Intraneuronal dysproteostasis and extraneuronal microenvironmental abnormalities in Alzheimer’s disease(AD)collectively culminate in neuronal deterioration.In the context of AD,autophagy dysfunction,a multi-link obst...Intraneuronal dysproteostasis and extraneuronal microenvironmental abnormalities in Alzheimer’s disease(AD)collectively culminate in neuronal deterioration.In the context of AD,autophagy dysfunction,a multi-link obstacle involving autophagy downregulation and lysosome defects in neurons/microglia is highly implicated in intra/extraneuronal pathological processes.Therefore,multidimensional autophagy regulation strategies co-manipulating“autophagy induction”and“lysosome degradation”in dual targets(neuron and microglia)are more reliable for AD treatment.Accordingly,we designed an RP-1 peptide-modified reactive oxygen species(ROS)-responsive micelles(RT-NM)loading rapamycin or gypenoside XVII.Guided by RP-1 peptide,the ligand of receptor for advanced glycation end products(RAGE),RT-NM efficiently targeted neurons and microglia in AD-affected region.This nanocombination therapy activated the whole autophagy-lysosome pathway by autophagy induction(rapamycin)and lysosome improvement(gypenoside XVII),thus enhancing autophagic degradation of neurotoxic aggregates and inflammasomes,and promoting Aβ phagocytosis.Resultantly,it decreased aberrant protein burden,alleviated neuroinflammation,and eventually ameliorated memory defects in 3×Tg-AD transgenic mice.Our research developed a multidimensional autophagy nano-regulator to boost the efficacy of autophagy-centered AD therapy.展开更多
Apigenin （4＇,5,7-trihydroxyflavone） is a member of the flavone subclass of flavonoids present in fruits and vegetables. The involvement of autophagy in the apigenin-induced apoptotic death of human breast cancer ce...Apigenin （4＇,5,7-trihydroxyflavone） is a member of the flavone subclass of flavonoids present in fruits and vegetables. The involvement of autophagy in the apigenin-induced apoptotic death of human breast cancer cells was investigated. Cell proliferation and viability were assessed by 3-（4,5-dimethylthiazol- 2-yl）-2,5-diphenyltetrazolium bromide （MTT） and clonogenic assays. Flow cytometry, fluorescent staining and Western blot analysis were employed to detect apoptosis and autophagy, and the role of autophagy was assessed using autophagy inhibitors. Apigenin dose- and time-dependently repressed the proliferation and clonogenic survival of the human breast cancer T47D and MDA-MB-231 cell lines. The death of T47D and MDA-MB-231 cells was due to apoptosis associated with increased levels of Caspase3, PARP cleavage and Bax/Bcl-2 ratios. The results from flow cytometry and fluorescent staining also verified the occurrence of apoptosis. In addition, the apigenin-treated cells exhibited autophagy, as characterized by the appearance of autophagosomes under fluorescence microscopy and the accumulation of acidic vesicular organelles （AVOs） by flow cytometry. Furthermore, the results of the Western blot analysis revealed that the level of LC3-Ⅱ, the processed form of LC3-Ⅰ, was increased. Treatment with the autophagy inhibitor, 3-methyladenine （3-MA）, significantly enhanced the apoptosis induced by apigenin, which was accompanied by an increase in the level of PARP cleavage. Similar results were also confirmed by flow cytometry and fluorescence microscopy. These results indicate that apigenin has apoptosis- and autophagy-inducing effects in breast cancer cells. Autophagy plays a cyto-protective role in apigenin-induced apoptosis, and the combination of apigenin and an autophagy inhibitor may be a promising strategy for breast cancer control.展开更多
Background:Accurate mapping of tree species is highly desired in the management and research of plantation forests,whose ecosystem services are currently under threats.Time-series multispectral satellite images,e.g.,f...Background:Accurate mapping of tree species is highly desired in the management and research of plantation forests,whose ecosystem services are currently under threats.Time-series multispectral satellite images,e.g.,from Landsat-8(L8)and Sentinel-2(S2),have been proven useful in mapping general forest types,yet we do not know quantitatively how their spectral features(e.g.,red-edge)and temporal frequency of data acquisitions(e.g.,16-day vs.5-day)contribute to plantation forest mapping to the species level.Moreover,it is unclear to what extent the fusion of L8 and S2 will result in improvements in tree species mapping of northern plantation forests in China.Methods:We designed three sets of classification experiments(i.e.,single-date,multi-date,and spectral-temporal)to evaluate the performances of L8 and S2 data for mapping keystone timber tree species in northern China.We first used seven pairs of L8 and S2 images to evaluate the performances of L8 and S2 key spectral features for separating these tree species across key growing stages.Then we extracted the spectral-temporal features from all available images of different temporal frequency of data acquisition(i.e.,L8 time series,S2 time series,and fusion of L8 and S2)to assess the contribution of image temporal frequency on the accuracy of tree species mapping in the study area.Results:1)S2 outperformed L8 images in all classification experiments,with or without the red edge bands(0.4%–3.4%and 0.2%–4.4%higher for overall accuracy and macro-F1,respectively);2)NDTI(the ratio of SWIR1 minus SWIR2 to SWIR1 plus SWIR2)and Tasseled Cap coefficients were most important features in all the classifications,and for time-series experiments,the spectral-temporal features of red band-related vegetation indices were most useful;3)increasing the temporal frequency of data acquisition can improve overall accuracy of tree species mapping for up to 3.2%(from 90.1%using single-date imagery to 93.3%using S2 time-series),yet similar overall accuracies were achieved using S2 time-series(93.3%)and the fusion of S2 and L8(93.2%).Conclusions:This study quantifies the contributions of L8 and S2 spectral and temporal features in mapping keystone tree species of northern plantation forests in China and suggests that for mapping tree species in China's northern plantation forests,the effects of increasing the temporal frequency of data acquisition could saturate quickly after using only two images from key phenological stages.展开更多
Maianthemum is a genus with more than 35 species from the tribe Polygonateae(Asparagaceae),widely distributed between North to Central Americas and eastern Asia with high diversity in the easternHimalayas to the Hengd...Maianthemum is a genus with more than 35 species from the tribe Polygonateae(Asparagaceae),widely distributed between North to Central Americas and eastern Asia with high diversity in the easternHimalayas to the Hengduan Mountains of SW China.Although most species from SW China form a well-supported clade,phylogenetic relationships within this clade remain unclear.With a broad level of taxon sampling and an extensive character sampling fromeight DNA regions,this study intends to revisit the phylogeny and biogeography of the genus to better understand the divergence patterns of species from SW China.Phylogenetic results suggested the monophyly of Maianthemum with recognition of nine strongly supported clades,but backbone relationships among these clades remained largely uncertain.For the SWChina clade,individuals from the same species are grouped into different lineages.Our results revealed that the fast radiation of the SWChina cladewas occurred in the eastern Himalayas,followed by subsequent radiation in the Hengduan Mountains in the Pliocene.Intercontinental disjunctions of Maianthemum in the Northern Hemisphere appear to have occurred multiple times during the late Miocene to the Pliocene,likely resulted by a combination of both vicariance and long-distance dispersal events.展开更多
A simple and novel method has been proposed to determine the enantiomeric composition ofracemate praziquantel(PzQ)by using the analysis of ultraviolet(UV)spectroscopy combinedwith partial least squares(PLS),This metho...A simple and novel method has been proposed to determine the enantiomeric composition ofracemate praziquantel(PzQ)by using the analysis of ultraviolet(UV)spectroscopy combinedwith partial least squares(PLS),This method does not rely on the use of expensive carbohydratessuch as cyclodextrins,but on the use of inexpensive sucrose,which is equally effective as car-bohydrate.PZQ has two enantiomers.Through measuring the slight diference in the UV spectralabsorption of PzQ due to different interactions between its two enantiomers and sucrose,theenantiomeric composition was determined by a quantitative model based on PLS analysis.Themodel showed that the correlation coeficients of calibration set and validation set were 0.9971and 0.9972,respectively.The root mean square error of calibration(RMSEC)and the root meansquare error of prediction(RMSEP)were 0.0167 and 0.0129,respectively,Then,the independentdata of PZQ tablets were also used to test how well the quantitative model of PLS predicted theenantiomeric composition,The ratio of S-PZQ in tablet was 0.492,determined by high-perfor-mance liquid chromatography as the reference value,Six solutions of the tablet samples were prepared,and the ratios of S-PZQ in tablet samples in the validation set were predicted by the PLS model.,Theirrelative erors with the reference value were not more than 4%.Therefore,the established model couldbe accurate and employed to predict the enantiomeric compositions of PzQ tablets.展开更多
In formulas that use the probabilistic method to calculate the stability of the CWR, the value of the cross-resistance of the track beds hasn’t fully taken into account the influence of the type of the parameter comb...In formulas that use the probabilistic method to calculate the stability of the CWR, the value of the cross-resistance of the track beds hasn’t fully taken into account the influence of the type of the parameter combination of the track bed, making the calculation results for a particular line undifferentiated. The analogy of the trajectory of the lateral displacement of the trackless bed is proposed. It is proposed that the lateral resistance of the track bed is also ambiguous within the allowable lateral displacement limit, and equivalent randomization is performed. Through the analysis of the characteristics of the appearance parameters of the track bed, a calculation formula containing multiple surface parameters for the lateral resistance of the track bed was established, and the values of various factors were reasonably analyzed. The purpose of this paper is to point out that in the stability evaluation formula, the value of the lateral parameters of the ballast bed lacks the consideration of the surface parameters. Based on the surface parameters, a model to evaluate the lateral resistance of the track bed is proposed. It can be seen as a refinement of the formula.展开更多
Background: Long-term remote ischemic conditioning (RIC) has been proven to be beneficial in multiple diseases, such as cerebral and cardiovascular diseases. However, the hyperacute and acute effects of a single RIC s...Background: Long-term remote ischemic conditioning (RIC) has been proven to be beneficial in multiple diseases, such as cerebral and cardiovascular diseases. However, the hyperacute and acute effects of a single RIC stimulus are still not clear. Quantitative proteomic analyses of plasma proteins following RIC application have been conducted in preclinical and clinical studies but exhibit high heterogeneity in results due to wide variations in experimental setups and sampling procedures. Hence, this study aimed to explore the immediate effects of RIC on plasma proteome in healthy young adults to exclude confounding factors of disease entity, such as medications and gender. Methods: Young healthy male participants were enrolled after a systematic physical examination and 6-month lifestyle observation. Individual RIC sessions included five cycles of alternative ischemia and reperfusion, each lasting for 5 min in bilateral forearms. Blood samples were collected at baseline, 5 min after RIC, and 2 h after RIC, and then samples were processed for proteomic analysis using liquid chromatography-tandem mass spectrometry method. Results: Proteins related to lipid metabolism (e.g., Apolipoprotein F), coagulation factors (hepatocyte growth factor activator preproprotein), members of complement cascades (mannan-binding lectin serine protease 1 isoform 2 precursor), and inflammatory responses (carboxypeptidase N catalytic chain precursor) were differentially altered at their serum levels following the RIC intervention. The most enriched pathways were protein glycosylation and complement/coagulation cascades. Conclusions: One-time RIC stimulus may induce instant cellular responses like anti-inflammation, coagulation, and fibrinolysis balancing, and lipid metabolism regulation which are protective in different perspectives. Protective effects of single RIC in hyperacute and acute phases may be exploited in clinical emergency settings due to apparently beneficial alterations in plasma proteome profile. Furthermore, the beneficial effects of long-term (repeated) RIC interventions in preventing chronic cardiovascular diseases among general populations can also be expected based on our study findings.展开更多
Annual land use land cover(LULC)change information at medium spatial resolution(i.e.at 30 m)is required in numerous subjects,such as biophysical modelling,land management and global change studies.Annual LULC informat...Annual land use land cover(LULC)change information at medium spatial resolution(i.e.at 30 m)is required in numerous subjects,such as biophysical modelling,land management and global change studies.Annual LULC information,however,is usually not available at continental or national scale due to reasons such as insufficient remote sensing data coverage or lack of computational capabilities.Here we integrate high temporal resolution and coarse spatial resolution satellite images(i.e.,Moderate Resolution Imaging Spectroradiometer(MODIS)and Global Inventory Modelling and Mapping Studies(GIMMS)normalized difference vegetation index(NDVI))with high spatial resolution datasets(China’s Land-Use/cover Datasets(CLUDs)derived from 30-meter Landsat TM/ETM+/OLI)to generate reliable annual nominal 30 m LULC maps for the whole of China between 1980 and 2015.We also test the performance of a statistical based change detection algorithm(Breaks for Additive Seasonal and Trend),originally designed for tracking forest change,in classifying all-type LULC change.As a result,a nominal 30 m annual land use/land cover datasets(CLUD-A)from 1980 to 2015 was developed for the whole China.The mapping results were assessed with a change sample dataset,a regional annual validation sample set and a three-year China sample set.Of the detected change years,75.61%matched the exact time of conversion within±1 year.Annual mapping results provided a detail process of urbanization,deforestation,afforestation,water and cropland dynamics over the past 36 years.The consistent characterization of land change dynamics for China can be further used in scientific research and to support land management for policy-makers.展开更多
Background：Acute minor ischemic stroke （AMIS） or transient ischemic attack （TIA） is a common cerebrovascular event with a considerable high recurrence.Prior research demonstrated the effectiveness of regular long...Background：Acute minor ischemic stroke （AMIS） or transient ischemic attack （TIA） is a common cerebrovascular event with a considerable high recurrence.Prior research demonstrated the effectiveness of regular long-term remote ischemic conditioning （RIC） in secondary stroke prevention in patients with intracranial stenosis.We hypothesized that RIC can serve as an effective adjunctive therapy to pharmacotherapy in preventing ischemic events in patients with AMIS/TIA.This study aimed to investigate the feasibility,safety,and preliminary efficacy of daily RIC in inhibiting cerebrovascular/cardiovascular events after AMIS/TIA.Methods：This is a single-arm,open-label,multicenter Phase IIa futility study with a sample size of 165.Patients with AMIS/TIA receive RIC as an additional therapy to secondary stroke prevention regimen.RIC consists of five cycles of 5-min inflation （200 mmHg） and 5-min deflation of cuffs on bilateral upper limbs twice a day for 90 days.The antiplatelet strategy is based on individual physician＇s best practice：aspirin alone,clopidogrel alone,or combination of aspirin and clopidogrel.We will assess the recurrence rate of ischemic stroke/TIA within 3 months as the primary outcomes.Conclusions：The data gathered from the study will be used to determine whether a further large-scale,multicenter randomized controlled Phase Ⅱ trial is warranted in patients with AMIS/TIA.Trial Registration：ClinicalTrials.gov,NCT03004820;https：//www.clinicaltrials.gov/ct2/show/NCT03004820.展开更多
基金supported by National Natural Science Foundation of China(Nos.82073780 and 82273868,China)Shanghai Municipal Natural Science Foundation(No.19ZR1406200,China)。
文摘Intraneuronal dysproteostasis and extraneuronal microenvironmental abnormalities in Alzheimer’s disease(AD)collectively culminate in neuronal deterioration.In the context of AD,autophagy dysfunction,a multi-link obstacle involving autophagy downregulation and lysosome defects in neurons/microglia is highly implicated in intra/extraneuronal pathological processes.Therefore,multidimensional autophagy regulation strategies co-manipulating“autophagy induction”and“lysosome degradation”in dual targets(neuron and microglia)are more reliable for AD treatment.Accordingly,we designed an RP-1 peptide-modified reactive oxygen species(ROS)-responsive micelles(RT-NM)loading rapamycin or gypenoside XVII.Guided by RP-1 peptide,the ligand of receptor for advanced glycation end products(RAGE),RT-NM efficiently targeted neurons and microglia in AD-affected region.This nanocombination therapy activated the whole autophagy-lysosome pathway by autophagy induction(rapamycin)and lysosome improvement(gypenoside XVII),thus enhancing autophagic degradation of neurotoxic aggregates and inflammasomes,and promoting Aβ phagocytosis.Resultantly,it decreased aberrant protein burden,alleviated neuroinflammation,and eventually ameliorated memory defects in 3×Tg-AD transgenic mice.Our research developed a multidimensional autophagy nano-regulator to boost the efficacy of autophagy-centered AD therapy.
基金supported by the National Natural Science Foundation of China (Grant no. 81001186)the Tianjin Municipal Natural Science Foundation (Grant no. 10JCYBJ C14100,11JCZDJC28000,13JCYBJC21800)
文摘Apigenin （4＇,5,7-trihydroxyflavone） is a member of the flavone subclass of flavonoids present in fruits and vegetables. The involvement of autophagy in the apigenin-induced apoptotic death of human breast cancer cells was investigated. Cell proliferation and viability were assessed by 3-（4,5-dimethylthiazol- 2-yl）-2,5-diphenyltetrazolium bromide （MTT） and clonogenic assays. Flow cytometry, fluorescent staining and Western blot analysis were employed to detect apoptosis and autophagy, and the role of autophagy was assessed using autophagy inhibitors. Apigenin dose- and time-dependently repressed the proliferation and clonogenic survival of the human breast cancer T47D and MDA-MB-231 cell lines. The death of T47D and MDA-MB-231 cells was due to apoptosis associated with increased levels of Caspase3, PARP cleavage and Bax/Bcl-2 ratios. The results from flow cytometry and fluorescent staining also verified the occurrence of apoptosis. In addition, the apigenin-treated cells exhibited autophagy, as characterized by the appearance of autophagosomes under fluorescence microscopy and the accumulation of acidic vesicular organelles （AVOs） by flow cytometry. Furthermore, the results of the Western blot analysis revealed that the level of LC3-Ⅱ, the processed form of LC3-Ⅰ, was increased. Treatment with the autophagy inhibitor, 3-methyladenine （3-MA）, significantly enhanced the apoptosis induced by apigenin, which was accompanied by an increase in the level of PARP cleavage. Similar results were also confirmed by flow cytometry and fluorescence microscopy. These results indicate that apigenin has apoptosis- and autophagy-inducing effects in breast cancer cells. Autophagy plays a cyto-protective role in apigenin-induced apoptosis, and the combination of apigenin and an autophagy inhibitor may be a promising strategy for breast cancer control.
基金supported by National Natural Science Foundation of China(Grant No.41901382)Open Fund of State Key Laboratory of Remote Sensing Science(Grant No.OFSLRSS201917)the HZAU research startup fund(No.11041810340,No.11041810341).
文摘Background:Accurate mapping of tree species is highly desired in the management and research of plantation forests,whose ecosystem services are currently under threats.Time-series multispectral satellite images,e.g.,from Landsat-8(L8)and Sentinel-2(S2),have been proven useful in mapping general forest types,yet we do not know quantitatively how their spectral features(e.g.,red-edge)and temporal frequency of data acquisitions(e.g.,16-day vs.5-day)contribute to plantation forest mapping to the species level.Moreover,it is unclear to what extent the fusion of L8 and S2 will result in improvements in tree species mapping of northern plantation forests in China.Methods:We designed three sets of classification experiments(i.e.,single-date,multi-date,and spectral-temporal)to evaluate the performances of L8 and S2 data for mapping keystone timber tree species in northern China.We first used seven pairs of L8 and S2 images to evaluate the performances of L8 and S2 key spectral features for separating these tree species across key growing stages.Then we extracted the spectral-temporal features from all available images of different temporal frequency of data acquisition(i.e.,L8 time series,S2 time series,and fusion of L8 and S2)to assess the contribution of image temporal frequency on the accuracy of tree species mapping in the study area.Results:1)S2 outperformed L8 images in all classification experiments,with or without the red edge bands(0.4%–3.4%and 0.2%–4.4%higher for overall accuracy and macro-F1,respectively);2)NDTI(the ratio of SWIR1 minus SWIR2 to SWIR1 plus SWIR2)and Tasseled Cap coefficients were most important features in all the classifications,and for time-series experiments,the spectral-temporal features of red band-related vegetation indices were most useful;3)increasing the temporal frequency of data acquisition can improve overall accuracy of tree species mapping for up to 3.2%(from 90.1%using single-date imagery to 93.3%using S2 time-series),yet similar overall accuracies were achieved using S2 time-series(93.3%)and the fusion of S2 and L8(93.2%).Conclusions:This study quantifies the contributions of L8 and S2 spectral and temporal features in mapping keystone tree species of northern plantation forests in China and suggests that for mapping tree species in China's northern plantation forests,the effects of increasing the temporal frequency of data acquisition could saturate quickly after using only two images from key phenological stages.
基金This study was supported by grants from Natural Sciences Foundation of China(31760055)Natural Sciences Foundation of Hunan Province(2019JJ40232 and 2019JJ40233)+2 种基金Comprehensive Scientific Investigation of Biodiversity from the Wuling Mountains(2014FY110100)the Hunan Provincial Innovation Foundation for Postgraduate(CX2018B724)the John D.and Catherine T.MacArthur Foundation.
文摘Maianthemum is a genus with more than 35 species from the tribe Polygonateae(Asparagaceae),widely distributed between North to Central Americas and eastern Asia with high diversity in the easternHimalayas to the Hengduan Mountains of SW China.Although most species from SW China form a well-supported clade,phylogenetic relationships within this clade remain unclear.With a broad level of taxon sampling and an extensive character sampling fromeight DNA regions,this study intends to revisit the phylogeny and biogeography of the genus to better understand the divergence patterns of species from SW China.Phylogenetic results suggested the monophyly of Maianthemum with recognition of nine strongly supported clades,but backbone relationships among these clades remained largely uncertain.For the SWChina clade,individuals from the same species are grouped into different lineages.Our results revealed that the fast radiation of the SWChina cladewas occurred in the eastern Himalayas,followed by subsequent radiation in the Hengduan Mountains in the Pliocene.Intercontinental disjunctions of Maianthemum in the Northern Hemisphere appear to have occurred multiple times during the late Miocene to the Pliocene,likely resulted by a combination of both vicariance and long-distance dispersal events.
基金supported by National Natural Science Foundation of China(No.81102504)Key Technologies R&D Program of Shandong Province(No.2016GSF201003)the Scienti¯c Research Foundation for the Returned Overseas Chinese Scholars,State Education Ministry(the 50th Batch).
文摘A simple and novel method has been proposed to determine the enantiomeric composition ofracemate praziquantel(PzQ)by using the analysis of ultraviolet(UV)spectroscopy combinedwith partial least squares(PLS),This method does not rely on the use of expensive carbohydratessuch as cyclodextrins,but on the use of inexpensive sucrose,which is equally effective as car-bohydrate.PZQ has two enantiomers.Through measuring the slight diference in the UV spectralabsorption of PzQ due to different interactions between its two enantiomers and sucrose,theenantiomeric composition was determined by a quantitative model based on PLS analysis.Themodel showed that the correlation coeficients of calibration set and validation set were 0.9971and 0.9972,respectively.The root mean square error of calibration(RMSEC)and the root meansquare error of prediction(RMSEP)were 0.0167 and 0.0129,respectively,Then,the independentdata of PZQ tablets were also used to test how well the quantitative model of PLS predicted theenantiomeric composition,The ratio of S-PZQ in tablet was 0.492,determined by high-perfor-mance liquid chromatography as the reference value,Six solutions of the tablet samples were prepared,and the ratios of S-PZQ in tablet samples in the validation set were predicted by the PLS model.,Theirrelative erors with the reference value were not more than 4%.Therefore,the established model couldbe accurate and employed to predict the enantiomeric compositions of PzQ tablets.
文摘In formulas that use the probabilistic method to calculate the stability of the CWR, the value of the cross-resistance of the track beds hasn’t fully taken into account the influence of the type of the parameter combination of the track bed, making the calculation results for a particular line undifferentiated. The analogy of the trajectory of the lateral displacement of the trackless bed is proposed. It is proposed that the lateral resistance of the track bed is also ambiguous within the allowable lateral displacement limit, and equivalent randomization is performed. Through the analysis of the characteristics of the appearance parameters of the track bed, a calculation formula containing multiple surface parameters for the lateral resistance of the track bed was established, and the values of various factors were reasonably analyzed. The purpose of this paper is to point out that in the stability evaluation formula, the value of the lateral parameters of the ballast bed lacks the consideration of the surface parameters. Based on the surface parameters, a model to evaluate the lateral resistance of the track bed is proposed. It can be seen as a refinement of the formula.
基金supported by the National Key R&D Program of China(2017YFC1308400)the National Natural Science Foundation(81371289)+1 种基金and the Beijing Natural Science Foundation(7212047)and Capital Medical Development Scientific Research Fund(2022-2-2015).
文摘Background: Long-term remote ischemic conditioning (RIC) has been proven to be beneficial in multiple diseases, such as cerebral and cardiovascular diseases. However, the hyperacute and acute effects of a single RIC stimulus are still not clear. Quantitative proteomic analyses of plasma proteins following RIC application have been conducted in preclinical and clinical studies but exhibit high heterogeneity in results due to wide variations in experimental setups and sampling procedures. Hence, this study aimed to explore the immediate effects of RIC on plasma proteome in healthy young adults to exclude confounding factors of disease entity, such as medications and gender. Methods: Young healthy male participants were enrolled after a systematic physical examination and 6-month lifestyle observation. Individual RIC sessions included five cycles of alternative ischemia and reperfusion, each lasting for 5 min in bilateral forearms. Blood samples were collected at baseline, 5 min after RIC, and 2 h after RIC, and then samples were processed for proteomic analysis using liquid chromatography-tandem mass spectrometry method. Results: Proteins related to lipid metabolism (e.g., Apolipoprotein F), coagulation factors (hepatocyte growth factor activator preproprotein), members of complement cascades (mannan-binding lectin serine protease 1 isoform 2 precursor), and inflammatory responses (carboxypeptidase N catalytic chain precursor) were differentially altered at their serum levels following the RIC intervention. The most enriched pathways were protein glycosylation and complement/coagulation cascades. Conclusions: One-time RIC stimulus may induce instant cellular responses like anti-inflammation, coagulation, and fibrinolysis balancing, and lipid metabolism regulation which are protective in different perspectives. Protective effects of single RIC in hyperacute and acute phases may be exploited in clinical emergency settings due to apparently beneficial alterations in plasma proteome profile. Furthermore, the beneficial effects of long-term (repeated) RIC interventions in preventing chronic cardiovascular diseases among general populations can also be expected based on our study findings.
基金supported by the National Key R&D Program of China(Grant Nos.2017YFA0604401 and 2019YFA0606601)the Tsinghua University Initiative Scientific Research Program(Grant No.2019Z02CAU)the Youth Innovation Promotion Association,Chinese Academy of Sciences(Grant No.Y4YR1300QM)。
文摘Annual land use land cover(LULC)change information at medium spatial resolution(i.e.at 30 m)is required in numerous subjects,such as biophysical modelling,land management and global change studies.Annual LULC information,however,is usually not available at continental or national scale due to reasons such as insufficient remote sensing data coverage or lack of computational capabilities.Here we integrate high temporal resolution and coarse spatial resolution satellite images(i.e.,Moderate Resolution Imaging Spectroradiometer(MODIS)and Global Inventory Modelling and Mapping Studies(GIMMS)normalized difference vegetation index(NDVI))with high spatial resolution datasets(China’s Land-Use/cover Datasets(CLUDs)derived from 30-meter Landsat TM/ETM+/OLI)to generate reliable annual nominal 30 m LULC maps for the whole of China between 1980 and 2015.We also test the performance of a statistical based change detection algorithm(Breaks for Additive Seasonal and Trend),originally designed for tracking forest change,in classifying all-type LULC change.As a result,a nominal 30 m annual land use/land cover datasets(CLUD-A)from 1980 to 2015 was developed for the whole China.The mapping results were assessed with a change sample dataset,a regional annual validation sample set and a three-year China sample set.Of the detected change years,75.61%matched the exact time of conversion within±1 year.Annual mapping results provided a detail process of urbanization,deforestation,afforestation,water and cropland dynamics over the past 36 years.The consistent characterization of land change dynamics for China can be further used in scientific research and to support land management for policy-makers.
基金PICNIC-One study is supported by the grants from the National Natural Science Foundation of China （No. 81325007 and No. 81620108011）, the Capital Health Research and Special Development （No. 2016-4-1032）, the American Stroke Association （No. 14SDG 1829003）, and the National Institute of Health （No. P20GM 109040）.
文摘Background：Acute minor ischemic stroke （AMIS） or transient ischemic attack （TIA） is a common cerebrovascular event with a considerable high recurrence.Prior research demonstrated the effectiveness of regular long-term remote ischemic conditioning （RIC） in secondary stroke prevention in patients with intracranial stenosis.We hypothesized that RIC can serve as an effective adjunctive therapy to pharmacotherapy in preventing ischemic events in patients with AMIS/TIA.This study aimed to investigate the feasibility,safety,and preliminary efficacy of daily RIC in inhibiting cerebrovascular/cardiovascular events after AMIS/TIA.Methods：This is a single-arm,open-label,multicenter Phase IIa futility study with a sample size of 165.Patients with AMIS/TIA receive RIC as an additional therapy to secondary stroke prevention regimen.RIC consists of five cycles of 5-min inflation （200 mmHg） and 5-min deflation of cuffs on bilateral upper limbs twice a day for 90 days.The antiplatelet strategy is based on individual physician＇s best practice：aspirin alone,clopidogrel alone,or combination of aspirin and clopidogrel.We will assess the recurrence rate of ischemic stroke/TIA within 3 months as the primary outcomes.Conclusions：The data gathered from the study will be used to determine whether a further large-scale,multicenter randomized controlled Phase Ⅱ trial is warranted in patients with AMIS/TIA.Trial Registration：ClinicalTrials.gov,NCT03004820;https：//www.clinicaltrials.gov/ct2/show/NCT03004820.
