Biomarke rs are required for the early detection,prognosis prediction,and monitoring of amyotrophic lateral sclerosis,a progressive disease.Proteomics is an unbiased and quantitative method that can be used to detect ...Biomarke rs are required for the early detection,prognosis prediction,and monitoring of amyotrophic lateral sclerosis,a progressive disease.Proteomics is an unbiased and quantitative method that can be used to detect neurochemical signatures to aid in the identification of candidate biomarke rs.In this study,we used a label-free quantitative proteomics approach to screen for substantially differentially regulated proteins in ten patients with sporadic amyotrophic lateral scle rosis compared with five healthy controls.Su bstantial upregulation of serum proteins related to multiple functional clusters was observed in patients with spo radic amyotrophic lateral sclerosis.Potential biomarke rs were selected based on functionality and expression specificity.To validate the proteomics profiles,blood samples from an additional cohort comprising 100 patients with sporadic amyotrophic lateral sclerosis and 100 healthy controls were subjected to enzyme-linked immunosorbent assay.Eight substantially upregulated serum proteins in patients with spora dic amyotrophic lateral sclerosis were selected,of which the cathelicidin-related antimicrobial peptide demonstrated the best discriminative ability between patients with sporadic amyotrophic lateral sclerosis and healthy controls(area under the curve[AUC]=0.713,P<0.0001).To further enhance diagnostic accuracy,a multi-protein combined discriminant algorithm was developed incorporating five proteins(hemoglobin beta,cathelicidin-related antimicrobial peptide,talin-1,zyxin,and translationally-controlled tumor protein).The algo rithm achieved an AUC of 0.811 and a P-value of<0.0001,resulting in 79%sensitivity and 71%specificity for the diagnosis of sporadic amyotrophic lateral scle rosis.Subsequently,the ability of candidate biomarkers to discriminate between early-stage amyotrophic lateral sclerosis patients and controls,as well as patients with different disease severities,was examined.A two-protein panel comprising talin-1 and translationally-controlled tumor protein effectively distinguished early-stage amyotrophic lateral sclerosis patients from controls(AUC=0.766,P<0.0001).Moreove r,the expression of three proteins(FK506 binding protein 1A,cathelicidin-related antimicrobial peptide,and hemoglobin beta-1)was found to increase with disease progression.The proteomic signatures developed in this study may help facilitate early diagnosis and monitor the progression of sporadic amyotrophic lateral sclerosis when used in co mbination with curre nt clinical-based parameters.展开更多
In addition to the occurrence of atmospheric blocking, the climatology of the characteristics of blocking events, including duration, intensity, and extension, in four seasons over the Northern Hemisphere was analyzed...In addition to the occurrence of atmospheric blocking, the climatology of the characteristics of blocking events, including duration, intensity, and extension, in four seasons over the Northern Hemisphere was analyzed for the period 1950-2009. The seasonality and spatial variations of these characteristics were studied according to their longitudinal distributions. In general, there were sharp discrepancies in the blocking characteristics between winter and summer, and these differences were more prominent over the Atlantic and Pacific Oceans. The blocking not only occurred more frequently but also underwent stronger amplification in winter; likewise, the blocking occurred less frequently and underwent weaker amplification in summer. There are very strong interrelationships among different blocking characteristics, suggesting that they are supported by similar physical factors. In addition, the relationship between blocking over different regions and East Asian circulation was examined. Ural-Siberia is a major blocking formation region in all seasons that may exert a downstream impact on East Asia. The impact is generally weak in summer, which is due to its lower intensity and smaller duration. However, the extratropical circulation over East Asia in summer can be disturbed persistently by the frequent occurrence of blocking over the Asian continent or the Western Pacific. In particular, the blocking frequency over the Western Pacific significantly increased during the study period. This climatological information provides a background for studying the impact of blocking on East Asian circulation under both present and future climate conditions.展开更多
Calorie restriction(CR)or a fasting regimen is considered one of the most potent non-pharmacological interventions to prevent chronic metabolic disorders,ameliorate autoimmune diseases,and attenuate aging.Despite effo...Calorie restriction(CR)or a fasting regimen is considered one of the most potent non-pharmacological interventions to prevent chronic metabolic disorders,ameliorate autoimmune diseases,and attenuate aging.Despite efforts,the mechanisms by which CR improves health,particularly brain health,are still not fully understood.Metabolic homeostasis is vital for brain function,and a detailed metabolome atlas of the brain is essential for understanding the networks connecting different brain regions.展开更多
Beijing often suffers under heavy smog.During such events which occur mostly in autumn and winter,people are desperate for fresh air.The formation of heavy smog is due to foremost human induced air pollution,but geogr...Beijing often suffers under heavy smog.During such events which occur mostly in autumn and winter,people are desperate for fresh air.The formation of heavy smog is due to foremost human induced air pollution,but geographic and meteorological conditions,especially below a surface inversion,play an important role.We propose to destroy the inversion by pumping air from above the inversion layer to the surface layer to alleviate the severity of the smog.While long-term air quality improvement depends on the reduction of air pollution emission,air pumping may provide relief in the interim for the Beijing citizens.We estimate that an air pumping at a rate 2×10~7m^3s^(–1)can lead to significantly improved air quality in Beijing,due to(1)direct clean air input;(2)increased instability and vertical mixing and(3)a positive radiation-mixing feedback.The pumping requires an energy input of 10 GW,comparable with the energy consumption in Beijing for air conditioning in summer.We propose to use wind energy from Inner Mongolia for the pumping,which has currently an installed wind energy capacity of 70GW.展开更多
基金supported by the grants from Shanghai Shuguang Plan Project,No.18SG15(to SC)Shanghai Outstanding Young Scholars Project+2 种基金Shanghai Talent Development Project,No.2019044(to SC)Medical-engineering cross fund of Shanghai Jiao Tong University,No.YG2022QN009(to QZ)the National Natural Science Foundation of China,No.82201558(to QZ)。
文摘Biomarke rs are required for the early detection,prognosis prediction,and monitoring of amyotrophic lateral sclerosis,a progressive disease.Proteomics is an unbiased and quantitative method that can be used to detect neurochemical signatures to aid in the identification of candidate biomarke rs.In this study,we used a label-free quantitative proteomics approach to screen for substantially differentially regulated proteins in ten patients with sporadic amyotrophic lateral scle rosis compared with five healthy controls.Su bstantial upregulation of serum proteins related to multiple functional clusters was observed in patients with spo radic amyotrophic lateral sclerosis.Potential biomarke rs were selected based on functionality and expression specificity.To validate the proteomics profiles,blood samples from an additional cohort comprising 100 patients with sporadic amyotrophic lateral sclerosis and 100 healthy controls were subjected to enzyme-linked immunosorbent assay.Eight substantially upregulated serum proteins in patients with spora dic amyotrophic lateral sclerosis were selected,of which the cathelicidin-related antimicrobial peptide demonstrated the best discriminative ability between patients with sporadic amyotrophic lateral sclerosis and healthy controls(area under the curve[AUC]=0.713,P<0.0001).To further enhance diagnostic accuracy,a multi-protein combined discriminant algorithm was developed incorporating five proteins(hemoglobin beta,cathelicidin-related antimicrobial peptide,talin-1,zyxin,and translationally-controlled tumor protein).The algo rithm achieved an AUC of 0.811 and a P-value of<0.0001,resulting in 79%sensitivity and 71%specificity for the diagnosis of sporadic amyotrophic lateral scle rosis.Subsequently,the ability of candidate biomarkers to discriminate between early-stage amyotrophic lateral sclerosis patients and controls,as well as patients with different disease severities,was examined.A two-protein panel comprising talin-1 and translationally-controlled tumor protein effectively distinguished early-stage amyotrophic lateral sclerosis patients from controls(AUC=0.766,P<0.0001).Moreove r,the expression of three proteins(FK506 binding protein 1A,cathelicidin-related antimicrobial peptide,and hemoglobin beta-1)was found to increase with disease progression.The proteomic signatures developed in this study may help facilitate early diagnosis and monitor the progression of sporadic amyotrophic lateral sclerosis when used in co mbination with curre nt clinical-based parameters.
基金supported by a grant from the Research Grants Council of the Hong Kong Special Administrative Region (Grant No. 104410)a grant from Germany/Hong Kong Joint Research Scheme (Grant No.G HK023/09)The figures were prepared by the NCAR Command Language (Version 6.0.0) [Software] (2012),Boulder,Colorado:UCAR/NCAR/CLSL/VETS
文摘In addition to the occurrence of atmospheric blocking, the climatology of the characteristics of blocking events, including duration, intensity, and extension, in four seasons over the Northern Hemisphere was analyzed for the period 1950-2009. The seasonality and spatial variations of these characteristics were studied according to their longitudinal distributions. In general, there were sharp discrepancies in the blocking characteristics between winter and summer, and these differences were more prominent over the Atlantic and Pacific Oceans. The blocking not only occurred more frequently but also underwent stronger amplification in winter; likewise, the blocking occurred less frequently and underwent weaker amplification in summer. There are very strong interrelationships among different blocking characteristics, suggesting that they are supported by similar physical factors. In addition, the relationship between blocking over different regions and East Asian circulation was examined. Ural-Siberia is a major blocking formation region in all seasons that may exert a downstream impact on East Asia. The impact is generally weak in summer, which is due to its lower intensity and smaller duration. However, the extratropical circulation over East Asia in summer can be disturbed persistently by the frequent occurrence of blocking over the Asian continent or the Western Pacific. In particular, the blocking frequency over the Western Pacific significantly increased during the study period. This climatological information provides a background for studying the impact of blocking on East Asian circulation under both present and future climate conditions.
基金This work was supported by the National Natural Science Foundation of China(NSFC 22004013,82271524,and 21934006)Doctoral Scientific Research Foundation of the Liaoning Science and Technology Department(2020-BS-200)the Central Guidance on Local Science and Technology Development Fund of Dalian Science and Technology Bureau.
文摘Calorie restriction(CR)or a fasting regimen is considered one of the most potent non-pharmacological interventions to prevent chronic metabolic disorders,ameliorate autoimmune diseases,and attenuate aging.Despite efforts,the mechanisms by which CR improves health,particularly brain health,are still not fully understood.Metabolic homeostasis is vital for brain function,and a detailed metabolome atlas of the brain is essential for understanding the networks connecting different brain regions.
基金supported by the National Natural Science Foundation of China(Grant No.91537211)
文摘Beijing often suffers under heavy smog.During such events which occur mostly in autumn and winter,people are desperate for fresh air.The formation of heavy smog is due to foremost human induced air pollution,but geographic and meteorological conditions,especially below a surface inversion,play an important role.We propose to destroy the inversion by pumping air from above the inversion layer to the surface layer to alleviate the severity of the smog.While long-term air quality improvement depends on the reduction of air pollution emission,air pumping may provide relief in the interim for the Beijing citizens.We estimate that an air pumping at a rate 2×10~7m^3s^(–1)can lead to significantly improved air quality in Beijing,due to(1)direct clean air input;(2)increased instability and vertical mixing and(3)a positive radiation-mixing feedback.The pumping requires an energy input of 10 GW,comparable with the energy consumption in Beijing for air conditioning in summer.We propose to use wind energy from Inner Mongolia for the pumping,which has currently an installed wind energy capacity of 70GW.
