Objective: The human cluster of differentiation(CD)300A, a type-I transmembrane protein with immunoreceptor tyrosine-based inhibitory motifs, was investigated as a potential immune checkpoint for human natural killer(...Objective: The human cluster of differentiation(CD)300A, a type-I transmembrane protein with immunoreceptor tyrosine-based inhibitory motifs, was investigated as a potential immune checkpoint for human natural killer(NK) cells targeting hematologic malignancies(HMs).Methods: We implemented a stimulation system involving the CD300A ligand, phosphatidylserine(PS), exposed to the outer surface of malignant cells. Additionally, we utilized CD300A overexpression, a CD300A blocking system, and a xenotransplantation model to evaluate the impact of CD300A on NK cell efficacy against HMs in in vitro and in vivo settings. Furthermore, we explored the association between CD300A and HM progression in patients.Results: Our findings indicated that PS hampers the function of NK cells. Increased CD300A expression inhibited HM lysis by NK cells. CD300A overexpression shortened the survival of HM-xenografted mice by impairing transplanted NK cells. Blocking PS–CD300A signals with antibodies significantly amplified the expression of lysis function-related proteins and effector cytokines in NK cells, thereby augmenting the ability to lyse HMs. Clinically, heightened CD300A expression correlated with shorter survival and an “exhausted” phenotype of intratumoral NK cells in patients with HMs or solid tumors.Conclusions: These results propose CD300A as a potential target for invigorating NK cell-based treatments against HMs.展开更多
The outbreak of COVID-19 and the spread of infectious pathogens through bioaerosols have once again aroused widespread concern worldwide.Isolation ward is an important place to prevent the spread of infectious bioaero...The outbreak of COVID-19 and the spread of infectious pathogens through bioaerosols have once again aroused widespread concern worldwide.Isolation ward is an important place to prevent the spread of infectious bioaerosols.However,infection of health care workers(HCWs)in the isolation ward often occurs,so it is ur-gent to carry out relevant research to reduce the cross-infection between HCWs and patients.In this paper,the temporal and spatial distribution characteristics of bioaerosols under three mixed ventilation modes in a single ward were studied,namely,upper supply side return air of Case 1 and side supply and side return ventilation are Case 2 and Case 3 respectively.The results show that the removal efficiency of bioaerosol in the ventilation mode of Case 3,in which directional airflow is formed from the air supply inlet to the release source and then to the exhaust outlet,is 46.6%and 67.7%higher than that of Case 1 and Case 2,respectively.In addition,ventilation methods based on mixed theory do not guarantee good air quality in the breathing zone(1.3 m to 1.7 m)of HCWs,which may increase the inhalation risk for HCWs.It is hoped that our results can provide some useful suggestions for optimizing the airflow layout of the isolation ward,reducing the risk of cross-infection,and virus elimination.展开更多
基金supported by the National Key R&D Program of China (2019YFA0508502/3 and 2021YFC2300604)the Natural Science Foundation of China (Reference numbers 82388201, 82241216, and 32270963)+1 种基金the Research Funds of Center for Advanced Interdisciplinary Science and Biomedicine of IHM (QYZD20220008)the Anhui Key Research and Development Plan (Reference number 2023z04020011)。
文摘Objective: The human cluster of differentiation(CD)300A, a type-I transmembrane protein with immunoreceptor tyrosine-based inhibitory motifs, was investigated as a potential immune checkpoint for human natural killer(NK) cells targeting hematologic malignancies(HMs).Methods: We implemented a stimulation system involving the CD300A ligand, phosphatidylserine(PS), exposed to the outer surface of malignant cells. Additionally, we utilized CD300A overexpression, a CD300A blocking system, and a xenotransplantation model to evaluate the impact of CD300A on NK cell efficacy against HMs in in vitro and in vivo settings. Furthermore, we explored the association between CD300A and HM progression in patients.Results: Our findings indicated that PS hampers the function of NK cells. Increased CD300A expression inhibited HM lysis by NK cells. CD300A overexpression shortened the survival of HM-xenografted mice by impairing transplanted NK cells. Blocking PS–CD300A signals with antibodies significantly amplified the expression of lysis function-related proteins and effector cytokines in NK cells, thereby augmenting the ability to lyse HMs. Clinically, heightened CD300A expression correlated with shorter survival and an “exhausted” phenotype of intratumoral NK cells in patients with HMs or solid tumors.Conclusions: These results propose CD300A as a potential target for invigorating NK cell-based treatments against HMs.
基金supported by the Natural Science Foundation for Distinguished Young Scholars of Hubei Province of China (2023AFA065)the National Key Research and Development Program (2019YFB2205100)Hubei Province Key Scientific and Technological Project (2022AEA001)。
基金This work was supported by the National Natural Science Foundation of China(Nos.42122058 and 41977368)the National Key R&D Program of China(2021YFF0604000)Natural Science Foundation of Hebei Province(No.E2021502046,and Fundamental Research Funds for the Central Universities(Nos.2021MS075 and 2020YJ007).
文摘The outbreak of COVID-19 and the spread of infectious pathogens through bioaerosols have once again aroused widespread concern worldwide.Isolation ward is an important place to prevent the spread of infectious bioaerosols.However,infection of health care workers(HCWs)in the isolation ward often occurs,so it is ur-gent to carry out relevant research to reduce the cross-infection between HCWs and patients.In this paper,the temporal and spatial distribution characteristics of bioaerosols under three mixed ventilation modes in a single ward were studied,namely,upper supply side return air of Case 1 and side supply and side return ventilation are Case 2 and Case 3 respectively.The results show that the removal efficiency of bioaerosol in the ventilation mode of Case 3,in which directional airflow is formed from the air supply inlet to the release source and then to the exhaust outlet,is 46.6%and 67.7%higher than that of Case 1 and Case 2,respectively.In addition,ventilation methods based on mixed theory do not guarantee good air quality in the breathing zone(1.3 m to 1.7 m)of HCWs,which may increase the inhalation risk for HCWs.It is hoped that our results can provide some useful suggestions for optimizing the airflow layout of the isolation ward,reducing the risk of cross-infection,and virus elimination.
