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
Background:Oxidative stress and neuroinflammation are key factors in the pathophysiology of Alzheimer's disease(AD).Exercise and Aklil-ol-Malek may reduce AD symptoms.Therefore,the current study investigated the ef...Background:Oxidative stress and neuroinflammation are key factors in the pathophysiology of Alzheimer's disease(AD).Exercise and Aklil-ol-Malek may reduce AD symptoms.Therefore,the current study investigated the effect of weight training and Aklil-ol-Malek consumption on histopathological and inflammatory changes in hippocampal tissue of male AD model rats.Method:We prepared 558-week-old male Wistar rats and transferred them to an animal laboratory.The rats were randomly divided intofive groups:healthy control group,Alzheimer's control group,Alzheimer's group+weight training,Alzheimer's group+Aklil-ol-Malek supplement,and Alzheimer's group+Aklilol-Malek supplement+weight training.AD was induced in the 4 groups.The weight training protocol and Aklil-ol-Malek supplementation were examined as an intervention.The designated groups were administered Aklil-ol-Malek supplements.The anesthetized rats'hippocampi were extracted for further analysis 72 hours after the last session of the protocol.After the induction of AD and supplementation,two-way analysis of variance was used to examine the differences between groups(p<0.05).Results:The results showed a decrease in the expression of CRP and NFE2L2 genes in rats in the Aklil-olMalek and weight training group compared with thefindings in rats in the Alzheimer's group.Changes in the expression of BACE1 were not significant in rats in the weight training with Aklil-ol-Malek group.Conclusion:An intervention receiving exercise and Aklil-ol-Malek extract positively improved health and reduced AD progression.These results were likely to have been caused by the physiological effects of exercise and the antioxidant properties of Aklil-ol-Malek.展开更多
L1_(2)precipitates are known to significantly enhance the strength and ductility of single-phase face-centered cubic(FCC)medium-or high-entropy alloys(M/HEAs).However,further improvements in mechanical properties rema...L1_(2)precipitates are known to significantly enhance the strength and ductility of single-phase face-centered cubic(FCC)medium-or high-entropy alloys(M/HEAs).However,further improvements in mechanical properties remain untapped,as alloy design has historically focused on systems with specific CrCoNi-or FeCoCrNi-based FCC matrix and Ni_(3)Al L1_(2)phase compositions.This study introduces novel Co-Ni-Mo-Al alloys with L1_(2)precipitates by systematically altering Al content,aiming to bridge this research gap by revealing the strengthening mechanisms.The(CoNi)_(81)Mo_(12)Al_(7)alloy achieves yield strength of 1086 MPa,tensile strength of 1520 MPa,and ductility of 35%,demonstrating an impressive synergy of strength,ductility,and strain-hardening capacity.Dislocation analysis via transmission electron microscopy,supported by generalized stacking fault energy(GSFE)calculations using density functional theory(DFT),demonstrates that Mo substitution for Al in the L1_(2)phase alters dislocation behavior,promoting the formation of multiple deformation modes,including stacking faults,super-dislocation pairs,Lomer-Cottrell locks,and unusual nano-twin formation even at low strains.These behaviors are facilitated by the low stacking fault energy(SFE)of the FCC matrix,overlapping of SFs,and dislocation dissociation across anti-phase boundaries(APBs).The increased energy barrier for superlattice intrinsic stacking fault(SISF)formation compared to APBs,due to Mo substitution,further influences dislocation activity.This work demonstrates a novel strategy for designing high-performance M/HEAs by expanding the range of FCC matrix and L1_(2)compositions through precipitation hardening.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
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.
文摘Background:Oxidative stress and neuroinflammation are key factors in the pathophysiology of Alzheimer's disease(AD).Exercise and Aklil-ol-Malek may reduce AD symptoms.Therefore,the current study investigated the effect of weight training and Aklil-ol-Malek consumption on histopathological and inflammatory changes in hippocampal tissue of male AD model rats.Method:We prepared 558-week-old male Wistar rats and transferred them to an animal laboratory.The rats were randomly divided intofive groups:healthy control group,Alzheimer's control group,Alzheimer's group+weight training,Alzheimer's group+Aklil-ol-Malek supplement,and Alzheimer's group+Aklilol-Malek supplement+weight training.AD was induced in the 4 groups.The weight training protocol and Aklil-ol-Malek supplementation were examined as an intervention.The designated groups were administered Aklil-ol-Malek supplements.The anesthetized rats'hippocampi were extracted for further analysis 72 hours after the last session of the protocol.After the induction of AD and supplementation,two-way analysis of variance was used to examine the differences between groups(p<0.05).Results:The results showed a decrease in the expression of CRP and NFE2L2 genes in rats in the Aklil-olMalek and weight training group compared with thefindings in rats in the Alzheimer's group.Changes in the expression of BACE1 were not significant in rats in the weight training with Aklil-ol-Malek group.Conclusion:An intervention receiving exercise and Aklil-ol-Malek extract positively improved health and reduced AD progression.These results were likely to have been caused by the physiological effects of exercise and the antioxidant properties of Aklil-ol-Malek.
基金financially supported by the National Research Foundation of Korea grant funded by the Korea government(MSIT)(Nos.NRF-2022R1A5A1030054,NRF-RS-2024-00345498,and NRFRS-2023-00281508)by Korea Institute for Advancement of Technology(KIAT)grant funded by the Korea Government(MOTIE)(HRD Program for Industrial Innovation-No P0023676)+1 种基金funded by the Deutsche Forschungsgemeinschaft(DFG,German Research Foundation)-No 519607530funding from the European Research Council(ERC)under the European Union’s Horizon 2020 research and innovation program(Grant Agreement No 865855).
文摘L1_(2)precipitates are known to significantly enhance the strength and ductility of single-phase face-centered cubic(FCC)medium-or high-entropy alloys(M/HEAs).However,further improvements in mechanical properties remain untapped,as alloy design has historically focused on systems with specific CrCoNi-or FeCoCrNi-based FCC matrix and Ni_(3)Al L1_(2)phase compositions.This study introduces novel Co-Ni-Mo-Al alloys with L1_(2)precipitates by systematically altering Al content,aiming to bridge this research gap by revealing the strengthening mechanisms.The(CoNi)_(81)Mo_(12)Al_(7)alloy achieves yield strength of 1086 MPa,tensile strength of 1520 MPa,and ductility of 35%,demonstrating an impressive synergy of strength,ductility,and strain-hardening capacity.Dislocation analysis via transmission electron microscopy,supported by generalized stacking fault energy(GSFE)calculations using density functional theory(DFT),demonstrates that Mo substitution for Al in the L1_(2)phase alters dislocation behavior,promoting the formation of multiple deformation modes,including stacking faults,super-dislocation pairs,Lomer-Cottrell locks,and unusual nano-twin formation even at low strains.These behaviors are facilitated by the low stacking fault energy(SFE)of the FCC matrix,overlapping of SFs,and dislocation dissociation across anti-phase boundaries(APBs).The increased energy barrier for superlattice intrinsic stacking fault(SISF)formation compared to APBs,due to Mo substitution,further influences dislocation activity.This work demonstrates a novel strategy for designing high-performance M/HEAs by expanding the range of FCC matrix and L1_(2)compositions through precipitation hardening.
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.
