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Whether it is possible to create suitable plants for cadmium phytoremediation by introducing Datura stramonium L. genes into tobacco (Nicotiana tabacum L.) remains unclear. Hydroponic experiments were performed on N. tabacum L. var. MTLY, a newly developed hybrid variety, and the parents. Seedlings at the six-leaf stage were treated with 0 (control), 10 µM, 180 µM and 360 µM CdCl2 for 7 days, and their differences in Cd tolerance and accumulation and physiological and metabolic responses were evaluated. When subjected to 360 µM Cd, the growth of "MTLY", in terms of the dry weight, plant height and root length, was obviously better than N. tabacum L. var. LY2 (female parent). In contrast to D. stramonium (male parent) and "LY2", "MTLY" accumulated more Cd in shoots (127.6–3837.1 mg kg−1) and roots (121.6–1167.7 mg kg−1). Moreover, unlike "LY2", "MTLY" could accumulate more Cd in its shoots than roots. Its bioconcentration factor (BCF) and translocation factor (TF) values reached 95.9–149.7 and 1.0–3.5, respectively, which were far greater than those of "LY2". High-dose Cd stress significantly increased reactive oxygen species (ROS) and malondialdehyde (MDA) levels and decreased chlorophyll contents in tobacco seedlings, especially in "LY2". Various enzymatic and non-enzymatic antioxidants in the three materials showed different responses to Cd stress. The change of the phenolic compounds and alkaloids in "MTLY" was basically similar to that in D. stramonium, but their levels were apparently higher than those in "LY2". Results indicated that distant hybridization could be one of the effective methods for introducing metal-hyperaccumulator genes into a high biomass species, which contributed to enhancing the Cd tolerance, accumulation and detoxification in tobacco. This study has great significance in obtaining elite germplasm for phytoremediation. The exact mechanisms in molecules and genetics and the practical effectiveness in cadmium-contaminated soil remain to be further elucidated. [ABSTRACT FROM AUTHOR]

Ensifer alkalisoli YIC4027T is a dominant rhizobium that has been isolated from the root nodules of Sesbania cannabina. Motility and chemotaxis are critical to maintaining competitiveness in establishing the symbiotic relationship. E. alkalisoli carries two gene clusters, che1 and che2, containing chemotaxis-related gene homologues. To determine the respective role of each gene cluster, we constructed mutants and compared them with the wild type in a free-living state and in symbiosis with the host plant. A swimming analysis revealed that the che1 cluster was the major pathway controlling the chemotaxis and swimming bias, while the che2 cluster had a minor role in these behaviors. However, the Δche2 mutant was impaired in exopolysaccharide (EPS) production. During symbiosis, the Δche1 mutant was more severely impaired in its competitive root colonization and nodulation ability than the Δche2 mutant. Taken together, our data strongly suggested that both of the che clusters contribute to the competitive symbiotic association, the che1-like homologue being the main regulator of the chemotactic response and the che2 cluster regulating EPS production. These data illustrated a novel strategy of motile rhizobia bacteria to utilize the two pathways containing the homologous genes to enhance the efficiency of nodule formation by regulating distinct motility parameters or other cellular functions. [ABSTRACT FROM AUTHOR]

The CRISPR-Cas system is a bacterial and archaea adaptive immune system and is a newly recognized mechanism for controlling antibiotic resistance gene transfer. Acinetobacter baumannii (A. baumannii) is an important organism responsible for a variety of nosocomial infections. A. baumannii infections have become problematic worldwide because of the resistance of A. baumannii to multiple antibiotics. Thus, it is clinically significant to explore the relationship between the CRISPR-Cas system and drug resistance in A. baumannii. This study aimed to analyze the genomic characteristics of the A. baumannii strain AB3 containing the type I-Fb CRISPR-Cas system, which was isolated from a tertiary care hospital in China, and to investigate the relationship between the CRISPR-Cas system and antibiotic resistance in this strain. The whole-genome sequencing (WGS) of the AB43 strain was performed using Illumina and PacBio sequencing. The complete genome of AB43 consisted of a 3,854,806 bp chromosome and a 104,309 bp plasmid. The specific characteristics of the CRISPR-Cas system in AB43 are described as follows: (1) The strain AB43 carries a complete type I-Fb CRISPR-Cas system; (2) Homology analysis confirmed that the cas genes in AB43 share high sequence similarity with the same subtype cas genes; (3) A total of 28 of 105 A. baumannii AB43 CRISPR spacers matched genes in the bacteriophage genome database and the plasmid database, implying that the CRISPR-Cas system in AB43 provides immunity against invasive bacteriophage and plasmids; (4) None of the CRISPR spacers in A. baumannii AB43 were matched with antimicrobial resistance genes in the NCBI database. In addition, we analyzed the presence of antibiotic resistance genes and insertion sequences in the AB43 strain and found that the number of antibiotic resistance genes was not lower than in the "no CRISPR-Cas system" strain. This study supports the idea that the CRISPR-Cas system may inhibit drug-resistance gene expression via endogenous gene regulation, except to the published mechanism that the CRISPR-Cas system efficiently limits the acquisition of antibiotic resistance genes that make bacteria sensitive to antibiotics. [ABSTRACT FROM AUTHOR]

Simple Summary: Wool is an important raw material in the textile industry. Its fiber fineness is directly related to the wool product quality. Higher quality wool products require finer wool fiber diameters. Therefore, methods for more effectively optimizing the wool fiber diameter have become an important research focus. Single nucleotide polymorphisms (SNPs) are efficient and stable molecular markers which have been extensively used to study wool fiber diameter. The SLIT3 and ZNF280B genes are involved in multiple biological processes and have multiple biological functions. However, the relationship between their polymorphisms and wool fiber diameter remains unreported. This study was conducted to investigate the relationship between different genotypes and wool fiber diameter by typing SNP sites in SLIT3 and ZNF280B. Our results revealed the major genotypes in the SLIT3 and ZNF280B genes which effect wool fiber diameter. These SNP sites may potentially be used as molecular marker sites for optimizing wool fiber diameter. The SLIT3 gene encodes a secreted protein, and the ZNF280B gene is a member of the transcription factor family. Both genes have multiple biological functions. This study was conducted to investigate the association between SLIT3 and ZNF280B gene polymorphisms and wool fiber diameter and to determine potential molecular marker sites for breeding sheep with fine wool. We used Kompetitive Allele-Specific PCR to type the single nucleotide polymorphism (SNP) loci in the SLIT3 and ZNF280B genes within 1081 Alpine Merino sheep and associated these SNPs with wool fiber diameter. The results revealed one SNP in SLIT3 and ZNF280B, which were each related to sheep fiber diameter. The wool fiber diameters of sheep with the CC genotype in SLIT3 g.478807C>G and AA genotype in ZNF280B g.677G>A were the smallest and differed significantly from the diameters of other genotypes (p < 0.05). These results suggest potential molecular marker sites for fine-wool sheep breeding. [ABSTRACT FROM AUTHOR]

Wool fiber is a textile material that is highly valued based on its diameter, which is crucial in determining its economic value. To analyze the molecular mechanisms regulating wool fiber diameter, we used a Data-independent acquisition-based quantitative proteomics approach to analyze the skin proteome of Alpine Merino sheep with four fiber diameter ranges. From three contrasts of defined groups, we identified 275, 229, and 190 differentially expressed proteins (DEPs). Further analysis using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways revealed that pathways associated with cyclic adenosine monophosphate and peroxisome proliferator-activated receptor signaling are relevant to wool fiber diameter. Using the K-means method, we investigated the DEP expression patterns across wool diameter ranges. Using weighted gene co-expression network analysis, we identified seven key proteins (CIDEA, CRYM, MLX, TPST2, GPD1, GOPC, and CAMK2G) that may be involved in regulating wool fiber diameter. Our findings provide a theoretical foundation for identifying DEPs and pathways associated with wool fiber diameter in Alpine Merino sheep to enable a better understanding of the molecular mechanisms underlying the genetic regulation of wool fiber quality. [ABSTRACT FROM AUTHOR]

Simple Summary: Alpine Merino sheep are a new breed of sheep adapted to the cold and arid ecological zone 2400–4070 m above sea level; the breed has important economic significance for high-altitude areas. This study evaluated the effects of different dietary energy levels (9.7 MJ/kg, 10.1 MJ/kg, 10.5 MJ/kg) on the growth and meat quality of weaned Alpine Merino lambs. The results showed that compared with the low-energy diet (9.7 MJ/kg), the high-energy (10.5 MJ/kg) diet promoted the growth and development of lambs, increased the live weight and carcass weight of lambs before slaughter, significantly reduced the yellowness and redness scores of lamb muscles, and increased the meat's content of monounsaturated fatty acids. This experiment was conducted to study the effects of dietary energy level on the growth performance and meat quality of weaned Alpine Merino lambs. The study ran for a total of 104 days (20-day pretrial, 84-day trial). From three groups of test lambs, we randomly selected ten lambs per group to determine slaughter performance, meat quality characteristics, and organ indexes. The slaughter performances of the lambs improved as the dietary energy level increased. The live weight before the slaughter of the lambs was significantly higher in the high group than in the low and medium groups. The carcass weight was significantly higher in the high group than in the low group. Dietary energy level had little effect on the organ weight of lambs. Meat quality differed among the three dietary energy levels. The muscle yellowness and redness scores decreased significantly as the energy levels increased. The C18:0, C21:0, C20:1, C18:2n6c, and C20:2 contents in the muscle were significantly higher in the high group than in the medium and low groups. The C18:3n6 content in the muscle was significantly higher in the low group than in the medium group. The C20:5n3 content in the longissimus dorsi was significantly higher in the high group than in the medium and low groups. The monounsaturated and unsaturated fatty acid contents in the muscle were significantly higher in the high group than in the low group. A dietary energy level of 10.5 MJ/kg is suitable for fattening weaned male Alpine Merino lambs. [ABSTRACT FROM AUTHOR]

Heat stress is an important environmental factor affecting livestock production worldwide. Primary hepatocytes and preadipocytes derived from Hu sheep were used to establish a heat stress model. Quantitative reverse transcriptase-PCR (qRT-PCR) analysis showed that heat induction significantly increased the expression levels of heat stress protein (HSP) genes and the N6-methyladenosine (m6A) methylation modification genes: methyltransferase-like protein 3 (METTL3), methyltransferase-like protein 14 (METTL14), and fat mass and obesity associated protein (FTO). Heat stress simultaneously promoted cell apoptosis. Transcriptome sequencing identified 3980 upregulated genes and 2420 downregulated genes related to heat stress. A pathway enrichment analysis of these genes revealed significant enrichment in fatty acid biosynthesis, degradation, and the PI3K-Akt and peroxisome proliferator-activated receptor (PPAR) signaling pathways. Overexpression of METTL3 in primary hepatocytes led to significant downregulation of HSP60, HSP70, and HSP110, and significantly increased mRNA m6A methylation; FTO interference generated the opposite results. Primary adipocytes showed similar results. Transcriptome analysis of cells under METTL3 (or FTO) inference and overexpression revealed differentially expressed genes enriched in the mitogen-activated protein kinase (MAPK) signaling pathways, as well as the PI3K-Akt and Ras signaling pathways. We speculate that METTL3 may increase the level of m6A methylation to inhibit fat deposition and/or inhibit the expression of HSP genes to enhance the body's resistance to heat stress, while the FTO gene generated the opposite molecular mechanism. This study provides a scientific basis and theoretical support for sheep feeding and management practices during heat stress. [ABSTRACT FROM AUTHOR]

In the process of policy financing guaranteeing help to SMEs to make innovations in green technologies, multiple parties continue to play strategic games for their interests. Evolutionary game theory is a practical tool for analyzing multi-agent strategies, which can help us to explore how policy financing guarantees help to SMEs to achieve effective credit enhancement. This paper constructs a four-party evolutionary game model among SMEs, banks, guarantee agencies, and the government, and obtains four evolutionary stable strategies by analyzing various players' replicator dynamics. In addition, we carry out numerical simulations on the key parameters affecting the stability of the game system. The findings suggest that keeping the fixed risk-ratio between guarantee agencies and banks constant reduces the government's financial burden and strengthens the re-guarantee system's construction at the initial stage of SME financing, which can indirectly increase the enthusiasm for cooperation between banks and guarantee agencies. The interest subsidy policy is more effective in promoting SMEs' compliance and bank–guarantee cooperation in the short term. Meanwhile, the government should increase the supervision of defaulting SMEs and cooperate with financial institutions to improve the credit system for SMEs. [ABSTRACT FROM AUTHOR]

The time-dependent behavior of power-law fluid has a significant influence on the grouting effects of reinforcing loose gravel soil. In this paper, based on basic rheological equations and the time-dependent behavior of rheological parameters (consistency coefficient and rheological index), rheological equations and penetration equations of time-dependent power-law fluid are proposed. Its penetration grouting diffusion mechanism for reinforcing loose gravel soil was then theoretically induced. A set of indoor experimental devices for simulating penetration grouting was designed to simulate the penetration grouting of power-law fluid with different time-dependent behaviors for reinforcing loose gravel soil. Then, relying on the COMSOL Multiphysics platform and Darcy's law, three-dimensional numerical calculation programs for this mechanism were obtained using secondary-development programming technology. Thus, the numerical simulations of the penetration grouting process of power-law fluid with different time-dependent behaviors for reinforcing loose gravel soil were carried out. This theoretical mechanism was validated by comparing results from theoretical analyses, indoor experiments, and numerical simulations. Research results show that the three-dimensional numerical calculation programs can successfully simulate the penetration diffusion patterns of a time-dependent power-law fluid in loose gravel soil. The theoretical calculation values and numerical simulation values of the diffusion radius obtained from this mechanism are closer to indoor experimental values than those obtained from the penetration grouting diffusion theory of power-law fluid without considering time-dependent behavior. This mechanism can better reflect the penetration grouting diffusion laws of a power-law fluid in loose gravel soil than the theory, which can provide theoretical support and guidance for practical grouting construction. [ABSTRACT FROM AUTHOR]

A drug delivery system was specifically designed for the treatment of rheumatoid arthritis (RA) by local percutaneous administration and the nano-controlled release of methotrexate (MTX). The release behavior of MTX from the synthesized MTX-mSiO2@PDA system was investigated in vitro and in vivo. The obtained results show that after 48 h, twice as much MTX (cumulative amount) is released at pH 5.5 than at pH 7.4. This suggests that the MTX-mSiO2@PDA system exhibits a good pH sensitivity. In vitro local percutaneous administration experiments revealed that the cumulative amount of MTX transferred from MTX-mSiO2@PDA to pH 5.0 receptor fluid through the whole skin was approximately three times greater than the amount transferred to pH 7.4 receptor fluid after 24 h. Moreover, in vivo experiments conducted on a complete induced arthritis (CIA) model in DBA/1 mice demonstrated that the thickness of a mouse's toes decreases to nearly 65% of the initial level after 27 days of local percutaneous MTX-mSiO2@PDA administration. Compared to the mice directly injected with MTX, those administered with MTX-mSiO2@PDA by local percutaneous application exhibit much lower toe thickness deviation, which indicates that the latter group experiences a better cure stability. Overall, these results demonstrate that the local percutaneous administration of MTX delivery systems characterized by nano-controlled release may play an important role in RA therapy. [ABSTRACT FROM AUTHOR]

Various congenital and acquired urinary system abnormalities can cause structural damage to patients' bladders. This study aimed to construct and evaluate a novel surgical patch encapsulated with adipose-derived stem cells (ADSCs) for bladder tissue regeneration. The surgical patch consists of multiple biomaterials, including bladder acellular matrix (BAM), collagen type I from rat tail, microparticle emulsion cross-linking polylactic-co-glycolic acid (PLGA)-chitosan (CS) with PLGA-sodium alginate (SA), and growth factors. ADSCs were seeded on the surgical patch. Approximately 50% of the bladder was excised and replaced with a surgical patch. Histological, immunohistochemical and urodynamic analyses were performed at the 2nd, 4th, and 8th weeks after surgery, respectively. The PLGA-CS, PLGA-SA or surgical patch showed no cytotoxicity to ADSCs. PLGA-CS cross-linked with PLGA-SA at a ratio of 5:5 exhibited a loose microporous structure and was chosen as the candidate for ADSC seeding. We conducted bladder repair surgery in rats using the patch, successfully presenting urothelium layers, muscle bundles, and vessel regeneration and replacing 50% of the rat's natural bladder in vivo. Experiments through qualitative and quantitative evaluation demonstrate the application potential of the composite biomaterials in promoting the repair and reconstruction of bladder tissue. [ABSTRACT FROM AUTHOR]

The development of an efficient and convenient material to improve skin tissue regeneration is a major challenge in healthcare. Inspired by the theory of moist wound healing, portable chitooligosaccharide (COS)/sodium alginate (SA) dual-net gel films containing multiple metal ions were prepared by a casting and in-situ spray method, which can be used to significantly promote wound healing without the use of therapeutic drugs. A variety of divalent cations was introduced in this experiment to improve the advantages of each metal ion by forming metal ion chelates with COS. Moreover, the physicochemical properties and antioxidant properties of nIon2+-COS/SA gel films were systematically characterized and evaluated by in vitro experiments. The gel films showed good antibacterial activity against Gram-negative and Gram-positive bacteria. In addition, the gel films showed good cytocompatibility in cellular experiments, and the gel films with Zn2+ and Sr2+ addition significantly accelerated wound healing in whole skin defect model experiments. Therefore, this nIon2+-COS/SA gel film is an ideal candidate material for wound dressing. [ABSTRACT FROM AUTHOR]

Hybridization of livestock can be used to improve varieties, and different hybrid combinations produce unique breeding effects. In this study, male Southdown and Suffolk sheep were selected to hybridize with female Hu sheep to explore the effects of male parentage on muscle growth and the development of offspring. Using data-independent acquisition technology, we identified 119, 187, and 26 differentially abundant proteins (DAPs) between Hu × Hu (HH) versus Southdown × Hu (NH), HH versus Suffolk × Hu (SH), and NH versus SH crosses. Two DAPs, MYOZ2 and MYOM3, were common to the three hybrid groups and were mainly enriched in muscle growth and development-related pathways. At the myoblast proliferation stage, MYOZ2 expression decreased cell viability and inhibited proliferation. At the myoblast differentiation stage, MYOZ2 expression promoted myoblast fusion and enhanced the level of cell fusion. These findings provide new insights into the key proteins and metabolic pathways involved in the effect of male parentage on muscle growth and the development of hybrid offspring in sheep. [ABSTRACT FROM AUTHOR]

Leaf blade width, curvature, and cuticular wax are important agronomic traits of rice. Here, we report the rice Oschr4-5 mutant characterized by pleiotropic phenotypes, including narrow and rolled leaves, enhanced cuticular wax deposition and reduced plant height and tiller number. The reduced leaf width is caused by a reduced number of longitudinal veins and increased auxin content. The cuticular wax content was significantly higher in the Oschr4-5 mutant, resulting in reduced water loss rate and enhanced drought tolerance. Molecular characterization reveals that a single-base deletion results in a frame-shift mutation from the second chromodomain of OsCHR4, a CHD3 (chromodomain helicase DNA-binding) family chromatin remodeler, in the Oschr4-5 mutant. Expressions of seven wax biosynthesis genes (GL1-4, WSL4, OsCER7, LACS2, LACS7, ROC4 and BDG) and four auxin biosynthesis genes (YUC2, YUC3, YUC5 and YUC6) was up-regulated in the Oschr4-5 mutant. Chromatin immunoprecipitation assays revealed that the transcriptionally active histone modification H3K4me3 was increased, whereas the repressive H3K27me3 was reduced in the upregulated genes in the Oschr4-5 mutant. Therefore, OsCHR4 regulates leaf morphogenesis and cuticle wax formation by epigenetic modulation of auxin and wax biosynthetic genes expression. [ABSTRACT FROM AUTHOR]

Simple Summary: Mining SNPs or genes associated with important traits is important for fine-wool sheep breeding. We screened 20 SNPs associated with important traits of Alpine Merino sheep, such as birth weight, bundle strength, cleaning rate, and fiber diameter, of which 8 were monomorphic locis and 12 were polymorphic locis. These findings provide a theoretical basis for genomic selection and molecular breeding. SNPs associated with important traits of fine-wool sheep that were previously obtained through genome-wide association analysis screening were verified and analyzed. A total of 20 SNPs related to birth weight, bundle strength, cleaning rate, and fiber diameter were screened using whole-genome resequencing, and the SNPshot assay was used to detect and analyze polymorphisms. This study found that, among the 20 SNPs associated with important traits in Alpine Merino sheep, 8 were monomorphic and 12 were polymorphic, of which 6 showed moderate polymorphisms and 6 showed low polymorphisms. The heterozygosity of the 12 polymorphic loci ranged from 0.10 to 0.49, the effective number of alleles ranged from 1.11 to 1.98, and the polymorphic information content ranged from 0.09 to 0.37. The chi-square test showed that only RHPN2:g.42678119T>G and RALYL:g.90030866A>G were in Hardy–Weinberg disequilibrium (p < 0.05); the other loci were in equilibrium (p > 0.05). These SNPs associated with important traits in Alpine Merino sheep provide a theoretical basis for genomic selection and molecular design breeding. [ABSTRACT FROM AUTHOR]

Simple Summary: The weight features of Alpine Merino Sheep, particularly their live weight in the 14th month (WT), are crucial in production and breeding, as they live at high altitudes and in highland areas where oxygen is scarce. Genome selection (GS) offers the advantages of minimizing breeding costs and generational intervals, and the main objective of genome selection breeding is the accuracy of GS. Genome-wide association studies (GWASs) were used in this study to extract the variation information related to the 14-month-old body weight trait of Alpine Merino Sheep, identify candidate genes associated with this trait, and employ GWAS results as prior information to conduct GS research on the trait to determine the most suitable GS breeding model for the target trait. Alpine Merino Sheep is a novel breed reared from Australian Merino Sheep as the father and Gansu Alpine Fine-Wool Sheep as the mother, living all year in cold and arid alpine areas with exceptional wool quality and meat performance. Body weight is an important economic trait of the Alpine Merino Sheep, but there is limited research on identifying the genes associated with live weight in the 14th month for improving the accuracy of the genomic prediction of this trait. Therefore, this study's sample comprised 1310 Alpine Merino Sheep ewes, and the Fine Wool Sheep 50K Panel was used for genome-wide association study (GWAS) analysis to identify candidate genes. Moreover, the trial population (1310 ewes) in this study was randomly divided into two groups. One group was used as the population for GWAS analysis and screened for the most significant top 5%, top 10%, top 15%, and top 20% SNPs to obtain prior marker information. The other group was used to estimate the genetic parameters based on the weight assigned by heritability combined with different prior marker information. The aim of this study was to compare the accuracy of genomic breeding value estimation when combined with prior marker information from GWAS analysis with the optimal linear unbiased prediction method for genome selection (GBLUP) for the breeding value of target traits. Finally, the accuracy was evaluated using the five-fold cross-validation method. This research provides theoretical and technical support to improve the accuracy of sheep genome selection and better guide breeding. The results demonstrated that eight candidate genes were associated with GWAS analysis, and the gene function query and literature search results suggested that FAM184B, NCAPG, MACF1, ANKRD44, DCAF16, FUK, LCORL, and SYN3 were candidate genes affecting live weight in the 14th month (WT), which regulated the growth of muscle and bone in sheep. In genome selection analysis, the heritability of GBLUP to calculate the WT was 0.335–0.374, the accuracy after five-fold cross-verification was 0.154–0.190, and after assigning different weights to the top 5%, top 10%, top 15%, and top 20% of the GWAS results in accordance with previous information to construct the G matrix, the accuracy of the WT in the GBLUP model was improved by 2.59–7.79%. [ABSTRACT FROM AUTHOR]

Lactobacillus plantarum is a catalase-negative species and distributes in human intestinal tracts. However, the cytoprotective effects of the catalase-activated L. plantarum strain have yet to be exploited against reactive oxygen species (ROS). Here, a catalase-activated L. plantarum CGMCC 6888 (CatA+) was obtained using exogenous added heme. The scavenging free radical abilities of this strain were obviously increased. Moreover, the activated catalase A in L. plantarum CGMCC 6888 endowed the intestinal epithelium NCM460 with lower ROS content after degrading H2O2. In addition, the transcription levels of Nrf2 and Nrf2-related antioxidant enzyme genes (HO-1, GCLC, NQO-1 and TXNRD1) and tight junction protein genes (ZO-1, OCLN, and JAM-1) were upregulated significantly when co-incubated with CGMCC 6888/CatA+. This work confirmed that the catalase A conferred L. plantarum with the strong protection effects in the intestinal epithelial cells against ROS. [ABSTRACT FROM AUTHOR]

Hair follicle development and wool shedding in sheep are poorly understood. This study investigated the population structures and genetic differences between sheep with different wool types to identify candidate genes related to these traits. We used Illumina ovine SNP 50K chip genotyping data of 795 sheep populations comprising 27 breeds with two wool types, measuring the population differentiation index (Fst), nucleotide diversity (θπ ratio), and extended haplotype homozygosity among populations (XP-EHH) to detect the selective signatures of hair sheep and fine-wool sheep. The top 5% of the Fst and θπ ratio values, and values of XP-EHH < −2 were considered strongly selected SNP sites. Annotation showed that the PRX, SOX18, TGM3, and TCF3 genes related to hair follicle development and wool shedding were strongly selected. Our results indicated that these methods identified important genes related to hair follicle formation, epidermal differentiation, and hair follicle stem cell development, and provide a meaningful reference for further study on the molecular mechanisms of economically important traits in sheep. [ABSTRACT FROM AUTHOR]

Simple Summary: Body weight traits are economically important in the sheep industry, and it is critical to explore their underlying genetic architecture. Hence, four body weight traits, including birth, weaning, yearling, and adult weights were examined. Through a genome-wide association study on Chinese fine-wool sheep, several candidate single-nucleotide polymorphisms (SNPs) and genes were found potentially associated with the traits of interest. The results of this study may facilitate the potential use of the genes involved in growth and production traits for the genetic improvement of productivity in sheep. Body weight is an important economic trait for sheep and it is vital for their successful production and breeding. Therefore, identifying the genomic regions and biological pathways that contribute to understanding variability in body weight traits is significant for selection purposes. In this study, the genome-wide associations of birth, weaning, yearling, and adult weights of 460 fine-wool sheep were determined using resequencing technology. The results showed that 113 single nucleotide polymorphisms (SNPs) reached the genome-wide significance levels for the four body weight traits and 30 genes were annotated effectively, including AADACL3, VGF, NPC1, and SERPINA12. The genes annotated by these SNPs significantly enriched 78 gene ontology terms and 25 signaling pathways, and were found to mainly participate in skeletal muscle development and lipid metabolism. These genes can be used as candidate genes for body weight in sheep, and provide useful information for the production and genomic selection of Chinese fine-wool sheep. [ABSTRACT FROM AUTHOR]

Enterovirus 71 (EV-A71) is the main causative pathogen of childhood hand, foot and mouth disease. Effective medicine is currently unavailable for the treatment of this viral disease. Using the fragment-hopping strategy, a series of 2-aryl-isoindolin-1-one compounds were designed, synthesized and investigated for their in vitro antiviral activity towards multiple EV-A71 clinical isolates (H, BrCr, Shenzhen98, Jiangsu52) in Vero cell culture in this study. The structure–activity relationship (SAR) studies identified 2-phenyl-isoindolin-1-ones as a new potent chemotype with potent antiviral activity against EV-A71. Ten out of the 24 tested compounds showed significant antiviral activity (EC50 < 10 µM) towards four EV-A71 strains. Compounds A3 and A4 exhibited broad and potent antiviral activity with the 50% effective concentration (EC50) values in the range of 1.23–1.76 μM. Moreover, the selectivity indices of A3 and A4 were significantly higher than those of the reference compound, pirodavir. The western blotting experiment indicated that the viral VP1 was significantly decreased at both the protein and RNA level in a dose-dependent manner following treatment with compound A3. Moreover, compound A3 inhibited the viral replication by acting on the virus entry stage. In summary, this study led to the discovery of 2-aryl-isoindolin-1-ones as a promising scaffold with potent anti-EV-A71 activities, which deserves further in-depth studies. [ABSTRACT FROM AUTHOR]