In situ synchrotron angle-dispersive x-ray diffraction experiments on niobium powders have been conducted at pressures up to 61 GPa and room temperature using the diamond anvil cell technique. From the full width at h...In situ synchrotron angle-dispersive x-ray diffraction experiments on niobium powders have been conducted at pressures up to 61 GPa and room temperature using the diamond anvil cell technique. From the full width at half maximum of the measured diffraction lines, the yield strength was derived with the line-width analysis theory. The niobium powder sample was found to be compressed more packed firstly and then yielded at~14 GPa–18 GPa. Following an initial increase in the yield strength with pressure, an obvious decrease was observed occurring at ~42 GPa–47 GPa accompanying with a typical pressure dependence above 47 GPa. The experimentally observed anomalous softening of the yield strength in niobium surprisingly follows the trend of the predicted unusual softening in the shear modulus by the recent theoretical investigations. The possible mechanisms, applicable to interpret the yield strength softening of materials at high pressure,were also discussed in detail.展开更多
Ubiquitination-mediated protein degradation is integral to plant immunity,with E3 ubiquitin ligases acting as key factors in this process.Here,we report the functions of OsATL32,a plasma membrane-localized Arabidopsis...Ubiquitination-mediated protein degradation is integral to plant immunity,with E3 ubiquitin ligases acting as key factors in this process.Here,we report the functions of OsATL32,a plasma membrane-localized Arabidopsis Tóxicos En Levadura(ATL)-type E3 ubiquitin ligase,in rice(Oryza sativa)immunity and its associated regulatory network.We found that the expression of OsATL32 is downregulated in both compatible and incompatible interactions between rice and the rice blast fungus Magnaporthe oryzae.The OsATL32 protein level declines in response to infection by a compatible M.oryzae strain or to chitin treatment.OsATL32 negatively regulates rice resistance to blast and bacterial leaf blight diseases,as well as chitin-triggered immunity.Biochemical and genetic studies revealed that OsATL32 suppresses pathogen-induced reactive oxygen species(ROS)accumulation by mediating ubiquitination and degradation of the ROS-producing OsRac5–OsRbohB module,which enhances rice immunity against M.oryzae.The protein phosphatase PHOSPHATASE AND TENSIN HOMOLOG enhances rice blast resistance by dephosphorylating OsATL32 and promoting its degradation,preventing its negative effect on rice immunity.This study provides insights into the molecular mechanism by which the E3 ligase OsATL32 targets a ROS-producing module to undermine rice immunity.展开更多
Type 2 diabetes mellitus (T2DM) has become a prevalent health problem in China,especially in urban areas.Early prevention strategies are needed to reduce the associated mortality and morbidity.We applied the combinati...Type 2 diabetes mellitus (T2DM) has become a prevalent health problem in China,especially in urban areas.Early prevention strategies are needed to reduce the associated mortality and morbidity.We applied the combination of rules and different machine learning techniques to assess the risk of development of T2DM in an urban Chinese adult population.A retrospective analysis was performed on 8000 people with non-diabetes and 3845 people with T2DM in Nanjing.Multilayer Perceptron (MLP),AdaBoost (AD),Trees Random Forest (TRF),Support Vector Machine (SVM),and Gradient Tree Boosting (GTB) machine learning techniques with 10 cross validation methods were used with the proposed model for the prediction of the risk of development of T2DM.The performance of these models was evaluated with accuracy,precision,sensitivity,specificity,and area under receiver operating characteristic (ROC) curve (AUC).After comparison,the prediction accuracy of the different five machine models was 0.87,0.86,0.86,0.86 and 0.86 respectively.The combination model using the same voting weight of each component was built on T2DM,which was performed better than individual models.The findings indicate that,combining machine learning models could provide an accurate assessment model for T2DM risk prediction.展开更多
Background Subjective well-being(SWB),also known as happiness,plays an important role in evaluating both mental and physical health.Adolescents deserve specific attention because they are under a great variety of stre...Background Subjective well-being(SWB),also known as happiness,plays an important role in evaluating both mental and physical health.Adolescents deserve specific attention because they are under a great variety of stresses and are at risk for mental disorders during adulthood.Aim The present paper aims to predict undergraduate students1 SWB by machine learning method.Methods Gradient Boosting Classifier which was an innovative yet validated machine learning approach was used to analyse data from 10518 Chinese adolescents.The online survey included 298 factors such as depression and personality.Quality control procedure was used to minimise biases due to online survey reports.We applied feature selection to achieve the balance between optimal prediction and result interpretation.Results The top 20 happiness risks and protective factors were finally brought into the predicting model.Approximately 90%individuals'SWB can be predicted correctly,and the sensitivity and specificity were about 92%and 90%,respectively.Conclusions This result identifies at-risk individuals according to new characteristics and established the foundation for adolescent prevention strategies.展开更多
The equations of state(EOSs)of materials are the cornerstone of condensed matter physics,material science,and geophysics.However,acquiring an accurate EOS in diamond anvil cell(DAC)experiments continues to prove probl...The equations of state(EOSs)of materials are the cornerstone of condensed matter physics,material science,and geophysics.However,acquiring an accurate EOS in diamond anvil cell(DAC)experiments continues to prove problematic because the current lack of an accurate pressure scale with clarified sources of uncertainty makes it difficult to determine a precise pressure value at high pressure,and nonhydrostaticity affects both the volume and pressure determination.This study will discuss the advantages and drawbacks of various pressure scales,and propose an absolute pressure scale and correction methods for the effects of non-hydrostaticity.At the end of this paper,we analyze the accuracy of the determined EOS in the DAC experiments we can achieve to date.展开更多
目的探讨适应性支持通气(adaptive support ventilation,ASV)在全麻苏醒期患者中的应用效果。方法采用便利抽样法选取全麻手术后带气管导管转入PACU观察的患者120例,采用随机数字表法分为对照组和试验组(每组60例)。对照组采用容量控制...目的探讨适应性支持通气(adaptive support ventilation,ASV)在全麻苏醒期患者中的应用效果。方法采用便利抽样法选取全麻手术后带气管导管转入PACU观察的患者120例,采用随机数字表法分为对照组和试验组(每组60例)。对照组采用容量控制同步间歇指令通气(volume control‑synchronized intermittent mandatory ventilation,VC‑SIMV),试验组采用ASV,比较两组拔管前人机对抗发生率、苏醒期间镇静药物使用率、手动更改呼吸机参数的比例、PACU苏醒时间和拔管后低氧血症发生率。结果试验组拔管前人机对抗发生率、苏醒期间镇静药物使用率、手动更改呼吸机参数的比例均低于对照组(P<0.05),PACU苏醒时间少于对照组(P<0.05);两组低氧血症发生率差异无统计学意义(P>0.05)。结论相比于传统的VC‑SIMV模式,ASV应用于全麻带气管导管转入PACU苏醒的患者,能提供更好的人机协调性、简化通气管理、缩短患者苏醒时间。展开更多
NAC transcription factors(TFs) play critical roles in plant immunity by modulating the expression of downstream genes via binding to specific cis-elements in promoters. Here, we report the function and regulatory netw...NAC transcription factors(TFs) play critical roles in plant immunity by modulating the expression of downstream genes via binding to specific cis-elements in promoters. Here, we report the function and regulatory network of a pathogenand defense phytohormone-inducible NAC TF gene, ONAC083, in rice(Oryza sativa) immunity.ONAC083 localizes to the nucleus and exhibits transcriptional activation activity that depends on its C-terminal region. Knockout of ONAC083enhances rice immunity against Magnaporthe oryzae, strengthening pathogen-induced defense responses, and boosting chitin-induced pattern-triggered immunity(PTI), whereas ONAC083 overexpression has opposite effects. We identified ONAC083-binding sites in the promoters of 82genes, and showed that ONAC083 specifically binds to a conserved element with the core sequence ACGCAA. ONAC083 activated the transcription of the genes OsRFPH2-6, OsTrx1, and OsPUP4 by directly binding to the ACGCAA element. OsRFPH2-6, encoding a RING-H2 protein with an N-terminal transmembrane region and a C-terminal typical RING domain, negatively regulated rice immunity against M. oryzae and chitin-triggered PTI. These data demonstrate that ONAC083 negatively contributes to rice immunity against M. oryzae by directly activating the transcription of OsRFPH2-6 through the ACGCAA element in its promoter. Overall, our study provides new insight into the molecular regulatory network of NAC TFs in rice immunity.展开更多
Human pluripotent stem cells provide an inexhaustible model to study human embryogenesis in vitro.Recent studies have provided diverse models to generate human blastoids by self-organization of different pluripotent s...Human pluripotent stem cells provide an inexhaustible model to study human embryogenesis in vitro.Recent studies have provided diverse models to generate human blastoids by self-organization of different pluripotent stem cells or somatic reprogramming intermediates.However,whether blastoids can be generated from other cell types or whether they can recapitulate postimplantation development in vitro is unknown.Here,we develop a strategy to generate human blastoids from heterogeneous intermediates with epiblast,trophectoderm,and primitive endoderm signatures of the primed-to-naïve conversion process,which resemble natural blastocysts in morphological architecture,composition of cell lineages,transcriptome,and lineage differentiation potential.In addition,these blastoids reflect many features of human peri-implantation and pregastrulation development when further cultured in an in vitro 3D culture system.In summary,our study provides an alternative strategy to generate human blastoids and offers insights into human early embryogenesis by modeling peri-and postimplantation development in vitro.展开更多
Despite the current guideline's recommendation of a timely stepwise intensification therapy,the "clinical inertia",termed as the delayed treatment intensification,commonly exists in the real world,which ...Despite the current guideline's recommendation of a timely stepwise intensification therapy,the "clinical inertia",termed as the delayed treatment intensification,commonly exists in the real world,which may be partly due to the relatively little substantial evidence and no clear consensus regarding the efficacy and safety of triple oral agents in patients inadequately controlled with dual therapy.In this clinical trial performed in 237 centers in China,5,535 type 2 diabetic patients inadequately controlled by previous therapies were treated with a stable metformin/sitagliptin dual therapy for 20 weeks.The patients who did not reach the glycated hemoglobin A1c(HbA1c) goal were then further randomized into glimepiride,gliclazide,repaglinide,or acarbose group for an additional 24-week triple therapy.A mean HbAlc reduction of 0.85%was observed when sitagliptin was added to the patients inadequately controlled with metformin in 16 weeks.Further HbAlc reductions in the 24-week triple therapy stage were 0.65%in glimepiride group,0.70%in gliclazide group,0.61%in repaglinide group,and 0.45%in acarbose group.The non-inferiority criterion for primary hypotheses was met for gliclazide and repaglinide,but not for acarbose,compared with glimepiride,when added to metformin/sitagliptin dual therapy.The incidences of adverse events(AEs) were 29.2%in the dual therapy stage and30.3%in the triple therapy stage.Metformin/sitagliptin as baseline therapy,with the addition of a third oral antihyperglycemic agent,including glimepiride,gliclazide,repaglinide,or acarbose,was effective,safe and well-tolerated for achieving an HbAlc<7.0%goal in type 2 diabetic patients inadequately controlled with previous therapies.The timely augmentation of up to three oral antihyperglycemic agents is valid and of important clinical benefit to prevent patients from exposure to unnecessarily prolonged hyperglycemia.展开更多
With the booming development of industrialization and urbanization, popularization of high calorie diet and sedentary lifestyle, and the rapid growth of aging, the prevalence of diabetes increased nearly 10 times duri...With the booming development of industrialization and urbanization, popularization of high calorie diet and sedentary lifestyle, and the rapid growth of aging, the prevalence of diabetes increased nearly 10 times during the past three decades in China.展开更多
基金Project supported by the National Natural Science Foundation of China(Grant Nos.U1530134,U1730248,11772312,and 11504354)
文摘In situ synchrotron angle-dispersive x-ray diffraction experiments on niobium powders have been conducted at pressures up to 61 GPa and room temperature using the diamond anvil cell technique. From the full width at half maximum of the measured diffraction lines, the yield strength was derived with the line-width analysis theory. The niobium powder sample was found to be compressed more packed firstly and then yielded at~14 GPa–18 GPa. Following an initial increase in the yield strength with pressure, an obvious decrease was observed occurring at ~42 GPa–47 GPa accompanying with a typical pressure dependence above 47 GPa. The experimentally observed anomalous softening of the yield strength in niobium surprisingly follows the trend of the predicted unusual softening in the shear modulus by the recent theoretical investigations. The possible mechanisms, applicable to interpret the yield strength softening of materials at high pressure,were also discussed in detail.
基金supported by grants from the National Natural Science Foundation of China(32072403 and 31871945)the National Key Research and Development Program of China(2016YFD0100600).
文摘Ubiquitination-mediated protein degradation is integral to plant immunity,with E3 ubiquitin ligases acting as key factors in this process.Here,we report the functions of OsATL32,a plasma membrane-localized Arabidopsis Tóxicos En Levadura(ATL)-type E3 ubiquitin ligase,in rice(Oryza sativa)immunity and its associated regulatory network.We found that the expression of OsATL32 is downregulated in both compatible and incompatible interactions between rice and the rice blast fungus Magnaporthe oryzae.The OsATL32 protein level declines in response to infection by a compatible M.oryzae strain or to chitin treatment.OsATL32 negatively regulates rice resistance to blast and bacterial leaf blight diseases,as well as chitin-triggered immunity.Biochemical and genetic studies revealed that OsATL32 suppresses pathogen-induced reactive oxygen species(ROS)accumulation by mediating ubiquitination and degradation of the ROS-producing OsRac5–OsRbohB module,which enhances rice immunity against M.oryzae.The protein phosphatase PHOSPHATASE AND TENSIN HOMOLOG enhances rice blast resistance by dephosphorylating OsATL32 and promoting its degradation,preventing its negative effect on rice immunity.This study provides insights into the molecular mechanism by which the E3 ligase OsATL32 targets a ROS-producing module to undermine rice immunity.
基金This work was supported by grants from the National Natural Science Foundation of China (No.81570737, No.81370947, No.81570736, No.81770819, No.81500612, No.81400832, No.81600637, No.81600632, and No.81703294)the National Key Research and Development Program of China (No.2016YFC1304804 and No.2017YFC1309605)+4 种基金the Jiangsu Provincial Key Medical Discipline (No.ZDXKB2016012)the Key Project of Nanjing Clinical Medical Sciencethe Key Research and Development Program of Jiangsu Province of China (No.BE2015604 and No.BE2016606)the Jiangsu Provincial Medical Talent (No.ZDRCA2016062)the Nanjing Science and Technology Development Project (No.201605019).
文摘Type 2 diabetes mellitus (T2DM) has become a prevalent health problem in China,especially in urban areas.Early prevention strategies are needed to reduce the associated mortality and morbidity.We applied the combination of rules and different machine learning techniques to assess the risk of development of T2DM in an urban Chinese adult population.A retrospective analysis was performed on 8000 people with non-diabetes and 3845 people with T2DM in Nanjing.Multilayer Perceptron (MLP),AdaBoost (AD),Trees Random Forest (TRF),Support Vector Machine (SVM),and Gradient Tree Boosting (GTB) machine learning techniques with 10 cross validation methods were used with the proposed model for the prediction of the risk of development of T2DM.The performance of these models was evaluated with accuracy,precision,sensitivity,specificity,and area under receiver operating characteristic (ROC) curve (AUC).After comparison,the prediction accuracy of the different five machine models was 0.87,0.86,0.86,0.86 and 0.86 respectively.The combination model using the same voting weight of each component was built on T2DM,which was performed better than individual models.The findings indicate that,combining machine learning models could provide an accurate assessment model for T2DM risk prediction.
基金This work was supported by the National Key Research and Development Program(2016YFC0906400,2016YFC1307000,2016YFC0905000)the National Nature Science Foundation of China(81421061,81361120389)+2 种基金the Shanghai Key Laboratory of Psychotic Disorders(13dz2260500)the Shanghai Leading Academic Discipline Project(B205)the Fundamental Research Funds for the Central Universities(16JXRZ01).
文摘Background Subjective well-being(SWB),also known as happiness,plays an important role in evaluating both mental and physical health.Adolescents deserve specific attention because they are under a great variety of stresses and are at risk for mental disorders during adulthood.Aim The present paper aims to predict undergraduate students1 SWB by machine learning method.Methods Gradient Boosting Classifier which was an innovative yet validated machine learning approach was used to analyse data from 10518 Chinese adolescents.The online survey included 298 factors such as depression and personality.Quality control procedure was used to minimise biases due to online survey reports.We applied feature selection to achieve the balance between optimal prediction and result interpretation.Results The top 20 happiness risks and protective factors were finally brought into the predicting model.Approximately 90%individuals'SWB can be predicted correctly,and the sensitivity and specificity were about 92%and 90%,respectively.Conclusions This result identifies at-risk individuals according to new characteristics and established the foundation for adolescent prevention strategies.
基金supported by the National Natural Science Foundation of China under Grant No.11504354Research Foundation of National Key Laboratory of Shock Wave and Detonation Physics under Grants No.9140C6703010703 and 9140C6703010803.
文摘The equations of state(EOSs)of materials are the cornerstone of condensed matter physics,material science,and geophysics.However,acquiring an accurate EOS in diamond anvil cell(DAC)experiments continues to prove problematic because the current lack of an accurate pressure scale with clarified sources of uncertainty makes it difficult to determine a precise pressure value at high pressure,and nonhydrostaticity affects both the volume and pressure determination.This study will discuss the advantages and drawbacks of various pressure scales,and propose an absolute pressure scale and correction methods for the effects of non-hydrostaticity.At the end of this paper,we analyze the accuracy of the determined EOS in the DAC experiments we can achieve to date.
基金supported by grants from the National Natural Science Foundation of China (31871945, 32072403)the National Key Research and Development Program of China (2016YFD0100600)。
文摘NAC transcription factors(TFs) play critical roles in plant immunity by modulating the expression of downstream genes via binding to specific cis-elements in promoters. Here, we report the function and regulatory network of a pathogenand defense phytohormone-inducible NAC TF gene, ONAC083, in rice(Oryza sativa) immunity.ONAC083 localizes to the nucleus and exhibits transcriptional activation activity that depends on its C-terminal region. Knockout of ONAC083enhances rice immunity against Magnaporthe oryzae, strengthening pathogen-induced defense responses, and boosting chitin-induced pattern-triggered immunity(PTI), whereas ONAC083 overexpression has opposite effects. We identified ONAC083-binding sites in the promoters of 82genes, and showed that ONAC083 specifically binds to a conserved element with the core sequence ACGCAA. ONAC083 activated the transcription of the genes OsRFPH2-6, OsTrx1, and OsPUP4 by directly binding to the ACGCAA element. OsRFPH2-6, encoding a RING-H2 protein with an N-terminal transmembrane region and a C-terminal typical RING domain, negatively regulated rice immunity against M. oryzae and chitin-triggered PTI. These data demonstrate that ONAC083 negatively contributes to rice immunity against M. oryzae by directly activating the transcription of OsRFPH2-6 through the ACGCAA element in its promoter. Overall, our study provides new insight into the molecular regulatory network of NAC TFs in rice immunity.
基金the Ministry of Science and Technology of China(Nos.2021YFA1102000,2021YFC2700300,2019YFA0110000,and 2018YFA0108900)the National Natural Science Foundation of China(NSFC)(Nos.31721003,32022024,32270850,32100633,31871486,32070652,and 81630035)the Science and Technology Commission of Shanghai Municipality(Nos.19JC1415300 and 21JC1405500).
文摘Human pluripotent stem cells provide an inexhaustible model to study human embryogenesis in vitro.Recent studies have provided diverse models to generate human blastoids by self-organization of different pluripotent stem cells or somatic reprogramming intermediates.However,whether blastoids can be generated from other cell types or whether they can recapitulate postimplantation development in vitro is unknown.Here,we develop a strategy to generate human blastoids from heterogeneous intermediates with epiblast,trophectoderm,and primitive endoderm signatures of the primed-to-naïve conversion process,which resemble natural blastocysts in morphological architecture,composition of cell lineages,transcriptome,and lineage differentiation potential.In addition,these blastoids reflect many features of human peri-implantation and pregastrulation development when further cultured in an in vitro 3D culture system.In summary,our study provides an alternative strategy to generate human blastoids and offers insights into human early embryogenesis by modeling peri-and postimplantation development in vitro.
基金supported by Merck&Co.,Inc.,Kenilworth,NJ,the 5010 Project of Sun Yat-sen UniversityProgram for Changjiang Scholars and Innovative Research Team in University(to Jianping Weng)
文摘Despite the current guideline's recommendation of a timely stepwise intensification therapy,the "clinical inertia",termed as the delayed treatment intensification,commonly exists in the real world,which may be partly due to the relatively little substantial evidence and no clear consensus regarding the efficacy and safety of triple oral agents in patients inadequately controlled with dual therapy.In this clinical trial performed in 237 centers in China,5,535 type 2 diabetic patients inadequately controlled by previous therapies were treated with a stable metformin/sitagliptin dual therapy for 20 weeks.The patients who did not reach the glycated hemoglobin A1c(HbA1c) goal were then further randomized into glimepiride,gliclazide,repaglinide,or acarbose group for an additional 24-week triple therapy.A mean HbAlc reduction of 0.85%was observed when sitagliptin was added to the patients inadequately controlled with metformin in 16 weeks.Further HbAlc reductions in the 24-week triple therapy stage were 0.65%in glimepiride group,0.70%in gliclazide group,0.61%in repaglinide group,and 0.45%in acarbose group.The non-inferiority criterion for primary hypotheses was met for gliclazide and repaglinide,but not for acarbose,compared with glimepiride,when added to metformin/sitagliptin dual therapy.The incidences of adverse events(AEs) were 29.2%in the dual therapy stage and30.3%in the triple therapy stage.Metformin/sitagliptin as baseline therapy,with the addition of a third oral antihyperglycemic agent,including glimepiride,gliclazide,repaglinide,or acarbose,was effective,safe and well-tolerated for achieving an HbAlc<7.0%goal in type 2 diabetic patients inadequately controlled with previous therapies.The timely augmentation of up to three oral antihyperglycemic agents is valid and of important clinical benefit to prevent patients from exposure to unnecessarily prolonged hyperglycemia.
文摘With the booming development of industrialization and urbanization, popularization of high calorie diet and sedentary lifestyle, and the rapid growth of aging, the prevalence of diabetes increased nearly 10 times during the past three decades in China.