AIM: To investigate the loss of heterozygosity (LOH) and mutation of tumor suppressor gene PTEN in gastric cancer and precancerous lesions. METHODS: Thirty cases of normal gastric mucosa, advanced and early stage gast...AIM: To investigate the loss of heterozygosity (LOH) and mutation of tumor suppressor gene PTEN in gastric cancer and precancerous lesions. METHODS: Thirty cases of normal gastric mucosa, advanced and early stage gastric cancer, intestinal metaplasia, atrophic gastritis, and atypical hyperplasia were analyzed for PTEN LOH and mutations within the entire coding region of PTEN gene by PCR-SSCP denaturing PAGE gel electrophoresis, and PTEN mutation was detected by PCR-SSCP sequencing followed by silver staining. RESULTS: LOH rate found in respectively atrophic gastritis was 10% (3/30), intestinal metaplasia 10% (3/30), atypical hyperplasia 13.3% (4/30), early stage gastric cancer 20% (6/30), and advanced stage gastric cancer 33.3% (9/30), None of the precancerous lesions and early stage gastric cancer showed PTEN mutations, but 10% (3/30) of the advanced stage gastric cancers, which were all positive for LOH, showed PTEN mutation. CONCLUSION: LOH of PTEN gene appears in precancerous lesions, and PTEN mutations are restricted to advanced gastric cancer, LOH and mutation of PTEN gene are closely related to the infiltration and metastasis of gastric cancer.展开更多
AIM: To evaluate the effects of nitroester drugs on human sphincter of Oddi (SO) motility and their antagonistic effects against morphine which shows excitatory effect on Oddi's sphincter motility.METHODS: The eff...AIM: To evaluate the effects of nitroester drugs on human sphincter of Oddi (SO) motility and their antagonistic effects against morphine which shows excitatory effect on Oddi's sphincter motility.METHODS: The effects of these drugs on SO were evaluated by means of choledochofiberoscopy manometry.A total of 67 patients having T-tubes after cholecystectomy and choledochotomy were involved in the study, they were randomly divided into glyceryl trinitrate (GTN) group,isosorbide dinitrate (ISDN) group, pentaerythritol tetranitrate (PTN) group, morphine associated with GTN group, morphine associated with ISDN group and morphine associated with PTN group. Basal pressure of Oddi's sphincter (BPOS), amplitude of phasic contractions (SOCA), frequency of phasic contractions (SOF), duration of phasic contractions (SOD), duodenal pressure (DP) and common bile duct pressure (CBDP) were scored and analyzed. Morphine was given intramuscularly while nitroester drugs were applied sublingually.RESULTS: BPOS and SOCA decreased significantly after administration of ISDN and GTN, BPOS reduced from 10.95±7.49 mmHg to 5.92±4.04 mmHg (P＜0.05) evidently after application of PTN. BPOS increased from 7.37±5.58mmHg to 16.60±13.87 mmHg, SOCA increased from 54.09±38.37 mmHg to 100.70±43.51 mmHg, SOF increased from 7.15±3.20 mmHg to 10.38±2.93 mmHg and CBDP increased 3.75±1.95 mmHg to 10.49±8.21 mmHg (P＜0.01)evidently after injection of morphine. After associated application of ISDN and GTN, the four indications above decreased obviously. As for application associated with PTN,SOCA and SOF decreased separately from 100.64±44.99mmHg to 66.17±35.88 mmHg and from 10.70±2.76 mmHg to 9.04±1.71 mmHg (P＜0.05) markedly.CONCLUSION: The regular dose of GTN, ISDN and PTN showed inhibitory effect on SO motility, morphine showed excitatory effect on SO while GTN, ISDN and PTN could antagonize the effect of morphine. Among the three nitroester drugs, the effect of ISDN on SO was most significant.展开更多
Dear Editor,Base editors can achieve targeted C-to-T and A-to-G conversion without the generation of DNA double-strand breaks(DSBs)or the requirement of a donor template,showing the potential to generate new mutations...Dear Editor,Base editors can achieve targeted C-to-T and A-to-G conversion without the generation of DNA double-strand breaks(DSBs)or the requirement of a donor template,showing the potential to generate new mutations or to correct pathogenic mutations(Gaudelli et al.,2018).However,for conventional base editors,efficient base editing requires the presence of an NGG protospacer adjacent motif(PAM)that lies 12–16 nt downstream of the target bases,which generally limits the application of these base editors(Gaudelli et al.,2018).展开更多
Regional sea level variability is linked to regional terrestrial water and the El Ni?o-Southern Oscillation(ENSO).This study assessed the relationships between the sea level variations in the South China Sea(SCS)and E...Regional sea level variability is linked to regional terrestrial water and the El Ni?o-Southern Oscillation(ENSO).This study assessed the relationships between the sea level variations in the South China Sea(SCS)and ENSO,the impact of terrestrial water storage(TWS)on non-steric sea level(NSSL),and the contributions of steric sea level(SSL)and NSSL to sea level anomaly(SLA),respectively.From 2003 to 2015,the SLAs exhibited a long-term trend of 6.65±0.78 mm/yr,which was primarily attributed to the SSLs.Additionally,during 2003-2015,ENSO events alternating with varying intensities might also be responsible for the unusually high SLA trend.Compared to the SSLs,the NSSLs contributed the seasonal signals to the SLAs,while the NSSLs changes were largely explained by the TWS in the Mekong River Basin at the seasonal scale and in the Pearl River Basin and Red River Basin at other time scales.In contrast to the TWS,the contributions of precipitation and evapotranspiration were relatively minor.A negative correlation between the sea level variations and ENSO was also found,with cross-correlation coefficients between the oceanic Ni?o index and SLAs/SSLs/NSSLs of -0.36/-0.37/-0.62 with lags of 2/3/2 months,respectively.These findings systematically reassessed the contributions of different components to the sea level variations.This study provided a benchmark for in-depth analysis of the impacts of terrestrial water and other potential causes on sea level rise in the SCS.展开更多
Top-down attention mechanisms require the selection of specificobjects or locations;however,the brain mechanism involved when attention is allocated across different modalities is not well understood.The aim of this s...Top-down attention mechanisms require the selection of specificobjects or locations;however,the brain mechanism involved when attention is allocated across different modalities is not well understood.The aim of this study was to use functional magnetic resonance imaging to define the neural mechanisms underlyingdivided and selective spatial attention.A concurrent audiovisual stimulus was used,and subjects were prompted to focus on a visual,auditory and audiovisual stimulus in a Posner paradigm.Ourbehavioral results confirmed the better performance of selectiveattention compared to devided attention.We found differences in the activation level of the frontoparietal network,visual/auditorycortex,the putamen and the salience network under differentattention conditions.We further used Granger causality(GC)toexplore effective connectivity differences between tasks.Differences in GC connectivity between visual and auditory selective tasksreflected the visual dominance effect under spatial attention.In addition,our results supported the role of the putamen inredistributing attention and the functional separation of the saliencenetwork.In summary,we explored the audiovisual top-down allocation of attention and observed the differences in neuralmechanisms under endogenous attention modes,which revealedthe differences in cross-modal expression in visual and auditory attention under attentional modulation.展开更多
The urgent need for effective cancer treatments,particularly for advanced and relapsed cases in which standard therapies are inadequate,has spurred the development of innovative therapeutic drugs1,2.Among the strategi...The urgent need for effective cancer treatments,particularly for advanced and relapsed cases in which standard therapies are inadequate,has spurred the development of innovative therapeutic drugs1,2.Among the strategies to expedite drug development,the use of single-arm trials(SATs)is emerging as a promising avenue with substantial potential to shorten drug approval timelines and accelerate market entry.展开更多
We present a novel method to rapidly assess drug efficacy in targeted cancer therapy,where antineoplastic agents are conjugated to antibodies targeting surface markers on tumor cells.We have fabricated and characteriz...We present a novel method to rapidly assess drug efficacy in targeted cancer therapy,where antineoplastic agents are conjugated to antibodies targeting surface markers on tumor cells.We have fabricated and characterized a device capable of rapidly assessing tumor cell sensitivity to drugs using multifrequency impedance spectroscopy in combination with supervised machine learning for enhanced classification accuracy.Currently commercially available devices for the automated analysis of cell viability are based on staining,which fundamentally limits the subsequent characterization of these cells as well as downstream molecular analysis.Our approach requires as little as 20μL of volume and avoids staining allowing for further downstream molecular analysis.To the best of our knowledge,this manuscript presents the first comprehensive attempt to using high-dimensional data and supervised machine learning,particularly phase change spectra obtained from multi-frequency impedance cytometry as features for the support vector machine classifier,to assess viability of cells without staining or labelling.展开更多
Background A crucial element of human-machine interaction,the automatic detection of emotional states from human speech has long been regarded as a challenging task for machine learning models.One vital challenge in s...Background A crucial element of human-machine interaction,the automatic detection of emotional states from human speech has long been regarded as a challenging task for machine learning models.One vital challenge in speech emotion recognition(SER)is learning robust and discriminative representations from speech.Although machine learning methods have been widely applied in SER research,the inadequate amount of available annotated data has become a bottleneck impeding the extended application of such techniques(e.g.,deep neural networks).To address this issue,we present a deep learning method that combines knowledge transfer and self-attention for SER tasks.Herein,we apply the log-Mel spectrogram with deltas and delta-deltas as inputs.Moreover,given that emotions are time dependent,we apply temporal convolutional neural networks to model the variations in emotions.We further introduce an attention transfer mechanism,which is based on a self-attention algorithm to learn long-term dependencies.The self-attention transfer network(SATN)in our proposed approach takes advantage of attention transfer to learn attention from speech recognition,followed by transferring this knowledge into SER.An evaluation built on Interactive Emotional Dyadic Motion Capture(IEMOCAP)dataset demonstrates the effectiveness of the proposed model.展开更多
The RNA interference(RNAi)phenomenon is a recently observed process in which the introduction of a double-stranded,small interfering RNA(siRNA)into a cell causes the specific degradation of a homologous single-strande...The RNA interference(RNAi)phenomenon is a recently observed process in which the introduction of a double-stranded,small interfering RNA(siRNA)into a cell causes the specific degradation of a homologous single-stranded RNA.It represents an exciting new technology that could have therapeutic applications for the treatment of viral infections.Since hepatitis G virus(HGV)genome is a positive-sense single-stranded RNA,the replication of HGV does not lead to an integrated DNA genome,suggesting a particularly attractive target for RNAi study that could eliminate viral RNA from infected cells.The eukaryotic expression vector pVAX.EH containing the cDNA sequences of the entire HGV structural genes and hygromycin resistance gene downstream from the encephalomyocarditis virus(ECMV)internal ribosome entry site(IRES)was constructed and transfected into human hepatoma cell Huh-7.The modified cleavage products of the structural proteins of HGV expressed in hygromycin-resistant cell line Huh-7-EH were confirmed by RT-PCR and Western blot methods.Two specific HGV E2 siRNAs(1-E2siRNA,2-E2 siRNA)synthesized with T7 RNA polymerase by transcription in vitro were transfected into the Huh-7-EH cells.With the analyses of Western blot and the formation of hygromycin-resistant colonies,the inhibitions of expression of HGV structural protein by two HGV E2siRNAs were detected and found lasting at least one week.The inhibition of 2-E2 siRNA was stronger and only 1%of the cells treated with 2-E2 siRNA formed hygromycin-resistant colonies.These results support that specific HGV 2-E2 siRNAs mediate the degradation of mRNA spanning from HGV structural gene cDNA to hygromycin resistance gene in a majority of cells.In conclusion,the Huh-7-EH cells expressing HGV structural proteins stably can be used as a cell model for studying the replication of HGV and RNAi and the enlargement of RNAi may exist,in mammalian cells.展开更多
X65 low carbon steel was exposed to Co-60 radiation source with 1.25 MeV gamma rays, and cumulatively absorbed gamma irradiation doses（1, 2, and 3 Mgy） were obtained after different exposure time（333, 667, and 100...X65 low carbon steel was exposed to Co-60 radiation source with 1.25 MeV gamma rays, and cumulatively absorbed gamma irradiation doses（1, 2, and 3 Mgy） were obtained after different exposure time（333, 667, and 1000 h）. The effect of cumulative gamma irradiation on microstructure and corrosion behaviour of the carbon steel in unirradiated aerobic Beishan groundwater at 25℃ was investigated by using positron annihilation, scanning vibrating electrode, and electrochemical techniques. Cumulative gamma irradiation increases vacancy intensity and decreases open circuit potential（OCP） of carbon steel. They indicate that the irradiated carbon steel is activated. Measured current density distribution above the irradiated carbon steel shows that cumulative gamma irradiation accelerates localized corrosion after 0.5 h of immersion. In contrast, the analysis of electrochemical impedance spectroscopy of the irradiated carbon steel indicates that localized corrosion is transformed into general corrosion after 12 h of immersion, which is also accelerated by cumulative gamma irradiation.展开更多
The coronavirus disease 2019(COVID-19)pandemic caused by severe acute respiratory syndrome coronavirus 2(SARSCoV-2)is a global crisis.Clinical candidates with high efficacy,ready availability,and that do not develop r...The coronavirus disease 2019(COVID-19)pandemic caused by severe acute respiratory syndrome coronavirus 2(SARSCoV-2)is a global crisis.Clinical candidates with high efficacy,ready availability,and that do not develop resistance are in urgent need.Despite that screening to repurpose clinically approved drugs has provided a variety of hits shown to be effective against SARS-CoV-2 infection in cell culture,there are few confirmed antiviral candidates in vivo.In this study,94 compounds showing high antiviral activity against SARS-CoV-2 in Vero E6 cells were identified from 2,580 FDA-approved small-molecule drugs.Among them,24 compounds with low cytotoxicity were selected,and of these,17 compounds also effectively suppressed SARS-CoV-2 infection in He La cells transduced with human ACE2.Six compounds disturb multiple processes of the SARSCoV-2 life cycle.Their prophylactic efficacies were determined in vivo using Syrian hamsters challenged with SARS-CoV-2infection.Seven compounds reduced weight loss and promoted weight regain of hamsters infected not only with the original strain but also the D614G variant.Except for cisatracurium,six compounds reduced hamster pulmonary viral load,and IL-6 and TNF-αm RNAwhen assayed at 4 d postinfection.In particular,sertraline,salinomycin,and gilteritinib showed similar protective effects as remdesivir in vivo and did not induce antiviral drug resistance after 10 serial passages of SARS-CoV-2 in vitro,suggesting promising application for COVID-19 treatment.展开更多
2.98 kGy/h(1007 h) gamma irradiation and 90 ℃(2000 h) thermal aging were exerted to X65 grade low carbon steel buried in Gaomiaozi bentonite containing 17 wt% Beishan groundwater. The average corrosion rate of X65 lo...2.98 kGy/h(1007 h) gamma irradiation and 90 ℃(2000 h) thermal aging were exerted to X65 grade low carbon steel buried in Gaomiaozi bentonite containing 17 wt% Beishan groundwater. The average corrosion rate of X65 low carbon steel was measured. The elemental and phase distribution on cross section was characterized by using electron probe micro-analysis, high-resolution X-ray diffraction, and micro-X-ray diffraction. The following conclusions can be made: the average aerobic corrosion rate of the carbon steel is(45.16 ± 1.53) μm/year. Taking the original surface as boundary, the corrosion scale is divided into an internal dense product layer(DPL) mainly composed of Fe_3O_4 with segregated FeCO_3 at the corrosion front and an external DPL mainly composed of Fe_3O_4 with segregated α-Fe_2O_3 and bentonite at some relics.Si, S, and Cl are concentrated at the corrosion front of the internal DPL, while Si and Al are concentrated at the external DPL.展开更多
An efficient catalytic system consisting of vanadyl sulfate/sodium nitrite was disclosed previously for the oxidation of benzylic alcohols into aldehydes with molecular oxygen.However,the roles of catalyst components ...An efficient catalytic system consisting of vanadyl sulfate/sodium nitrite was disclosed previously for the oxidation of benzylic alcohols into aldehydes with molecular oxygen.However,the roles of catalyst components were not investigated.In this paper,we examined catalytic oxidation of benzyl alcohol as a model reaction,especially by infrared spectroscopy.The role of each component is discussed including nitrite,vanadyl,sulphate,and water.Sodium nitrite could be converted into nitrate and nitric acid.The vanadium(IV)could be smoothly oxidized into vanadium(V)under mild and acidic conditions without any organic ligands.The transformation of sulfate and bisulfate,the cessation of an induction period,and the oxidation of benzyl alcohol were closely interrelated.The multiple roles of water are discussed,including reduction of the induction period,participation in redox cycles of nitric compounds,deactivation of vanadium,and as a byproduct of oxidation.This study contributes to further development of aerobic oxidation using vanadium based catalysts.展开更多
Diet/sugar-free soft drinks are considered to be healthier than regular soft drinks.However,few studies have examined the relationship between the types of soft drinks(regular and diet/sugar-free)and lung cancer(LC)/a...Diet/sugar-free soft drinks are considered to be healthier than regular soft drinks.However,few studies have examined the relationship between the types of soft drinks(regular and diet/sugar-free)and lung cancer(LC)/all-cancer(AC)risk.In this study,we comprehensively assessed the influence of the type of soft drink consumption on LC/AC risk based on the Prostate,Lung,Colorectal,and Ovarian(PLCO)Cancer Screening Trial.Multivariable Cox proportional hazards and competing risks Fine-Gray regression models adjusted for relevant confounders were used to estimate hazard ratios(HRs)and subdistribution HRs for different types of soft drink consumption.In the PLCO population,female subgroup,and the ever/current smoker subgroup,consumption of both regular and diet soft drinks was associated with a significantly reduced risk of LC compared with no soft drinks at all.For the non-lung cancer(NLC)risk,consumption of only diet soft drinks had a significant positive association for the total population and female subgroup.Based on our findings,it was suggested that partial replacement of regular soft drinks with diet soft drinks might be beneficial to LC prevention,especially for females and ever/current smokers.Additionally,completely replacing regular soft drinks with diet soft drinks might be detrimental to NLC prevention,especially for females.展开更多
1 Introduction Interaction of radio-frequency wave with plasma in magnetic confinement devices has been a very important discipline of plasma physics. To approach more realistic description of wave-plasma interaction...1 Introduction Interaction of radio-frequency wave with plasma in magnetic confinement devices has been a very important discipline of plasma physics. To approach more realistic description of wave-plasma interaction in a time scale longer than the kinetic time scales bounce-average is needed. The long time evolution of the kinetic distribution can be treated by Fokker-Planck equation. The behavior of the plasma and the most interesting macroscopic effects are obtained by balancing the diffusion term with a collision term.展开更多
Loss-cone instabilities are studied for linear fusion devices. The gyro-kinetic equation for such a configuration is rigorously constructed in terms of action-angle variables by making use of canonical transformation....Loss-cone instabilities are studied for linear fusion devices. The gyro-kinetic equation for such a configuration is rigorously constructed in terms of action-angle variables by making use of canonical transformation. The dispersion relation, including for the first time, finite bounce frequency is obtained and numerically solved. The loss-cone modes are found near ion-cyclotron frequency. The growth rates are greatly reduced and approaching zero with increasing beta value. The results suggest that loss-cone instabilities are unlikely to be threatening to linear fusion devices since a new longitudinal invariant is found and gives a constraint which helps confinement.展开更多
Mitigation of ELMs by electrostatic field is studied. The perpendicular heating in cyclotron waves tends to pile up the resonant particles toward the low magnetic field side in which a electrostatic field may result [...Mitigation of ELMs by electrostatic field is studied. The perpendicular heating in cyclotron waves tends to pile up the resonant particles toward the low magnetic field side in which a electrostatic field may result [J. Y. Hsu, V. S. Chan, R. W. Harvey, R. Prater, and S. K. Wong, Phys. Rev. Lett. 53, 564 (1984)]. The electrostatic field can make circulating particles trapped or make trapped particles circulating depending on the field direction. The trapped- particle population and bootstrap current change accordantly. Modulating bootstrap current, mitigation of type-1 ELM by the electrostatic field is possible. The electrostatic potential needed for the mitigation is quantitatively estimated. Experiments by either ECRH or biasing are being prepared to verify the theory.展开更多
Editor's note: The exhibition 'Impressionist Masterpieces from France's National Collections', which marks the start of the Year of France in China, debuted in Beijing in October 2004 and moved on to S...Editor's note: The exhibition 'Impressionist Masterpieces from France's National Collections', which marks the start of the Year of France in China, debuted in Beijing in October 2004 and moved on to Shanghai and Hong Kong after six weeks in the Chinese capital. The exhibits consist of 51 masterpieces by major French impressionists, such as Claude Monet's series of paintings 'Waterlilies', Edgar Degas' series 'Ballet Dancers' and Pierre-August Renoir's series 'Women, Children.' This was the first large-scale exhibition of impressionist paintings ever displayed in China.展开更多
1 Introduction Internal kink mode driven by the supra-thermal electrons is reported on DⅢ-D tokamak. This instability is most active when electron cyclotron current drive （ECCD） is applied on the high field side o...1 Introduction Internal kink mode driven by the supra-thermal electrons is reported on DⅢ-D tokamak. This instability is most active when electron cyclotron current drive （ECCD） is applied on the high field side of the flux surface. It has a bursting behavior with poloidal/toroidal mode number=n/n=1/1. In positive magnetic shear plasma this mode becomes fishbone instability. The mode frequency is about 10 kHz. Strong m=1 MHD activities are also observed in HL-IM tokamak during off-axis electron cyclotron resonance heating （ECRH） when the cyclotron location is placed just outside the q= 1 flux surface at high field side .展开更多
1 Introduction Internal kink mode driven by barely trapped suprakthermal electrons is reported on D Ⅲ-D tokama . This instability is most active when electron cyclotron current drive （ ECCD ） is applied on the hi...1 Introduction Internal kink mode driven by barely trapped suprakthermal electrons is reported on D Ⅲ-D tokama . This instability is most active when electron cyclotron current drive （ ECCD ） is applied on the high field side of the flux surface. It has a bursting behavior with poloidal/toroidal mode number m/n = 1/1. In positive magnetic shear plasma this mode becomes fishbone instability.展开更多
基金Supported by the National Natural Science Foundation of China,No. 30070845
文摘AIM: To investigate the loss of heterozygosity (LOH) and mutation of tumor suppressor gene PTEN in gastric cancer and precancerous lesions. METHODS: Thirty cases of normal gastric mucosa, advanced and early stage gastric cancer, intestinal metaplasia, atrophic gastritis, and atypical hyperplasia were analyzed for PTEN LOH and mutations within the entire coding region of PTEN gene by PCR-SSCP denaturing PAGE gel electrophoresis, and PTEN mutation was detected by PCR-SSCP sequencing followed by silver staining. RESULTS: LOH rate found in respectively atrophic gastritis was 10% (3/30), intestinal metaplasia 10% (3/30), atypical hyperplasia 13.3% (4/30), early stage gastric cancer 20% (6/30), and advanced stage gastric cancer 33.3% (9/30), None of the precancerous lesions and early stage gastric cancer showed PTEN mutations, but 10% (3/30) of the advanced stage gastric cancers, which were all positive for LOH, showed PTEN mutation. CONCLUSION: LOH of PTEN gene appears in precancerous lesions, and PTEN mutations are restricted to advanced gastric cancer, LOH and mutation of PTEN gene are closely related to the infiltration and metastasis of gastric cancer.
文摘AIM: To evaluate the effects of nitroester drugs on human sphincter of Oddi (SO) motility and their antagonistic effects against morphine which shows excitatory effect on Oddi's sphincter motility.METHODS: The effects of these drugs on SO were evaluated by means of choledochofiberoscopy manometry.A total of 67 patients having T-tubes after cholecystectomy and choledochotomy were involved in the study, they were randomly divided into glyceryl trinitrate (GTN) group,isosorbide dinitrate (ISDN) group, pentaerythritol tetranitrate (PTN) group, morphine associated with GTN group, morphine associated with ISDN group and morphine associated with PTN group. Basal pressure of Oddi's sphincter (BPOS), amplitude of phasic contractions (SOCA), frequency of phasic contractions (SOF), duration of phasic contractions (SOD), duodenal pressure (DP) and common bile duct pressure (CBDP) were scored and analyzed. Morphine was given intramuscularly while nitroester drugs were applied sublingually.RESULTS: BPOS and SOCA decreased significantly after administration of ISDN and GTN, BPOS reduced from 10.95±7.49 mmHg to 5.92±4.04 mmHg (P＜0.05) evidently after application of PTN. BPOS increased from 7.37±5.58mmHg to 16.60±13.87 mmHg, SOCA increased from 54.09±38.37 mmHg to 100.70±43.51 mmHg, SOF increased from 7.15±3.20 mmHg to 10.38±2.93 mmHg and CBDP increased 3.75±1.95 mmHg to 10.49±8.21 mmHg (P＜0.01)evidently after injection of morphine. After associated application of ISDN and GTN, the four indications above decreased obviously. As for application associated with PTN,SOCA and SOF decreased separately from 100.64±44.99mmHg to 66.17±35.88 mmHg and from 10.70±2.76 mmHg to 9.04±1.71 mmHg (P＜0.05) markedly.CONCLUSION: The regular dose of GTN, ISDN and PTN showed inhibitory effect on SO motility, morphine showed excitatory effect on SO while GTN, ISDN and PTN could antagonize the effect of morphine. Among the three nitroester drugs, the effect of ISDN on SO was most significant.
基金supported by the National Key Research and Development Program of China Stem Cell and Translational Research(2019YFA0110700)the National Natural Science Foundation of China(32000359)。
文摘Dear Editor,Base editors can achieve targeted C-to-T and A-to-G conversion without the generation of DNA double-strand breaks(DSBs)or the requirement of a donor template,showing the potential to generate new mutations or to correct pathogenic mutations(Gaudelli et al.,2018).However,for conventional base editors,efficient base editing requires the presence of an NGG protospacer adjacent motif(PAM)that lies 12–16 nt downstream of the target bases,which generally limits the application of these base editors(Gaudelli et al.,2018).
基金supported by the Natural Science Foundation of Hubei Province,China(Grant No.2022CFB064)the National Natural Science Foundation of China(Grant Nos.41974003&41674007)。
文摘Regional sea level variability is linked to regional terrestrial water and the El Ni?o-Southern Oscillation(ENSO).This study assessed the relationships between the sea level variations in the South China Sea(SCS)and ENSO,the impact of terrestrial water storage(TWS)on non-steric sea level(NSSL),and the contributions of steric sea level(SSL)and NSSL to sea level anomaly(SLA),respectively.From 2003 to 2015,the SLAs exhibited a long-term trend of 6.65±0.78 mm/yr,which was primarily attributed to the SSLs.Additionally,during 2003-2015,ENSO events alternating with varying intensities might also be responsible for the unusually high SLA trend.Compared to the SSLs,the NSSLs contributed the seasonal signals to the SLAs,while the NSSLs changes were largely explained by the TWS in the Mekong River Basin at the seasonal scale and in the Pearl River Basin and Red River Basin at other time scales.In contrast to the TWS,the contributions of precipitation and evapotranspiration were relatively minor.A negative correlation between the sea level variations and ENSO was also found,with cross-correlation coefficients between the oceanic Ni?o index and SLAs/SSLs/NSSLs of -0.36/-0.37/-0.62 with lags of 2/3/2 months,respectively.These findings systematically reassessed the contributions of different components to the sea level variations.This study provided a benchmark for in-depth analysis of the impacts of terrestrial water and other potential causes on sea level rise in the SCS.
基金The study was supported by the National Natural Science Foundation of China(Grant Nos.62171300,61727807).
文摘Top-down attention mechanisms require the selection of specificobjects or locations;however,the brain mechanism involved when attention is allocated across different modalities is not well understood.The aim of this study was to use functional magnetic resonance imaging to define the neural mechanisms underlyingdivided and selective spatial attention.A concurrent audiovisual stimulus was used,and subjects were prompted to focus on a visual,auditory and audiovisual stimulus in a Posner paradigm.Ourbehavioral results confirmed the better performance of selectiveattention compared to devided attention.We found differences in the activation level of the frontoparietal network,visual/auditorycortex,the putamen and the salience network under differentattention conditions.We further used Granger causality(GC)toexplore effective connectivity differences between tasks.Differences in GC connectivity between visual and auditory selective tasksreflected the visual dominance effect under spatial attention.In addition,our results supported the role of the putamen inredistributing attention and the functional separation of the saliencenetwork.In summary,we explored the audiovisual top-down allocation of attention and observed the differences in neuralmechanisms under endogenous attention modes,which revealedthe differences in cross-modal expression in visual and auditory attention under attentional modulation.
基金supported by grants from the China Society for Drug Regulation(Grant No.2023-Y-Y-002)。
文摘The urgent need for effective cancer treatments,particularly for advanced and relapsed cases in which standard therapies are inadequate,has spurred the development of innovative therapeutic drugs1,2.Among the strategies to expedite drug development,the use of single-arm trials(SATs)is emerging as a promising avenue with substantial potential to shorten drug approval timelines and accelerate market entry.
基金This work was funded by the PhRMA foundation,the National Science Foundation IDBR award grant no.1556253the National Science Foundation CAREER award grant no.1846740 awarded to MJ and the Breast Cancer Research Foundation grant awarded to JRB.
文摘We present a novel method to rapidly assess drug efficacy in targeted cancer therapy,where antineoplastic agents are conjugated to antibodies targeting surface markers on tumor cells.We have fabricated and characterized a device capable of rapidly assessing tumor cell sensitivity to drugs using multifrequency impedance spectroscopy in combination with supervised machine learning for enhanced classification accuracy.Currently commercially available devices for the automated analysis of cell viability are based on staining,which fundamentally limits the subsequent characterization of these cells as well as downstream molecular analysis.Our approach requires as little as 20μL of volume and avoids staining allowing for further downstream molecular analysis.To the best of our knowledge,this manuscript presents the first comprehensive attempt to using high-dimensional data and supervised machine learning,particularly phase change spectra obtained from multi-frequency impedance cytometry as features for the support vector machine classifier,to assess viability of cells without staining or labelling.
基金the National Natural Science Foundation of China(62071330)the National Science Fund for Distinguished Young Scholars(61425017)+3 种基金the Key Program of the National Natural Science Foundation(61831022)the Key Program of the Natural Science Foundation of Tianjin(18JCZDJC36300)the Open Projects Program of the National Laboratory of Pattern Recognition and the Senior Visiting Scholar Program of Tianjin Normal Universitythe Innovative Medicines Initiative 2 Joint Undertaking(115902),which receives support from the European Union's Horizon 2020 research and innovation program and EFPIA.
文摘Background A crucial element of human-machine interaction,the automatic detection of emotional states from human speech has long been regarded as a challenging task for machine learning models.One vital challenge in speech emotion recognition(SER)is learning robust and discriminative representations from speech.Although machine learning methods have been widely applied in SER research,the inadequate amount of available annotated data has become a bottleneck impeding the extended application of such techniques(e.g.,deep neural networks).To address this issue,we present a deep learning method that combines knowledge transfer and self-attention for SER tasks.Herein,we apply the log-Mel spectrogram with deltas and delta-deltas as inputs.Moreover,given that emotions are time dependent,we apply temporal convolutional neural networks to model the variations in emotions.We further introduce an attention transfer mechanism,which is based on a self-attention algorithm to learn long-term dependencies.The self-attention transfer network(SATN)in our proposed approach takes advantage of attention transfer to learn attention from speech recognition,followed by transferring this knowledge into SER.An evaluation built on Interactive Emotional Dyadic Motion Capture(IEMOCAP)dataset demonstrates the effectiveness of the proposed model.
基金This work was supported by the National Basic Research(973)Progrum of China(No.2003CB514129)the National INatural Science Foundation of China(Grant No.30170514).
文摘The RNA interference(RNAi)phenomenon is a recently observed process in which the introduction of a double-stranded,small interfering RNA(siRNA)into a cell causes the specific degradation of a homologous single-stranded RNA.It represents an exciting new technology that could have therapeutic applications for the treatment of viral infections.Since hepatitis G virus(HGV)genome is a positive-sense single-stranded RNA,the replication of HGV does not lead to an integrated DNA genome,suggesting a particularly attractive target for RNAi study that could eliminate viral RNA from infected cells.The eukaryotic expression vector pVAX.EH containing the cDNA sequences of the entire HGV structural genes and hygromycin resistance gene downstream from the encephalomyocarditis virus(ECMV)internal ribosome entry site(IRES)was constructed and transfected into human hepatoma cell Huh-7.The modified cleavage products of the structural proteins of HGV expressed in hygromycin-resistant cell line Huh-7-EH were confirmed by RT-PCR and Western blot methods.Two specific HGV E2 siRNAs(1-E2siRNA,2-E2 siRNA)synthesized with T7 RNA polymerase by transcription in vitro were transfected into the Huh-7-EH cells.With the analyses of Western blot and the formation of hygromycin-resistant colonies,the inhibitions of expression of HGV structural protein by two HGV E2siRNAs were detected and found lasting at least one week.The inhibition of 2-E2 siRNA was stronger and only 1%of the cells treated with 2-E2 siRNA formed hygromycin-resistant colonies.These results support that specific HGV 2-E2 siRNAs mediate the degradation of mRNA spanning from HGV structural gene cDNA to hygromycin resistance gene in a majority of cells.In conclusion,the Huh-7-EH cells expressing HGV structural proteins stably can be used as a cell model for studying the replication of HGV and RNAi and the enlargement of RNAi may exist,in mammalian cells.
基金supported by Key Research Program of Frontier Sciences,Chinese Academy of Sciences[QYZDY-SSWJSC012]National Natural Science Foundation[No.51771211]+1 种基金the National Key Research and Development Program of China[2017YFB0702100,2016YFE0105200]Key Program of the Chinese Academy of Sciences[ZDRW-CN-2017-1]
文摘X65 low carbon steel was exposed to Co-60 radiation source with 1.25 MeV gamma rays, and cumulatively absorbed gamma irradiation doses（1, 2, and 3 Mgy） were obtained after different exposure time（333, 667, and 1000 h）. The effect of cumulative gamma irradiation on microstructure and corrosion behaviour of the carbon steel in unirradiated aerobic Beishan groundwater at 25℃ was investigated by using positron annihilation, scanning vibrating electrode, and electrochemical techniques. Cumulative gamma irradiation increases vacancy intensity and decreases open circuit potential（OCP） of carbon steel. They indicate that the irradiated carbon steel is activated. Measured current density distribution above the irradiated carbon steel shows that cumulative gamma irradiation accelerates localized corrosion after 0.5 h of immersion. In contrast, the analysis of electrochemical impedance spectroscopy of the irradiated carbon steel indicates that localized corrosion is transformed into general corrosion after 12 h of immersion, which is also accelerated by cumulative gamma irradiation.
基金supported by the National Natural Science Foundation of China(31570170)the National Key Research and Development Program of China(2016YFC1200401)。
文摘The coronavirus disease 2019(COVID-19)pandemic caused by severe acute respiratory syndrome coronavirus 2(SARSCoV-2)is a global crisis.Clinical candidates with high efficacy,ready availability,and that do not develop resistance are in urgent need.Despite that screening to repurpose clinically approved drugs has provided a variety of hits shown to be effective against SARS-CoV-2 infection in cell culture,there are few confirmed antiviral candidates in vivo.In this study,94 compounds showing high antiviral activity against SARS-CoV-2 in Vero E6 cells were identified from 2,580 FDA-approved small-molecule drugs.Among them,24 compounds with low cytotoxicity were selected,and of these,17 compounds also effectively suppressed SARS-CoV-2 infection in He La cells transduced with human ACE2.Six compounds disturb multiple processes of the SARSCoV-2 life cycle.Their prophylactic efficacies were determined in vivo using Syrian hamsters challenged with SARS-CoV-2infection.Seven compounds reduced weight loss and promoted weight regain of hamsters infected not only with the original strain but also the D614G variant.Except for cisatracurium,six compounds reduced hamster pulmonary viral load,and IL-6 and TNF-αm RNAwhen assayed at 4 d postinfection.In particular,sertraline,salinomycin,and gilteritinib showed similar protective effects as remdesivir in vivo and did not induce antiviral drug resistance after 10 serial passages of SARS-CoV-2 in vitro,suggesting promising application for COVID-19 treatment.
基金supported by Key Research Program of Frontier Sciences, Chinese Academy of Sciences (QYZDYSSWJSC012)the National Natural Science Foundation of China (No. 51771211)+1 种基金the National Key Research and Development Program of China (2017YFB0702100, 2016YFE0105200)Key Program of the Chinese Academy of Sciences (ZDRW-CN-2017-1)
文摘2.98 kGy/h(1007 h) gamma irradiation and 90 ℃(2000 h) thermal aging were exerted to X65 grade low carbon steel buried in Gaomiaozi bentonite containing 17 wt% Beishan groundwater. The average corrosion rate of X65 low carbon steel was measured. The elemental and phase distribution on cross section was characterized by using electron probe micro-analysis, high-resolution X-ray diffraction, and micro-X-ray diffraction. The following conclusions can be made: the average aerobic corrosion rate of the carbon steel is(45.16 ± 1.53) μm/year. Taking the original surface as boundary, the corrosion scale is divided into an internal dense product layer(DPL) mainly composed of Fe_3O_4 with segregated FeCO_3 at the corrosion front and an external DPL mainly composed of Fe_3O_4 with segregated α-Fe_2O_3 and bentonite at some relics.Si, S, and Cl are concentrated at the corrosion front of the internal DPL, while Si and Al are concentrated at the external DPL.
基金financially supported by the National Natural Science Foundation of China(21203180,21233008)
文摘An efficient catalytic system consisting of vanadyl sulfate/sodium nitrite was disclosed previously for the oxidation of benzylic alcohols into aldehydes with molecular oxygen.However,the roles of catalyst components were not investigated.In this paper,we examined catalytic oxidation of benzyl alcohol as a model reaction,especially by infrared spectroscopy.The role of each component is discussed including nitrite,vanadyl,sulphate,and water.Sodium nitrite could be converted into nitrate and nitric acid.The vanadium(IV)could be smoothly oxidized into vanadium(V)under mild and acidic conditions without any organic ligands.The transformation of sulfate and bisulfate,the cessation of an induction period,and the oxidation of benzyl alcohol were closely interrelated.The multiple roles of water are discussed,including reduction of the induction period,participation in redox cycles of nitric compounds,deactivation of vanadium,and as a byproduct of oxidation.This study contributes to further development of aerobic oxidation using vanadium based catalysts.
基金supported by the National Natural Science Foundation of China (Projects No. 82173620to Y.Z. and 82204156 to D.Y.)Priority Academic Program Development of Jiangsu Higher Education Institution
文摘Diet/sugar-free soft drinks are considered to be healthier than regular soft drinks.However,few studies have examined the relationship between the types of soft drinks(regular and diet/sugar-free)and lung cancer(LC)/all-cancer(AC)risk.In this study,we comprehensively assessed the influence of the type of soft drink consumption on LC/AC risk based on the Prostate,Lung,Colorectal,and Ovarian(PLCO)Cancer Screening Trial.Multivariable Cox proportional hazards and competing risks Fine-Gray regression models adjusted for relevant confounders were used to estimate hazard ratios(HRs)and subdistribution HRs for different types of soft drink consumption.In the PLCO population,female subgroup,and the ever/current smoker subgroup,consumption of both regular and diet soft drinks was associated with a significantly reduced risk of LC compared with no soft drinks at all.For the non-lung cancer(NLC)risk,consumption of only diet soft drinks had a significant positive association for the total population and female subgroup.Based on our findings,it was suggested that partial replacement of regular soft drinks with diet soft drinks might be beneficial to LC prevention,especially for females and ever/current smokers.Additionally,completely replacing regular soft drinks with diet soft drinks might be detrimental to NLC prevention,especially for females.
文摘1 Introduction Interaction of radio-frequency wave with plasma in magnetic confinement devices has been a very important discipline of plasma physics. To approach more realistic description of wave-plasma interaction in a time scale longer than the kinetic time scales bounce-average is needed. The long time evolution of the kinetic distribution can be treated by Fokker-Planck equation. The behavior of the plasma and the most interesting macroscopic effects are obtained by balancing the diffusion term with a collision term.
基金supported by the Natural Science Foundation for Young Scientists of China (No. 11605143)National Natural Science Foundation of China (Nos. 11575055,11261140327,11005035,11205053)+3 种基金the project,Plasma Confinement in the Advanced Magnetic Mirror (WX-2015-01-01)the Open Research Subject of the Key Laboratory of Advanced Computation in Xihua University (Nos. szjj2017-011 and szjj2017-012)the Young Scholarship Plan of Xihua University (No. 0220170201)the National Key Research and Development Program of China (No. 2017YFE0300405)
文摘Loss-cone instabilities are studied for linear fusion devices. The gyro-kinetic equation for such a configuration is rigorously constructed in terms of action-angle variables by making use of canonical transformation. The dispersion relation, including for the first time, finite bounce frequency is obtained and numerically solved. The loss-cone modes are found near ion-cyclotron frequency. The growth rates are greatly reduced and approaching zero with increasing beta value. The results suggest that loss-cone instabilities are unlikely to be threatening to linear fusion devices since a new longitudinal invariant is found and gives a constraint which helps confinement.
文摘Mitigation of ELMs by electrostatic field is studied. The perpendicular heating in cyclotron waves tends to pile up the resonant particles toward the low magnetic field side in which a electrostatic field may result [J. Y. Hsu, V. S. Chan, R. W. Harvey, R. Prater, and S. K. Wong, Phys. Rev. Lett. 53, 564 (1984)]. The electrostatic field can make circulating particles trapped or make trapped particles circulating depending on the field direction. The trapped- particle population and bootstrap current change accordantly. Modulating bootstrap current, mitigation of type-1 ELM by the electrostatic field is possible. The electrostatic potential needed for the mitigation is quantitatively estimated. Experiments by either ECRH or biasing are being prepared to verify the theory.
文摘Editor's note: The exhibition 'Impressionist Masterpieces from France's National Collections', which marks the start of the Year of France in China, debuted in Beijing in October 2004 and moved on to Shanghai and Hong Kong after six weeks in the Chinese capital. The exhibits consist of 51 masterpieces by major French impressionists, such as Claude Monet's series of paintings 'Waterlilies', Edgar Degas' series 'Ballet Dancers' and Pierre-August Renoir's series 'Women, Children.' This was the first large-scale exhibition of impressionist paintings ever displayed in China.
文摘1 Introduction Internal kink mode driven by the supra-thermal electrons is reported on DⅢ-D tokamak. This instability is most active when electron cyclotron current drive （ECCD） is applied on the high field side of the flux surface. It has a bursting behavior with poloidal/toroidal mode number=n/n=1/1. In positive magnetic shear plasma this mode becomes fishbone instability. The mode frequency is about 10 kHz. Strong m=1 MHD activities are also observed in HL-IM tokamak during off-axis electron cyclotron resonance heating （ECRH） when the cyclotron location is placed just outside the q= 1 flux surface at high field side .
基金Supported by National Natural Science Foundation of China （ 19885006, 10175020 and 10135020 ）
文摘1 Introduction Internal kink mode driven by barely trapped suprakthermal electrons is reported on D Ⅲ-D tokama . This instability is most active when electron cyclotron current drive （ ECCD ） is applied on the high field side of the flux surface. It has a bursting behavior with poloidal/toroidal mode number m/n = 1/1. In positive magnetic shear plasma this mode becomes fishbone instability.
