Pancreatitis is a common gastrointestinal disorder that causes hospitalization with significant morbidity and mortality.The mechanistic pathophysiology of pancreatitis is complicated,limiting the discovery of pharmaco...Pancreatitis is a common gastrointestinal disorder that causes hospitalization with significant morbidity and mortality.The mechanistic pathophysiology of pancreatitis is complicated,limiting the discovery of pharmacological intervention methods.Here,we show that the administration of ATN-161,an antagonist of Integrin-a5,significantly mitigates the pathological condition of acute pancreatitis induced by caerulein.We find that CK19-positive pancreatic ductal cells align parallel to blood vessels in the pancreas.In the caerulein-induced acute pancreatitis model,the newly emergent CK19-positive cells are highly vascularized,with a significant increase in vascular density and endothelial cell number.Single-cell RNA sequencing analysis shows that ductal and endothelial cells are intimate interacting partners,suggesting the existence of a ductal-endothelial interface in the pancreas.Pancreatitis dramatically reduces the crosstalk in the ductal-endothelial interface but promotes the Spp-1/Integrin-a5 signaling.Blocking this signaling with ATN-161 significantly reduces acinar-to-ductal metaplasia,pathological angiogenesis,and restores other abnormal defects induced by caerulein.Our work reveals the therapeutic potential of ATN-161 as an uncharacterized pharmacological method to alleviate the symptoms of pancreatitis.展开更多
The formation of a blood vessel network is crucial for organ development and regeneration.Over the past three decades,the central molecular mechanisms governing blood vessel growth have been extensively studied.Recent...The formation of a blood vessel network is crucial for organ development and regeneration.Over the past three decades,the central molecular mechanisms governing blood vessel growth have been extensively studied.Recent evidence indicates that vascular endothelial cells—the specialized cells lining the inner surface of blood vessels—exhibit signifcant heterogeneity to meet the specifc needs of diferent organs.This review focuses on the current understanding of endothelial cell heterogeneity,which includes both intra-organ and inter-organ heterogeneity.Intra-organ heterogeneity encompasses arterio-venous and tip-stalk endothelial cell specialization,while inter-organ heterogeneity refers to organ-specifc transcriptomic profles and functions.Advances in single-cell RNA sequenc-ing(scRNA-seq)have enabled the identifcation of new endothelial subpopulations and the comparison of gene expression patterns across diferent subsets of endothelial cells.Integrating scRNA-seq with other high-throughput sequencing technologies promises to deepen our understanding of endothelial cell heterogeneity at the epigenetic level and in a spatially resolved context.To further explore human endothelial cell heterogeneity,vascular orga-noids ofer powerful tools for studying gene function in three-dimensional culture systems and for investigating endothelial-tissue interactions using human cells.Developing organ-specifc vascular organoids presents unique opportunities to unravel inter-organ endothelial cell heterogeneity and its implications for human disease.Emerging technologies,such as scRNA-seq and vascular organoids,are poised to transform our understanding of endothelial cell heterogeneity and pave the way for innovative therapeutic strategies to address human vascular diseases.展开更多
Background:As one of the non-pharmacological interventions to control the transmission of COVID-19,determining the quarantine duration is mainly based on the accurate estimates of the incubation period.However,patient...Background:As one of the non-pharmacological interventions to control the transmission of COVID-19,determining the quarantine duration is mainly based on the accurate estimates of the incubation period.However,patients with coarse information of the exposure date,as well as infections other than the symptomatic,were not taken into account in previously published studies.Thus,by using the statistical method dealing with the interval-censored data,we assessed the quarantine duration for both common and uncommon infections.The latter type includes the presymptomatic,the asymptomatic and the recurrent test positive patients.Methods:As of 10 December 2020,information on cases have been collected from the English and Chinese databases,including Pubmed,Google scholar,CNKI(China National Knowledge Infrastructure)and Wanfang.Official websites and medias were also searched as data sources.All data were transformed into doubly interval-censored and the accelerated failure time model was applied.By estimating the incubation period and the time-to-event distribution of worldwide COVID-19 patients,we obtain the large percentiles for determining and suggesting the quarantine policies.For symptomatic and presymptomatic COVID-19 patients,the incubation time is the duration from exposure to symptom onset.For the asymptomatic,we substitute the date of first positive result of nucleic acid testing for that of symptom onset.Furthermore,the time from hospital discharge or getting negative test result to the positive recurrence has been calculated for recurrent positive patients.Results:A total of 1920 laboratory confirmed COVID-19 cases were included.Among all uncommon infections,34.1%(n=55)of them developed symptoms or were identified beyond fourteen days.Based on all collected cases,the 95th and 99th percentiles were estimated to be 16.2 days(95%Cl 15.5-17.0)and 22.9 days(21.7-24.3)respectively.Besides,we got similar estimates based on merely symptomatic and presymptomatic infections as 15.1 days(14.4-15.7)and 21.1 days(20.0-22.2).Conclusions:There are a certain number of infected people who require longer quarantine duration.Our findings well support the current practice of the extended active monitoring.To further prevent possible transmissions induced and facilitated by such infectious outliers after the 14-days quarantine,properly prolonging the quarantine duration could be prudent for high-risk scenarios and in regions with insufficient test resources.展开更多
基金supported by the National Key R&D Program of China(2022YFA1103200)the Fundamental Research Funds for the Central Universities(2024ZYGXZR077)+7 种基金National Natural Science Foundation of China(32270866,32300693,32471155,3247086822107045)Guangzhou basic and applied basic research funding(2024A04J6259)The Pearl River Talent Recruitment Program(2023ZT10Y154,2021ZT09Y233,2023QN10Y147)South China University of Technology(D6241240)Talent Program and Basic Research Project of Guangzhou Institutes of Biomedicine and Health,Chinese Academy of Sciences(1103792101,GIBHBRP23-02,GIBHBRP24-01)Cooperation Fund of CHCAMS and SZCH(E010221005,CFA202201006)Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine,Guangdong-Hong Kong Joint Laboratory for Stem Cell and Regenerative Medicine,Guangzhou Institutes of Biomedicine and Health,Chinese Academy of Sciences(KLRB202201,KLRB202305)partially supported by Science and Technology Planning Project of Guangdong Province,China(2023B1212060050,2023B1212120009)。
文摘Pancreatitis is a common gastrointestinal disorder that causes hospitalization with significant morbidity and mortality.The mechanistic pathophysiology of pancreatitis is complicated,limiting the discovery of pharmacological intervention methods.Here,we show that the administration of ATN-161,an antagonist of Integrin-a5,significantly mitigates the pathological condition of acute pancreatitis induced by caerulein.We find that CK19-positive pancreatic ductal cells align parallel to blood vessels in the pancreas.In the caerulein-induced acute pancreatitis model,the newly emergent CK19-positive cells are highly vascularized,with a significant increase in vascular density and endothelial cell number.Single-cell RNA sequencing analysis shows that ductal and endothelial cells are intimate interacting partners,suggesting the existence of a ductal-endothelial interface in the pancreas.Pancreatitis dramatically reduces the crosstalk in the ductal-endothelial interface but promotes the Spp-1/Integrin-a5 signaling.Blocking this signaling with ATN-161 significantly reduces acinar-to-ductal metaplasia,pathological angiogenesis,and restores other abnormal defects induced by caerulein.Our work reveals the therapeutic potential of ATN-161 as an uncharacterized pharmacological method to alleviate the symptoms of pancreatitis.
基金supported by the National Key R&D Program of China(2024YFA1802200)the Fundamental Research Funds for the Central Uni-versities(2024ZYGXZR077)+6 种基金National Natural Science Foundation of China(32270866,32300693,32471155,32470868)Guangzhou basic and applied basic research funding(2024A04J6259,2025A04J7029)GuangDong Basic and Applied Basic Research Foundation(2023B1515120006)The Pearl River Talent Recruitment Program(2023ZT10Y154,2023QN10Y147,2021ZT09Y233)Talent Program and Basic Research Project of Guangzhou Institutes of Biomedicine and Health,Chinese Academy of Sciences(1103792101,GIBHBRP23-02,GIBH-BRP24-01)Guangdong Provincial Key Laboratory of Stem Cell and Regenera-tive Medicine,Guangdong-Hong Kong Joint Laboratory for Stem Cell and Regenerative Medicine,Guangzhou Institutes of Biomedicine and Health,Chinese Academy of Sciences(YHJ2024001,KLRB202201,KLRB202305)partially supported by Science and Technology Planning Project of Guang-dong Province,China(2023B1212060050,2023B1212120009).
文摘The formation of a blood vessel network is crucial for organ development and regeneration.Over the past three decades,the central molecular mechanisms governing blood vessel growth have been extensively studied.Recent evidence indicates that vascular endothelial cells—the specialized cells lining the inner surface of blood vessels—exhibit signifcant heterogeneity to meet the specifc needs of diferent organs.This review focuses on the current understanding of endothelial cell heterogeneity,which includes both intra-organ and inter-organ heterogeneity.Intra-organ heterogeneity encompasses arterio-venous and tip-stalk endothelial cell specialization,while inter-organ heterogeneity refers to organ-specifc transcriptomic profles and functions.Advances in single-cell RNA sequenc-ing(scRNA-seq)have enabled the identifcation of new endothelial subpopulations and the comparison of gene expression patterns across diferent subsets of endothelial cells.Integrating scRNA-seq with other high-throughput sequencing technologies promises to deepen our understanding of endothelial cell heterogeneity at the epigenetic level and in a spatially resolved context.To further explore human endothelial cell heterogeneity,vascular orga-noids ofer powerful tools for studying gene function in three-dimensional culture systems and for investigating endothelial-tissue interactions using human cells.Developing organ-specifc vascular organoids presents unique opportunities to unravel inter-organ endothelial cell heterogeneity and its implications for human disease.Emerging technologies,such as scRNA-seq and vascular organoids,are poised to transform our understanding of endothelial cell heterogeneity and pave the way for innovative therapeutic strategies to address human vascular diseases.
基金the Shanxi health commission for the grant of the special foundation on COVID-19(Grant number:No.6)Shanxi department of science and technology for the grant of the major science and technology project of Shanxi province(Grant Number:202005D121008).
文摘Background:As one of the non-pharmacological interventions to control the transmission of COVID-19,determining the quarantine duration is mainly based on the accurate estimates of the incubation period.However,patients with coarse information of the exposure date,as well as infections other than the symptomatic,were not taken into account in previously published studies.Thus,by using the statistical method dealing with the interval-censored data,we assessed the quarantine duration for both common and uncommon infections.The latter type includes the presymptomatic,the asymptomatic and the recurrent test positive patients.Methods:As of 10 December 2020,information on cases have been collected from the English and Chinese databases,including Pubmed,Google scholar,CNKI(China National Knowledge Infrastructure)and Wanfang.Official websites and medias were also searched as data sources.All data were transformed into doubly interval-censored and the accelerated failure time model was applied.By estimating the incubation period and the time-to-event distribution of worldwide COVID-19 patients,we obtain the large percentiles for determining and suggesting the quarantine policies.For symptomatic and presymptomatic COVID-19 patients,the incubation time is the duration from exposure to symptom onset.For the asymptomatic,we substitute the date of first positive result of nucleic acid testing for that of symptom onset.Furthermore,the time from hospital discharge or getting negative test result to the positive recurrence has been calculated for recurrent positive patients.Results:A total of 1920 laboratory confirmed COVID-19 cases were included.Among all uncommon infections,34.1%(n=55)of them developed symptoms or were identified beyond fourteen days.Based on all collected cases,the 95th and 99th percentiles were estimated to be 16.2 days(95%Cl 15.5-17.0)and 22.9 days(21.7-24.3)respectively.Besides,we got similar estimates based on merely symptomatic and presymptomatic infections as 15.1 days(14.4-15.7)and 21.1 days(20.0-22.2).Conclusions:There are a certain number of infected people who require longer quarantine duration.Our findings well support the current practice of the extended active monitoring.To further prevent possible transmissions induced and facilitated by such infectious outliers after the 14-days quarantine,properly prolonging the quarantine duration could be prudent for high-risk scenarios and in regions with insufficient test resources.
