Background Shensong Yangxin （SSYX） is one of the compound recipe of Chinese materia medica. This study was conducted to investigate the effects of SSYX on sodium current （/Na）, L-type calcium current （/Ca.L）, tr...Background Shensong Yangxin （SSYX） is one of the compound recipe of Chinese materia medica. This study was conducted to investigate the effects of SSYX on sodium current （/Na）, L-type calcium current （/Ca.L）, transient outward potassium current （/to）, delayed rectifier current （/K）, and inward rectifier potassium currents （/K1） in isolated ventricular myocytes. Methods Whole cell patch-clamp technique was used to study ion channel currents in enzymatically isolated guinea pig or rat ventricular myocytes. Results SSYX decreased peak Na by （44.84±7.65）% from 27.21±5.35 to 14.88±2..75 pA/pF （n=-5, P〈0.05）. The medicine significantly inhibited the /Ca,L. At concentrations of 0.25, 0.50, and 1.00 g/100 ml, the peak/Ca,L was reduced by （19.22±1.10）%, （44.82±6.50）% and （50.69±5.64）%, respectively （n=5, all P〈0.05）. SSYX lifted the I-V curve of both /Na and /Ca,L without changing the threshold, peak and reversal potentials. At the concentration of 0.5%, the drug blocked the transient component of /to by 50.60% at membrane voltage of 60 mV and negatively shifted the inactive curve and delayed the recovery from channel inactivation. The tail current density of /K was decreased by （30.77±1.11）% （n=5, P〈0.05） at membrane voltage of 50 mV after exposure to the medicine and the time-dependent activity of /K was also inhibited. Similar to the effect on /K, the SSYX inhibited /K1 by 33.10% at the test potential of -100 mV with little effect on reversal potential and the rectification property. Conclusions The experiments revealed that SSYX could block multiple ion channels such as /Na /Ca,L, /k, /to and /K1, which may change the action potential duration and contribute to some of its antiarrhythmic effects.展开更多
BACKGROUND: Survivin is known to be overexpressed in various human malignancies, including pancreatic cancer, and mediates cancer cell proliferation and tumor growth, so the regulation of this molecule could be a new ...BACKGROUND: Survivin is known to be overexpressed in various human malignancies, including pancreatic cancer, and mediates cancer cell proliferation and tumor growth, so the regulation of this molecule could be a new strategy for treating pancreatic cancer. In this study, short hairpin RNAs (shRNAs) specific to survivin were introduced into human pancreatic cancer Patu8988 cells to investigate the inhibitory effects on survivin expression and cell proliferation in vitro and in vivo. METHODS: Three kinds of shRNA specific to the survivin gene were designed and cloned into eukaryotic expression plasmid pGenesil-1 vector. Subsequently the recombinant plasmids were transfected into human pancreatic cancer Patu8988 cells with lipfectamine (TM) 2000 reagent. The mRNA and protein expressions of survivin in the transiently transfected Patu8988 cells were determined by RT-PCR, flow cytometry, and Western blotting analysis. The proliferation inhibition rates of stably transfected Patu8988 cells were determined by MTT assay. The antitumor activities of the three kinds of survivin-shRNA plasmids were evaluated in BALB/c nude mice inoculated with Patu8988 cells and bearing human pancreatic cancer. RESULTS: The three survivin-shRNA plasmids named pGenesil-1-survivin-1, pGenesil-1-survivin-2 and pGenesil-1-survivin-1+2 (with double interfering RNA sites) were successfully constructed, and were confirmed by restriction enzyme cutting and sequencing. At 48 hours after transfection, the expression of survivin mRNA and protein was inhibited in Patu8988 cells transfected with pGenesil-1-survivin-1, pGenesil-1-survivin-2, and pGenesil-1-survivin-1+2 when compared with that of either pGenesil-1-NC (with scrambled small interfering RNA) transfected cells or control cells (P<0.05). The MTT results showed that the proliferation rates of Patu8988 cells stably transfected with survivin-shRNA plasmids were reduced when compared with that of either pGenesil-1-NC transfected cells or control cells (P<0.01). Furthermore, when Patu8988 cells st展开更多
Perceiving pitch is a central function of the human auditory system;congenital amusia is a disorder of pitch perception.The underlying neural mechanisms of congenital amusia have been actively discussed.However,little...Perceiving pitch is a central function of the human auditory system;congenital amusia is a disorder of pitch perception.The underlying neural mechanisms of congenital amusia have been actively discussed.However,little attention has been paid to the changes in the motor rain within congenital amusia.In this case-control study,17 participants with congenital amusia and 14 healthy controls underwent functional magnetic resonance imaging while resting with their eyes closed.A voxel-based degree centrality method was used to identify abnormal functional network centrality by comparing degree centrality values between the congenital amusia group and the healthy control group.We found decreased degree centrality values in the right primary sensorimotor areas in participants with congenital amusia relative to controls,indicating potentially decreased centrality of the corresponding brain regions in the auditory-sensory motor feedback network.We found a significant positive correlation between the degree centrality values and the Montreal Battery of Evaluation of Amusia scores.In conclusion,our study identified novel,hitherto undiscussed candidate brain regions that may partly contribute to or be modulated by congenital amusia.Our evidence supports the view that sensorimotor coupling plays an important role in memory and musical discrimination.The study was approved by the Ethics Committee of the Second Xiangya Hospital,Central South University,China(No.WDX20180101GZ01)on February 9,2019.展开更多
The twisted intramolecular charge transfer and the excited state relaxation of 1-aminoanthraquinone （1-NH2-AQ） in different solvents are investigated using quantum chemical calculations in this paper. The geometries...The twisted intramolecular charge transfer and the excited state relaxation of 1-aminoanthraquinone （1-NH2-AQ） in different solvents are investigated using quantum chemical calculations in this paper. The geometries of the ground state are optimized both in gas and solvents based on the high-level ab initio calculations, the lowest excited singlet state geometry is optimized only in gas for simplicity. An intramolecular charge transfer property is substantiated by the large change of dipole moments between the So and S1 states. The mechanism of twisted intramolecular charge transfer is proposed by the conformational relaxation on the potential surface of the $1 state. Quantum chemical calculations present that internal conversion and intersystem crossing are important approaches to the ultrafast deactivation of the S~ state via the twisting of the amino group, The smaller energy difference between the So and S1 state shows that the internal conversion process is much faster in a polar solvent than in a nonpolar solvent. Energy intersections between the T2 and S1 state in cyclohexane and dioxane indicate a faster intersystem crossing process in them than in ethanol. These theoretical results agree well with the previous experimental results. Energy barriers are predicted on the potential surface of the S1 state, and they have a positive correlation to solvent viscosity, and the timescale of twisted intra-molecular charge transfer in dioxane is predicted to be longer than in cyclohexane and ethanol.展开更多
A new data assimilation algorithm （Quasi- EnKF） in ocean modeling, based on the Ensemble Kalman Filter scheme, is proposed in this paper. This algorithm assimilates not only surface measurements （sea surface height...A new data assimilation algorithm （Quasi- EnKF） in ocean modeling, based on the Ensemble Kalman Filter scheme, is proposed in this paper. This algorithm assimilates not only surface measurements （sea surface height）, but also deep （-2000 m） temperature observations from the Gulf of Mexico into regional ocean models. With the use of the Princeton Ocean Model （POM）, integrated for approximately two years by assimilating both surface and deep observations, this new algorithm was compared to an existing assimilation algorithm （Mellor-Ezer Scheme） at different resolutions. The results show that, by comparing the observations, the new algorithm out-performs the existing one.展开更多
文摘Background Shensong Yangxin （SSYX） is one of the compound recipe of Chinese materia medica. This study was conducted to investigate the effects of SSYX on sodium current （/Na）, L-type calcium current （/Ca.L）, transient outward potassium current （/to）, delayed rectifier current （/K）, and inward rectifier potassium currents （/K1） in isolated ventricular myocytes. Methods Whole cell patch-clamp technique was used to study ion channel currents in enzymatically isolated guinea pig or rat ventricular myocytes. Results SSYX decreased peak Na by （44.84±7.65）% from 27.21±5.35 to 14.88±2..75 pA/pF （n=-5, P〈0.05）. The medicine significantly inhibited the /Ca,L. At concentrations of 0.25, 0.50, and 1.00 g/100 ml, the peak/Ca,L was reduced by （19.22±1.10）%, （44.82±6.50）% and （50.69±5.64）%, respectively （n=5, all P〈0.05）. SSYX lifted the I-V curve of both /Na and /Ca,L without changing the threshold, peak and reversal potentials. At the concentration of 0.5%, the drug blocked the transient component of /to by 50.60% at membrane voltage of 60 mV and negatively shifted the inactive curve and delayed the recovery from channel inactivation. The tail current density of /K was decreased by （30.77±1.11）% （n=5, P〈0.05） at membrane voltage of 50 mV after exposure to the medicine and the time-dependent activity of /K was also inhibited. Similar to the effect on /K, the SSYX inhibited /K1 by 33.10% at the test potential of -100 mV with little effect on reversal potential and the rectification property. Conclusions The experiments revealed that SSYX could block multiple ion channels such as /Na /Ca,L, /k, /to and /K1, which may change the action potential duration and contribute to some of its antiarrhythmic effects.
基金supported by grants from the Social Bureau Foundation of Suzhou (SZD0614)the Foundation of Health Bureau of Jiangsu Province (Z200622)
文摘BACKGROUND: Survivin is known to be overexpressed in various human malignancies, including pancreatic cancer, and mediates cancer cell proliferation and tumor growth, so the regulation of this molecule could be a new strategy for treating pancreatic cancer. In this study, short hairpin RNAs (shRNAs) specific to survivin were introduced into human pancreatic cancer Patu8988 cells to investigate the inhibitory effects on survivin expression and cell proliferation in vitro and in vivo. METHODS: Three kinds of shRNA specific to the survivin gene were designed and cloned into eukaryotic expression plasmid pGenesil-1 vector. Subsequently the recombinant plasmids were transfected into human pancreatic cancer Patu8988 cells with lipfectamine (TM) 2000 reagent. The mRNA and protein expressions of survivin in the transiently transfected Patu8988 cells were determined by RT-PCR, flow cytometry, and Western blotting analysis. The proliferation inhibition rates of stably transfected Patu8988 cells were determined by MTT assay. The antitumor activities of the three kinds of survivin-shRNA plasmids were evaluated in BALB/c nude mice inoculated with Patu8988 cells and bearing human pancreatic cancer. RESULTS: The three survivin-shRNA plasmids named pGenesil-1-survivin-1, pGenesil-1-survivin-2 and pGenesil-1-survivin-1+2 (with double interfering RNA sites) were successfully constructed, and were confirmed by restriction enzyme cutting and sequencing. At 48 hours after transfection, the expression of survivin mRNA and protein was inhibited in Patu8988 cells transfected with pGenesil-1-survivin-1, pGenesil-1-survivin-2, and pGenesil-1-survivin-1+2 when compared with that of either pGenesil-1-NC (with scrambled small interfering RNA) transfected cells or control cells (P<0.05). The MTT results showed that the proliferation rates of Patu8988 cells stably transfected with survivin-shRNA plasmids were reduced when compared with that of either pGenesil-1-NC transfected cells or control cells (P<0.01). Furthermore, when Patu8988 cells st
基金supported by the National Natural Science Foundation of China,No.81771172(to DXW),81671671(to JL)the Second Xiangya Hospital Start-Up Fund,China。
文摘Perceiving pitch is a central function of the human auditory system;congenital amusia is a disorder of pitch perception.The underlying neural mechanisms of congenital amusia have been actively discussed.However,little attention has been paid to the changes in the motor rain within congenital amusia.In this case-control study,17 participants with congenital amusia and 14 healthy controls underwent functional magnetic resonance imaging while resting with their eyes closed.A voxel-based degree centrality method was used to identify abnormal functional network centrality by comparing degree centrality values between the congenital amusia group and the healthy control group.We found decreased degree centrality values in the right primary sensorimotor areas in participants with congenital amusia relative to controls,indicating potentially decreased centrality of the corresponding brain regions in the auditory-sensory motor feedback network.We found a significant positive correlation between the degree centrality values and the Montreal Battery of Evaluation of Amusia scores.In conclusion,our study identified novel,hitherto undiscussed candidate brain regions that may partly contribute to or be modulated by congenital amusia.Our evidence supports the view that sensorimotor coupling plays an important role in memory and musical discrimination.The study was approved by the Ethics Committee of the Second Xiangya Hospital,Central South University,China(No.WDX20180101GZ01)on February 9,2019.
基金Project supported by the Program of Outstanding Innovation Team of Hubei Normal University,China(Grant No.T201502)the Natural Science Foundation of Hubei Province,China(Grant Nos.2014CFB349 and 2016CFC742)the National Natural Science Foundation of China(Grant No.11674355)
文摘The twisted intramolecular charge transfer and the excited state relaxation of 1-aminoanthraquinone （1-NH2-AQ） in different solvents are investigated using quantum chemical calculations in this paper. The geometries of the ground state are optimized both in gas and solvents based on the high-level ab initio calculations, the lowest excited singlet state geometry is optimized only in gas for simplicity. An intramolecular charge transfer property is substantiated by the large change of dipole moments between the So and S1 states. The mechanism of twisted intramolecular charge transfer is proposed by the conformational relaxation on the potential surface of the $1 state. Quantum chemical calculations present that internal conversion and intersystem crossing are important approaches to the ultrafast deactivation of the S~ state via the twisting of the amino group, The smaller energy difference between the So and S1 state shows that the internal conversion process is much faster in a polar solvent than in a nonpolar solvent. Energy intersections between the T2 and S1 state in cyclohexane and dioxane indicate a faster intersystem crossing process in them than in ethanol. These theoretical results agree well with the previous experimental results. Energy barriers are predicted on the potential surface of the S1 state, and they have a positive correlation to solvent viscosity, and the timescale of twisted intra-molecular charge transfer in dioxane is predicted to be longer than in cyclohexane and ethanol.
文摘A new data assimilation algorithm （Quasi- EnKF） in ocean modeling, based on the Ensemble Kalman Filter scheme, is proposed in this paper. This algorithm assimilates not only surface measurements （sea surface height）, but also deep （-2000 m） temperature observations from the Gulf of Mexico into regional ocean models. With the use of the Princeton Ocean Model （POM）, integrated for approximately two years by assimilating both surface and deep observations, this new algorithm was compared to an existing assimilation algorithm （Mellor-Ezer Scheme） at different resolutions. The results show that, by comparing the observations, the new algorithm out-performs the existing one.
