The extensive use of diesel engines has led to significant emissions of pollutants,especially soot particles,which pose serious risks to both the environment and human health.At present,developing catalysts with low–...The extensive use of diesel engines has led to significant emissions of pollutants,especially soot particles,which pose serious risks to both the environment and human health.At present,developing catalysts with low–temperature activity,low cost,and high stability remains the core challenge in eliminating soot from diesel engine exhaust.This paper first reviews the mechanisms of soot catalytic oxidation.Based on these mechanisms,the current design directions for soot catalysts are summarized and discussed.On the one hand,the effects of modification methods such as doping,loading,and solid solution on the performance of manganese-based catalysts are reviewed from the perspective of intrinsic activity.On the other hand,the research progress on manganese-based catalysts with specific morphological structures for soot oxidation is explored.Following the identification of design strategies,the commonly used preparation methods to achieve these designs are also outlined.Finally,the paper highlights the challenges associated with manganese-based catalysts in soot catalysis and discusses future research and development directions.展开更多
This paper presents Part II of a review on DFACS,which specifically focuses on the modeling and analysis of disturbances and noises in DFACSs.In Part I,the system composition and dynamics model of the DFACS were prese...This paper presents Part II of a review on DFACS,which specifically focuses on the modeling and analysis of disturbances and noises in DFACSs.In Part I,the system composition and dynamics model of the DFACS were presented.In this paper,we discuss the effects of disturbance forces and noises on the system,and summarize various analysis and modeling methods for these interferences,including the integral method,frequency domain analysis method,and magnitude evaluation method.By analyzing the impact of disturbances and noises on the system,the paper also summarizes the system’s performance under slight interferences.Additionally,we highlight current research difficulties in the field of DFACS noise analysis.Overall,this paper provides valuable insights into the modeling and analysis of disturbances and noises in DFACSs,and identifies key areas for future research.展开更多
The Drag-Free and Attitude Control System(DFACS)is a critical platform for various space missions,including high precision satellite navigation,geoscience and gravity field measurement,and space scientific experiments...The Drag-Free and Attitude Control System(DFACS)is a critical platform for various space missions,including high precision satellite navigation,geoscience and gravity field measurement,and space scientific experiments.This paper presents a comprehensive review of over sixty years of research on the design and dynamics model of DFACS.Firstly,we examine the open literature on DFACS and its applications in Drag-Free missions,providing readers with necessary background information on the field.Secondly,we analyze the system configurations and main characteristics of different DFACSs,paying particular attention to the coupling mechanism between the system configuration and dynamics model.Thirdly,we summarize the dynamics modeling methods and main dynamics models of DFACS from multiple perspectives,including common fundamentals and specific applications.Lastly,we identify current challenges and technological difficulties in the system design and dynamics modeling of DFACS,while suggesting potential avenues for future research.This paper aims to provide readers with a comprehensive understanding of the state-of-the-art in DFACS research,as well as the future prospects and challenges in this field.展开更多
The pursuit of high-performance is worth considerable effort in catalysis for energy efficiency and environmental sustainability. To develop redox catalysts with superior performance for soot combustion, a series of M...The pursuit of high-performance is worth considerable effort in catalysis for energy efficiency and environmental sustainability. To develop redox catalysts with superior performance for soot combustion, a series of Mn_(x)Co_(y) oxides were synthesized using MgO template substitution.This method greatly improves the preparation and catalytic efficiency and is more in line with the current theme of green catalysts and sustainable development. The resulting Mn_(1)Co_(2.3) has a strong activation capability of gaseous oxygen due to a high concentration of Co^(3+) and Mn^(3+). The Mn doping enhanced the intrinsic activity by prompting oxygen vacancy formation and gaseous oxygen adsorption. The nanosheet morphology with abundant mesoporous significantly increased the solid–solid contact efficiency and improved the adsorption capability of gaseous reactants. The novel design of Mn_(1)Co_(2.3)oxide enhanced its catalytic performance through a synergistic effect of Mn doping and the porous nanosheet morphology, showing significant potential for the preparation of high-performance soot combustion catalysts.展开更多
The widespread use of diesel engines results in significant environmental contamination due to emitted pollutants,particularly soot particles.These pollut-ants are detrimental to public health.At present,one of the mo...The widespread use of diesel engines results in significant environmental contamination due to emitted pollutants,particularly soot particles.These pollut-ants are detrimental to public health.At present,one of the most effective ways to remove soot particles is the catalytic diesel particulate filter after-treatment tech-nology,which requires the catalyst to have superior low temperature activity.Compared with cerium oxide which is widely used,cobalt oxide in transition metal oxides has been widely studied in recent years because of its high redox ability and easy to control morphology.This paper elaborates on the influence of modification techniques such as doping,loading,and solid solution on the catalytic performance of cobalt-based catalysts in soot oxidation.Along the same lines,it further reviews the research progress on cobalt-based oxide catalysts with specific dimensional structures and morphologies in soot oxidation.Finally,it provides an outlook on the challenges faced by the theoretical basis and applied research of cobalt-based catalysts in soot oxidation.展开更多
Parthenogenetic embryonic stem （pES） cells provide a valuable in vitro model system for studying the molecular mechanisms that underlie genomic imprinting. However, the pluripotency of pES cells and the expression p...Parthenogenetic embryonic stem （pES） cells provide a valuable in vitro model system for studying the molecular mechanisms that underlie genomic imprinting. However, the pluripotency of pES cells and the expression profiles of paternally expressed imprinted genes have not been fully explored. In this study, three mouse pES cell lines were established and the differentiation potential of these cells in extended culture was evaluated. The undifferentiated cells had a normal karyotype and homozygous genome, and expressed ES-cell-specific molecular markers. The cells remained undifferentiated after more than 50 passages and exhibited pluripotent differentiation capacity. All three lines of the established ES cells produced teratomas; two lines of ES cells produced chimeras and germline transmission. Furthermore, activation of the paternally expressed imprinted genes Snrpn, U2afl-rsl, Peg3, Impact, Zfp127, Dlkl and Mest in these cells was detected. Some paternally expressed imprinted genes were found to be expressed in the blastocyst stage of parthenogenetically activated embryos in vitro and their expression level increased with extended pES cell culture. Furthermore, our data show that the activation of these paternally expressed imprinted genes in pES cells was associated with a change in the methylation of the related differentially methylated regions. These findings provide direct evidence for the pluripotency of pES cells and demonstrate the association between the DNA methylation pattern and the activa- tion of paternally expressed imprinted genes in pES cells. Thus, the established ES cell lines provide a valuable model for studying epigenetic regulation in mammalian development.展开更多
A mapping function between the Reynolds-averaged Navier-Stokes mean flow variables and transition intermittency factor is constructed by fully connected artificial neural network(ANN),which replaces the governing equa...A mapping function between the Reynolds-averaged Navier-Stokes mean flow variables and transition intermittency factor is constructed by fully connected artificial neural network(ANN),which replaces the governing equation of the intermittency factor in transition-predictive Spalart-Allmaras(SA)-γmodel.By taking SA-γmodel as the benchmark,the present ANN model is trained at two airfoils with various angles of attack,Mach numbers and Reynolds numbers,and tested with unseen airfoils in different flow states.The a posteriori tests manifest that the mean pressure coefficient,skin friction coefficient,size of laminar separation bubble,mean streamwise velocity,Reynolds shear stress and lift/drag/moment coefficient from the present two-way coupling ANN model almost coincide with those from the benchmark SA-γmodel.Furthermore,the ANN model proves to exhibit a higher calculation efficiency and better convergence quality than traditional SA-γmodel.展开更多
Hot deformation behavior of an Fe-20Mn-19Cr-0.5C-0.6N high-nitrogen austenitic steel has been studied by isothermal compression tests in deformation temperature range of 800-1200℃ and strain rate range of 0.01-10 s^-...Hot deformation behavior of an Fe-20Mn-19Cr-0.5C-0.6N high-nitrogen austenitic steel has been studied by isothermal compression tests in deformation temperature range of 800-1200℃ and strain rate range of 0.01-10 s^-1. Results indicate that the Fe-20Mn-19Cr-0.5C-0.6N steel has high deformation resistance due to strong hindering effect on dislocation moving by nitrogen-induced lattice misfit. The twinning-induced plasticity effect is gradually suppressed with the increase in deformation temperature, and high-temperature plastic deformation mechanism by twinning is gradually replaced by dislocation planar slip. The deformation resistance is up to 343 MPa at deformation conditions of (1000 ℃, 0.01 s^-1), which is over 100 MPa higher than that in martensitic steel and 50 MPa higher than that in austenitic steel. Besides, value of deformation activation energy for the Fe-20Mn-19Cr-0.6N steel is up to 784 kJ mol^-1. Power dissipation efficiency is lower than 0.13, while hot processing map exhibits a very wide range of working area. The optimum hot working process obtains at deformation temperature range of 950-1200℃ and strain rate range of 0.01-10 s^-1, when deformation acti-vation energy is less than 662.6 kJ mol^-1, power dissipation efficiency exceeds 0.22, dynamic recrystallization fraction is over 46.1% and microstructures are without instable characteristics.展开更多
Zhigancao decoction is a traditional prescription for treating irregular pulse and palpitations in China.As the monarch drug of Zhigancao decoction,the bioactive molecules of licorice against heart diseases remain elu...Zhigancao decoction is a traditional prescription for treating irregular pulse and palpitations in China.As the monarch drug of Zhigancao decoction,the bioactive molecules of licorice against heart diseases remain elusive.We established the HRESIMS-guided method leading to the isolation of three novel bicyclic peptides,glycnsisitins A-C(1-3),with distinctive C-C and C-O-C side-chain-toside-chain linkages from the roots of Glycyrrhiza uralensis(Licorice).Glycnsisitin A demonstrated stronger cardioprotective activity than glycnsisitins B and C in an in vitro model of doxorubicin(DOX)-induced cardiomyocyte injury.Glycnsisitin A treatment not only reduced the mortality of heart failure(HF)mice in a dose-dependent manner but also significantly attenuated DOX-induced cardiac dysfunction and myocardial fibrosis.Gene set enrichment analysis(GSEA)of the differentially expressed genes indicated that the cardioprotective effect of glycnsisitin A was mainly attributed to its ability to maintain iron homeostasis in the myocardium.Mechanistically,glycnsisitin A interacted with transferrin and facilitated its binding to the transferrin receptor(TFRC),which caused increased uptake of iron in cardiomyocytes.These findings highlight the key role of bicyclic peptides as bioactive molecules of Zhigancao decoction for the treatment of HF,and glycnsisitin A constitutes a promising therapeutic agent for the treatment of HF.展开更多
Nuclear receptor corepressor(NCoR1)interacts with various nuclear receptors and regulates the anabolism and catabolism of lipids.An imbalance in lipid/energy homeostasis is also an important factor in obesity and meta...Nuclear receptor corepressor(NCoR1)interacts with various nuclear receptors and regulates the anabolism and catabolism of lipids.An imbalance in lipid/energy homeostasis is also an important factor in obesity and metabolic syndrome development.In this study,we found that the deletion of NCoR1 in intestinal epithelial cells(IECs)mainly activated the nuclear receptor PPARa and attenuated metabolic syndrome by stimulating thermogenesis.The increase in brown adipose tissue thermogenesis was mediated by gut-derived tricarboxylic acid cycle intermediate succinate,whose production was significantly enhanced by PPARa activation in the fed state.Additionally,NCoR1 deletion derepressed intestinal LXR,increased cholesterol excretion,and impaired duodenal lipid absorption by decreasing bile acid hydrophobicity,thereby reversing the possible negative effects of intestinal PPARa activation.Therefore,the simultaneous regulatory effect of intestinal NCoR1 on both lipid intake and energy expenditure strongly suggests that it is a promising target for developing metabolic syndrome treatment.展开更多
Protein kinase Cα(PKCα)regulates diverse biological functions of cancer cells and is a promising therapeutic target.However,clinical trials of PKC-targeted therapies have not yielded satisfactory results.Recent stud...Protein kinase Cα(PKCα)regulates diverse biological functions of cancer cells and is a promising therapeutic target.However,clinical trials of PKC-targeted therapies have not yielded satisfactory results.Recent studies have also indicated a tumor-suppressive role of PKCs via unclear molecular mechanisms.In this study,we found that PKCαinhibition enhances CD8+T-cell-mediated tumor evasion and abolishes antitumor activity in immunocompetent mice.We further identified PKCαas a critical regulator of programmed cell death-ligand 1(PD-L1)and found that it enhances T-cell-dependent antitumor immunity in breast cancer by interacting with PD-L1 and suppressing PD-L1 expression.We demonstrated that PKCα-mediated PD-L1 phosphorylation promotes PD-L1 degradation throughβtransducin repeat-containing protein.Notably,the efficacy of PKCαinhibitors was intensified by synergizing with anti-PD-L1 mAb therapy to boost antitumor T-cell immunity in vivo.Clinical analysis revealed that PKCαexpression is positively correlated with T-cell function and the interferon-gamma signature in patients with breast cancer.This study demonstrated the antitumor capability of PKCα,identified potential therapeutic strategies to avoid tumor evasion via PKC-targeted therapies,and provided a proof of concept for targeting PKCαin combination with anti-PD-L1 mAb therapy as a potential therapeutic approach against breast cancer,especially TNBC.展开更多
Vitamin D_3 has been found to produce therapeutic effects on obesity-associated insulin resistance and dyslipidemia through its potent anti-inflammatory activity, but the precise immunomodulatory mechanism remains poo...Vitamin D_3 has been found to produce therapeutic effects on obesity-associated insulin resistance and dyslipidemia through its potent anti-inflammatory activity, but the precise immunomodulatory mechanism remains poorly understood. In the present study we found that 1,25-dihydroxyvitamin D_3[1,25(OH)_2D_3], the biologically active form of vitamin D_3, significantly attenuated monosodium glutamate(MSG)-induced obesity and insulin resistance as indicated by body weight reduction, oral glucose tolerance improvement, and a glucose infusion rate increase as detected with hyperinsulinemiceuglycemic clamp. Moreover, 1,25(OH)_2D_3 not only restored pancreatic islet functions but also improved lipid metabolism in insulin-targeted tissues. The protective effects of 1,25(OH)_2D_3 on glycolipid metabolism were attributed to its ability to inhibit an obesity-activated inflammatory response in insulin secretory and targeted tissues, as indicated by reduced infiltration of macrophages in pancreas islets and adipose tissue while enhancing the expression of Tgf-β1 in liver tissue, which was accompanied byincreased infiltration of Treg cells in immune organs such as spleen and lymph node as well as in insulintargeted tissues such as liver, adipose, and muscle. Together, our findings suggest that 1,25(OH)_2D_3 serves as a beneficial immunomodulator for the prevention and treatment of obesity or metabolic syndrome through its anti-inflammatory effects.展开更多
The cell cycle inhibitor P21 has been implicated in cell senescence and plays an important role in the injury-repair process following lung injury.Pulmonary fibrosis(PF)is a fibrotic lung disorder characterized by cel...The cell cycle inhibitor P21 has been implicated in cell senescence and plays an important role in the injury-repair process following lung injury.Pulmonary fibrosis(PF)is a fibrotic lung disorder characterized by cell senescence in lung alveolar epithelial cells.In this study,we report that P21 expression was increased in alveolar epithelial type 2 cells(AEC2 s)in a time-dependent manner following multiple bleomycin-induced PF.Repeated injury of AEC2 s resulted in telomere shortening and triggered P21-dependent cell senescence.AEC2 s with elevated expression of P21 lost their self-renewal and differentiation abilities.In particular,elevated P21 not only induced cell cycle arrest in AEC2 s but also bound to P300 andβ-catenin and inhibited AEC2 differentiation by disturbing the P300-β-catenin interaction.Meanwhile,senescent AEC2 s triggered myofibroblast activation by releasing profibrotic cytokines.Knockdown of P21 restored AEC2-mediated lung alveolar regeneration in mice with chronic PF.The results of our study reveal a mechanism of P21-mediated lung regeneration failure during PF development,which suggests a potential strategy for the treatment of fibrotic lung diseases.展开更多
Abdominal aortic aneurysm (AAA) is an inflammatory vascular disorder with high mortality. Accumulating evidence shows that toll-like receptor 2 (TLR2) plays a critical role in the regulation of wound-repairing process...Abdominal aortic aneurysm (AAA) is an inflammatory vascular disorder with high mortality. Accumulating evidence shows that toll-like receptor 2 (TLR2) plays a critical role in the regulation of wound-repairing process after tissue injury. We wondered if TLR2 signaling contributed to the pathogenesis of AAA and that targeting TLR2 would attenuate AAA development and progression. In this study, enhanced expression of TLR2 and its ligands were observed in human AAA tissue. Neutralization of TLR2 protected against AAA development and caused established AAA to regress in mouse models of AAA. In addition, TLR2-deficient mice also failed to develop AAA. The prophylactic and therapeutic effects of blocking TLR2 were accompanied by a significant resolution of inflammation and vascular remodeling, as indicated by the decreased expression or activity of MMP-2/9, alpha-SMA, inflammatory cytokines, and transcription factors NF-kappa B, AP-1 and STAT1/3 in AAA tissue. Mechanistically, blocking TLR2 decreased the expression and interaction of TLR2 and several endogenous ligands, which diminished chronic inflammation and vascular remodeling in the vascular tissue of AAA. Our studies indicate that the interactions between TLR2 and its endogenous ligands contribute to the pathogenesis of AAA and that targeting TLR2 offers great potential toward the development of therapeutic agents against AAA. (C) 2015 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.展开更多
Pulmonary fibrosis(PF)is a chronic,progressive,fatal interstitial lung disease with limited available therapeutic strategies.We recently reported that the protein kinase glycogen synthase kinase-3β(GSK-3β)interacts ...Pulmonary fibrosis(PF)is a chronic,progressive,fatal interstitial lung disease with limited available therapeutic strategies.We recently reported that the protein kinase glycogen synthase kinase-3β(GSK-3β)interacts with and inactivates the ubiquitin-editing enzyme A20 to suppress the degradation of the transcription factor CCAAT/enhancer-binding protein beta(C/EBPβ)in alveolar macrophages(AMs),resulting in a profibrotic phenotype of AMs and promoting the development of PF.Here,we showed that chronic lung injury upregulated the stress response protein tribbles homolog 3(TRIB3),which interacted with GSK-3βand stabilized GSK-3βfrom ubiquitination and degradation.Elevated GSK-3βexpression phosphorylated A20 to inhibit its ubiquitin-editing activity,causing the accumulation of C/EBPβand the production of several profibrotic factors in AMs and promoting PF development.Activated C/EBPβ,in turn,increased the transcription of TRIB3 and GSK-3β,thereby establishing a positive feedback loop in AMs.The knockdown of TRIB3 expression or the pharmacologic disruption of the TRIB3-GSK-3βinteraction was an effective PF treatment.Our study reveals an intact profibrotic axis of TRIB3-GSK-3β-A20-C/EBPβin AMs,which represents a target that may provide a promising treatment strategy for PF.展开更多
The Tribbles(TRIB) family of pseudokinase proteins has been shown to play key roles in cell cycle, metabolic diseases, chronic inflammatory disease, and cancer development. A better understanding of the mechanisms of ...The Tribbles(TRIB) family of pseudokinase proteins has been shown to play key roles in cell cycle, metabolic diseases, chronic inflammatory disease, and cancer development. A better understanding of the mechanisms of TRIB pseudokinases could provide new insights for disease development and help promote TRIB proteins as novel therapeutic targets for drug discovery. At the 2 nd International Symposium on Tribbles and Diseases held on May 7–9, 2018 in Beijing, China, a group of leading Tribbles scientists reported their findings and ongoing studies about the effects of the different TRIB proteins in the areas of immunity, metabolism, fundamental cell biology and cancer. Here, we summarize important and insightful overviews from 4 keynote lectures, 13 plenary lectures and 8 short talks that took place during this meeting. These findings may offer new insights for the understanding of the roles of TRIB pseudokinases in the development of various diseases.展开更多
Immune cells play key roles in cancer and chronic inflammatory disease. A better understanding of the mechanisms and risks will help develop novel target therapies. At the 2017 International Workshop of the Chinese Ac...Immune cells play key roles in cancer and chronic inflammatory disease. A better understanding of the mechanisms and risks will help develop novel target therapies. At the 2017 International Workshop of the Chinese Academy of Medical Sciences Initiative for Innovative Medicine on Tumor Immunology held in Beijing, China, on May 12, 2017, a number of speakers reported new findings and ongoing studies on immune-related diseases such as cancer, fibrotic disease, diabetes, and others. A considerably insightful overview was provided on cancer immunity, tumor microenvironments,and new immunotherapy for cancer. In addition, chronic inflammatory diseases were discussed. These findings may offer new insights into targeted immunotherapy.展开更多
Pulmonary fibrosis(PF)is the pathological structure of incurable fibroproliferative lung diseases that are attributed to the repeated lung injury-caused failure of lung alveolar regeneration(LAR).Here,we report that r...Pulmonary fibrosis(PF)is the pathological structure of incurable fibroproliferative lung diseases that are attributed to the repeated lung injury-caused failure of lung alveolar regeneration(LAR).Here,we report that repetitive lung damage results in a progressive accumulation of the transcriptional repressor SLUG in alveolar epithelial type II cells(AEC2s).The abnormal increased SLUG inhibits AEC2s from self-renewal and differentiation into alveolar epithelial type I cells(AEC1s).We found that the elevated SLUG represses the expression of the phosphate transporter SLC34A2 in AEC2s,which reduces intracellular phosphate and represses the phosphorylation of JNK and P38 MAPK,two critical kinases supporting LAR,leading to LAR failure.TRIB3,a stress sensor,interacts with the E3 ligase MDM2 to suppress SLUG degradation in AEC2s by impeding MDM2-catalyzed SLUG ubiquitination.Targeting SLUG degradation by disturbing the TRIB3/MDM2 interaction using a new synthetic staple peptide restores LAR capacity and exhibits potent therapeutic efficacy against experimental PF.Our study reveals a mechanism of the TRIB3—MDM2—SLUG—SLC34A2 axis causing the LAR failure in PF,which confers a potential strategy for treating patients with fibroproliferative lung diseases.展开更多
基金sponsored by the National Natural Science Foundation of China(Grant 22406050)the Top-Notch Personnel Fund of Henan Agricultural University(Grant 30501029)+2 种基金the Natural Science Foundation of Henan Province(Grant 232300420293)the Science and Technology Project of China Tobacco Shaanxi Industrial Co.,Ltd.(Grant BA000-ZB24010)the Postgraduate Education Reform and Quality Improvement Project of Henan Province(Grant YJS2024JD17).
文摘The extensive use of diesel engines has led to significant emissions of pollutants,especially soot particles,which pose serious risks to both the environment and human health.At present,developing catalysts with low–temperature activity,low cost,and high stability remains the core challenge in eliminating soot from diesel engine exhaust.This paper first reviews the mechanisms of soot catalytic oxidation.Based on these mechanisms,the current design directions for soot catalysts are summarized and discussed.On the one hand,the effects of modification methods such as doping,loading,and solid solution on the performance of manganese-based catalysts are reviewed from the perspective of intrinsic activity.On the other hand,the research progress on manganese-based catalysts with specific morphological structures for soot oxidation is explored.Following the identification of design strategies,the commonly used preparation methods to achieve these designs are also outlined.Finally,the paper highlights the challenges associated with manganese-based catalysts in soot catalysis and discusses future research and development directions.
基金This research was supported by National Key R&D Program of China:Gravitational Wave Detection Project(Nos.2021YFC2202601,2021YFC2202603)National Natural Science Foundation of China(No.12172288).
文摘This paper presents Part II of a review on DFACS,which specifically focuses on the modeling and analysis of disturbances and noises in DFACSs.In Part I,the system composition and dynamics model of the DFACS were presented.In this paper,we discuss the effects of disturbance forces and noises on the system,and summarize various analysis and modeling methods for these interferences,including the integral method,frequency domain analysis method,and magnitude evaluation method.By analyzing the impact of disturbances and noises on the system,the paper also summarizes the system’s performance under slight interferences.Additionally,we highlight current research difficulties in the field of DFACS noise analysis.Overall,this paper provides valuable insights into the modeling and analysis of disturbances and noises in DFACSs,and identifies key areas for future research.
基金This research was supported by National Key R&D Program of China:Gravitational Wave Detection Project,China(Nos.2021YFC2202601,2021YFC2202603)National Natural Science Foundation of China(No.12172288).
文摘The Drag-Free and Attitude Control System(DFACS)is a critical platform for various space missions,including high precision satellite navigation,geoscience and gravity field measurement,and space scientific experiments.This paper presents a comprehensive review of over sixty years of research on the design and dynamics model of DFACS.Firstly,we examine the open literature on DFACS and its applications in Drag-Free missions,providing readers with necessary background information on the field.Secondly,we analyze the system configurations and main characteristics of different DFACSs,paying particular attention to the coupling mechanism between the system configuration and dynamics model.Thirdly,we summarize the dynamics modeling methods and main dynamics models of DFACS from multiple perspectives,including common fundamentals and specific applications.Lastly,we identify current challenges and technological difficulties in the system design and dynamics modeling of DFACS,while suggesting potential avenues for future research.This paper aims to provide readers with a comprehensive understanding of the state-of-the-art in DFACS research,as well as the future prospects and challenges in this field.
基金supported by the top talent program of Henan Agricultural University[grant numbers 30501029].
文摘The pursuit of high-performance is worth considerable effort in catalysis for energy efficiency and environmental sustainability. To develop redox catalysts with superior performance for soot combustion, a series of Mn_(x)Co_(y) oxides were synthesized using MgO template substitution.This method greatly improves the preparation and catalytic efficiency and is more in line with the current theme of green catalysts and sustainable development. The resulting Mn_(1)Co_(2.3) has a strong activation capability of gaseous oxygen due to a high concentration of Co^(3+) and Mn^(3+). The Mn doping enhanced the intrinsic activity by prompting oxygen vacancy formation and gaseous oxygen adsorption. The nanosheet morphology with abundant mesoporous significantly increased the solid–solid contact efficiency and improved the adsorption capability of gaseous reactants. The novel design of Mn_(1)Co_(2.3)oxide enhanced its catalytic performance through a synergistic effect of Mn doping and the porous nanosheet morphology, showing significant potential for the preparation of high-performance soot combustion catalysts.
基金National Natural Science Foundation of China,Grant/Award Number:22406050Top-Notch Personnel Fund of Henan Agricultural University,Grant/Award Number:30501029+2 种基金Natural Science Foundation of Henan Province,Grant/Award Number:232300420293Science and Technology Project of China Tobacco Shaanxi Industrial Co.,Ltd,Grant/Award Number:2024610000340104Postgraduate Education Reform and Quality Improvement Project of Henan Province,Grant/Award Number:YJS2024JD17。
文摘The widespread use of diesel engines results in significant environmental contamination due to emitted pollutants,particularly soot particles.These pollut-ants are detrimental to public health.At present,one of the most effective ways to remove soot particles is the catalytic diesel particulate filter after-treatment tech-nology,which requires the catalyst to have superior low temperature activity.Compared with cerium oxide which is widely used,cobalt oxide in transition metal oxides has been widely studied in recent years because of its high redox ability and easy to control morphology.This paper elaborates on the influence of modification techniques such as doping,loading,and solid solution on the catalytic performance of cobalt-based catalysts in soot oxidation.Along the same lines,it further reviews the research progress on cobalt-based oxide catalysts with specific dimensional structures and morphologies in soot oxidation.Finally,it provides an outlook on the challenges faced by the theoretical basis and applied research of cobalt-based catalysts in soot oxidation.
文摘Parthenogenetic embryonic stem （pES） cells provide a valuable in vitro model system for studying the molecular mechanisms that underlie genomic imprinting. However, the pluripotency of pES cells and the expression profiles of paternally expressed imprinted genes have not been fully explored. In this study, three mouse pES cell lines were established and the differentiation potential of these cells in extended culture was evaluated. The undifferentiated cells had a normal karyotype and homozygous genome, and expressed ES-cell-specific molecular markers. The cells remained undifferentiated after more than 50 passages and exhibited pluripotent differentiation capacity. All three lines of the established ES cells produced teratomas; two lines of ES cells produced chimeras and germline transmission. Furthermore, activation of the paternally expressed imprinted genes Snrpn, U2afl-rsl, Peg3, Impact, Zfp127, Dlkl and Mest in these cells was detected. Some paternally expressed imprinted genes were found to be expressed in the blastocyst stage of parthenogenetically activated embryos in vitro and their expression level increased with extended pES cell culture. Furthermore, our data show that the activation of these paternally expressed imprinted genes in pES cells was associated with a change in the methylation of the related differentially methylated regions. These findings provide direct evidence for the pluripotency of pES cells and demonstrate the association between the DNA methylation pattern and the activa- tion of paternally expressed imprinted genes in pES cells. Thus, the established ES cell lines provide a valuable model for studying epigenetic regulation in mammalian development.
基金the financial supports provided by the National Natural Science Foundation of China(Nos.91852112 and 11988102)。
文摘A mapping function between the Reynolds-averaged Navier-Stokes mean flow variables and transition intermittency factor is constructed by fully connected artificial neural network(ANN),which replaces the governing equation of the intermittency factor in transition-predictive Spalart-Allmaras(SA)-γmodel.By taking SA-γmodel as the benchmark,the present ANN model is trained at two airfoils with various angles of attack,Mach numbers and Reynolds numbers,and tested with unseen airfoils in different flow states.The a posteriori tests manifest that the mean pressure coefficient,skin friction coefficient,size of laminar separation bubble,mean streamwise velocity,Reynolds shear stress and lift/drag/moment coefficient from the present two-way coupling ANN model almost coincide with those from the benchmark SA-γmodel.Furthermore,the ANN model proves to exhibit a higher calculation efficiency and better convergence quality than traditional SA-γmodel.
基金This work was financially supported by the National Natural Science Foundation of China (NSFC) under project No. 51301042The authors would like to thank Dr. Nan Li of Central Iron and Steel Research Institute (CISRI) for the help of isothermal compression tests.
文摘Hot deformation behavior of an Fe-20Mn-19Cr-0.5C-0.6N high-nitrogen austenitic steel has been studied by isothermal compression tests in deformation temperature range of 800-1200℃ and strain rate range of 0.01-10 s^-1. Results indicate that the Fe-20Mn-19Cr-0.5C-0.6N steel has high deformation resistance due to strong hindering effect on dislocation moving by nitrogen-induced lattice misfit. The twinning-induced plasticity effect is gradually suppressed with the increase in deformation temperature, and high-temperature plastic deformation mechanism by twinning is gradually replaced by dislocation planar slip. The deformation resistance is up to 343 MPa at deformation conditions of (1000 ℃, 0.01 s^-1), which is over 100 MPa higher than that in martensitic steel and 50 MPa higher than that in austenitic steel. Besides, value of deformation activation energy for the Fe-20Mn-19Cr-0.6N steel is up to 784 kJ mol^-1. Power dissipation efficiency is lower than 0.13, while hot processing map exhibits a very wide range of working area. The optimum hot working process obtains at deformation temperature range of 950-1200℃ and strain rate range of 0.01-10 s^-1, when deformation acti-vation energy is less than 662.6 kJ mol^-1, power dissipation efficiency exceeds 0.22, dynamic recrystallization fraction is over 46.1% and microstructures are without instable characteristics.
基金supported by Chinese Academy of Medical Sciences(CAMS)Innovation Fund for Medical Sciences(2022-I2M-2-002,2021-I2M-1-016,and 2022-I2M-1-014,China)the Beijing Outstanding Young Scientist Program(BJJWZYJH01201910023028,China)Chinese Academy of Medical Sciences(CAMS)Central Public-interest Scientific Institution Basal Research Fund(2018PT35004,Molecular Mechanism and Target Discovery of Metabolic Disorder and Tumorigenesis,CAMS Key Laboratory).
文摘Zhigancao decoction is a traditional prescription for treating irregular pulse and palpitations in China.As the monarch drug of Zhigancao decoction,the bioactive molecules of licorice against heart diseases remain elusive.We established the HRESIMS-guided method leading to the isolation of three novel bicyclic peptides,glycnsisitins A-C(1-3),with distinctive C-C and C-O-C side-chain-toside-chain linkages from the roots of Glycyrrhiza uralensis(Licorice).Glycnsisitin A demonstrated stronger cardioprotective activity than glycnsisitins B and C in an in vitro model of doxorubicin(DOX)-induced cardiomyocyte injury.Glycnsisitin A treatment not only reduced the mortality of heart failure(HF)mice in a dose-dependent manner but also significantly attenuated DOX-induced cardiac dysfunction and myocardial fibrosis.Gene set enrichment analysis(GSEA)of the differentially expressed genes indicated that the cardioprotective effect of glycnsisitin A was mainly attributed to its ability to maintain iron homeostasis in the myocardium.Mechanistically,glycnsisitin A interacted with transferrin and facilitated its binding to the transferrin receptor(TFRC),which caused increased uptake of iron in cardiomyocytes.These findings highlight the key role of bicyclic peptides as bioactive molecules of Zhigancao decoction for the treatment of HF,and glycnsisitin A constitutes a promising therapeutic agent for the treatment of HF.
基金supported by grants from the Chinese Academy of Medical Sciences(CAMS)Innovation Fund for Medical Sciences(2021-I2M-1-016,2016-I2M-1-011,2016-I2M-3-008 and 2017-I2M-1-008,China)the Special Research Fund for Central Universities,Peking Union Medical College(3332022047,China)+4 种基金the Beijing Outstanding Young Scientist Program(BJJWZYJH01201910023028,China)the National Natural Science Foundation of China(81703588,82473984,81622010,81770800,and 81874316)the CAMS Central Public-interest Scientific Institution Basal Research Fund(2017RC31009 and 2018PT35004,China)the Drug Innovation Major Project from the National Science and Technology Department(2018ZX09711001-003-005 and 2018ZX09711001-003-001,China)the National Key R&D Program of China(2017YFA0205400 and 2022YFC2505204,China).
文摘Nuclear receptor corepressor(NCoR1)interacts with various nuclear receptors and regulates the anabolism and catabolism of lipids.An imbalance in lipid/energy homeostasis is also an important factor in obesity and metabolic syndrome development.In this study,we found that the deletion of NCoR1 in intestinal epithelial cells(IECs)mainly activated the nuclear receptor PPARa and attenuated metabolic syndrome by stimulating thermogenesis.The increase in brown adipose tissue thermogenesis was mediated by gut-derived tricarboxylic acid cycle intermediate succinate,whose production was significantly enhanced by PPARa activation in the fed state.Additionally,NCoR1 deletion derepressed intestinal LXR,increased cholesterol excretion,and impaired duodenal lipid absorption by decreasing bile acid hydrophobicity,thereby reversing the possible negative effects of intestinal PPARa activation.Therefore,the simultaneous regulatory effect of intestinal NCoR1 on both lipid intake and energy expenditure strongly suggests that it is a promising target for developing metabolic syndrome treatment.
基金supported by grants from the National Natural Science Foundation of China(82173853,82173379,82373914,82073892)Chinese Academy of Medical Sciences(CAMS)Innovation Fund for Medical Sciences(2022-I2M-2-002,2021-I2M-1e026 and 2021-I2M-1e016,China)+2 种基金CAMS Central Public-interest Scientific Institution Basal Research Fund(2018PT35004,China)Beijing Outstanding Young Scientist Program(BJJWZYJH01201910023028,China)Peking Union Medical College Graduate Innovation Fund(2019-1007-05,China).
文摘Protein kinase Cα(PKCα)regulates diverse biological functions of cancer cells and is a promising therapeutic target.However,clinical trials of PKC-targeted therapies have not yielded satisfactory results.Recent studies have also indicated a tumor-suppressive role of PKCs via unclear molecular mechanisms.In this study,we found that PKCαinhibition enhances CD8+T-cell-mediated tumor evasion and abolishes antitumor activity in immunocompetent mice.We further identified PKCαas a critical regulator of programmed cell death-ligand 1(PD-L1)and found that it enhances T-cell-dependent antitumor immunity in breast cancer by interacting with PD-L1 and suppressing PD-L1 expression.We demonstrated that PKCα-mediated PD-L1 phosphorylation promotes PD-L1 degradation throughβtransducin repeat-containing protein.Notably,the efficacy of PKCαinhibitors was intensified by synergizing with anti-PD-L1 mAb therapy to boost antitumor T-cell immunity in vivo.Clinical analysis revealed that PKCαexpression is positively correlated with T-cell function and the interferon-gamma signature in patients with breast cancer.This study demonstrated the antitumor capability of PKCα,identified potential therapeutic strategies to avoid tumor evasion via PKC-targeted therapies,and provided a proof of concept for targeting PKCαin combination with anti-PD-L1 mAb therapy as a potential therapeutic approach against breast cancer,especially TNBC.
基金supported by grants from the National Natural Science Foundation of China (81773800 and 81471070)the CAMS Innovation Fund for Medical Sciences (CIFMS, 2016I2M-1-010 to Xiao-wei Zhang and 2016-I2M-1-012 to Wen Jin)
文摘Vitamin D_3 has been found to produce therapeutic effects on obesity-associated insulin resistance and dyslipidemia through its potent anti-inflammatory activity, but the precise immunomodulatory mechanism remains poorly understood. In the present study we found that 1,25-dihydroxyvitamin D_3[1,25(OH)_2D_3], the biologically active form of vitamin D_3, significantly attenuated monosodium glutamate(MSG)-induced obesity and insulin resistance as indicated by body weight reduction, oral glucose tolerance improvement, and a glucose infusion rate increase as detected with hyperinsulinemiceuglycemic clamp. Moreover, 1,25(OH)_2D_3 not only restored pancreatic islet functions but also improved lipid metabolism in insulin-targeted tissues. The protective effects of 1,25(OH)_2D_3 on glycolipid metabolism were attributed to its ability to inhibit an obesity-activated inflammatory response in insulin secretory and targeted tissues, as indicated by reduced infiltration of macrophages in pancreas islets and adipose tissue while enhancing the expression of Tgf-β1 in liver tissue, which was accompanied byincreased infiltration of Treg cells in immune organs such as spleen and lymph node as well as in insulintargeted tissues such as liver, adipose, and muscle. Together, our findings suggest that 1,25(OH)_2D_3 serves as a beneficial immunomodulator for the prevention and treatment of obesity or metabolic syndrome through its anti-inflammatory effects.
基金supported by grants from National Key R&D Program of China(2017YFA0205400)National Natural Science Foundation of China(81773781 to Zhuowei Hu+4 种基金81503128 to Xiaoxi Lv)from CAMS Innovation Found for Medical Sciences(2016-I2M-1-007 to Zhuowei Hu,Fang Hua2016-I2M-1008 to Xiaoxi Lv2016-I2M-1-011 to Ke Li2016-I2M-3-008 to Bing Cui,Shanshan Liu,Jiaojiao Yu,and Jinmei Yu,China)。
文摘The cell cycle inhibitor P21 has been implicated in cell senescence and plays an important role in the injury-repair process following lung injury.Pulmonary fibrosis(PF)is a fibrotic lung disorder characterized by cell senescence in lung alveolar epithelial cells.In this study,we report that P21 expression was increased in alveolar epithelial type 2 cells(AEC2 s)in a time-dependent manner following multiple bleomycin-induced PF.Repeated injury of AEC2 s resulted in telomere shortening and triggered P21-dependent cell senescence.AEC2 s with elevated expression of P21 lost their self-renewal and differentiation abilities.In particular,elevated P21 not only induced cell cycle arrest in AEC2 s but also bound to P300 andβ-catenin and inhibited AEC2 differentiation by disturbing the P300-β-catenin interaction.Meanwhile,senescent AEC2 s triggered myofibroblast activation by releasing profibrotic cytokines.Knockdown of P21 restored AEC2-mediated lung alveolar regeneration in mice with chronic PF.The results of our study reveal a mechanism of P21-mediated lung regeneration failure during PF development,which suggests a potential strategy for the treatment of fibrotic lung diseases.
基金supported by grants from the National Natural Science Foundation of China (Nos.81030056 and 81400286)Dr.Xiaowei Zhang is supported by a grant from Basic Research Program of Institute of Materia Medica (No.2014RC04)
文摘Abdominal aortic aneurysm (AAA) is an inflammatory vascular disorder with high mortality. Accumulating evidence shows that toll-like receptor 2 (TLR2) plays a critical role in the regulation of wound-repairing process after tissue injury. We wondered if TLR2 signaling contributed to the pathogenesis of AAA and that targeting TLR2 would attenuate AAA development and progression. In this study, enhanced expression of TLR2 and its ligands were observed in human AAA tissue. Neutralization of TLR2 protected against AAA development and caused established AAA to regress in mouse models of AAA. In addition, TLR2-deficient mice also failed to develop AAA. The prophylactic and therapeutic effects of blocking TLR2 were accompanied by a significant resolution of inflammation and vascular remodeling, as indicated by the decreased expression or activity of MMP-2/9, alpha-SMA, inflammatory cytokines, and transcription factors NF-kappa B, AP-1 and STAT1/3 in AAA tissue. Mechanistically, blocking TLR2 decreased the expression and interaction of TLR2 and several endogenous ligands, which diminished chronic inflammation and vascular remodeling in the vascular tissue of AAA. Our studies indicate that the interactions between TLR2 and its endogenous ligands contribute to the pathogenesis of AAA and that targeting TLR2 offers great potential toward the development of therapeutic agents against AAA. (C) 2015 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.
基金supported by grants from the National Key R&D Program of China(2017YFA0205400)the National Natural Science Foundation of China(81530093,81773781,81803604,81874316,81622010,and 81770800)+2 种基金Chinese Academy of Medical Sciences Central Public-interest Scientific Institution Basal Research Fund(2018PT35004,Molecular Mechanism and Target Discovery of Metabolic Disorder and Tumorigenesis,CAMS Key Lab,China)Beijing Outstanding Young Scientist Program(BJJWZYJH01201910023028,China)CAMS Innovation Fund for Medical Sciences(2016-I2M-3-008,China)。
文摘Pulmonary fibrosis(PF)is a chronic,progressive,fatal interstitial lung disease with limited available therapeutic strategies.We recently reported that the protein kinase glycogen synthase kinase-3β(GSK-3β)interacts with and inactivates the ubiquitin-editing enzyme A20 to suppress the degradation of the transcription factor CCAAT/enhancer-binding protein beta(C/EBPβ)in alveolar macrophages(AMs),resulting in a profibrotic phenotype of AMs and promoting the development of PF.Here,we showed that chronic lung injury upregulated the stress response protein tribbles homolog 3(TRIB3),which interacted with GSK-3βand stabilized GSK-3βfrom ubiquitination and degradation.Elevated GSK-3βexpression phosphorylated A20 to inhibit its ubiquitin-editing activity,causing the accumulation of C/EBPβand the production of several profibrotic factors in AMs and promoting PF development.Activated C/EBPβ,in turn,increased the transcription of TRIB3 and GSK-3β,thereby establishing a positive feedback loop in AMs.The knockdown of TRIB3 expression or the pharmacologic disruption of the TRIB3-GSK-3βinteraction was an effective PF treatment.Our study reveals an intact profibrotic axis of TRIB3-GSK-3β-A20-C/EBPβin AMs,which represents a target that may provide a promising treatment strategy for PF.
基金supported by National Key R&D Program of China(Grant No.2017YFA0205400,China)the National Natural Science Foundation of China(Grant Nos.81530093 and 81773781,China)+43 种基金Chinese Academy of Medical Sciences(CAMS)Innovation Fund for Medical Sciences(Grant No.2016-I2M-1-007,China)CAMS Central Public-interest Scientific Institution Basic Research Fund(Grant No.2017PT3104,China)supported by grants of the National Natural Science Foundation of China(Grant No.81874316,China)the CAMS Innovation Fund for Medical Sciences(Grant No.2016-I2M-3-008,China)supported by grants of from the BBSRC and NWCR(Grant Nos.1088 and 1097,UK)supported by grants of NSF(Grant No.IOS-1456023,USA)NIH(Grant No.NIH R21 CA197317,USA)supported by grants of Ministry of Education,Singapore(Grant Nos.MOE2014-T2-1-012 and 2012-T1-001-036,Singapore)supported by grants from the Health Research Council of New Zealandsupported by a Rutherford Discovery Fellowship from the New Zealand government administered by the Royal Society of New Zealandsupported by Funda??o para a Ciência e a Tecnologia(FCT)Research Center Grant UID/BIM/04773/2013 Centre for Biomedical Research 1334a research grant from Liga Portuguesa Contra o Cancro–Núcleo Regional do Sul(LPCC/NRS,Portugal)a FCT 2014 research grant SFRH/BPD/100434/2014a Pro Regem grant PD/BD/114258/2016(Portugal)supported by European Marie Sklodowska Curie ITN Project TRAIN-TRIBBLES Research and Innovation Network(Grant No.721532,EU)Innovation Network and the British Heart Foundation(PG/16/44/32146,UK)supported by grants from The Howat Foundation Ltd.(UK),Children with Cancer UK,Bloodwise and the Friends of Paul O'Gorman(UK)supported by grants of P-CREATE from Japan Agency for Medical Research and Developmentsupported by grants from the NIH(NIAID,USA),Alex's Lemonade Stand Foundation(USA)and the Samuel Waxman Cancer Research Foundation(USA)supported by European Marie Sklodowska Curie ITN Project TRAIN-TRIBBLES Research and Innovation Network(Grant No.721532,EU)the "Fondation Centaure"(RTRS),which supports a French transplantation research network,the IHU-Cesti project,the DHU Oncogreffefinancial support managed by the National Research Agency via the"Investment into the Future" program(Grant Nos.ANR-10-IBHU-005and ANR-11-LABX-0016-01,France)supported by Nantes Métropole and Région Pays de la Loire(France)supported by grants of the British Heart Foundation(PG/16/44/32146,UK)supported by European Marie Sklodowska Curie ITN Project TRAIN-TRIBBLES Research and Innovation Network(Grant No.721532,EU)supported by European Marie Sklodowska Curie ITN Project TRAIN-TRIBBLES Research and Innovation Network(Grant No.721532,EU)supported by a joint Ph.D studentship beween the A*Star Institute and the University of Sheffield(UK)supported by funding from the National Institutes of Health National Heart,Lung,and Blood Institute(R01HL141745,USA)supported by European Marie Sklodowska Curie ITN Project TRAIN-TRIBBLES Research and Innovation Network(Grant No.721532,EU)supported by European Marie Sklodowska Curie ITNProject TRAIN-TRIBBLES Research and Innovation Network(Grant No.721532,EU)supported by the National Natural Science Foundation of China(Grant No.81503128,China)CAMS Innovation Fund for Medical Sciences(Grant No.2016-I2M-1-008,China)supported by National Institute of Health(NS R01-035546,USA)supported by the National Natural Science Foundation of China(Grant No.81400140,China)CAMS Innovation Fund for Medical Sciences(Grant No.2016-I2M-1-011,China)supported by European Marie Sklodowska Curie ITN Project TRAIN-TRIBBLES Research and Innovation Network(Grant No.721532,EU)supported by Spanish Ministry of Economy and Competitiveness(MINECO)and Fondo Europeo de desarrollo Regional(FEDER)(Grant No.INNPACTO/IPT-2012-0614-010000,Spain)supported by the National Natural Science Foundation of China(Grant Nos.81400286 and 81530093,China)the CAMS Innovation Fund for Medical Sciences(Grant No.2016-I2M-1-010,China)supported by the National Natural Science Foundation of China(Grant Nos.81472717 and 81673474,China)Beijing Natural Science Foundation(Grant No.7162133,China)the CAMS Innovation Fund for Medical Sciences(Grant No.2016-I2M-1-007,China)supported by the National Natural Science Foundation of China(Grant No.81703564,China)supported by the National Natural Science Foundation of China(Grant No.81603129,China)
文摘The Tribbles(TRIB) family of pseudokinase proteins has been shown to play key roles in cell cycle, metabolic diseases, chronic inflammatory disease, and cancer development. A better understanding of the mechanisms of TRIB pseudokinases could provide new insights for disease development and help promote TRIB proteins as novel therapeutic targets for drug discovery. At the 2 nd International Symposium on Tribbles and Diseases held on May 7–9, 2018 in Beijing, China, a group of leading Tribbles scientists reported their findings and ongoing studies about the effects of the different TRIB proteins in the areas of immunity, metabolism, fundamental cell biology and cancer. Here, we summarize important and insightful overviews from 4 keynote lectures, 13 plenary lectures and 8 short talks that took place during this meeting. These findings may offer new insights for the understanding of the roles of TRIB pseudokinases in the development of various diseases.
基金supported by grants of 81530093 from the National Natural Science Foundation of China81661128007, 81472653 and 81530080 from National Natural Science Foundation of China+26 种基金supported by grants of 31390431 from the National Natural Science Foundation of Chinasupported by grants of Natural Sciences Foundation of China(31301007 and 81272525)supported by grants of 81622010 from the National Natural Science Foundation of Chinasupported by grants of 81472717 and 81673474 from the National Natural Science Foundation of China81661128007, 81472653 and 81530080 from National Natural Science Foundation of Chinasupported by grants of 81400286 and 81530093 from the National Natural Science Foundation of Chinasupported by grants of 81400140 from the National Natural Science Foundation of Chinasupported by grants of 81503128 from the National Natural Science Foundation of China2016I2M-1-008 from Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciencessupported by grants of 2014CB542103 from National Basic Research Program of China81502473 from National Natural Science Fund for Young Scholars of Chinasupported by US National Institutes of Health grants (CA217510, CA123088, CA099985, CA193136 and CA152470)supported by grants from the Canadian Institutes of Health Research(FRN 123516 and 152954)the Ontario Institute for Cancer Research(ORBiT)supported by NIH grant GM072744Ministry of Science and Technology of China grant 2016YFA0101100the Fundamental Research Fund for the Central University(No. 2017KFQWJX002) from Huazhong University of Science and TechnologyCore fund (Wang2016) for Development of Cell and Gene Therapy Centre of Academy of Medical Sciences,Zhengzhou UniversityThe MRC (MR/M015696/1)2017YFA0205400 from Ministry of Science and Technology of China2016ZX310190 and 2016ZX320014 from Central Public-interest Scientific Institution Basal Research Fund7162133 from Beijing Natural Science Foundation2016-I2M-4-001 from CAMS Innovation Fund for Medical Sciences2016-I2M-1-007 from the CAMS Innovation Fund for Medical Sciences2016-I2M-1010 from the CAMS Innovation Fund for Medical Sciences2016-I2M-1011 from the CAMS Innovation Fund for Medical Sciences2016-I2M-1008 from CAMS Innovation Fund for Medical Sciences
文摘Immune cells play key roles in cancer and chronic inflammatory disease. A better understanding of the mechanisms and risks will help develop novel target therapies. At the 2017 International Workshop of the Chinese Academy of Medical Sciences Initiative for Innovative Medicine on Tumor Immunology held in Beijing, China, on May 12, 2017, a number of speakers reported new findings and ongoing studies on immune-related diseases such as cancer, fibrotic disease, diabetes, and others. A considerably insightful overview was provided on cancer immunity, tumor microenvironments,and new immunotherapy for cancer. In addition, chronic inflammatory diseases were discussed. These findings may offer new insights into targeted immunotherapy.
基金supported by grants from National Key R&D Program of China(2017YFA0205400)National Natural Science Foundation of China(82173875 to Xiaoxi Lv+3 种基金81973344 and 81673474 to Fang Hua)CAMS Innovation Found for Medical Sciences(2021-I2M-1—026 to Xiaoxi Lv)Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences(2022-JKCS-05 to Xiaoxi Lv)Fundamental Research Funds for the Central Universities(3332019150 to Tingting Zhang)。
文摘Pulmonary fibrosis(PF)is the pathological structure of incurable fibroproliferative lung diseases that are attributed to the repeated lung injury-caused failure of lung alveolar regeneration(LAR).Here,we report that repetitive lung damage results in a progressive accumulation of the transcriptional repressor SLUG in alveolar epithelial type II cells(AEC2s).The abnormal increased SLUG inhibits AEC2s from self-renewal and differentiation into alveolar epithelial type I cells(AEC1s).We found that the elevated SLUG represses the expression of the phosphate transporter SLC34A2 in AEC2s,which reduces intracellular phosphate and represses the phosphorylation of JNK and P38 MAPK,two critical kinases supporting LAR,leading to LAR failure.TRIB3,a stress sensor,interacts with the E3 ligase MDM2 to suppress SLUG degradation in AEC2s by impeding MDM2-catalyzed SLUG ubiquitination.Targeting SLUG degradation by disturbing the TRIB3/MDM2 interaction using a new synthetic staple peptide restores LAR capacity and exhibits potent therapeutic efficacy against experimental PF.Our study reveals a mechanism of the TRIB3—MDM2—SLUG—SLC34A2 axis causing the LAR failure in PF,which confers a potential strategy for treating patients with fibroproliferative lung diseases.
