Highly Sensitive MoS_2–Indocyanine Green Hybrid for Photoacoustic Imaging of Orthotopic Brain Glioma at Deep Site

Photoacoustic technology in combination with molecular imaging is a highly effective method for accurately diagnosing brain glioma. For glioma detection at a deeper site, contrast agents with higher photoacoustic imaging sensitivity are needed. Herein, we report a MoS_2–ICG hybrid with indocyanine green(ICG) conjugated to the surface of MoS_2 nanosheets. The hybrid significantly enhanced photoacoustic imaging sensitivity compared to MoS_2 nanosheets. This conjugation results in remarkably high optical absorbance across a broad near-infrared spectrum, redshifting of the ICG absorption peak and photothermal/photoacoustic conversion efficiency enhancement of ICG. A tumor mass of 3.5 mm beneath the mouse scalp was clearly visualized by using MoS_2–ICG as a contrast agent for the in vivo photoacoustic imaging of orthotopic glioma, which is nearly twofold deeper than the tumors imaged in our previous report using MoS_2 nanosheet. Thus, combined with its good stability and high biocompatibility, the MoS_2–ICG hybrid developed in this study has a great potential for high-efficiency tumor molecular imaging in translational medicine.

Customized anterior segment photoacoustic imaging for ophthalmic burn evaluation in vivo

Photoacoustic imaging has many advantages in ophthalmic application including high-resolution,requirement of no exogenous contrast agent,and noninvasive acquisition of both morphologic and functional information.However,due to the limited depth of focus of the imaging method and large curvature of the eye,it remains a challenge to obtain high quality vascular image of entire anterior segment.Here,we proposed a new method to achieve high quality imaging of anterior segment.The new method applied a curvature imaging strategy based on only one time scanning,and hence is time efficient and more suitable for ophthalmic imaging compared to previously reported methods using similar strategy.A custom-built photoacoustic imaging system was adapted for ophthalmic application and a customized image processing method was developed to quantitatively analyze both morphologic and functional information in vasculature of the anterior segment.The results showed that the new method improved the image quality of anterior segment significantly compared to that of conventional high resolution photoacoustic imaging.More importantly,we applied the new method to study ophthalmic disease in an in vivo mouse model for the first time.The results verified the suitability and advantages of the new method for imaging the entire anterior segment and the numerous potentials of applying it in ophthalmic imaging in future.

Recovery of photoacoustic images based on accurate ultrasound positioning

Photoacoustic microscopy is an in vivo imaging technology based on the photoacoustic effect.It is widely used in various biomedical studies because it can provide high-resolution images while being label-free,safe,and harmless to biological tissue.Polygon-scanning is an effective scanning method in photoacoustic microscopy that can realize fast imaging of biological tissue with a large field of view.However,in polygon-scanning,fluctuations of the rotating motor speed and the geometric error of the rotating mirror cause image distortions,which seriously affect the photoacoustic-microscopy imaging quality.To improve the image quality of photoacoustic microscopy using polygon-scanning,an image correction method is proposed based on accurate ultrasound positioning.In this method,the photoacoustic and ultrasound imaging data of the sample are simultaneously obtained,and the angle information of each mirror used in the polygon-scanning is extracted from the ultrasonic data to correct the photoacoustic images.Experimental results show that the proposed method can significantly reduce image distortions in photoacoustic microscopy,with the image dislocation offset decreasing from 24.774 to 10.365μm.

青藏高原牦牛驯化的考古学与遗传学研究进展及展望

家牦牛在史前人类定居青藏高原的过程中起到了巨大作用,但牦牛的驯化过程仍存在诸多未解决的科学问题.本文梳理了牦牛驯化的考古学和遗传学研究进展,展望了开展牦牛驯化与人类定居青藏高原过程研究的未来方向.家牦牛最早的考古学证据来自距今3750年前的青藏高原南部拉萨河谷,但现代遗传学研究显示,牦牛的驯化可追溯至全新世中期,驯化地点最有可能位于西藏东南部的昌都地区,其种群数量增长与人类大规模长年定居青藏高原高海拔地区的历史高度相关,且黄牛的基因渗入对牦牛的驯化过程产生了深刻影响.基于现有研究进展,本文建议:(1)针对青藏高原考古遗址开展系统性的动物考古学研究;(2)应用ZooMS和古DNA技术筛选和鉴定牦牛骨骼遗存,结合古环境DNA进行遗传学研究,追溯牦牛驯化的时间和地点;(3)开展野牦牛与黄牛的杂交驯化模式研究,理解牦牛驯化及其扩散对史前人类在青藏高原生存和发展的促进作用.

Recent selection and introgression facilitated high-altitude adaptation in cattle

During the past 3000 years,cattle on the Qinghai-Xizang Plateau have developed adaptive phenotypes under the selective pressure of hypoxia,ultraviolet(UV)radiation,and extreme cold.The genetic mechanism underlying this rapid adaptation is not yet well understood.Here,we present whole-genome resequencing data for 258 cattle from 32 cattle breeds/populations,including 89 Tibetan cattle representing eight populations distributed at altitudes ranging from 3400 m to 4300 m.Our genomic analysis revealed that Tibetan cattle exhibited a continuous phylogeographic cline from the East Asian taurine to the South Asian indicine ancestries.We found that recently selected genes in Tibetan cattle were related to body size(HMGA2 and NCAPG)and energy expenditure(DUOXA2).We identified signals of sympatric introgression from yak into Tibetan cattle at different altitudes,covering 0.64%–3.26%of their genomes,which included introgressed genes responsible for hypoxia response(EGLN1),cold adaptation(LRP11),DNA damage repair(LATS1),and UV radiation resistance(GNPAT).We observed that introgressed yak alleles were associated with noncoding variants,including those in present EGLN1.In Tibetan cattle,three yak introgressed SNPs in the EGLN1 promoter region reduced the expression of EGLN1,suggesting that these genomic variants enhance hypoxia tolerance.Taken together,our results indicated complex adaptation processes in Tibetan cattle,where recently selected genes and introgressed yak alleles jointly facilitated rapid adaptation to high-altitude environments.

Evidence of hybridization of cattle and aurochs on the Tibetan Plateau3750 years ago

Wild aurochs(Bos primigenius)were once widespread across Eurasia and North Africa but became extinct around the 17th century[1].Aurochs are considered the ancestor of modern taurine(B.taurus taurus)and indicine(B.t.indicus)cattle,which were independently domesticated within regions restricted to Southwest Asia and South Asia,respectively[2,3].Extensive gene flow from local aurochs to domestic cattle has been well documented in Southwest Asia,Europe,and Africa[3,4],raising questions about the mechanisms underlying both the domestication and dispersal of early cattle.

Evolution and legacy of East Asian aurochs

Aurochs(Bos primigenius),once widely distributed in Afro-Eurasia,became extinct in the early 1600 s.However,their phylogeography and relative contributions to domestic cattle remain unknown.In this study,we analyzed 16 genomes of ancient aurochs and three mitogenomes of ancient bison(Bison priscus)excavated in East Asia,dating from 43,000 to 3,590 years ago.These newly generated data with previously published genomic information on aurochs as well as ancient/extant domestic cattle worldwide through genome analysis.Ourfindings revealed significant genetic divergence between East Asian aurochs and their European,Near Eastern,and African counterparts on the basis of both mitochondrial and nuclear genomic data.Furthermore,we identified evidence of geneflow from East Asian aurochs into ancient and present-day taurine cattle,suggesting their potential role in facilitating the environmental adaptation of domestic cattle.

An atlas of CNV maps in cattle, goat and sheep

Copy number variation(CNV)is the most prevalent type of genetic structural variation that has been recognized as an important source of phenotypic variation in humans,animals and plants.However,the mechanisms underlying the evolution of CNVs and their function in natural or artificial selection remain unknown.Here,we generated CNV region(CNVR)datasets which were diverged or shared among cattle,goat,and sheep,including 886 individuals from 171 diverse populations.Using 9 environmental factors for genome-wide association study(GWAS),we identified a series of candidate CNVRs,including genes relating to immunity,tick resistance,multi-drug resistance,and muscle development.The number of CNVRs shared between species is significantly higher than expected(P<0.00001),and these CNVRs may be more persist than the single nucleotide polymorphisms(SNPs)shared between species.We also identified genomic regions under long-term balancing selection and uncovered the potential diversity of the selected CNVRs close to the important functional genes.This study provides the evidence that balancing selection might be more common in mammals than previously considered,and might play an important role in the daily activities of these ruminant species.

Genomic analyses reveal distinct genetic architectures and selective pressures in Chinese donkeys

Donkey(Equus asinus)is an important livestock animal in China because of its draft and medicinal value.After a long period of natural and artificial selection,the variety and phenotype of donkeys have become abundant.We clarified the genetic and demographic characteristics of Chinese domestic donkeys and the selection pressures by analyzing 78 whole genomes from 12 breeds.According to population structure,most Chinese domestic donkeys showed a dominant ancestral type.However,the Chinese donkeys still represented a significant geographical distribution trend.In the selective sweep,gene annotation,functional enrichment,and differential expression analyses between large and small donkey groups,we identified selective signals,including NCAPG and LCORL,which are related to rapid growth and large body size.Our findings elucidate the evolutionary history and formation of different donkey breeds and provide theoretical insights into the genetic mechanism underlying breed characteristics and molecular breeding programs of donkey clades.

BGVD:An Integrated Database for Bovine Sequencing Variations and Selective Signatures

Next-generation sequencing has yielded a vast amount of cattle genomic data for global characterization of population genetic diversity and identification of genomic regions under natural and artificial selection.However,efficient storage,querying,and visualization of such large datasets remain challenging.Here,we developed a comprehensive database,the Bovine Genome Variation Database(BGVD).It provides six main functionalities:gene search,variation search,genomic signature search,Genome Browser,alignment search tools,and the genome coordinate conversion tool.BGVD contains information on genomic variations comprising^60.44 M SNPs,~6.86 M indels,76,634 CNV regions,and signatures of selective sweeps in 432 samples from modern cattle worldwide.Users can quickly retrieve distribution patterns of these variations for 54 cattle breeds through an interactive source of breed origin map,using a given gene symbol or genomic region for any of the three versions of the bovine reference genomes(ARS-UCD1.2,UMD3.1.1,and Btau5.0.1).Signals of selection sweep are displayed as Manhattan plots and Genome Browser tracks.To further investigate and visualize the relationships between variants and signatures of selection,the Genome Browser integrates all variations,selection data,and resources,from NCBI,the UCSC Genome Browser,and Animal QTLdb.Collectively,all these features make the BGVD a useful archive for in-depth data mining and analyses of cattle biology and cattle breeding on a global scale.BGVD is publicly available at http://animal.nwsuaf.edu.cn/BosVar.

Global dispersal and adaptive evolution of domestic cattle:a genomic perspective

Domestic cattle have spread across the globe and inhabit variable and unpredictable environments.They have been exposed to a plethora of selective pressures and have adapted to a variety of local ecological and management conditions,including UV exposure,diseases,and stall-feeding systems.These selective pressures have resulted in unique and important phenotypic and genetic differences among modern cattle breeds/populations.Ongoing efforts to sequence the genomes of local and commercial cattle breeds/populations,along with the growing availability of ancient bovid DNA data,have significantly advanced our understanding of the genomic architecture,recent evolution of complex traits,common diseases,and local adaptation in cattle.Here,we review the origin and spread of domestic cattle and illustrate the environmental adaptations of local cattle breeds/populations.

Local ancestry and selection in admixed Sanjiang cattle

The majority of native cattle are taurine×indicine cattle of diverse phenotypes in the central region of China.Sanjiang cattle,a typical breed in the central region,play a central role in human livelihood and have good adaptability,including resistance to dampness,heat,roughage,and disease,and are thus regarded as an important genetic resource.However,the genetic history of the successful breed remains unknown.Here,we sequenced 10 Sanjiang cattle genomes and compared them to the 70 genomes of 5 representative populations worldwide.We characterized the genomic diversity and breed formation process of Sanjiang cattle and found that Sanjiang cattle have a mixed ancestry of indicine(55.6%)and taurine(33.2%)dating to approximately 30 generations ago,which has shaped the genome of Sanjiang cattle.Through ancestral fragment inference,selective sweep and transcriptomic analysis,we identified several genes linked to lipid metabolism,immune regulation,and stress reactions across the mosaic genome of Sanjiang cattle showing an excess of taurine or indicine ancestry.Taurine ancestry might contribute to meat quality,and indicine ancestry is more conducive to adaptation to hot climate conditions,making Sanjiang cattle a valuable genetic resource for the central region of China.Our results will help us understand the evolutionary history and ancestry components of Sanjiang cattle,which will provide a reference for resource conservation and selective breeding of Chinese native cattle.

Bovine HSD17B8 gene and its relationship with growth and meat quality traits

17 β-Hydroxysteroid dehydrogenase type 8 （HSD17B8） is an important regulator of lipid and steroid metabolism. In the present study, we aimed to assess the effects of HSD17B8 on growth and meat quality traits in cattle. Transcription profile analysis showed that HSD17B8 was primarily expressed in the salpinx, liver, and testis. Meanwhile, we identified three SNPs （SNPI： intron 1-A91G; SNP2： exon 1-A90G; and SNP3： intron 8-A86G） of the bovine HSD17B8 gene and investigated its haplotype frequencies and linkage disequilibrium. The detected SNPs were found associated with growth traits （body weight, body length, height at withers, heart girth, hip width, and average daily gain） in native cattle populations （Nanyang and Jiaxian） as well as the meat quality traits （Warner- Bratzler shear force, rib area, dressing percentage, carcass weight, and backfat thickness） in commercial breeds （Angus, Hereford, Limousin, Luxi, Simmental, and Jinnan）. Our results provided evidence that polymorphisms in the HSD17B8 gene were associated with growth traits and meat quality traits. Moreover, our findings might be used for marker-assisted selection in beef cattle breeding program