Background:As is widely known,an increasing number of forest areas were managed to preserve and enhance the health of forest ecosystems.However,previous research on forest management has often overlooked the importanc...Background:As is widely known,an increasing number of forest areas were managed to preserve and enhance the health of forest ecosystems.However,previous research on forest management has often overlooked the importance of structure-based.Aims:Our objectives were to define the direction of structure-based forest management.Subsequently,we investigated the relationships between forest structure and the regeneration,growth,and mortality of trees under different thinning treatments.Ultimately,the drivers of forest structural change were explored.Methods:On the basis of 92 sites selected from northeastern China,with different recovery time (from 1 to 15years) and different thinning intensities (0–59.9%) since the last thinning.Principal component analysis (PCA)identified relationships among factors determining forest spatial structure.The structural equation model (SEM)was used to analyze the driving factors behind the changes in forest spatial structure after thinning.Results:Light thinning (0–20%trees removed) promoted forest regeneration,and heavy thinning (over 35% of trees removed) facilitated forest growth.However,only moderate thinning (20%–35%trees removed) created a reasonable spatial structure.While dead trees were clustered,and they were hardly affected by thinning intensity.Additionally,thinning intensity,recovery time,and altitude indirectly improve the spatial structure of the forest by influencing diameter at breast height (DBH) and canopy area.Conclusion:Creating larger DBH and canopy area through thinning will promote the formation of complex forest structures,which cultivates healthy and stable forests.展开更多
Research on high voltage(HV)silicon carbide(SiC)power semiconductor devices has attracted much attention in recent years.This paper overviews the development and status of HV SiC devices.Meanwhile,benefits of HV SiC d...Research on high voltage(HV)silicon carbide(SiC)power semiconductor devices has attracted much attention in recent years.This paper overviews the development and status of HV SiC devices.Meanwhile,benefits of HV SiC devices are presented.The technologies and challenges for HV SiC device application in converter design are discussed.The state-of-the-art applications of HV SiC devices are also reviewed.展开更多
Ground-borne noise caused by track vibration became one of major problem affecting urban rail transit development. Resilient rail fasteners come to be a main measure of reducing ground-borne noise. Low stiffness of fa...Ground-borne noise caused by track vibration became one of major problem affecting urban rail transit development. Resilient rail fasteners come to be a main measure of reducing ground-borne noise. Low stiffness of fastener contributes to ensuring the good effect of vibration isolation, but causing higher vibration of rails, while the tuned damper fastener can make it up. In this paper, the simulation of rail receptance is used to fit on site measured data, then the data are used to build a vehicle-track-foundation model to do the calculations, like vibration reduction of track systems and rails. According to the results, the tuned damper fastener can reduce the vibration of slab as well as rails.展开更多
Background:The initial randomized,double-blinded,actively controlled,phase III ANEAS study(NCT03849768)demonstrated that aumolertinib showed superior efficacy relative to gefitinib as first-line therapy in epidermal g...Background:The initial randomized,double-blinded,actively controlled,phase III ANEAS study(NCT03849768)demonstrated that aumolertinib showed superior efficacy relative to gefitinib as first-line therapy in epidermal growth factor receptor(EGFR)-mutated advanced non-small cell lung cancer(NSCLC).Metastatic disease in the central nervous system(CNS)remains a challenge in the management of NSCLC.This study aimed to compare the efficacy of aumolertinib versus gefitinib among patients with baseline CNS metastases in the ANEAS study.Methods:Eligible patients were enrolled and randomly assigned in a 1:1 ratio to orally receive either aumolertinib or gefitinib in a double-blinded fashion.Patients with asymptomatic,stable CNS metastases were included.Follow-up imaging of the same modality as the initial CNS imaging was performed every 6 weeks for 15 months,then every 12weeks.CNS responsewas assessed by a neuroradiological blinded,independent central review(neuroradiological-BICR).The primary endpoint for this subgroup analysis was CNS progression-free survival(PFS).Results:Of the 429 patients enrolled and randomized in the ANEAS study,106 patients were found to have CNS metastases(CNS Full Analysis Set,cFAS)at baseline by neuroradiological-BICR,and 60 of them had CNS target lesions(CNS Evaluable for Response,cEFR).Treatment with aumolertinib significantly prolonged median CNS PFS compared with gefitinib in both cFAS(29.0 vs.8.3 months;hazard ratio[HR]=0.31;95%confidence interval[CI],0.17-0.56;P<0.001)and cEFR(29.0 vs.8.3 months;HR=0.26;95%CI,0.11-0.57;P<0.001).The confirmed CNS overall response rate in cEFRwas 85.7%and 75.0%in patients treated with aumolertinib and gefitinib,respectively.Competing risk analysis showed that the estimated probability of CNS progression without prior non-CNS progression or death was consistently lower with aumolertinib than with gefitinib in patients with and without CNSmetastases at baseline.No new safety findings were observed.Conclusions:These results indicate a potential advantage of aumolertinib over gefitinib in terms of CNS PFS and the risk of CNS progression in patients with EGFR-mutated advanced NSCLC with baseline CNS metastases.展开更多
We designed a disulfide-crosslinked mini-protein with a two-helical topology consisting of L-and Damino acids,which was exceptionally stable in serum.Therefore,we further used it as a scaffold to design mini-proteins ...We designed a disulfide-crosslinked mini-protein with a two-helical topology consisting of L-and Damino acids,which was exceptionally stable in serum.Therefore,we further used it as a scaffold to design mini-proteins targeting p53 positive tumor cells.Based on bifunctional grafting,key residues from the transactivation domain of p53 and a designed unnatural amino acid were grafted into the helix constituted by L-amino acids to confer the mini-protein with MDM2 inhibitory activity.Meanwhile,ten Arg residues were introduced to improve its membrane penetrating capacity.Among the mini-proteins,UPROL-10e showed nano-molar binding affinity on MDM2 and cellular toxicity on p53 expressing HCT116cells.展开更多
Exercise intervention at the early stage of type 2 diabetes mellitus(T2DM)can aid in the maintenance of blood glucose homeostasis and prevent the development of macrovascular and microvascular complications.However,th...Exercise intervention at the early stage of type 2 diabetes mellitus(T2DM)can aid in the maintenance of blood glucose homeostasis and prevent the development of macrovascular and microvascular complications.However,the exercise-regulated pathways that prevent the development of T2DM remain largely unclear.In this study,two forms of exercise intervention,treadmill training and voluntary wheel running,were conducted for high-fat diet(HFD)-induced obese mice.We observed that both forms of exercise intervention alleviated HFD-induced insulin resistance and glucose intolerance.Skeletal muscle is recognized as the primary site for postprandial glucose uptake and for responsive alteration beyond exercise training.Metabolomic profiling of the plasma and skeletal muscle in Chow,HFD,and HFD-exercise groups revealed robust alterations in metabolic pathways by exercise intervention in both cases.Overlapping analysis identified nine metabolites,including beta-alanine,leucine,valine,and tryptophan,which were reversed by exercise treatment in both the plasma and skeletal muscle.Transcriptomic analysis of gene expression profiles in the skeletal muscle revealed several key pathways involved in the beneficial effects of exercise on metabolic homeostasis.In addition,integrative transcriptomic and metabolomic analyses uncovered strong correlations between the concentrations of bioactive metabolites and the expression levels of genes involved in energy metabolism,insulin sensitivity,and immune response in the skeletal muscle.This work established two models of exercise intervention in obese mice and provided mechanistic insights into the beneficial effects of exercise intervention on systemic energy homeostasis.展开更多
Alzheimer’s disease(AD)is a progressive and fatal neurodegenerative condition and the most prevalent cause of dementia.This disease is characterized by progressive cognitive impairment.The prevalence of AD is current...Alzheimer’s disease(AD)is a progressive and fatal neurodegenerative condition and the most prevalent cause of dementia.This disease is characterized by progressive cognitive impairment.The prevalence of AD is currently affecting more than 35 million people and is rising worldwide.No efficient therapy is currently available due to low drug potency and a number of various obstacles to delivery.Recent nanotechnological advancements have the potential to offer promising therapeutic options.Progress on nanomaterials as well as their applications in biomedicine is receiving increasing attention,especially the advantages of nanomaterial-based drug delivery systems.The aim of this review is to comprehensively summarize the latest developments in nanomaterial-based strategies for AD treatment,including nanoparticles,liposomes and other options for the delivery of therapeutic compounds and scaffolds for cell delivery strategies.Future research directions are also proposed.We hope this review can provide important information to guide the future development of nanomaterials in AD treatment.展开更多
With the development of the social media and Internet, discovering latent information from massive information is becoming particularly relevant to improving user experience. Research efforts based on preferences and ...With the development of the social media and Internet, discovering latent information from massive information is becoming particularly relevant to improving user experience. Research efforts based on preferences and relationships between users have attracted more and more attention. Predictive problems, such as inferring friend relationship and co-author relationship between users have been explored. However, many such methods are based on analyzing either node features or the network structures separately, few have tried to tackle both of them at the same time. In this paper, in order to discover latent co-interests' relationship, we not only consider users' attributes but network information as well. In addition, we propose an Interest-based Factor Graph Model (I-FGM) to incorporate these factors. Experiments on two data sets (bookmarking and music network) demonstrate that this predictive method can achieve better results than the other three methods (ANN, NB, and SVM).展开更多
基金financially supported by the Innovation Foundation for Doctoral Program of Forestry Engineering of Northeast Forestry University,grant number:LYGC202117the China Scholarship Council(CSC),grant number:202306600046+1 种基金the Research and Development Plan of Applied Technology in Heilongjiang Province of China,grant number:GA19C006Research and Demonstration on Functional Improvement Technology of Forest Ecological Security Barrier in Heilongjiang Province,grant number:GA21C030。
文摘Background:As is widely known,an increasing number of forest areas were managed to preserve and enhance the health of forest ecosystems.However,previous research on forest management has often overlooked the importance of structure-based.Aims:Our objectives were to define the direction of structure-based forest management.Subsequently,we investigated the relationships between forest structure and the regeneration,growth,and mortality of trees under different thinning treatments.Ultimately,the drivers of forest structural change were explored.Methods:On the basis of 92 sites selected from northeastern China,with different recovery time (from 1 to 15years) and different thinning intensities (0–59.9%) since the last thinning.Principal component analysis (PCA)identified relationships among factors determining forest spatial structure.The structural equation model (SEM)was used to analyze the driving factors behind the changes in forest spatial structure after thinning.Results:Light thinning (0–20%trees removed) promoted forest regeneration,and heavy thinning (over 35% of trees removed) facilitated forest growth.However,only moderate thinning (20%–35%trees removed) created a reasonable spatial structure.While dead trees were clustered,and they were hardly affected by thinning intensity.Additionally,thinning intensity,recovery time,and altitude indirectly improve the spatial structure of the forest by influencing diameter at breast height (DBH) and canopy area.Conclusion:Creating larger DBH and canopy area through thinning will promote the formation of complex forest structures,which cultivates healthy and stable forests.
基金This work made use of the Engineering Research Center Shared Facilities supported by the Engineering Research Center Program of the National Science Foundation and DOE under ARPA-E and Power America Program and the CURENT Industry Partnership Program.
文摘Research on high voltage(HV)silicon carbide(SiC)power semiconductor devices has attracted much attention in recent years.This paper overviews the development and status of HV SiC devices.Meanwhile,benefits of HV SiC devices are presented.The technologies and challenges for HV SiC device application in converter design are discussed.The state-of-the-art applications of HV SiC devices are also reviewed.
文摘Ground-borne noise caused by track vibration became one of major problem affecting urban rail transit development. Resilient rail fasteners come to be a main measure of reducing ground-borne noise. Low stiffness of fastener contributes to ensuring the good effect of vibration isolation, but causing higher vibration of rails, while the tuned damper fastener can make it up. In this paper, the simulation of rail receptance is used to fit on site measured data, then the data are used to build a vehicle-track-foundation model to do the calculations, like vibration reduction of track systems and rails. According to the results, the tuned damper fastener can reduce the vibration of slab as well as rails.
基金Hansoh Pharmaceutical Group Co.LtdNational Natural Science Foundation of China,Grant/Award Numbers:82030045,82241227+3 种基金National Multi-disciplinary Treatment Project for Major Diseases,Grant/Award Number:2020NMDTPCollaborative Innovation Center for Clinical and Translational Science by Ministry of Education&Shanghai,Grant/Award Numbers:CCTS-202204,CCTS-202304Shanghai Chest Hospital Basic Research Project,Grant/Award Number:2023YNKT-1Pujiang Program,Grant/Award Number:22PJ1420700。
文摘Background:The initial randomized,double-blinded,actively controlled,phase III ANEAS study(NCT03849768)demonstrated that aumolertinib showed superior efficacy relative to gefitinib as first-line therapy in epidermal growth factor receptor(EGFR)-mutated advanced non-small cell lung cancer(NSCLC).Metastatic disease in the central nervous system(CNS)remains a challenge in the management of NSCLC.This study aimed to compare the efficacy of aumolertinib versus gefitinib among patients with baseline CNS metastases in the ANEAS study.Methods:Eligible patients were enrolled and randomly assigned in a 1:1 ratio to orally receive either aumolertinib or gefitinib in a double-blinded fashion.Patients with asymptomatic,stable CNS metastases were included.Follow-up imaging of the same modality as the initial CNS imaging was performed every 6 weeks for 15 months,then every 12weeks.CNS responsewas assessed by a neuroradiological blinded,independent central review(neuroradiological-BICR).The primary endpoint for this subgroup analysis was CNS progression-free survival(PFS).Results:Of the 429 patients enrolled and randomized in the ANEAS study,106 patients were found to have CNS metastases(CNS Full Analysis Set,cFAS)at baseline by neuroradiological-BICR,and 60 of them had CNS target lesions(CNS Evaluable for Response,cEFR).Treatment with aumolertinib significantly prolonged median CNS PFS compared with gefitinib in both cFAS(29.0 vs.8.3 months;hazard ratio[HR]=0.31;95%confidence interval[CI],0.17-0.56;P<0.001)and cEFR(29.0 vs.8.3 months;HR=0.26;95%CI,0.11-0.57;P<0.001).The confirmed CNS overall response rate in cEFRwas 85.7%and 75.0%in patients treated with aumolertinib and gefitinib,respectively.Competing risk analysis showed that the estimated probability of CNS progression without prior non-CNS progression or death was consistently lower with aumolertinib than with gefitinib in patients with and without CNSmetastases at baseline.No new safety findings were observed.Conclusions:These results indicate a potential advantage of aumolertinib over gefitinib in terms of CNS PFS and the risk of CNS progression in patients with EGFR-mutated advanced NSCLC with baseline CNS metastases.
基金supported by the National Natural Science Foundation of China(Nos.3217110331 and 8212200560)Major new drug development in Shandong Province(No.2020CXGC010503)。
文摘We designed a disulfide-crosslinked mini-protein with a two-helical topology consisting of L-and Damino acids,which was exceptionally stable in serum.Therefore,we further used it as a scaffold to design mini-proteins targeting p53 positive tumor cells.Based on bifunctional grafting,key residues from the transactivation domain of p53 and a designed unnatural amino acid were grafted into the helix constituted by L-amino acids to confer the mini-protein with MDM2 inhibitory activity.Meanwhile,ten Arg residues were introduced to improve its membrane penetrating capacity.Among the mini-proteins,UPROL-10e showed nano-molar binding affinity on MDM2 and cellular toxicity on p53 expressing HCT116cells.
基金supported by grants from the National Key Research and Development Program of China(2018YFA0800403 and 2021YFC2701903)the Training Program of the Major Research Plan of the National Natural Science Foundation of China(91857110)+5 种基金the National Natural Science Foundation of China(81670740,82100904,and 32000817)the National Natural Science Fund for Excellent Young Scholars of China(81722012)Zhejiang Provincial Natural Science Foundation of China(LZ21H070001 and LQ21C110001)the Innovative Institute of Basic Medical Sciences of Zhejiang University,the Fundamental Research Funds for the Central Universities,the Construction Fund of Medical Key Disciplines of Hangzhou,Hangzhou Science and Technology Bureau(20150733Q13 and ZD20200129)the Construction Fund of Key Medical Disciplines of Hangzhou(OO20200055)the K.C.Wong Education Foundation.
文摘Exercise intervention at the early stage of type 2 diabetes mellitus(T2DM)can aid in the maintenance of blood glucose homeostasis and prevent the development of macrovascular and microvascular complications.However,the exercise-regulated pathways that prevent the development of T2DM remain largely unclear.In this study,two forms of exercise intervention,treadmill training and voluntary wheel running,were conducted for high-fat diet(HFD)-induced obese mice.We observed that both forms of exercise intervention alleviated HFD-induced insulin resistance and glucose intolerance.Skeletal muscle is recognized as the primary site for postprandial glucose uptake and for responsive alteration beyond exercise training.Metabolomic profiling of the plasma and skeletal muscle in Chow,HFD,and HFD-exercise groups revealed robust alterations in metabolic pathways by exercise intervention in both cases.Overlapping analysis identified nine metabolites,including beta-alanine,leucine,valine,and tryptophan,which were reversed by exercise treatment in both the plasma and skeletal muscle.Transcriptomic analysis of gene expression profiles in the skeletal muscle revealed several key pathways involved in the beneficial effects of exercise on metabolic homeostasis.In addition,integrative transcriptomic and metabolomic analyses uncovered strong correlations between the concentrations of bioactive metabolites and the expression levels of genes involved in energy metabolism,insulin sensitivity,and immune response in the skeletal muscle.This work established two models of exercise intervention in obese mice and provided mechanistic insights into the beneficial effects of exercise intervention on systemic energy homeostasis.
基金financially supported by Hunan Provincial Key Laboratory of Micro&Nano Materials Interface Sciencethe National Natural Science Foundation of China(Nos.81603670,81873169,21773311,21972169)+1 种基金Hunan Provincial Natural Science Foundation of China(Nos.2017JJ3459,2020JJ4803)the Hunan Provincial Science and Technology Plan Project,China(No.2019TP1001)。
文摘Alzheimer’s disease(AD)is a progressive and fatal neurodegenerative condition and the most prevalent cause of dementia.This disease is characterized by progressive cognitive impairment.The prevalence of AD is currently affecting more than 35 million people and is rising worldwide.No efficient therapy is currently available due to low drug potency and a number of various obstacles to delivery.Recent nanotechnological advancements have the potential to offer promising therapeutic options.Progress on nanomaterials as well as their applications in biomedicine is receiving increasing attention,especially the advantages of nanomaterial-based drug delivery systems.The aim of this review is to comprehensively summarize the latest developments in nanomaterial-based strategies for AD treatment,including nanoparticles,liposomes and other options for the delivery of therapeutic compounds and scaffolds for cell delivery strategies.Future research directions are also proposed.We hope this review can provide important information to guide the future development of nanomaterials in AD treatment.
基金the National Natural Science Foundation of China (No. 61170192)the Natural Science Foundations of Municipality of Chongqing(No. CSTC2012JJB40012)
文摘With the development of the social media and Internet, discovering latent information from massive information is becoming particularly relevant to improving user experience. Research efforts based on preferences and relationships between users have attracted more and more attention. Predictive problems, such as inferring friend relationship and co-author relationship between users have been explored. However, many such methods are based on analyzing either node features or the network structures separately, few have tried to tackle both of them at the same time. In this paper, in order to discover latent co-interests' relationship, we not only consider users' attributes but network information as well. In addition, we propose an Interest-based Factor Graph Model (I-FGM) to incorporate these factors. Experiments on two data sets (bookmarking and music network) demonstrate that this predictive method can achieve better results than the other three methods (ANN, NB, and SVM).