The internal temperature of cast-in-place concrete bridges undergoes strong variations during the construction as a result of environmental factors.In order to determine precisely such variations,the present study rel...The internal temperature of cast-in-place concrete bridges undergoes strong variations during the construction as a result of environmental factors.In order to determine precisely such variations,the present study relies on the finite element method,used to model the bridge box girder section and simulate the internal temperature distribution during construction.The numerical results display good agreement with measured temperature values.It is shown that when the external temperature is higher,and the internal and external temperature difference is relatively small,the deviation of the fitting line from existing specifications(Chinese specification,American specification,New Zealand specification)is relatively large and vice versa.展开更多
Development of the medium and low voltage DC distribution system is of great significance to a regional transmission of electric energy,increasing a penetration rate of new energy,and enhancing a safety of the operati...Development of the medium and low voltage DC distribution system is of great significance to a regional transmission of electric energy,increasing a penetration rate of new energy,and enhancing a safety of the operation of the AC/DC interconnected grid.This paper first summarizes the medium and low voltage DC distribution system schemes and plans put forward by many countries,and then elaborate status of under-construction medium and low voltage DC distribution system project cases in China.Based on these project cases,this paper analyzes key issues involved in the medium and low voltage DC distribution system topologies,equipment,operation control technologies and DC fault protections,in order to provide theoretical and technical reference for future medium and low voltage DC distribution system-related projects.Finally,this paper combines a current China research status to summarize and give a prediction about the future research direction of medium and low voltage DC distribution system,which can provide reference for the research of medium and low voltage DC distribution system.展开更多
With the continuous development of power electronic devices,intelligent control systems,and other technologies,the voltage level and transmission capacity of voltage source converter (VSC)-high-voltage direct current ...With the continuous development of power electronic devices,intelligent control systems,and other technologies,the voltage level and transmission capacity of voltage source converter (VSC)-high-voltage direct current (HVDC) technology will continue to increase,while the system losses and costs will gradually decrease.Therefore,it can be foreseen that VSC-HVDC transmission technology will be more widely applied in future large-scale renewable energy development projects.Adopting VSC-HVDC transmission technology can be used to overcome issues encountered by large-scale renewable energy transmission and integration projects,such as a weak local power grid,lack of support for synchronous power supply,and insufficient accommodation capacity.However,this solution also faces many technical challenges because of the differences between renewable energy and traditional synchronous power generation systems.Based on actual engineering practices that are used worldwide,this article analyzes the technical challenges encountered by integrating large-scale renewable energy systems that adopt the use of VSC-HVDC technology,while aiming to provide support for future research and engineering projects related to VSC-HVDC-based large-scale renewable energy integration projects.展开更多
To ensure the stable operation of power systems with large proportions of wind power,China has published a series of national,industry,and enterprise standards for wind power.The increase in the number of standards an...To ensure the stable operation of power systems with large proportions of wind power,China has published a series of national,industry,and enterprise standards for wind power.The increase in the number of standards and the expansion of their application scope have given rise to a situation where multiple standards overlap and conflict with regard to the establishment of models and their applicability,resulting in unclear standard application scenarios.Therefore,it is imperative to analyze the development of wind-turbine and wind-farm modeling,along with the relevant standards.This paper presents the methods for wind-turbine modeling,the equivalent model of wind farms based on the general model of wind turbines,and the technical provisions and application scenarios involved in the relevant domestic and international standards.The adaptability of the relevant standards is examined.The results of this study are helpful for advancing wind power generation in China and ensuring the safe and stable operation of large-scale wind power systems.展开更多
Community residents play an important role in the development of rural tourism. Taking the interest demands of stakeholders and non-cooperative game process as main line,the conflict of interest between community resi...Community residents play an important role in the development of rural tourism. Taking the interest demands of stakeholders and non-cooperative game process as main line,the conflict of interest between community residents and tourists and between community residents themselves as guidance,it built an interest relation model for community participating in rural tourism. Besides,it elaborated non-cooperative relation and their interest pattern for stakeholders of rural tourism,and discussed behavior interaction process and results of core stakeholders of rural tourism. Finally,it came up with pertinent recommendations for harmonious and healthy development of rural tourism.展开更多
Group 2 innate lymphoid cells(ILC2s)play important tissue resident roles in anti-parasite immunity,allergic immune response,tissue homeostasis,and tumor immunity.ILC2s are considered tissue resident cells with little ...Group 2 innate lymphoid cells(ILC2s)play important tissue resident roles in anti-parasite immunity,allergic immune response,tissue homeostasis,and tumor immunity.ILC2s are considered tissue resident cells with little proliferation at steady state.Recent studies have shown that a subset of small intestinal ILC2s could leave their residing tissues,circulate and migrate to different organs,including lung,liver,mesenteric LN and spleen,upon activation.However,it remains unknown whether other ILC populations with migratory behavior exist.In this study,we find two major colon ILC2 populations with potential to migrate to the lung in response to IL-25 stimulation.One subset expresses IL-17A and resembles inflammatory ILC2s(iILC2s)but lacks CD27 expression,whereas the other expresses CD27 but not IL-17A.In addition,the IL-17A^(+)ILC2s express lower levels of CD127,CD25,and ST2 than CD27^(+)ILC2s,which express higher levels of IL-5 and IL-13.Surprisingly,we found that both colon ILC2 populations still maintained their colonic features of preferential expression of IL-17A and CD27,IL-5/IL-13,respectively.Together,our study identifies two migratory colon ILC2 subsets with unique surface markers and cytokine profiles which are critical in regulating lung and colon immunity and homeostasis.展开更多
Group 3 innate lymphoid cells(ILC3s)play important roles in maintaining intestinal homeostasis by protecting the host from pathogen infections and tissue inflammation.The transcription factor PLZF(promyelocytic leukem...Group 3 innate lymphoid cells(ILC3s)play important roles in maintaining intestinal homeostasis by protecting the host from pathogen infections and tissue inflammation.The transcription factor PLZF(promyelocytic leukemia zinc finger),encoded by zinc finger BTB domain containing 16(Zbtb16),is highly and transiently expressed in ILC precursors(ILCPs).However,the role of PLZF in regulating ILC3 development and function remains unknown.Here,we show that PLZF was specifically expressed in mature intestinal ILC3s compared with other ILC subsets.PLZF was dispensable for ILC3 development.However,PLZF deficiency in ILC3s resulted in increased innate interleukin-22(IL-22)secretion and protection against gut infection and inflammation.Mechanistically,PLZF negatively regulated IL-22 expression by ILC3s in a cell-intrinsic manner by binding to the IL-22 promoter region for transcriptional repression.Together,our data suggest that PLZF restricts intestinal ILC3 function to regulate gut immune homeostasis.展开更多
Knowledge of the spatial distribution of interseismic deformations is essential to better understand earthquake cycles.The existing methods for improving the reliability of the obtained deformations often rely on visu...Knowledge of the spatial distribution of interseismic deformations is essential to better understand earthquake cycles.The existing methods for improving the reliability of the obtained deformations often rely on visual inspection and prior model corrections that are time-consuming,labor-intensive,and do not consider the spatial distribution of interseismic deformations.Interferometric Synthetic Aperture Radar(InSAR)data provides wide-scale coverage for interseismic deformation monitoring over a wide area.However,the interseismic signal featured as millimeter-scale and long-wave deformations is often contaminated with noise.In the present study,a new workfow to correct the interferometric phase and quantitatively select interferograms is proposed to improve the accuracy of interseismic deformation measurements.Initially,the Generic Atmospheric Correction Online Service(GACOS),Intermittent Code for Atmospheric Noise Depression through Iterative Stacking(I-CANDIS),and plate model are combined to correct the atmospheric screen and long-wave ramp phase.Subsequently,the Pearson’s Correlation Coefcient(PCC)between the interferometric phase and the Global Navigation Satellite System(GNSS)constrained interseismic model as well as the STandard Deviation(STD)of the interferometric phase are introduced as criteria to optimize the selection of interferograms.Finally,the intermittent stacking method is used to generate an average velocity map.A comprehensive test using Sentinel-1 images covering the Haiyuan Fault Zone validate the efectiveness of our workfow in measuring interseismic deformations.This demonstrates that the proposed joint InSAR-GNSS workfow can be extended to study the subtle interseismic deformations of major fault systems in Tibet and worldwide.展开更多
Background and Aims:Hepatectomy is an effective treatment for selected patients with large hepatocellular carcinoma(HCC).This study aimed to develop a nomogram in-corporating non-tumoral liver volume(non-TLV)and liver...Background and Aims:Hepatectomy is an effective treatment for selected patients with large hepatocellular carcinoma(HCC).This study aimed to develop a nomogram in-corporating non-tumoral liver volume(non-TLV)and liver function markers to predict the patients’overall survival(OS)and disease-free survival(DFS).Methods:Data of 198 consecutive large HCC patients who underwent hepa-tectomy at the Zhongshan Hospital Xiamen University were collected.Another 68 patients from the Mengchao Hepatobil-iary Surgery Hospital served as an external validation cohort.The nomograms were developed based on the independent prognostic factors screened by multivariate Cox regression analyses.Concordance index(C-index),calibration curves,and time-dependent receiver operating characteristic(ROC)curves were used to measure the discrimination and predic-tive accuracy of the models.Results:High HBV DNA level,low non-TLV/ICG,vascular invasion,and a poorly differenti-ated tumor were confirmed as independent risk factors for both OS and DFS.The model established in this study pre-dicted 5-year post-operative survival and DFS in good agree-ment with the actual observation confirmed by the calibra-tion curves.The C-indexes of the nomograms in predicting OS and DFS were 0.812 and 0.823 in the training cohort,0.821 and 0.846 in the internal validation cohort,and 0.724 and 0.755 in the external validation cohort.The areas under the ROC curves(AUCs)of nomograms for predicted OS and DFS at 1,3,and 5 year were 0.85,0.86,0.83 and 0.76,0.76,0.63,respectively.Conclusions:Nomograms with non-TLV/ICG predicted the prognosis of single large HCC patients ac-curately and effectively.展开更多
Glucose metabolism plays a key role in thymocyte development. The mammalian target of rapamycin complex 2 (mT0RC2) is a critical regulator of cell growth and metabolism, but its role in early thymocyte development and...Glucose metabolism plays a key role in thymocyte development. The mammalian target of rapamycin complex 2 (mT0RC2) is a critical regulator of cell growth and metabolism, but its role in early thymocyte development and metabolism has not been fully studied. We show here that genetic ablation of Sinl, an essential component of mTORC2, in T lineage cells results in severely impaired thymocyte development at the CD4^- CD8^- double negative (DN) stages but not at the CD4^+ CD8^+ double positive (DP) or later stages. Notably, Sinl-deficient DN thymocytes show markedly reduced proliferation and glycolysis.Importantly, we discover that the M2 isoform of pyruvate kinase (PKM2) is a novel and crucial Sinl effector in promoting DN thymocyte development and metabolism. At the molecular level, we show that Sinl-mTORC2 controls PKM2 expression through an AKT-dependent PPAR-y nuclear translocation. Together, our study unravels a novel mTORC2-PPAR-γ-PKM2 pathway in immune-metabolic regulation of early thymocyte development.展开更多
T cell-mediated immunity in the intestine is stringently controlled to ensure proper immunity against pathogenic microbes and to prevent autoimmunity,a known cause of inflammatory bowel disease.However,precisely how T...T cell-mediated immunity in the intestine is stringently controlled to ensure proper immunity against pathogenic microbes and to prevent autoimmunity,a known cause of inflammatory bowel disease.However,precisely how T cells regulate intestine immunity remains to be fully understood.In this study,we found that mitogen-activated protein kinase kinase kinase 2(MAP3K2)is required for the CD4^(+)T cell-mediated inflammation in the intestine.Using a T cell transfer colitis model,we found that MAP3K2-deficient naïve CD4^(+)T cells had a dramatically reduced ability to induce colitis compared to wild type T cells.In addition,significantly fewer IFN-γ-but more IL-17A-producing CD4^(+)T cells in the intestines of mice receiving MAP3K2-deficient T cells than in those from mice receiving wild type T cells was observed.Interestingly,under well-defined in vitro differentiation conditions,MAP3K2-deficient naïve T cells were not impaired in their ability to differentiate into Th1,Th17 and Treg.Furthermore,the MAP3K2-regulated colitis severity was mediated by Th1 but not Th17 cells in the intestine.At the molecular level,we showed that MAP3K2-mediated Th1 cell differentiation in the intestine was regulated by IL-18 and required specific JNK activation.Together,our study reveals a novel regulatory role of MAP3K2 in intestinal T cell immunity via the IL-18-MAP3K2-JNK axis and may provide a novel target for intervention in T cell-mediated colitis.展开更多
Proper control of B cell growth and metabolism is crucial for B-cell-mediated immunity,but the underlying molecular mechanisms remain incompletely understood.In this study,Sin1,a key component of mTOR complex 2(mTORC2...Proper control of B cell growth and metabolism is crucial for B-cell-mediated immunity,but the underlying molecular mechanisms remain incompletely understood.In this study,Sin1,a key component of mTOR complex 2(mTORC2),specifically regulates B cell growth and metabolism.Genetic ablation of Sin1 in B cells reduces the cell size at either the transitional stage or upon antigen stimulation and severely impairs metabolism.Sin1 deficiency also severely impairs B-cell proliferation,antibody responses,and anti-viral immunity.At the molecular level,Sin1 controls the expression and stability of the c-Myc protein and maintains the activity of mTORC1 through the Akt-dependent inactivation of GSK3 and TSC1/2,respectively.Therefore,our study reveals a novel and specific role for Sin1 in coordinating the activation of mTORC2 and mTORC1 to control B cell growth and metabolism.展开更多
Early detection and intervention are key strategies to reduce mortality,increase longterm survival,and improve the therapeutic effects of hepatocellular carcinoma(HCC)patients.Herein,the isobaric tag for relative and ...Early detection and intervention are key strategies to reduce mortality,increase longterm survival,and improve the therapeutic effects of hepatocellular carcinoma(HCC)patients.Herein,the isobaric tag for relative and absolute quantitation(iTRAQ)-based quantitative proteomic strategy was used to study the secretomes in conditioned media from HCC cancerous tissues,surrounding noncancerous tissues,and distal noncancerous tissues to identify diagnostic and prognostic biomarkers for HCC.In total,22 and 49 dysregulated secretory proteins were identified in the cancerous and surrounding noncancerous tissues,respectively,compared with the distal noncancerous tissues.Among these proteins,carbonic anhydrase II(CA2)was identified to be significantly upregulated in the secretome of cancerous tissues;correspondingly,the serum concentrations of CA2 were remarkably increased in HCC patients compared with that in normal populations.Interestingly,a significant increase of serum CA2 in recurrent HCC patients after radical resection was also confirmed compared with HCC patients without recurrence,and the serum level of CA2 could act as an independent prognostic factor for time to recurrence and overall survival.Regarding the mechanism,the secreted CA2 enhances the migration and invasion of HCC cells by activating the epithelial mesenchymal transition pathway.Taken together,this study identified a novel biomarker for HCC diagnosis and prognosis,and provided a valuable resource of HCC secretome for investigating serological biomarkers.展开更多
After the Industrial Revolution,the ever-increasing atmospheric CO_(2)concentration has resulted in significant problems for human beings.Nearly all countries in the world are actively taking measures to fight for car...After the Industrial Revolution,the ever-increasing atmospheric CO_(2)concentration has resulted in significant problems for human beings.Nearly all countries in the world are actively taking measures to fight for carbon neutrality.In recent years,negative carbon emission technologies have attracted much attention due to their ability to reduce or recycle excess CO_(2)in the atmosphere.This review summarizes the state-of-the-art negative carbon emission technologies,from the artificial enhancement of natural carbon sink technology to the physical,chemical,or biological methods for carbon capture,as well as CO_(2)utilization and conversion.Finally,we expound on the challenges and outlook for improving negative carbon emission technology to accelerate the pace of achieving carbon neutrality.展开更多
In this paper, the authors give a new proof of Block and Weinberger’s Bochner vanishing theorem built on direct computations in the K-theory of the localization algebra.
基金supported by National Natural Science Foundation of China(Grant No.51778314).
文摘The internal temperature of cast-in-place concrete bridges undergoes strong variations during the construction as a result of environmental factors.In order to determine precisely such variations,the present study relies on the finite element method,used to model the bridge box girder section and simulate the internal temperature distribution during construction.The numerical results display good agreement with measured temperature values.It is shown that when the external temperature is higher,and the internal and external temperature difference is relatively small,the deviation of the fitting line from existing specifications(Chinese specification,American specification,New Zealand specification)is relatively large and vice versa.
基金supported by the National Key Rese arch and Development Program of China(2018YFB0904100)Science and Technology Project of State Grid(SGHB0000KXJS1800685)
文摘Development of the medium and low voltage DC distribution system is of great significance to a regional transmission of electric energy,increasing a penetration rate of new energy,and enhancing a safety of the operation of the AC/DC interconnected grid.This paper first summarizes the medium and low voltage DC distribution system schemes and plans put forward by many countries,and then elaborate status of under-construction medium and low voltage DC distribution system project cases in China.Based on these project cases,this paper analyzes key issues involved in the medium and low voltage DC distribution system topologies,equipment,operation control technologies and DC fault protections,in order to provide theoretical and technical reference for future medium and low voltage DC distribution system-related projects.Finally,this paper combines a current China research status to summarize and give a prediction about the future research direction of medium and low voltage DC distribution system,which can provide reference for the research of medium and low voltage DC distribution system.
基金State Grid Corporation of China Science and Technology Project: Research on Power Transmission of Largescale Renewable Energy Base by VSC-LCC hybrid HVDC(No. NY71-19-037)
文摘With the continuous development of power electronic devices,intelligent control systems,and other technologies,the voltage level and transmission capacity of voltage source converter (VSC)-high-voltage direct current (HVDC) technology will continue to increase,while the system losses and costs will gradually decrease.Therefore,it can be foreseen that VSC-HVDC transmission technology will be more widely applied in future large-scale renewable energy development projects.Adopting VSC-HVDC transmission technology can be used to overcome issues encountered by large-scale renewable energy transmission and integration projects,such as a weak local power grid,lack of support for synchronous power supply,and insufficient accommodation capacity.However,this solution also faces many technical challenges because of the differences between renewable energy and traditional synchronous power generation systems.Based on actual engineering practices that are used worldwide,this article analyzes the technical challenges encountered by integrating large-scale renewable energy systems that adopt the use of VSC-HVDC technology,while aiming to provide support for future research and engineering projects related to VSC-HVDC-based large-scale renewable energy integration projects.
基金supported in part by the Joint Research Fund in Smart Grid (U1966208) under a cooperative agreement between the National Natural Science Foundation of China (NSFC) and State Grid Corporation of China (SGCC)
文摘To ensure the stable operation of power systems with large proportions of wind power,China has published a series of national,industry,and enterprise standards for wind power.The increase in the number of standards and the expansion of their application scope have given rise to a situation where multiple standards overlap and conflict with regard to the establishment of models and their applicability,resulting in unclear standard application scenarios.Therefore,it is imperative to analyze the development of wind-turbine and wind-farm modeling,along with the relevant standards.This paper presents the methods for wind-turbine modeling,the equivalent model of wind farms based on the general model of wind turbines,and the technical provisions and application scenarios involved in the relevant domestic and international standards.The adaptability of the relevant standards is examined.The results of this study are helpful for advancing wind power generation in China and ensuring the safe and stable operation of large-scale wind power systems.
文摘Community residents play an important role in the development of rural tourism. Taking the interest demands of stakeholders and non-cooperative game process as main line,the conflict of interest between community residents and tourists and between community residents themselves as guidance,it built an interest relation model for community participating in rural tourism. Besides,it elaborated non-cooperative relation and their interest pattern for stakeholders of rural tourism,and discussed behavior interaction process and results of core stakeholders of rural tourism. Finally,it came up with pertinent recommendations for harmonious and healthy development of rural tourism.
基金supported by the National Natural Science Foundation of China(31930035,91942311,32061143028)Shanghai Science and Technology Commission(20410714000)+1 种基金the National Key Research and Developmental Program of China(2021YFA1301400)generous support from Flow cytometry Core and Sequencing Core at Shanghai Institute of Immunology and animal facility of Shanghai Jiao Tong University School of Medicine。
文摘Group 2 innate lymphoid cells(ILC2s)play important tissue resident roles in anti-parasite immunity,allergic immune response,tissue homeostasis,and tumor immunity.ILC2s are considered tissue resident cells with little proliferation at steady state.Recent studies have shown that a subset of small intestinal ILC2s could leave their residing tissues,circulate and migrate to different organs,including lung,liver,mesenteric LN and spleen,upon activation.However,it remains unknown whether other ILC populations with migratory behavior exist.In this study,we find two major colon ILC2 populations with potential to migrate to the lung in response to IL-25 stimulation.One subset expresses IL-17A and resembles inflammatory ILC2s(iILC2s)but lacks CD27 expression,whereas the other expresses CD27 but not IL-17A.In addition,the IL-17A^(+)ILC2s express lower levels of CD127,CD25,and ST2 than CD27^(+)ILC2s,which express higher levels of IL-5 and IL-13.Surprisingly,we found that both colon ILC2 populations still maintained their colonic features of preferential expression of IL-17A and CD27,IL-5/IL-13,respectively.Together,our study identifies two migratory colon ILC2 subsets with unique surface markers and cytokine profiles which are critical in regulating lung and colon immunity and homeostasis.
基金grant 2020YFA0509200(to LS)from the Ministry of Science and Technology of Chinagrant 81971487(to LS)from the National Natural Science Foundation of China+1 种基金grants 20ZR1430200 and 20142202300(to LS)from the Science and Technology Commission of Shanghai Municipalitygrant 20194Y0275(to JS)from the Shanghai Municipal Health Commission,and the Shanghai Frontiers Science Center of Cellular Homeostasis and Human Diseases.
文摘Group 3 innate lymphoid cells(ILC3s)play important roles in maintaining intestinal homeostasis by protecting the host from pathogen infections and tissue inflammation.The transcription factor PLZF(promyelocytic leukemia zinc finger),encoded by zinc finger BTB domain containing 16(Zbtb16),is highly and transiently expressed in ILC precursors(ILCPs).However,the role of PLZF in regulating ILC3 development and function remains unknown.Here,we show that PLZF was specifically expressed in mature intestinal ILC3s compared with other ILC subsets.PLZF was dispensable for ILC3 development.However,PLZF deficiency in ILC3s resulted in increased innate interleukin-22(IL-22)secretion and protection against gut infection and inflammation.Mechanistically,PLZF negatively regulated IL-22 expression by ILC3s in a cell-intrinsic manner by binding to the IL-22 promoter region for transcriptional repression.Together,our data suggest that PLZF restricts intestinal ILC3 function to regulate gut immune homeostasis.
基金the National Natural Science Foundation of China(42174023)Frontier cross research project of Central South University(Grant number:2023QYJC006).
文摘Knowledge of the spatial distribution of interseismic deformations is essential to better understand earthquake cycles.The existing methods for improving the reliability of the obtained deformations often rely on visual inspection and prior model corrections that are time-consuming,labor-intensive,and do not consider the spatial distribution of interseismic deformations.Interferometric Synthetic Aperture Radar(InSAR)data provides wide-scale coverage for interseismic deformation monitoring over a wide area.However,the interseismic signal featured as millimeter-scale and long-wave deformations is often contaminated with noise.In the present study,a new workfow to correct the interferometric phase and quantitatively select interferograms is proposed to improve the accuracy of interseismic deformation measurements.Initially,the Generic Atmospheric Correction Online Service(GACOS),Intermittent Code for Atmospheric Noise Depression through Iterative Stacking(I-CANDIS),and plate model are combined to correct the atmospheric screen and long-wave ramp phase.Subsequently,the Pearson’s Correlation Coefcient(PCC)between the interferometric phase and the Global Navigation Satellite System(GNSS)constrained interseismic model as well as the STandard Deviation(STD)of the interferometric phase are introduced as criteria to optimize the selection of interferograms.Finally,the intermittent stacking method is used to generate an average velocity map.A comprehensive test using Sentinel-1 images covering the Haiyuan Fault Zone validate the efectiveness of our workfow in measuring interseismic deformations.This demonstrates that the proposed joint InSAR-GNSS workfow can be extended to study the subtle interseismic deformations of major fault systems in Tibet and worldwide.
基金the grants of the Medical and Health Key project of Xiamen(3502Z20191106).
文摘Background and Aims:Hepatectomy is an effective treatment for selected patients with large hepatocellular carcinoma(HCC).This study aimed to develop a nomogram in-corporating non-tumoral liver volume(non-TLV)and liver function markers to predict the patients’overall survival(OS)and disease-free survival(DFS).Methods:Data of 198 consecutive large HCC patients who underwent hepa-tectomy at the Zhongshan Hospital Xiamen University were collected.Another 68 patients from the Mengchao Hepatobil-iary Surgery Hospital served as an external validation cohort.The nomograms were developed based on the independent prognostic factors screened by multivariate Cox regression analyses.Concordance index(C-index),calibration curves,and time-dependent receiver operating characteristic(ROC)curves were used to measure the discrimination and predic-tive accuracy of the models.Results:High HBV DNA level,low non-TLV/ICG,vascular invasion,and a poorly differenti-ated tumor were confirmed as independent risk factors for both OS and DFS.The model established in this study pre-dicted 5-year post-operative survival and DFS in good agree-ment with the actual observation confirmed by the calibra-tion curves.The C-indexes of the nomograms in predicting OS and DFS were 0.812 and 0.823 in the training cohort,0.821 and 0.846 in the internal validation cohort,and 0.724 and 0.755 in the external validation cohort.The areas under the ROC curves(AUCs)of nomograms for predicted OS and DFS at 1,3,and 5 year were 0.85,0.86,0.83 and 0.76,0.76,0.63,respectively.Conclusions:Nomograms with non-TLV/ICG predicted the prognosis of single large HCC patients ac-curately and effectively.
基金the National Natural Science Foundation of China (31470845, 81430033, and 31670896)Shanghai Science and Technology Commission (13JC1404700)Shanghai Rising-Star Program (16QA1403300).
文摘Glucose metabolism plays a key role in thymocyte development. The mammalian target of rapamycin complex 2 (mT0RC2) is a critical regulator of cell growth and metabolism, but its role in early thymocyte development and metabolism has not been fully studied. We show here that genetic ablation of Sinl, an essential component of mTORC2, in T lineage cells results in severely impaired thymocyte development at the CD4^- CD8^- double negative (DN) stages but not at the CD4^+ CD8^+ double positive (DP) or later stages. Notably, Sinl-deficient DN thymocytes show markedly reduced proliferation and glycolysis.Importantly, we discover that the M2 isoform of pyruvate kinase (PKM2) is a novel and crucial Sinl effector in promoting DN thymocyte development and metabolism. At the molecular level, we show that Sinl-mTORC2 controls PKM2 expression through an AKT-dependent PPAR-y nuclear translocation. Together, our study unravels a novel mTORC2-PPAR-γ-PKM2 pathway in immune-metabolic regulation of early thymocyte development.
基金the National Natural Science Foundation of China(81430033,81871269,91942311 and 31930035)。
文摘T cell-mediated immunity in the intestine is stringently controlled to ensure proper immunity against pathogenic microbes and to prevent autoimmunity,a known cause of inflammatory bowel disease.However,precisely how T cells regulate intestine immunity remains to be fully understood.In this study,we found that mitogen-activated protein kinase kinase kinase 2(MAP3K2)is required for the CD4^(+)T cell-mediated inflammation in the intestine.Using a T cell transfer colitis model,we found that MAP3K2-deficient naïve CD4^(+)T cells had a dramatically reduced ability to induce colitis compared to wild type T cells.In addition,significantly fewer IFN-γ-but more IL-17A-producing CD4^(+)T cells in the intestines of mice receiving MAP3K2-deficient T cells than in those from mice receiving wild type T cells was observed.Interestingly,under well-defined in vitro differentiation conditions,MAP3K2-deficient naïve T cells were not impaired in their ability to differentiate into Th1,Th17 and Treg.Furthermore,the MAP3K2-regulated colitis severity was mediated by Th1 but not Th17 cells in the intestine.At the molecular level,we showed that MAP3K2-mediated Th1 cell differentiation in the intestine was regulated by IL-18 and required specific JNK activation.Together,our study reveals a novel regulatory role of MAP3K2 in intestinal T cell immunity via the IL-18-MAP3K2-JNK axis and may provide a novel target for intervention in T cell-mediated colitis.
基金This study was partially supported by grant PR093728(DoD to B.S.)the National Natural Science Foundation of China(grant numbers 31470845 and 81430033 to B.S.,31422020 to F.L.and 31600704 to H.H.Z.)+2 种基金grant 13JC1404700 from the Program of Science and Technology Commission of Shanghai Municipality(B.S.)the Ministry of Science and Technology of China(Program 2014CB943600,F.L.)Chinese Mega Project on Infectious Diseases(No.2018ZX10302301).
文摘Proper control of B cell growth and metabolism is crucial for B-cell-mediated immunity,but the underlying molecular mechanisms remain incompletely understood.In this study,Sin1,a key component of mTOR complex 2(mTORC2),specifically regulates B cell growth and metabolism.Genetic ablation of Sin1 in B cells reduces the cell size at either the transitional stage or upon antigen stimulation and severely impairs metabolism.Sin1 deficiency also severely impairs B-cell proliferation,antibody responses,and anti-viral immunity.At the molecular level,Sin1 controls the expression and stability of the c-Myc protein and maintains the activity of mTORC1 through the Akt-dependent inactivation of GSK3 and TSC1/2,respectively.Therefore,our study reveals a novel and specific role for Sin1 in coordinating the activation of mTORC2 and mTORC1 to control B cell growth and metabolism.
基金supported by the National Natural Science Foundation of China(Grant Nos.81702910 and 81672376)the Educational Commission of Fujian Province,China(Grant No.2018B013)the Natural Science Foundation of Fujian Province,China(Grant Nos.2019J01298,2017J01159,and 2016J01417)
文摘Early detection and intervention are key strategies to reduce mortality,increase longterm survival,and improve the therapeutic effects of hepatocellular carcinoma(HCC)patients.Herein,the isobaric tag for relative and absolute quantitation(iTRAQ)-based quantitative proteomic strategy was used to study the secretomes in conditioned media from HCC cancerous tissues,surrounding noncancerous tissues,and distal noncancerous tissues to identify diagnostic and prognostic biomarkers for HCC.In total,22 and 49 dysregulated secretory proteins were identified in the cancerous and surrounding noncancerous tissues,respectively,compared with the distal noncancerous tissues.Among these proteins,carbonic anhydrase II(CA2)was identified to be significantly upregulated in the secretome of cancerous tissues;correspondingly,the serum concentrations of CA2 were remarkably increased in HCC patients compared with that in normal populations.Interestingly,a significant increase of serum CA2 in recurrent HCC patients after radical resection was also confirmed compared with HCC patients without recurrence,and the serum level of CA2 could act as an independent prognostic factor for time to recurrence and overall survival.Regarding the mechanism,the secreted CA2 enhances the migration and invasion of HCC cells by activating the epithelial mesenchymal transition pathway.Taken together,this study identified a novel biomarker for HCC diagnosis and prognosis,and provided a valuable resource of HCC secretome for investigating serological biomarkers.
基金support from National Natural Science Foundation of China(22176086)Natural Science Foundation of Jiangsu Province(BK20210189)+2 种基金State Key Laboratory of Pollution Control and Resource Reuse(PCRR-ZZ-202106)the Fundamental Research Funds for the Central Universities(021114380183,021114380189),China Association for Science and Technology(20220615ZZ08010008)the Research Funds from Frontiers Science Center for Critical Earth Material Cycling of Nanjing University,and Research Funds for Jiangsu Distinguished Professor.H.L.and H.R.would like to acknowledge the support from China Association for Sci-ence and Technology(20220615ZZ08010008).
文摘After the Industrial Revolution,the ever-increasing atmospheric CO_(2)concentration has resulted in significant problems for human beings.Nearly all countries in the world are actively taking measures to fight for carbon neutrality.In recent years,negative carbon emission technologies have attracted much attention due to their ability to reduce or recycle excess CO_(2)in the atmosphere.This review summarizes the state-of-the-art negative carbon emission technologies,from the artificial enhancement of natural carbon sink technology to the physical,chemical,or biological methods for carbon capture,as well as CO_(2)utilization and conversion.Finally,we expound on the challenges and outlook for improving negative carbon emission technology to accelerate the pace of achieving carbon neutrality.
基金This work was supported by the National Natural Science Foundation of China(Nos.11811530291,11831006,11771092)。
文摘In this paper, the authors give a new proof of Block and Weinberger’s Bochner vanishing theorem built on direct computations in the K-theory of the localization algebra.
