Mammalian T-cell responses require synergism between the first signal and co-stimulatory signal.However,whether and how dual signaling regulates the T-cell response in early vertebrates remains unknown.In the present ...Mammalian T-cell responses require synergism between the first signal and co-stimulatory signal.However,whether and how dual signaling regulates the T-cell response in early vertebrates remains unknown.In the present study,we discovered that the Nile tilapia(Oreochromis niloticus)encodes key components of the LAT signalosome,namely,LAT,ITK,GRB2,VAV1,SLP-76,GADS,and PLC-γ1.These components are evolutionarily conserved,and CD3εmAb-induced T-cell activation markedly increased their expression.Additionally,at least ITK,GRB2,and VAV1 were found to interact with LAT for signalosome formation.Downstream of the first signal,the NF-κB,MAPK/ERK,and PI3K-AKT pathways were activated upon CD3εmAb stimulation.Furthermore,treatment of lymphocytes with CD28 mAbs triggered the AKT-mTORC1 pathway downstream of the co-stimulatory signal.Combined CD3εand CD28 mAb stimulation enhanced ERK1/2 and S6 phosphorylation and elevated NFAT1,c-Fos,IL-2,CD122,and CD44 expression,thereby signifying T-cell activation.Moreover,rather than relying on the first or co-stimulatory signal alone,both signals were required for T-cell proliferation.Full T-cell activation was accompanied by marked apoptosis and cytotoxic responses.These findings suggest that tilapia relies on dual signaling to maintain an optimal T-cell response,providing a novel perspective for understanding the evolution of the adaptive immune system.展开更多
This study constructs 196 transition metals(TM)@S_(x)N_(y) single-atom catalysts(SACs)(x=0-4 and y=0-4)and employs the eXtreme Gradient Boosting(XGBoost)classification model in machine learning(ML)for effectively dist...This study constructs 196 transition metals(TM)@S_(x)N_(y) single-atom catalysts(SACs)(x=0-4 and y=0-4)and employs the eXtreme Gradient Boosting(XGBoost)classification model in machine learning(ML)for effectively distinguishing qualified and unqualified catalysts.The prediction accuracy rate is high,up to 95%.The SHapley Additive exPlanations(SHAP)analysis reveals that the N≡N bond length and the number of outermost d electrons(N_(d))can well describe the nitrogen(N2)reduction reaction(NRR)activity.The relationships between N≡N,N_(d),the adsorption energies of different intermediates(ΔE_(*N_(2)),ΔE_(*N_(2)H),and ΔE_(*NH_(2))),the general descriptor(φ),and the Gibbs free energy of key steps(ΔG_(*N_(2)),ΔG_(*N_(2)-*N_(2)H),and ΔG_(*N_H(2)-*NH_(3)))indicate that moderate nitrogen activation can enhance the reaction activity.Among the 17 screened SACs,Mo@S3N1,and W@S_(3)N_(1) demonstrate the best catalytic performance,with limiting potential(U_(L))values of only-0.26 and-0.25 V under implicit solvation conditions.The electronic properties and variations in N≡N and TM-N bond lengths are investigated to reveal the origin of NRR activity.This study provides the decisive features and NRR dataset for ML research,as well as a feasible strategy for rational design of NRR SACs.展开更多
基金supported by the National Key Research and Development Program(2022YFD2400804)National Natural Science Foundation of China(32022086,31972822)Natural Science Foundation of Shanghai(20ZR1417500)。
文摘Mammalian T-cell responses require synergism between the first signal and co-stimulatory signal.However,whether and how dual signaling regulates the T-cell response in early vertebrates remains unknown.In the present study,we discovered that the Nile tilapia(Oreochromis niloticus)encodes key components of the LAT signalosome,namely,LAT,ITK,GRB2,VAV1,SLP-76,GADS,and PLC-γ1.These components are evolutionarily conserved,and CD3εmAb-induced T-cell activation markedly increased their expression.Additionally,at least ITK,GRB2,and VAV1 were found to interact with LAT for signalosome formation.Downstream of the first signal,the NF-κB,MAPK/ERK,and PI3K-AKT pathways were activated upon CD3εmAb stimulation.Furthermore,treatment of lymphocytes with CD28 mAbs triggered the AKT-mTORC1 pathway downstream of the co-stimulatory signal.Combined CD3εand CD28 mAb stimulation enhanced ERK1/2 and S6 phosphorylation and elevated NFAT1,c-Fos,IL-2,CD122,and CD44 expression,thereby signifying T-cell activation.Moreover,rather than relying on the first or co-stimulatory signal alone,both signals were required for T-cell proliferation.Full T-cell activation was accompanied by marked apoptosis and cytotoxic responses.These findings suggest that tilapia relies on dual signaling to maintain an optimal T-cell response,providing a novel perspective for understanding the evolution of the adaptive immune system.
基金supported by National Natural Science Foundation of China(Nos.52271136 and 22373063)the Natural Science Foundation of Shaanxi Province in China(Nos.2021JC-06 and 2019TD-020)Fundamental Research Funds for the Central Universities of China(No.GK202203002).
文摘This study constructs 196 transition metals(TM)@S_(x)N_(y) single-atom catalysts(SACs)(x=0-4 and y=0-4)and employs the eXtreme Gradient Boosting(XGBoost)classification model in machine learning(ML)for effectively distinguishing qualified and unqualified catalysts.The prediction accuracy rate is high,up to 95%.The SHapley Additive exPlanations(SHAP)analysis reveals that the N≡N bond length and the number of outermost d electrons(N_(d))can well describe the nitrogen(N2)reduction reaction(NRR)activity.The relationships between N≡N,N_(d),the adsorption energies of different intermediates(ΔE_(*N_(2)),ΔE_(*N_(2)H),and ΔE_(*NH_(2))),the general descriptor(φ),and the Gibbs free energy of key steps(ΔG_(*N_(2)),ΔG_(*N_(2)-*N_(2)H),and ΔG_(*N_H(2)-*NH_(3)))indicate that moderate nitrogen activation can enhance the reaction activity.Among the 17 screened SACs,Mo@S3N1,and W@S_(3)N_(1) demonstrate the best catalytic performance,with limiting potential(U_(L))values of only-0.26 and-0.25 V under implicit solvation conditions.The electronic properties and variations in N≡N and TM-N bond lengths are investigated to reveal the origin of NRR activity.This study provides the decisive features and NRR dataset for ML research,as well as a feasible strategy for rational design of NRR SACs.
