Genome-wide association study identifies 12 new genetic loci associated with growth traits in pigs

Growth traits are among the most important economic traits in pigs and are regulated by polygenes with complex regulatory mechanisms.As the major indicators of growth performance,the backfat thickness(BFT),loin eye area(LEA),and days to 100 kg(D100)traits are commonly used to the genetics improvement in pigs.However,the available genetic markers for these traits are limited.To uncover novel loci and candidate genes associated with growth performance,we collected the phenotypic information of BFT,LEA,and D100 in 1,186 pigs and genotyped all these individuals using the Neogen GGP porcine 80K BeadChip.We performed a genome-wide association study(GWAS)using 4 statistical models,including mixed linear models(MLM),fixed and random model circulating probability unification(FarmCPU),settlement of MLM under progressively exclusive relationships(SUPER),Bayesian-information and linkage-disequilibrium Iteratively nested keyway(Blink),and identified 5,3,and 6 high-confidence single nucleotide polymorphisms(SNPs)associated with BFT,LEA,and D100,respectively.Variant annotation and quantitative trait locus(QTL)mapping analysis suggested that6 genes(SKAP2,SATB1,PDE7B,PPP1R16B,WNT3,and WNT9B)were potentially associated with growth performance in pigs.Transcriptome analysis suggested that the expression of Src Kinase Associated Phosphoprotein 2(SKAP2)was higher in prenatal muscles than in postnatal muscles,and the expression of Phosphodiesterase 7B(PDE7B)continuously increased during the prenatal stages and gradually decreased after birth,implying their potential roles in prenatal skeletal muscle development.Overall,this study provides new candidate loci and genes for the genetic improvement of pigs.

Combustion mechanism and control approaches of underground coal fires:a review

With the large-scale mining of coal resources,the huge economic losses and environmental problems caused by underground coal fires have become increasingly prominent,and the research on the status quo and response strategies of underground coal fires is of great significance to accelerate the green prevention and control of coal fires,energy conservation and emission reduction.In this paper,we summarized and sorted out the research status of underground coal fires,focused on the theoretical and technical issues such as underground coal fire combustion mechanism,multiphysics coupling effect of coal fire combustion,fire prevention and extinguishing technology for underground coal fires,and beneficial utilization technology,and described the latest research progress of the prevention and control for underground coal fire hazards.Finally,the key research problems in the field of underground coal fire hazards prevention and control were proposed in the direction of the basic theory,technology research,comprehensive management and utilization,with a view to providing ideas and solutions for the management of underground coal fires.

Developmental stage-specific A-to-I editing pattern in the postnatal pineal gland of pigs(Sus scrofa)

Background: RNA editing is a widespread post-transcriptional modification mechanism in mammalian genomes.Although many editing sites have been identified in domestic pigs(Sus scrofa), little is known about the characteristics and dynamic regulation of RNA editing in the pineal gland(PG), a small neuroendocrine gland that synthesizes and secretes melatonin, which is primarily responsible to modulate sleep patterns.Results: This study analyzed the expression of adenosine-to-inosine(A-to-I) editing regulators and profiled the first dynamic A-to-I RNA editome during postnatal PG development. The results identified ADAR1 as the most abundantly expressed ADAR enzyme, which was down-regulated during postnatal PG development. Furthermore,47,284 high-confidence RNA editing sites were identified, the majority of which(93.6%) were of the canonical A-to-I editing type, followed by C-to-T editing. Analysis of its characteristics showed that the A-to-I editing sites mostly localized in SINE retrotransposons PRE-1/Pre0_SS. Moreover, a strong deficiency and preference for guanine nucleotides at positions of one base upstream or downstream were found, respectively. The overall editing level at the puberty stage was higher than at both infancy and adulthood stages. Additionally, genome-wide RNA editing was found to exhibit a dynamic stage-specific fashion(postnatally). Genes that underwent developmental changes in RNA editing were associated with catabolic processes as well as protein localization and transport functions,implying that RNA editing might be responsible for the molecular machineries of the postnatal developing PG.Remarkably, RNA editing in 3′-UTRs might regulate gene expression by influencing miRNA binding during PG development.Conclusions: This study profiles the first comprehensive developmental RNA editome in the pig PG, which contributes to the understanding of the importance of post-transcriptionally mediated regulation during mammalian postnatal PG development. Moreover, this study widely extends RNA editome resources in mammals.

The Global Attractors and Dimensions Estimation for the Higher-Order Nonlinear Kirchhoff-Type Equation with Strong Damping

The initial boundary value problems for a class of high order Kirchhoff type equations with nonlinear strongly damped terms are considered. We establish the existence and uniqueness of the global solution of the problem by using prior estimates and Galerkin’s method under proper assumptions for the rigid term. Then the compact method is used to prove the existence of a compact family of global attractors in the solution semigroup generated by the problem. Finally, the Frechet differentiability of the operator semigroup and the decay of the volume element of linearization problem are proved, and the Hausdorff dimension and Fractal dimension of the family of global attractors are obtained.

miR-378a-3p responds to physical activity by modulating insulin-mediated glucose uptake and tricarboxylic acid cycle in skeletal muscle

Aerobic exercise training alters gene expression in skeletal muscle,and miRNAs significantly contribute to motion response.However,the molecular mechanisms by which miRNAs regulate the response to exercise training are not well understood.Here,we found that the abundance of miR-378a-3p in skeletal muscle significantly decreased after exercise training.miR-378a-3p knockout mice showed increased insulin sensitivity,insulin-mediated glucose uptake.

Single-cell analysis reveals the lncRNA-MEG3/miRNA-133a-3p/PRRT2 axis regulates skeletal muscle regeneration and myogenesis

Skeletal muscle is the largest motor and metabolic organ of the body, which has a robust capacity for regeneration following injury or disease. Delayed regeneration after skeletal muscle injury reduces muscle contractility and leads to dysfunction of innervation. Therefore, identifying the regulation components in skeletal muscle regeneration and determining their molecular mechanisms are important to discover novel therapeutic markers for muscular diseases. Long non-coding RNA (LncRNA) has been implicated in skeletal muscle regeneration. Recent developed single-cell RNA sequencing (scRNA-seq) provides a higher resolution of cellular differences than bulk RNA-seq. Here, we re-analyzed single-cell transcriptomes data of skeletal muscle regeneration and identified lncRNA maternally expressed gene 3 (lncRNA-MEG3) was highly expressed in muscle satellite cells (MuSCs). Further study showed that lncRNA-MEG3 regulates skeletal muscle regeneration via sponging miR-133a-3p to regulate proline-rich transmembrane protein 2 (PRRT2) expression level. These results suggested that lncRNA-MEG3 might be a potential target for skeletal muscle diseases.

Longitudinal epitranscriptome profiling reveals the crucial role of N^(6)-methyladenosine methylation in porcine prenatal skeletal muscle development

N6-methyladenosine(m6A)represents the most abundantly occurring m RNA modification and is involved in the regulation of skeletal muscle development.However,the status and function of m6A methylation in prenatal myogenesis remains unclear.In this study,we first demonstrated that knockdown of METTL14,an m6A methyltransferase,inhibited the differentiation and promoted the proliferation of C2 C12 myoblast cells.Then,using a refined m6A-specific methylated RNA immunoprecipitation(RIP)with next generation sequencing(Me RIP-seq)method that is optimal for use with samples containing small amounts of RNA,we performed transcriptome-wide m6A profiling for six prenatal skeletal muscle developmental stages spanning two important waves of porcine myogenesis.The results revealed that,along with a continuous decrease in the m RNA expression of the m6A reader protein insulin-like growth factor 2 m RNA-binding protein 1(IGF2 BP1),the m6A methylome underwent highly dynamic changes across different development stages,with most of the affected genes being enriched in pathways related to skeletal muscle development.RNA immunoprecipitation confirmed that IGF2 BP1 targets 76 genes involved in pathways associated with muscle development,including the key marker genes MYH2 and Myo G.Moreover,small interfering RNA(si RNA)-mediated knockdown of IGF2 BP1 induced phenotypic changes in C2C12 myoblasts similar to those observed with knockdown of METTL14.In conclusion,we clarified the dynamics of m6A methylation and identified key genes involved in the regulatory network of porcine skeletal muscle development.

气泡驱动型微马达功能材料可控制备研究新进展

气泡驱动型微马达功能材料由于能分解化学物质产生气泡,从而驱动自身运动、强化流体混合与传质,因此在污染治理、药物传送、环境监测、物质分离以及疾病诊断等方面展现出了独特的优势和极大的应用前景.制备该微马达功能材料的关键在于如何在其中可控构建非对称的结构.本文主要介绍了近年来可控制备具有多样化结构和功能的气泡驱动型微马达功能材料的研究新进展,着重介绍了如何基于非对称结构的构建来设计和制备颗粒状和管状等结构的新型微马达功能材料,以及如何在微马达中巧妙整合多样化功能组分和结构来实现其多功能化,以期为创新设计和可控制备具有独特结构和先进功能的气泡驱动型微马达功能材料提供新的途径和指导.

A reporter gene assay for determining the biological activity of therapeutic antibodies targeting TIGIT

T cell immunoglobulin and ITIM domain(TIGIT)is a novel immune checkpoint that has been considered as a target in cancer immunotherapy.Current available bioassays for measuring the biological activity of therapeutic antibodies targeting TIGIT are restricted to mechanistic investigations because donor primary T cells are highly variable.Here,we designed a reporter gene assay comprising two cell lines,namely,CHO-CD112-CD3 scFv,which stably expresses CD 112(PVRL2,nectin-2)and a membranebound anti-CD3 single-chain fragment variable(scFv)as the target cell,and Jurkat-NFAT-TIGIT,which stably expresses TIGIT as well as the nuclear factor of activated T-cells(NFAT)response element-controlled luciferase gene,as the effector cell.The anti-CD3 scFv situated on the target cells activates Jurkat-NFATTIGIT cells through binding and crosslinking CD3 molecules of the effector cell,whereas interactions between CD 112 and TIGIT prevent activation.The presence of anti-TIGIT mAbs disrupts their interaction,which in turn reverses the inactivation and luciferase expression.Optimization and validation studies have demonstrated that this assay is superior in terms of specificity,accuracy,linearity,and precision.In summary,this reliable and effective reporter gene assay may potentially be utilized in lot release control,stability assays,screening,and development of novel TIGIT-targeted therapeutic antibodies.

MiR-743a-5p regulates differentiation of myoblast by targeting Mob1b in skeletal muscle development and regeneration

The microRNAs (miRNAs) play an important role in regulating myogenesis by targeting mRNA. However, the understanding of miRNAs in skeletal muscle development and diseases is unclear. In this study, we firstly performed the transcriptome profiling in differentiating C2C12 myoblast cells. Totally, we identified 187 miRNAs and 4260 mRNAs significantly differentially expressed that were involved in myoblast differentiation. We carried out validation of microarray data based on 5 mRNAs and 5 miRNAs differentially expressed and got a consistent result. Then we constructed and validated the significantly up- and down-regulated mRNA-miRNA interaction networks. Four interaction pairs (miR-145a-5p-Fscn1, miR-200c-5p-Tmigd1, miR-27a-5p-Sln and miR-743a-5p-Mob1b) with targeted relationships in differentiated myoblast cells were demonstrated. They are all closely related to myoblast development. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated cell cycle signals important for exploring skeletal muscle development and disease. Functionally, we discovered that miR-743a targeting gene Mps One Binder Kinase Activator-Like 1B (Mob1b) gene in differentiated C2C12. The up-regulated miR-743a can promote the differentiation of C2C12 myoblast. While the down-regulated Mob1b plays a negative role in differentiation. In addition, the expression profile of miR-743a and Mob1b are consistent with skeletal muscle recovery after Cardiotoxin (CTX) injury. Our study revealed that miR-743a-5p regulates myoblast differentiation by targeting Mob1b involved in skeletal muscle development and regeneration. Our findings made a further exploration for mechanisms in myogenesis and might provide potential possible miRNA-based target therapies for skeletal muscle regeneration and disease in the near future.

Bioinformatic identification of key genes and pathways that may be involved in the pathogenesis of HBV-associated acute liver failure

In order to explore the molecular mechanisms behind the pathogenesis of acute liver failure(ALF)associated with hepatitis B virus(HBV)infection,the present study aimed to identify potential key genes and pathways involved using samples from patients with HBV-associated ALF.The GSE38941 array dataset was downloaded from the Gene Expression Omnibus database,and differentially expressed genes(DEGs)between 10 liver samples from 10 healthy donors and 17 liver specimens from 4 patients with HBV-associated ALF were analyzed using the Linear Models for Microarray Data package.Gene Ontology and KEGG pathway enrichment analyses of the DEGs were performed,followed by functional annotation of the genes and construction of a proteineprotein interaction(PPI)network.Subnetwork modules were subsequently identified and analyzed.In total,3142 DEGs were identified,of which 1755 were upregulated and 1387 were downregulated.The extracellular exosome,immune response,and inflammatory response pathways may potentially be used as biomarkers of ALF pathogenesis.In total,17 genes(including CCR5,CXCR4,ALB,C3,VGEFA,and IGF1)were identified as hub genes in the PPI network and may therefore be potential marker genes for HBV-associated ALF.

Fluorescent bovine serum albumin-silver nanoclusters loaded with paclitaxel can traverse the blood-brain barrier to inhibit the migration of glioma

Objective::Glioma is the most common and aggressive primary brain tumor. Here, we aimed to establish a nano-drug carrier system to traverse the blood-brain barrier for the treatment and inhibition of glioma migration.Methods::The synthesis of bovine serum albumin protected-silver nanoclusters (BSA-AgNCs) was performed using chemical reduction. The drug paclitaxel (PTX) can be loaded into BSA-AgNCs through electrostatic and hydrophobic interactions to formulate spherical BSA-AgNC-PTX nanoparticles (BSA-AgNC-PTX NPs). A glioma mouse model was established by injecting U251-GFP-Luc cells into the mouse striatum, and all surgical procedures were approved by the Animal Ethics Committee of Nanchang University (SYXK2019-0003) on December 29, 2019.Results::The BSA-AgNC-PTX NPs were able to efficiently pass through the blood-brain barrier, both in vitro and in vivo, to deliver the drug to the tumor site. The in vivo assessment of BSA-AgNC-PTX NPs in glioblastoma multiforme-bearing mice revealed the significant inhibition of tumor growth and migration, prolonging the survival of the mice.Conclusion::These results indicated that BSA-AgNCs might represent an ideal nanocarrier for the treatment of glioma and has the potential to be used in the treatment of a variety of central nervous system diseases.