Indocyanine green(ICG) is capable of inducing a photothermal effect and the production of cytotoxic reactive oxygen species for cancer therapy. However, the major challenge in applying ICG molecules for antitumor ther...Indocyanine green(ICG) is capable of inducing a photothermal effect and the production of cytotoxic reactive oxygen species for cancer therapy. However, the major challenge in applying ICG molecules for antitumor therapy is associated with their instability in aqueous conditions and rapid clearance from blood circulation,which causes insufficient bioavailability at the tumor site.Herein, we conjugated ICG molecules with Prussian blue nanoparticles enclosing a Fe_3O_4 nanocore, which was facilitated by cationic polyethyleneimine via electrostatic adsorption. The nanocarrier-loaded ICG formed stable aggregates that enhanced cellular uptake and prevented fluorescence quenching. Moreover, the strong superparamagnetism of the Fe_3O_4 core in the obtained nanocomposites further improved cellular internalization of the drugs guided by a localized magnetic field. The therapeutic efficacy of this nanoplatform was evaluated using tumor models established in nude mice, which demonstrated remarkable tumor ablation in vivo due to strong photothermal/photodynamic effects. This study provides promising evidence that this multifunctional nanoagent might function as an efficient mediator for combining photothermal and photodynamic cancer therapy.展开更多
The in vitro expansion of stem cells is important for their application in different life science fields such as cellular tissue and organ repair.An objective of this paper was to achieve static cell culture in vitro ...The in vitro expansion of stem cells is important for their application in different life science fields such as cellular tissue and organ repair.An objective of this paper was to achieve static cell culture in vitro through peptide hydrogel-supported microspheres(MSs).The peptides,with their gel-forming properties,microstructures,and mechanical strengths characterized,were found to have good support for the MSs and to be injectable.The internal structures of poly(L-lactic acid)microspheres(PLLA-MSs)and polystyrene microspheres(PS-MSs)made in thelaboratory were observed and statistically analyzed in terms of particle size and pore size,following which the co-cultured MSs with cells were found to have good cell adhesion.In addition,three-dimensional(3D)culturing of cells was performed on the peptide and microcarrier composite scaffolds to measure cell viability and cell proliferation.The results showed that the peptides could be stimulated by the culture medium to self-assembly form a 3D fiber network structure.Under the peptide-Ms composite scaffold-based cell culture system,further enhancement of the cell culture effect was measured.The peptide-Ms composite scaffolds have great potential for the application in 3D cell culture and in vitro cellexpansion.展开更多
SARS-CoV-2 infection causes complicated clinical manifestations with variable multi-organ injuries,how-ever,the underlying mechanism,in particular immune responses in different organs,remains elusive.In this study,com...SARS-CoV-2 infection causes complicated clinical manifestations with variable multi-organ injuries,how-ever,the underlying mechanism,in particular immune responses in different organs,remains elusive.In this study,comprehensive transcriptomic alterations of 14 tissues from rhesus macaque infected with SARS-CoV-2 were analyzed.Compared to normal controls,SARS-CoV-2 infection resulted in dysregulation of genes involving diverse functions in various examined tissues/organs,with drastic transcriptomic changes in cerebral cortex and right ventricle.Intriguingly,cerebral cortex exhibited a hyperinflammatory state evidenced by sig-nificant upregulation of inflammation response-related genes.Meanwhile,expressions of coagulation,angio-genesis and fibrosis factors were also up-regulated in cerebral cortex.Based on our findings,neuropilin 1(NRP1),a receptor of SARS-CoV-2,was significantly elevated in cerebral cortex post infection,accompanied by active immune response releasing inflammatory factors and signal transmission among tissues,which enhanced infection of the central nervous system(CNS)in a positive feedback way,leading to viral encephalitis.Overall,our study depicts a multi-tissue/organ tran-scriptomic landscapes of rhesus macaque with early infection of SARS-CoV-2,and provides important insights into the mechanistic basis for COVID-19-asso-ciated clinical complications.展开更多
Ultrasound is widely used in biomedical engineering and has applications in conventional diagnosis and drug delivery.Recent advances in ultrasound-induced drug delivery have been summarized previously in several revie...Ultrasound is widely used in biomedical engineering and has applications in conventional diagnosis and drug delivery.Recent advances in ultrasound-induced drug delivery have been summarized previously in several reviews that have primarily focused on the fabrication of drug delivery carriers.This review discusses the mechanisms underlying ultrasound-induced drug delivery and factors affecting delivery efficiency,including the characteristics of drug delivery carriers and ultrasound parameters.Firstly,biophysical effects induced by ultrasound,namely thermal effects,cavitation effects,and acoustic radiation forces,are illustrated.Secondly,the use of these biophysical effects to enhance drug delivery by affecting drug carriers and corresponding tissues is clarified in detail.Thirdly,recent advances in ultrasound-triggered drug delivery are detailed.Safety issues and optimization strategies to improve therapeutic outcomes and reduce side effects are summarized.Finally,current progress and future directions are discussed.展开更多
Although DNA 5-hydroxymethylcytosine(5 hmC)is recognized as an important epigenetic mark in cancer,its precise role in lymph node metastasis remains elusive.In this study,we investigated how 5 hmC associates with lymp...Although DNA 5-hydroxymethylcytosine(5 hmC)is recognized as an important epigenetic mark in cancer,its precise role in lymph node metastasis remains elusive.In this study,we investigated how 5 hmC associates with lymph node metastasis in breast cancer.Accompanying with high expression of TET1 and TET2 proteins,large numbers of genes in the metastasis-positive primary tumors exhibit higher 5 hmC levels than those in the metastasis-negative primary tumors.In contrast,the TET protein expression and DNA 5 hmC decrease significantly within the metastatic lesions in the lymph nodes compared to those in their matched primary tumors.Through genomewide analysis of 8 sets of primary tumors,we identified 100 high-confidence metastasis-associated5 hmC signatures,and it is found that increased levels of DNA 5 hmC and gene expression of MAP7 D1 associate with high risk of lymph node metastasis.Furthermore,we demonstrate that MAP7 D1,regulated by TET1,promotes tumor growth and metastasis.In conclusion,the dynamic5 hmC profiles during lymph node metastasis suggest a link between DNA 5 hmC and lymph node metastasis.Meanwhile,the role of MAP7 D1 in breast cancer progression suggests that the metastasis-associated 5 hmC signatures are potential biomarkers to predict the risk for lymph node metastasis,which may serve as diagnostic and therapeutic targets for metastatic breast cancer.展开更多
A chronic autoimmune disease named rheumatoid arthritis(RA)is characterized mainly by synovitis,which has high morbidity,disability and mortality rates.In addition,the aetiology and pathogenesis of RA have not been fu...A chronic autoimmune disease named rheumatoid arthritis(RA)is characterized mainly by synovitis,which has high morbidity,disability and mortality rates.In addition,the aetiology and pathogenesis of RA have not been fully determined.RA is usually accompanied by persistent arthritic pain,swelling,stiffness,and functional disorders;in severe cases,it may result in cardiovascular,pulmonary,psychological and skeletal diseases(Scott et al.,2010).展开更多
基金financial support from Fundamental Research Funds for Central Universities (XDJK2016A010 and XDJK2017C001)National Natural Science Foundation of China (51703186 and 31671037)Southwest University (SWU116032 and SWU115059)
文摘Indocyanine green(ICG) is capable of inducing a photothermal effect and the production of cytotoxic reactive oxygen species for cancer therapy. However, the major challenge in applying ICG molecules for antitumor therapy is associated with their instability in aqueous conditions and rapid clearance from blood circulation,which causes insufficient bioavailability at the tumor site.Herein, we conjugated ICG molecules with Prussian blue nanoparticles enclosing a Fe_3O_4 nanocore, which was facilitated by cationic polyethyleneimine via electrostatic adsorption. The nanocarrier-loaded ICG formed stable aggregates that enhanced cellular uptake and prevented fluorescence quenching. Moreover, the strong superparamagnetism of the Fe_3O_4 core in the obtained nanocomposites further improved cellular internalization of the drugs guided by a localized magnetic field. The therapeutic efficacy of this nanoplatform was evaluated using tumor models established in nude mice, which demonstrated remarkable tumor ablation in vivo due to strong photothermal/photodynamic effects. This study provides promising evidence that this multifunctional nanoagent might function as an efficient mediator for combining photothermal and photodynamic cancer therapy.
基金supported by the National Key Research andDevelopment Program of China(Grant No.2021YFC2101400).
文摘The in vitro expansion of stem cells is important for their application in different life science fields such as cellular tissue and organ repair.An objective of this paper was to achieve static cell culture in vitro through peptide hydrogel-supported microspheres(MSs).The peptides,with their gel-forming properties,microstructures,and mechanical strengths characterized,were found to have good support for the MSs and to be injectable.The internal structures of poly(L-lactic acid)microspheres(PLLA-MSs)and polystyrene microspheres(PS-MSs)made in thelaboratory were observed and statistically analyzed in terms of particle size and pore size,following which the co-cultured MSs with cells were found to have good cell adhesion.In addition,three-dimensional(3D)culturing of cells was performed on the peptide and microcarrier composite scaffolds to measure cell viability and cell proliferation.The results showed that the peptides could be stimulated by the culture medium to self-assembly form a 3D fiber network structure.Under the peptide-Ms composite scaffold-based cell culture system,further enhancement of the cell culture effect was measured.The peptide-Ms composite scaffolds have great potential for the application in 3D cell culture and in vitro cellexpansion.
基金supported by grants from National Key R&D Program of China(2020YFC0848900)CAS Key Research Projects of the Frontier Science(QYZDY-SSW-SMC027)+5 种基金National Natural Science Foundation of China(31625016 and 81788101)K.C.Wong Education Foundation(GJTD-2019-08)Chinese Academy of Medical Sciences(CAMS)Initiative for Innovative Medicine(2016-I2M-2-001,2017-I2M-2-006,2020-I2M-CoV19-003,2020-I2M-CoV19-007)the Youth Innovation Promotion Association,CAS(2018133)China National Postdoctoral Program for Innovative Talents(BX2021291)Shanghai Municipal Science and Technology Major Project(2017SHZDZX01).
文摘SARS-CoV-2 infection causes complicated clinical manifestations with variable multi-organ injuries,how-ever,the underlying mechanism,in particular immune responses in different organs,remains elusive.In this study,comprehensive transcriptomic alterations of 14 tissues from rhesus macaque infected with SARS-CoV-2 were analyzed.Compared to normal controls,SARS-CoV-2 infection resulted in dysregulation of genes involving diverse functions in various examined tissues/organs,with drastic transcriptomic changes in cerebral cortex and right ventricle.Intriguingly,cerebral cortex exhibited a hyperinflammatory state evidenced by sig-nificant upregulation of inflammation response-related genes.Meanwhile,expressions of coagulation,angio-genesis and fibrosis factors were also up-regulated in cerebral cortex.Based on our findings,neuropilin 1(NRP1),a receptor of SARS-CoV-2,was significantly elevated in cerebral cortex post infection,accompanied by active immune response releasing inflammatory factors and signal transmission among tissues,which enhanced infection of the central nervous system(CNS)in a positive feedback way,leading to viral encephalitis.Overall,our study depicts a multi-tissue/organ tran-scriptomic landscapes of rhesus macaque with early infection of SARS-CoV-2,and provides important insights into the mechanistic basis for COVID-19-asso-ciated clinical complications.
基金supported by the National Natural Science Foundation of China(31971169,81822022,81771846,81571810)the Beijing Natural Science Foundation(7182180)+2 种基金National Key Research and Development Program of China(2018YFC0116003,2016YFA0201400)Beijing Talents Foundation(2018000021223ZK48)Peking University Third Hospital(BYSYZD2019018,jyzc2018-02,BYSY2015023)。
文摘Ultrasound is widely used in biomedical engineering and has applications in conventional diagnosis and drug delivery.Recent advances in ultrasound-induced drug delivery have been summarized previously in several reviews that have primarily focused on the fabrication of drug delivery carriers.This review discusses the mechanisms underlying ultrasound-induced drug delivery and factors affecting delivery efficiency,including the characteristics of drug delivery carriers and ultrasound parameters.Firstly,biophysical effects induced by ultrasound,namely thermal effects,cavitation effects,and acoustic radiation forces,are illustrated.Secondly,the use of these biophysical effects to enhance drug delivery by affecting drug carriers and corresponding tissues is clarified in detail.Thirdly,recent advances in ultrasound-triggered drug delivery are detailed.Safety issues and optimization strategies to improve therapeutic outcomes and reduce side effects are summarized.Finally,current progress and future directions are discussed.
基金supported by the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences(Grant Nos.2016ZX310182-2 and 2016ZX310176-6 to NY)the Medical Epigenetics Research Center,Chinese Academy of Medical Sciences(Grant Nos.2017PT31035 and 2018PT31035 to NY)the National Natural Science Foundation of China(Grant No.81773163 to JF)
文摘Although DNA 5-hydroxymethylcytosine(5 hmC)is recognized as an important epigenetic mark in cancer,its precise role in lymph node metastasis remains elusive.In this study,we investigated how 5 hmC associates with lymph node metastasis in breast cancer.Accompanying with high expression of TET1 and TET2 proteins,large numbers of genes in the metastasis-positive primary tumors exhibit higher 5 hmC levels than those in the metastasis-negative primary tumors.In contrast,the TET protein expression and DNA 5 hmC decrease significantly within the metastatic lesions in the lymph nodes compared to those in their matched primary tumors.Through genomewide analysis of 8 sets of primary tumors,we identified 100 high-confidence metastasis-associated5 hmC signatures,and it is found that increased levels of DNA 5 hmC and gene expression of MAP7 D1 associate with high risk of lymph node metastasis.Furthermore,we demonstrate that MAP7 D1,regulated by TET1,promotes tumor growth and metastasis.In conclusion,the dynamic5 hmC profiles during lymph node metastasis suggest a link between DNA 5 hmC and lymph node metastasis.Meanwhile,the role of MAP7 D1 in breast cancer progression suggests that the metastasis-associated 5 hmC signatures are potential biomarkers to predict the risk for lymph node metastasis,which may serve as diagnostic and therapeutic targets for metastatic breast cancer.
基金supported by the National Natural Science Foundation of China(81871363,81822022,81771846,and 81571810)Beijing Talents Foundation(2018000021223ZK48)grants from Peking University Third Hospital(BYSYZD2019018,jyzc2018-02,and BYSY2015023)。
文摘A chronic autoimmune disease named rheumatoid arthritis(RA)is characterized mainly by synovitis,which has high morbidity,disability and mortality rates.In addition,the aetiology and pathogenesis of RA have not been fully determined.RA is usually accompanied by persistent arthritic pain,swelling,stiffness,and functional disorders;in severe cases,it may result in cardiovascular,pulmonary,psychological and skeletal diseases(Scott et al.,2010).