Accelerating the development of students is the basic goal of postgraduate talent cultivation.The final research results,employment situation and satisfaction of postgraduate students with school education are more im...Accelerating the development of students is the basic goal of postgraduate talent cultivation.The final research results,employment situation and satisfaction of postgraduate students with school education are more important indicators of the quality of talent cultivation in a university.For having a deeper understanding of the satisfaction of postgraduates in Harbin Institute of Technology(Weihai)in terms of motivation,tutor situation,management service and employment situation,a questionnaire survey was conducted on postgraduates.The survey results show that the overall satisfaction of postgraduates is high.In terms of studying motivation,most postgraduates think that their majors are more related to employment;in terms of professors,most of them can get along well with their professors and learn from the advantages of their professors;in terms of school management,they respond well to the"library",but think that the"dormitory"and"canteen"need further improvement;in terms of employment,most of postgraduates choose to be employed,while a few of them choose to further their studies,most of which have applied to study in domestic or foreign universities.展开更多
COVID-19 patients exhibit differential disease severity after SARS-CoV-2 infection.It is currently unknown as to the correlation between the magnitude of neutralizing antibody(NAb)responses and the disease severity in...COVID-19 patients exhibit differential disease severity after SARS-CoV-2 infection.It is currently unknown as to the correlation between the magnitude of neutralizing antibody(NAb)responses and the disease severity in COVID-19 patients.In a cohort of 59 recovered patients with disease severity including severe,moderate,mild,and asymptomatic,we observed the positive correlation between serum neutralizing capacity and disease severity,in particular,the highest NAb capacity in sera from the patients with severe disease,while a lack of ability of asymptomatic patients to mount competent NAbs.Furthermore,the compositions of NAb subtypes were also different between recovered patients with severe symptoms and with mild-tomoderate symptoms.These results reveal the tremendous heterogeneity of SARS-CoV-2-specific NAb responses and their correlations to disease severity,highlighting the needs of future vaccination in COVID-19 patients recovered from asymptomatic or mild illness.展开更多
Background:Existing treatments for cholangiocarcinoma have poor efficacy.However,chimeric antigen receptor-T(CAR-T)cells are emerging as a potential therapeutic strategy.Solid tumors possess multiple adverse factors i...Background:Existing treatments for cholangiocarcinoma have poor efficacy.However,chimeric antigen receptor-T(CAR-T)cells are emerging as a potential therapeutic strategy.Solid tumors possess multiple adverse factors in an immunosuppressive microenvironment that impair CAR-T cell infiltration and function.This study aimed to improve the function of CAR-T cells through knock down immune checkpoints and immunosuppressive molecular receptors.Methods:We evaluated the expression of epidermal growth factor receptor(EGFR)and B7 homolog 3 protein(B7H3)antigens in cholangiocarcinoma tissues using immunohistochemistry and screened specific immune checkpoints in the cholangiocarcinoma microenvironment via flow cytometry.Subsequently,we engineered CAR-T cells targeting EGFR and B7H3 antigens.We simultaneously knocked down immune checkpoints and immunosuppressive molecular receptors in CAR-T cells by constructing two clusters of small hairpin RNAs and evaluated the engineered CAR-T cells for antitumor activity both in vitro,using tumor cell lines and cholangiocarcinoma organoid models,and in vivo,using humanized mouse models.Results:We observed high expression of EGFR and B7H3 antigens in cholangiocarcinoma tissues.EGFR-CAR-T and B7H3-CAR-T cells demonstrated specific anti-tumor activity.We found an abundance of programmed cell death protein 1(PD-1),T cell immunoglobulin and mucin domain-containing protein 3(Tim-3),and T cell immunoglobulin and ITIM domain(Tigit)on infiltrated CD8^(+)T cells in the cholangiocarcinoma microenvironment.We then decreased the expression of these 3 proteins on the surface of CAR-T cells,named PTG-scFV-CAR-T cells.Furthermore,we knocked-down the expression of transforming growth factor beta receptor(TGFβR),interleukin-10 receptor(IL-10R),and interleukin-6 receptor(IL-6R)of PTG-scFV-CAR-T cells.Those cells,named PTG-T16R-scFVCAR-T cells,potently killed tumor cells in vitro and promoted apoptosis of tumor cells in a cholangiocarcinoma organoidmodel.Finally,the PTG-T16R-scFv-CART cells showed greater inhibitory effect on tumor growth in vivo,and were superior in prolonging the survival of mice.Conclusions:Our results revealed that PTG-T16R-scFV-CAR-T cells with knockdown of sextuplet inhibitory molecules exhibited strong immunity against cholangiocarcinoma and long-term efficacy both in vitro and in vivo.This strategy provides an effective and personalized immune cell therapy against cholangiocarcinoma.展开更多
Dear Editor,The Omicron(B.1.1.529)variant of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)was first identified in November 2021,in South Africa and Botswana.The first Omicron sub-lineage that emerged was...Dear Editor,The Omicron(B.1.1.529)variant of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)was first identified in November 2021,in South Africa and Botswana.The first Omicron sub-lineage that emerged was BA.1,which was supplanted by BA.2 in many countries.One of the most notable features of the Omicron variant is its ability to evade neutralizing antibodies(nAbs)targeting the original virus lineages.展开更多
The worldwide pandemic caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has resulted in more than 4.5 million deaths.Although coronaviruses have a proofreading mechanism to maintain the stability o...The worldwide pandemic caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has resulted in more than 4.5 million deaths.Although coronaviruses have a proofreading mechanism to maintain the stability of their long genomic RNAs,mutations emerge continuously,and new variants conferring advantages rapidly become the dominant lineages[1].Strategies to fight the COVID-19 pandemic using either vaccines or nonpharmaceutical interventions have specifically been threatened by the emergence of SARS-CoV-2 variants of concern(VOCs)[2].展开更多
Coronavirus disease 2019(COVID-19),caused by infection with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),has rapidly become a global pandemic.Most discharge criteria for patients with COVID-19 recommend...Coronavirus disease 2019(COVID-19),caused by infection with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),has rapidly become a global pandemic.Most discharge criteria for patients with COVID-19 recommend two consecutive negative reverse-transcriptase polymerase-chain reaction(RT-PCR)test results from respiratory specimens over a 24-hour interval.Reports are accumulating of recurrent viral RNA-positive(RP)nasopharyngeal or anal specimens from recovered patients in China,Italy,South Korea,and France.1–8 Two cohort studies reported that 14.5%(38/262)and 16.7%(69/414)of patients with COVID-19 retesting were positive for SARS-CoV-2 RNA after discharge.2,6 The potential causes of RP specimens may be related to several aspects,such as virological factors,including residual viral reservoir,intermittent viral release,tissue distribution or false negatives,as well as immunological and sampling methodological factors.3,9,10 Given that an increasing number of RP cases have been reported worldwide,this phenomenon cannot be simply ascribed to false-negative testing.It indeed occurs,as truly discharged patients could suffer reactivation or could be reinfected with SARS-CoV-2.3 The risk of possible retransmission still exists,and the serological characteristics remain largely unknown,which could jeopardize the management of recovered COVID-19 patients.展开更多
基金was supported by Postgraduate Education and Teaching Reform Project of Shandong Province(SDYJG21018)Postgraduate Education and Teaching Reform Project of Harbin Institute of Technology at Weihai(WH2019002)Postgraduate Education and Teaching Reform Project of Harbin Institute of Technology(21HX1001).
文摘Accelerating the development of students is the basic goal of postgraduate talent cultivation.The final research results,employment situation and satisfaction of postgraduate students with school education are more important indicators of the quality of talent cultivation in a university.For having a deeper understanding of the satisfaction of postgraduates in Harbin Institute of Technology(Weihai)in terms of motivation,tutor situation,management service and employment situation,a questionnaire survey was conducted on postgraduates.The survey results show that the overall satisfaction of postgraduates is high.In terms of studying motivation,most postgraduates think that their majors are more related to employment;in terms of professors,most of them can get along well with their professors and learn from the advantages of their professors;in terms of school management,they respond well to the"library",but think that the"dormitory"and"canteen"need further improvement;in terms of employment,most of postgraduates choose to be employed,while a few of them choose to further their studies,most of which have applied to study in domestic or foreign universities.
基金supported by grants from the National Science and Technology Major Project(No.2017ZX10202102-006-002 to L.Y.)the National Natural Science Fund for Distinguished Young Scholars(No.31825011 to L.Y.)the National Science and Technology Major Project(2016ZX09J16105-001-002 to L.Y.).
文摘COVID-19 patients exhibit differential disease severity after SARS-CoV-2 infection.It is currently unknown as to the correlation between the magnitude of neutralizing antibody(NAb)responses and the disease severity in COVID-19 patients.In a cohort of 59 recovered patients with disease severity including severe,moderate,mild,and asymptomatic,we observed the positive correlation between serum neutralizing capacity and disease severity,in particular,the highest NAb capacity in sera from the patients with severe disease,while a lack of ability of asymptomatic patients to mount competent NAbs.Furthermore,the compositions of NAb subtypes were also different between recovered patients with severe symptoms and with mild-tomoderate symptoms.These results reveal the tremendous heterogeneity of SARS-CoV-2-specific NAb responses and their correlations to disease severity,highlighting the needs of future vaccination in COVID-19 patients recovered from asymptomatic or mild illness.
基金Guangzhou Science and Technology Innovation development Special fund,Grant/Award Number:202102020386Basic and Applied Basic Research Fund Committee of Guangdong Province,Grant/Award Numbers:2021A1515111209,2022A1515010547+1 种基金Science Foundation of Guangdong Provincial Bureau of traditional Chinese Medicine,Grant/Award Number:20211090National Natural Science Foundation of China,Grant/Award Numbers:82103331,82171825,82202036。
文摘Background:Existing treatments for cholangiocarcinoma have poor efficacy.However,chimeric antigen receptor-T(CAR-T)cells are emerging as a potential therapeutic strategy.Solid tumors possess multiple adverse factors in an immunosuppressive microenvironment that impair CAR-T cell infiltration and function.This study aimed to improve the function of CAR-T cells through knock down immune checkpoints and immunosuppressive molecular receptors.Methods:We evaluated the expression of epidermal growth factor receptor(EGFR)and B7 homolog 3 protein(B7H3)antigens in cholangiocarcinoma tissues using immunohistochemistry and screened specific immune checkpoints in the cholangiocarcinoma microenvironment via flow cytometry.Subsequently,we engineered CAR-T cells targeting EGFR and B7H3 antigens.We simultaneously knocked down immune checkpoints and immunosuppressive molecular receptors in CAR-T cells by constructing two clusters of small hairpin RNAs and evaluated the engineered CAR-T cells for antitumor activity both in vitro,using tumor cell lines and cholangiocarcinoma organoid models,and in vivo,using humanized mouse models.Results:We observed high expression of EGFR and B7H3 antigens in cholangiocarcinoma tissues.EGFR-CAR-T and B7H3-CAR-T cells demonstrated specific anti-tumor activity.We found an abundance of programmed cell death protein 1(PD-1),T cell immunoglobulin and mucin domain-containing protein 3(Tim-3),and T cell immunoglobulin and ITIM domain(Tigit)on infiltrated CD8^(+)T cells in the cholangiocarcinoma microenvironment.We then decreased the expression of these 3 proteins on the surface of CAR-T cells,named PTG-scFV-CAR-T cells.Furthermore,we knocked-down the expression of transforming growth factor beta receptor(TGFβR),interleukin-10 receptor(IL-10R),and interleukin-6 receptor(IL-6R)of PTG-scFV-CAR-T cells.Those cells,named PTG-T16R-scFVCAR-T cells,potently killed tumor cells in vitro and promoted apoptosis of tumor cells in a cholangiocarcinoma organoidmodel.Finally,the PTG-T16R-scFv-CART cells showed greater inhibitory effect on tumor growth in vivo,and were superior in prolonging the survival of mice.Conclusions:Our results revealed that PTG-T16R-scFV-CAR-T cells with knockdown of sextuplet inhibitory molecules exhibited strong immunity against cholangiocarcinoma and long-term efficacy both in vitro and in vivo.This strategy provides an effective and personalized immune cell therapy against cholangiocarcinoma.
基金This work was supported by the National Key Research and Development Program of China 2022YFC0870700the Natural Science Foundation of China 92169201 and 82150710553,and Joint-Innovation Program in Healthcare for Special Scientific Research Projects of Guangzhou to H.Z+2 种基金This work was supported by the Natural Science Foundation of China,92169108 and 32000613 to Y.Z.the Shenzhen Science and Technology Innovation Commission Key project JSGG20200225152648408Special project for 2019-nCoV epidemic emergency prevention of the Shenzhen Science and Technology Innovation Commission JSGG20220606141401003 to Y.H.
文摘Dear Editor,The Omicron(B.1.1.529)variant of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)was first identified in November 2021,in South Africa and Botswana.The first Omicron sub-lineage that emerged was BA.1,which was supplanted by BA.2 in many countries.One of the most notable features of the Omicron variant is its ability to evade neutralizing antibodies(nAbs)targeting the original virus lineages.
基金This work was supported by the National Special Research Program of China for Important Infectious Diseases(2017ZX10202102 and 2018ZX10302103)the Special 2019-nCoV Project of the National Key Research and Development Program of China(2020YFC0841400)+9 种基金the Emergency Key Program of Guangzhou Laboratory(EKPG21-24)the Special 2019-nCoV Program of the Natural Science Foundation of China(NSFC)(82041002)the Special Research and Development Program of Guangzhou(202008070010)the Important Key Program of NSFC(81730060)to HZThis work was also supported by the Zhongnanshan Medical Foundation of Guangdong Province(ZNSA-2021004)the Emergency Key Program of Guangzhou Laboratory(EKPG21-29)to XTThis work was supported by the National Natural Science Foundation of China(32100743,82171825)to XH.This work was also supported by the National Natural Science Foundation of China(81971918)the Shenzhen Science and Technology Program(Grant Nos.JSGG20200225150431472 and JCYJ20200109142601702)the Pearl River S&T Nova Program of Guangzhou(201806010118)and the Fundamental Research Funds for the Central Universities,Sun Yat-sen University(2021qntd43)to TPThis work was supported by National Natural Science Foundation of China(32100743,82171825)to X.H.
文摘The worldwide pandemic caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has resulted in more than 4.5 million deaths.Although coronaviruses have a proofreading mechanism to maintain the stability of their long genomic RNAs,mutations emerge continuously,and new variants conferring advantages rapidly become the dominant lineages[1].Strategies to fight the COVID-19 pandemic using either vaccines or nonpharmaceutical interventions have specifically been threatened by the emergence of SARS-CoV-2 variants of concern(VOCs)[2].
基金supported by the National Special Research Program of China for Important Infectious Diseases(2018ZX10302103 and 2017ZX10202102)the Special 2019-nCov Program of the Natural Science Foundation of China(NSFC)(82041002)+6 种基金the Important Key Program of the NSFC(81730060)the Joint-Innovation Program in Healthcare for Special Scientific Research Projects of Guangzhou(201803040002)to H.Z.Furtherthe authors received support from the Natural Science Foundation of China(81672024)the Natural Science Foundation of Guangdong Province of China(2017A030306005)the Guangdong Innovative and Entrepreneurial Research Team Program(2016ZT06S638)to K.D.the Department of Science and Technology of Guangdong Province(2020B111108001)to F.L.the National Natural Science Foundation of China(81701989)to B.L.
文摘Coronavirus disease 2019(COVID-19),caused by infection with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),has rapidly become a global pandemic.Most discharge criteria for patients with COVID-19 recommend two consecutive negative reverse-transcriptase polymerase-chain reaction(RT-PCR)test results from respiratory specimens over a 24-hour interval.Reports are accumulating of recurrent viral RNA-positive(RP)nasopharyngeal or anal specimens from recovered patients in China,Italy,South Korea,and France.1–8 Two cohort studies reported that 14.5%(38/262)and 16.7%(69/414)of patients with COVID-19 retesting were positive for SARS-CoV-2 RNA after discharge.2,6 The potential causes of RP specimens may be related to several aspects,such as virological factors,including residual viral reservoir,intermittent viral release,tissue distribution or false negatives,as well as immunological and sampling methodological factors.3,9,10 Given that an increasing number of RP cases have been reported worldwide,this phenomenon cannot be simply ascribed to false-negative testing.It indeed occurs,as truly discharged patients could suffer reactivation or could be reinfected with SARS-CoV-2.3 The risk of possible retransmission still exists,and the serological characteristics remain largely unknown,which could jeopardize the management of recovered COVID-19 patients.
