自噬是细胞用来维持体内平衡的一种自我消耗机制,部分研究提示,高危型人乳头瘤病毒(high-risk human papillomavirus,HR-HPV)通过作用于宿主细胞自噬促进宫颈癌的发生。HR-HPV具有将病毒基因组整合到宿主DNA中进而感染宿主细胞的能力,HR...自噬是细胞用来维持体内平衡的一种自我消耗机制,部分研究提示,高危型人乳头瘤病毒(high-risk human papillomavirus,HR-HPV)通过作用于宿主细胞自噬促进宫颈癌的发生。HR-HPV具有将病毒基因组整合到宿主DNA中进而感染宿主细胞的能力,HR-HPV L1、L2蛋白协助病毒进入细胞,并通过与靶细胞膜上的细胞表面受体相互作用激活PI3K/AKT/mTOR信号通路以抑制自噬过程,使得病毒颗粒不间断地向细胞内运输。HR-HPV L1、L2蛋白可在细胞质中表达并转移到细胞核,通过影响细胞自噬协助病毒逃避免疫监视。虽然目前已有针对HR-HPV L1、L2蛋白的HPV预防性疫苗,但明确HR-HPV L1、L2蛋白对宫颈癌自噬具体的调节方式,或能为宫颈癌的防治拓展新思路。展开更多
Postoperative cognitive dysfunction is a seve re complication of the central nervous system that occurs after anesthesia and surgery,and has received attention for its high incidence and effect on the quality of life ...Postoperative cognitive dysfunction is a seve re complication of the central nervous system that occurs after anesthesia and surgery,and has received attention for its high incidence and effect on the quality of life of patients.To date,there are no viable treatment options for postoperative cognitive dysfunction.The identification of postoperative cognitive dysfunction hub genes could provide new research directions and therapeutic targets for future research.To identify the signaling mechanisms contributing to postoperative cognitive dysfunction,we first conducted Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of the Gene Expression Omnibus GSE95426 dataset,which consists of mRNAs and long non-coding RNAs differentially expressed in mouse hippocampus3 days after tibial fracture.The dataset was enriched in genes associated with the biological process"regulation of immune cells,"of which Chill was identified as a hub gene.Therefore,we investigated the contribution of chitinase-3-like protein 1 protein expression changes to postoperative cognitive dysfunction in the mouse model of tibial fractu re surgery.Mice were intraperitoneally injected with vehicle or recombinant chitinase-3-like protein 124 hours post-surgery,and the injection groups were compared with untreated control mice for learning and memory capacities using the Y-maze and fear conditioning tests.In addition,protein expression levels of proinflammatory factors(interleukin-1βand inducible nitric oxide synthase),M2-type macrophage markers(CD206 and arginase-1),and cognition-related proteins(brain-derived neurotropic factor and phosphorylated NMDA receptor subunit NR2B)were measured in hippocampus by western blotting.Treatment with recombinant chitinase-3-like protein 1 prevented surgery-induced cognitive impairment,downregulated interleukin-1βand nducible nitric oxide synthase expression,and upregulated CD206,arginase-1,pNR2B,and brain-derived neurotropic factor expression compared with vehicle treatment.Intraperitoneal administration of the specific ERK inhibitor PD98059 diminished the effects of recombinant chitinase-3-like protein 1.Collectively,our findings suggest that recombinant chitinase-3-like protein 1 ameliorates surgery-induced cognitive decline by attenuating neuroinflammation via M2 microglial polarization in the hippocampus.Therefore,recombinant chitinase-3-like protein1 may have therapeutic potential fo r postoperative cognitive dysfunction.展开更多
Face-centered cubic(FCC)-structured multicomponent alloys typically exhibit good ductility but low strength.To simultaneously improve strength and ductility,a multicomponent alloy,Ni_(43.9)Co_(22.4)Fe_(8.8)Al_(10.7)Ti...Face-centered cubic(FCC)-structured multicomponent alloys typically exhibit good ductility but low strength.To simultaneously improve strength and ductility,a multicomponent alloy,Ni_(43.9)Co_(22.4)Fe_(8.8)Al_(10.7)Ti_(11.7)B_(2.5)(at%)with a unique microstructure was developed in this work.The microstructure,which includes 17.8%nanosized L12 precipitates and 26.6%micron-sized annealing twins distributed within~8μm fine FCC grains,was achieved through cryogenic rolling and subsequent annealing.The alloy exhibits a yield strength(YS)of 1063 MPa,ultimate tensile strength(UTS)of 1696 MPa,and excellent elongation of~26%.The L1_(2) precipitates and high-density grain boundaries act as a barrier to the dislocation movement,resulting in a substantial strengthening effect.In addition,the dislocations can cut through the L1_(2) precipitates that are coherent with the FCC matrix,whereas the twin boundaries can effectively absorb and store dislocations,leading to a high work-hardening rate.Furthermore,the stacking faults,Lomer-Cottrell locks,and 9-layer rhombohedral stacking sequence(9R)structures formed during tensile deformation significantly enhance strain hardening by blocking dislocation movement and accumulating dislocations,resulting in excellent comprehensive tensile properties.Theoretical calculations reveal that the grain boundaries,L1_(2)precipitates,and twin boundaries contribute the strengths of 263.8,412.6,and 68.7 MPa,respectively,accounting for 71.9%of the YS.This study introduces a promising strategy for developing multicomponent alloys with significant strength-ductility synergies.展开更多
Precipitation–strengthened high entropy alloys (HEAs) exhibit excellent strength–ductility combinations due to precipitation hindering dislocation gliding and work hardening ability of the matrix. However, the effec...Precipitation–strengthened high entropy alloys (HEAs) exhibit excellent strength–ductility combinations due to precipitation hindering dislocation gliding and work hardening ability of the matrix. However, the effect of compositions on the microstructure and related deformation mechanism of HEAs is still unclear. In this study, we developed two types of L1_(2)–strengthened Al_(5)Ti_(8)Fe_(x)(CoNi)_(86.9–x)B_(0.1) (x = 17, 28) HEAs to study the effect of Fe content on the deformation mechanism. Our results reveal that an increased Fe concentration substantially increases the strength and ductility of Al_(5)Ti_(8)Fe_(x)(CoNi)_(86.9–x)B_(0.1) HEAs at room temperature. For the Al_(5)Ti_(8)Fe17(CoNi)_(69.9)B_(0.1) HEA, the presence of a large amount of ordered L1_(2) phase leads to strain strengthening governed by dynamically refined slip bands. For the Al_(5)Ti_(8)Fe28(CoNi)58.9B_(0.1) HEA, the increasing Fe content raises the stacking fault energy of the matrix and reduces the stability of the FCC matrix, making it less stable than the BCC structure. Additionally, the reduced volume fraction of the ordered L1_(2) precipitated phase and the increased stack fault energy of the FCC matrix lead to an increase in the cross-slip frequency during deformation, which in turn promotes avalanche glide of dislocations on highly stressed crystallographic slip planes and the generation of microbands. The microbands and phase transformation inside the microbands promote the strain strengthening, resulting in enhanced strength and ductility. These findings clarify the effect of the Fe content on the deformation behaviours and provide new insight into the formation mechanism of microbands in precipitation-strengthened HEAs, which will open new avenues for the design of ultra-strong yet ductile alloys in the future.展开更多
The mechanical,thermodynamic properties and electrical conductivities of L1_(2)-Al_(3)X(X=Zr,Sc,Er,Yb,Hf)structural phases in aluminum conductors were investigated through a first-principles study.The results demonstr...The mechanical,thermodynamic properties and electrical conductivities of L1_(2)-Al_(3)X(X=Zr,Sc,Er,Yb,Hf)structural phases in aluminum conductors were investigated through a first-principles study.The results demonstrate that all structural phases have good alloy-forming ability and structural stability,where Al_(3)Zr is the most superior.Al_(3)Zr,Al_(3)Hf and Al_(3)Sc have enhanced shear and deformation resistance in comparison to other phases.Within the temperature range of 200−600 K,Al_(3)Er and Al_(3)Yb possess the greatest thermodynamic stability,followed by Al_(3)Hf,Al_(3)Zr and Al_(3)Sc.Al_(3)Er and Al_(3)Yb have higher thermodynamic stability than Al_(3)Hf,Al_(3)Zr and Al_(3)Sc.All structural phases exhibit substantial metallic properties,indicating their good electrical conductivity.The electrical conductivities of Al_(3)Hf and Al_(3)Zr are higher than those of Al_(3)Er,Al_(3)Yb and Al_(3)Sc.The covalent bond properties in Al_(3)Sc,Al_(3)Er and Al_(3)Yb enhance the hardness,brittleness and thermodynamic stability of the structural phase.The thermodynamic stability of Al_(3)Sc is significantly reduced by ionic bonds.展开更多
基金supported by the National Natural Science Foundation of China,Nos.81730033,82171193(to XG)the Key Talent Project for Strengthening Health during the 13^(th)Five-Year Plan Period,No.ZDRCA2016069(to XG)+1 种基金the National Key R&D Program of China,No.2018YFC2001901(to XG)Jiangsu Provincial Medical Key Discipline,No.ZDXK202232(to XG)。
文摘Postoperative cognitive dysfunction is a seve re complication of the central nervous system that occurs after anesthesia and surgery,and has received attention for its high incidence and effect on the quality of life of patients.To date,there are no viable treatment options for postoperative cognitive dysfunction.The identification of postoperative cognitive dysfunction hub genes could provide new research directions and therapeutic targets for future research.To identify the signaling mechanisms contributing to postoperative cognitive dysfunction,we first conducted Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of the Gene Expression Omnibus GSE95426 dataset,which consists of mRNAs and long non-coding RNAs differentially expressed in mouse hippocampus3 days after tibial fracture.The dataset was enriched in genes associated with the biological process"regulation of immune cells,"of which Chill was identified as a hub gene.Therefore,we investigated the contribution of chitinase-3-like protein 1 protein expression changes to postoperative cognitive dysfunction in the mouse model of tibial fractu re surgery.Mice were intraperitoneally injected with vehicle or recombinant chitinase-3-like protein 124 hours post-surgery,and the injection groups were compared with untreated control mice for learning and memory capacities using the Y-maze and fear conditioning tests.In addition,protein expression levels of proinflammatory factors(interleukin-1βand inducible nitric oxide synthase),M2-type macrophage markers(CD206 and arginase-1),and cognition-related proteins(brain-derived neurotropic factor and phosphorylated NMDA receptor subunit NR2B)were measured in hippocampus by western blotting.Treatment with recombinant chitinase-3-like protein 1 prevented surgery-induced cognitive impairment,downregulated interleukin-1βand nducible nitric oxide synthase expression,and upregulated CD206,arginase-1,pNR2B,and brain-derived neurotropic factor expression compared with vehicle treatment.Intraperitoneal administration of the specific ERK inhibitor PD98059 diminished the effects of recombinant chitinase-3-like protein 1.Collectively,our findings suggest that recombinant chitinase-3-like protein 1 ameliorates surgery-induced cognitive decline by attenuating neuroinflammation via M2 microglial polarization in the hippocampus.Therefore,recombinant chitinase-3-like protein1 may have therapeutic potential fo r postoperative cognitive dysfunction.
基金supported by the Major Science and Technology Project of Gansu Province(Nos.23ZDGA010 and 22ZD6GA008)the National Natural Science Foundation of China(No.51564035).
文摘Face-centered cubic(FCC)-structured multicomponent alloys typically exhibit good ductility but low strength.To simultaneously improve strength and ductility,a multicomponent alloy,Ni_(43.9)Co_(22.4)Fe_(8.8)Al_(10.7)Ti_(11.7)B_(2.5)(at%)with a unique microstructure was developed in this work.The microstructure,which includes 17.8%nanosized L12 precipitates and 26.6%micron-sized annealing twins distributed within~8μm fine FCC grains,was achieved through cryogenic rolling and subsequent annealing.The alloy exhibits a yield strength(YS)of 1063 MPa,ultimate tensile strength(UTS)of 1696 MPa,and excellent elongation of~26%.The L1_(2) precipitates and high-density grain boundaries act as a barrier to the dislocation movement,resulting in a substantial strengthening effect.In addition,the dislocations can cut through the L1_(2) precipitates that are coherent with the FCC matrix,whereas the twin boundaries can effectively absorb and store dislocations,leading to a high work-hardening rate.Furthermore,the stacking faults,Lomer-Cottrell locks,and 9-layer rhombohedral stacking sequence(9R)structures formed during tensile deformation significantly enhance strain hardening by blocking dislocation movement and accumulating dislocations,resulting in excellent comprehensive tensile properties.Theoretical calculations reveal that the grain boundaries,L1_(2)precipitates,and twin boundaries contribute the strengths of 263.8,412.6,and 68.7 MPa,respectively,accounting for 71.9%of the YS.This study introduces a promising strategy for developing multicomponent alloys with significant strength-ductility synergies.
基金supported by the National Key Research and Development Program(No.2022YFB3707103)the Natural Science Foundation of China(No.52174375)+2 种基金the Key Research and Development Program of Shaanxi(No.2022JBGS2-04)the Fund of the State Key Laboratory of Solidification Processing in NWPU(No.2023-TS-13)the Training Program of Innovation and Entrepreneurship for Undergraduates(No.S202310699761).
文摘Precipitation–strengthened high entropy alloys (HEAs) exhibit excellent strength–ductility combinations due to precipitation hindering dislocation gliding and work hardening ability of the matrix. However, the effect of compositions on the microstructure and related deformation mechanism of HEAs is still unclear. In this study, we developed two types of L1_(2)–strengthened Al_(5)Ti_(8)Fe_(x)(CoNi)_(86.9–x)B_(0.1) (x = 17, 28) HEAs to study the effect of Fe content on the deformation mechanism. Our results reveal that an increased Fe concentration substantially increases the strength and ductility of Al_(5)Ti_(8)Fe_(x)(CoNi)_(86.9–x)B_(0.1) HEAs at room temperature. For the Al_(5)Ti_(8)Fe17(CoNi)_(69.9)B_(0.1) HEA, the presence of a large amount of ordered L1_(2) phase leads to strain strengthening governed by dynamically refined slip bands. For the Al_(5)Ti_(8)Fe28(CoNi)58.9B_(0.1) HEA, the increasing Fe content raises the stacking fault energy of the matrix and reduces the stability of the FCC matrix, making it less stable than the BCC structure. Additionally, the reduced volume fraction of the ordered L1_(2) precipitated phase and the increased stack fault energy of the FCC matrix lead to an increase in the cross-slip frequency during deformation, which in turn promotes avalanche glide of dislocations on highly stressed crystallographic slip planes and the generation of microbands. The microbands and phase transformation inside the microbands promote the strain strengthening, resulting in enhanced strength and ductility. These findings clarify the effect of the Fe content on the deformation behaviours and provide new insight into the formation mechanism of microbands in precipitation-strengthened HEAs, which will open new avenues for the design of ultra-strong yet ductile alloys in the future.
基金National Natural Science Foundation of China (No. 52274403)。
文摘The mechanical,thermodynamic properties and electrical conductivities of L1_(2)-Al_(3)X(X=Zr,Sc,Er,Yb,Hf)structural phases in aluminum conductors were investigated through a first-principles study.The results demonstrate that all structural phases have good alloy-forming ability and structural stability,where Al_(3)Zr is the most superior.Al_(3)Zr,Al_(3)Hf and Al_(3)Sc have enhanced shear and deformation resistance in comparison to other phases.Within the temperature range of 200−600 K,Al_(3)Er and Al_(3)Yb possess the greatest thermodynamic stability,followed by Al_(3)Hf,Al_(3)Zr and Al_(3)Sc.Al_(3)Er and Al_(3)Yb have higher thermodynamic stability than Al_(3)Hf,Al_(3)Zr and Al_(3)Sc.All structural phases exhibit substantial metallic properties,indicating their good electrical conductivity.The electrical conductivities of Al_(3)Hf and Al_(3)Zr are higher than those of Al_(3)Er,Al_(3)Yb and Al_(3)Sc.The covalent bond properties in Al_(3)Sc,Al_(3)Er and Al_(3)Yb enhance the hardness,brittleness and thermodynamic stability of the structural phase.The thermodynamic stability of Al_(3)Sc is significantly reduced by ionic bonds.
