The S38C railway axle undergoes induction hardening,resulting in a gradient-distributed microstructure and mechanical properties.The accurate identification of gradient-distributed plastic parameters for the S38C axle...The S38C railway axle undergoes induction hardening,resulting in a gradient-distributed microstructure and mechanical properties.The accurate identification of gradient-distributed plastic parameters for the S38C axle remains a challenging task.To tackle this challenge,the present study proposes a novel approach for identifying the gradient-distributed plastic parameters for the S38C axle by integrating nano-indentation techniques with the machine learning method.Firstly,nano-indentation tests are conducted along the radial direction of the S38C axle to obtain the gradient-distributed load-displacement curves,nano-hardness,and elastic modulus.Subsequently,the dimensionless analysis is performed to obtain the representative stress,strain,and yield stress from load-displacement curves.These parameters are then incorporated into the machine learning method as physical information to identify the gradient-distributed plastic parameters of the S38C axle.The results indicate that the proposed method based on the physics-informed neural network and multi-fidelity neural network successfully identifies the gradient-distributed plastic parameters of the S38C axles and demonstrates superior prediction accuracy and generalization compared with the purely data-driven machine learning method.展开更多
Alzheimer’s disease is initially thought to be caused by age-associated accumulation of plaques,in recent years,research has increasingly associated Alzheimer’s disease with lysosomal storage and metabolic disorders...Alzheimer’s disease is initially thought to be caused by age-associated accumulation of plaques,in recent years,research has increasingly associated Alzheimer’s disease with lysosomal storage and metabolic disorders,and the explanation of its pathogenesis has shifted from amyloid and tau accumulation to oxidative stress and impaired lipid and glucose metabolism aggravated by hypoxic conditions.However,the underlying mechanisms linking those cellular processes and conditions to disease progression have yet to be defined.Here,we applied a disease similarity approach to identify unknown molecular targets of Alzheimer’s disease by using transcriptomic data from congenital diseases known to increase Alzheimer’s disease risk,namely Down syndrome,Niemann-Pick type C disease,and mucopolysaccharidoses I.We uncovered common pathways,hub genes,and miRNAs across in vitro and in vivo models of these diseases as potential molecular targets for neuroprotection and amelioration of Alzheimer’s disease pathology,many of which have never been associated with Alzheimer’s disease.We then investigated common molecular alterations in brain samples from a Niemann-Pick type C disease mouse model by juxtaposing them with brain samples of both human and mouse models of Alzheimer’s disease.Detailed phenotypic,molecular,chronological,and biological aging analyses revealed that the Npc1tm(I1061T)Dso mouse model can serve as a potential short-lived in vivo model for brain aging and Alzheimer’s disease research.This research represents the first comprehensive approach to congenital disease association with neurodegeneration and a new perspective on Alzheimer’s disease research while highlighting shortcomings and lack of correlation in diverse in vitro models.Considering the lack of an Alzheimer’s disease mouse model that recapitulates the physiological hallmarks of brain aging,the short-lived Npc1^(tm(I1061T)Dso) mouse model can further accelerate the research in these fields and offer a unique model for understanding the molecular mechanisms of Alzheimer’s disease from a perspective of accelerated brain aging.展开更多
BACKGROUND Data regarding complex Crohn’s perianal fistulas(CPF)epidemiology are limited,and optimal treatment strategies are elusive.An improved understanding of how CPF treatment options are used in the real-world ...BACKGROUND Data regarding complex Crohn’s perianal fistulas(CPF)epidemiology are limited,and optimal treatment strategies are elusive.An improved understanding of how CPF treatment options are used in the real-world setting and factors associated with CPF development,treatment failure,and reasons for undergoing multiple surgeries may help to inform optimal patient management strategies,reduce treatment burden,and improve outcomes in patients with CPF.AIM To describe the epidemiology,treatments,outcomes,and associated risk/protective factors for complex CPF.METHODS Electronic databases(MEDLINE,EMBASE,EBM Reviews,EconLit)were searched.Two reviewers independently used populations,interventions,comparators,outcomes,study designs,and time criteria to identify relevant studies.Observational studies published in English from January 1,2015 to February 17,2022 with>50 patients were included,even if complex CPF was not defined.Items of interest included complex CPF definitions,epidemiology,treatment patterns,morbidity,mortality,and risk factors associated with complex CPF development,treatment failure,and undergoing multiple surgeries.Data were reported using descriptive statistics.RESULTS Overall,140 studies were included.Complex CPF definitions were heterogeneous and rarely reported(24 studies).Hence,data mostly related to CPF in general.CPF prevalence was variable(range:1.5%-81.0%).Incidence was wide-ranging and mostly reported cumulatively at 1-year post-Crohn’s disease diagnosis(range:3.5%-50.1%).Overall healing and failure rates after treatment were in the range of 10.5%-80.2%and 3.6%-83.0%,respectively.Abscesses were the most frequently reported morbidity(n=18).No CPF-related deaths were reported.No consistent risk or protective factors were identified.CONCLUSION Epidemiology,treatment patterns,and risk factors for CPF vary,likely due to inconsistent CPF and clinical outcome definitions.Standardization would facilitate comparability,which may inform optimal complex CPF treatment strategies.展开更多
The Mohorovicic discontinuity(Moho)boundary separating the Earth’s crust and mantle reflects the evolutionary trajectory of the Earth’s crust,yielding crucial insights into crustal formation,tectonic evolution,and p...The Mohorovicic discontinuity(Moho)boundary separating the Earth’s crust and mantle reflects the evolutionary trajectory of the Earth’s crust,yielding crucial insights into crustal formation,tectonic evolution,and profound dynamic processes.However,the prevailing Moho models for China and its adjacent areas suffer from limited accuracy,owing to the irregular and sparse distribution of seismic data collection.In this study,we employ gravimetric data to derive Moho depth,and employ Bott’s regularization method,integrating gravity and seismic data to reconstruct the Moho structure with high precision in a three-dimensional framework across China and its adjacent areas.By optimizing gravity potential field separation and interface inversion techniques,we present a detailed and accurate zoning scheme for classifying China and its adjacent areas into 35 gradient belts,6 primary tectonic units,and 35 secondary tectonic units,based on the spatial distribution characteristics of the Moho discontinuity.Notably,our tectonic pattern division results surpass previous studies in terms of resolution,providing a wealth of tectonic information.Leveraging the Moho depth model of China and its adjacent areas,we discuss orogenic belts,sedimentary basins,fault systems,plate boundaries,and land-sea coupled tectonic patterns.We meticulously summarize the Moho depth distribution characteristics of each tectonic unit,while exploring the macrostructural framework and geological significance of the study area.Our findings highlight the close relationship between China and its adjacent areas Moho depth model and deep geodynamics,elucidating the tectonic evolution both between and within tectonic plates,as well as the tectonic effects induced by mantle dynamics.These insights have crucial implications for the study of deep geodynamics in China and its adjacent areas.展开更多
In order to explore the fertilizing ways and dynamic changes of soil carbon and nitrogen in the main producing areas of tobacco in Guizhou,research was conducted to study the variations of dissolved organic carbon and...In order to explore the fertilizing ways and dynamic changes of soil carbon and nitrogen in the main producing areas of tobacco in Guizhou,research was conducted to study the variations of dissolved organic carbon and nitrogen,total organic carbon and nitrogen and their ratio of tobacco-topsoil in organic fertilization pattern and conventional cultivation pattern （No fertilizer as control） by pot experiment.The results were as follows：（1） The effects of different fertilization patterns on soil dissolved organic carbon and nitrogen and total organic carbon and nitrogen were significantly different.The content of DOC,DON,TOC and TON in tobaccotopsoil was decreased with the advancing of growth period in conventional fertilization pattern.In the conventional fertilization pattern,the accumulation of DOC and TOC was increased first and then decreased,and the accumulation of DON and TON was decreased first and then increased.（2） The TOC content at the different growing stage and DOC content at the middle and later stage of tobacco were significantly improved in organic fertilization patterns.The accumulation of DON and TON in the conventional fertilization pattern was significantly higher than those in the organic fertilizer pattern and control at the rosette stage and vigorous stage.In the harvest period,the content of DOC,DON,TOC and TON of tobacco-topsoil in the conventional fertilization and organic fertilization pattern was significantly higher than those in the control.（3）The DOC/DON ratio and the TOC/TiON ratio was increased gradually with the advancing of growth period in conventional fertilization pattern,but they were increased first and then decreased in the organic fertilization pattern and CK.The DOC/DON and TOC/TON ratio of tobacco-topsoil in different fertilization patterns was showed as Y J＞ CK＞ CG at the different growing stage.The experiment results revealed that：The organic fertilization pattern may improve significantly the accumulation of DOC,DON,TOC and TON of tobacco-topsoil at the middle and later stage and the DOC/DON and TOC/TON ratio at the different growth stage.It contributed to the continuous and balanced supply of nutrients at the middle and later stage of tobacco and the soil fertility.展开更多
基金supported by the National Key Research and Development Plan(Grant No.2022YFB3401901)the National Natural Science Foundation of China(Grant Nos.12192210,12192214,12072295,and 12222209)+1 种基金Independent Project of State Key Laboratory of Rail Transit Vehicle System(Grant No.2023TPL-T03)Fundamental Research Funds for the Central Universities(Grant No.2682023CG004).
文摘The S38C railway axle undergoes induction hardening,resulting in a gradient-distributed microstructure and mechanical properties.The accurate identification of gradient-distributed plastic parameters for the S38C axle remains a challenging task.To tackle this challenge,the present study proposes a novel approach for identifying the gradient-distributed plastic parameters for the S38C axle by integrating nano-indentation techniques with the machine learning method.Firstly,nano-indentation tests are conducted along the radial direction of the S38C axle to obtain the gradient-distributed load-displacement curves,nano-hardness,and elastic modulus.Subsequently,the dimensionless analysis is performed to obtain the representative stress,strain,and yield stress from load-displacement curves.These parameters are then incorporated into the machine learning method as physical information to identify the gradient-distributed plastic parameters of the S38C axle.The results indicate that the proposed method based on the physics-informed neural network and multi-fidelity neural network successfully identifies the gradient-distributed plastic parameters of the S38C axles and demonstrates superior prediction accuracy and generalization compared with the purely data-driven machine learning method.
基金supported by the NIA/NIH(1K01AG060040).Studies performed by JN were funded by the NICHD/NIH(5R00HD096117)Microscopy Core Facility supported,in part,with funding from NIH-NCI Cancer Center Support Grant P30 CA016059.
文摘Alzheimer’s disease is initially thought to be caused by age-associated accumulation of plaques,in recent years,research has increasingly associated Alzheimer’s disease with lysosomal storage and metabolic disorders,and the explanation of its pathogenesis has shifted from amyloid and tau accumulation to oxidative stress and impaired lipid and glucose metabolism aggravated by hypoxic conditions.However,the underlying mechanisms linking those cellular processes and conditions to disease progression have yet to be defined.Here,we applied a disease similarity approach to identify unknown molecular targets of Alzheimer’s disease by using transcriptomic data from congenital diseases known to increase Alzheimer’s disease risk,namely Down syndrome,Niemann-Pick type C disease,and mucopolysaccharidoses I.We uncovered common pathways,hub genes,and miRNAs across in vitro and in vivo models of these diseases as potential molecular targets for neuroprotection and amelioration of Alzheimer’s disease pathology,many of which have never been associated with Alzheimer’s disease.We then investigated common molecular alterations in brain samples from a Niemann-Pick type C disease mouse model by juxtaposing them with brain samples of both human and mouse models of Alzheimer’s disease.Detailed phenotypic,molecular,chronological,and biological aging analyses revealed that the Npc1tm(I1061T)Dso mouse model can serve as a potential short-lived in vivo model for brain aging and Alzheimer’s disease research.This research represents the first comprehensive approach to congenital disease association with neurodegeneration and a new perspective on Alzheimer’s disease research while highlighting shortcomings and lack of correlation in diverse in vitro models.Considering the lack of an Alzheimer’s disease mouse model that recapitulates the physiological hallmarks of brain aging,the short-lived Npc1^(tm(I1061T)Dso) mouse model can further accelerate the research in these fields and offer a unique model for understanding the molecular mechanisms of Alzheimer’s disease from a perspective of accelerated brain aging.
基金Supported by Takeda Pharmaceuticals USA,Inc.Medical writing support was provided by Luke Humphreys,PhD,of Oxford PharmaGenesis,Oxford,UK and was funded by Takeda Development Center Americas,Inc.
文摘BACKGROUND Data regarding complex Crohn’s perianal fistulas(CPF)epidemiology are limited,and optimal treatment strategies are elusive.An improved understanding of how CPF treatment options are used in the real-world setting and factors associated with CPF development,treatment failure,and reasons for undergoing multiple surgeries may help to inform optimal patient management strategies,reduce treatment burden,and improve outcomes in patients with CPF.AIM To describe the epidemiology,treatments,outcomes,and associated risk/protective factors for complex CPF.METHODS Electronic databases(MEDLINE,EMBASE,EBM Reviews,EconLit)were searched.Two reviewers independently used populations,interventions,comparators,outcomes,study designs,and time criteria to identify relevant studies.Observational studies published in English from January 1,2015 to February 17,2022 with>50 patients were included,even if complex CPF was not defined.Items of interest included complex CPF definitions,epidemiology,treatment patterns,morbidity,mortality,and risk factors associated with complex CPF development,treatment failure,and undergoing multiple surgeries.Data were reported using descriptive statistics.RESULTS Overall,140 studies were included.Complex CPF definitions were heterogeneous and rarely reported(24 studies).Hence,data mostly related to CPF in general.CPF prevalence was variable(range:1.5%-81.0%).Incidence was wide-ranging and mostly reported cumulatively at 1-year post-Crohn’s disease diagnosis(range:3.5%-50.1%).Overall healing and failure rates after treatment were in the range of 10.5%-80.2%and 3.6%-83.0%,respectively.Abscesses were the most frequently reported morbidity(n=18).No CPF-related deaths were reported.No consistent risk or protective factors were identified.CONCLUSION Epidemiology,treatment patterns,and risk factors for CPF vary,likely due to inconsistent CPF and clinical outcome definitions.Standardization would facilitate comparability,which may inform optimal complex CPF treatment strategies.
基金supported by the National Natural Science Foundation of China(Grant Nos.42474121 and 42192535)the Basic Frontier Science Research Program of the Chinese Academy of Sciences(Grant No.ZDBS-LY-DQC028).
文摘The Mohorovicic discontinuity(Moho)boundary separating the Earth’s crust and mantle reflects the evolutionary trajectory of the Earth’s crust,yielding crucial insights into crustal formation,tectonic evolution,and profound dynamic processes.However,the prevailing Moho models for China and its adjacent areas suffer from limited accuracy,owing to the irregular and sparse distribution of seismic data collection.In this study,we employ gravimetric data to derive Moho depth,and employ Bott’s regularization method,integrating gravity and seismic data to reconstruct the Moho structure with high precision in a three-dimensional framework across China and its adjacent areas.By optimizing gravity potential field separation and interface inversion techniques,we present a detailed and accurate zoning scheme for classifying China and its adjacent areas into 35 gradient belts,6 primary tectonic units,and 35 secondary tectonic units,based on the spatial distribution characteristics of the Moho discontinuity.Notably,our tectonic pattern division results surpass previous studies in terms of resolution,providing a wealth of tectonic information.Leveraging the Moho depth model of China and its adjacent areas,we discuss orogenic belts,sedimentary basins,fault systems,plate boundaries,and land-sea coupled tectonic patterns.We meticulously summarize the Moho depth distribution characteristics of each tectonic unit,while exploring the macrostructural framework and geological significance of the study area.Our findings highlight the close relationship between China and its adjacent areas Moho depth model and deep geodynamics,elucidating the tectonic evolution both between and within tectonic plates,as well as the tectonic effects induced by mantle dynamics.These insights have crucial implications for the study of deep geodynamics in China and its adjacent areas.
基金Supported by The General Program of National Natural Science Foundation of China(312771673)Programs for Science and Technology Development of Tobacco Monopoly Bureau in Guizhou Province(20121126)~~
文摘In order to explore the fertilizing ways and dynamic changes of soil carbon and nitrogen in the main producing areas of tobacco in Guizhou,research was conducted to study the variations of dissolved organic carbon and nitrogen,total organic carbon and nitrogen and their ratio of tobacco-topsoil in organic fertilization pattern and conventional cultivation pattern （No fertilizer as control） by pot experiment.The results were as follows：（1） The effects of different fertilization patterns on soil dissolved organic carbon and nitrogen and total organic carbon and nitrogen were significantly different.The content of DOC,DON,TOC and TON in tobaccotopsoil was decreased with the advancing of growth period in conventional fertilization pattern.In the conventional fertilization pattern,the accumulation of DOC and TOC was increased first and then decreased,and the accumulation of DON and TON was decreased first and then increased.（2） The TOC content at the different growing stage and DOC content at the middle and later stage of tobacco were significantly improved in organic fertilization patterns.The accumulation of DON and TON in the conventional fertilization pattern was significantly higher than those in the organic fertilizer pattern and control at the rosette stage and vigorous stage.In the harvest period,the content of DOC,DON,TOC and TON of tobacco-topsoil in the conventional fertilization and organic fertilization pattern was significantly higher than those in the control.（3）The DOC/DON ratio and the TOC/TiON ratio was increased gradually with the advancing of growth period in conventional fertilization pattern,but they were increased first and then decreased in the organic fertilization pattern and CK.The DOC/DON and TOC/TON ratio of tobacco-topsoil in different fertilization patterns was showed as Y J＞ CK＞ CG at the different growing stage.The experiment results revealed that：The organic fertilization pattern may improve significantly the accumulation of DOC,DON,TOC and TON of tobacco-topsoil at the middle and later stage and the DOC/DON and TOC/TON ratio at the different growth stage.It contributed to the continuous and balanced supply of nutrients at the middle and later stage of tobacco and the soil fertility.
