Chronic liver injury leads to progressive liver fibrosis and ultimately cirrhosis,a major cause of morbidity and mortality worldwide.However,there are currently no effective anti-fibrotic therapies available,especiall...Chronic liver injury leads to progressive liver fibrosis and ultimately cirrhosis,a major cause of morbidity and mortality worldwide.However,there are currently no effective anti-fibrotic therapies available,especially for latestage patients,which is partly attributed to the major knowledge gap regarding liver cell heterogeneity and cellspecific responses in different fibrosis stages.To reveal the multicellular networks regulating mammalian liver fibrosis from mild to severe phenotypes,we generated a single-nucleus transcriptomic atlas encompassing 49919nuclei corresponding to all main liver cell types at different stages of murine carbon tetrachloride(CCl_(4))-induced progressive liver fibrosis.Integrative analysis distinguished the sequential responses to injury of hepatocytes,hepatic stellate cells and endothelial cells.Moreover,we reconstructed the cell-cell interactions and gene regulatory networks implicated in these processes.These integrative analyses uncovered previously overlooked aspects of hepatocyte proliferation exhaustion and disrupted pericentral metabolic functions,dysfunction for clearance by apoptosis of activated hepatic stellate cells,accumulation of pro-fibrotic signals,and the switch from an anti-angiogenic to a pro-angiogenic program during CCl_(4)-induced progressive liver fibrosis.Our dataset thus constitutes a useful resource for understanding the molecular basis of progressive liver fibrosis using a relevant animal model.展开更多
Wave overtopping at a sea dike was observed using video images during a storm in July 2018 at Rizhao Coast,China.A shore-based video monitoring system was mounted to collect coastal images with a sample frequency of 1...Wave overtopping at a sea dike was observed using video images during a storm in July 2018 at Rizhao Coast,China.A shore-based video monitoring system was mounted to collect coastal images with a sample frequency of 1 Hz in the beginning 10 min of each hour during daylight.A method to extract the frequency,location,width and duration of individual overtopping events based on the shore-based video monitoring system was developed.A total of 6252 individual overtopping events were detected over a 360m long sea dike during the storm of 10 h in a safe and labor-saving way,enabling a detailed analysis of the temporal and spatial variation of wave overtopping.The temporal variation of overtopping duration,frequency and volume is basically in sync with the change of tidal level(R=0.87,0.82 and 0.76,respectively).The increase of wave height increases the overtopping frequency significantly.We found a high correlation between the hourly observed data and the predicted results of two commonly used formulae.Unlike the previous field measurements of overtopping that were limited in a single location,significant spatial variation of overtopping in the alongshore direction is found.The overtopping volume varies with a factor of 6 within the range of several wave lengths.It is further revealed that the spatial variation of overtopping is highly correlated with the alongshore variation of surf zone width with a correlation coefficient of 0.895.The present study suggests the feasibility of shore-based video monitoring technique to capture the main features of wave overtopping at coastal dikes,providing new possibilities to monitor wave overtopping in the field and to improve prediction tools.展开更多
A running mean bias （RMB） correction ap- proach was applied to the forecasts of near-surface variables in a seasonal short-range ensemble forecasting experiment with 57 consecutive cases during summer 2010 in the no...A running mean bias （RMB） correction ap- proach was applied to the forecasts of near-surface variables in a seasonal short-range ensemble forecasting experiment with 57 consecutive cases during summer 2010 in the northern China region. To determine a proper training window length for calculating RMB, window lengths from 2 to 20 days were evaluated, and 16 days was taken as an optimal window length, since it receives most of the benefit from extending the window length. The raw and 16-day RMB corrected ensembles were then evaluated for their ensemble mean forecast skills. The results show that the raw ensemble has obvious bias in all near-surface variables. The RMB correction can remove the bias reasonably well, and generate an unbiased ensemble. The bias correction not only reduces the ensemble mean forecast error, but also results in a better spreaderror relationship. Moreover, two methods for computing calibrated probabilistic forecast （PF） were also evaluated through the 57 case dates： 1） using the relative frequency from the RMB-eorrected ensemble; 2） computing the forecasting probabilities based on a historical rank histogram. The first method outperforms the second one, as it can improve both the reliability and the resolution of the PFs, while the second method only has a small effect on the reliability, indicating the necessity and importance of removing the systematic errors from the ensemble.展开更多
基金supported by the National Natural Science Foundation of China(32200688,92068106,U20A2015,32211530050)Guangdong Basic and Applied Basic Research Foundation(2021B1515120075,2021A1515110180)Science and Technology Program of Guangzhou(202201010408,202201011037)。
文摘Chronic liver injury leads to progressive liver fibrosis and ultimately cirrhosis,a major cause of morbidity and mortality worldwide.However,there are currently no effective anti-fibrotic therapies available,especially for latestage patients,which is partly attributed to the major knowledge gap regarding liver cell heterogeneity and cellspecific responses in different fibrosis stages.To reveal the multicellular networks regulating mammalian liver fibrosis from mild to severe phenotypes,we generated a single-nucleus transcriptomic atlas encompassing 49919nuclei corresponding to all main liver cell types at different stages of murine carbon tetrachloride(CCl_(4))-induced progressive liver fibrosis.Integrative analysis distinguished the sequential responses to injury of hepatocytes,hepatic stellate cells and endothelial cells.Moreover,we reconstructed the cell-cell interactions and gene regulatory networks implicated in these processes.These integrative analyses uncovered previously overlooked aspects of hepatocyte proliferation exhaustion and disrupted pericentral metabolic functions,dysfunction for clearance by apoptosis of activated hepatic stellate cells,accumulation of pro-fibrotic signals,and the switch from an anti-angiogenic to a pro-angiogenic program during CCl_(4)-induced progressive liver fibrosis.Our dataset thus constitutes a useful resource for understanding the molecular basis of progressive liver fibrosis using a relevant animal model.
基金This work was supported by the Fundamental Research Funds for the Central Universities(Grant Nos.B200202064,B200201064)the National Science Fund for Distinguished Young Scholars(Grant No.51425901)+2 种基金the Key Laboratory of Ministry of Education for Coastal Disaster and Protection,Hohai University(Grant No.202003)Projects supported by the Key Program of National Natural Science Foundation of China(Grant No.41930538)the National Natural Science Foundation of China(Grant No.51879096,51909076).
文摘Wave overtopping at a sea dike was observed using video images during a storm in July 2018 at Rizhao Coast,China.A shore-based video monitoring system was mounted to collect coastal images with a sample frequency of 1 Hz in the beginning 10 min of each hour during daylight.A method to extract the frequency,location,width and duration of individual overtopping events based on the shore-based video monitoring system was developed.A total of 6252 individual overtopping events were detected over a 360m long sea dike during the storm of 10 h in a safe and labor-saving way,enabling a detailed analysis of the temporal and spatial variation of wave overtopping.The temporal variation of overtopping duration,frequency and volume is basically in sync with the change of tidal level(R=0.87,0.82 and 0.76,respectively).The increase of wave height increases the overtopping frequency significantly.We found a high correlation between the hourly observed data and the predicted results of two commonly used formulae.Unlike the previous field measurements of overtopping that were limited in a single location,significant spatial variation of overtopping in the alongshore direction is found.The overtopping volume varies with a factor of 6 within the range of several wave lengths.It is further revealed that the spatial variation of overtopping is highly correlated with the alongshore variation of surf zone width with a correlation coefficient of 0.895.The present study suggests the feasibility of shore-based video monitoring technique to capture the main features of wave overtopping at coastal dikes,providing new possibilities to monitor wave overtopping in the field and to improve prediction tools.
基金supported by a project of the National Natural Science Foundation of China (Grant No. 41305099)
文摘A running mean bias （RMB） correction ap- proach was applied to the forecasts of near-surface variables in a seasonal short-range ensemble forecasting experiment with 57 consecutive cases during summer 2010 in the northern China region. To determine a proper training window length for calculating RMB, window lengths from 2 to 20 days were evaluated, and 16 days was taken as an optimal window length, since it receives most of the benefit from extending the window length. The raw and 16-day RMB corrected ensembles were then evaluated for their ensemble mean forecast skills. The results show that the raw ensemble has obvious bias in all near-surface variables. The RMB correction can remove the bias reasonably well, and generate an unbiased ensemble. The bias correction not only reduces the ensemble mean forecast error, but also results in a better spreaderror relationship. Moreover, two methods for computing calibrated probabilistic forecast （PF） were also evaluated through the 57 case dates： 1） using the relative frequency from the RMB-eorrected ensemble; 2） computing the forecasting probabilities based on a historical rank histogram. The first method outperforms the second one, as it can improve both the reliability and the resolution of the PFs, while the second method only has a small effect on the reliability, indicating the necessity and importance of removing the systematic errors from the ensemble.
