Radical gastrectomy has been recognized as the standard surgical treatment for advanced gastric cancer, and essentially applied in a wide variety of clinical settings. The thoroughness of lymph node dissection is an i...Radical gastrectomy has been recognized as the standard surgical treatment for advanced gastric cancer, and essentially applied in a wide variety of clinical settings. The thoroughness of lymph node dissection is an important prognostic factor for patients with advanced gastric cancer. Splenic lymph node dissection is required during D2 radical gastrectomy for upper stomach cancer. This is often accompanied by removal of the spleen in the past few decades. A growing number of investigators believe, however, that the spleen plays an important role as an immune organ, and thus they encourage the application of a spleen- preserving method for splenic hilum lymph node dissection.展开更多
Aging increases the risk ofliver diseases and systemic susceptibility to aging-related diseases.However,cell type-specific changes and the underlying mechanism of liver aging in higher vertebrates remain incompletely ...Aging increases the risk ofliver diseases and systemic susceptibility to aging-related diseases.However,cell type-specific changes and the underlying mechanism of liver aging in higher vertebrates remain incompletely characterized.Here,we constructed the first single-nucleus transcriptomic landscape of primate liver aging,in which we resolved cell type-specific gene expression fluctuation in hepatocytes across three liver zonations and detected aberrant cell-cell interactions between hepatocytes and niche cells.Upon in-depth dissection of this rich dataset,we identifed impaired lipid metabolism and upregulation of chronic inflammation-related genes prominently associated with declined liver functions during aging.In particular,hyperactivated sterol regulatory element-binding protein(SREBP)signaling was a hallmark of the aged liver,and consequently,forced activation of SREBP2 in human primary hepatocytes recapitulated in vivo aging phenotypes,manifesting as impaired detoxification and accelerated cellular senescence.This study expands our knowledge of primate liver aging and informs the development of diagnostics and therapeutic interventions for liver aging and associated diseases.展开更多
Background:Although vascular endothelial growth factor A(VEGF-A)is known to play a key role in causing retinal edema,whether and how VEGF-A induces intracellular edema in the retina still remains unclear.Methods:Sprag...Background:Although vascular endothelial growth factor A(VEGF-A)is known to play a key role in causing retinal edema,whether and how VEGF-A induces intracellular edema in the retina still remains unclear.Methods:Sprague-Dawley rats were rendered diabetic with intraperitoneal injection of streptozotocin.Intravitreal injection of ranibizumab was performed 8 weeks after diabetes onset.rMC-1 cells(rat Müller cell line)were treated with glyoxal for 24 h with or without ranibizumab.The expression levels of inwardly rectifying K^(+)channel 4.1(Kir4.1),aquaporin 4(AQP4),Dystrophin 71(Dp71),VEGF-A,glutamine synthetase(GS)and sodium-potassium-ATPase(Na^(+)-K^(+)-ATPase)were examined using Western blot.VEGF-A in the supernatant of the cell culture was detected with ELISA.The intracellular potassium and sodium levels were detected with specific indicators.Results:Compared with normal control,protein expressions of Kir4.1 and AQP4 were down-regulated significantly in diabetic rat retinas,which were prevented by ranibizumab.The above changes were recapitulated in vitro.Similarly,the intracellular potassium level in glyoxal-treated rMC-1 cells was increased,while the intracellular sodium level and Na^(+)-K^(+)-ATPase protein level remained unchanged,compared with control.However,ranibizumab treatment decreased intracellular sodium,but not potassium.Conclusion:Ranibizumab protected Müller cells from diabetic intracellular edema through the up-regulation of Kir4.1 and AQP4 by directly binding VEGF-A.It also caused a reduction in intracellular osmotic pressure.展开更多
A major goal of developmental biology is to understand the progression of embryonic cell lineages from pluripotency to adulthood.During embryogenesis,cells proliferate and spread out,new cell types arise,while many pr...A major goal of developmental biology is to understand the progression of embryonic cell lineages from pluripotency to adulthood.During embryogenesis,cells proliferate and spread out,new cell types arise,while many progenitors fade away during differentiation.Early studies of cell-fate regulation and lineage tracing have enriched out knowledge about the developmental processes.Yet,a complete picture about the spatiotemporal cellular composition of the developing embryo and the cellular interactions coordinating embryonic development is lacked for most of the model systems that we study.展开更多
文摘Radical gastrectomy has been recognized as the standard surgical treatment for advanced gastric cancer, and essentially applied in a wide variety of clinical settings. The thoroughness of lymph node dissection is an important prognostic factor for patients with advanced gastric cancer. Splenic lymph node dissection is required during D2 radical gastrectomy for upper stomach cancer. This is often accompanied by removal of the spleen in the past few decades. A growing number of investigators believe, however, that the spleen plays an important role as an immune organ, and thus they encourage the application of a spleen- preserving method for splenic hilum lymph node dissection.
基金supported by the National Key Research and Development Program of China (Grant Nos.2022YFA1103700,2020YFA0804000,2020YFA0112200,2021YFF1201000,2022YFA1103800,2021YFA1101401,the STI2030-Major Projects-2021ZD0202400)the National Natural Science Foundation of China (Grant Nos.92049116,81921006,82125011,92149301,92168201,91949209,92049304,32121001,82192863,82122024,82071588,32000500,82271600)+9 种基金the Strategic Priority Research Program of the Chinese Academy of Sciences (XDA16000000)CAS Project for Young Scientists in Basic Research (YSBR-076,YSBR-012)the Program of the Beijing Natural Science Foundation (Z190019)the Pilot Project for Public Welfare Development and Reform of Beijing-affiliated Medical Research Institutes (No.11000022T000000461062)Youth Innovation Promotion Association of CAS (E1CAZW0401,2023092,2022083)Young Elite Scientists Sponsorship Program by CAST (YESS20200012,YESS20210002)the Informatization Plan of Chinese Academy of Sciences (CAS-WX2021SF-0301,CAS-WX2022SDC-XK14,CAS-WX2021SF-0101)New Cormerstone Science Foundation through the XPLORER PRIZE (2021-1045)Excellent Young Talents Program of Capital Medical University (No.12300927)Excellent Young Talents Training Program for the Construction of Beijing Municipal University Teacher Team (BPHR202203105).
文摘Aging increases the risk ofliver diseases and systemic susceptibility to aging-related diseases.However,cell type-specific changes and the underlying mechanism of liver aging in higher vertebrates remain incompletely characterized.Here,we constructed the first single-nucleus transcriptomic landscape of primate liver aging,in which we resolved cell type-specific gene expression fluctuation in hepatocytes across three liver zonations and detected aberrant cell-cell interactions between hepatocytes and niche cells.Upon in-depth dissection of this rich dataset,we identifed impaired lipid metabolism and upregulation of chronic inflammation-related genes prominently associated with declined liver functions during aging.In particular,hyperactivated sterol regulatory element-binding protein(SREBP)signaling was a hallmark of the aged liver,and consequently,forced activation of SREBP2 in human primary hepatocytes recapitulated in vivo aging phenotypes,manifesting as impaired detoxification and accelerated cellular senescence.This study expands our knowledge of primate liver aging and informs the development of diagnostics and therapeutic interventions for liver aging and associated diseases.
基金supported by grants from the National Natural Science Foundation of China(81570852,81970810,81970811)National Major Scientific and Technological Special Project for“Significant New Drugs Development”during the Thirtieth Five-year Plan Period(2019ZX09301113).
文摘Background:Although vascular endothelial growth factor A(VEGF-A)is known to play a key role in causing retinal edema,whether and how VEGF-A induces intracellular edema in the retina still remains unclear.Methods:Sprague-Dawley rats were rendered diabetic with intraperitoneal injection of streptozotocin.Intravitreal injection of ranibizumab was performed 8 weeks after diabetes onset.rMC-1 cells(rat Müller cell line)were treated with glyoxal for 24 h with or without ranibizumab.The expression levels of inwardly rectifying K^(+)channel 4.1(Kir4.1),aquaporin 4(AQP4),Dystrophin 71(Dp71),VEGF-A,glutamine synthetase(GS)and sodium-potassium-ATPase(Na^(+)-K^(+)-ATPase)were examined using Western blot.VEGF-A in the supernatant of the cell culture was detected with ELISA.The intracellular potassium and sodium levels were detected with specific indicators.Results:Compared with normal control,protein expressions of Kir4.1 and AQP4 were down-regulated significantly in diabetic rat retinas,which were prevented by ranibizumab.The above changes were recapitulated in vitro.Similarly,the intracellular potassium level in glyoxal-treated rMC-1 cells was increased,while the intracellular sodium level and Na^(+)-K^(+)-ATPase protein level remained unchanged,compared with control.However,ranibizumab treatment decreased intracellular sodium,but not potassium.Conclusion:Ranibizumab protected Müller cells from diabetic intracellular edema through the up-regulation of Kir4.1 and AQP4 by directly binding VEGF-A.It also caused a reduction in intracellular osmotic pressure.
文摘A major goal of developmental biology is to understand the progression of embryonic cell lineages from pluripotency to adulthood.During embryogenesis,cells proliferate and spread out,new cell types arise,while many progenitors fade away during differentiation.Early studies of cell-fate regulation and lineage tracing have enriched out knowledge about the developmental processes.Yet,a complete picture about the spatiotemporal cellular composition of the developing embryo and the cellular interactions coordinating embryonic development is lacked for most of the model systems that we study.