Severe influenza infections are often associated with the excessive induction of pro-inflammatory cytokines,which is also referred to as"cytokine storms".Several studies have shown that cytokine storms are d...Severe influenza infections are often associated with the excessive induction of pro-inflammatory cytokines,which is also referred to as"cytokine storms".Several studies have shown that cytokine storms are directly associated with influenzainduced fatal acute lung injury and acute respiratory distress syndrome.Due to the narrow administration window,current antiviral therapies are often inadequate.The efforts to use immunomodulatory agents alone or in combination with antiviral agents in the treatment of influenza in animal models have resulted in the achievement of protective effects accompanied with reduced cytokine production.Currently,there are no immunomodulatory drugs for influenza available for clinical use.Animal models,despite being ideal to study the anti-inflammatory responses to influenza virus infection,are very costly and time-consuming.Therefore,there is an urgent need to establish fast and economical screening methods using cellbased models to screen and develop novel immunomodulatory agents.In this study,we screened seven human cell lines and found that the human monocytic cell U937 supports the replication of different subtypes of influenza viruses as well as the production of the important pro-inflammatory cytokines and was selected to develop the cell-based model.The U937 cell model was validated by testing a panel of known antiviral and immunomodulatory agents and screening a drug library consisting of 1280 compounds comprised mostly of FDA-approved drugs.We demonstrated that the U937 cell model is robust and suitable for the high-throughput screening of immunomodulators and antivirals against influenza infection.展开更多
Magnetic nanoparticles(MNPs)have become a research hotspot and widely used in the biomedical field in recent decades due to their unique magnetic properties.This minireview summarizes the specific gene transfection of...Magnetic nanoparticles(MNPs)have become a research hotspot and widely used in the biomedical field in recent decades due to their unique magnetic properties.This minireview summarizes the specific gene transfection of magnetic particles(magnetofection)during eversy dynamic process of gene delivery(gene binding,cellular uptake,endosomal escape,intracellular trafficking and in vivo targeting).Meanwhile,the synergistic biomedical application of magnetofection and the effects of MNPs have also been discussed,including magnetic resonance imaging(MRI),magnetic mediated hyperthermia(MMH),Fenton reaction and autophagy.Finally,the clinical prospect of magnetofection was briefly expected.展开更多
Reversible protonic ceramic electrochemical cells(R-PCECs)are ideal,high-effi ciency devices that are environmentally friendly and have a modular design.This paper studies BaFe_(0.6)Zr_(0.1)Y_(0.3)O_(3−δ)(BFZY3)as a ...Reversible protonic ceramic electrochemical cells(R-PCECs)are ideal,high-effi ciency devices that are environmentally friendly and have a modular design.This paper studies BaFe_(0.6)Zr_(0.1)Y_(0.3)O_(3−δ)(BFZY3)as a cobalt-free perovskite oxygen electrode for high-performance R-PCECs where Y ions doping can increase the concentration of oxygen vacancies with a remarkable increase in catalytic performance.The cell with confi guration of Ni-BZCYYb/BZCYYb/BFZY3 demonstrated promising performance in dual modes of fuel cells(FCs)and electrolysis cells(ECs)at 650℃with low polarization resistance of 0.13Ωcm^(2),peak power density of 546.59 mW/cm^(2)in FC mode,and current density of−1.03 A/cm^(2)at 1.3 V in EC mode.The alternative operation between FC and EC modes for up to eight cycles with a total of 80 h suggests that the cell with BFZY3 is exceptionally stable and reversible over the long term.The results indicated that BFZY3 has considerable potential as an air electrode material for R-PCECs,permitting effi cient oxygen reduction and water splitting.展开更多
The severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has caused a global pandemic of novel coronavirus disease(COVID-19).The neutralizing monoclonal antibodies(mAbs)targeting the receptor-binding domain(RBD)...The severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has caused a global pandemic of novel coronavirus disease(COVID-19).The neutralizing monoclonal antibodies(mAbs)targeting the receptor-binding domain(RBD)of SARS-CoV-2 are among the most promising strategies to prevent and treat COVID-19.However,SARS-CoV-2 variants of concern(VOCs)profoundly reduced the efficacies of most of mAbs and vaccines approved for clinical use.Herein,we demonstrated mAb 35B5 efficiently neutralizes both wild-type(WT)SARS-CoV-2 and VOCs.展开更多
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
Abnormal glucose and lipid metabolism in COVID-19 patients were recently reported with unclear mechanism.In this study,we retrospectively investigated a cohort of COVID-19 patients without pre-existing metabolic-relat...Abnormal glucose and lipid metabolism in COVID-19 patients were recently reported with unclear mechanism.In this study,we retrospectively investigated a cohort of COVID-19 patients without pre-existing metabolic-related diseases,and found new-onset in suli n resista nee,hyperglycemia,and decreased HDL-C in these patie nts.Mecha nistically,SARS-CoV-2 infecti on in creased the expression of RE1-silencing transcription factor(REST),which modulated the expression of secreted metabolic factors including myeloperoxidase,apelin,and myostatin at the transcriptional level,resulting in the perturbation of glucose and lipid metabolism.Furthermore,several lipids,including(±)5-HETE,(±)12-HETE,propionic acid,and isobutyric acid were identified as the potential biomarkers of COVID-19-induced metabolic dysregulation,especially in insulin resistance.Taken together,our study revealed insulin resistance as the direct cause of hyperglycemia upon COVID-19,and further illustrated the underlying mechanisms,providing potential therapeutic targets for COVID-19-induced metabolic complications.展开更多
基金supported by the Important Hubei Science and Technology Innovation Plan 2015ACA062 (to Xulin Chen)the Natural Science Foundation of Hubei Province (2018CFB244, to Jungang Chen)
文摘Severe influenza infections are often associated with the excessive induction of pro-inflammatory cytokines,which is also referred to as"cytokine storms".Several studies have shown that cytokine storms are directly associated with influenzainduced fatal acute lung injury and acute respiratory distress syndrome.Due to the narrow administration window,current antiviral therapies are often inadequate.The efforts to use immunomodulatory agents alone or in combination with antiviral agents in the treatment of influenza in animal models have resulted in the achievement of protective effects accompanied with reduced cytokine production.Currently,there are no immunomodulatory drugs for influenza available for clinical use.Animal models,despite being ideal to study the anti-inflammatory responses to influenza virus infection,are very costly and time-consuming.Therefore,there is an urgent need to establish fast and economical screening methods using cellbased models to screen and develop novel immunomodulatory agents.In this study,we screened seven human cell lines and found that the human monocytic cell U937 supports the replication of different subtypes of influenza viruses as well as the production of the important pro-inflammatory cytokines and was selected to develop the cell-based model.The U937 cell model was validated by testing a panel of known antiviral and immunomodulatory agents and screening a drug library consisting of 1280 compounds comprised mostly of FDA-approved drugs.We demonstrated that the U937 cell model is robust and suitable for the high-throughput screening of immunomodulators and antivirals against influenza infection.
基金National Key Research and Development Program of China(No.2017YFC1104601)National Natural Science Foundation of China(NSFC,No.81873921)+1 种基金SinoGerman cooperation group project(No.GZ1512)Sichuan Science and Technology Program(No.2019JDJQ0027)。
文摘Magnetic nanoparticles(MNPs)have become a research hotspot and widely used in the biomedical field in recent decades due to their unique magnetic properties.This minireview summarizes the specific gene transfection of magnetic particles(magnetofection)during eversy dynamic process of gene delivery(gene binding,cellular uptake,endosomal escape,intracellular trafficking and in vivo targeting).Meanwhile,the synergistic biomedical application of magnetofection and the effects of MNPs have also been discussed,including magnetic resonance imaging(MRI),magnetic mediated hyperthermia(MMH),Fenton reaction and autophagy.Finally,the clinical prospect of magnetofection was briefly expected.
基金support from the National Key Research&Development Project(2022YFB4002201)National Natural Science Foundation of China(Nos.52172199,52072135,52002121)+1 种基金Hubei Province(2023BAB115)Jiangsu Province(BZ2022027).
文摘Reversible protonic ceramic electrochemical cells(R-PCECs)are ideal,high-effi ciency devices that are environmentally friendly and have a modular design.This paper studies BaFe_(0.6)Zr_(0.1)Y_(0.3)O_(3−δ)(BFZY3)as a cobalt-free perovskite oxygen electrode for high-performance R-PCECs where Y ions doping can increase the concentration of oxygen vacancies with a remarkable increase in catalytic performance.The cell with confi guration of Ni-BZCYYb/BZCYYb/BFZY3 demonstrated promising performance in dual modes of fuel cells(FCs)and electrolysis cells(ECs)at 650℃with low polarization resistance of 0.13Ωcm^(2),peak power density of 546.59 mW/cm^(2)in FC mode,and current density of−1.03 A/cm^(2)at 1.3 V in EC mode.The alternative operation between FC and EC modes for up to eight cycles with a total of 80 h suggests that the cell with BFZY3 is exceptionally stable and reversible over the long term.The results indicated that BFZY3 has considerable potential as an air electrode material for R-PCECs,permitting effi cient oxygen reduction and water splitting.
基金We thank Guangdong Center for Human Pathogen Culture Collection(GDPCC)for providing SARS-CoV-2 isolates.We thank Dr.Junyu Xiao(Peking University)for providing the plasmids encoding the ectodomains of the SARS-CoV-2 S-2P and S-6P mutants.This work was supported by grants from the National Natural Science Fund for Distinguished Young Scholars(No.31825011 to L.Y.)the National Science and Technology Major Project(No.2017ZX10202102-006-002 to L.Y.)+2 种基金Guangdong Innovative and Entrepreneurial Research Team Program(2016ZT06S638 to K.D.)High-level Biosafety Laboratory Construction and Operation Program of the Science and Technology Projects of Guangdong Province of China to K.D.,the National Natural Science Fund(81925024 to Y.Z.)the National Key Research and Development Program of China(2017YFA0503900 to Y.Z.),and the Fundamental Research Funds for the Central Universities to Y.Z.
文摘The severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has caused a global pandemic of novel coronavirus disease(COVID-19).The neutralizing monoclonal antibodies(mAbs)targeting the receptor-binding domain(RBD)of SARS-CoV-2 are among the most promising strategies to prevent and treat COVID-19.However,SARS-CoV-2 variants of concern(VOCs)profoundly reduced the efficacies of most of mAbs and vaccines approved for clinical use.Herein,we demonstrated mAb 35B5 efficiently neutralizes both wild-type(WT)SARS-CoV-2 and VOCs.
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This study was supported by the joint emergency grants for prevention and control of SARS-CoV-2 of Ministry of Science and Technology of China,Guangdong Science and Technology Department and Guangzhou Municipal Science and Technology Bureau(2020B111108001)Guangdong Science and Technology Department(2020B121206001&2020B1212030004)The funders had no role in study design,data collection and analysis,or preparation of the manuscript.
文摘Abnormal glucose and lipid metabolism in COVID-19 patients were recently reported with unclear mechanism.In this study,we retrospectively investigated a cohort of COVID-19 patients without pre-existing metabolic-related diseases,and found new-onset in suli n resista nee,hyperglycemia,and decreased HDL-C in these patie nts.Mecha nistically,SARS-CoV-2 infecti on in creased the expression of RE1-silencing transcription factor(REST),which modulated the expression of secreted metabolic factors including myeloperoxidase,apelin,and myostatin at the transcriptional level,resulting in the perturbation of glucose and lipid metabolism.Furthermore,several lipids,including(±)5-HETE,(±)12-HETE,propionic acid,and isobutyric acid were identified as the potential biomarkers of COVID-19-induced metabolic dysregulation,especially in insulin resistance.Taken together,our study revealed insulin resistance as the direct cause of hyperglycemia upon COVID-19,and further illustrated the underlying mechanisms,providing potential therapeutic targets for COVID-19-induced metabolic complications.
