Background Chinese indigenous pigs are popular with consumers for their juiciness,flavour and meat quality,but they have lower meat production.Insulin-like growth factor 2(IGF2) is a maternally imprinted growth factor...Background Chinese indigenous pigs are popular with consumers for their juiciness,flavour and meat quality,but they have lower meat production.Insulin-like growth factor 2(IGF2) is a maternally imprinted growth factor that promotes skeletal muscle growth by regulating cell proliferation and differentiation.A single nucleotide polymorphism(SNP) within intron 3 of porcine IGF2 disrupts a binding site for the repressor,zinc finger BED-type containing 6(ZBED6),leading to up-regulation of IGF2 and causing major effects on muscle growth,heart size,and backfat thickness.This favorable mutation is common in Western commercial pig populations,but absent in most Chinese indigenous pig breeds.To improve meat production of Chinese indigenous pigs,we used cytosine base editor 3(CBE3)to introduce IGF2 intron3-C3071T mutation into porcine embryonic fibroblasts(PEFs) isolated from a male Liang Guang Small Spotted pig(LGSS),and single-cell clones harboring the desired mutation were selected for somatic cell nuclear transfer(SCNT) to generate the founder line of IGF2^(T/T) pigs.Results We found the heterozygous progeny IGF2^(C/T) pigs exhibited enhanced expression of IGF2,increased lean meat by 18%-36%,enlarged loin muscle area by 3%-17%,improved intramuscular fat(IMF) content by 18%-39%,marbling score by 0.75-1,meat color score by 0.53-1.25,and reduced backfat thickness by 5%-16%.The enhanced accumulation of intramuscular fat in IGF2^(C/T) pigs was identified to be regulated by the PI3K-AKT/AMPK pathway,which activated SREBP1 to promote adipogenesis.Conclusions We demonstrated the introduction of IGF2-intron3-C3071T in Chinese LGSS can improve both meat production and quality,and first identified the regulation of IMF deposition by IGF2 through SREBP1 via the PI3KAKT/AMPK signaling pathways.Our study provides a further understanding of the biological functions of IGF2and an example for improving porcine economic traits through precise base editing.展开更多
Magnesium(Mg)-based bone implants degrade rapidly in the physiological environment of the human body which affects their structural integrity and biocompatibility before adequate bone repair.Rare earth elements(REEs)h...Magnesium(Mg)-based bone implants degrade rapidly in the physiological environment of the human body which affects their structural integrity and biocompatibility before adequate bone repair.Rare earth elements(REEs)have demonstrated their effectiveness in tailoring the corrosion and mechanical behavior of Mg alloys.This study methodically investigated the impacts of scandium(Sc)and terbium(Tb)in tailoring the corrosion resistance,mechanical properties,and biocompatibility of Mg–0.5Zn–0.35Zr–0.15Mn(MZZM)alloys fabricated via casting and hot extrusion.Results indicate that addition of Sc and Tb improved the strength of MZZM alloys via grain size reduction and solid solution strengthening mechanisms.The extruded MZZM–(1–2)Sc–(1–2)Tb(wt.%)alloys exhibit compressive strengths within the range of 336–405 MPa,surpassing the minimum required strength of 200 MPa for bone implants by a significant margin.Potentiodynamic polarization tests revealed low corrosion rates of as–cast MZZM(0.25 mm/y),MZZM–2Tb(0.45 mm/y),MZZM–1Sc–1Tb(0.18 mm/y),and MZZM–1Sc–2Tb(0.64 mm/y),and extruded MZZM(0.17 mm/y),MZZM–1Sc(0.15 mm/y),MZZM-2Sc(0.45 mm/y),MZZM-1Tb(0.17 mm/y),MZZM-2Tb(0.10 mm/y),MZZM–1Sc-1Tb(0.14 mm/y),MZZM-1Sc-2Tb(0.40 mm/y),and MZZM–2Sc–2Tb(0.51 mm/y)alloys,which were found lower compared to corrosion rate of high-purity Mg(~1.0 mm/y)reported in the literature.Furthermore,addition of Sc,or Tb,or Sc and Tb to MZZM alloys did not adversely affect the viability of SaOS2 cells,but enhanced their initial cell attachment,proliferation,and spreading shown via polygonal shapes and filipodia.This study emphasizes the benefits of incorporating Sc and Tb elements in MZZM alloys,as they effectively enhance corrosion resistance,mechanical properties,and biocompatibility simultaneously.展开更多
Zinc(Zn) and its alloys have been proposed as biodegradable implant materials due to their unique combination of biodegradability, biocompatibility, and biofunctionality. However, the insufficient mechanical propertie...Zinc(Zn) and its alloys have been proposed as biodegradable implant materials due to their unique combination of biodegradability, biocompatibility, and biofunctionality. However, the insufficient mechanical properties of pure Zn greatly limit its clinical application. Here, we report on the microstructure, mechanical properties, friction and wear behavior, corrosion and degradation properties, hemocompatibility, and cytocompatibility of Zn–3 Cu and Zn–3 Cu–0.2 Ti alloys under three different conditions of as-cast(AC),hot-rolling(HR), and hot-rolling plus cold-rolling(HR + CR). The HR + CR Zn–3 Cu–0.2 Ti exhibited the best set of comprehensive properties among all the alloy samples, with yield strength of 211.0 MPa, ultimate strength of 271.1 MPa, and elongation of 72.1 %. Immersion tests of the Zn–3 Cu and Zn–3 Cu–0.2 Ti alloys in Hanks’ solution for 3 months indicated that the AC samples showed the lowest degradation rate,followed by the HR samples, and then the HR + CR samples, while the HR + CR Zn–3 Cu exhibited the highest degradation rate of 23.9 m/a. Friction and wear testing of the Zn–3 Cu and Zn–3 Cu–0.2 Ti alloys in Hanks’ solution indicated that the AC samples showed the highest wear resistance, followed by the HR samples, and then the HR + CR samples, while the AC Zn–3 Cu–0.2 Ti showed the highest wear resistance.The diluted extracts of HR + CR Zn–3 Cu and Zn–3 Cu–0.2 Ti at a concentration of ≤25 % exhibited noncytotoxicity. Furthermore, both the HR + CR Zn–3 Cu and Zn–3 Cu–0.2 Ti exhibited effective antibacterial properties against S. aureus.展开更多
Zinc(Zn)and its biocompatible and biodegradable alloys have substantial potential for use in orthopedic implants.Nevertheless,pure Zn with a hexagonal close-packed crystal structure has only two independent slip syste...Zinc(Zn)and its biocompatible and biodegradable alloys have substantial potential for use in orthopedic implants.Nevertheless,pure Zn with a hexagonal close-packed crystal structure has only two independent slip systems,therefore exhibiting extremely low elongation and yield strength in its ascast condition,which restricts its clinical applications.In this study,as-cast Zn–xTi(titanium)(x=0.05,0.10,0.20,and 0.30 wt.%)binary alloys were hot-rolled and their microstructures,mechanical properties,wear resistance,and cytocompatibility were comprehensively investigated for orthopedic implant applications.The microstructures of both as-cast and hot-rolled Zn–xTi alloys consisted of anα-Zn matrix phase and a TiZn16 phase,while Zn–0.2 Ti and Zn–0.3 Ti exhibited a finerα-Zn phase due to the grainrefining effect of Ti.The hot-rolled Zn–0.2 Ti alloy exhibited the highest yield strength(144.5 MPa),ultimate strength(218.7 MPa),and elongation(54.2%)among all the Zn–x Ti alloys.The corrosion resistance of Zn–xTi alloys in Hanks’solution decreased with increasing addition of Ti,and the hot-rolled Zn–0.3 Ti alloy exhibited the highest corrosion rates of 432μm/y as measured by electrochemical testing and 57.9μm/y as measured by immersion testing.The as-cast Zn–xTi alloys showed lower wear losses than their hot-rolled counterparts.The extracts of hot-rolled Zn–x Ti alloys at concentrations of≤25%showed no cytotoxicity to MG-63 osteosarcoma cells and the extracts of Zn–xTi alloys exhibited enhanced cytocompatibility with increasing Ti content.展开更多
Ti-Nb alloys have great potential in biomedical applications as bone-implant materials due to their low elastic modulus,superelasticity,high corrosion resistance,and good biocompatibility.However,the low yield strengt...Ti-Nb alloys have great potential in biomedical applications as bone-implant materials due to their low elastic modulus,superelasticity,high corrosion resistance,and good biocompatibility.However,the low yield strength and poor superelasticity of Ti-Nb alloys restrict their practical clinical applications.Here,we report the mechanical properties and superelasticity,corrosion behavior,and biocompatibility of a Ti-26 at.%Nb-1.2 vol.%TiC(Ti-26Nb-1.2TiC)shape memory composite(SMC)prepared by vacuum arc melting and hot rolling.The yield strength,critical stress for inducing martensitic transformation,and elongation of the Ti-26Nb-1.2TiC SMC and a Ti-26Nb alloy were 460 and 337 MPa,251 and 115 MPa,and 27.2%and 24.1%,respectively.The recovery rate of the SMC under 4%pre-strain reached 91.4%,which was 1.2 times that of the Ti-26Nb.Electrochemical tests in Hanks’solution revealed that the corrosion current density,passive current density,and corrosion rate of the SMC were lower than those of the Ti-26Nb.Both the Ti-26Nb alloy and Ti-26Nb-1.2TiC SMC showed good cell viability with grade 0 cytotoxicity in relation to MG-63 osteosarcoma cells.展开更多
基金supported by the National Natural Science Foundation of China (3207269732030102)+2 种基金CARS-PIG-35R&D Programmes of Guangdong Province (2018B020203003)Laboratory of Lingnan Modern Agriculture Project (NZ2021006)。
文摘Background Chinese indigenous pigs are popular with consumers for their juiciness,flavour and meat quality,but they have lower meat production.Insulin-like growth factor 2(IGF2) is a maternally imprinted growth factor that promotes skeletal muscle growth by regulating cell proliferation and differentiation.A single nucleotide polymorphism(SNP) within intron 3 of porcine IGF2 disrupts a binding site for the repressor,zinc finger BED-type containing 6(ZBED6),leading to up-regulation of IGF2 and causing major effects on muscle growth,heart size,and backfat thickness.This favorable mutation is common in Western commercial pig populations,but absent in most Chinese indigenous pig breeds.To improve meat production of Chinese indigenous pigs,we used cytosine base editor 3(CBE3)to introduce IGF2 intron3-C3071T mutation into porcine embryonic fibroblasts(PEFs) isolated from a male Liang Guang Small Spotted pig(LGSS),and single-cell clones harboring the desired mutation were selected for somatic cell nuclear transfer(SCNT) to generate the founder line of IGF2^(T/T) pigs.Results We found the heterozygous progeny IGF2^(C/T) pigs exhibited enhanced expression of IGF2,increased lean meat by 18%-36%,enlarged loin muscle area by 3%-17%,improved intramuscular fat(IMF) content by 18%-39%,marbling score by 0.75-1,meat color score by 0.53-1.25,and reduced backfat thickness by 5%-16%.The enhanced accumulation of intramuscular fat in IGF2^(C/T) pigs was identified to be regulated by the PI3K-AKT/AMPK pathway,which activated SREBP1 to promote adipogenesis.Conclusions We demonstrated the introduction of IGF2-intron3-C3071T in Chinese LGSS can improve both meat production and quality,and first identified the regulation of IMF deposition by IGF2 through SREBP1 via the PI3KAKT/AMPK signaling pathways.Our study provides a further understanding of the biological functions of IGF2and an example for improving porcine economic traits through precise base editing.
基金the financial support provided by the Australian Research Council(ARC)through the Future Fellowship(FT160100252)the Discovery Project(DP170102557)for this research。
文摘Magnesium(Mg)-based bone implants degrade rapidly in the physiological environment of the human body which affects their structural integrity and biocompatibility before adequate bone repair.Rare earth elements(REEs)have demonstrated their effectiveness in tailoring the corrosion and mechanical behavior of Mg alloys.This study methodically investigated the impacts of scandium(Sc)and terbium(Tb)in tailoring the corrosion resistance,mechanical properties,and biocompatibility of Mg–0.5Zn–0.35Zr–0.15Mn(MZZM)alloys fabricated via casting and hot extrusion.Results indicate that addition of Sc and Tb improved the strength of MZZM alloys via grain size reduction and solid solution strengthening mechanisms.The extruded MZZM–(1–2)Sc–(1–2)Tb(wt.%)alloys exhibit compressive strengths within the range of 336–405 MPa,surpassing the minimum required strength of 200 MPa for bone implants by a significant margin.Potentiodynamic polarization tests revealed low corrosion rates of as–cast MZZM(0.25 mm/y),MZZM–2Tb(0.45 mm/y),MZZM–1Sc–1Tb(0.18 mm/y),and MZZM–1Sc–2Tb(0.64 mm/y),and extruded MZZM(0.17 mm/y),MZZM–1Sc(0.15 mm/y),MZZM-2Sc(0.45 mm/y),MZZM-1Tb(0.17 mm/y),MZZM-2Tb(0.10 mm/y),MZZM–1Sc-1Tb(0.14 mm/y),MZZM-1Sc-2Tb(0.40 mm/y),and MZZM–2Sc–2Tb(0.51 mm/y)alloys,which were found lower compared to corrosion rate of high-purity Mg(~1.0 mm/y)reported in the literature.Furthermore,addition of Sc,or Tb,or Sc and Tb to MZZM alloys did not adversely affect the viability of SaOS2 cells,but enhanced their initial cell attachment,proliferation,and spreading shown via polygonal shapes and filipodia.This study emphasizes the benefits of incorporating Sc and Tb elements in MZZM alloys,as they effectively enhance corrosion resistance,mechanical properties,and biocompatibility simultaneously.
基金supported financially by the Research Funds of the Wenzhou Science and Technology Bureau (Nos.ZG2019022 and 2018ZG008)support for this research by the Australian Research Council (ARC) through the Discovery Project (No.DP170102557)+1 种基金the Future Fellowship(No.FT160100252)support of the ARC Research Hub for Advanced Manufacturing of Medical Devices (No.IH150100024)。
文摘Zinc(Zn) and its alloys have been proposed as biodegradable implant materials due to their unique combination of biodegradability, biocompatibility, and biofunctionality. However, the insufficient mechanical properties of pure Zn greatly limit its clinical application. Here, we report on the microstructure, mechanical properties, friction and wear behavior, corrosion and degradation properties, hemocompatibility, and cytocompatibility of Zn–3 Cu and Zn–3 Cu–0.2 Ti alloys under three different conditions of as-cast(AC),hot-rolling(HR), and hot-rolling plus cold-rolling(HR + CR). The HR + CR Zn–3 Cu–0.2 Ti exhibited the best set of comprehensive properties among all the alloy samples, with yield strength of 211.0 MPa, ultimate strength of 271.1 MPa, and elongation of 72.1 %. Immersion tests of the Zn–3 Cu and Zn–3 Cu–0.2 Ti alloys in Hanks’ solution for 3 months indicated that the AC samples showed the lowest degradation rate,followed by the HR samples, and then the HR + CR samples, while the HR + CR Zn–3 Cu exhibited the highest degradation rate of 23.9 m/a. Friction and wear testing of the Zn–3 Cu and Zn–3 Cu–0.2 Ti alloys in Hanks’ solution indicated that the AC samples showed the highest wear resistance, followed by the HR samples, and then the HR + CR samples, while the AC Zn–3 Cu–0.2 Ti showed the highest wear resistance.The diluted extracts of HR + CR Zn–3 Cu and Zn–3 Cu–0.2 Ti at a concentration of ≤25 % exhibited noncytotoxicity. Furthermore, both the HR + CR Zn–3 Cu and Zn–3 Cu–0.2 Ti exhibited effective antibacterial properties against S. aureus.
基金the Wenzhou Science and Technology Bureau through the project ZG2019022 and 2018ZG008financial support for this research by the Australian Research Council(ARC)through the Discovery Project DP170102557+1 种基金Future Fellowship FT160100252the support of the ARC Research Hub for Advanced Manufacturing of Medical Devices(IH150100024)。
文摘Zinc(Zn)and its biocompatible and biodegradable alloys have substantial potential for use in orthopedic implants.Nevertheless,pure Zn with a hexagonal close-packed crystal structure has only two independent slip systems,therefore exhibiting extremely low elongation and yield strength in its ascast condition,which restricts its clinical applications.In this study,as-cast Zn–xTi(titanium)(x=0.05,0.10,0.20,and 0.30 wt.%)binary alloys were hot-rolled and their microstructures,mechanical properties,wear resistance,and cytocompatibility were comprehensively investigated for orthopedic implant applications.The microstructures of both as-cast and hot-rolled Zn–xTi alloys consisted of anα-Zn matrix phase and a TiZn16 phase,while Zn–0.2 Ti and Zn–0.3 Ti exhibited a finerα-Zn phase due to the grainrefining effect of Ti.The hot-rolled Zn–0.2 Ti alloy exhibited the highest yield strength(144.5 MPa),ultimate strength(218.7 MPa),and elongation(54.2%)among all the Zn–x Ti alloys.The corrosion resistance of Zn–xTi alloys in Hanks’solution decreased with increasing addition of Ti,and the hot-rolled Zn–0.3 Ti alloy exhibited the highest corrosion rates of 432μm/y as measured by electrochemical testing and 57.9μm/y as measured by immersion testing.The as-cast Zn–xTi alloys showed lower wear losses than their hot-rolled counterparts.The extracts of hot-rolled Zn–x Ti alloys at concentrations of≤25%showed no cytotoxicity to MG-63 osteosarcoma cells and the extracts of Zn–xTi alloys exhibited enhanced cytocompatibility with increasing Ti content.
基金supported by the National Natural Science Foundation of China (Grant Nos.51971190 and 11872053)support for this research by the Australian Research Council (ARC)through the Discovery Project (No.DP210101862)Future Fellowship (No.FT160100252).
文摘Ti-Nb alloys have great potential in biomedical applications as bone-implant materials due to their low elastic modulus,superelasticity,high corrosion resistance,and good biocompatibility.However,the low yield strength and poor superelasticity of Ti-Nb alloys restrict their practical clinical applications.Here,we report the mechanical properties and superelasticity,corrosion behavior,and biocompatibility of a Ti-26 at.%Nb-1.2 vol.%TiC(Ti-26Nb-1.2TiC)shape memory composite(SMC)prepared by vacuum arc melting and hot rolling.The yield strength,critical stress for inducing martensitic transformation,and elongation of the Ti-26Nb-1.2TiC SMC and a Ti-26Nb alloy were 460 and 337 MPa,251 and 115 MPa,and 27.2%and 24.1%,respectively.The recovery rate of the SMC under 4%pre-strain reached 91.4%,which was 1.2 times that of the Ti-26Nb.Electrochemical tests in Hanks’solution revealed that the corrosion current density,passive current density,and corrosion rate of the SMC were lower than those of the Ti-26Nb.Both the Ti-26Nb alloy and Ti-26Nb-1.2TiC SMC showed good cell viability with grade 0 cytotoxicity in relation to MG-63 osteosarcoma cells.
