Natural killer(NK)cells have emerged as promising therapeutic agents for treating colorectal cancer because of their innate ability to recognize and eliminate tumor cells without prior sensitization.In this review,NK ...Natural killer(NK)cells have emerged as promising therapeutic agents for treating colorectal cancer because of their innate ability to recognize and eliminate tumor cells without prior sensitization.In this review,NK cell-based immunotherapeutic approaches,including cytokine therapy,immune checkpoint inhibition,antibody-dependent cellular cytotoxicity,and adoptive cell transfer,are comprehensively examined,and their respective clinical potential and limitations are highlighted.We discuss critical challenges in NK cell expansion,genetic engineering(particularly chimeric antigen receptor-NK development),and tumor microenvironment-mediated immunosuppression.Furthermore,we explore innovative strategies such as combination therapies,nanotechnology-enhanced delivery,and personalized medicine approaches that aim to overcome the current barriers.The review concludes with future directions emphasizing the need for standardized manufacturing protocols,new strategies to improve NK cell persistence,and clinical validation of emerging technologies,positioning NK cell immunotherapy as a transformative modality for colorectal cancer treatment.展开更多
The effects of deep cryogenic-cycling treatment(DCT)on the mechanical properties,soft magnetic properties,and atomic scale structure of the Fe_(73.5)Si_(13.5)B_(9)Nb_(3)Cu_(1)amorphous nanocrystalline alloy were inves...The effects of deep cryogenic-cycling treatment(DCT)on the mechanical properties,soft magnetic properties,and atomic scale structure of the Fe_(73.5)Si_(13.5)B_(9)Nb_(3)Cu_(1)amorphous nanocrystalline alloy were investigated.The DCT samples were obtained by subjecting the as-annealed samples to a thermal cycling process between the temperature of the supercooled liquid zone and the temperature of liquid nitrogen.Through flat plate bending testing,hardness measurements,and nanoindentation experiment,it is found that the bending toughness of the DCT samples is improved and the soft magnetic properties are also slightly enhanced.These are attributed to the rejuvenation behavior of the DCT samples,which demonstrate a higher enthalpy of relaxation.Therefore,DCT is an effective method to enhance the bending toughness of Fe-based amorphous nanocrystalline alloys without degrading the soft magnetic properties.展开更多
Background: Tumor angiogenesis is related to solid tumor occurrence. Ubiquitin-specific peptidase 13 (USP13) is a deubiquitinating enzyme with a pivotal effect on tumor proliferation, metastasis, and tumorigenesis. No...Background: Tumor angiogenesis is related to solid tumor occurrence. Ubiquitin-specific peptidase 13 (USP13) is a deubiquitinating enzyme with a pivotal effect on tumor proliferation, metastasis, and tumorigenesis. Nonetheless, its effect on colorectal cancer (CRC) angiogenesis remains poorly understood. Methods: Human umbilical vein endothelial cells (HUVECs) and CRC cells were cultivated, followed by USP13 knockdown/overexpression using shRNA lentiviral vectors or plasmids. Conditioned media (CM) from treated CRC cells were collected to assess HUVEC migration, invasion, and tube formation. Phosphatase and tensin homolog (PTEN) overexpression and recombinant vascular endothelial growth factor A (VEGFA) rescue experiments were performed. Molecular mechanisms were analyzed via Western blot (PTEN, p-AKT, VEGFA), co-immunoprecipitation (PTEN ubiquitination), and in vivo nude mice study to detect the role of USP13 in tumor angiogenesis. Results: USP13 expression in CRC cells is downregulated and negatively related to platelet endothelial cell adhesion molecule-1 (CD31) expression. Furthermore, the conditioned medium from CRC cells with USP13 knockdown significantly promoted HUVEC migration, invasion, and tube formation, while USP13 overexpression exerted the opposite effect. Additionally, USP13 overexpression significantly increased PTEN expression while decreasing protein kinase B (AKT) phosphorylation levels. Concurrently, USP13 overexpression significantly reduced PTEN ubiquitination, whereas USP13 knockdown remarkably increased this modification. Overexpression of PTEN in sh-USP13 CRC cells decreased the expression levels of VEGFA and p-AKT. USP13 also inhibited tumor angiogenesis through downregulating VEGFA, and recombinant VEGFA blocked the inhibition of the conditioned medium from USP13-overexpressing CRC cells against HUVEC angiogenesis in vivo. Conclusions: USP13 downregulated VEGFA and inhibited tumor angiogenesis via the PTEN-AKT pathway.展开更多
In this study, the enclosure system exhibited perfect nitrogen removal performance with in situ oxygen-enhanced indigenous aerobic denitrifying bacteria in an enclosure experiment. We explored changes in the microbial...In this study, the enclosure system exhibited perfect nitrogen removal performance with in situ oxygen-enhanced indigenous aerobic denitrifying bacteria in an enclosure experiment. We explored changes in the microbial community during the nitrogen removal process using the MiSeq high-throughput sequencing technology. The results revealed a total of 7974 and 33653 operational taxonomic units(OTUs) for water and sediment systems, respectively, with 97% similarity. The OTUs were found to be affiliated with eight main phyla(Proteobacteria, Actinobacteria, Cyanobacteria, Bacteroidetes, Planctomycetes, Chloroflexi, Firmicutes, and Actinobacteria). The diversity of the enhanced system was found to be higher than that of the control system. Principal component analysis(PCA) revealed that significant spatial and temporal differences were exhibited in the microbial community during nitrogen removal in the enclosure experiment. Redundancy analysis(RDA)indicated that physical parameters(temperature, dissolved oxygen, and pH), nitrogen(total nitrogen and nitrate), functional genes(nirK and nirS), and dissolved organic carbon(DOC) were the most important factors affecting bacterial community function and composition. Lastly, the results suggested that the variation in the microbial community could be analyzed through the MiSeq high-throughput sequencing technology,which may provide technical support for future field tests.展开更多
The isothermally compression deformation behavior of an elevated Cu/Li weight ratio Al–Cu–Li alloy was investigated under various deformation conditions.The isothermal compression tests were carried out in a tempera...The isothermally compression deformation behavior of an elevated Cu/Li weight ratio Al–Cu–Li alloy was investigated under various deformation conditions.The isothermal compression tests were carried out in a temperature range from 300 to 500℃ and at a strain rate range from 0.001 to 10 s^-1.The results show that the peak stress level decreases with temperature increasing and strain rate decreasing,which is represented by the Zener–Hollomon parameter Z in the hyperbolic sine equation with the hot deformation activation energy of 218.5 k J/mol.At low Z value,the dynamic recrystallized grain is well formed with clean high-angle boundaries.At high Z value,a high dislocation density with poorly developed cellularity and considerable fine dynamic precipitates are observed.Based on the experimental data and dynamic material model,the processing maps at strain of 0.3,0.5 and 0.7 were developed to demonstrate the hot workability of the alloy.The results show that the main softening mechanism at high Z value is precipitate coarsening and dynamic recovery;the dynamic recrystallization of the alloy can be easily observed as ln Z ≤ 29.44,with peak efficiency of power dissipation of around 70%.At strains of 0.3,0.5 and 0.7,the flow instability domains are found at higher strain rates,which mainly locate at the upper part of processing maps.In addition,when the strain rate is 0.001 or 0.02 s^-1,there is a particular instability domain at 300–350℃.展开更多
Cyclic olefin polymers（COPs） with high glass transition temperature, high transparency（higher than 80%） in the visible light range, excellent thermal stability and outstanding mechanical properties have been synth...Cyclic olefin polymers（COPs） with high glass transition temperature, high transparency（higher than 80%） in the visible light range, excellent thermal stability and outstanding mechanical properties have been synthesized by effective ring opening metathesis polymerization（ROMP） of exo-1,4,4 a,9,9 a,10-hexahydro-9,10（1′,2′）-benzeno-l,4-methanoanthracene（HBM） and dicyclopentadiene（DCPD） or norbornene（NBE） using WCl6/i-Bu3Al/ethanol/1-hexene catalyst system, followed by hydrogenation of double bonds. 1-Hexene acted as a molecular weight controller in the polymerization reaction, tuning the number-average molecular weight（Mn） of P-HBM from 5.8 × 10^4 to 41.1 × 10^4. The monomer composition and thermal properties of the copolymers were characterized by nuclear magnetic resonance（NMR）, differential scanning calorimetry（DSC） and thermogravimetric analysis（TGA）. The saturated polymers exhibited high decomposition temperatures（Td） around 340 ℃ and glass transition temperatures（Tg） in the range from 117.5 ℃ to 219.7 ℃. What is more, tensile tests indicated that the mechanical properties of the COPs could be effectively tuned in a wide range by introducing varying amount of small cyclic olefin such as DCPD or NBE.展开更多
This paper is devoted to the five parameters nonconforming finite element schemes with moving grids for velocity-pressure mixed formulations of the nonstationary Stokes problem in 2-D. We show that this element has an...This paper is devoted to the five parameters nonconforming finite element schemes with moving grids for velocity-pressure mixed formulations of the nonstationary Stokes problem in 2-D. We show that this element has anisotropic behavior and derive anisotropic error estimations in some certain norms of the velocity and the pressure based on some novel techniques. Especially through careful analysis we get an interesting result on consistency error estimation, which has never been seen for mixed finite element methods in the previously literatures.展开更多
Aims Riparian corridors play vital roles in the maintenance of biodiversity.Nonetheless,plant species diversity and vegetation coverage in riparian corridors are seriously threatened by increasing pressure owing to li...Aims Riparian corridors play vital roles in the maintenance of biodiversity.Nonetheless,plant species diversity and vegetation coverage in riparian corridors are seriously threatened by increasing pressure owing to livestock consumption and anthropogenic disturbance;even the stability of river courses has been threatened.The establishment of enclosures is a widely used strategy to restore degraded grassland ecosystems,but its impact on degraded herbaceous riparian vegetation and soil properties remains unclear.The aim of this study was to evaluate whether species composition,richness,diversity,and soil properties can be recovered by the enclosure.Methods Twenty long-term monitoring sample plots were set in the Liaohe main stream river,Liaohe main stream river was enclosed for grazing and farmland exclusion in 2012.The height,coverage and individual numbers of plant were recorded for species richness and diversity evaluation from 2012 to 2017;soil nutrients were measured for comparative analysis in 2012 and 2017.We examined the effects of the establishment of enclosures on plant species diversity and soil properties from 2012 to 2017 in the riparian corridors of the Liaohe River system in China.Important Findings Plant species richness and diversity significantly increased from 2012 to 2017.The dominance of Asteraceae plants increased,while the abundance of Gramineae plants decreased over time.The difference in abundance increased each year since enclosure was implemented in 2012.The concentrations of phosphorus and potassium in the soil significantly decreased as a result of the combined effects of vegetation restoration and prohibition of farming practices following the establishment of enclosures.There was also a lag time related to the response of soil organic matter to the establishment of enclosures.In conclusion,our study provides new evidence regarding the response of species diversity,species composition and soil properties following riparian vegetation restoration efforts through enclosure development.展开更多
基金Supported by Shaanxi Natural Science Foundation of China,No.2025JC-YBMS-916and Xi’an Municipal Health Commission of China,No.2023ms11.
文摘Natural killer(NK)cells have emerged as promising therapeutic agents for treating colorectal cancer because of their innate ability to recognize and eliminate tumor cells without prior sensitization.In this review,NK cell-based immunotherapeutic approaches,including cytokine therapy,immune checkpoint inhibition,antibody-dependent cellular cytotoxicity,and adoptive cell transfer,are comprehensively examined,and their respective clinical potential and limitations are highlighted.We discuss critical challenges in NK cell expansion,genetic engineering(particularly chimeric antigen receptor-NK development),and tumor microenvironment-mediated immunosuppression.Furthermore,we explore innovative strategies such as combination therapies,nanotechnology-enhanced delivery,and personalized medicine approaches that aim to overcome the current barriers.The review concludes with future directions emphasizing the need for standardized manufacturing protocols,new strategies to improve NK cell persistence,and clinical validation of emerging technologies,positioning NK cell immunotherapy as a transformative modality for colorectal cancer treatment.
基金supported by Liaoning Joint Fund of NSFC(No.U1908219)。
文摘The effects of deep cryogenic-cycling treatment(DCT)on the mechanical properties,soft magnetic properties,and atomic scale structure of the Fe_(73.5)Si_(13.5)B_(9)Nb_(3)Cu_(1)amorphous nanocrystalline alloy were investigated.The DCT samples were obtained by subjecting the as-annealed samples to a thermal cycling process between the temperature of the supercooled liquid zone and the temperature of liquid nitrogen.Through flat plate bending testing,hardness measurements,and nanoindentation experiment,it is found that the bending toughness of the DCT samples is improved and the soft magnetic properties are also slightly enhanced.These are attributed to the rejuvenation behavior of the DCT samples,which demonstrate a higher enthalpy of relaxation.Therefore,DCT is an effective method to enhance the bending toughness of Fe-based amorphous nanocrystalline alloys without degrading the soft magnetic properties.
基金supported by the Clinical Frontier Technology Program of the First Affiliated Hospital of Jinan University,China(No.JNU1AF-CFTP-2022-a01223)Guangzhou Science and Technology Plan City-School Joint Funding Project(2024A03J0825)+2 种基金Science and Technology Projects in Guangzhou(202201020566)Medical Joint Fund of Jinan University(YXJC2022005)the Fundamental Research Funds for the Central Universities(21623319).
文摘Background: Tumor angiogenesis is related to solid tumor occurrence. Ubiquitin-specific peptidase 13 (USP13) is a deubiquitinating enzyme with a pivotal effect on tumor proliferation, metastasis, and tumorigenesis. Nonetheless, its effect on colorectal cancer (CRC) angiogenesis remains poorly understood. Methods: Human umbilical vein endothelial cells (HUVECs) and CRC cells were cultivated, followed by USP13 knockdown/overexpression using shRNA lentiviral vectors or plasmids. Conditioned media (CM) from treated CRC cells were collected to assess HUVEC migration, invasion, and tube formation. Phosphatase and tensin homolog (PTEN) overexpression and recombinant vascular endothelial growth factor A (VEGFA) rescue experiments were performed. Molecular mechanisms were analyzed via Western blot (PTEN, p-AKT, VEGFA), co-immunoprecipitation (PTEN ubiquitination), and in vivo nude mice study to detect the role of USP13 in tumor angiogenesis. Results: USP13 expression in CRC cells is downregulated and negatively related to platelet endothelial cell adhesion molecule-1 (CD31) expression. Furthermore, the conditioned medium from CRC cells with USP13 knockdown significantly promoted HUVEC migration, invasion, and tube formation, while USP13 overexpression exerted the opposite effect. Additionally, USP13 overexpression significantly increased PTEN expression while decreasing protein kinase B (AKT) phosphorylation levels. Concurrently, USP13 overexpression significantly reduced PTEN ubiquitination, whereas USP13 knockdown remarkably increased this modification. Overexpression of PTEN in sh-USP13 CRC cells decreased the expression levels of VEGFA and p-AKT. USP13 also inhibited tumor angiogenesis through downregulating VEGFA, and recombinant VEGFA blocked the inhibition of the conditioned medium from USP13-overexpressing CRC cells against HUVEC angiogenesis in vivo. Conclusions: USP13 downregulated VEGFA and inhibited tumor angiogenesis via the PTEN-AKT pathway.
基金supported by the National Science and Technology Pillar Program(Grant No.2012BAC04B02)the National Natural Science Foundation of China(Grant No.51478378)
文摘In this study, the enclosure system exhibited perfect nitrogen removal performance with in situ oxygen-enhanced indigenous aerobic denitrifying bacteria in an enclosure experiment. We explored changes in the microbial community during the nitrogen removal process using the MiSeq high-throughput sequencing technology. The results revealed a total of 7974 and 33653 operational taxonomic units(OTUs) for water and sediment systems, respectively, with 97% similarity. The OTUs were found to be affiliated with eight main phyla(Proteobacteria, Actinobacteria, Cyanobacteria, Bacteroidetes, Planctomycetes, Chloroflexi, Firmicutes, and Actinobacteria). The diversity of the enhanced system was found to be higher than that of the control system. Principal component analysis(PCA) revealed that significant spatial and temporal differences were exhibited in the microbial community during nitrogen removal in the enclosure experiment. Redundancy analysis(RDA)indicated that physical parameters(temperature, dissolved oxygen, and pH), nitrogen(total nitrogen and nitrate), functional genes(nirK and nirS), and dissolved organic carbon(DOC) were the most important factors affecting bacterial community function and composition. Lastly, the results suggested that the variation in the microbial community could be analyzed through the MiSeq high-throughput sequencing technology,which may provide technical support for future field tests.
基金supported by the Foundation for Science and Technology Development Project of Shandong (No.2014GGX102006)
文摘The isothermally compression deformation behavior of an elevated Cu/Li weight ratio Al–Cu–Li alloy was investigated under various deformation conditions.The isothermal compression tests were carried out in a temperature range from 300 to 500℃ and at a strain rate range from 0.001 to 10 s^-1.The results show that the peak stress level decreases with temperature increasing and strain rate decreasing,which is represented by the Zener–Hollomon parameter Z in the hyperbolic sine equation with the hot deformation activation energy of 218.5 k J/mol.At low Z value,the dynamic recrystallized grain is well formed with clean high-angle boundaries.At high Z value,a high dislocation density with poorly developed cellularity and considerable fine dynamic precipitates are observed.Based on the experimental data and dynamic material model,the processing maps at strain of 0.3,0.5 and 0.7 were developed to demonstrate the hot workability of the alloy.The results show that the main softening mechanism at high Z value is precipitate coarsening and dynamic recovery;the dynamic recrystallization of the alloy can be easily observed as ln Z ≤ 29.44,with peak efficiency of power dissipation of around 70%.At strains of 0.3,0.5 and 0.7,the flow instability domains are found at higher strain rates,which mainly locate at the upper part of processing maps.In addition,when the strain rate is 0.001 or 0.02 s^-1,there is a particular instability domain at 300–350℃.
基金financial support by the National Natural Science Foundation of China(Nos.21234006 and U1510124)
文摘Cyclic olefin polymers（COPs） with high glass transition temperature, high transparency（higher than 80%） in the visible light range, excellent thermal stability and outstanding mechanical properties have been synthesized by effective ring opening metathesis polymerization（ROMP） of exo-1,4,4 a,9,9 a,10-hexahydro-9,10（1′,2′）-benzeno-l,4-methanoanthracene（HBM） and dicyclopentadiene（DCPD） or norbornene（NBE） using WCl6/i-Bu3Al/ethanol/1-hexene catalyst system, followed by hydrogenation of double bonds. 1-Hexene acted as a molecular weight controller in the polymerization reaction, tuning the number-average molecular weight（Mn） of P-HBM from 5.8 × 10^4 to 41.1 × 10^4. The monomer composition and thermal properties of the copolymers were characterized by nuclear magnetic resonance（NMR）, differential scanning calorimetry（DSC） and thermogravimetric analysis（TGA）. The saturated polymers exhibited high decomposition temperatures（Td） around 340 ℃ and glass transition temperatures（Tg） in the range from 117.5 ℃ to 219.7 ℃. What is more, tensile tests indicated that the mechanical properties of the COPs could be effectively tuned in a wide range by introducing varying amount of small cyclic olefin such as DCPD or NBE.
基金This research is supported by the National Science Foundation of China（No.10371113）.The authors would like to thank the anonymous referees for their helpful suggestions.
文摘This paper is devoted to the five parameters nonconforming finite element schemes with moving grids for velocity-pressure mixed formulations of the nonstationary Stokes problem in 2-D. We show that this element has anisotropic behavior and derive anisotropic error estimations in some certain norms of the velocity and the pressure based on some novel techniques. Especially through careful analysis we get an interesting result on consistency error estimation, which has never been seen for mixed finite element methods in the previously literatures.
基金supported by the National Key Technology R&D Program(2017YFC1200100)the special S&T project on treatment and control of water pollution(2012ZX07202-004)+3 种基金National Natural Science Foundation of China(31901209)China Postdoctoral Science Foundation(2018M641492)Liaoning Natural Science Foundation(20180551024)the Shenyang Science and Technology Bureau(SYSY2016-16,SYSY2017-010).
文摘Aims Riparian corridors play vital roles in the maintenance of biodiversity.Nonetheless,plant species diversity and vegetation coverage in riparian corridors are seriously threatened by increasing pressure owing to livestock consumption and anthropogenic disturbance;even the stability of river courses has been threatened.The establishment of enclosures is a widely used strategy to restore degraded grassland ecosystems,but its impact on degraded herbaceous riparian vegetation and soil properties remains unclear.The aim of this study was to evaluate whether species composition,richness,diversity,and soil properties can be recovered by the enclosure.Methods Twenty long-term monitoring sample plots were set in the Liaohe main stream river,Liaohe main stream river was enclosed for grazing and farmland exclusion in 2012.The height,coverage and individual numbers of plant were recorded for species richness and diversity evaluation from 2012 to 2017;soil nutrients were measured for comparative analysis in 2012 and 2017.We examined the effects of the establishment of enclosures on plant species diversity and soil properties from 2012 to 2017 in the riparian corridors of the Liaohe River system in China.Important Findings Plant species richness and diversity significantly increased from 2012 to 2017.The dominance of Asteraceae plants increased,while the abundance of Gramineae plants decreased over time.The difference in abundance increased each year since enclosure was implemented in 2012.The concentrations of phosphorus and potassium in the soil significantly decreased as a result of the combined effects of vegetation restoration and prohibition of farming practices following the establishment of enclosures.There was also a lag time related to the response of soil organic matter to the establishment of enclosures.In conclusion,our study provides new evidence regarding the response of species diversity,species composition and soil properties following riparian vegetation restoration efforts through enclosure development.
