MgAl2O4 particle-reinforced AC4C based alloy composites were fabricated by the stirring-casting method. The effects of the average sizes and the size distributions of MgAl2O4 particles on the dispersibility were inves...MgAl2O4 particle-reinforced AC4C based alloy composites were fabricated by the stirring-casting method. The effects of the average sizes and the size distributions of MgAl2O4 particles on the dispersibility were investigated, and the microstructures, strength, and fatigue properties of MgAl2O4 particle-reinforced AC4C based alloy composites were evaluated. Tensile strength in the MgAl2O4 particle-reinforced AC4C based alloy composite was increased by using the classified particles. The fatigue limit at 107 cycles in the MgA1204 particle-reinforced AC4C-Cu composite increased by 27% compared to the unreinforced alloy at 250 ~C. Dislocations were observed in the matrix around the MgAl204 particle which resulted from the mismatch of thermal expansion coefficients between MgAl2O4 and Al, and resisted failure and caused fatigue cracks to propagate around the MgAl2O4 particles, resulting in extensive crack deflection and crack bowing which contributed to the improvement of fatigue strength.展开更多
Although a single nucleotide polymorphism for N-acetyltransferase 10(NAT10)has been identified in patients with early-onset stroke,the role of NAT10 in ischemic injury and the related underlying mechanisms remains elu...Although a single nucleotide polymorphism for N-acetyltransferase 10(NAT10)has been identified in patients with early-onset stroke,the role of NAT10 in ischemic injury and the related underlying mechanisms remains elusive.Here,we provide evidence that NAT10,the only known RNA N4-acetylcytidine(ac4C)modification“writer”,is increased in the damaged cortex of patients with acute ischemic stroke and the peri-infarct cortex of mice subjected to photothrombotic(PT)stroke.Pharmacological inhibition of NAT10 with remodelin on Days 3–7 post-stroke or astrocytic depletion of NAT10 via targeted virus attenuates ischemia-induced infarction and improves functional recovery in PT mice.Mechanistically,NAT10 enhances ac4C acetylation of the inflammatory cytokine tissue inhibitor of metalloproteinase 1(Timp1)mRNA transcript,which increases TIMP1 expression and results in the accumulation of microtubule-associated protein 1 light chain 3(LC3)and progression of astrocyte autophagy.These findings demonstrate that NAT10 regulates astrocyte autophagy by targeting Timp1 ac4C after stroke.This study highlights the critical role of ac4C in the regulation of astrocyte autophagy and proposes a promising strategy to improve post-stroke outcomes via NAT10 inhibition.展开更多
Thermal deformation of aluminum alloy casting materials for manufacturing the tire mold was numerically investigated.The AC7A and AC4C casting material was selected as casting material and the metal casting device was...Thermal deformation of aluminum alloy casting materials for manufacturing the tire mold was numerically investigated.The AC7A and AC4C casting material was selected as casting material and the metal casting device was used in order to manufacture the mold product of automobile tire in the actual industrial field.The temperature distribution and the cooling time of casting materials were numerically calculated by finite element analysis (FEA).Also,the thermal deformation such as displacement and stress distribution was calculated from the temperature results.The thermal deformation was closely related to the temperature difference between the surface and inside of the casting.The numerical analysis results reveal that the thermal deformation of AC7A casting material is higher than that of AC4C casting material.Also,the thermal deformation results at the central part are larger than that on the side of casting because of the shrinkage caused by the cooling speed difference.展开更多
The epigenomic landscape regulates gene expression and chromatin dynamics,with histone and RNA modifications playing crucial roles.Although studies have elucidated the interactions among chromatin modifications,DNA me...The epigenomic landscape regulates gene expression and chromatin dynamics,with histone and RNA modifications playing crucial roles.Although studies have elucidated the interactions among chromatin modifications,DNA methylation,and mRNA modifications,the relationships among RNA modifications and their collective influence on RNA metabolism remain poorly understood.Grasping these epigenetic mechanisms is essential for improving crop resilience and productivity.In this study,we explored the co-occurrence and functional interactions of three significant mRNA modifications in Arabidopsis(Arabidopsis thaliana)and rice(Oryza sativa):N^(4)-acetylcytidine(ac^(4)C),N^(6)-methyladenosine(m^(6)A),and 5-methylcytosine(m^(5)C).Our results indicate that these modifications frequently coexist in the same transcripts,exhibiting distinct spatial distributions across species.Notably,the m^(6)A modification enhances the ac^(4)C-mediated destabilization of RNA secondary structures,especially when modifications are clustered,thereby promoting RNA stability.In Arabidopsis,the ac^(4)C modification improved translational efficiency and the m^(6)A modification amplified this effect in a distance-dependent manner;by contrast,in rice the influence of m^(6)A is independent of distance.The m^(5)C modification has minimal impact on RNA structure or stability but modulates m^(6)A-associated transcript stability in a contextdependent manner.Our findings shed light on the dynamic regulatory code of combinatorial RNA modifications,highlighting species-specific mechanisms of post-transcriptional regulation.This research offers valuable insights into the intricate interplay of RNA modifications,with implications for advancing agricultural biotechnology through a deeper understanding of plant RNA functionality.展开更多
Background:N-acetyltransferase 10(NAT10)is the only enzyme known tomediate the N4-acetylcytidine(ac4C)modification of mRNA and is crucial formRNA stability and translation efficiency.However,its role in cancer develop...Background:N-acetyltransferase 10(NAT10)is the only enzyme known tomediate the N4-acetylcytidine(ac4C)modification of mRNA and is crucial formRNA stability and translation efficiency.However,its role in cancer development and prognosis has not yet been explored.This study aimed to examine the possible role of NAT10 in colon cancer.Methods:The expression levels ofNAT10were evaluated by immunohistochemical analyses with a colon cancer tissue microarray,and its prognostic value in patients was further analyzed.Quantitative real-time polymerase chain reaction(qRT-PCR)and Western blotting were performed to analyze NAT10 expression in harvested colon cancer tissues and cell lines.Stable NAT10-knockdown and NAT10-overexpressing colon cancer cell lines were constructed using lentivirus.The biological functions of NAT10 in colon cancer cell lines were analyzed in vitro by Cell Counting Kit-8(CCK-8),wound healing,Transwell,cell cycle,and ferroptosis assays.Xenograft models were used to analyze the effect of NAT10 on the tumorigenesis and metastasis of colon cancer cells in vivo.Dot blotting,acetylated RNA immunoprecipitation-qPCR,and RNA stability analyses were performed to explore the mechanism by which NAT10 functions in colon cancer progression.Results:NAT10 was upregulated in colon cancer tissues and various colon cancer cell lines.This increased NAT10 expression was associated with shorter patient survival.Knockdown of NAT10 in two colon cancer cell lines(HT-29 and LoVo)impaired the proliferation,migration,invasion,tumor formation and metastasis of these cells,whereas overexpression of NAT10 promoted these abilities.Further analysis revealed that NAT10 exerted a strong effect on the mRNA stability and expression of ferroptosis suppressor protein 1(FSP1)in HT-29 and LoVo cells.In these cells,FSP1 mRNA was found to be modified by ac4C acetylation,and this epigenetic modification was associated with the inhibition of ferroptosis.Conclusions:Our study revealed that NAT10 plays a critical role in colon cancer development by affecting FSP1 mRNA stability and ferroptosis,suggesting that NAT10 could be a novel prognostic and therapeutic target in colon cancer.展开更多
Geminiviruses (family Geminiviridae) are among the most devastating plant pathogens worldwide, causing heavy losses on food and cash crops and representing a threat to global food security and sustainability. These vi...Geminiviruses (family Geminiviridae) are among the most devastating plant pathogens worldwide, causing heavy losses on food and cash crops and representing a threat to global food security and sustainability. These viruses have very compact genomes comprising one (monopartite) or two (bipartite) circular singlestranded DNA (ssDNA) molecules, each ranging from 2.6 to 2.8 kb.展开更多
文摘MgAl2O4 particle-reinforced AC4C based alloy composites were fabricated by the stirring-casting method. The effects of the average sizes and the size distributions of MgAl2O4 particles on the dispersibility were investigated, and the microstructures, strength, and fatigue properties of MgAl2O4 particle-reinforced AC4C based alloy composites were evaluated. Tensile strength in the MgAl2O4 particle-reinforced AC4C based alloy composite was increased by using the classified particles. The fatigue limit at 107 cycles in the MgA1204 particle-reinforced AC4C-Cu composite increased by 27% compared to the unreinforced alloy at 250 ~C. Dislocations were observed in the matrix around the MgAl204 particle which resulted from the mismatch of thermal expansion coefficients between MgAl2O4 and Al, and resisted failure and caused fatigue cracks to propagate around the MgAl2O4 particles, resulting in extensive crack deflection and crack bowing which contributed to the improvement of fatigue strength.
基金supported by grants from the National Natural Science Foundation of China(32200818 to Ling Yang,82371243,82171234 and 81971041 to Zhiqiang Pan,82201391 to Qihui Wang,82104147 to Guangtian Wang)the Jiangsu Provincial Association of Science and Technology Youth Science and Technology Talent Recruitment Project(Ling Yang,China)+2 种基金the Jiangsu-Specially Appointed Professor Project,the Jiangsu Province 333 High-Level Talent Cultivation Project,Key Project of Natural Science Foundation of Jiangsu Education Department(22KJA320008 to Zhiqiang Pan,China)Jiangsu Training Program of Innovation and Entrepreneurship for Undergraduates(202310313014Z to Angrong Wu,China)the Starting Grants of Excellent Talents of Xuzhou Medical University(Ling Yang,China).
文摘Although a single nucleotide polymorphism for N-acetyltransferase 10(NAT10)has been identified in patients with early-onset stroke,the role of NAT10 in ischemic injury and the related underlying mechanisms remains elusive.Here,we provide evidence that NAT10,the only known RNA N4-acetylcytidine(ac4C)modification“writer”,is increased in the damaged cortex of patients with acute ischemic stroke and the peri-infarct cortex of mice subjected to photothrombotic(PT)stroke.Pharmacological inhibition of NAT10 with remodelin on Days 3–7 post-stroke or astrocytic depletion of NAT10 via targeted virus attenuates ischemia-induced infarction and improves functional recovery in PT mice.Mechanistically,NAT10 enhances ac4C acetylation of the inflammatory cytokine tissue inhibitor of metalloproteinase 1(Timp1)mRNA transcript,which increases TIMP1 expression and results in the accumulation of microtubule-associated protein 1 light chain 3(LC3)and progression of astrocyte autophagy.These findings demonstrate that NAT10 regulates astrocyte autophagy by targeting Timp1 ac4C after stroke.This study highlights the critical role of ac4C in the regulation of astrocyte autophagy and proposes a promising strategy to improve post-stroke outcomes via NAT10 inhibition.
基金Project supported by Research Funds from Chosun University(2009),Korea
文摘Thermal deformation of aluminum alloy casting materials for manufacturing the tire mold was numerically investigated.The AC7A and AC4C casting material was selected as casting material and the metal casting device was used in order to manufacture the mold product of automobile tire in the actual industrial field.The temperature distribution and the cooling time of casting materials were numerically calculated by finite element analysis (FEA).Also,the thermal deformation such as displacement and stress distribution was calculated from the temperature results.The thermal deformation was closely related to the temperature difference between the surface and inside of the casting.The numerical analysis results reveal that the thermal deformation of AC7A casting material is higher than that of AC4C casting material.Also,the thermal deformation results at the central part are larger than that on the side of casting because of the shrinkage caused by the cooling speed difference.
基金support from the National Natural Science Foundation of China(32270623)the Natural Science Foundation of Hunan Province(2024JJ2016)+2 种基金Hunan Science and Technology Innovation Plan(2025ZYJ003)China Tobacco Hunan Industrial Co.,Ltd.Research Project(KY2023YC0015)support from the China Tobacco Genome Project(110202101037,JY-14).
文摘The epigenomic landscape regulates gene expression and chromatin dynamics,with histone and RNA modifications playing crucial roles.Although studies have elucidated the interactions among chromatin modifications,DNA methylation,and mRNA modifications,the relationships among RNA modifications and their collective influence on RNA metabolism remain poorly understood.Grasping these epigenetic mechanisms is essential for improving crop resilience and productivity.In this study,we explored the co-occurrence and functional interactions of three significant mRNA modifications in Arabidopsis(Arabidopsis thaliana)and rice(Oryza sativa):N^(4)-acetylcytidine(ac^(4)C),N^(6)-methyladenosine(m^(6)A),and 5-methylcytosine(m^(5)C).Our results indicate that these modifications frequently coexist in the same transcripts,exhibiting distinct spatial distributions across species.Notably,the m^(6)A modification enhances the ac^(4)C-mediated destabilization of RNA secondary structures,especially when modifications are clustered,thereby promoting RNA stability.In Arabidopsis,the ac^(4)C modification improved translational efficiency and the m^(6)A modification amplified this effect in a distance-dependent manner;by contrast,in rice the influence of m^(6)A is independent of distance.The m^(5)C modification has minimal impact on RNA structure or stability but modulates m^(6)A-associated transcript stability in a contextdependent manner.Our findings shed light on the dynamic regulatory code of combinatorial RNA modifications,highlighting species-specific mechanisms of post-transcriptional regulation.This research offers valuable insights into the intricate interplay of RNA modifications,with implications for advancing agricultural biotechnology through a deeper understanding of plant RNA functionality.
基金National Natural Science Foundation of China,Grant/Award Numbers:81902386,81972869,82002479The Natural Science Foundation of Jiangsu Province,Grant/Award Numbers:BK20211065,BK20200179+2 种基金China Postdoctoral Science Foundation,Grant/Award Number:2021M700547Youth Talent Science and Technology Project of Changzhou Health Commission,Grant/Award Number:QN202103The open fund of state key laboratory of Pharmaceutical Biotechnology,Nanjing University,China,Grant/Award Number:KF-202203。
文摘Background:N-acetyltransferase 10(NAT10)is the only enzyme known tomediate the N4-acetylcytidine(ac4C)modification of mRNA and is crucial formRNA stability and translation efficiency.However,its role in cancer development and prognosis has not yet been explored.This study aimed to examine the possible role of NAT10 in colon cancer.Methods:The expression levels ofNAT10were evaluated by immunohistochemical analyses with a colon cancer tissue microarray,and its prognostic value in patients was further analyzed.Quantitative real-time polymerase chain reaction(qRT-PCR)and Western blotting were performed to analyze NAT10 expression in harvested colon cancer tissues and cell lines.Stable NAT10-knockdown and NAT10-overexpressing colon cancer cell lines were constructed using lentivirus.The biological functions of NAT10 in colon cancer cell lines were analyzed in vitro by Cell Counting Kit-8(CCK-8),wound healing,Transwell,cell cycle,and ferroptosis assays.Xenograft models were used to analyze the effect of NAT10 on the tumorigenesis and metastasis of colon cancer cells in vivo.Dot blotting,acetylated RNA immunoprecipitation-qPCR,and RNA stability analyses were performed to explore the mechanism by which NAT10 functions in colon cancer progression.Results:NAT10 was upregulated in colon cancer tissues and various colon cancer cell lines.This increased NAT10 expression was associated with shorter patient survival.Knockdown of NAT10 in two colon cancer cell lines(HT-29 and LoVo)impaired the proliferation,migration,invasion,tumor formation and metastasis of these cells,whereas overexpression of NAT10 promoted these abilities.Further analysis revealed that NAT10 exerted a strong effect on the mRNA stability and expression of ferroptosis suppressor protein 1(FSP1)in HT-29 and LoVo cells.In these cells,FSP1 mRNA was found to be modified by ac4C acetylation,and this epigenetic modification was associated with the inhibition of ferroptosis.Conclusions:Our study revealed that NAT10 plays a critical role in colon cancer development by affecting FSP1 mRNA stability and ferroptosis,suggesting that NAT10 could be a novel prognostic and therapeutic target in colon cancer.
基金National Science Foundation (NSF), grant number IOS-1212576.
文摘Geminiviruses (family Geminiviridae) are among the most devastating plant pathogens worldwide, causing heavy losses on food and cash crops and representing a threat to global food security and sustainability. These viruses have very compact genomes comprising one (monopartite) or two (bipartite) circular singlestranded DNA (ssDNA) molecules, each ranging from 2.6 to 2.8 kb.
