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To address the limited inversion accuracy caused by low-fidelity data in satellite gravimetry, this study proposes a data preprocessing framework based on iterative residual correction. Utilizing Level-1B observations from the Gravity Recovery and Climate Experiment Follow-On (GRACE-FO) satellite (January 2020), outliers were systematically detected and removed, while data gaps were compensated through spline interpolation. Experimental results demonstrate that the proposed method effectively mitigates data discontinuities and anomalous perturbations, achieving a significant improvement in data quality. Furthermore, a 60-order Earth gravity field model derived via the energy balance approach was validated against contemporaneous models published by the University of Texas Center for Space Research (CSR), German Research Centre for Geosciences (GFZ), and Jet Propulsion Laboratory (JPL). The results reveal a two-order-of-magnitude enhancement in inversion precision, with model accuracy improving from 10−6–10−7 to 10−8–10−9. This method provides a robust solution for enhancing the reliability of gravity field recovery in satellite-based geodetic missions.

Advances in high-throughput sequencing technologies have reduced the cost of genotyping dramatically and led to genomic prediction being widely used in animal and plant breeding, and increasingly in human genetics. Inspired by the efficient computing of linear mixed model and the accurate prediction of Bayesian methods, we propose a machine learning-based method incorporating cross-validation, multiple regression, grid search, and bisection algorithms named KAML that aims to combine the advantages of prediction accuracy with computing efficiency. KAML exhibits higher prediction accuracy than existing methods, and it is available at https://github.com/YinLiLin/KAML .

The Farm Animal Genotype-Tissue Expression (FarmGTEx) project has been established to develop a public resource of genetic regulatory variants in livestock, which is essential for linking genetic polymorphisms to variation in phenotypes, helping fundamental biological discovery and exploitation in animal breeding and human biomedicine. Here we show results from the pilot phase of PigGTEx by processing 5,457 RNA-sequencing and 1,602 whole-genome sequencing samples passing quality control from pigs. We build a pig genotype imputation panel and associate millions of genetic variants with five types of transcriptomic phenotypes in 34 tissues. We evaluate tissue specificity of regulatory effects and elucidate molecular mechanisms of their action using multi-omics data. Leveraging this resource, we decipher regulatory mechanisms underlying 207 pig complex phenotypes and demonstrate the similarity of pigs to humans in gene expression and the genetic regulation behind complex phenotypes, supporting the importance of pigs as a human biomedical model. The pilot phase of PigGTEx, re-analyzing 5,457 published RNA-seq samples, presents a pan-tissue catalog of molecular quantitative trait loci. Cross-species comparisons identify traits with shared genetic regulation in humans.

Although major advances in genomics have initiated an exciting new era of research, a lack of information regarding cis -regulatory elements has limited the genetic improvement or manipulation of pigs as a meat source and biomedical model. Here, we systematically characterize cis -regulatory elements and their functions in 12 diverse tissues from four pig breeds by adopting similar strategies as the ENCODE and Roadmap Epigenomics projects, which include RNA-seq, ATAC-seq, and ChIP-seq. In total, we generate 199 datasets and identify more than 220,000 cis -regulatory elements in the pig genome. Surprisingly, we find higher conservation of cis -regulatory elements between human and pig genomes than those between human and mouse genomes. Furthermore, the differences of topologically associating domains between the pig and human genomes are associated with morphological evolution of the head and face. Beyond generating a major new benchmark resource for pig epigenetics, our study provides basic comparative epigenetic data relevant to using pigs as models in human biomedical research. To date, little is known about the regulatory landscape of the pig genome. Here, the authors characterize cis -regulatory elements in the pig genome using RNA-seq, ChIP-Seq and ATAC-seq, finding a higher degree of usage conservation between pig and human than mouse and human.

Japanese encephalitis virus (JEV) is a mosquito-borne zoonotic flavivirus that causes encephalitis and reproductive disorders in mammalian species. However, the host factors critical for its entry, replication, and assembly are poorly understood. Here, we design a porcine genome-scale CRISPR/Cas9 knockout (PigGeCKO) library containing 85,674 single guide RNAs targeting 17,743 protein-coding genes, 11,053 long ncRNAs, and 551 microRNAs. Subsequently, we use the PigGeCKO library to identify key host factors facilitating JEV infection in porcine cells. Several previously unreported genes required for JEV infection are highly enriched post-JEV selection. We conduct follow-up studies to verify the dependency of JEV on these genes, and identify functional contributions for six of the many candidate JEV-related host genes, including EMC3 and CALR . Additionally, we identify that four genes associated with heparan sulfate proteoglycans (HSPGs) metabolism, specifically those responsible for HSPGs sulfurylation, facilitate JEV entry into porcine cells. Thus, beyond our development of the largest CRISPR-based functional genomic screening platform for pig research to date, this study identifies multiple potentially vulnerable targets for the development of medical and breeding technologies to treat and prevent diseases caused by JEV. Here the authors report the construction of a genome-scale porcine CRISPR/Cas9 library, called PigGeCKO, for screening and analyses of host resistance genes and factors associated with Japanese encephalitis virus replication.

Emerging coronaviruses (CoVs) pose a severe threat to human and animal health worldwide. To identify host factors required for CoV infection, we used α-CoV transmissible gastroenteritis virus (TGEV) as a model for genome-scale CRISPR knockout (KO) screening. Transmembrane protein 41B (TMEM41B) was found to be a bona fide host factor involved in infection by CoV and three additional virus families. We found that TMEM41B is critical for the internalization and early-stage replication of TGEV. Notably, our results also showed that cells lacking TMEM41B are unable to form the double-membrane vesicles necessary for TGEV replication, indicating that TMEM41B contributes to the formation of CoV replication organelles. Lastly, our data from a mouse infection model showed that the KO of this factor can strongly inhibit viral infection and delay the progression of a CoV disease. Our study revealed that targeting TMEM41B is a highly promising approach for the development of broad-spectrum anti-viral therapeutics.

Background Gene expression programs are intimately linked to the interplay of active cis regulatory elements mediated by chromatin contacts and associated RNAs. Genome-wide association studies (GWAS) have identified many variants in these regulatory elements that can contribute to phenotypic diversity. However, the functional interpretation of these variants remains nontrivial due to the lack of chromatin contact information or limited contact resolution. Furthermore, the distribution and role of chromatin-associated RNAs in gene expression and chromatin conformation remain poorly understood. To address this, we first present a comprehensive interaction map of nuclear dynamics of 3D chromatin-chromatin interactions (H3K27ac BL-HiChIP) and RNA-chromatin interactions (GRID-seq) to reveal genomic variants that contribute to complex skeletal muscle traits. Results In a genome-wide scan, we provide systematic fine mapping and gene prioritization from GWAS leading signals that underlie phenotypic variability of growth rate, meat quality, and carcass performance. A set of candidate functional variants and 54 target genes previously not detected were identified, with 71% of these candidate functional variants choosing to skip over their nearest gene to regulate the target gene in a long-range manner. The effects of three functional variants regulating KLF6 (related to days to 100 kg), MXRA8 (related to lean meat percentage), and TAF11 (related to loin muscle depth) were observed in two pig populations. Moreover, we find that this multi-omics interaction map consists of functional communities that are enriched in specific biological functions, and GWAS target genes can serve as core genes for exploring peripheral trait-relevant genes. Conclusions Our results provide a valuable resource of candidate functional variants for complex skeletal muscle-related traits and establish an integrated approach to complement existing 3D genomics by exploiting RNA-chromatin and chromatin-chromatin interactions for future association studies.

The lack of integrated analysis of genome-wide association studies (GWAS) and 3D epigenomics restricts a deep understanding of the genetic mechanisms of meat-related traits. With the application of techniques as ChIP-seq and Hi-C, the annotations of cis-regulatory elements in the pig genome have been established, which offers a new opportunity to elucidate the genetic mechanisms and identify major genetic variants and candidate genes that are significantly associated with important economic traits. Among these traits, loin muscle depth (LMD) is an important one as it impacts the lean meat content. In this study, we integrated cis-regulatory elements and genome-wide association studies (GWAS) to identify candidate genes and genetic variants regulating LMD. Five single nucleotide polymorphisms (SNPs) located on porcine chromosome 17 were significantly associated with LMD in Yorkshire pigs. A 10 kb quantitative trait locus (QTL) was identified as a candidate functional genomic region through the integration of linkage disequilibrium and linkage analysis (LDLA) and high-throughput chromosome conformation capture (Hi-C) analysis. The BMP2 gene was identified as a candidate gene for LMD based on the integrated results of GWAS, Hi-C meta-analysis, and cis-regulatory element data. The identified QTL region was further verified through target region sequencing. Furthermore, through using dual-luciferase assays and electrophoretic mobility shift assays (EMSA), two SNPs, including SNP rs321846600, located in the enhancer region, and SNP rs1111440035, located in the promoter region, were identified as candidate SNPs that may be functionally related to the LMD. Based on the results of GWAS, Hi-C, and cis-regulatory elements, the BMP2 gene was identified as an important candidate gene regulating variation in LMD. The SNPs rs321846600 and rs1111440035 were identified as candidate SNPs that are functionally related to the LMD of Yorkshire pigs. Our results shed light on the advantages of integrating GWAS with 3D epigenomics in identifying candidate genes for quantitative traits. This study is a pioneering work for the identification of candidate genes and related genetic variants regulating one key production trait (LMD) in pigs by integrating genome-wide association studies and 3D epigenomics.

To elucidate the genes involved in the formation of white and black plumage in ducks, RNA from white and black feather bulbs of an F(2) population were analyzed using RNA-Seq. A total of 2,642 expressed sequence tags showed significant differential expression between white and black feather bulbs. Among these tags, 186 matched 133 annotated genes that grouped into 94 pathways. A number of genes controlling melanogenesis showed differential expression between the two types of feather bulbs. This differential expression was confirmed by qPCR analysis and demonstrated that Tyr (Tyrosinase) and Tyrp1 (Tyrosinase-related protein-1) were expressed not in W-W (white feather bulb from white dorsal plumage) and W-WB (white feather bulb from white-black dorsal plumage) but in B-B (black feather bulb from black dorsal plumage) and B-WB (black feather bulb from white-black dorsal plumage) feather bulbs. Tyrp2 (Tyrosinase-related protein-2) gene did not show expression in the four types of feather bulbs but expressed in retina. C-kit (The tyrosine kinase receptor) expressed in all of the samples but the relative mRNA expression in B-B or B-WB was approximately 10 fold higher than that in W-W or W-WB. Additionally, only one of the two Mitf isoforms was associated with plumage color determination. Downregulation of c-Kit and Mitf in feather bulbs may be the cause of white plumage in the duck.

Yunzhi Dang, Department of Radiation Oncology, Shaanxi Provincial People’s Hospital, Xi’an, Shaanxi, 710086, People’s Republic of China, Email dangyunzhi@xiyi.edu.cnAbstract: Radiation skin injury (RSI) is a common complication during tumor radiotherapy, significantly impacting patients’ quality of life and treatment outcomes. In recent years, with the rapid development of biomedical material technologies, the application of novel dressings in the prevention and treatment of RSI has made remarkable progress. This review summarizes the mechanisms underlying RSI and its prevention and treatment strategies, with a particular focus on the applications of traditional pharmacological interventions and advanced medical dressings in RSI management. In pharmacological interventions, antioxidants, anti-inflammatory agents, and growth factors have shown potential value, but their stability, bioavailability, and side effects require further clarification and optimization. In the realm of novel dressings, bioactive dressings and smart responsive dressings are current research hotspots. The former promotes tissue repair by delivering bioactive substances, while the latter intelligently adjusts their properties and drug release based on wound conditions (eg, pH, temperature, and enzyme responsiveness). Although these advanced dressings still face challenges in clinical applications, such as cost control, large-scale production, and long-term safety evaluation, their prospects in RSI prevention and treatment are promising with the continuous optimization of fabrication technologies and stabilization strategies. This review aims to provide new insights into the prevention and treatment of RSI and to promote the clinical translation and application of related biomedical materials.