For the problem that when wheat is sucked up by the air suction method,the seeds are aligned in a small area,making it difficult for the contact seed cleaning mechanism to clean the seeds.The mechanism of seed cleanin...For the problem that when wheat is sucked up by the air suction method,the seeds are aligned in a small area,making it difficult for the contact seed cleaning mechanism to clean the seeds.The mechanism of seed cleaning airflow on wheat seed was studied,the flow velocity distribution relationship of the jet section was defined,the mathematical model of the jet velocity of circular and plane sections was established,and the key factors that could have a significant influence on seed cleaning effect were explored.A non-contact positive pressure air flow seed cleaning method was proposed.After theoretical calculations,it is concluded that the core section lengths of the circular section jet and the inline jet are 24.8 mm and 28.8 mm,respectively.The clearing distance is set to 20 mm.Through the single-factor test,the best air tube nozzle shape was clarified as a vertical inline nozzle.The angle of seed cleaning,the air velocity of seed cleaning,and the negative supply pressure were selected as influencing factors,and the seed leakage index,seed reabsorption index,and seed qualification index as the evaluation indicators to conduct a 3-factor 5-horizontal rotation test.A mathematical regression model of influencing factors and evaluation indexes was established to analyze the influence of these factors and indexes.The optimal operation parameters were obtained as the seed cleaning Angle of 19°,the seed cleaning air velocity of 58 m/s,and the negative pressure of 8.5 kPa.Under the optimal parameters,the seed leakage suction index is 8.23%,the seed reabsorption index is 0.33%,and the seed qualification index is 91.44%,which meets the design requirements.展开更多
Background In 2015,herpes simplex virus 1(HSV-1)-derived talimogene laherparepvec(T-VEC)was the first oncolytic virus approved by the US Food and Drug Administration as a therapeutic agent for cancer treatment.However...Background In 2015,herpes simplex virus 1(HSV-1)-derived talimogene laherparepvec(T-VEC)was the first oncolytic virus approved by the US Food and Drug Administration as a therapeutic agent for cancer treatment.However,its antitumor application is limited to local treatment of melanoma,and there is a lack of understanding of the mechanisms underlying the regulation of HSV-1 replication in cancer cells and the associated antitumor immunity.We hypothesized that increasing the replication capacity of HSV-1 in tumor cells would enhance the antitumor effect of this virus.Methods We systematically identified IFN-stimulated genes induced by HSV-1 by performing functional screens and clarified the mechanism by which BACH1 acts against HSV-1.Then,we tested the effect of BACH1 deficiency on immunogenic cell death induced by HSV-1.Furthermore,we investigated the antitumor effect of BACH1 deficiency on HSV-1 in MCA205 and B16 murine tumor models.Results We identified eight IFN-stimulated genes(ISGs)controlling HSV-1 replication,among which BTB and CNC homology 1(BACH1)suppressed HSV-1 replication by inhibiting the transcription of ICP4,ICP27,and UL39.Loss of Bach1 function not only increased HSV-1 proliferation but also promoted HSV-1-induced cell apoptosis,HMGB1 secretion,and calreticulin exposure in tumor cells.More importantly,hemin,an FDA-approved drug known to downregulate BACH1,significantly enhanced HSV-1-mediated antitumor activity with increased T lymphocyte infiltration at the tumor site.Conclusions Our studies uncovered a novel antiviral activity of BACH1 and provided a new strategy for improving the clinical efficiency of the oncolytic virus HSV-1.展开更多
In the version of this article initially published,a grant name and the acknowledgment information were missing.The grant name and acknowledgment information have been added at the end of Acknowledgments:J.L.is suppor...In the version of this article initially published,a grant name and the acknowledgment information were missing.The grant name and acknowledgment information have been added at the end of Acknowledgments:J.L.is supported by WU Jieping Medical Foundation(320.6750.2021-17-12).We thank Dr.Chunfu Zheng for providing the HSV-1 BAC plasmid.The results and conclusions were not affected.展开更多
The tumor microenvironment(TME),including infiltrated immune cells,is known to play an important role in tumor growth;however,the mechanisms underlying tumor immunogenicity have not been fully elucidated.Here,we disco...The tumor microenvironment(TME),including infiltrated immune cells,is known to play an important role in tumor growth;however,the mechanisms underlying tumor immunogenicity have not been fully elucidated.Here,we discovered an unexpected role for the transcription factor SIX1 in regulating the tumor immune microenvironment.Based on analyses of patient datasets,we found that SIX1 was upregulated in human tumor tissues and that its expression levels were negatively correlated with immune cell infiltration in the TME and the overall survival rates of cancer patients.Deletion of Six1 in cancer cells significantly reduced tumor growth in an immune-dependent manner with enhanced antitumor immunity in the TME.Mechanistically,SIX1 was required for the expression of multiple collagen genes via the TGFBR2-dependent Smad2/3 activation pathway,and collagen deposition in the TME hampered immune cell infiltration and activation.Thus,our study uncovers a crucial role for SIX1 in modulating tumor immunogenicity and provides proof-of-concept evidence for targeting SIX1 in cancer immunotherapy.展开更多
Dear Editor,Immune-mediated tumor elimination depends on the production of cytokines and the recruitment of immune cells in the tumor microenvironment.Cell death-related signals such as ATP release from tumor cells ar...Dear Editor,Immune-mediated tumor elimination depends on the production of cytokines and the recruitment of immune cells in the tumor microenvironment.Cell death-related signals such as ATP release from tumor cells are crucial for the activation of downstream immune responses.^(1)GOLM1,also known as GOLPH2 and GP73 as a Golgi transmembrane protein involved in the transport of protein cargo through the Golgi apparatus has been extensively studied in various cancers for its multifunctional roles in promoting cancer proliferation and metastasis through the AKT/mTOR pathway.展开更多
基金the National Natural Science Foundation of China(Grant No.52175260)the China Agriculture Research System(Grant No.CARS-03)+3 种基金the Key Research and development plan of Hainan Province(Grant No.ZDYF2022XDNY184)Project of Scientific Research in Colleges and Universities of Hainan Province(Grant No.Hnky2022-93)Research Start-up Fund Project of Hainan University(Grant No.KYQD(ZR)-22036)the authors wish to thank them for their generous financial assistance.
文摘For the problem that when wheat is sucked up by the air suction method,the seeds are aligned in a small area,making it difficult for the contact seed cleaning mechanism to clean the seeds.The mechanism of seed cleaning airflow on wheat seed was studied,the flow velocity distribution relationship of the jet section was defined,the mathematical model of the jet velocity of circular and plane sections was established,and the key factors that could have a significant influence on seed cleaning effect were explored.A non-contact positive pressure air flow seed cleaning method was proposed.After theoretical calculations,it is concluded that the core section lengths of the circular section jet and the inline jet are 24.8 mm and 28.8 mm,respectively.The clearing distance is set to 20 mm.Through the single-factor test,the best air tube nozzle shape was clarified as a vertical inline nozzle.The angle of seed cleaning,the air velocity of seed cleaning,and the negative supply pressure were selected as influencing factors,and the seed leakage index,seed reabsorption index,and seed qualification index as the evaluation indicators to conduct a 3-factor 5-horizontal rotation test.A mathematical regression model of influencing factors and evaluation indexes was established to analyze the influence of these factors and indexes.The optimal operation parameters were obtained as the seed cleaning Angle of 19°,the seed cleaning air velocity of 58 m/s,and the negative pressure of 8.5 kPa.Under the optimal parameters,the seed leakage suction index is 8.23%,the seed reabsorption index is 0.33%,and the seed qualification index is 91.44%,which meets the design requirements.
基金This project was financially supported by the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(2021-I2M-1-047 and 2019-I2M-5-049)National Science Funds of China(82073181,81802870 and 82102371)+5 种基金Nonprofit Central Research Institute Fund of Chinese Academy of Medical Sciences(2020-PT310-006,2019XK310002 and 2018TX31001)as well as NIH R01AI069120,AI158154,and AI140718 grants,the UCLA AIDS InstituteUCLA David Geffen School of Medicine-Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research Award ProgramH.Y.is supported by science funds from Jiangsu Province(BK20211554,BK20170407)the Innovative and Entrepreneurial Team grant(2018-2021)from Jiangsu ProvinceL.L.is supported by Innovative and Entrepreneurial Doctor grant(2020-2022)from Jiangsu Province.
文摘Background In 2015,herpes simplex virus 1(HSV-1)-derived talimogene laherparepvec(T-VEC)was the first oncolytic virus approved by the US Food and Drug Administration as a therapeutic agent for cancer treatment.However,its antitumor application is limited to local treatment of melanoma,and there is a lack of understanding of the mechanisms underlying the regulation of HSV-1 replication in cancer cells and the associated antitumor immunity.We hypothesized that increasing the replication capacity of HSV-1 in tumor cells would enhance the antitumor effect of this virus.Methods We systematically identified IFN-stimulated genes induced by HSV-1 by performing functional screens and clarified the mechanism by which BACH1 acts against HSV-1.Then,we tested the effect of BACH1 deficiency on immunogenic cell death induced by HSV-1.Furthermore,we investigated the antitumor effect of BACH1 deficiency on HSV-1 in MCA205 and B16 murine tumor models.Results We identified eight IFN-stimulated genes(ISGs)controlling HSV-1 replication,among which BTB and CNC homology 1(BACH1)suppressed HSV-1 replication by inhibiting the transcription of ICP4,ICP27,and UL39.Loss of Bach1 function not only increased HSV-1 proliferation but also promoted HSV-1-induced cell apoptosis,HMGB1 secretion,and calreticulin exposure in tumor cells.More importantly,hemin,an FDA-approved drug known to downregulate BACH1,significantly enhanced HSV-1-mediated antitumor activity with increased T lymphocyte infiltration at the tumor site.Conclusions Our studies uncovered a novel antiviral activity of BACH1 and provided a new strategy for improving the clinical efficiency of the oncolytic virus HSV-1.
文摘In the version of this article initially published,a grant name and the acknowledgment information were missing.The grant name and acknowledgment information have been added at the end of Acknowledgments:J.L.is supported by WU Jieping Medical Foundation(320.6750.2021-17-12).We thank Dr.Chunfu Zheng for providing the HSV-1 BAC plasmid.The results and conclusions were not affected.
基金This project was financially supported by the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(2021-1-I2M-047,2016-I2M-1-005 and 2019-I2M-1-003)National Science funds of China(82073181,81802870,82102371 and 2017YFA0506200)+4 种基金Nonprofit Central Research Institute Fund of the Chinese Academy of Medical Sciences(2020-PT310-006,2019XK310002 and 2018TX31001)HY is supported by science funds from Jiangsu Province(BK20211554,BK20170407)the Innovative and Entrepreneurial Team grant(2018-2021)from Jiangsu ProvinceLL is supported by the Chinese Postdoctoral Science Foundation(2019M650564)Innovative and Entrepreneurial Doctor grant(2020-2022)from Jiangsu Province.
文摘The tumor microenvironment(TME),including infiltrated immune cells,is known to play an important role in tumor growth;however,the mechanisms underlying tumor immunogenicity have not been fully elucidated.Here,we discovered an unexpected role for the transcription factor SIX1 in regulating the tumor immune microenvironment.Based on analyses of patient datasets,we found that SIX1 was upregulated in human tumor tissues and that its expression levels were negatively correlated with immune cell infiltration in the TME and the overall survival rates of cancer patients.Deletion of Six1 in cancer cells significantly reduced tumor growth in an immune-dependent manner with enhanced antitumor immunity in the TME.Mechanistically,SIX1 was required for the expression of multiple collagen genes via the TGFBR2-dependent Smad2/3 activation pathway,and collagen deposition in the TME hampered immune cell infiltration and activation.Thus,our study uncovers a crucial role for SIX1 in modulating tumor immunogenicity and provides proof-of-concept evidence for targeting SIX1 in cancer immunotherapy.
基金supported by the CAMS Initiative for Innovative Medicine(No.2016-I2M-1-005,2019-I2M-1-003)National Science and Technology Major Project for“Significant New Drugs Innovation and Development”(2015ZX09102023)+5 种基金National Natural Science Foundation of China(NSFC 91542201,81590765,82073181,81802870,81702987,81871286)Natural Science Foundation of Jiangsu Province Grant(BK20170407,BK20151253,BK20161246)Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences(3332018131,2020-PT310-006)L.L.is supported by the Chinese Postdoctoral Science Foundation(2019M650564)the Innovation and Entrepreneurial Doctor grant(2020-2022)M.S.is supported by the Key Project of Jiangsu Provincial Health Commission(No.K2019021).
文摘Dear Editor,Immune-mediated tumor elimination depends on the production of cytokines and the recruitment of immune cells in the tumor microenvironment.Cell death-related signals such as ATP release from tumor cells are crucial for the activation of downstream immune responses.^(1)GOLM1,also known as GOLPH2 and GP73 as a Golgi transmembrane protein involved in the transport of protein cargo through the Golgi apparatus has been extensively studied in various cancers for its multifunctional roles in promoting cancer proliferation and metastasis through the AKT/mTOR pathway.