The rhizome of Gastrodia elata(GE), a herb medicine, has been used for treatment of neuronal disorders in Eastern Asia for hundreds of years. Parishin C is a major ingredient of GE. In this study, the i.c.v. injection...The rhizome of Gastrodia elata(GE), a herb medicine, has been used for treatment of neuronal disorders in Eastern Asia for hundreds of years. Parishin C is a major ingredient of GE. In this study, the i.c.v. injection of soluble Aβ1–42oligomers model of LTP injury was used. We investigated the effects of parishin C on the improvement of LTP in soluble Aβ1–42oligomer–injected rats and the underlying electrophysiological mechanisms. Parishin C(i.p. or i.c.v.) significantly ameliorated LTP impairment induced by i.c.v. injection of soluble Aβ1–42oligomers. In cultured hippocampal neurons,soluble Aβ1–42oligomers significantly inhibited NMDAR currents while not affecting AMPAR currents and voltage-dependent currents. Pretreatment with parishin C protected NMDA receptor currents from the damage induced by Aβ. In summary, parishin C improved LTP deficits induced by soluble Aβ1–42oligomers. The protection by parishin C against Aβ-induced LTP damage might be related to NMDA receptors.展开更多
Chiglitazar(Carfloglitazar)is a novel peroxisome proliferator-activated receptor(PPAR)pan-agonist that has shown promising effects on glycemic control and lipid regulation in patients with type 2 diabetes.In this rand...Chiglitazar(Carfloglitazar)is a novel peroxisome proliferator-activated receptor(PPAR)pan-agonist that has shown promising effects on glycemic control and lipid regulation in patients with type 2 diabetes.In this randomized phase 3 trial,we compared the efficacy and safety of chiglitazar with sitagliptin in patients with type 2 diabetes who had insufficient glycemic control despite a strict diet and exercise regimen.Eligible patients were randomized(1:1:1)to receive chiglitazar 32 mg(n=245),chiglitazar 48 mg(n=246),or sitagliptin 100 mg(n=248)once daily for 24 weeks.The primary endpoint was the change in glycosylated hemoglobin A_(1C)(HbA_(1c))from baseline at week 24 with the non-inferiority of chiglitazar over sitagliptin.Both chiglitazar and sitagliptin significantly reduced HbA1c at week 24 with values of-1.40%,-1.47%,and-1.39%for chiglitazar 32 mg,chiglitazar 48 mg,and sitagliptin 100 mg,respectively.Chiglitazar 32 and 48 mg were both non-inferior to sitagliptin 100 mg,with mean differences of-0.04%(95%confidential interval(Cl)-0.22 to 0.15)and-0.08%(95%Cl-0.27 to 0.10),respectively.Compared with sitagliptin,greater reduction in fasting and 2-h postprandial plasma glucose and fasting insulin was observed with chiglitazar.Overall adverse event rates were similar between the groups.A small increase in mild edema in the chiglitazar 48 mg group and slight weight gain in both chiglitazar groups were reported.The overall results demonstrated that chiglitazar possesses good efficacy and safety profile in patients with type 2 diabetes inadequately controlled with lifestyle interventions,thereby providing adequate supporting evidence for using this PPAR pan-agonist as a treatment option for type 2 diabetes.展开更多
The improvements and validation of several parameterization schemes in the second version of the Beijing Climate Center Atmosphere–Vegetation Interaction Model(BCC_AVIM2.0) are introduced in this study. The main upda...The improvements and validation of several parameterization schemes in the second version of the Beijing Climate Center Atmosphere–Vegetation Interaction Model(BCC_AVIM2.0) are introduced in this study. The main updates include a replacement of the water-only lake module by the common land model lake module(Co LM-lake) with a more realistic snow–ice–water–soil framework, a parameterization scheme for rice paddies added in the vegetation module, renewed parameterizations of snow cover fraction and snow surface albedo to accommodate the varied snow aging effect during different stages of a snow season, a revised parameterization to calculate the threshold temperature to initiate freeze(thaw) of soil water(ice) rather than being fixed at 0°C in BCC_AVIM1.0, a prognostic phenology scheme for vegetation growth instead of empirically prescribed dates for leaf onset/fall, and a renewed scheme to depict solar radiation transfer through the vegetation canopy. The above updates have been implemented in BCC_AVIM2.0 to serve as the land component of the BCC Climate System Model(BCC_CSM). Preliminary results of BCC_AVIM in the ongoing Land Surface, Snow, and Soil Moisture Model Intercomparison Project(LS3 MIP) of the Coupled Model Intercomparison Project Phase 6(CMIP6) show that the overall performance of BCC_AVIM2.0 is better than that of BCC_AVIM1.0 in the simulation of surface energy budgets at the seasonal timescale. Comparing the simulations of annual global land average before and after the updates in BCC_AVIM2.0 reveals that the bias of net surface radiation is reduced from-12.0 to-11.7 W m-2 and the root mean square error(RMSE) is reduced from 20.6 to 19.0 W m-2;the bias and RMSE of latent heat flux are reduced from 2.3 to-0.1 W m-2 and from 15.4 to14.3 W m-2, respectively;the bias of sensible heat flux is increased from 2.5 to 5.1 W m-2 but the RMSE is reduced from 18.4 to 17.0 W m-2.展开更多
The Circular Electron Positron Collider(CEPC)is a large scientific project initiated and hosted by China,fostered through extensive collaboration with international partners.The complex comprises four accelerators:a 3...The Circular Electron Positron Collider(CEPC)is a large scientific project initiated and hosted by China,fostered through extensive collaboration with international partners.The complex comprises four accelerators:a 30 GeV Linac,a 1.1 GeV Damping Ring,a Booster capable of achieving energies up to 180 GeV,and a Collider operating at varying energy modes(Z,W,H,and tt).The Linac and Damping Ring are situated on the surface,while the subterranean Booster and Collider are housed in a 100 km circumference underground tunnel,strategically accommodating future expansion with provisions for a potential Super Proton Proton Collider(SPPC).The CEPC primarily serves as a Higgs factory.In its baseline design with synchrotron radiation(SR)power of 30 MW per beam,it can achieve a luminosity of 5×10^(34)cm^(-2)s^(-1)per interaction point(IP),resulting in an integrated luminosity of 13 ab^(-1)for two IPs over a decade,producing 2.6 million Higgs bosons.Increasing the SR power to 50 MW per beam expands the CEPC's capability to generate 4.3 million Higgs bosons,facilitating precise measurements of Higgs coupling at sub-percent levels,exceeding the precision expected from the HL-LHC by an order of magnitude.This Technical Design Report(TDR)follows the Preliminary Conceptual Design Report(Pre-CDR,2015)and the Conceptual Design Report(CDR,2018),comprehensively detailing the machine's layout,performance metrics,physical design and analysis,technical systems design,R&D and prototyping efforts,and associated civil engineering aspects.Additionally,it includes a cost estimate and a preliminary construction timeline,establishing a framework for forthcoming engineering design phase and site selection procedures.Construction is anticipated to begin around 2027-2028,pending government approval,with an estimated duration of 8 years.The commencement of experiments and data collection could potentially be initiated in the mid-2030s.展开更多
目的评价痔病和肛裂生命质量量表(HEMO-FISS-QoL questionnaire,HF-QoL)中文版(Chinese version of HF-QoL,HF-QoL-C)在中国痔病人群中的信效度。方法本研究于2021年11月至2022年11月采用自制一般资料问卷、HF-QoL-C、36条目简明健康状...目的评价痔病和肛裂生命质量量表(HEMO-FISS-QoL questionnaire,HF-QoL)中文版(Chinese version of HF-QoL,HF-QoL-C)在中国痔病人群中的信效度。方法本研究于2021年11月至2022年11月采用自制一般资料问卷、HF-QoL-C、36条目简明健康状况调查问卷(the 36-item short form health survey,SF-36)、Goligher分级、Giordano痔病症状严重程度评分(Giordano severity of hemorrhoidal symptom questionnaire,GSQ)等在6家医院肛肠科对痔病患者进行问卷调查,回收有效问卷760份。运用SPSS 21.0和AMOS 26.0软件对数据进行信度和效度分析。结果HF-QoL-C和各维度Cronbach'sα系数为0.831~0.960,分半系数为0.832~0.915;主成分探索性因子分析提取出4个公因子;验证性因子分析显示结构效度尚可接受(χ^(2)/df=8.152,RSMEA=0.097,CFI=0.881,IFI=0.881,NFI=0.867);HF-QoL-C与SF36(r=-0.694)、GSQ(r=0.501)存在相关性(均P<0.01);HF-QoL-C总分和维度得分在手术和药物治疗患者、在痔病Goligher各分级、在痔脱出的不同范围之间存在差异(均P<0.001);HF-QoL-C总分及各维度得分未发现天花板效应(0.3%~2.0%),在心理功能和性生活两个维度存在地板效应(16.7%,35.1%)。结论HF-QoL-C具有良好的信度和效度,可用作评价国内患者痔病对生命质量影响的测量工具。展开更多
Three phthalide-derived analogues,oxaspiroangelioic acids A–C(1–3),were isolated as minor components of an aqueous extract of the Angelica sinensis root heads(guitou).Oxaspiroangelioic acids A and B were racemates s...Three phthalide-derived analogues,oxaspiroangelioic acids A–C(1–3),were isolated as minor components of an aqueous extract of the Angelica sinensis root heads(guitou).Oxaspiroangelioic acids A and B were racemates separated into enantiomers by chiral HPLC.Their structures including absolute configurations were determined by spectroscopic data analysis,single crystal X-ray diffraction,exciton chirality method [7_(T)D$IF]and electronic circular dichroism(ECD) calculation.These compounds share an undescribed carbon skeleton,for which biosynthetic pathways are proposed.Compound 1 and its enantiomers showed almost identical activity inhibiting Tandem of P domains in a weak inwardly rectifying K^(+)channel 1(TREK-1).展开更多
It is necessary to quantitatively identify different diseases and nitrogen-water stress for the guidance in spraying specific fungicides and fertilizer applications.The winter wheat diseases,in combination with nitrog...It is necessary to quantitatively identify different diseases and nitrogen-water stress for the guidance in spraying specific fungicides and fertilizer applications.The winter wheat diseases,in combination with nitrogen-water stress,are therefore common causes of yield loss in winter wheat in China.Powdery mildew(Blumeria graminis)and stripe rust(Puccinia striiformis f.sp.Tritici)are two of the most prevalent winter wheat diseases in China.This study investigated the potential of continuous wavelet analysis to identify the powdery mildew,stripe rust and nitrogen-water stress using canopy hyperspectral data.The spectral normalization process was applied prior to the analysis.Independent t-tests were used to determine the sensitivity of the spectral bands and vegetation index.In order to reduce the number of wavelet regions,correlation analysis and the independent t-test were used in conjunction to select the features of greatest importance.Based on the selected spectral bands,vegetation indices and wavelet features,the discriminate models were established using Fisher’s linear discrimination analysis(FLDA)and support vector machine(SVM).The results indicated that wavelet features were superior to spectral bands and vegetation indices in classifying different stresses,with overall accuracies of 0.91,0.72,and 0.72 respectively for powdery mildew,stripe rust and nitrogen-water by using FLDA,and 0.79,0.67 and 0.65 respectively by using SVM.FLDA was more suitable for differentiating stresses in winter wheat,with respective accuracies of 78.1%,95.6%and 95.7%for powdery mildew,stripe rust,and nitrogen-water stress.Further analysis was performed whereby the wavelet features were then split into high-scale and low-scale feature subsets for identification.The accuracies of high-scale and low-scale features with an overall accuracy(OA)of 0.61 and 0.73 respectively were lower than those of all wavelet features with an OA of 0.88.The detection of the severity of stripe rust using this method showed an enhanced reliability(R^展开更多
基金the National Nature Science Foundation of China(No.81373387)National Major Special Project on New Drug Innovation of China(No.2012ZX09301002-004)
文摘The rhizome of Gastrodia elata(GE), a herb medicine, has been used for treatment of neuronal disorders in Eastern Asia for hundreds of years. Parishin C is a major ingredient of GE. In this study, the i.c.v. injection of soluble Aβ1–42oligomers model of LTP injury was used. We investigated the effects of parishin C on the improvement of LTP in soluble Aβ1–42oligomer–injected rats and the underlying electrophysiological mechanisms. Parishin C(i.p. or i.c.v.) significantly ameliorated LTP impairment induced by i.c.v. injection of soluble Aβ1–42oligomers. In cultured hippocampal neurons,soluble Aβ1–42oligomers significantly inhibited NMDAR currents while not affecting AMPAR currents and voltage-dependent currents. Pretreatment with parishin C protected NMDA receptor currents from the damage induced by Aβ. In summary, parishin C improved LTP deficits induced by soluble Aβ1–42oligomers. The protection by parishin C against Aβ-induced LTP damage might be related to NMDA receptors.
基金the Chinese National and Provincial Major Project for New Drug Innovation(National:2008ZX09101-002,2013ZX09401301Provincial:2011A080501010)Shenzhen Municipal Major Project(2010-1746)。
文摘Chiglitazar(Carfloglitazar)is a novel peroxisome proliferator-activated receptor(PPAR)pan-agonist that has shown promising effects on glycemic control and lipid regulation in patients with type 2 diabetes.In this randomized phase 3 trial,we compared the efficacy and safety of chiglitazar with sitagliptin in patients with type 2 diabetes who had insufficient glycemic control despite a strict diet and exercise regimen.Eligible patients were randomized(1:1:1)to receive chiglitazar 32 mg(n=245),chiglitazar 48 mg(n=246),or sitagliptin 100 mg(n=248)once daily for 24 weeks.The primary endpoint was the change in glycosylated hemoglobin A_(1C)(HbA_(1c))from baseline at week 24 with the non-inferiority of chiglitazar over sitagliptin.Both chiglitazar and sitagliptin significantly reduced HbA1c at week 24 with values of-1.40%,-1.47%,and-1.39%for chiglitazar 32 mg,chiglitazar 48 mg,and sitagliptin 100 mg,respectively.Chiglitazar 32 and 48 mg were both non-inferior to sitagliptin 100 mg,with mean differences of-0.04%(95%confidential interval(Cl)-0.22 to 0.15)and-0.08%(95%Cl-0.27 to 0.10),respectively.Compared with sitagliptin,greater reduction in fasting and 2-h postprandial plasma glucose and fasting insulin was observed with chiglitazar.Overall adverse event rates were similar between the groups.A small increase in mild edema in the chiglitazar 48 mg group and slight weight gain in both chiglitazar groups were reported.The overall results demonstrated that chiglitazar possesses good efficacy and safety profile in patients with type 2 diabetes inadequately controlled with lifestyle interventions,thereby providing adequate supporting evidence for using this PPAR pan-agonist as a treatment option for type 2 diabetes.
基金Supported by the National Key Research and Development Program of China(2017YFA0604300,2016YFA0602100,and2016YFA0602602)National Natural Science Foundation of China(41275075 and 91437219)
文摘The improvements and validation of several parameterization schemes in the second version of the Beijing Climate Center Atmosphere–Vegetation Interaction Model(BCC_AVIM2.0) are introduced in this study. The main updates include a replacement of the water-only lake module by the common land model lake module(Co LM-lake) with a more realistic snow–ice–water–soil framework, a parameterization scheme for rice paddies added in the vegetation module, renewed parameterizations of snow cover fraction and snow surface albedo to accommodate the varied snow aging effect during different stages of a snow season, a revised parameterization to calculate the threshold temperature to initiate freeze(thaw) of soil water(ice) rather than being fixed at 0°C in BCC_AVIM1.0, a prognostic phenology scheme for vegetation growth instead of empirically prescribed dates for leaf onset/fall, and a renewed scheme to depict solar radiation transfer through the vegetation canopy. The above updates have been implemented in BCC_AVIM2.0 to serve as the land component of the BCC Climate System Model(BCC_CSM). Preliminary results of BCC_AVIM in the ongoing Land Surface, Snow, and Soil Moisture Model Intercomparison Project(LS3 MIP) of the Coupled Model Intercomparison Project Phase 6(CMIP6) show that the overall performance of BCC_AVIM2.0 is better than that of BCC_AVIM1.0 in the simulation of surface energy budgets at the seasonal timescale. Comparing the simulations of annual global land average before and after the updates in BCC_AVIM2.0 reveals that the bias of net surface radiation is reduced from-12.0 to-11.7 W m-2 and the root mean square error(RMSE) is reduced from 20.6 to 19.0 W m-2;the bias and RMSE of latent heat flux are reduced from 2.3 to-0.1 W m-2 and from 15.4 to14.3 W m-2, respectively;the bias of sensible heat flux is increased from 2.5 to 5.1 W m-2 but the RMSE is reduced from 18.4 to 17.0 W m-2.
基金support from diverse funding sources,including the National Key Program for S&T Research and Development of the Ministry of Science and Technology(MOST),Yifang Wang's Science Studio of the Ten Thousand Talents Project,the CAS Key Foreign Cooperation Grant,the National Natural Science Foundation of China(NSFC)Beijing Municipal Science&Technology Commission,the CAS Focused Science Grant,the IHEP Innovation Grant,the CAS Lead Special Training Programthe CAS Center for Excellence in Particle Physics,the CAS International Partnership Program,and the CAS/SAFEA International Partnership Program for Creative Research Teams.
文摘The Circular Electron Positron Collider(CEPC)is a large scientific project initiated and hosted by China,fostered through extensive collaboration with international partners.The complex comprises four accelerators:a 30 GeV Linac,a 1.1 GeV Damping Ring,a Booster capable of achieving energies up to 180 GeV,and a Collider operating at varying energy modes(Z,W,H,and tt).The Linac and Damping Ring are situated on the surface,while the subterranean Booster and Collider are housed in a 100 km circumference underground tunnel,strategically accommodating future expansion with provisions for a potential Super Proton Proton Collider(SPPC).The CEPC primarily serves as a Higgs factory.In its baseline design with synchrotron radiation(SR)power of 30 MW per beam,it can achieve a luminosity of 5×10^(34)cm^(-2)s^(-1)per interaction point(IP),resulting in an integrated luminosity of 13 ab^(-1)for two IPs over a decade,producing 2.6 million Higgs bosons.Increasing the SR power to 50 MW per beam expands the CEPC's capability to generate 4.3 million Higgs bosons,facilitating precise measurements of Higgs coupling at sub-percent levels,exceeding the precision expected from the HL-LHC by an order of magnitude.This Technical Design Report(TDR)follows the Preliminary Conceptual Design Report(Pre-CDR,2015)and the Conceptual Design Report(CDR,2018),comprehensively detailing the machine's layout,performance metrics,physical design and analysis,technical systems design,R&D and prototyping efforts,and associated civil engineering aspects.Additionally,it includes a cost estimate and a preliminary construction timeline,establishing a framework for forthcoming engineering design phase and site selection procedures.Construction is anticipated to begin around 2027-2028,pending government approval,with an estimated duration of 8 years.The commencement of experiments and data collection could potentially be initiated in the mid-2030s.
文摘目的评价痔病和肛裂生命质量量表(HEMO-FISS-QoL questionnaire,HF-QoL)中文版(Chinese version of HF-QoL,HF-QoL-C)在中国痔病人群中的信效度。方法本研究于2021年11月至2022年11月采用自制一般资料问卷、HF-QoL-C、36条目简明健康状况调查问卷(the 36-item short form health survey,SF-36)、Goligher分级、Giordano痔病症状严重程度评分(Giordano severity of hemorrhoidal symptom questionnaire,GSQ)等在6家医院肛肠科对痔病患者进行问卷调查,回收有效问卷760份。运用SPSS 21.0和AMOS 26.0软件对数据进行信度和效度分析。结果HF-QoL-C和各维度Cronbach'sα系数为0.831~0.960,分半系数为0.832~0.915;主成分探索性因子分析提取出4个公因子;验证性因子分析显示结构效度尚可接受(χ^(2)/df=8.152,RSMEA=0.097,CFI=0.881,IFI=0.881,NFI=0.867);HF-QoL-C与SF36(r=-0.694)、GSQ(r=0.501)存在相关性(均P<0.01);HF-QoL-C总分和维度得分在手术和药物治疗患者、在痔病Goligher各分级、在痔脱出的不同范围之间存在差异(均P<0.001);HF-QoL-C总分及各维度得分未发现天花板效应(0.3%~2.0%),在心理功能和性生活两个维度存在地板效应(16.7%,35.1%)。结论HF-QoL-C具有良好的信度和效度,可用作评价国内患者痔病对生命质量影响的测量工具。
基金Financial support from the National Natural Sciences Foundation of China (No.81630094)CAMS Innovation Fund for Medical Science (No.2017-I2M-3-010, China)The Drug Innovation Major Project (Nos.2018ZX09711001-004 and 2018ZX09711001-001, China)。
文摘Three phthalide-derived analogues,oxaspiroangelioic acids A–C(1–3),were isolated as minor components of an aqueous extract of the Angelica sinensis root heads(guitou).Oxaspiroangelioic acids A and B were racemates separated into enantiomers by chiral HPLC.Their structures including absolute configurations were determined by spectroscopic data analysis,single crystal X-ray diffraction,exciton chirality method [7_(T)D$IF]and electronic circular dichroism(ECD) calculation.These compounds share an undescribed carbon skeleton,for which biosynthetic pathways are proposed.Compound 1 and its enantiomers showed almost identical activity inhibiting Tandem of P domains in a weak inwardly rectifying K^(+)channel 1(TREK-1).
基金supported by Free Exploration Project of the State Key Laboratory of Remote Sensing Science at Institute of Remote Sensing and Digital Earth,Chinese Academy of Sciences(17ZY-01)the National Natural Science Foundation of China(61661136004)Hainan Provincial Department of Science and Technology under Grant(ZDKJ2016021).
文摘It is necessary to quantitatively identify different diseases and nitrogen-water stress for the guidance in spraying specific fungicides and fertilizer applications.The winter wheat diseases,in combination with nitrogen-water stress,are therefore common causes of yield loss in winter wheat in China.Powdery mildew(Blumeria graminis)and stripe rust(Puccinia striiformis f.sp.Tritici)are two of the most prevalent winter wheat diseases in China.This study investigated the potential of continuous wavelet analysis to identify the powdery mildew,stripe rust and nitrogen-water stress using canopy hyperspectral data.The spectral normalization process was applied prior to the analysis.Independent t-tests were used to determine the sensitivity of the spectral bands and vegetation index.In order to reduce the number of wavelet regions,correlation analysis and the independent t-test were used in conjunction to select the features of greatest importance.Based on the selected spectral bands,vegetation indices and wavelet features,the discriminate models were established using Fisher’s linear discrimination analysis(FLDA)and support vector machine(SVM).The results indicated that wavelet features were superior to spectral bands and vegetation indices in classifying different stresses,with overall accuracies of 0.91,0.72,and 0.72 respectively for powdery mildew,stripe rust and nitrogen-water by using FLDA,and 0.79,0.67 and 0.65 respectively by using SVM.FLDA was more suitable for differentiating stresses in winter wheat,with respective accuracies of 78.1%,95.6%and 95.7%for powdery mildew,stripe rust,and nitrogen-water stress.Further analysis was performed whereby the wavelet features were then split into high-scale and low-scale feature subsets for identification.The accuracies of high-scale and low-scale features with an overall accuracy(OA)of 0.61 and 0.73 respectively were lower than those of all wavelet features with an OA of 0.88.The detection of the severity of stripe rust using this method showed an enhanced reliability(R^
