Irreversible destruction of bronchi and alveoli can lead to multiple incurable lung diseases. Identifying lung stem/progenitor cells with regenerative capacity and utilizing them to reconstruct functional tissue is on...Irreversible destruction of bronchi and alveoli can lead to multiple incurable lung diseases. Identifying lung stem/progenitor cells with regenerative capacity and utilizing them to reconstruct functional tissue is one of the biggest hopes to reverse the damage and cure such diseases. Here we showed that a rare population of SOX9^＋ basal cells （BCs） located at airway epithelium rugae can regenerate adult human lung. Human SOX9^＋ BCs can be readily isolated by bronchoscopic brushing and indefinitely expanded in feeder-free condition. Expanded human SOX9^＋ BCs can give rise to alveolar and bronchiolar epithelium after being transplanted into injured mouse lung, with air-blood exchange system reconstructed and recipient＇s lung function improved. Manipulation of lung microenvironment with Pirfenidone to suppress TGF-β signaling could further boost the transplantation efficiency. Moreover, we conducted the first autologous SOX9^＋ BCs transplantation clinical trial in two bronchiectasis patients. Lung tissue repair and pulmonary function enhancement was observed in patients 3-12 months after cell transplantation. Alto- gether our current work indicated that functional adult human lung structure can be reconstituted by orthotopic transplantation of tissue-specific stem/progenitor cells, which could be translated into a mature regenerative therapeutic strategy in near future.展开更多
Alveoli serve as the functional units of the lungs,responsible for the critical task of blood-gas exchange.Com-prising type I(AT1)and type II(AT2)cells,the alveolar epithelium is continuously subject to external aggre...Alveoli serve as the functional units of the lungs,responsible for the critical task of blood-gas exchange.Com-prising type I(AT1)and type II(AT2)cells,the alveolar epithelium is continuously subject to external aggressors like pathogens and airborne particles.As such,preserving lung function requires both the homeostatic renewal and reparative regeneration of this epithelial layer.Dysfunctions in these processes contribute to various lung diseases.Recent research has pinpointed specific cell subgroups that act as potential stem or progenitor cells for the alveolar epithelium during both homeostasis and regeneration.Additionally,endothelial cells,fibroblasts,and immune cells synergistically establish a nurturing microenvironment-or“niche”-that modulates these ep-ithelial stem cells.This review aims to consolidate the latest findings on the identities of these stem cells and the components of their niche,as well as the molecular mechanisms that govern them.Additionally,this article highlights diseases that arise due to perturbations in stem cell-niche interactions.We also discuss recent technical innovations that have catalyzed these discoveries.Specifically,this review underscores the heterogeneity,plastic-ity,and dynamic regulation of these stem cell-niche systems.It is our aspiration that a deeper understanding of the fundamental cellular and molecular mechanisms underlying alveolar homeostasis and regeneration will open avenues for identifying novel therapeutic targets for conditions such as chronic obstructive pulmonary disease(COPD),fibrosis,coronavirus disease 2019(COVID-19),and lung cancer.展开更多
Bionics provides a positive and beneficial impact on the development of various materials and systems, which has been widely used in energy storage, heat transfer enhancement, and solar thermochemical reactions. In th...Bionics provides a positive and beneficial impact on the development of various materials and systems, which has been widely used in energy storage, heat transfer enhancement, and solar thermochemical reactions. In this paper, the idea of heat storage unit with biomimetic alveoli structure is proposed and introduced to increase the heat transfer area and improve the thermal performance of the packed-bed latent heat thermal energy storage(LHTES) system. The effects of heat storage unit structure on temperature distribution, liquid fraction, thermal storage capacity, and other performance indexes of the conventional model and biomimetic model are analyzed. The numerical results indicate that the biomimetic alveoli structure can improve the thermal response of heat storage unit, increase the specific surface area, and achieve a faster heat storage process of the packed-bed compared with the conventional structure. Among various existing models, the double-cell model has a significant improvement.Compared with the conventional model, the maximum increase of liquid fraction and charging efficiency are 9.8% and 6.4%,respectively. This study can provide references to optimize packed-bed LHTES and improve its thermal performance under practical conditions.展开更多
Patients developing hemoptysis or pulmonary infiltrates together with glomerulonephritis, particu- larly the rapidly progressive cases, are considered to be pulmonary renal syndrome （PRS）. The occur- rence of PRS, a...Patients developing hemoptysis or pulmonary infiltrates together with glomerulonephritis, particu- larly the rapidly progressive cases, are considered to be pulmonary renal syndrome （PRS）. The occur- rence of PRS, an etiologically rare heterogeneous group of diseases, constitutes a medical emergency associated with a high risk of fatal outcome.展开更多
为了比较周岁与成年黑藏羊肺组织形态学特点及抗氧化能力,试验选择青海省海北州贵南县自然放牧条件下12月龄和24月龄健康雄性黑藏羊各5只,按月龄分为两组,分别为周岁羊组(12月龄)和成年羊组(24月龄)。两组屠宰后各采集右肺隔叶两份,其...为了比较周岁与成年黑藏羊肺组织形态学特点及抗氧化能力,试验选择青海省海北州贵南县自然放牧条件下12月龄和24月龄健康雄性黑藏羊各5只,按月龄分为两组,分别为周岁羊组(12月龄)和成年羊组(24月龄)。两组屠宰后各采集右肺隔叶两份,其中一份经H.E.染色显微镜下观察试验羊肺组织形态;另一份应用Image-Pro Plus 6.0图像分析系统测量试验羊肺泡隔厚度、单个肺泡面积和单位面积内肺泡数,并测量肺动脉末端分支和细小动脉的管径和中膜厚度,计算肺组织血管平均直径和中膜厚度/血管平均直径;同时采用试剂盒测定试验羊肺组织总抗氧化能力(T-AOC)、超氧化物歧化酶(SOD)活性、过氧化氢酶(CAT)活性、谷胱甘肽过氧化物酶(GSH-Px)活性以及丙二醛(MDA)含量。结果表明:与周岁羊组比较,成年羊组肺泡隔厚度和单位面积肺泡数显著增加(P<0.05),单个肺泡面积、肺组织血管平均直径、中膜厚度显著减小(P<0.05);中膜厚度/血管平均直径减小,但差异不显著(P>0.05);肺组织T-AOC、SOD活性、GSH-Px活性和CAT活性略有提高,MDA含量略有降低,但均差异不显著(P>0.05)。说明随着黑藏羊年龄的增长,肺脏逐渐适应了高原低氧的环境,但抗氧化能力并未发生明显的变化。展开更多
文摘Irreversible destruction of bronchi and alveoli can lead to multiple incurable lung diseases. Identifying lung stem/progenitor cells with regenerative capacity and utilizing them to reconstruct functional tissue is one of the biggest hopes to reverse the damage and cure such diseases. Here we showed that a rare population of SOX9^＋ basal cells （BCs） located at airway epithelium rugae can regenerate adult human lung. Human SOX9^＋ BCs can be readily isolated by bronchoscopic brushing and indefinitely expanded in feeder-free condition. Expanded human SOX9^＋ BCs can give rise to alveolar and bronchiolar epithelium after being transplanted into injured mouse lung, with air-blood exchange system reconstructed and recipient＇s lung function improved. Manipulation of lung microenvironment with Pirfenidone to suppress TGF-β signaling could further boost the transplantation efficiency. Moreover, we conducted the first autologous SOX9^＋ BCs transplantation clinical trial in two bronchiectasis patients. Lung tissue repair and pulmonary function enhancement was observed in patients 3-12 months after cell transplantation. Alto- gether our current work indicated that functional adult human lung structure can be reconstituted by orthotopic transplantation of tissue-specific stem/progenitor cells, which could be translated into a mature regenerative therapeutic strategy in near future.
基金supported by the National Institutes of Health grant HL 105947 and HL 155272 to Y.L.
文摘Alveoli serve as the functional units of the lungs,responsible for the critical task of blood-gas exchange.Com-prising type I(AT1)and type II(AT2)cells,the alveolar epithelium is continuously subject to external aggressors like pathogens and airborne particles.As such,preserving lung function requires both the homeostatic renewal and reparative regeneration of this epithelial layer.Dysfunctions in these processes contribute to various lung diseases.Recent research has pinpointed specific cell subgroups that act as potential stem or progenitor cells for the alveolar epithelium during both homeostasis and regeneration.Additionally,endothelial cells,fibroblasts,and immune cells synergistically establish a nurturing microenvironment-or“niche”-that modulates these ep-ithelial stem cells.This review aims to consolidate the latest findings on the identities of these stem cells and the components of their niche,as well as the molecular mechanisms that govern them.Additionally,this article highlights diseases that arise due to perturbations in stem cell-niche interactions.We also discuss recent technical innovations that have catalyzed these discoveries.Specifically,this review underscores the heterogeneity,plastic-ity,and dynamic regulation of these stem cell-niche systems.It is our aspiration that a deeper understanding of the fundamental cellular and molecular mechanisms underlying alveolar homeostasis and regeneration will open avenues for identifying novel therapeutic targets for conditions such as chronic obstructive pulmonary disease(COPD),fibrosis,coronavirus disease 2019(COVID-19),and lung cancer.
基金supported by the National Key Research and Development Program of China (Grant No. 2018YFA0702300)the National Natural Science Foundation of China (Grant Nos. 52006094 and 52076064)the Taishan Scholars of Shandong Province (Grant No. tsqn201812105)。
文摘Bionics provides a positive and beneficial impact on the development of various materials and systems, which has been widely used in energy storage, heat transfer enhancement, and solar thermochemical reactions. In this paper, the idea of heat storage unit with biomimetic alveoli structure is proposed and introduced to increase the heat transfer area and improve the thermal performance of the packed-bed latent heat thermal energy storage(LHTES) system. The effects of heat storage unit structure on temperature distribution, liquid fraction, thermal storage capacity, and other performance indexes of the conventional model and biomimetic model are analyzed. The numerical results indicate that the biomimetic alveoli structure can improve the thermal response of heat storage unit, increase the specific surface area, and achieve a faster heat storage process of the packed-bed compared with the conventional structure. Among various existing models, the double-cell model has a significant improvement.Compared with the conventional model, the maximum increase of liquid fraction and charging efficiency are 9.8% and 6.4%,respectively. This study can provide references to optimize packed-bed LHTES and improve its thermal performance under practical conditions.
文摘Patients developing hemoptysis or pulmonary infiltrates together with glomerulonephritis, particu- larly the rapidly progressive cases, are considered to be pulmonary renal syndrome （PRS）. The occur- rence of PRS, an etiologically rare heterogeneous group of diseases, constitutes a medical emergency associated with a high risk of fatal outcome.
文摘为了比较周岁与成年黑藏羊肺组织形态学特点及抗氧化能力,试验选择青海省海北州贵南县自然放牧条件下12月龄和24月龄健康雄性黑藏羊各5只,按月龄分为两组,分别为周岁羊组(12月龄)和成年羊组(24月龄)。两组屠宰后各采集右肺隔叶两份,其中一份经H.E.染色显微镜下观察试验羊肺组织形态;另一份应用Image-Pro Plus 6.0图像分析系统测量试验羊肺泡隔厚度、单个肺泡面积和单位面积内肺泡数,并测量肺动脉末端分支和细小动脉的管径和中膜厚度,计算肺组织血管平均直径和中膜厚度/血管平均直径;同时采用试剂盒测定试验羊肺组织总抗氧化能力(T-AOC)、超氧化物歧化酶(SOD)活性、过氧化氢酶(CAT)活性、谷胱甘肽过氧化物酶(GSH-Px)活性以及丙二醛(MDA)含量。结果表明:与周岁羊组比较,成年羊组肺泡隔厚度和单位面积肺泡数显著增加(P<0.05),单个肺泡面积、肺组织血管平均直径、中膜厚度显著减小(P<0.05);中膜厚度/血管平均直径减小,但差异不显著(P>0.05);肺组织T-AOC、SOD活性、GSH-Px活性和CAT活性略有提高,MDA含量略有降低,但均差异不显著(P>0.05)。说明随着黑藏羊年龄的增长,肺脏逐渐适应了高原低氧的环境,但抗氧化能力并未发生明显的变化。
