Objectives This study aimed to explore the lagged and cumulative effects of risk factors on disability in older adults using distributed lag non-linear models(DLNMs).Methods We utilized data from the China Health and ...Objectives This study aimed to explore the lagged and cumulative effects of risk factors on disability in older adults using distributed lag non-linear models(DLNMs).Methods We utilized data from the China Health and Retirement Longitudinal Study(CHARLS).After feature selection via Elastic Net Regularization,we applied DLNMs to evaluate the lagged effects of risk factors.Disability was defined as the presence of any difficulties in basic activities of daily living(BADL).The cumulative relative risk(CRR)was calculated by summing the lag-specific risk estimates,representing the cumulative disability risk over the specified lag period.Effect modifications and sensitivity analyses were also performed.Results This study included a total of 2,318 participants.Early-phase lag factors,such as the difficulty in stooping(CRR=3.58;95%CI:2.31-5.55;P<0.001)and walking(CRR=2.77;95%CI:1.39-5.55;P<0.001),exerted the strongest effects immediately upon occurrence.Mid-phase lag factors,such as arthritis(CRR=1.51;95%CI:1.10-2.06;P=0.001),showed a resurgence in disability risk within 2-3 years.Late-phase lag factors,including depressive symptoms(CRR=2.38;95%CI:1.30-4.35;P<0.001)and elevated systolic blood pressure(CRR=1.64;95%CI:1.06-2.79;P=0.02),exhibited significant long-term cumulative risks.Conversely,grip strength(CRR=0.80;95%CI:0.54-0.95;P=0.02)and social participation(CRR=0.89;95%CI:0.73-0.99;P=0.04)were significant protective factors.Conclusions The findings underscore the importance of tailored interventions that account for various lag characteristics of different factors to effectively mitigate disability risk.Future studies should explore the underlying biological and sociological mechanisms of these lagged effects,identify intervention strategies that target risk factors with different lagged patterns,and evaluate their effectiveness.展开更多
近几年来,深度学习无所不在,赋能于各个领域.尤其是人工智能与传统科学的结合(AI for science,AI4Science)引发广泛关注.在AI4Science领域,利用人工智能算法求解PDEs(AI4PDEs)已成为计算力学研究的焦点.AI4PDEs的核心是将数据与方程相融...近几年来,深度学习无所不在,赋能于各个领域.尤其是人工智能与传统科学的结合(AI for science,AI4Science)引发广泛关注.在AI4Science领域,利用人工智能算法求解PDEs(AI4PDEs)已成为计算力学研究的焦点.AI4PDEs的核心是将数据与方程相融合,并且几乎可以求解任何偏微分方程问题,由于其融合数据的优势,相较于传统算法,其计算效率通常提升数万倍.因此,本文全面综述了AI4PDEs的研究,总结了现有AI4PDEs算法、理论,并讨论了其在固体力学中的应用,包括正问题和反问题,展望了未来研究方向,尤其是必然会出现的计算力学大模型.现有AI4PDEs算法包括基于物理信息神经网络(physicsinformed neural network,PINNs)、深度能量法(deep energy methods,DEM)、算子学习(operator learning),以及基于物理神经网络算子(physics-informed neural operator,PINO).AI4PDEs在科学计算中有许多应用,本文聚焦于固体力学,正问题包括线弹性、弹塑性,超弹性、以及断裂力学;反问题包括材料参数,本构,缺陷的识别,以及拓朴优化.AI4PDEs代表了一种全新的科学模拟方法,通过利用大量数据在特定问题上提供近似解,然后根据具体的物理方程进行微调,避免了像传统算法那样从头开始计算,因此AI4PDEs是未来计算力学大模型的雏形,能够大大加速传统数值算法.我们相信,利用人工智能助力科学计算不仅仅是计算领域的未来重要方向,同时也是计算力学的未来,即是智能计算力学。展开更多
This paper investigates the issue of fault-tolerant control for swarm systems subject to switched graphs,actuator faults and obstacles.A geometric-based partial differential equation(PDE)framework is proposed to unify...This paper investigates the issue of fault-tolerant control for swarm systems subject to switched graphs,actuator faults and obstacles.A geometric-based partial differential equation(PDE)framework is proposed to unify collision-free trajectory generation and fault-tolerant control.To deal with the fault-induced force imbalances,the Riemannian metric is proposed to coordinate nominal controllers and the global one.Then,Riemannianbased trajectory length optimization is solved by gradient's dynamic model-heat flow PDE,under which a feasible trajectory satisfying motion constraints is achieved to guide the faulty system.Such virtual control force emerges autonomously through this metric adjustments.Further,the tracking error is rigorously proven to be exponential boundedness.Simulation results confirm the validity of these theoretical findings.展开更多
Idiopathic pulmonary fibrosis(IPF)is a progressive lung disease and its incidence rate is rapidly rising.However,effective therapies for the treatment of IPF are still lacking.Phosphodiesterase 4(PDE4)inhibitors were ...Idiopathic pulmonary fibrosis(IPF)is a progressive lung disease and its incidence rate is rapidly rising.However,effective therapies for the treatment of IPF are still lacking.Phosphodiesterase 4(PDE4)inhibitors were reported to be potential anti-fibrotic agents.Herein,structure-based hit-to-lead optimization of natural isoaurostatin(8.98μmol/L)resulted in several potent inhibitors of PDE4 with half maximal inhibitory concentration(IC_(50))values ranging from 35 nmol/L to 126 nmol/L.Co-crystal structures revealed that isoaurostatin compounds exhibited different binding patterns from the classic PDE4 inhibitor rolipram and the analogues would favor to be Z configurations other than the corresponding E isomers.Finally,lead 2–9 showed remarkable in vitro/in vivo anti-fibrotic effects indicating its potential as a novel anti-IPF agent.展开更多
This opinion article discusses the original research work of Yünkül et al.(the Authors)published in the Journal of Mountain Science 21(9):3108–3122.Employing non-linear regression,fuzzy logic and artificial...This opinion article discusses the original research work of Yünkül et al.(the Authors)published in the Journal of Mountain Science 21(9):3108–3122.Employing non-linear regression,fuzzy logic and artificial neural network modeling techniques,the Authors interrogated a large database assembled from the existing research literature to assess the performance of twelve equation rules in predicting the undrained shear strength(s_(u))mobilized for remolded fine-grained soils at different values of liquidity index(I_(L))and water content ratio.Based on their analyses,the Authors proposed a simple and reportedly reliable correlation(i.e.,Eq.9 in their paper)for predicting s_(u) over the I_(L) range of 0.15 to 3.00.This article describes various shortcomings in the Authors’assembled database(including potentially anomalous data and covering an excessively wide I_(L) range in relation to routine geotechnical and transportation engineering applications)and their proposed s_(u)=f(I_(L))correlation.Contrary to the Authors’assertions,their proposed correlation is not reliable for fine-grained soils with consistencies in the general firm to stiff range(i.e.,for 0.15<I_(L)<0.40),increasingly overestimating s_(u) for reducing I_(L),and eventually predicting s_(u)→+∞for I_(L)→0.15+(while producing mathematically undefined s_(u) for I_(L)<0.15),thus rendering their correlation unconservative and potentially leading to unsafe geotechnical designs.Exponential or regular-power type s_(u)=f(I_(L))models are more s_(u)itable when developing correlations that are applicable over the full plastic range(of 0<I_(L)<1),thereby providing reasonably conservative s_(u) predictions for use in the preliminary design for routine geotechnical engineering applications.展开更多
Icariin is a pure compound derived from Epimedium brevicornu Maxim,and it helps the regulation of male reproduction.Nevertheless,the role and underlying mechanisms of Icariin in mediating male germ cell development re...Icariin is a pure compound derived from Epimedium brevicornu Maxim,and it helps the regulation of male reproduction.Nevertheless,the role and underlying mechanisms of Icariin in mediating male germ cell development remain to be clarified.Here,we have demonstrated that Icariin promoted proliferation and DNA synthesis of mouse spermatogonial stem cells(SSCs).Furthermore,surface plasmon resonance iron(SPRi)and molecular docking(MOE)assays revealed that phosphodiesterase 5A(PDE5A)was an important target of Icariin in mouse SSCs.Mechanically,Icariin decreased the expression level of PDE5A.Interestingly,hydrogen peroxides(H2O2)enhanced the expression level of phosphorylation H2A.X(p-H2A.X),whereas Icariin diminished the expression level of p-H2A.X and DNA damage caused by H2O2 in mouse SSCs.Finally,our in vivo animal study indicated that Icariin protected male reproduction.Collectively,these results implicate that Icariin targets PDE5A to regulate mouse SSC viability and DNA damage and improves male reproductive capacity.This study thus sheds new insights into molecular mechanisms underlying the fate decisions of mammalian SSCs and offers a scientific basis for the clinical application of Icariin in male reproduction.展开更多
Many experiments have supported the contact models,such as the GW and MB models,but the majority of previous validations have been performed under light loads,resulting in a linear relationship between normal force an...Many experiments have supported the contact models,such as the GW and MB models,but the majority of previous validations have been performed under light loads,resulting in a linear relationship between normal force and contact area.However,the real contact area fraction should never equal one;there must be a limit smaller than the apparent area,implying that the real contact area cannot increase linearly indefinitely.In this paper,the real contact area between two polymethylmethacrylate(PMMA)blocks under heavy load is measured using the total reflection method,and the contact area is analyzed using the image processing method.The results show that the real contact area increases with normal load linearly in light loads but non-linearly in heavy loads;the number of contact spots increases with load linearly in light loads but also non-linearly in heavy loads,synchronous with the change in the real contact area.The GW,MB,and Zhao,Maietta,and Chang(ZMC)models were used to predict the experiment results,but none of them predicted the non-linear stage.A revised GW model based on the bulk deformation hypothesis performs better in predicting the non-linear stage.The study’s findings can be applied to PMMA or other similar materials,and they can serve as a useful reference for future research on the contact mechanisms of other materials.展开更多
Organisms have evolved a strain limiting mechanism,reflected as a non-linear elastic constitutive,to prevent large deformations from threatening soft tissue integrity.Compared with linear elastic substrates,the wrinkl...Organisms have evolved a strain limiting mechanism,reflected as a non-linear elastic constitutive,to prevent large deformations from threatening soft tissue integrity.Compared with linear elastic substrates,the wrinkle of films on non-linear elastic substrates has received less attention.In this article,a unique wrinkle evolution of the film-substrate system with a J-shaped non-linear stress-strain relation is reported.The result shows that a concave hexagonal array pattern is formed with the shrinkage strain of the film-substrate systems developing.As the interconnection of hexagonal arrays,a unit cell ridge network appears with properties such as chirality and helix.The subparagraph maze pattern formed with high compression is mainly composed of special single-cell ridge networks such as spiral single cores,chiral double cores,and combined multi-cores.This evolutionary model is highly consistent with the results of experiments,and it also predicts wrinkle morphology that has not yet been reported.These findings can serve as a novel explanation for the surface wrinkle of biological soft tissue,as well as provide references for the preparation of artificial biomaterials and programmable soft matter.展开更多
基金supported by ScientificResearch Fund of National Health Commission of the People’s Republic of China-Major Science and Technology Program for Medicine and Health in Zhejiang Province(WKJ-ZJ-2406).
文摘Objectives This study aimed to explore the lagged and cumulative effects of risk factors on disability in older adults using distributed lag non-linear models(DLNMs).Methods We utilized data from the China Health and Retirement Longitudinal Study(CHARLS).After feature selection via Elastic Net Regularization,we applied DLNMs to evaluate the lagged effects of risk factors.Disability was defined as the presence of any difficulties in basic activities of daily living(BADL).The cumulative relative risk(CRR)was calculated by summing the lag-specific risk estimates,representing the cumulative disability risk over the specified lag period.Effect modifications and sensitivity analyses were also performed.Results This study included a total of 2,318 participants.Early-phase lag factors,such as the difficulty in stooping(CRR=3.58;95%CI:2.31-5.55;P<0.001)and walking(CRR=2.77;95%CI:1.39-5.55;P<0.001),exerted the strongest effects immediately upon occurrence.Mid-phase lag factors,such as arthritis(CRR=1.51;95%CI:1.10-2.06;P=0.001),showed a resurgence in disability risk within 2-3 years.Late-phase lag factors,including depressive symptoms(CRR=2.38;95%CI:1.30-4.35;P<0.001)and elevated systolic blood pressure(CRR=1.64;95%CI:1.06-2.79;P=0.02),exhibited significant long-term cumulative risks.Conversely,grip strength(CRR=0.80;95%CI:0.54-0.95;P=0.02)and social participation(CRR=0.89;95%CI:0.73-0.99;P=0.04)were significant protective factors.Conclusions The findings underscore the importance of tailored interventions that account for various lag characteristics of different factors to effectively mitigate disability risk.Future studies should explore the underlying biological and sociological mechanisms of these lagged effects,identify intervention strategies that target risk factors with different lagged patterns,and evaluate their effectiveness.
文摘近几年来,深度学习无所不在,赋能于各个领域.尤其是人工智能与传统科学的结合(AI for science,AI4Science)引发广泛关注.在AI4Science领域,利用人工智能算法求解PDEs(AI4PDEs)已成为计算力学研究的焦点.AI4PDEs的核心是将数据与方程相融合,并且几乎可以求解任何偏微分方程问题,由于其融合数据的优势,相较于传统算法,其计算效率通常提升数万倍.因此,本文全面综述了AI4PDEs的研究,总结了现有AI4PDEs算法、理论,并讨论了其在固体力学中的应用,包括正问题和反问题,展望了未来研究方向,尤其是必然会出现的计算力学大模型.现有AI4PDEs算法包括基于物理信息神经网络(physicsinformed neural network,PINNs)、深度能量法(deep energy methods,DEM)、算子学习(operator learning),以及基于物理神经网络算子(physics-informed neural operator,PINO).AI4PDEs在科学计算中有许多应用,本文聚焦于固体力学,正问题包括线弹性、弹塑性,超弹性、以及断裂力学;反问题包括材料参数,本构,缺陷的识别,以及拓朴优化.AI4PDEs代表了一种全新的科学模拟方法,通过利用大量数据在特定问题上提供近似解,然后根据具体的物理方程进行微调,避免了像传统算法那样从头开始计算,因此AI4PDEs是未来计算力学大模型的雏形,能够大大加速传统数值算法.我们相信,利用人工智能助力科学计算不仅仅是计算领域的未来重要方向,同时也是计算力学的未来,即是智能计算力学。
基金supported in part by the National Natural Science Foundation of China under Grant 62303144,62020106003,U22A2044in part by the Zhejiang Provincial Natural Science Foundation of China under Grant LQ23F030013.
文摘This paper investigates the issue of fault-tolerant control for swarm systems subject to switched graphs,actuator faults and obstacles.A geometric-based partial differential equation(PDE)framework is proposed to unify collision-free trajectory generation and fault-tolerant control.To deal with the fault-induced force imbalances,the Riemannian metric is proposed to coordinate nominal controllers and the global one.Then,Riemannianbased trajectory length optimization is solved by gradient's dynamic model-heat flow PDE,under which a feasible trajectory satisfying motion constraints is achieved to guide the faulty system.Such virtual control force emerges autonomously through this metric adjustments.Further,the tracking error is rigorously proven to be exponential boundedness.Simulation results confirm the validity of these theoretical findings.
基金supported by the Natural Science Foundation of China(Nos.22277019,82150204,22307031,22377023,22077143,and 82003594)Key Project of Guangdong Natural Science Foundation(No.2016A030311033)+2 种基金Fundamental Research Funds for Hainan University(Nos.KYQD(ZR)-21031,KYQD(ZR)-21108,KYQD(ZR)-23003,and XTCX2022JKA01)Guangdong Provincial Key Laboratory of Construction Foundation(No.2023B1212060022)Science Foundation of Hainan Province(Nos.KJRC2023B10,824YXQN420,and 324MS018)。
文摘Idiopathic pulmonary fibrosis(IPF)is a progressive lung disease and its incidence rate is rapidly rising.However,effective therapies for the treatment of IPF are still lacking.Phosphodiesterase 4(PDE4)inhibitors were reported to be potential anti-fibrotic agents.Herein,structure-based hit-to-lead optimization of natural isoaurostatin(8.98μmol/L)resulted in several potent inhibitors of PDE4 with half maximal inhibitory concentration(IC_(50))values ranging from 35 nmol/L to 126 nmol/L.Co-crystal structures revealed that isoaurostatin compounds exhibited different binding patterns from the classic PDE4 inhibitor rolipram and the analogues would favor to be Z configurations other than the corresponding E isomers.Finally,lead 2–9 showed remarkable in vitro/in vivo anti-fibrotic effects indicating its potential as a novel anti-IPF agent.
文摘This opinion article discusses the original research work of Yünkül et al.(the Authors)published in the Journal of Mountain Science 21(9):3108–3122.Employing non-linear regression,fuzzy logic and artificial neural network modeling techniques,the Authors interrogated a large database assembled from the existing research literature to assess the performance of twelve equation rules in predicting the undrained shear strength(s_(u))mobilized for remolded fine-grained soils at different values of liquidity index(I_(L))and water content ratio.Based on their analyses,the Authors proposed a simple and reportedly reliable correlation(i.e.,Eq.9 in their paper)for predicting s_(u) over the I_(L) range of 0.15 to 3.00.This article describes various shortcomings in the Authors’assembled database(including potentially anomalous data and covering an excessively wide I_(L) range in relation to routine geotechnical and transportation engineering applications)and their proposed s_(u)=f(I_(L))correlation.Contrary to the Authors’assertions,their proposed correlation is not reliable for fine-grained soils with consistencies in the general firm to stiff range(i.e.,for 0.15<I_(L)<0.40),increasingly overestimating s_(u) for reducing I_(L),and eventually predicting s_(u)→+∞for I_(L)→0.15+(while producing mathematically undefined s_(u) for I_(L)<0.15),thus rendering their correlation unconservative and potentially leading to unsafe geotechnical designs.Exponential or regular-power type s_(u)=f(I_(L))models are more s_(u)itable when developing correlations that are applicable over the full plastic range(of 0<I_(L)<1),thereby providing reasonably conservative s_(u) predictions for use in the preliminary design for routine geotechnical engineering applications.
基金supported by the grants from the National Nature Science Foundation of China(No.32170862)Developmental Biology and Breeding(No.2022XKQ0205)+2 种基金the Research Team for Reproduction Health and Translational Medicine of Hunan Normal University(No.2023JC101)Graduate Scientific Research Innovation Project of Hunan Province(No.CX2022520)Shanghai Key Laboratory of Reproductive Medicine(2022SKLRM01).
文摘Icariin is a pure compound derived from Epimedium brevicornu Maxim,and it helps the regulation of male reproduction.Nevertheless,the role and underlying mechanisms of Icariin in mediating male germ cell development remain to be clarified.Here,we have demonstrated that Icariin promoted proliferation and DNA synthesis of mouse spermatogonial stem cells(SSCs).Furthermore,surface plasmon resonance iron(SPRi)and molecular docking(MOE)assays revealed that phosphodiesterase 5A(PDE5A)was an important target of Icariin in mouse SSCs.Mechanically,Icariin decreased the expression level of PDE5A.Interestingly,hydrogen peroxides(H2O2)enhanced the expression level of phosphorylation H2A.X(p-H2A.X),whereas Icariin diminished the expression level of p-H2A.X and DNA damage caused by H2O2 in mouse SSCs.Finally,our in vivo animal study indicated that Icariin protected male reproduction.Collectively,these results implicate that Icariin targets PDE5A to regulate mouse SSC viability and DNA damage and improves male reproductive capacity.This study thus sheds new insights into molecular mechanisms underlying the fate decisions of mammalian SSCs and offers a scientific basis for the clinical application of Icariin in male reproduction.
基金Supported by National Natural Science Foundation of China(Grant No.11872033)Beijing Municipal Natural Science Foundation(Grant No.3172017)。
文摘Many experiments have supported the contact models,such as the GW and MB models,but the majority of previous validations have been performed under light loads,resulting in a linear relationship between normal force and contact area.However,the real contact area fraction should never equal one;there must be a limit smaller than the apparent area,implying that the real contact area cannot increase linearly indefinitely.In this paper,the real contact area between two polymethylmethacrylate(PMMA)blocks under heavy load is measured using the total reflection method,and the contact area is analyzed using the image processing method.The results show that the real contact area increases with normal load linearly in light loads but non-linearly in heavy loads;the number of contact spots increases with load linearly in light loads but also non-linearly in heavy loads,synchronous with the change in the real contact area.The GW,MB,and Zhao,Maietta,and Chang(ZMC)models were used to predict the experiment results,but none of them predicted the non-linear stage.A revised GW model based on the bulk deformation hypothesis performs better in predicting the non-linear stage.The study’s findings can be applied to PMMA or other similar materials,and they can serve as a useful reference for future research on the contact mechanisms of other materials.
基金This work was supported by the Youth Project of Hunan Provincial Department of Education(Grant No.22B0334)the Bridge and Tunnel Engineering Innovation Project of Changsha University of Science&Technology(Grant No.11ZDXK11)and the Practical Innovation and Entrepreneurship Capacity Improvement Plan of Changsha University of Science and Technology(Grant No.CLSJCX23029).
文摘Organisms have evolved a strain limiting mechanism,reflected as a non-linear elastic constitutive,to prevent large deformations from threatening soft tissue integrity.Compared with linear elastic substrates,the wrinkle of films on non-linear elastic substrates has received less attention.In this article,a unique wrinkle evolution of the film-substrate system with a J-shaped non-linear stress-strain relation is reported.The result shows that a concave hexagonal array pattern is formed with the shrinkage strain of the film-substrate systems developing.As the interconnection of hexagonal arrays,a unit cell ridge network appears with properties such as chirality and helix.The subparagraph maze pattern formed with high compression is mainly composed of special single-cell ridge networks such as spiral single cores,chiral double cores,and combined multi-cores.This evolutionary model is highly consistent with the results of experiments,and it also predicts wrinkle morphology that has not yet been reported.These findings can serve as a novel explanation for the surface wrinkle of biological soft tissue,as well as provide references for the preparation of artificial biomaterials and programmable soft matter.
