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.

Failure transition of shear-to-dilation band of rock salt under triaxial stresses

Great potential of underground gas/energy storage in salt caverns seems to be a promising solution to support renewable energy.In the underground storage method,the operating cycle unfortunately may reach up to daily or even hourly,which generates complicated pressures on the salt cavern.Furthermore,the mechanical behavior of rock salt may change and present distinct failure characteristics under different stress states,which affects the performance of salt cavern during the time period of full service.To reproduce a similar loading condition on the cavern surrounding rock mass,the cyclic triaxial loading/unloading tests are performed on the rock salt to explore the mechanical transition behavior and failure characteristics under different confinement.Experimental results show that the rock salt samples pre-sent a diffused shear failure band with significant bulges at certain locations in low confining pressure conditions(e.g.5 MPa,10 MPa and 15 MPa),which is closely related to crystal misorientation and grain boundary sliding.Under the elevated confinement(e.g.20 MPa,30 MPa and 40 MPa),the dilation band dominates the failure mechanism,where the large-size halite crystals are crushed to be smaller size and new pores are developing.The failure transition mechanism revealed in the paper provides additional insight into the mechanical performance of salt caverns influenced by complicated stress states.

Benzodiazepines in complex biological matrices: Recent updates on pretreatment and detection methods

Benzodiazepines(BDZs)are used in clinics for anxiolysis,anticonvulsants,sedative hypnosis,and muscle relaxation.They have high consumptions worldwide because of their easy availability and potential addiction.They are often used for suicide or criminal practices such as abduction and drug-facilitated sexual assault.The pharmacological effects of using small doses of BDZs and their detections from complex biological matrices are challenging.Efficient pretreatment methods followed by accurate and sensitive detections are necessary.Herein,pretreatment methods for the extraction,enrichment,and preconcentration of BDZs as well as the strategies for their screening,identification,and quantitation developed in the past five years have been reviewed.Moreover,recent advances in various methods are summarized.Characteristics and advantages of each method are encompassed.Future directions of the pretreatment and detection methods for BDZs are also reviewed.

Distribution of wetlands and salt lakes in the Yadong region of Tibet based on remote sensing, and their geo-climatic environmental changes

Based on the 16 scenes GF-1 satellite multi-spectral remote sensing images,through the adoption of data processing methods including orthorectification,geometric rectification,data fusion and image mosaic,integrated with field surveys,the remote sensing interpretation signs for the inland wetland types have been built,and the remote sensing survey of inland wetlands in Yadong region has been initiated,with six types of inland wetlands recognized in Yadong region,namely permanent rivers,seasonal rivers,lakes,salt lakes,alpine meadows,and inundated land.The spatial distribution characteristics and the spreading rules of these wetlands have also been revealed.Based on full understanding of the overall characteristics of the inland wetlands in the Yadong region,using the three phases of TM images acquired in 1989,2003 and 2008 as well as the PMS2 data gathered by GF-1 in 2014,and the wide-range data(WFV3)gathered by GF-1 in 2020.As to the typical salt lakes,a long-time salt lakes transition study was carried out.The results show that the typical salt lakes in Yadong have been shrinking in the past three decades.The average annual shrinkage of Duoqing Co(Co means lake in Tibetan)was stronger than that of Gala Co,which are respective 87.30 hectares(usually short as ha;1 ha equals to 0.01 km^(2))/a and 24.20 ha/a;the shrinkage degree of Gala Co was higher than that of Duoqing Co,shrank by 59.27% and 35.73% respectively.Based on the remote sensing survey results and an integrated analysis of the predecessors’researchers,the reason for the shrinkage of the salt lakes is more inclined to geological factors.Geological process is manifested by a series of extensional faults at the bottom of the lake basin generated from tectonic activities,providing fluid infiltration channels,and inducing the eventual leakage of lake water to the lower strata.The result provides an important instance for understanding the evolution characteristics of wetlands and salt lakes in specific environment of the Tibetan Plateau.

Sub-picosecond electron bunch length measurement using coherent transition radiation at SXFEL

Longitudinal electron bunch length plays a significant role in single-pass free-electron lasers(FEL), as the high-gain FEL process depends strongly on the high peak current of electron bunches. Longitudinal electron bunch length was measured by detecting the interferogram of coherent transition radiation generated by electron bunches using a THz interferometer and a Golay cell(spectral range0.02-20 THz) at Shanghai X-ray free-electron laser. The detailed process of measurement and data analysis are discussed herein. Furthermore, the electron bunch length was estimated based on the dispersive strength R_(56) of the bunch compressor and the energy spread δ of electron bunches, which were obtained via experiments. The comparison showed that the measured bunch length was consistent with the estimated bunch length.

A Proposal for an Integrated Model to Evaluate the Circadian Effects of Mesopic Light Sources

With the increasing attention on circadian effects driven by light,lighting industry has inspired a revolution of photobiological lighting design.Due to diverse evaluation criteria for visual and non⁃visual systems,models that combine these evaluation parameters are indeed urgent.Thus,an integrated model for mesopic lighting evaluation of circadian effects was proposed.The circadian efficiency function adopted in this study was synthesized by CIE 1931 XYZ 2 deg color matching functions and standard scotopic sensitivity function.Then,the integrated model composed of International Commission on Illumination 1931 xy chromaticity coordinates,scotopic/photopic ratio,and illuminance could be obtained with synthesized circadian efficiency function.The model showed that for light sources with fixed chromaticity coordinates and fixed illuminance,enhancing the circadian effects is equivalent to increasing the scotopic/photopic ratio,which suggests a useful method for practitioners to explore the photobiologically reasonable spectrum for mesopic lighting.Light⁃emitting diodes spectra optimized by four⁃component color⁃mixing method were employed to figure out the property of the integrated model.

m^(6)A reader YTHDF1 promotes cardiac fibrosis by enhancing AXL translation

Cardiac fibrosis caused by ventricular remodeling and dysfunction such as post-myocardial infarction(MI)can lead to heart failure.RNA N6-methyladenosine(m^(6)A)methylation has been shown to play a pivotal role in the occurrence and development of many illnesses.In investigating the biological function of the m^(6)A reader YTHDF1 in cardiac fibrosis,adeno-associated virus 9 was used to knock down or overexpress the YTHDF1 gene in mouse hearts,and MI surgery in vivo and transforming growth factor-β(TGF-β)-activated cardiac fibroblasts in vitro were performed to establish fibrosis models.Our results demonstrated that silencing YTHDF1 in mouse hearts can significantly restore impaired cardiac function and attenuate myocardial fibrosis,whereas YTHDF1 overexpression could further enhance cardiac dysfunction and aggravate the occurrence of ventricular pathological remodeling and fibrotic development.Mechanistically,zinc finger BED-type containing 6 mediated the transcriptional function of the YTHDF1 gene promoter.YTHDF1 augmented AXL translation and activated the TGF-β-Smad2/3 signaling pathway,thereby aggravating the occurrence and development of cardiac dysfunction and myocardial fibrosis.Consistently,our data indicated that YTHDF1 was involved in activation,proliferation,and migration to participate in cardiac fibrosis in vitro.Our results revealed that YTHDF1 could serve as a potential therapeutic target for myocardial fibrosis.

Effect of nano-TiC dopant size on magnetic properties and corrosion resistance of hot-deformed NdFeB

Effects of dopant size on the magnetic properties and corrosion behavior of hot-deformed NdFeB with the intergranular additions of nano-TiC were investigated using X-ray diffraction(XRD),X-ray photoelectron spectrometer(XPS),scanning electron microscopy(SEM),electrochemical and magnetic measurement technologies.Additions of 50 nm-TiC,unlike 30 nm- and 40 nm-TiC,are found to increase the magnetic energy product and comprehensive magnetic properties,due in main to the improvement of magnet orientation by more strip-shaped Nd-rich phases.Nano-TiC dopants especially with a size of40 nm can increase the electrochemical corrosion resistance of magnets.It is attributed to the hindrance of additives on the reaction channel formation and their barrier effect on the oxidations of Nd and Fe.For 40 nm-TiC doped magnet,the charge transfer resistance in electric double layer structure reaches 15000 Ω·cm^(2) that is one order of magnitude higher than other cases,which is responsible for the lowe st corrosion current density and accordingly the best anti-corrosion properties.