We have developed a protein array system,named"Phospho-Totum",which reproduces the phosphorylation state of a sample on the array.The protein array contains 1471 proteins from 273 known signaling pathways.Ac...We have developed a protein array system,named"Phospho-Totum",which reproduces the phosphorylation state of a sample on the array.The protein array contains 1471 proteins from 273 known signaling pathways.According to the activation degrees of tyrosine kinases in the sample,the corresponding groups of substrate proteins on the array are phosphorylated under the same conditions.In addition to measuring the phosphorylation levels of the 1471 substrates,we have developed and performed the artificial intelligence-assisted tools to further characterize the phosphorylation state and estimate pathway activation,tyrosine kinase activation,and a list of kinase inhibitors that produce phosphorylation states similar to that of the sample.The Phospho-Totum system,which seamlessly links and interrogates the measurements and analyses,has the potential to not only elucidate pathophysiological mechanisms in diseases by reproducing the phosphorylation state of samples,but also be useful for drug discovery,particularly for screening targeted kinases for potential drug kinase inhibitors.展开更多
Designing integrated overall water-splitting catalysts that maintain high efficiency and stability under various conditions is an important trend for future development,yet it remains a significant challenge.Herein,no...Designing integrated overall water-splitting catalysts that maintain high efficiency and stability under various conditions is an important trend for future development,yet it remains a significant challenge.Herein,novel nanoflower-like tri-metallic Ni-Ru-Mo phosphide catalyst((Ni-Ru-Mo)P@F-CDs),integrated with F-doped carbon dots(F-CDs),were synthesized via a straightforward hydrothermal process and subsequent phosphatization.Attributable to precise interface engineering and electronic structure optimization,(Ni-Ru-Mo)P@F-CDs exhibit exceptional bi-functional catalytic activity in alkaline conditions,achieving remarkably low overpotentials of 231 and 123 mV for oxygen evolution reaction(OER)and hydrogen evolution reaction(HER),respectively,at a current density of 100 mA cm^(−2).Industrially,only 1.426 V is needed for the same efficacy.Additionally,the catalyst requires merely 1.508 and 1.564 V for overall water splitting in 1 M KOH and simulated seawater,respectively,at 100 mA cm^(−2).The catalyst also shows excellent stability,with minimal performance decline over 100 h within 100-200 mA cm^(−2).Density functional theory calculations indicate that the interface structure synergistically optimizes Gibbs free energy for H^(*) and O^(*) intermediates during HER and OER,respectively,accelerating electrochemical water-splitting kinetics.展开更多
Hybrid supercapacitors have shown great potentials to fulfill the demand of future diverse applications such as electric vehicles and portable/wearable electronics.In particular,aqueous zinc-ion hybrid supercapacitors...Hybrid supercapacitors have shown great potentials to fulfill the demand of future diverse applications such as electric vehicles and portable/wearable electronics.In particular,aqueous zinc-ion hybrid supercapacitors(ZHSCs)have gained much attention due to their low-cost,high energy density,and environmental friendliness.Nevertheless,typical ZHSCs use Zn metal anode and normal liquid electrolyte,causing the dendrite issue,restricted working temperature,and inferior device flexibility.Herein,a novel flexible Zn-ion hybrid supercapacitor(FZHSC)is developed by using activated carbon(AC)anode,δ-MnO_(2) cathode,and innovative PVA-based gel electrolyte.In this design,heavy Zn anode and its dendrite issue are avoided and layered cathode with large interlayer spacing is employed.In addition,flexible electrodes are prepared and integrated with an anti-freezing,stretchable,and compressible hydrogel electrolyte,which is attained by simultaneously using glycerol additive and freezing/thawing technique to regulate the hydrogen bond and microstructure.The resulting FZHSC exhibits good rate capability,high energy density(47.86 Wh kg^(−1);3.94 mWh cm^(−3)),high power density(5.81 kW kg^(−1);480 mW cm^(−3)),and excellent cycling stability(~91%capacity retention after 30000 cycles).Furthermore,our FZHSC demonstrates outstanding flexibility with capacitance almost unchanged even after various continuous shape deformations.The hydrogel electrolyte still maintains high ionic conductivity at ultralow temperatures(≤−30℃),enabling the FZHSC cycled well,and powering electronic timer robustly within an all-climate temperature range of−30~80℃.This work highlights that the promising Zn metal-free aqueous ZHSCs can be designed with great multifunctionality for more practical application scenarios.展开更多
In previous studies,we showed that TP53-induced glycolysis and apoptosis regulator（TIGAR） protects neurons against ischemic brain injury.In the present study,we investigated the developmental changes of TIGAR level ...In previous studies,we showed that TP53-induced glycolysis and apoptosis regulator（TIGAR） protects neurons against ischemic brain injury.In the present study,we investigated the developmental changes of TIGAR level in mouse brain and the correlation of TIGAR expression with the vulnerability of neurons to ischemic injury.We found that the TIGAR level was high in the embryonic stage,dropped at birth,partially recovered in the early postnatal period,and then continued to decline to a lower level in early adult and aged mice.The TIGAR expression was higher after ischemia/reperfusion in mouse brain 8and 12 weeks after birth.Four-week-old mice had smaller infarct volumes,lower neurological scores,and lower mortality rates after ischemia than 8- and12-week-old mice.TIGAR expression also increased in response to oxygen glucose deprivation（OGD）/reoxygenation insult or H_2O_2 treatment in cultured primary neurons from different embryonic stages（E16 and E20）.The neurons cultured from the early embryonic period had a greater resistance to OGD and oxidative insult.Higher TIGAR levels correlated with higher pentose phosphate pathway activity and less oxidative stress.Older mice and more mature neurons had more severe DNA and mitochondrial damage than younger mice and less mature neurons in response to ischemia/reperfusion or OGD/reoxygenation insult.Supplementation of cultured neurons with nicotinamide adenine dinuclectide phosphate（NADPH） significantly reduced ischemic injury.These results suggest that TIGAR expression changes during development and its expression level may be correlated with the vulnerability of neurons to ischemic injury.展开更多
The cadmium sulphide (CdS) film is grown on cadmium telluride (CdTe) nanorods (NRs) arrays by different methods such as chemical bath deposition (CBD), magnetron sputtering (MS), and homogenous precipitation (HP) tech...The cadmium sulphide (CdS) film is grown on cadmium telluride (CdTe) nanorods (NRs) arrays by different methods such as chemical bath deposition (CBD), magnetron sputtering (MS), and homogenous precipitation (HP) techniques. The impact of various deposition methods is explored in detail on the growth of CdTe/CdS composite film, the CdTe/CdS interface property, and solar cell efficiency. Compared to the CBD and HP methods, the MS method can improve the growth of the CdS on CdTe NRs with high crystalline quality. The device based on the CdS film prepared by the MS method demonstrates excellent photovoltaic performance, which has the potential for applications in solar cells.展开更多
The knowledge of two-phase cloud dispersion mechanism from HLG(hazardous liquefied gas) release is the prerequisite for accurate assessment and precise rescue of such accidents. In this paper, an experiment of two-pha...The knowledge of two-phase cloud dispersion mechanism from HLG(hazardous liquefied gas) release is the prerequisite for accurate assessment and precise rescue of such accidents. In this paper, an experiment of two-phase cloud dispersion from liquefied CO_(2) hole release is performed. The source terms, such as vapour mass fraction, release velocity and mean droplet diameter, are calculated based on thermodynamic theory. Taking phase transition of CO_(2) droplets to gas into account, CFD(computational fluid dynamics) model for two-phase cloud dispersion is established. The predicted cloud temperatures at the downstream agree well with the experimental data, with the maximum relative error of 5.8% and average relative error of 2.3%. The consequence distances in the downstream direction and in the crosswise direction calculated through two-phase model are larger than those through single-phase model,with the relative differences of 57.8% and 53.6% respectively. CO_(2) concentration calculated by twophase model is smaller in the vicinity of release hole, and larger beyond 0.135 m downstream. A smaller leakage rate results in a lower CO_(2) concentration and a higher cloud temperature.展开更多
The 40 Gbit/s optical solitons transmission system in photonic crystal fiber was investigated by fast Fourier transform method, and the maximum transmission distance of system was calculated numerically. By the eye pa...The 40 Gbit/s optical solitons transmission system in photonic crystal fiber was investigated by fast Fourier transform method, and the maximum transmission distance of system was calculated numerically. By the eye pattern of system, the transmission performances of system were studied. Results show that when polarization mode dispersion coefficient Dp is smaller than , the influence of the PMD on the transmission distance was neglectable. When the dispersion coefficient D is larger than 1.5 ps/km/nm, the transmission distance decreases rapidly. The positive or negative of three order group-velocity dispersion makes no differences on the system transmission.展开更多
Background:The efficacy and optimal dose of the new acid-suppressant vonoprazan(VPZ)for quadruple therapy remain uncertain.This study aimed to compare the efficacy and safety of 20mg VPZ daily(VOD)and 20mg VPZ twice d...Background:The efficacy and optimal dose of the new acid-suppressant vonoprazan(VPZ)for quadruple therapy remain uncertain.This study aimed to compare the efficacy and safety of 20mg VPZ daily(VOD)and 20mg VPZ twice daily(VTD)with a proton pump inhibitor(PPI)twice daily in quadruple therapy.Methods:We retrospectively analyzed the data of 954 patients treated with quadruple therapy to eradicate Helicobacter pylori.Eradication rates and adverse events were compared between the VOD and VTD groups,and between the VOD and PPI groups.Multivariate analysis was conducted to identify the predictors of eradication failure.Results:Eradication was successful in 875(91.7%)of the 954 patients.The total,initial,and rescue eradication rates in the VOD group were 92.1%,93.3%,and 77.8%,respectively.In both the crude and multivariate analyses,the VOD group showed eradication rates comparable to those of the VTD and PPI groups(all P>0.05).Age>60years(odds ratio[OR]=2.165,P=0.012)and use of rescue therapy(OR=3.496,P<0.001)were independent risk factors for eradication failure,whereas VPZ at a low dosing frequency of 20mg daily was not.A total of 787 patients(82.5%)were followed up(mean follow-up time,6.7±2.0months).Compared with the VOD group,the VTD group was more likely to experience adverse events(OR=2.073,P=0.035).Conclusion:VPZ at a low dose of 20mg daily is an effective and safe component of the quadruple therapy for H.pylori eradication.展开更多
The specification of theαβ/γδlineage and the maturation of medullary thymic epithelial cells(mTECs)coordinate central tolerance to self-antigens.However,the mechanisms underlying this biological process remain poo...The specification of theαβ/γδlineage and the maturation of medullary thymic epithelial cells(mTECs)coordinate central tolerance to self-antigens.However,the mechanisms underlying this biological process remain poorly clarified.Here,we report that dual-stage loss of TOX in thymocytes hierarchically impaired mTEC maturation,promoted thymic IL-17A-producingγδT-cell(Tγδ17)lineage commitment,and led to the development of fatal autoimmune hepatitis(AIH)via different mechanisms.Transfer ofγδT cells from TOX-deficient mice reproduced AIH.TOX interacted with and stabilized the TCF1 protein to maintain the balance ofγδT-cell development in thymic progenitors,and overexpression of TCF1 normalizedαβ/γδlineage specification and activation.In addition,TOX expression was downregulated inγδT cells from AIH patients and was inversely correlated with the AIH diagnostic score.Our findings suggest multifaceted roles of TOX in autoimmune control involving mTEC and Tγδ17 development and provide a potential diagnostic marker for AIH.展开更多
Introduction Circular RNAs(circRNAs)are a unique class of single-stranded RNA molecules that are covalently closed and lack 5 and 3 ends.They were first discovered in eukaryotic cells>30 years ago,but technical lim...Introduction Circular RNAs(circRNAs)are a unique class of single-stranded RNA molecules that are covalently closed and lack 5 and 3 ends.They were first discovered in eukaryotic cells>30 years ago,but technical limitations hindered the characterization of circRNAs until the 2010s.Recent advances in high-throughput RNA sequencing(RNA-seq),coupled with circRNA enrichment using RNase R treatment and new bioinformatic tools,have led to the discovery of a large number of circRNAs in various eukaryotic organisms,including mammals,insects.展开更多
Soil microorganisms play a key role in the function of soil ecosystem,yet our knowledge about how microbial communities respond to the typically sandy soil environmental properties along the soil profile is still insu...Soil microorganisms play a key role in the function of soil ecosystem,yet our knowledge about how microbial communities respond to the typically sandy soil environmental properties along the soil profile is still insufficient.We investigated the soil microbial community patterns from top(0–20 cm)to clay-layer(>80 cm)of the typical sandy soils in three regions in China with different levels of precipitation,including Lishu County in Jilin Province(LS),Langfang City in Hebei Province(LF)and Zhengzhou City in Henan Province(ZZ).Our findings showed that small-size aggregates(<0.5 mm)rather than large ones(³0.5 mm)dominated the soil profile.The relative abundances of Actinobacteria,Crenarchaeota and Firmicutes were highly related to aggregate proportions of the deep clay-layer soil.The network analysis revealed the distinct community patterns among modules,evidencing niche differentiation along the soil profile.The keystone species OTU_11292 was observed having migrated clearly into the other module of the clay-layer soil.Different roles of the OTU_30(belonging to Gemmatimonadetes)in soil processes might partly explain the different microbial distribution between top-and clay-layer soils.These findings provided new insights into the candidate mechanisms of microbial diversity maintenance and community patterning of sandy soils,which were necessary for better understanding of ecological rules guiding long-term agricultural practice.展开更多
In this paper,we combine the generalized multiscale finite element method(GMsFEM)with the balanced truncation(BT)method to address a parameterdependent elliptic problem.Basically,in progress of a model reduction we tr...In this paper,we combine the generalized multiscale finite element method(GMsFEM)with the balanced truncation(BT)method to address a parameterdependent elliptic problem.Basically,in progress of a model reduction we try to obtain accurate solutions with less computational resources.It is realized via a spectral decomposition from the dominant eigenvalues,that is used for an enrichment of multiscale basis functions in the GMsFEM.The multiscale bases computations are localized to specified coarse neighborhoods,and follow an offline-online process in which eigenvalue problems are used to capture the underlying system behaviors.In the BT on reduced scales,we present a local-global strategy where it requires the observability and controllability of solutions to a set of Lyapunov equations.As the Lyapunov equations need expensive computations,the efficiency of our combined approach is shown to be readily flexible with respect to the online space and an reduced dimension.Numerical experiments are provided to validate the robustness of our approach for the parameter-dependent elliptic model.展开更多
基金supported by the State Key Program of National Natural Science Foundation of China(Grant No.82230114 to F.H.)the National Key Research and Development Program of China(Grant No.2022YFE0104800 to F.H.).
文摘We have developed a protein array system,named"Phospho-Totum",which reproduces the phosphorylation state of a sample on the array.The protein array contains 1471 proteins from 273 known signaling pathways.According to the activation degrees of tyrosine kinases in the sample,the corresponding groups of substrate proteins on the array are phosphorylated under the same conditions.In addition to measuring the phosphorylation levels of the 1471 substrates,we have developed and performed the artificial intelligence-assisted tools to further characterize the phosphorylation state and estimate pathway activation,tyrosine kinase activation,and a list of kinase inhibitors that produce phosphorylation states similar to that of the sample.The Phospho-Totum system,which seamlessly links and interrogates the measurements and analyses,has the potential to not only elucidate pathophysiological mechanisms in diseases by reproducing the phosphorylation state of samples,but also be useful for drug discovery,particularly for screening targeted kinases for potential drug kinase inhibitors.
基金Natural Science Foundation Joint Innovation Fund of Shandong Province,Grant/Award Num ber:ZR2021 LFG019。
文摘Designing integrated overall water-splitting catalysts that maintain high efficiency and stability under various conditions is an important trend for future development,yet it remains a significant challenge.Herein,novel nanoflower-like tri-metallic Ni-Ru-Mo phosphide catalyst((Ni-Ru-Mo)P@F-CDs),integrated with F-doped carbon dots(F-CDs),were synthesized via a straightforward hydrothermal process and subsequent phosphatization.Attributable to precise interface engineering and electronic structure optimization,(Ni-Ru-Mo)P@F-CDs exhibit exceptional bi-functional catalytic activity in alkaline conditions,achieving remarkably low overpotentials of 231 and 123 mV for oxygen evolution reaction(OER)and hydrogen evolution reaction(HER),respectively,at a current density of 100 mA cm^(−2).Industrially,only 1.426 V is needed for the same efficacy.Additionally,the catalyst requires merely 1.508 and 1.564 V for overall water splitting in 1 M KOH and simulated seawater,respectively,at 100 mA cm^(−2).The catalyst also shows excellent stability,with minimal performance decline over 100 h within 100-200 mA cm^(−2).Density functional theory calculations indicate that the interface structure synergistically optimizes Gibbs free energy for H^(*) and O^(*) intermediates during HER and OER,respectively,accelerating electrochemical water-splitting kinetics.
基金supported by grants from the National Natural Science Foundation of China(Grant Nos.52072136,51972257,51872104,and 52172229)the Ningxia Key R&D Program(2019BFG02018)the Fundamental Research Funds for the Central Universities(WUT:2021IVA115,2021IVA071).
文摘Hybrid supercapacitors have shown great potentials to fulfill the demand of future diverse applications such as electric vehicles and portable/wearable electronics.In particular,aqueous zinc-ion hybrid supercapacitors(ZHSCs)have gained much attention due to their low-cost,high energy density,and environmental friendliness.Nevertheless,typical ZHSCs use Zn metal anode and normal liquid electrolyte,causing the dendrite issue,restricted working temperature,and inferior device flexibility.Herein,a novel flexible Zn-ion hybrid supercapacitor(FZHSC)is developed by using activated carbon(AC)anode,δ-MnO_(2) cathode,and innovative PVA-based gel electrolyte.In this design,heavy Zn anode and its dendrite issue are avoided and layered cathode with large interlayer spacing is employed.In addition,flexible electrodes are prepared and integrated with an anti-freezing,stretchable,and compressible hydrogel electrolyte,which is attained by simultaneously using glycerol additive and freezing/thawing technique to regulate the hydrogen bond and microstructure.The resulting FZHSC exhibits good rate capability,high energy density(47.86 Wh kg^(−1);3.94 mWh cm^(−3)),high power density(5.81 kW kg^(−1);480 mW cm^(−3)),and excellent cycling stability(~91%capacity retention after 30000 cycles).Furthermore,our FZHSC demonstrates outstanding flexibility with capacitance almost unchanged even after various continuous shape deformations.The hydrogel electrolyte still maintains high ionic conductivity at ultralow temperatures(≤−30℃),enabling the FZHSC cycled well,and powering electronic timer robustly within an all-climate temperature range of−30~80℃.This work highlights that the promising Zn metal-free aqueous ZHSCs can be designed with great multifunctionality for more practical application scenarios.
基金supported by the Natural Science Foundation of China (30930035 and 81271459)a "973" project from the Ministry of Science and Technology of China (2011CB51000)+1 种基金the Priority Academic Program Development of Jiangsu Higher Education Institutes (PAPD)the Graduate Education Innovation Project of Jiangsu Province (CXZZ12_0850)
文摘In previous studies,we showed that TP53-induced glycolysis and apoptosis regulator（TIGAR） protects neurons against ischemic brain injury.In the present study,we investigated the developmental changes of TIGAR level in mouse brain and the correlation of TIGAR expression with the vulnerability of neurons to ischemic injury.We found that the TIGAR level was high in the embryonic stage,dropped at birth,partially recovered in the early postnatal period,and then continued to decline to a lower level in early adult and aged mice.The TIGAR expression was higher after ischemia/reperfusion in mouse brain 8and 12 weeks after birth.Four-week-old mice had smaller infarct volumes,lower neurological scores,and lower mortality rates after ischemia than 8- and12-week-old mice.TIGAR expression also increased in response to oxygen glucose deprivation（OGD）/reoxygenation insult or H_2O_2 treatment in cultured primary neurons from different embryonic stages（E16 and E20）.The neurons cultured from the early embryonic period had a greater resistance to OGD and oxidative insult.Higher TIGAR levels correlated with higher pentose phosphate pathway activity and less oxidative stress.Older mice and more mature neurons had more severe DNA and mitochondrial damage than younger mice and less mature neurons in response to ischemia/reperfusion or OGD/reoxygenation insult.Supplementation of cultured neurons with nicotinamide adenine dinuclectide phosphate（NADPH） significantly reduced ischemic injury.These results suggest that TIGAR expression changes during development and its expression level may be correlated with the vulnerability of neurons to ischemic injury.
基金Project supported by Natural Science Foundation of Shandong Province,China(Grant No.ZR2019QF018)National Natural Science Foundation of China(Grant Nos.61904098 and 11904209)Natural Science Foundation of Heilongjiang Province of China(Grant No.2017001).
文摘The cadmium sulphide (CdS) film is grown on cadmium telluride (CdTe) nanorods (NRs) arrays by different methods such as chemical bath deposition (CBD), magnetron sputtering (MS), and homogenous precipitation (HP) techniques. The impact of various deposition methods is explored in detail on the growth of CdTe/CdS composite film, the CdTe/CdS interface property, and solar cell efficiency. Compared to the CBD and HP methods, the MS method can improve the growth of the CdS on CdTe NRs with high crystalline quality. The device based on the CdS film prepared by the MS method demonstrates excellent photovoltaic performance, which has the potential for applications in solar cells.
基金supported by the Natural Science Foundation of Shandong Province (ZR2021QB144)。
文摘The knowledge of two-phase cloud dispersion mechanism from HLG(hazardous liquefied gas) release is the prerequisite for accurate assessment and precise rescue of such accidents. In this paper, an experiment of two-phase cloud dispersion from liquefied CO_(2) hole release is performed. The source terms, such as vapour mass fraction, release velocity and mean droplet diameter, are calculated based on thermodynamic theory. Taking phase transition of CO_(2) droplets to gas into account, CFD(computational fluid dynamics) model for two-phase cloud dispersion is established. The predicted cloud temperatures at the downstream agree well with the experimental data, with the maximum relative error of 5.8% and average relative error of 2.3%. The consequence distances in the downstream direction and in the crosswise direction calculated through two-phase model are larger than those through single-phase model,with the relative differences of 57.8% and 53.6% respectively. CO_(2) concentration calculated by twophase model is smaller in the vicinity of release hole, and larger beyond 0.135 m downstream. A smaller leakage rate results in a lower CO_(2) concentration and a higher cloud temperature.
文摘The 40 Gbit/s optical solitons transmission system in photonic crystal fiber was investigated by fast Fourier transform method, and the maximum transmission distance of system was calculated numerically. By the eye pattern of system, the transmission performances of system were studied. Results show that when polarization mode dispersion coefficient Dp is smaller than , the influence of the PMD on the transmission distance was neglectable. When the dispersion coefficient D is larger than 1.5 ps/km/nm, the transmission distance decreases rapidly. The positive or negative of three order group-velocity dispersion makes no differences on the system transmission.
基金supported by the Guangdong Basic and Applied Basic Research Foundation[grant number 2022A1515110196].
文摘Background:The efficacy and optimal dose of the new acid-suppressant vonoprazan(VPZ)for quadruple therapy remain uncertain.This study aimed to compare the efficacy and safety of 20mg VPZ daily(VOD)and 20mg VPZ twice daily(VTD)with a proton pump inhibitor(PPI)twice daily in quadruple therapy.Methods:We retrospectively analyzed the data of 954 patients treated with quadruple therapy to eradicate Helicobacter pylori.Eradication rates and adverse events were compared between the VOD and VTD groups,and between the VOD and PPI groups.Multivariate analysis was conducted to identify the predictors of eradication failure.Results:Eradication was successful in 875(91.7%)of the 954 patients.The total,initial,and rescue eradication rates in the VOD group were 92.1%,93.3%,and 77.8%,respectively.In both the crude and multivariate analyses,the VOD group showed eradication rates comparable to those of the VTD and PPI groups(all P>0.05).Age>60years(odds ratio[OR]=2.165,P=0.012)and use of rescue therapy(OR=3.496,P<0.001)were independent risk factors for eradication failure,whereas VPZ at a low dosing frequency of 20mg daily was not.A total of 787 patients(82.5%)were followed up(mean follow-up time,6.7±2.0months).Compared with the VOD group,the VTD group was more likely to experience adverse events(OR=2.073,P=0.035).Conclusion:VPZ at a low dose of 20mg daily is an effective and safe component of the quadruple therapy for H.pylori eradication.
基金This work was supported by grants from the State Key Program of the National Natural Science Foundation(81930086 and 82120108012 to BS,82073157 and 81600487 to WT)the Science and Technology Project of Jiangsu Province(BE2018603 to BS)the Postgraduate Innovative Research Program of Jiangsu Province(KYCX20_0047 to QH).
文摘The specification of theαβ/γδlineage and the maturation of medullary thymic epithelial cells(mTECs)coordinate central tolerance to self-antigens.However,the mechanisms underlying this biological process remain poorly clarified.Here,we report that dual-stage loss of TOX in thymocytes hierarchically impaired mTEC maturation,promoted thymic IL-17A-producingγδT-cell(Tγδ17)lineage commitment,and led to the development of fatal autoimmune hepatitis(AIH)via different mechanisms.Transfer ofγδT cells from TOX-deficient mice reproduced AIH.TOX interacted with and stabilized the TCF1 protein to maintain the balance ofγδT-cell development in thymic progenitors,and overexpression of TCF1 normalizedαβ/γδlineage specification and activation.In addition,TOX expression was downregulated inγδT cells from AIH patients and was inversely correlated with the AIH diagnostic score.Our findings suggest multifaceted roles of TOX in autoimmune control involving mTEC and Tγδ17 development and provide a potential diagnostic marker for AIH.
基金supported by the National Natural Science Foundation of China to Y.Y.(31870814)Y.Y.is also sponsored by the Youth Innovation Promotion Association CAS,SA-SIBA Scholarship Program,and Shanghai Science and Technology Committee Rising-Star Program(19QA1410500).
文摘Introduction Circular RNAs(circRNAs)are a unique class of single-stranded RNA molecules that are covalently closed and lack 5 and 3 ends.They were first discovered in eukaryotic cells>30 years ago,but technical limitations hindered the characterization of circRNAs until the 2010s.Recent advances in high-throughput RNA sequencing(RNA-seq),coupled with circRNA enrichment using RNase R treatment and new bioinformatic tools,have led to the discovery of a large number of circRNAs in various eukaryotic organisms,including mammals,insects.
基金the financial supports of the National Basic Research Program of China(Grant no.2016YFD0200306)the National Natural Science Foundation of China(Grant no.41877412)the Scholarship of the‘National 1000(Young)Talents Program’of China.
文摘Soil microorganisms play a key role in the function of soil ecosystem,yet our knowledge about how microbial communities respond to the typically sandy soil environmental properties along the soil profile is still insufficient.We investigated the soil microbial community patterns from top(0–20 cm)to clay-layer(>80 cm)of the typical sandy soils in three regions in China with different levels of precipitation,including Lishu County in Jilin Province(LS),Langfang City in Hebei Province(LF)and Zhengzhou City in Henan Province(ZZ).Our findings showed that small-size aggregates(<0.5 mm)rather than large ones(³0.5 mm)dominated the soil profile.The relative abundances of Actinobacteria,Crenarchaeota and Firmicutes were highly related to aggregate proportions of the deep clay-layer soil.The network analysis revealed the distinct community patterns among modules,evidencing niche differentiation along the soil profile.The keystone species OTU_11292 was observed having migrated clearly into the other module of the clay-layer soil.Different roles of the OTU_30(belonging to Gemmatimonadetes)in soil processes might partly explain the different microbial distribution between top-and clay-layer soils.These findings provided new insights into the candidate mechanisms of microbial diversity maintenance and community patterning of sandy soils,which were necessary for better understanding of ecological rules guiding long-term agricultural practice.
基金The Research is supported by NSFC(Grant Nos.11771224,11301462),Jiangsu Province Qing Lan Project and Jiangsu Overseas Research Program for University Prominent Teachers to Shan Jiang.We would like to thank Professor Yalchin Efendiev in Texas A&M University for many useful discussions.And we appreciate the referees and editors for their insightful comments and helpful suggestions.
文摘In this paper,we combine the generalized multiscale finite element method(GMsFEM)with the balanced truncation(BT)method to address a parameterdependent elliptic problem.Basically,in progress of a model reduction we try to obtain accurate solutions with less computational resources.It is realized via a spectral decomposition from the dominant eigenvalues,that is used for an enrichment of multiscale basis functions in the GMsFEM.The multiscale bases computations are localized to specified coarse neighborhoods,and follow an offline-online process in which eigenvalue problems are used to capture the underlying system behaviors.In the BT on reduced scales,we present a local-global strategy where it requires the observability and controllability of solutions to a set of Lyapunov equations.As the Lyapunov equations need expensive computations,the efficiency of our combined approach is shown to be readily flexible with respect to the online space and an reduced dimension.Numerical experiments are provided to validate the robustness of our approach for the parameter-dependent elliptic model.
