Dear Editor,Infection with the novel coronavirus(SARS-CoV-2,which is the virus responsible for the coronavirus disease 2019(COVID-19))was first reported in Wuhan,China on December 31,2019.The outbreak of COVID-19 rema...Dear Editor,Infection with the novel coronavirus(SARS-CoV-2,which is the virus responsible for the coronavirus disease 2019(COVID-19))was first reported in Wuhan,China on December 31,2019.The outbreak of COVID-19 remains ongoing and was linked to more than 80,000 infected patients and more than 3,000 deaths in China as of March 7,2020(Holshue et al.,2020).展开更多
Detection of sentinel lymph nodes(SLNs)is critical to guide the treatment of breast cancer.However,distinguishing metastatic SLNs from normal and inflamed lymph nodes(LNs)during surgical resection remains a challenge....Detection of sentinel lymph nodes(SLNs)is critical to guide the treatment of breast cancer.However,distinguishing metastatic SLNs from normal and inflamed lymph nodes(LNs)during surgical resection remains a challenge.Here,we report a CD44 and scavenger receptor class B1 dual-targeting hyaluronic acid nanoparticle(5K-HA-HPPS)loaded with the near-infra-red fluorescent dye DiR-BOA for SLN imaging in breast cancer.The small sized(~40 nm)self-assembled 5K-HA-HPPSs accumulated rapidly in the SLNs after intradermal injection.Compared with normal popliteal LNs(N-LN),there were ~3.2-fold and ~2.4-fold increases in fluorescence intensity in tumour metastatic SLNs(T-MLN)and inflamed LNs(Inf-LN),respectively,6 h after nanoparticle inoculation.More importantly,photoacoustic microscopy(PAM)of 5KHA-HPPS showed a significantly distinct distribution in T-MLN compared with N-LN and Inf-LN.Signals were mainly distributed at the centre of T-MLN but at the periphery of N-LN and Inf-LN.The ratio of PA intensity(R)at the centre of the LNs compared with that at the periphery was 5.93±0.75 for T-MLNs of the 5K-HA-HPPS group,which was much higher than that for the Inf-LNs(R=0.2±0.07)and N-LNs(R=0.45±0.09).These results suggest that 5K-HA-HPPS injection combined with PAM provides a powerful tool for distinguishing metastatic SLNs from pLNs and inflamed LNs,thus guiding the removal of SLNs during breast cancer surgery.展开更多
The 2019 coronavirus disease(COVID-19)outbreak caused by the SARS-CoV-2 virus is an ongoing global health emergency.However,the virus'pathogenesis remains unclear,and there is no cure for the disease.We investigat...The 2019 coronavirus disease(COVID-19)outbreak caused by the SARS-CoV-2 virus is an ongoing global health emergency.However,the virus'pathogenesis remains unclear,and there is no cure for the disease.We investigated the dynamic changes of blood immune response in patients with COVID-19 at different stages by using 5'gene expression,T cell receptor(TCR),and B cell receptors(BCR)V(D)J transcriptome analysis at a single-cell resolution.We obtained single-cell mRNA sequencing(scRNA-seq)data of 341,420 peripheral blood mononuclear cells(PBMCs)and 185,430 donotypic T cells and 28,802 donotypic B cells from 25 samples of 16 patients with COVID-19 for dynamic studies.In addition,we used three control samples.We found expansion of dendritic cells(DCs),CD14+monocytes,and megakaryocytes progenitor cells(MP)/platelets and a reduction of naive CD4+T lymphocytes in patients with COVID-19,along with a significant decrease of CD8+T lymphocytes,and natural killer cells(NKs)in patients in critical condition.The type I interferon(IFN-I),mitogen-activated protein kinase(MAPK),and ferroptosis pathways were activated while the disease was active,and recovered gradually after patient conditions improved.Consistent with this finding,the mRNA level of IFN-I signal-induced gene IFI27 was significantly increased in patients with COVID-19 compared with that of the controls in a validation cohort that included 38 patients and 35 controls.The concentration of interferon-a(IFN-a)in the serum of patients with COVID-19 increased significantly compared with that of the controls in an additional cohort of 215 patients with COVID-19 and 106 controls,further suggesting the important role of the IFN-I pathway in the immune response of COVID-19.TCR and BCR sequences analyses indicated that patients with COVID-19 developed specific immune responses against SARS-CoV-2 antigens.Our study reveals a dynamic landscape of human blood immune responses to SARS-CoV-2 infection,providing clues for therapeutic potentials in treating COVID-19.展开更多
Glioblastoma(GBM),one of the most common primary intracranial malignant tumours,is very difficult to be completely excised by surgery due to its irregular shape.Here,we use an MRI/NIR fluorescence dual-modal imaging n...Glioblastoma(GBM),one of the most common primary intracranial malignant tumours,is very difficult to be completely excised by surgery due to its irregular shape.Here,we use an MRI/NIR fluorescence dual-modal imaging nanoprobe that includes superparamagnetic iron oxide nanoparticles(SPIONs)modified with indocyanine(Cy7)molecules and peptides(ANG orDANG)to locate malignant gliomas and guide accurate excision.Both peptides/Cy7-SPIONs probes displayed excellent tumour-homing properties and barrier penetrating abilities in vitro.展开更多
Antimony(Sb)nanoparticles(SbNP)encapsulated in multiwalled carbon nanotubes(MWCNTs)matrix has been fabricated by a facile two-step ball milling strategy,including a sand milling process to prepare Sb nanoparticles and...Antimony(Sb)nanoparticles(SbNP)encapsulated in multiwalled carbon nanotubes(MWCNTs)matrix has been fabricated by a facile two-step ball milling strategy,including a sand milling process to prepare Sb nanoparticles and following high-energy ball milling to synthesize SbNP-MWCNT composite.As an anode material for sodium-ion batteries(SIBs),the SbNP-MWCNT composite with high Sb content(80%)can deliver a reversible capacity of 471.1 mA hg^(-1)at 50 mA g^(-1)with an initial coulombic efficiency of 73.5%,excellent cycling stability(94.1%capacity retention at 800 mA g^(-1))and high rate capability(210.7 mA h g^(-1)at 3200 mA g^(-1)).The excellent electrochemical performance of the SbNP-MWCNT composite results from the synergistic effect of downsizing Sb particles and combining MWCNTs.展开更多
To assess the impact of the key non-synonymous amino acid substitutions in the RBD of the spike protein of SARS-CoV-2 variant B.1.617.1(dominant variant identified in the current India outbreak)on the infectivity and ...To assess the impact of the key non-synonymous amino acid substitutions in the RBD of the spike protein of SARS-CoV-2 variant B.1.617.1(dominant variant identified in the current India outbreak)on the infectivity and neutralization activities of the immune sera,L452R and E484Q(L452R-E484Q variant),pseudotyped virus was constructed(with the D614G background).The impact on binding with the neutralizing antibodies was also assessed with an ELISA assay.Pseudotyped virus carrying a L452R-E484Q variant showed a comparable infectivity compared with D614G.However,there was a significant reduction in the neutralization activity of the immune sera from non-human primates vaccinated with a recombinant receptor binding domain(RBD)protein,convalescent patients,and healthy vaccinees vaccinated with anmRNA vaccine.In addition,there was a reduction in binding of L452R-E484Q-D614G protein to the antibodies of theimmune sera fromvaccinated nonhuman primates.These results highlight the interplay between infectivity and other biologic factors involved in the natural evolution of SARS-CoV-2.Reduced neutralization activities against the L452R-E484Q variant will have an impact on health authority planning and implications for the vaccination strategy/newvaccine development.展开更多
Colonoscopy is an effective tool for early screening of colorectal diseases.However,the application of colonoscopy in distinguishing different intestinal diseases still faces great challenges of efficiency and accurac...Colonoscopy is an effective tool for early screening of colorectal diseases.However,the application of colonoscopy in distinguishing different intestinal diseases still faces great challenges of efficiency and accuracy.Here we constructed and evaluated a deep convolution neural network(CNN)model based on 117055 images from 16004 individuals,which achieved a high accuracy of 0.933 in the validation dataset in identifying patients with polyp,colitis,colorectal cancer(CRC)from normal.The proposed approach was further validated onmulti-center real-time colonoscopy videos and images,which achieved accurate diagnostic performance on detecting colorectal diseases with high accuracy and precision to generalize across external validation datasets.The diagnostic performance of the model was further compared to the skilled endoscopists and the novices.In addition,our model has potential in diagnosis of adenomatous polyp and hyperplastic polyp with an area under the receiver operating characteristic curve of 0.975.Our proposed CNN models have potential in assisting clinicians in making clinical decisions with efficiency during application.展开更多
基金supported by the grants from Sichuan Science and Technology Program(2020YFS0014 and 2020YFS0558)the Chinese Academy of Medical Sciences(2019-I2M-5032)Technology&Science&Technology Bureau of Chengdu(2020YF05-00060-SN and 2020-YF05-00075-SN)。
文摘Dear Editor,Infection with the novel coronavirus(SARS-CoV-2,which is the virus responsible for the coronavirus disease 2019(COVID-19))was first reported in Wuhan,China on December 31,2019.The outbreak of COVID-19 remains ongoing and was linked to more than 80,000 infected patients and more than 3,000 deaths in China as of March 7,2020(Holshue et al.,2020).
基金supported by the National Science Fund for Distinguished Young Scholars(81625012)the National Natural Science Foundation of China(61721092)+2 种基金the Fundamental Research Funds for the Central Universities(2019kfyXMBZ022)Programme for HUST Academic Frontier Youth Team(Zhang,Z.H.)the Innovation Fund of WNLO.
文摘Detection of sentinel lymph nodes(SLNs)is critical to guide the treatment of breast cancer.However,distinguishing metastatic SLNs from normal and inflamed lymph nodes(LNs)during surgical resection remains a challenge.Here,we report a CD44 and scavenger receptor class B1 dual-targeting hyaluronic acid nanoparticle(5K-HA-HPPS)loaded with the near-infra-red fluorescent dye DiR-BOA for SLN imaging in breast cancer.The small sized(~40 nm)self-assembled 5K-HA-HPPSs accumulated rapidly in the SLNs after intradermal injection.Compared with normal popliteal LNs(N-LN),there were ~3.2-fold and ~2.4-fold increases in fluorescence intensity in tumour metastatic SLNs(T-MLN)and inflamed LNs(Inf-LN),respectively,6 h after nanoparticle inoculation.More importantly,photoacoustic microscopy(PAM)of 5KHA-HPPS showed a significantly distinct distribution in T-MLN compared with N-LN and Inf-LN.Signals were mainly distributed at the centre of T-MLN but at the periphery of N-LN and Inf-LN.The ratio of PA intensity(R)at the centre of the LNs compared with that at the periphery was 5.93±0.75 for T-MLNs of the 5K-HA-HPPS group,which was much higher than that for the Inf-LNs(R=0.2±0.07)and N-LNs(R=0.45±0.09).These results suggest that 5K-HA-HPPS injection combined with PAM provides a powerful tool for distinguishing metastatic SLNs from pLNs and inflamed LNs,thus guiding the removal of SLNs during breast cancer surgery.
基金This work was supported by the Sichuan Science and Technology Program(2020YFS0014 and 2020YFS0558)the Chinese Academy of Medical Sciences(NO.2019-I2M-5-032)+1 种基金the National Key Research and Development Program of China(2016YFC20160905200)the National Natural Science Foundation of China(81790643,81970839 and 81670895).
文摘The 2019 coronavirus disease(COVID-19)outbreak caused by the SARS-CoV-2 virus is an ongoing global health emergency.However,the virus'pathogenesis remains unclear,and there is no cure for the disease.We investigated the dynamic changes of blood immune response in patients with COVID-19 at different stages by using 5'gene expression,T cell receptor(TCR),and B cell receptors(BCR)V(D)J transcriptome analysis at a single-cell resolution.We obtained single-cell mRNA sequencing(scRNA-seq)data of 341,420 peripheral blood mononuclear cells(PBMCs)and 185,430 donotypic T cells and 28,802 donotypic B cells from 25 samples of 16 patients with COVID-19 for dynamic studies.In addition,we used three control samples.We found expansion of dendritic cells(DCs),CD14+monocytes,and megakaryocytes progenitor cells(MP)/platelets and a reduction of naive CD4+T lymphocytes in patients with COVID-19,along with a significant decrease of CD8+T lymphocytes,and natural killer cells(NKs)in patients in critical condition.The type I interferon(IFN-I),mitogen-activated protein kinase(MAPK),and ferroptosis pathways were activated while the disease was active,and recovered gradually after patient conditions improved.Consistent with this finding,the mRNA level of IFN-I signal-induced gene IFI27 was significantly increased in patients with COVID-19 compared with that of the controls in a validation cohort that included 38 patients and 35 controls.The concentration of interferon-a(IFN-a)in the serum of patients with COVID-19 increased significantly compared with that of the controls in an additional cohort of 215 patients with COVID-19 and 106 controls,further suggesting the important role of the IFN-I pathway in the immune response of COVID-19.TCR and BCR sequences analyses indicated that patients with COVID-19 developed specific immune responses against SARS-CoV-2 antigens.Our study reveals a dynamic landscape of human blood immune responses to SARS-CoV-2 infection,providing clues for therapeutic potentials in treating COVID-19.
基金This work was supported by the Natural Science Foundation of China(Grant 81501462,81621003)the Sichuan Science and Technology Program(Grant 2019YJ0116)+2 种基金the Chengdu International Science and Technology Cooperation Funding(Grant 2019-GH02-00074-HZ)the 1-3-5 Project for Disciplines of Excellence-Clinical Research Incubation Project,West China Hospital,Sichuan Universityand the Functional and Molecular Imaging Key Laboratory of Sichuan Province(Grant 2012J00011).
文摘Glioblastoma(GBM),one of the most common primary intracranial malignant tumours,is very difficult to be completely excised by surgery due to its irregular shape.Here,we use an MRI/NIR fluorescence dual-modal imaging nanoprobe that includes superparamagnetic iron oxide nanoparticles(SPIONs)modified with indocyanine(Cy7)molecules and peptides(ANG orDANG)to locate malignant gliomas and guide accurate excision.Both peptides/Cy7-SPIONs probes displayed excellent tumour-homing properties and barrier penetrating abilities in vitro.
基金This work was support by the National Nature Science Foundation of China(21673165)Science and Technology Project of State Grid Corporation of China(No.SGRIDGKJ[2017]841)and JCKY2016130B010。
文摘Antimony(Sb)nanoparticles(SbNP)encapsulated in multiwalled carbon nanotubes(MWCNTs)matrix has been fabricated by a facile two-step ball milling strategy,including a sand milling process to prepare Sb nanoparticles and following high-energy ball milling to synthesize SbNP-MWCNT composite.As an anode material for sodium-ion batteries(SIBs),the SbNP-MWCNT composite with high Sb content(80%)can deliver a reversible capacity of 471.1 mA hg^(-1)at 50 mA g^(-1)with an initial coulombic efficiency of 73.5%,excellent cycling stability(94.1%capacity retention at 800 mA g^(-1))and high rate capability(210.7 mA h g^(-1)at 3200 mA g^(-1)).The excellent electrochemical performance of the SbNP-MWCNT composite results from the synergistic effect of downsizing Sb particles and combining MWCNTs.
文摘To assess the impact of the key non-synonymous amino acid substitutions in the RBD of the spike protein of SARS-CoV-2 variant B.1.617.1(dominant variant identified in the current India outbreak)on the infectivity and neutralization activities of the immune sera,L452R and E484Q(L452R-E484Q variant),pseudotyped virus was constructed(with the D614G background).The impact on binding with the neutralizing antibodies was also assessed with an ELISA assay.Pseudotyped virus carrying a L452R-E484Q variant showed a comparable infectivity compared with D614G.However,there was a significant reduction in the neutralization activity of the immune sera from non-human primates vaccinated with a recombinant receptor binding domain(RBD)protein,convalescent patients,and healthy vaccinees vaccinated with anmRNA vaccine.In addition,there was a reduction in binding of L452R-E484Q-D614G protein to the antibodies of theimmune sera fromvaccinated nonhuman primates.These results highlight the interplay between infectivity and other biologic factors involved in the natural evolution of SARS-CoV-2.Reduced neutralization activities against the L452R-E484Q variant will have an impact on health authority planning and implications for the vaccination strategy/newvaccine development.
基金This study was funded by the National Natural Science Foundation of China(Grant No.81902861 to F.Z.and 32000485 to X.H.)“Xinglin Scholars”Scientific Research Project Fund of Chengdu University of Traditional Chinese Medicine(Grant No.YYZX2019012 to F.Z.)+1 种基金the Scientific Research Fund of Technology Bureau in Dazhou(Grant No.17YYJC0004 to F.-W.Z.)the Key Research and Development Project Fund of Science and Technology Bureau in Dazhou,Sichuan Province(Grant No.20ZDYF0001 to F.-W.Z.).We express our deepest appreciation to J.Z,Y.C.for organizing the raw data and G.Y.for the revising the manuscript.
文摘Colonoscopy is an effective tool for early screening of colorectal diseases.However,the application of colonoscopy in distinguishing different intestinal diseases still faces great challenges of efficiency and accuracy.Here we constructed and evaluated a deep convolution neural network(CNN)model based on 117055 images from 16004 individuals,which achieved a high accuracy of 0.933 in the validation dataset in identifying patients with polyp,colitis,colorectal cancer(CRC)from normal.The proposed approach was further validated onmulti-center real-time colonoscopy videos and images,which achieved accurate diagnostic performance on detecting colorectal diseases with high accuracy and precision to generalize across external validation datasets.The diagnostic performance of the model was further compared to the skilled endoscopists and the novices.In addition,our model has potential in diagnosis of adenomatous polyp and hyperplastic polyp with an area under the receiver operating characteristic curve of 0.975.Our proposed CNN models have potential in assisting clinicians in making clinical decisions with efficiency during application.