cation channel of sperm 1 （CATSPER1） protein and the presence of CATSPER1 mRNA in human testis and ejaculated spermatozoa. The influence of anti-human CATSPER1 antibody upon ...Aim： To investigate the distribution of cation channel of sperm 1 （CATSPER1） protein and the presence of CATSPER1 mRNA in human testis and ejaculated spermatozoa. The influence of anti-human CATSPER1 antibody upon human sperm motility was used to evaluate the function of human CATSPER1 and to estimate its possible use as a target for immunocontraception. Methods： Human ejaculated sperm from normozoospermic donors （n = 12） and liquid nitrogen frozen human testis were used for the study of mRNA and protein expression of CATSPER1 by reverse transcription polymerase chain reaction （RT-PCR） and immunohistochemistry, respectively. Spermatozoa from normozoospermic donors （n = 12） were individually processed using a swim-up procedure and were then incubated with CATSPER1 antibody at final concentrations of 20, 4 and 0.8 μg/mL. After 1, 2 and 6 h incubation, progressive motility and fast progressive motility were measured by means of computer-assisted semen analysis. Results： CATSPER1 transcript was detected in both human testis and each human ejaculated semen sample. CATSPER1 protein expressed in the membrane of spermatid and was localized in the principal piece of the sperm tail. The application of CATSPER1 antibody at all concentrations significantly inhibited both progressive motility and fast progressive motility after 1, 2 and 6 h incubation, and significant dose-dependent changes were observed. Conclusion： CATSPER1 is meiotically and post-meiotically expressed in human testis tissue. CATSPER1 mRNA in human ejaculated spermatozoa could be a more feasible target for study and infertility screening than testis biopsy. In addition, our results suggest that human CATSPER1 could be a possible target for immunocontraception.展开更多
文摘The family of voltage-gated （Shaker-like） potassium channels in plants includes both inward-rectifying （Kin） channels that allow plant cells to accumulate K＋ and outward-rectifying （Kout） channels that mediate K＋ efflux. Despite their dose structural similarities, Kin and Kout channels differ in their gating sensitivity towards voltage and the extracellular K＋ concentration. We have carried out a systematic program of domain swapping between the Kout channel SKOR and the Kin channel KAT1 to examine the impacts on gating of the pore regions, the S4, S5, and the S6 helices. We found that, in particular, the N-terminal part of the S5 played a critical role in KAT1 and SKOR gating. Our findings were supported by molecular dynamics of KAT1 and SKOR homology models. In silico analysis revealed that during channel opening and closing, displacement of certain residues, especially in the S5 and S6 segments, is more pronounced in KAT1 than in SKOR. From our analysis of the S4-S6 region, we conclude that gating （and K＋-sensing in SKOR） depend on a number of structural elements that are dispersed over this -145-residue sequence and that these place additional constraints on configurational rearrangement of the channels during gating.
基金supported in part by the National Natural Science Foundation of China(81228021)US National Institutes of Health(DK081654)
文摘Canonical transient receptor potential 4(TRPC4) forms non-selective cation channels that contribute to phospholipase C-dependent Ca2+ entry into cells following stimulation of G protein coupled receptors and receptor tyrosine kinases.Moreover,the channels are regulated by pertussis toxin-sensitive Gi/o proteins,lipids,and various other signaling mechanisms.TRPC4-containing channels participate in the regulation of a variety of physiological functions,including excitability of both gastrointestinal smooth muscles and brain neurons.This review is to present recent advances in the understanding of physiology and development of small molecular modulators of TRPC4 channels.
基金the Key Research and Development Projects of Shaanxi Province(Study on the Effect of Wenyanghuazhuo Method on Autophagy-related Proteins in Adriamycin Nephropathy Rat Model,No.2020SF-340)a Grant from the Sci-tech Project of Shaanxi Province(Study on the Expression Regulation of STIM1/Orail and TRPC-related Channel Proteins in Renal Tissues of Adriamycin Nephropathy Rats by Aconiti Lateralis Radix and Wenyanghuazhuofang,No.2016SF-068)。
文摘OBJECTIVE:To determine the effect of Wenyang Huazhuo Fang(WHF),a Traditional Chinese Medicine decoction,on renal function in a rat model of doxorubicin-induced nephropathy,and to elucidate the underlying mechanism.METHODS:Sprague-Dawley rats were randomly divided into six groups:control,doxorubicin-nephropathy,and prednisone-treated(6.45 mg·kg^-1·d^-1)doxorubicin nephropathy groups,as well as high-(7.26 g·kg^-1·d^-1),medium-(2.42 g·kg-1·d-),and low-dose(0.81 g·kg^-1·d^-1)WHF-treated doxorubicin-nephropathy groups.The nephropathy rat model was established by two tail vein injections of doxorubicin,followed by prednisone or WHF treatment for 8 weeks.Body weights were monitored and urinary protein was measured every 2 weeks.After the end of the treatment period,the rats were euthanized.Serum biochemical indicators were determined and renal morphological alterations were assessed using histological staining.The expression of transient receptor potential cation channel subfamily C member 6(TRPC6),stromal interaction molecule 1(STIM1),and calcium release-activated calcium channel protein 1(Orai1)was detected using western blotting,and their mRNA levels were examined using quantitative real-time reverse transcription-polymerase chain reaction.RESULTS:WHF treatment was found to significantly ameliorate weight loss,proteinuria,hypoalbuminemia,and dyslipidemia in doxorubicin-nephropathy rats.The protein and mRNA levels of TRPC6,STIM1,and Orai1 were partially,but significantly suppressed by prednisone or WHF treatment.CONCLUSION:Treatment with WHF significantly ameliorates renal injury in a rat model of doxorubicin-induced nephropathy,which could be at least partially related to repression of the TRPC6 pathway.
文摘To investigate the mechanisms of microwave induced pacemaker cell injuries, Wistar rats and the primary pacemaker cells of newborn Wistar rats were exposed to microwave at average power density of 50 mW/cm2. Slower spontaneous beating rate, intercellular Ca2＋ aggregation and cell membrane perforation were detected immediately after the exposure. Moreover, hyperpolarizationactivated cyclic nucleotide-gated cation channel 4 （HCN4） was down-regulated immediately after the exposure and up-regulated at 12 h after the exposure. In the sinoatrial node （SAN） of the rats,
基金Supported by China Postdoctoral Science Foundation Grant:Pathogenesis of“Impassability Leads to Pain”about Bone Metastasis based on Proinflammatory Cytokines Activate TRPA1(No.2018M632971)Hunan Natural Science Foundation of China:Study on the Effect and Mechanism of Yanghe Decoction Regulating cxcl12/cxcr4 Biological Axis against Bone Metastasis of Breast Cancer in Yang Deficiency Syndrome(No.2020JJ8088)+1 种基金General Project of Natural Science Foundation of Hunan Province:Study on the Mechanism of Bone Loss in Breast Cancer Bone Metastasis by Warm Yang Method from the Pathway of TNF-α/NF-κB/Autophagy(No.2021JJ30418)Social Development Project of Key R&D Science and Technology Program of Hainan Province:Clinical Efficiency of Liushen Pill in Treatment of Bone Cancer Pain and Study on the Analgesic Mechanism of Bone Cancer Pain of Rat Model(No.ZDYF2021SHFZ225)。
文摘OBJECTIVE:To study the effect and underlying mechanisms of Chinese medicine Yanghe decoction(阳和汤)on pain relief in a rat model of bone metastasis of breast cancer induced by michigan cancer foundation-7(MCF-7).METHODS:Bone pain was induced in the tibia of rats injected with MCF-7 cells.The Chinese herbal remedy was used to decoct Yanghe decoction for the treatment of bone pain rats.The behavior study was carried out to evaluate the paw mechanical withdraw threshold and thermal withdraw latency.Liquid chromatography-mass spectrometry,Western blotting,quantitative real-time polymerase chain reaction,enzyme-linked immunosorbent assay(ELISA),immunohistochemical(IHC)staining were performed for analysis.RESULTS:Yanghe decoction could improve the defensive behavior similar to the transient receptor potential ankyrin 1(TRPA1)inhibitor.In morphology study,Yanghe decoction could attenuate the cellular growth as well as inflammatory infiltration in the metastasis group.Furthermore,Yanghe decoction downregulated the TRPA1 expression on the dorsal root ganglion from the metastatic rats at both transcriptional and protein level.Yanghe decoction alleviated the inflammation in metastatic tissues by hematoxylin-eosin and IHC analysis,and Yanghe decoction also reduced the inflammatory cytokines production in the serum including tumor necrosis factor-αand interleukin-6,interleukin-1 beta by ELISA.As the cytochromec oxidase subunit II/prostaglandin E2(PGE2)is required for cancer development,Yanghe decoction reduced the expression of PGE2 in the tissue and serum.CONCLUSION:Taken together,Yanghe decoction protected the rats from breast cancer bone metastasis through TRPA1 signaling mediated neuropathic pain and additional immune modulation in tumor microenvironment.
基金supported in part by National Natural Science Foundation of China under Grants No.61471298 and 61101102Natural Science Basic Research Plan in Shaanxi Province of China (Program No. 2015JM6297)
文摘Recently, single carrier block transmission(SCBT) has received much attention in high-rate phase-coherent underwater acoustic communication.However,minimum-mean-square-error(MMSE) linear FDE may suffer performance loss in the severely time dispersive underwater acoustic channel. To combat the channel distortion, a novel multi-channel receiver with maximum ratio combining and a low complex T/4 fractional iterative frequency domain equalization(FDE) is investigated to improve diversity gain and the bit error rate(BER) performance. The proposed method has been verified by the real data from a lake underwater acoustic communication test in November 2011. At 1.8 km, the useful data rates are around 1500 and 3000 bits/s for BPSK and QPSK respectively. The results show the improvements of system performance. Compared with MMSE FDE system, the output SNR improvement is 6.9 d B, and the BER is from 10-3 to no error bits for BPSK. The output SNR improvement is 5.3 d B, and the BER is from 1.91×10-2 to 2.2×10-4for QPSK.
文摘Transient receptor potential(TRP)channels are widely found throughout the animal kingdom.By serving as cellular sensors for a wide spectrum of physical and chemical stimuli,they play crucial physiological roles ranging from sensory transduction to cell cycle modulation.TRP channels are tetrameric protein complexes.While most TRP subunits can form functional homomeric channels,heteromerization of TRP channel subunits of either the same subfamily or different subfamilies has been widely observed.Heteromeric TRP channels exhibit many novel properties compared to their homomeric counterparts,indicating that co-assembly of TRP channel subunits has an important contribution to the diversity of TRP channel functions.
基金the National Key R&D Program of China(No.2019YFD0900800)the National Science Foundation for Young Scientists of China(No.41606171)+1 种基金the Marine S&T Fund of Shandong Province for Pilot National Laboratory for Marine Science and Technology(Qingdao)(No.2018SDKJ0502)the Science and Technology Service Network Program of Chinese Academy of Sciences(No.KFJ-STS-ZDTP-55)。
文摘A water flow simulation device capable of adjusting flow velocity was designed in flow velocity range of 0–30 cm/s,with which an indoor experiment was conducted to simulate the movement and adhesive behaviors of different-sized Apostichopus japonicus under different flow velocities.Observation showed that,in slow flow(~5 cm/s),A.japonicus moved more distance than in still water,and hardly moved in the riptide(~30 cm/s);and the adhesive capacity of A.japonicus was related to the flow velocity and attachment time.A.japonicus were able to attach to the bottom after any attachment time in the slow flow,after 10 s in the medium flow(~15 cm/s),and after 60 s in the riptide(~30 cm/s).In addition,larger A.japonicus were stronger with adhesive ability than smaller ones.The transcriptome data showed that the expression of transient receptor potential cation channel subfamily A,member 1(TRPA1)in the tube feet was increased significantly in a flowing water,but those in the tentacles and tube feet were not significantly changed.Fluorescence in-situ hybridization results showed that TRPA1 was expressed around the watervascular of tentacles,tube feet,body wall,and spines.Therefore,tube feet were important for sea cucumbers to keep themselves stable in relatively swift flow with adhesion ability.
文摘Aim： To investigate the distribution of cation channel of sperm 1 （CATSPER1） protein and the presence of CATSPER1 mRNA in human testis and ejaculated spermatozoa. The influence of anti-human CATSPER1 antibody upon human sperm motility was used to evaluate the function of human CATSPER1 and to estimate its possible use as a target for immunocontraception. Methods： Human ejaculated sperm from normozoospermic donors （n = 12） and liquid nitrogen frozen human testis were used for the study of mRNA and protein expression of CATSPER1 by reverse transcription polymerase chain reaction （RT-PCR） and immunohistochemistry, respectively. Spermatozoa from normozoospermic donors （n = 12） were individually processed using a swim-up procedure and were then incubated with CATSPER1 antibody at final concentrations of 20, 4 and 0.8 μg/mL. After 1, 2 and 6 h incubation, progressive motility and fast progressive motility were measured by means of computer-assisted semen analysis. Results： CATSPER1 transcript was detected in both human testis and each human ejaculated semen sample. CATSPER1 protein expressed in the membrane of spermatid and was localized in the principal piece of the sperm tail. The application of CATSPER1 antibody at all concentrations significantly inhibited both progressive motility and fast progressive motility after 1, 2 and 6 h incubation, and significant dose-dependent changes were observed. Conclusion： CATSPER1 is meiotically and post-meiotically expressed in human testis tissue. CATSPER1 mRNA in human ejaculated spermatozoa could be a more feasible target for study and infertility screening than testis biopsy. In addition, our results suggest that human CATSPER1 could be a possible target for immunocontraception.
