In this work,the effects of the frequency,pressure,gas composition,and secondary-electron emission coefficient on the discharge mode in capacitively coupled Ar/O_(2) plasmas were carefully studied through simulations....In this work,the effects of the frequency,pressure,gas composition,and secondary-electron emission coefficient on the discharge mode in capacitively coupled Ar/O_(2) plasmas were carefully studied through simulations.Three discharge modes,i.e.,α,γ,and drift-ambipolar(DA),were considered in this study.The results show that a mode transition from theγ-DA hybrid mode dominated by theγmode to the DA-αhybrid mode dominated by the DA mode is induced by increasing the frequency from 100 k Hz to 40 MHz.Furthermore,the electron temperature decreases with increasing frequency,while the plasma density first decreases and then increases.It was found that the electronegativity increases slightly with increasing pressure in the lowfrequency region,and it increases notably with increasing pressure in the high-frequency region.It was also observed that the frequency corresponding to the mode transition fromγto DA decreased when the secondary-electron emission coefficient was decreased.Finally,it was found that increasing the oxygen content weakens theγmode and enhances the DA mode.More importantly,the density of oxygen atoms and ozone will increase greatly with increasing oxygen content,which is of great significance for industrial applications.展开更多
Simulations are conducted on capacitively coupled Ar/O_(2)mixed gas discharges employing a one-dimensional fluid coupled with an electron Monte Carlo(MC)model.The research explores the impact of different O_(2)ratio a...Simulations are conducted on capacitively coupled Ar/O_(2)mixed gas discharges employing a one-dimensional fluid coupled with an electron Monte Carlo(MC)model.The research explores the impact of different O_(2)ratio and pressures on the discharge characteristics of Ar/O_(2)plasma.At a fixed Ar/O_(2)gas ratio,with the increasing pressure,higher ion densities,as well as a slight increase in electron density in the bulk region can be observed.The discharge remains dominated by the drift-ambipolar(DA)mode,and the flux of O(3P)at the electrode increases with the increasing pressure due to higher background gas density,while the fluxes of O(1D)and Ardecrease due to the pronounced loss rate.With the increasing proportion of O_(2),a change in the dominant discharge mode from a mode to DA mode can be detected,and the O_(2)-associated charged particle densities are significantly increased.However,Ar+density shows a trend of increasing and then decreasing,while for neutral fluxes at the electrode,Arflux decreases,and O(3P)flux increases with the reduced Ar gas proportion,while trends in O(1D)flux show slight differences.The evolution of the densities of the charged particle and the neutral fluxes under different discharge parameters are discussed in detail using the ionization characteristics as well as the transport properties.Hopefully,more comprehensive understanding of Ar/O_(2)discharge characteristics in this work will provide a valuable reference for the industry.展开更多
Potassium nitrate(KNO_(3))promotes adventitious root(AR)formation in apple stem cuttings.However,evidence for the possible involvement of cytokinin(CK)in KNO_(3)-mediated AR formation in apples is still lacking.In thi...Potassium nitrate(KNO_(3))promotes adventitious root(AR)formation in apple stem cuttings.However,evidence for the possible involvement of cytokinin(CK)in KNO_(3)-mediated AR formation in apples is still lacking.In this study,we cultured GL-3 apple microshoots in different treatment combinations.While the T1(KNO_(3)9.4 mmol L^(-1)+6-benzyl adenine(6-BA)2.22μmol L^(-1))and T3(6-BA 2.22μmol L^(-1))treatments completely inhibited AR formation,the control,T2(KNO_(3)9.4 mmol L^(-1)),and T4(KNO_(3)9.4 mmol L^(-1)+lovastatin(Lov)1.24μmol L^(-1))treatments developed ARs.However,T4-treated microshoots developed fewer and shorter ARs,indicating that optimum CK synthesis is needed for normal AR growth.This also suggests that these fewer and shorter ARs developed because of the presence of KNO_(3) in the same medium.The anatomy of the stem basal part indicated that the inhibition of CK biosynthesis delayed AR primordia formation.The endogenous levels of indole-3-acetic acid(IAA)and zeatin riboside(ZR)were higher in T2-treated microshoots,while the abscisic acid(ABA),gibberellic acid 3(GA_(3)),and brassinosteroid(BR)levels were higher in T4-treated microshoots.The expression levels of MdNRT1.1and MdNRT2.1 were higher in T2-treated microshoots at 3 and 8 days,while MdRR2 and MdCKX5 were higher at 8 and 16 days,respectively.Furthermore,higher IAA levels increased MdWOX11 expression,which in turn increased MdLBD16 and MdLBD29 expression in response to T2.The combined expression of these genes stimulated adventitious rooting by upregulating cell cycle-related genes(MdCYCD1;1 and MdCYCD3;1)in response to T2 treatment.This study shows that specific genes and hormonal pathways contribute to KNO_(3)-CK-mediated adventitious rooting in apples.展开更多
Probiotics could effectively eliminate excess reactive oxygen species(ROS)generated during aging or lipid metabolism disorders,but their mechanism is unclear.The major purpose of this study was to investigate the mech...Probiotics could effectively eliminate excess reactive oxygen species(ROS)generated during aging or lipid metabolism disorders,but their mechanism is unclear.The major purpose of this study was to investigate the mechanism of Lactiplantibacillus plantarun AR113 alleviating oxidative stress injury in the D-galactose induced aging mice.The result showed that pretreatment with L.plantarun AR113 significantly relieving H_(2)O_(2)induced cytotoxicity in HepG2 cells by maintain cell membrane integrity and increasing antioxidant enzyme activities.In D-galactose induced aging mice,L.plantarun AR113 could significantly attenuate liver damage and inflammatory infiltration by promoting endogenous glutathione(GSH)synthesis and activating the Nrf2/Keap1 signaling pathway in mice,and increasing the expression of regulated phaseⅡdetoxification enzymes and antioxidant enzymes.Further analysis shown that gavage of L.plantarun AR113 could significantly reduce the expression of G protein-coupled receptor 78(GPR78)and C/EBP homologous protein(CHOP)proteins,and promote the restoration of endoplasmic reticulum(ER)homeostasis,thereby activating cell anti-apoptotic pathways.These results were also confirmed in H_(2)O_(2)-treated HepG2 experiments.It indicated that L.plantarun AR113 could inhibit D-galactose-induced liver injury through dual inhibition of ER stress and oxidative stress.L.plantarun AR113 have good application potential in anti-aging and alleviating metabolic disorders.展开更多
Radio frequency capacitively coupled plasmas(RF CCPs)play a pivotal role in various applications in etching and deposition processes on a microscopic scale in semiconductor manufacturing.In the discharge process,the p...Radio frequency capacitively coupled plasmas(RF CCPs)play a pivotal role in various applications in etching and deposition processes on a microscopic scale in semiconductor manufacturing.In the discharge process,the plasma series resonance(PSR)effect is easily observed in electrically asymmetric and geometrically asymmetric discharges,which could largely influence the power absorption,ionization rate,etc.In this work,the PSR effect arising from geometrically and electrically asymmetric discharge in argon-oxygen mixture gas is mainly investigated by using a plasma equivalent circuit model coupled with a global model.At relatively low pressures,as Ar content(α)increases,the inductance of the bulk is weakened,which leads to a more obvious PSR phenomenon and a higher resonance frequency(ω_(psr)).When the Ar content is fixed,varying the pressure and gap distance could also have different effects on the PSR effect.With the increase of the pressure,the PSR frequency shifts towards the higher order,but in the case of much higher pressure,the PSR oscillation would be strongly damped by frequent electron-neutral collisions.With the increase of the gap distance,the PSR frequency becomes lower.In addition,electrically asymmetric waveforms applied to a geometrically asymmetric chamber may weaken or enhance the asymmetry of the discharge and regulate the PSR effect.In this work,the Ar/O_(2) electronegative mixture gas is introduced in a capacitive discharge to study the PSR effect under geometric asymmetry effect and electrical asymmetry effect,which can provide necessary guidance in laboratory research and current applications.展开更多
AIM: To investigate the expression of mi R-29 a in rat acute pancreatitis and its functional role in AR42 J cell apoptosis.METHODS: Twelve SD rats were divided into a control group and an acute edematous pancreatitis(...AIM: To investigate the expression of mi R-29 a in rat acute pancreatitis and its functional role in AR42 J cell apoptosis.METHODS: Twelve SD rats were divided into a control group and an acute edematous pancreatitis(AEP) group randomly. AEP was induced by intraperitoneal injection of L-arginine(150 mg/kg) in the AEP group and equal volume of 0.9% Na Cl was injected in the control group. The apoptosis of acinar cells in pancreatic tissue was determined by TUNEL assay. mi RNA chip assay was performed to examine the expression of mi RNAs in two groups. Besides, to further explore the role of mi R-29 a in apoptosis in vitro, recombinant rat TNF-α(50 ng/m L) was administered to treat the rat pancreatic acinar cell line AR42 J for inducing AR42 J cell apoptosis. Quantitative real-time PCR(q RT-PCR) was adopted to measure mi R-29 a expression. Then, mi RNA mimic, mi RNA antisense oligonucleotide(AMO) and control vector were used to transfect AR42 J cells. The expression of mi R-29 a was confirmed by q RT-PCR andthe apoptosis rate of AR42 J cells was detected by flow cytometry analysis. Western blot was used to detect the expression of activated caspase3. Moreover, we used bioinformatics software and luciferase assay to test whether TNFRSF1 A was the target gene of mi R-29 a. After transfection, q RT-PCR and Western blot was used to detect the expression of TNFRSF1 A in AR42 J cells after transfection.RESULTS: The expression of mi R-29 a was much higher in the AEP group compared with the control group as displayed by the mi RNA chip assay. After inducing apoptosis of AR42 J cells in vitro, the expression of mi R-29 a was significantly increased by 1.49 ± 0.04 times in comparison with the control group. As revealed by q RT-PCR assay, the expression of mi R-29 a was 2.68 ± 0.56 times higher in the mi R-29 a mimic group relative to the control vector group, accompanied with an obviously increased acinar cell apoptosis rate(42.83 ± 1.25 vs 24.97 ± 0.15, P < 0.05). Moreover, the expression of mi R-29 a in the mi RNA AMO group was 0.46 ± 0.05 times lower than the control vector group, and the cell apoptosis rate was much lower accordingly(17.27 ± 1.36 vs 24.97 ± 0.15, P < 0.05). The results of bioinformatics software and luciferase assay showed that TNFRSF1 A might be a target gene of mi R-29 a. TNFRSF1 A expression was up-regulated in the mi R-29 a mimic group, while the mi R-29 a AMO group showed the reverse trend.CONCLUSION: mi R-29 a might promote the apoptosis of AR42 J cells via up-regulating the expression of its target gene TNFRSF1 A.展开更多
Objective To study the interactive effect of job stress and genetic susceptibility （or gene polymorphism） on hypertension. Methods A cross-sectional epidemiological study was conducted in 452 workers from a thermal ...Objective To study the interactive effect of job stress and genetic susceptibility （or gene polymorphism） on hypertension. Methods A cross-sectional epidemiological study was conducted in 452 workers from a thermal power plant in China. Extrinsic effort, occupational reward, and over-commitment were measured. Hypertensive patients were defined by three phases of screening, reexamination, and final diagnosis. β2-AR genotypes and allele frequencies at amino acid positions 16 （β2-AR-16： Arg→Gly） and 27 （β2-AR-27： Gln→Glu） were identified by PCR-RFLE Results Job stress was related with the prevalence of hypertension in males （P〈0.05）, whereas no significant relationship was found in females （P〉0.05）. Differences in genotypes and allele frequencies of the β2-AR-16 were statistically significant between the hypertension and control groups （P〈0.05）, whereas those of β2-AR-27 were not （P〉0.05）. The prevalence of hypertension was higher in individuals carrying Gly16 allele than in those carrying Arg16 allele of the high job stress group （P〈0.01 or 0.05）. Conclusion High job stress and polymorphism of β2-AR-16 have an interactive effect on the prevalence of hypertension in male workers.展开更多
Metabolic flexibility has emerged as a critical determinant of CD8+T-cell antitumor activity,yet the mechanisms driving the metabolic flexibility of T cells have not been determined.In this study,we investigated the i...Metabolic flexibility has emerged as a critical determinant of CD8+T-cell antitumor activity,yet the mechanisms driving the metabolic flexibility of T cells have not been determined.In this study,we investigated the influence of the nuclear cap-binding complex(CBC)adaptor protein ARS2 on mature T cells.In doing so,we discovered a novel signaling axis that endows activated CD8+T cells with flexibility of glucose catabolism.ARS2 upregulation driven by CD28 signaling reinforced splicing factor recruitment to pre-mRNAs and affected approximately one-third of T-cell activation-induced alternative splicing events.Among these effects,the CD28-ARS2 axis suppressed the expression of the M1 isoform of pyruvate kinase in favor of PKM2,a key determinant of CD8+T-cell glucose utilization,interferon gamma production,and antitumor effector function.Importantly,PKM alternative splicing occurred independently of CD28-driven PI3K pathway activation,revealing a novel means by which costimulation reprograms glucose metabolism in CD8+T cells.展开更多
基金supported by National Natural Science Foundation of China(Nos.11805107 and 12275039)the Fundamental Research Funds in Heilongjiang Provincial Universities of China(No.145309625)。
文摘In this work,the effects of the frequency,pressure,gas composition,and secondary-electron emission coefficient on the discharge mode in capacitively coupled Ar/O_(2) plasmas were carefully studied through simulations.Three discharge modes,i.e.,α,γ,and drift-ambipolar(DA),were considered in this study.The results show that a mode transition from theγ-DA hybrid mode dominated by theγmode to the DA-αhybrid mode dominated by the DA mode is induced by increasing the frequency from 100 k Hz to 40 MHz.Furthermore,the electron temperature decreases with increasing frequency,while the plasma density first decreases and then increases.It was found that the electronegativity increases slightly with increasing pressure in the lowfrequency region,and it increases notably with increasing pressure in the high-frequency region.It was also observed that the frequency corresponding to the mode transition fromγto DA decreased when the secondary-electron emission coefficient was decreased.Finally,it was found that increasing the oxygen content weakens theγmode and enhances the DA mode.More importantly,the density of oxygen atoms and ozone will increase greatly with increasing oxygen content,which is of great significance for industrial applications.
基金the National Natural Science Foun-dation of China(Grant Nos.12020101005,11975067,and 12347131)the Fundamental Research Funds for the Cen-tral Universities(Grant No.DUT24BS069).
文摘Simulations are conducted on capacitively coupled Ar/O_(2)mixed gas discharges employing a one-dimensional fluid coupled with an electron Monte Carlo(MC)model.The research explores the impact of different O_(2)ratio and pressures on the discharge characteristics of Ar/O_(2)plasma.At a fixed Ar/O_(2)gas ratio,with the increasing pressure,higher ion densities,as well as a slight increase in electron density in the bulk region can be observed.The discharge remains dominated by the drift-ambipolar(DA)mode,and the flux of O(3P)at the electrode increases with the increasing pressure due to higher background gas density,while the fluxes of O(1D)and Ardecrease due to the pronounced loss rate.With the increasing proportion of O_(2),a change in the dominant discharge mode from a mode to DA mode can be detected,and the O_(2)-associated charged particle densities are significantly increased.However,Ar+density shows a trend of increasing and then decreasing,while for neutral fluxes at the electrode,Arflux decreases,and O(3P)flux increases with the reduced Ar gas proportion,while trends in O(1D)flux show slight differences.The evolution of the densities of the charged particle and the neutral fluxes under different discharge parameters are discussed in detail using the ionization characteristics as well as the transport properties.Hopefully,more comprehensive understanding of Ar/O_(2)discharge characteristics in this work will provide a valuable reference for the industry.
基金financially supported by the National Natural Science Foundation of China(32372675,32372657,32102359)the National Key Research and Development Project,China(2023YFD2301002)+5 种基金the Young Talent Fund of Association for Science and Technology in Shaanxi,China(20240218)the Science and Technology Major Project of Xinjiang Production and Construction Corps,China(2023AB077)the Chinese Universities Scientific Fund(2452023005)the China Apple Research System(CARS-27)the Cyrus Tang Foundationthe Fundamental Research Funds for the Central Universities,China。
文摘Potassium nitrate(KNO_(3))promotes adventitious root(AR)formation in apple stem cuttings.However,evidence for the possible involvement of cytokinin(CK)in KNO_(3)-mediated AR formation in apples is still lacking.In this study,we cultured GL-3 apple microshoots in different treatment combinations.While the T1(KNO_(3)9.4 mmol L^(-1)+6-benzyl adenine(6-BA)2.22μmol L^(-1))and T3(6-BA 2.22μmol L^(-1))treatments completely inhibited AR formation,the control,T2(KNO_(3)9.4 mmol L^(-1)),and T4(KNO_(3)9.4 mmol L^(-1)+lovastatin(Lov)1.24μmol L^(-1))treatments developed ARs.However,T4-treated microshoots developed fewer and shorter ARs,indicating that optimum CK synthesis is needed for normal AR growth.This also suggests that these fewer and shorter ARs developed because of the presence of KNO_(3) in the same medium.The anatomy of the stem basal part indicated that the inhibition of CK biosynthesis delayed AR primordia formation.The endogenous levels of indole-3-acetic acid(IAA)and zeatin riboside(ZR)were higher in T2-treated microshoots,while the abscisic acid(ABA),gibberellic acid 3(GA_(3)),and brassinosteroid(BR)levels were higher in T4-treated microshoots.The expression levels of MdNRT1.1and MdNRT2.1 were higher in T2-treated microshoots at 3 and 8 days,while MdRR2 and MdCKX5 were higher at 8 and 16 days,respectively.Furthermore,higher IAA levels increased MdWOX11 expression,which in turn increased MdLBD16 and MdLBD29 expression in response to T2.The combined expression of these genes stimulated adventitious rooting by upregulating cell cycle-related genes(MdCYCD1;1 and MdCYCD3;1)in response to T2 treatment.This study shows that specific genes and hormonal pathways contribute to KNO_(3)-CK-mediated adventitious rooting in apples.
基金supported by the National Science Fund for Distinguished Young Scholars(32025029)the Shanghai Education Committee Scientific Research Innovation Projects(2101070007800120)+1 种基金the Yili Health Science Foundation of Chinese Institute of Food Science and Technology(2021-Y06)the Shanghai Engineering Research Center of food microbiology program(19DZ2281100)。
文摘Probiotics could effectively eliminate excess reactive oxygen species(ROS)generated during aging or lipid metabolism disorders,but their mechanism is unclear.The major purpose of this study was to investigate the mechanism of Lactiplantibacillus plantarun AR113 alleviating oxidative stress injury in the D-galactose induced aging mice.The result showed that pretreatment with L.plantarun AR113 significantly relieving H_(2)O_(2)induced cytotoxicity in HepG2 cells by maintain cell membrane integrity and increasing antioxidant enzyme activities.In D-galactose induced aging mice,L.plantarun AR113 could significantly attenuate liver damage and inflammatory infiltration by promoting endogenous glutathione(GSH)synthesis and activating the Nrf2/Keap1 signaling pathway in mice,and increasing the expression of regulated phaseⅡdetoxification enzymes and antioxidant enzymes.Further analysis shown that gavage of L.plantarun AR113 could significantly reduce the expression of G protein-coupled receptor 78(GPR78)and C/EBP homologous protein(CHOP)proteins,and promote the restoration of endoplasmic reticulum(ER)homeostasis,thereby activating cell anti-apoptotic pathways.These results were also confirmed in H_(2)O_(2)-treated HepG2 experiments.It indicated that L.plantarun AR113 could inhibit D-galactose-induced liver injury through dual inhibition of ER stress and oxidative stress.L.plantarun AR113 have good application potential in anti-aging and alleviating metabolic disorders.
基金Project supported by the National Natural Science Foundation of China (Grant Nos.12020101005 and 11975067)。
文摘Radio frequency capacitively coupled plasmas(RF CCPs)play a pivotal role in various applications in etching and deposition processes on a microscopic scale in semiconductor manufacturing.In the discharge process,the plasma series resonance(PSR)effect is easily observed in electrically asymmetric and geometrically asymmetric discharges,which could largely influence the power absorption,ionization rate,etc.In this work,the PSR effect arising from geometrically and electrically asymmetric discharge in argon-oxygen mixture gas is mainly investigated by using a plasma equivalent circuit model coupled with a global model.At relatively low pressures,as Ar content(α)increases,the inductance of the bulk is weakened,which leads to a more obvious PSR phenomenon and a higher resonance frequency(ω_(psr)).When the Ar content is fixed,varying the pressure and gap distance could also have different effects on the PSR effect.With the increase of the pressure,the PSR frequency shifts towards the higher order,but in the case of much higher pressure,the PSR oscillation would be strongly damped by frequent electron-neutral collisions.With the increase of the gap distance,the PSR frequency becomes lower.In addition,electrically asymmetric waveforms applied to a geometrically asymmetric chamber may weaken or enhance the asymmetry of the discharge and regulate the PSR effect.In this work,the Ar/O_(2) electronegative mixture gas is introduced in a capacitive discharge to study the PSR effect under geometric asymmetry effect and electrical asymmetry effect,which can provide necessary guidance in laboratory research and current applications.
文摘AIM: To investigate the expression of mi R-29 a in rat acute pancreatitis and its functional role in AR42 J cell apoptosis.METHODS: Twelve SD rats were divided into a control group and an acute edematous pancreatitis(AEP) group randomly. AEP was induced by intraperitoneal injection of L-arginine(150 mg/kg) in the AEP group and equal volume of 0.9% Na Cl was injected in the control group. The apoptosis of acinar cells in pancreatic tissue was determined by TUNEL assay. mi RNA chip assay was performed to examine the expression of mi RNAs in two groups. Besides, to further explore the role of mi R-29 a in apoptosis in vitro, recombinant rat TNF-α(50 ng/m L) was administered to treat the rat pancreatic acinar cell line AR42 J for inducing AR42 J cell apoptosis. Quantitative real-time PCR(q RT-PCR) was adopted to measure mi R-29 a expression. Then, mi RNA mimic, mi RNA antisense oligonucleotide(AMO) and control vector were used to transfect AR42 J cells. The expression of mi R-29 a was confirmed by q RT-PCR andthe apoptosis rate of AR42 J cells was detected by flow cytometry analysis. Western blot was used to detect the expression of activated caspase3. Moreover, we used bioinformatics software and luciferase assay to test whether TNFRSF1 A was the target gene of mi R-29 a. After transfection, q RT-PCR and Western blot was used to detect the expression of TNFRSF1 A in AR42 J cells after transfection.RESULTS: The expression of mi R-29 a was much higher in the AEP group compared with the control group as displayed by the mi RNA chip assay. After inducing apoptosis of AR42 J cells in vitro, the expression of mi R-29 a was significantly increased by 1.49 ± 0.04 times in comparison with the control group. As revealed by q RT-PCR assay, the expression of mi R-29 a was 2.68 ± 0.56 times higher in the mi R-29 a mimic group relative to the control vector group, accompanied with an obviously increased acinar cell apoptosis rate(42.83 ± 1.25 vs 24.97 ± 0.15, P < 0.05). Moreover, the expression of mi R-29 a in the mi RNA AMO group was 0.46 ± 0.05 times lower than the control vector group, and the cell apoptosis rate was much lower accordingly(17.27 ± 1.36 vs 24.97 ± 0.15, P < 0.05). The results of bioinformatics software and luciferase assay showed that TNFRSF1 A might be a target gene of mi R-29 a. TNFRSF1 A expression was up-regulated in the mi R-29 a mimic group, while the mi R-29 a AMO group showed the reverse trend.CONCLUSION: mi R-29 a might promote the apoptosis of AR42 J cells via up-regulating the expression of its target gene TNFRSF1 A.
基金This research was supported by the Funds of Health Science & Technology Innovation Project of Henan Province
文摘Objective To study the interactive effect of job stress and genetic susceptibility （or gene polymorphism） on hypertension. Methods A cross-sectional epidemiological study was conducted in 452 workers from a thermal power plant in China. Extrinsic effort, occupational reward, and over-commitment were measured. Hypertensive patients were defined by three phases of screening, reexamination, and final diagnosis. β2-AR genotypes and allele frequencies at amino acid positions 16 （β2-AR-16： Arg→Gly） and 27 （β2-AR-27： Gln→Glu） were identified by PCR-RFLE Results Job stress was related with the prevalence of hypertension in males （P〈0.05）, whereas no significant relationship was found in females （P〉0.05）. Differences in genotypes and allele frequencies of the β2-AR-16 were statistically significant between the hypertension and control groups （P〈0.05）, whereas those of β2-AR-27 were not （P〉0.05）. The prevalence of hypertension was higher in individuals carrying Gly16 allele than in those carrying Arg16 allele of the high job stress group （P〈0.01 or 0.05）. Conclusion High job stress and polymorphism of β2-AR-16 have an interactive effect on the prevalence of hypertension in male workers.
基金supported by National Cancer Institute grants R00CA175189,R01AI155499(both to SHO),R01CA205246(to EAR),R01CA121044(to KPL),T32CA085183(to GAH and MML),and P30CA016056,involving the use of the Roswell Park Comprehensive Cancer Center Flow and Image Cytometry,Genomics,Laboratory Animal,and Immune Analysis Shared Resourcesby the Roswell Park Alliance Foundation.NMR experiments were carried out at the Center for Environmental and Systems Biochemistry Shared Resource Facility funded in part by the Markey Cancer Center(P30CA177558).
文摘Metabolic flexibility has emerged as a critical determinant of CD8+T-cell antitumor activity,yet the mechanisms driving the metabolic flexibility of T cells have not been determined.In this study,we investigated the influence of the nuclear cap-binding complex(CBC)adaptor protein ARS2 on mature T cells.In doing so,we discovered a novel signaling axis that endows activated CD8+T cells with flexibility of glucose catabolism.ARS2 upregulation driven by CD28 signaling reinforced splicing factor recruitment to pre-mRNAs and affected approximately one-third of T-cell activation-induced alternative splicing events.Among these effects,the CD28-ARS2 axis suppressed the expression of the M1 isoform of pyruvate kinase in favor of PKM2,a key determinant of CD8+T-cell glucose utilization,interferon gamma production,and antitumor effector function.Importantly,PKM alternative splicing occurred independently of CD28-driven PI3K pathway activation,revealing a novel means by which costimulation reprograms glucose metabolism in CD8+T cells.
