Most mammalian cells take up cholesterol from low-density lipoproteins(LDLs) via receptor-mediated endocytosis.After reaching lysosomes,LDL-derived cholesterol continues to transport to downstream organelles including...Most mammalian cells take up cholesterol from low-density lipoproteins(LDLs) via receptor-mediated endocytosis.After reaching lysosomes,LDL-derived cholesterol continues to transport to downstream organelles including the ER for specific structural and functional needs.Peroxisomes are recently found to receive cholesterol from lysosomes through lysosomeperoxisome membrane contacts.However,whether and how cholesterol is conveyed from peroxisomes to the ER remain unknown.Here,by combining high-resolution microscopic analyses and in vitro reconstitution of highly purified organelles or artificial liposomes,we demonstrate that peroxisomes form membrane contacts with the ER through the interaction between peroxisomal PI(4,5)P2 and ER-resident extended synaptotagmin-1,2 and 3(E-Syts).Depletion of peroxisomal PI(4,5)P2 or ESyts markedly decreases peroxisome-ER membrane contacts and induces cholesterol accumulation in lysosomes.Furthermore,we show that cholesterol is delivered from 3H-labeled peroxisomes or PI(4,5)P2-containing liposomes to the ER in vitro,and that the presence of peroxisomes augments cholesterol transfer from lysosomes to the ER.Together,our study reveals a new cholesterol transport pathway along the lysosome-peroxisome-ER membrane contacts in the cell.展开更多
Musculoskeletal disorders are common in clinical practice.Repairing critical-sized defects in musculoskeletal systems remains a challenge for researchers and surgeons,requiring the application of tissue engineering bi...Musculoskeletal disorders are common in clinical practice.Repairing critical-sized defects in musculoskeletal systems remains a challenge for researchers and surgeons,requiring the application of tissue engineering biomaterials.Successful application depends on the response of the host tissue to the biomaterial and specific healing process of each anatomical structure.The commonly-held view is that biomaterials should be biocompatible to minimize local host immune response.However,a growing number of studies have shown that active modulation of the immune cells,particularly macrophages,via biomaterials is an effective way to control immune response and promote tissue regeneration as well as biomaterial integration.Therefore,we critically review the role of macrophages in the repair of injured musculoskeletal system soft tissues,which have relatively poor regenerative capacities,as well as discuss further enhancement of target tissue regeneration via modulation of macrophage polarization by biomaterial-mediated immunomodulation(biomaterial properties and delivery systems).This active regulation approach rather than passive-evade strategy maximizes the potential of biomaterials to promote musculoskeletal system soft tissue regeneration and provides alternative therapeutic options for repairing critical-sized defects.展开更多
Superspreaders are critical infectious resources in multiple infectious diseases.They can be asymptomatic or present mild symptoms but can transmit pathogens to susceptible populations,leading to severe symptoms,and e...Superspreaders are critical infectious resources in multiple infectious diseases.They can be asymptomatic or present mild symptoms but can transmit pathogens to susceptible populations,leading to severe symptoms,and even death.Early identification of this population is extremely important to inhibit the spread of infectious diseases.Right now,the whole global world is suffering from a devastating infectious disease caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).In this article,a superspreader cluster event in coronavirus disease 2019(COVID-19)was identified by tracking contacting histories of infected patients.This cluster was found to be originated from an asymptomatic SARS-CoV-2 carrier,which resulted in 13 secondary cases getting infected.All the secondary patients presented with non-typical symptoms of COVID-19,such as fever,dry cough,and myalgia,one of which died of respiratory failure at the end.From this cluster,we learn that people with older ages,low immunity,multiple underlying diseases,especially pulmonary diseases,can contribute to a poor prognosis.Thus,asymptomatic superspreaders of COVID-19 can be extremely dangerous and must be handled time-efficiently.展开更多
Corneal injuries will cause corneal surface diseases that may lead to blindness in millions of people worldwide.There is a tremendous need for biomaterials that can promote corneal regeneration with practical feasibil...Corneal injuries will cause corneal surface diseases that may lead to blindness in millions of people worldwide.There is a tremendous need for biomaterials that can promote corneal regeneration with practical feasibility.Here we demonstrate a strategy of a protein coating for corneal injury regeneration.We synthesize an o-nitrosobenzaldehyde group(NB)-modified gelatin(GelNB),which could adhere directly to the corneal surface with covalent bonding to form a thin molecular coating.The molecular coating could avoid rapid clearance and provide a favorable environment for cell migration,thereby effectively accelerating corneal repair and regeneration.The histological structure of the regenerated cornea is more similar to the native cornea.This molecular coating can be used conveniently as an eye drop solution,which makes it a promising strategy for corneal regeneration.展开更多
基金supported by the National Natural Science Foundation of China (91754102, 31771568, 31690102, 31600651, 31701030)National Key Research and Development Project of the Ministry of Science and Technology of China (2016YFA0500100)+2 种基金Shenzhen City Technology Basic Research Program (JCYJ20170818144026198)Science and Technology Department of Hubei Province (2017CFB617)the 111 Project of Ministry of Education of China (B16036)
文摘Most mammalian cells take up cholesterol from low-density lipoproteins(LDLs) via receptor-mediated endocytosis.After reaching lysosomes,LDL-derived cholesterol continues to transport to downstream organelles including the ER for specific structural and functional needs.Peroxisomes are recently found to receive cholesterol from lysosomes through lysosomeperoxisome membrane contacts.However,whether and how cholesterol is conveyed from peroxisomes to the ER remain unknown.Here,by combining high-resolution microscopic analyses and in vitro reconstitution of highly purified organelles or artificial liposomes,we demonstrate that peroxisomes form membrane contacts with the ER through the interaction between peroxisomal PI(4,5)P2 and ER-resident extended synaptotagmin-1,2 and 3(E-Syts).Depletion of peroxisomal PI(4,5)P2 or ESyts markedly decreases peroxisome-ER membrane contacts and induces cholesterol accumulation in lysosomes.Furthermore,we show that cholesterol is delivered from 3H-labeled peroxisomes or PI(4,5)P2-containing liposomes to the ER in vitro,and that the presence of peroxisomes augments cholesterol transfer from lysosomes to the ER.Together,our study reveals a new cholesterol transport pathway along the lysosome-peroxisome-ER membrane contacts in the cell.
基金National key R&D program of China(2017YFA0104900)NSFC grants(81874019,81572115,81572157)325 Health High Level Talent project of Zhejiang province,Clinical top young talents cultivation project of Zhejiang university,the Fundamental Research Funds for the Central Universities.
文摘Musculoskeletal disorders are common in clinical practice.Repairing critical-sized defects in musculoskeletal systems remains a challenge for researchers and surgeons,requiring the application of tissue engineering biomaterials.Successful application depends on the response of the host tissue to the biomaterial and specific healing process of each anatomical structure.The commonly-held view is that biomaterials should be biocompatible to minimize local host immune response.However,a growing number of studies have shown that active modulation of the immune cells,particularly macrophages,via biomaterials is an effective way to control immune response and promote tissue regeneration as well as biomaterial integration.Therefore,we critically review the role of macrophages in the repair of injured musculoskeletal system soft tissues,which have relatively poor regenerative capacities,as well as discuss further enhancement of target tissue regeneration via modulation of macrophage polarization by biomaterial-mediated immunomodulation(biomaterial properties and delivery systems).This active regulation approach rather than passive-evade strategy maximizes the potential of biomaterials to promote musculoskeletal system soft tissue regeneration and provides alternative therapeutic options for repairing critical-sized defects.
文摘Superspreaders are critical infectious resources in multiple infectious diseases.They can be asymptomatic or present mild symptoms but can transmit pathogens to susceptible populations,leading to severe symptoms,and even death.Early identification of this population is extremely important to inhibit the spread of infectious diseases.Right now,the whole global world is suffering from a devastating infectious disease caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).In this article,a superspreader cluster event in coronavirus disease 2019(COVID-19)was identified by tracking contacting histories of infected patients.This cluster was found to be originated from an asymptomatic SARS-CoV-2 carrier,which resulted in 13 secondary cases getting infected.All the secondary patients presented with non-typical symptoms of COVID-19,such as fever,dry cough,and myalgia,one of which died of respiratory failure at the end.From this cluster,we learn that people with older ages,low immunity,multiple underlying diseases,especially pulmonary diseases,can contribute to a poor prognosis.Thus,asymptomatic superspreaders of COVID-19 can be extremely dangerous and must be handled time-efficiently.
基金This work was supported by the National Key R&D Program of China(2017YFA0104900)National Natural Science Foundation of China(31830029,32000957,81972053).
文摘Corneal injuries will cause corneal surface diseases that may lead to blindness in millions of people worldwide.There is a tremendous need for biomaterials that can promote corneal regeneration with practical feasibility.Here we demonstrate a strategy of a protein coating for corneal injury regeneration.We synthesize an o-nitrosobenzaldehyde group(NB)-modified gelatin(GelNB),which could adhere directly to the corneal surface with covalent bonding to form a thin molecular coating.The molecular coating could avoid rapid clearance and provide a favorable environment for cell migration,thereby effectively accelerating corneal repair and regeneration.The histological structure of the regenerated cornea is more similar to the native cornea.This molecular coating can be used conveniently as an eye drop solution,which makes it a promising strategy for corneal regeneration.
