The protein connector enhancer of kinase suppressor of Ras 2(CNKSR2),present in both the postsynaptic density and cytoplasm of neurons,is a scaffolding protein with several protein-binding domains.Variants of the CNKS...The protein connector enhancer of kinase suppressor of Ras 2(CNKSR2),present in both the postsynaptic density and cytoplasm of neurons,is a scaffolding protein with several protein-binding domains.Variants of the CNKSR2 gene have been implicated in neurodevelopmental disorders,particularly intellectual disability,although the precise mechanism involved has not yet been fully understood.Research has demonstrated that CNKSR2 plays a role in facilitating the localization of postsynaptic density protein complexes to the membrane,thereby influencing synaptic signaling and the morphogenesis of dendritic spines.However,the function of CNKSR2 in the cytoplasm remains to be elucidated.In this study,we used immunoprecipitation and high-resolution liquid chromatography-mass spectrometry to identify the interactors of CNKSR2.Through a combination of bioinformatic analysis and cytological experiments,we found that the CNKSR2 interactors were significantly enriched in the proteome of the centrosome.We also showed that CNKSR2 interacted with the microtubule protein DYNC1H1 and with the centrosome marker CEP290.Subsequent colocalization analysis confirmed the centrosomal localization of CNKSR2.When we downregulated CNKSR2 expression in mouse neuroblastoma cells(Neuro 2A),we observed significant changes in the expression of numerous centrosomal genes.This manipulation also affected centrosome-related functions,including cell size and shape,cell proliferation,and motility.Furthermore,we found that CNKSR2 interactors were highly enriched in de novo variants associated with intellectual disability and autism spectrum disorder.Our findings establish a connection between CNKSR2 and the centrosome,and offer new insights into the underlying mechanisms of neurodevelopmental disorders.展开更多
The Advanced Geosynchronous Radiation Imager(AGRI)is a mission-critical instrument for the Fengyun series of satellites.AGRI acquires full-disk images every 15 min and views East Asia every 5 min through 14 spectral b...The Advanced Geosynchronous Radiation Imager(AGRI)is a mission-critical instrument for the Fengyun series of satellites.AGRI acquires full-disk images every 15 min and views East Asia every 5 min through 14 spectral bands,enabling the detection of highly variable aerosol optical depth(AOD).Quantitative retrieval of AOD has hitherto been challenging,especially over land.In this study,an AOD retrieval algorithm is proposed that combines deep learning and transfer learning.The algorithm uses core concepts from both the Dark Target(DT)and Deep Blue(DB)algorithms to select features for the machinelearning(ML)algorithm,allowing for AOD retrieval at 550 nm over both dark and bright surfaces.The algorithm consists of two steps:①A baseline deep neural network(DNN)with skip connections is developed using 10 min Advanced Himawari Imager(AHI)AODs as the target variable,and②sunphotometer AODs from 89 ground-based stations are used to fine-tune the DNN parameters.Out-of-station validation shows that the retrieved AOD attains high accuracy,characterized by a coefficient of determination(R2)of 0.70,a mean bias error(MBE)of 0.03,and a percentage of data within the expected error(EE)of 70.7%.A sensitivity study reveals that the top-of-atmosphere reflectance at 650 and 470 nm,as well as the surface reflectance at 650 nm,are the two largest sources of uncertainty impacting the retrieval.In a case study of monitoring an extreme aerosol event,the AGRI AOD is found to be able to capture the detailed temporal evolution of the event.This work demonstrates the superiority of the transfer-learning technique in satellite AOD retrievals and the applicability of the retrieved AGRI AOD in monitoring extreme pollution events.展开更多
PCrNi3MoV steel is a medium-carbon,low-alloy quenched and tempered steel that finds its applications in military gun barrels due to the high wear resistance and ablation resistance.To study the penetration and failure...PCrNi3MoV steel is a medium-carbon,low-alloy quenched and tempered steel that finds its applications in military gun barrels due to the high wear resistance and ablation resistance.To study the penetration and failure modes of PCrNi3MoV plates impacted by tungsten spheres,tungsten spheres of various diameters(5 mm,8 mm,and 10 mm)were used to impact PCrNi3MoV steel plates with thicknesses of 6 mm,9 mm,and 14 mm.The penetration performance of the spheres was analyzed for different velocities,and the ultimate penetration velocity of the plate was obtained.It was found that the primary failure modes of the PCrNi3MoV plate were compression pitting failure and shear failure.Using the dimensional analysis method,a relationship between the bulge height of the steel plate and the fragment velocity,an equation for the ultimate penetration velocity,and a relationship between the target penetration energy and the fragment velocity were obtained.Then,a projectile-target action index was proposed to describe the process of tungsten spheres with different velocities impacting target plates.The results suggested that under the same thickness of the target plate,a larger-diameter fragment required more kinetic energy to obtain the same ultimate penetration effect as a smaller-diameter fragment.The equations obtained through dimensional analysis predicted values that agreed well with experimental values,indicating that these equations can be applied to engineering applications.展开更多
BACKGROUND:Poisoned patients often suffer damage to multiple systems,and those experiencing central nervous system disorders present more severe conditions,prolonged hospital stays,and increased mortality rates.We aim...BACKGROUND:Poisoned patients often suffer damage to multiple systems,and those experiencing central nervous system disorders present more severe conditions,prolonged hospital stays,and increased mortality rates.We aimed to assess the efficacy of rehabilitation interventions for patients with toxic encephalopathy.METHODS:This retrospective,observational,comparative cohort study was performed at the teaching hospital affiliated of Nanjing Medical University,from October 2020 to December 2022.Patients who met the diagnostic criteria for toxic encephalopathy and exclusion criteria were included,and patients were divided into three subgroups according to Glasgow Coma Scale(GCS).Demographic and clinical characteristics were collected.The effect of the rehabilitation intervention on patients were assessed in the improvement of consciousness status(Glasgow Coma Scale[GCS]score),muscle strength and movement and swallowing function(Fugl-Meyer Assessment[FMA]scale,Water Swallow Test[WST],and Standardized Swallowing Assessment[SSA]).Subgroup analysis was based on different toxic species.RESULTS:Out of the 464 patients with toxic encephalopathy,184 cases received rehabilitation treatments.For the severe toxic encephalopathy patients,patients without rehabilitation intervention have a 2.21 times higher risk of death compared to patients with rehabilitation intervention(Hazard ratio[HR]=2.21).Subgroup analysis revealed that rehabilitation intervention significantly increased the survival rate of patients with pesticide poisoning(P=0.02),while no significant improvement was observed in patients with drug/biological agent poisoning(P=0.44).After rehabilitation intervention,significant improvement in GCS and FMA were observed in severe patients with toxic encephalopathy(P<0.01).CONCLUSION:Active rehabilitation intervention for patients exposed to poisons that can potentially cause toxic encephalopathy may improve the prognosis and reduce the mortality rate in clinical practice.展开更多
Landscape fragmentation is generally viewed as an indicator of environmental stresses or risks,but the fragmentation intensity assessment also depends on the scale of data and the definition of spatial unit.This study...Landscape fragmentation is generally viewed as an indicator of environmental stresses or risks,but the fragmentation intensity assessment also depends on the scale of data and the definition of spatial unit.This study aimed to explore the scale-dependence of forest fragmentation intensity along a moisture gradient in Yinshan Mountain of North China,and to estimate environmental sensitivity of forest fragmentation in this semi-arid landscape.We developed an automatic classification algorithm using simple linear iterative clustering(SLIC)and Gaussian mixture model(GMM),and extracted tree canopy patches from Google Earth images(GEI),with an accuracy of 89.2%in the study area.Then we convert the tree canopy patches to forest category according to definition of forest that tree density greater than 10%,and compared it with forest categories from global land use datasets,FROM-GLC10 and GlobeLand30,with spatial resolutions of 10 m and 30 m,respectively.We found that the FROM-GLC10 and GlobeLand30 datasets underestimated the forest area in Yinshan Mountain by 16.88%and 21.06%,respectively;and the ratio of open forest(OF,10%<tree coverage<40%)to closed forest(CF,tree coverage>40%)areas in the underestimated part was 2:1.The underestimations concentrated in warmer and drier areas occupied mostly by large coverage of OFs with severely fragmented canopies.Fragmentation intensity of canopies positively correlated with spring temperature while negatively correlated with summer precipitation and terrain slope.When summer precipitation was less than 300 mm or spring temperature higher than 4℃,canopy fragmentation intensity rose drastically,while the forest area percentage kept stable.Our study suggested that the spatial configuration,e.g.,sparseness,is more sensitive to drought stress than area percentage.This highlights the importance of data resolution and proper fragmentation measurements for forest patterns and environmental interpretation,which is the base of reliable ecosystem predictions with regard to the future climate scenarios.展开更多
基金supported by the National Nature Science Foundation of China,No.32101020(to JL)the Natural Science Foundation of Shandong Province,Nos.ZR2020MC071(to JL),ZR2023MH327(to HZ)+1 种基金the Integrated Project of Major Research Plan of National Natural Science Foundation of China,No.92249303(to PL)the Natural Science Foundation of Qingdao,No.23-2-1-193-zyyd-jch(to HZ)。
文摘The protein connector enhancer of kinase suppressor of Ras 2(CNKSR2),present in both the postsynaptic density and cytoplasm of neurons,is a scaffolding protein with several protein-binding domains.Variants of the CNKSR2 gene have been implicated in neurodevelopmental disorders,particularly intellectual disability,although the precise mechanism involved has not yet been fully understood.Research has demonstrated that CNKSR2 plays a role in facilitating the localization of postsynaptic density protein complexes to the membrane,thereby influencing synaptic signaling and the morphogenesis of dendritic spines.However,the function of CNKSR2 in the cytoplasm remains to be elucidated.In this study,we used immunoprecipitation and high-resolution liquid chromatography-mass spectrometry to identify the interactors of CNKSR2.Through a combination of bioinformatic analysis and cytological experiments,we found that the CNKSR2 interactors were significantly enriched in the proteome of the centrosome.We also showed that CNKSR2 interacted with the microtubule protein DYNC1H1 and with the centrosome marker CEP290.Subsequent colocalization analysis confirmed the centrosomal localization of CNKSR2.When we downregulated CNKSR2 expression in mouse neuroblastoma cells(Neuro 2A),we observed significant changes in the expression of numerous centrosomal genes.This manipulation also affected centrosome-related functions,including cell size and shape,cell proliferation,and motility.Furthermore,we found that CNKSR2 interactors were highly enriched in de novo variants associated with intellectual disability and autism spectrum disorder.Our findings establish a connection between CNKSR2 and the centrosome,and offer new insights into the underlying mechanisms of neurodevelopmental disorders.
基金supported by the National Natural Science of Foundation of China(41825011,42030608,42105128,and 42075079)the Opening Foundation of Key Laboratory of Atmospheric Sounding,the CMA and the CMA Research Center on Meteorological Observation Engineering Technology(U2021Z03).
文摘The Advanced Geosynchronous Radiation Imager(AGRI)is a mission-critical instrument for the Fengyun series of satellites.AGRI acquires full-disk images every 15 min and views East Asia every 5 min through 14 spectral bands,enabling the detection of highly variable aerosol optical depth(AOD).Quantitative retrieval of AOD has hitherto been challenging,especially over land.In this study,an AOD retrieval algorithm is proposed that combines deep learning and transfer learning.The algorithm uses core concepts from both the Dark Target(DT)and Deep Blue(DB)algorithms to select features for the machinelearning(ML)algorithm,allowing for AOD retrieval at 550 nm over both dark and bright surfaces.The algorithm consists of two steps:①A baseline deep neural network(DNN)with skip connections is developed using 10 min Advanced Himawari Imager(AHI)AODs as the target variable,and②sunphotometer AODs from 89 ground-based stations are used to fine-tune the DNN parameters.Out-of-station validation shows that the retrieved AOD attains high accuracy,characterized by a coefficient of determination(R2)of 0.70,a mean bias error(MBE)of 0.03,and a percentage of data within the expected error(EE)of 70.7%.A sensitivity study reveals that the top-of-atmosphere reflectance at 650 and 470 nm,as well as the surface reflectance at 650 nm,are the two largest sources of uncertainty impacting the retrieval.In a case study of monitoring an extreme aerosol event,the AGRI AOD is found to be able to capture the detailed temporal evolution of the event.This work demonstrates the superiority of the transfer-learning technique in satellite AOD retrievals and the applicability of the retrieved AGRI AOD in monitoring extreme pollution events.
文摘PCrNi3MoV steel is a medium-carbon,low-alloy quenched and tempered steel that finds its applications in military gun barrels due to the high wear resistance and ablation resistance.To study the penetration and failure modes of PCrNi3MoV plates impacted by tungsten spheres,tungsten spheres of various diameters(5 mm,8 mm,and 10 mm)were used to impact PCrNi3MoV steel plates with thicknesses of 6 mm,9 mm,and 14 mm.The penetration performance of the spheres was analyzed for different velocities,and the ultimate penetration velocity of the plate was obtained.It was found that the primary failure modes of the PCrNi3MoV plate were compression pitting failure and shear failure.Using the dimensional analysis method,a relationship between the bulge height of the steel plate and the fragment velocity,an equation for the ultimate penetration velocity,and a relationship between the target penetration energy and the fragment velocity were obtained.Then,a projectile-target action index was proposed to describe the process of tungsten spheres with different velocities impacting target plates.The results suggested that under the same thickness of the target plate,a larger-diameter fragment required more kinetic energy to obtain the same ultimate penetration effect as a smaller-diameter fragment.The equations obtained through dimensional analysis predicted values that agreed well with experimental values,indicating that these equations can be applied to engineering applications.
基金funded by the National Natural Science Foundation of China(82372214).
文摘BACKGROUND:Poisoned patients often suffer damage to multiple systems,and those experiencing central nervous system disorders present more severe conditions,prolonged hospital stays,and increased mortality rates.We aimed to assess the efficacy of rehabilitation interventions for patients with toxic encephalopathy.METHODS:This retrospective,observational,comparative cohort study was performed at the teaching hospital affiliated of Nanjing Medical University,from October 2020 to December 2022.Patients who met the diagnostic criteria for toxic encephalopathy and exclusion criteria were included,and patients were divided into three subgroups according to Glasgow Coma Scale(GCS).Demographic and clinical characteristics were collected.The effect of the rehabilitation intervention on patients were assessed in the improvement of consciousness status(Glasgow Coma Scale[GCS]score),muscle strength and movement and swallowing function(Fugl-Meyer Assessment[FMA]scale,Water Swallow Test[WST],and Standardized Swallowing Assessment[SSA]).Subgroup analysis was based on different toxic species.RESULTS:Out of the 464 patients with toxic encephalopathy,184 cases received rehabilitation treatments.For the severe toxic encephalopathy patients,patients without rehabilitation intervention have a 2.21 times higher risk of death compared to patients with rehabilitation intervention(Hazard ratio[HR]=2.21).Subgroup analysis revealed that rehabilitation intervention significantly increased the survival rate of patients with pesticide poisoning(P=0.02),while no significant improvement was observed in patients with drug/biological agent poisoning(P=0.44).After rehabilitation intervention,significant improvement in GCS and FMA were observed in severe patients with toxic encephalopathy(P<0.01).CONCLUSION:Active rehabilitation intervention for patients exposed to poisons that can potentially cause toxic encephalopathy may improve the prognosis and reduce the mortality rate in clinical practice.
基金the Natural Science Foundation of China(Grant No.41790425).
文摘Landscape fragmentation is generally viewed as an indicator of environmental stresses or risks,but the fragmentation intensity assessment also depends on the scale of data and the definition of spatial unit.This study aimed to explore the scale-dependence of forest fragmentation intensity along a moisture gradient in Yinshan Mountain of North China,and to estimate environmental sensitivity of forest fragmentation in this semi-arid landscape.We developed an automatic classification algorithm using simple linear iterative clustering(SLIC)and Gaussian mixture model(GMM),and extracted tree canopy patches from Google Earth images(GEI),with an accuracy of 89.2%in the study area.Then we convert the tree canopy patches to forest category according to definition of forest that tree density greater than 10%,and compared it with forest categories from global land use datasets,FROM-GLC10 and GlobeLand30,with spatial resolutions of 10 m and 30 m,respectively.We found that the FROM-GLC10 and GlobeLand30 datasets underestimated the forest area in Yinshan Mountain by 16.88%and 21.06%,respectively;and the ratio of open forest(OF,10%<tree coverage<40%)to closed forest(CF,tree coverage>40%)areas in the underestimated part was 2:1.The underestimations concentrated in warmer and drier areas occupied mostly by large coverage of OFs with severely fragmented canopies.Fragmentation intensity of canopies positively correlated with spring temperature while negatively correlated with summer precipitation and terrain slope.When summer precipitation was less than 300 mm or spring temperature higher than 4℃,canopy fragmentation intensity rose drastically,while the forest area percentage kept stable.Our study suggested that the spatial configuration,e.g.,sparseness,is more sensitive to drought stress than area percentage.This highlights the importance of data resolution and proper fragmentation measurements for forest patterns and environmental interpretation,which is the base of reliable ecosystem predictions with regard to the future climate scenarios.