Single-base editing in IGF2 improves meat production and intramuscular fat deposition in Liang Guang Small Spotted pigs

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.

A sport and a pastime:Model design and computation in quantum many-body systems

We summarize the recent developments in the model design and computation for a few representative quantum manybody systems,encompassing quantum critical metals beyond the Hertz-Millis-Moriya framework with pseudogap and superconductivity,SYK non-Fermi-liquid with self-tuned quantum criticality and fluctuation induced superconductivity,and the flat-band quantum Moirélattice models in continuum where the interplay of quantum geometry of flat-band wave function and the long-range Coulomb interactions gives rise to novel insulating phases at integer fillings and superconductivity away from them.Although the narrative choreography seems simple,we show how important the appropriate model design and their tailor-made algorithmic developments-in other words,the scientific imagination inspired by the corresponding fast experimental developments in the aforementioned systems-compel us to invent and discover new knowledge and insights in the sport and pastime of quantum many-body research.

Solving quantum rotor model with different Monte Carlo techniques

We systematically test the performance of several Monte Carlo update schemes for the(2+1)d XY phase transition of quantum rotor model.By comparing the local Metropolis(LM),LM plus over-relaxation(OR),Wolff-cluster(WC),hybrid Monte Carlo(HM),hybrid Monte Carlo with Fourier acceleration(FA)schemes,it is clear that among the five different update schemes,at the quantum critical point,the WC and FA schemes acquire the smallest autocorrelation time and cost the least amount of CPU hours in achieving the same level of relative error,and FA enjoys a further advantage of easily implementable for more complicated interactions such as the long-range ones.These results bestow one with the necessary knowledge of extending the quantum rotor model,which plays the role of ferromagnetic/antiferromagnetic critical bosons or Z_(2)topological order,to more realistic and yet challenging models such as Fermi surface Yukawa-coupled to quantum rotor models.