ABCD4 is associated with mammary gland development in mammals.

BACKGROUND: Mammary gland development is a critical process in mammals, crucial for their reproductive success and offspring nourishment. However, the functional roles of key candidate genes associated with teat number, including ABCD4, VRTN, PROX2, and DLST, in this developmental process remain elusive. To address this gap in knowledge, we conducted an in-depth investigation into the dynamic expression patterns, functional implications, and regulatory networks of these candidate genes during mouse mammary gland development. RESULTS: In this study, the spatial and temporal patterns of key genes were characterized in mammary gland development. Using time-series single-cell data, we uncovered differences in the expression of A bcd4, Vrtn, Prox2, and Dlst in cell population of the mammary gland during embryonic and adult stages, while Vrtn was not detected in any cells. We found that only overexpression and knockdown of Abcd4 could inhibit proliferation and promote apoptosis of HC11 mammary epithelial cells, whereas Prox2 and Dlst had no significant effect on these cells. Using RNA-seq and qPCR, further analysis revealed that Abcd4 can induce widespread changes in the expression levels of genes involved in mammary gland development, such as Igfbp3, Ccl5, Tlr2, and Prlr, which were primarily associated with the MAPK, JAK-STAT, and PI3K-AKT pathways by functional enrichment. CONCLUSIONS: These findings revealed ABCD4 as a candidate gene pivotal for regulating mammary gland development and lactation during pregnancy by influencing PRLR expression.

Genetic introgression from commercial European pigs to the indigenous Chinese Lijiang breed and associated changes in phenotypes.

BACKGROUND: Gene flow is crucial for enhancing economic traits of livestock. In China, breeders have used hybridization strategies for decades to improve livestock performance. Here, we performed whole-genome sequencing of a native Chinese Lijiang pig (LJP) breed. By integrating previously published data, we explored the genetic structure and introgression of genetic components from commercial European pigs (EP) into the LJP, and examined the impact of this introgression on phenotypic traits. RESULTS: Our analysis revealed significant introgression of EP breeds into the LJP and other domestic pig breeds in China. Using a haplotype-based approach, we quantified introgression levels and compared EP to LJP and other Chinese domestic pigs. The results show that EP introgression is widely prevalent in Chinese domestic pigs, although there are significant differences between breeds. We propose that LJP could potentially act as a mediator for the transmission of EP haplotypes. We also examined the correlation between EP introgression and the number of thoracic vertebrae in LJP and identified VRTN and STUM as candidate genes for this trait. CONCLUSIONS: Our study provides evidence of introgressed European haplotypes in the LJP breed and describes the potential role of EP introgression on phenotypic changes of this indigenous breed.

CRISPR/Cas9-meditated gene knockout in pigs proves that LGALS12 deficiency suppresses the proliferation and differentiation of porcine adipocytes.

LGALS12, also known as galectin12, belongs to the galectin family with ß-galactoside-binding activity. We previously reported that LGALS12 is an important regulator of adipogenesis in porcine adipocytes in vitro, but its value in pig breeding needed to be explored in vivo. In this study, we used CRISPR/Cas9 to construct porcine fetal fibroblasts (PFFs) with a 43 bp deletion in LGALS12 exon 2. Using these PFFs as donor cells, a LGALS12 knockout pig model was generated via somatic cell nuclear transfer. Primary cultures of porcine intramuscular (IM) and subcutaneous (SC) adipocytes were established using cells from LGALS12 knockout pigs and wild-type pigs. A comparison of these cells proved that LGALS12 deficiency suppresses cell proliferation via the RAS-p38MAPK pathway and promotes lipolysis via the PKA pathway in both IM and SC adipocytes. In addition, we observed AKT activation only in IM adipocytes and suppression of the Wnt/ß-catenin only in SC adipocytes. Our findings suggest that LGALS12 deficiency affects the adipogenesis of IM and SC adipocytes through different mechanisms.

Haplotype genomic prediction of phenotypic values based on chromosome distance and gene boundaries using low-coverage sequencing in Duroc pigs.

BACKGROUND: Genomic selection using single nucleotide polymorphism (SNP) markers has been widely used for genetic improvement of livestock, but most current methods of genomic selection are based on SNP models. In this study, we investigated the prediction accuracies of haplotype models based on fixed chromosome distances and gene boundaries compared to those of SNP models for genomic prediction of phenotypic values. We also examined the reasons for the successes and failures of haplotype genomic prediction. METHODS: We analyzed a swine population of 3195 Duroc boars with records on eight traits: body judging score (BJS), teat number (TN), age (AGW), loin muscle area (LMA), loin muscle depth (LMD) and back fat thickness (BF) at 100 kg live weight, and average daily gain (ADG) and feed conversion rate (FCR) from 30 to100 kg live weight. Ten-fold validation was used to evaluate the prediction accuracy of each SNP model and each multi-allelic haplotype model based on 488,124 autosomal SNPs from low-coverage sequencing. Haplotype blocks were defined using fixed chromosome distances or gene boundaries. RESULTS: Compared to the best SNP model, the accuracy of predicting phenotypic values using a haplotype model was greater by 7.4% for BJS, 7.1% for AGW, 6.6% for ADG, 4.9% for FCR, 2.7% for LMA, 1.9% for LMD, 1.4% for BF, and 0.3% for TN. The use of gene-based haplotype blocks resulted in the best prediction accuracy for LMA, LMD, and TN. Compared to estimates of SNP additive heritability, estimates of haplotype epistasis heritability were strongly correlated with the increase in prediction accuracy by haplotype models. The increase in prediction accuracy was largest for BJS, AGW, ADG, and FCR, which also had the largest estimates of haplotype epistasis heritability, 24.4% for BJS, 14.3% for AGW, 14.5% for ADG, and 17.7% for FCR. SNP and haplotype heritability profiles across the genome identified several genes with large genetic contributions to phenotypes: NUDT3 for LMA, LMD and BF, VRTN for TN, COL5A2 for BJS, BSND for ADG, and CARTPT for FCR. CONCLUSIONS: Haplotype prediction models improved the accuracy for genomic prediction of phenotypes in Duroc pigs. For some traits, the best prediction accuracy was obtained with haplotypes defined using gene regions, which provides evidence that functional genomic information can improve the accuracy of haplotype genomic prediction for certain traits.

Genome­wide association study and genomic prediction for growth traits in yellow-plumage chicken using genotyping-by-sequencing.

BACKGROUND: Growth traits are of great importance for poultry breeding and production and have been the topic of extensive investigation, with many quantitative trait loci (QTL) detected. However, due to their complex genetic background, few causative genes have been confirmed and the underlying molecular mechanisms remain unclear, thus limiting our understanding of QTL and their potential use for the genetic improvement of poultry. Therefore, deciphering the genetic architecture is a promising avenue for optimising genomic prediction strategies and exploiting genomic information for commercial breeding. The objectives of this study were to: (1) conduct a genome-wide association study to identify key genetic factors and explore the polygenicity of chicken growth traits; (2) investigate the efficiency of genomic prediction in broilers; and (3) evaluate genomic predictions that harness genomic features. RESULTS: We identified five significant QTL, including one on chromosome 4 with major effects and four on chromosomes 1, 2, 17, and 27 with minor effects, accounting for 14.5 to 34.1% and 0.2 to 2.6% of the genomic additive genetic variance, respectively, and 23.3 to 46.7% and 0.6 to 4.5% of the observed predictive accuracy of breeding values, respectively. Further analysis showed that the QTL with minor effects collectively had a considerable influence, reflecting the polygenicity of the genetic background. The accuracy of genomic best linear unbiased predictions (BLUP) was improved by 22.0 to 70.3% compared to that of the conventional pedigree-based BLUP model. The genomic feature BLUP model further improved the observed prediction accuracy by 13.8 to 15.2% compared to the genomic BLUP model. CONCLUSIONS: A major QTL and four minor QTL were identified for growth traits; the remaining variance was due to QTL effects that were too small to be detected. The genomic BLUP and genomic feature BLUP models yielded considerably higher prediction accuracy compared to the pedigree-based BLUP model. This study revealed the polygenicity of growth traits in yellow-plumage chickens and demonstrated that the predictive ability can be greatly improved by using genomic information and related features.

Accelerated deciphering of the genetic architecture of agricultural economic traits in pigs using a low-coverage whole-genome sequencing strategy.

BACKGROUND: Uncovering the genetic architecture of economic traits in pigs is important for agricultural breeding. However, high-density haplotype reference panels are unavailable in most agricultural species, limiting accurate genotype imputation in large populations. Moreover, the infinitesimal model of quantitative traits implies that weak association signals tend to be spread across most of the genome, further complicating the genetic analysis. Hence, there is a need to develop new methods for sequencing large cohorts without large reference panels. RESULTS: We describe a Tn5-based highly accurate, cost- and time-efficient, low-coverage sequencing method to obtain 11.3 million whole-genome single-nucleotide polymorphisms in 2,869 Duroc boars at a mean depth of 0.73×. On the basis of these single-nucleotide polymorphisms, a genome-wide association study was performed, resulting in 14 quantitative trait loci (QTLs) for 7 of 21 important agricultural traits in pigs. These QTLs harbour genes, such as ABCD4 for total teat number and HMGA1 for back fat thickness, and provided a starting point for further investigation. The inheritance models of the different traits varied greatly. Most follow the minor-polygene model, but this can be attributed to different reasons, such as the shaping of genetic architecture by artificial selection for this population and sufficiently interconnected minor gene regulatory networks. CONCLUSIONS: Genome-wide association study results for 21 important agricultural traits identified 14 QTLs/genes and showed their genetic architectures, providing guidance for genetic improvement harnessing genomic features. The Tn5-based low-coverage sequencing method can be applied to large-scale genome studies for any species without a good reference panel and can be used for agricultural breeding.

Current trends in optimal medical therapy after PCI and its influence on clinical outcomes in China.

BACKGROUND: Limited data were available on the current trends in optimal medical therapy (OMT) after PCI and its influence on clinical outcomes in China. We aimed to evaluate the utilization and impact of OMT on the main adverse cardiovascular and cerebrovascular events (MACCEs) in post-PCI patients and analyzed the factors predictive of OMT after discharge. METHODS: We collected data from 3812 individuals from 2016.10 to 2017.09 at TEDA International Cardiovascular Hospital. They were classified into an OMT group and a non-OMT group according to their OMT status, which was defined as the combination of dual antiplatelet therapy, statins, ß-blockers, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers after PCI. Multivariable Cox regression models were developed to assess the association between OMT and MACCEs, defined as all-cause mortality, nonfatal myocardial infarction, stroke, and target vessel revascularization. A logistic regression model was established to analyze the factors predictive of OMT. RESULTS: Our results revealed that the proportion of patients receiving OMT and its component drugs decreased over time. A total of 36.0% of patients were still adherent to OMT at the end of follow-up. Binary logistic regression analysis revealed that baseline OMT (P < 0.001, OR = 52.868) was the strongest predictor of OMT after PCI. The Cox hazard model suggested that smoking after PCI was associated with the 1-year risk of MACCE (P = 0.001, HR = 2.060, 95% CI 1.346-3.151), while OMT (P = 0.001, HR = 0.486, 95% CI 0.312-0.756) was an independent protective factor against postoperative MACCEs. CONCLUSIONS: There was still a gap between OMT utilization after PCI and the recommendations in the evidence-based guidelines. Sociodemographic and clinical factors influence the application of OMT. The management of OMT and smoking cessation after PCI should be emphasized.

Improving read alignment through the generation of alternative reference via iterative strategy.

There is generally one standard reference sequence for each species. When extensive variations exist in other breeds of the species, it can lead to ambiguous alignment and inaccurate variant calling and, in turn, compromise the accuracy of downstream analysis. Here, with the help of the FPGA hardware platform, we present a method that generates an alternative reference via an iterative strategy to improve the read alignment for breeds that are genetically distant to the reference breed. Compared to the published reference genomes, by using the alternative reference sequences we built, the mapping rates of Chinese indigenous pigs and chickens were improved by 0.61-1.68% and 0.09-0.45%, respectively. These sequences also enable researchers to recover highly variable regions that could be missed using public reference sequences. We also determined that the optimal number of iterations needed to generate alternative reference sequences were seven and five for pigs and chickens, respectively. Our results show that, for genetically distant breeds, generating an alternative reference sequence can facilitate read alignment and variant calling and improve the accuracy of downstream analyses.

Retraction Note To: The relationship between subclinical thyroid dysfunction and the risk of fracture or low bone mineral density: a systematic review and meta-analysis of cohort studies.

The editors have retracted this article [1] because it shows significant overlap with a publication by Blum et al. [2] Limin Tian does not agree to this retraction. All the other authors have not responded to any correspondence from the editor about this retraction.

Selection of Optimal Ancestry Informative Markers for Classification and Ancestry Proportion Estimation in Pigs.

Using small sets of ancestry informative markers (AIMs) constitutes a cost-effective method to accurately estimate the ancestry proportions of individuals. This study aimed to generate a small and effective number of AIMs from ∼60 K single nucleotide polymorphism (SNP) data of porcine and estimate three ancestry proportions [East China pig (ECHP), South China pig (SCHP), and European commercial pig (EUCP)] from Asian breeds and European domestic breeds. A total of 186 samples of 10 pure breeds were divided into three groups: ECHP, SCHP, and EUCP. Using these samples and a one-vs.-rest SVM classifier, we found that using only seven AIMs could completely separate the three groups. Subsequently, we utilized supervised ADMIXTURE to calculate ancestry proportions and found that the 129 AIMs performed well on ancestry estimates when pseudo admixed individuals were used. Furthermore, another 969 samples of 61 populations were applied to evaluate the performance of the 129 AIMs. We also observed that the 129 AIMs were highly correlated with estimates using ∼60 K SNP data for three ancestry components: ECHP (Pearson correlation coefficient (r) = 0.94), SCHP (r = 0.94), and EUCP (r = 0.99). Our results provided an example of using a small number of pig AIMs for classifications and estimating ancestry proportions with high accuracy and in a cost-effective manner.

Adult serum 25(OH)D3 in Gansu province, northwest China: a cross-sectional study.

BACKGROUND AND OBJECTIVES: This analytical cross-sectional study investigated the prevalence of vitamin D deficiency and its association with metabolic risk factors in the adult population of Gansu Province, China. METHODS AND STUDY DESIGN: In total, 11,157 healthy participants (4,740 men and 6,417 women) were enrolled. A questionnaire was used to assess general characteristics and personal habits. We detected 25-hydroxyvitamin D and associated metabolic parameters through electrochemiluminescence immunoassays. RESULTS: The prevalence of severe deficiency (<10 ng/mL), deficiency (10-20 ng/mL), insufficiency (20-30 ng/mL), and sufficiency (>=30 ng/mL) among the participants was 17.3%, 64.6%, 11.8%, and 6.3%, respectively. Vitamin D deficiency was more prevalent in women than in men (82.5% vs 81.1%, p<0.001). The significant predictors of vitamin D deficiency included younger age and female sex (p<0.05), whereas sun exposure, physical activity, and calcium (Ca) supplementation were associated with less vitamin D deficiency (p<0.05). Serum 25(OH)D3 was inversely associated with parathyroid hormone (r=-0.279, p<0.001) and positively associated with serum Ca (r=0.239, p<0.001), serum P (r=0.090, p=0.018), LDL cholesterol (r=0.100, p=0.008), and BMI (r=0.093, p=0.014). No significant association was observed between serum 25(OH)D3 and metabolic disorders. CONCLUSIONS: Vitamin D deficiency is highly prevalent among the adult population of Gansu Province, northwest China, especially young physically inactive and overweight women with limited sunlight exposure, whose biomarkers put them at greater risk of osteoporosis and cardiovascular disease.

The association of neutrophil to lymphocyte ratio, mean platelet volume, and platelet distribution width with diabetic retinopathy and nephropathy: a meta-analysis.

The aim of the present study was to investigate the correlation of neutrophil to lymphocyte ratio (NLR), mean platelet volume (MPV), and platelet distribution width (PDW) with diabetic nephropathy (DN) and diabetic retinopathy (DR). We searched for eligible studies from PubMed, Embase, Web of Science, and CNKI up to 1 December 2017. Standardized mean difference (SMD) was calculated with a confidence interval (CI) of 95%. A total of 48 studies were included in our meta-analysis. Compared with patients with type Ⅱ diabetes mellitus (T2DM) and without DR, NLR, MPV, and PDW were higher in patients with DR (SMD = 0.77; 95% CI: 0.49-1.05; P<0.001; SMD = 0.68; 95% CI: 0.36-0.99; P<0.001; SMD = 0.52; 95% CI: 0.28-0.76; P<0.01). Compared with patients with T2DM and without DN, NLR, MPV, and PDW were higher in patients with DN (SMD = 0.63; 95% CI: 0.43-0.83; P<0.001; SMD = 0.81; 95% CI: 0.36-1.25; P<0.001; SMD = 0.70; 95% CI: 0.50-0.90; P<0.001). We also found that MPV was strongly associated with the severity of DR, and NLR was closely related to the degree of DN. Our findings indicated that NLR, MPV, and PDW could be recommended as inexpensive diagnostic biomarkers for DN and DR. However, considering several limitations in the present study, further high-quality clinical studies should be performed to investigate the relationship of NLR, MPV, and PDW to DN and DR.

Appraisal of clinical practice guidelines on the management of hypothyroidism in pregnancy using the Appraisal of Guidelines for Research and Evaluation II instrument.

PURPOSE: This study aimed to systematically evaluate the quality of guidelines for the management of hypothyroidism in pregnancy. METHOD: Systematic searches were conducted to identify hypothyroidism in pregnancy guidelines published in electronic databases and developers' websites. Four reviewers independently evaluated eligible guidelines using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) instrument. Agreement among reviewers was measured using the intraclass correlation coefficient (ICC). The number of recommendations, strength of recommendations, and levels of evidence were determined. The software used for analysis was SPSS version 12.0. RESULTS: Nine guidelines met the inclusion criteria and were appraised. The scope and purpose (65%) and clarity of presentation (70%) domains achieved relatively high scores, whereas the stakeholder involvement (41%), rigor of development (33%), applicability (36%), and editorial independence (31%) domains yielded low scores. The American Thyroid Association (ATA) guideline ranked the highest, whereas the 2012 Chinese Society of Endocrinology (CSE) guideline ranked the lowest among all the guidelines. The British Thyroid Association (BTA) and ATA guidelines were strongly recommended as dependable and helpful references to aid clinical decisions for medical providers, whereas the CSE guideline was not recommended. Most recommendations of the guidelines were relatively consistent. However, the nine guidelines varied with respect to their recommendations on thyroid scanning, dose of levothyroxine (L-T4) treatment, and target thyroid-stimulating hormone(TSH) level of L-T4 therapy. CONCLUSIONS: The quality of the guidelines on the management of hypothyroidism in pregnancy is highly variable. Additionally, these guidelines need significant improvement, especially in the rigor of development and applicability domains. Some improvements should be made to promote the development and implementation of guidelines, for example, conducting a comprehensive search strategy to include more potential evidence and establishing a standard grading system to evaluate the quality of evidence.

The relationship between subclinical thyroid dysfunction and the risk of fracture or low bone mineral density: a systematic review and meta-analysis of cohort studies.

Our aim was to assess the risk of fractures or low bone mineral density (BMD) associated with subclinical thyroid dysfunction among cohorts. We systematically searched Medline (via PubMed), EMBASE, Cochrane Library, Web of Science, CENTRAL and SinoMed up to 31 July 2016 to identify cohort studies which have analyzed associations between subclinical thyroid dysfunction and fracture or BMD. A total of 19 population-based cohorts including 79,368 participants with relationships between subclinical thyroid dysfunction and fractures or BMD were identified as eligible for this meta-analysis. Subclinical hypothyroidism was associated with relative risks (RRs) of 1.34 (95% confidence interval [CI] 1.14, 1.58; I 2 = 32%) for hip fracture, 1.27 (95% CI 1.02, 1.58; I 2 = 51.9%) for any location of fracture, and 1.25 (95% CI 1.04, 1.50) for forearm fracture. Subclinical hyperthyroidism was associated with RRs of 1.71 (95% CI 1.06, 2.76; I 2 = 0.0%) for spine fracture, 1.20 (95% CI 1.03, 1.39; I 2 = 0.0%) for non-spine fracture, 1.44 (95% CI 1.21, 1.71; I 2 = 0.0%) for hip fracture, and 1.38 (95% CI 1.21, 1.58; I 2 = 0.0%) for any location of fracture. Subgroup analysis was conducted according to whether thyroid/anti-thyroid drug users were excluded or not and the results were similar. The change in BMD at the hip (weighted mean difference [WMD] = -0.060, 95% CI -0.116, -0.004; I 2 = 0.0%) and femoral neck (WMD = -0.046, 95% CI -0.077, -0.015; I 2 = 0.0%) was significantly decreased in the subclinical hyperthyroidism group compared with the euthyroidism groups in females. We failed to find any associations between the change in BMD and subclinical hypothyroidism. The overall quality of evidence was low in all outcomes. Subclinical hyperthyroidism and subclinical hypothyroidism were associated with an increased risk of fractures. Although subclinical hyperthyroidism was related to reduced BMD, no evidence could prove a definite association between subclinical hypothyroidism and the risk of low BMD.

Relationship between Subclinical Thyroid Dysfunction and the Risk of Cardiovascular Outcomes: A Systematic Review and Meta-Analysis of Prospective Cohort Studies.

BACKGROUND: Evidence on the association between subclinical thyroid dysfunction and the risk of cardiovascular outcomes are conflicting. METHODS AND RESULTS: PubMed, EMbase, Web of Science, Cochrane Library, and China Biology Medicine (CBM) databases were searched from inception to July 10, 2016. A total of 16 studies were included for meta-analysis. We found that subclinical hypothyroidism was not correlated with coronary heart disease (CHD) (RR = 1.17; 95% CI, 0.91-1.52), total mortality (RR = 1.02; 95% CI, 0.93-1.13), cardiovascular mortality (RR = 1.06; 95% CI, 0.77-1.45), heart failure (RR = 1.17; 95% CI, 0.87-1.57), and atrial fibrillation (RR = 1.05; 95% CI, 0.91-1.21), except CHD mortality (RR = 1.37; 95% CI, 1.03-1.84). Subgroup analysis indicated a higher estimation risk in CHD (RR = 1.54; 95% CI, 1.00-2.39), cardiovascular mortality (RR = 2.14; 95% CI, 1.43-3.22), and CHD mortality (RR = 1.54; 95% CI, 1.11-2.15) among participants < 65 years. Furthermore, subclinical hyperthyroidism was found to be associated with CHD (RR = 1.20; 95% CI, 1.02-1.42), total mortality (RR = 1.27; 95% CI, 1.07-1.51), and CHD mortality (RR = 1.45; 95% CI, 1.12-1.86). CONCLUSIONS: Subclinical hypothyroidism is likely associated with an increased risk of CHD mortality, and subclinical hyperthyroidism is likely associated with increased risk of CHD, CHD mortality, and total mortality.

Prevalence of osteoporosis and related lifestyle and metabolic factors of postmenopausal women and elderly men: A cross-sectional study in Gansu province, Northwestern of China.

The aim of this study was to investigate the osteoporosis prevalence and the risks of postmenopausal women and elderly men in Gansu province.This cross-sectional study involved 3359 postmenopausal women and 3205 elderly males who were randomly selected from 7 areas in Gansu province. Areal bone mineral density (BMD) (g/cm) was measured at the distal one-third radius of the nonstressed forearm using dual-energy X-ray absorptiometry (DXA: Osteometer MediTech). Factors related to osteoporosis were analyzed.The prevalence of osteoporosis in the entire study population was 9.65% for postmenopausal women and 8.08% for elderly males by WHO criteria, while the rate of osteopenia were 27.09% for postmenopausal women and 26.68% for elderly males. Risk of osteoporosis was significantly associated with age, menopause age, duration of menopause, body mass index (BMI), educational level, and alcohol consumption in postmenopausal women. In elderly men, age, BMI, current smoking, alcohol consumption, physical activity, and sun exposure were associated with osteoporosis. The bone turnover markers osteocalcin (OC) and C-terminal cross-linked telopeptides of type I collagen (ß-CTX) were inversely correlated with BMD in both genders; serum P and 25(OH)D found no significant correlation with BMD. Serum Ca showed a positive effect on BMD in elderly men only.The osteoporosis prevalence of postmenopausal women and the men aged over 60 years in Gansu province is presented. Risk of osteoporosis was significantly associated with age, menopause age, year since menopause, BMI, and educational level in postmenopausal women. In elderly men, age, BMI, and current smoking were associated with osteoporosis. This study also found that higher OC and ß-CTX level were associated with lower BMD. Poor 25(OH)D, Ca, P status were not associated with an increased risk of low BMD.

Genome-wide analysis of structural variants reveals genetic differences in Chinese pigs.

Pigs have experienced long-term selections, resulting in dramatic phenotypic changes. Structural variants (SVs) are reported to exert extensive impacts on phenotypic changes. We built a high resolution and informative SV map based on high-depth sequencing data from 66 Chinese domestic and wild pigs. We inferred the SV formation mechanisms in the pig genome and used SVs as materials to perform a population-level analysis. We detected the selection signals on chromosome X for northern Chinese domestic pigs, as well as the differentiated loci across the whole genome. Analysis showed that these loci differ between southern and northern Chinese domestic pigs. Our results based on SVs provide new insights into genetic differences in Chinese pigs.

Melatonin suppresses autophagy in type 2 diabetic osteoporosis.

Type 2 diabetes mellitus is often complicated by osteoporosis, a process which may involve osteoblast autophagy. As melatonin suppresses autophagy under certain conditions, we its investigated the effects on bone autophagy during diabetes. We first assessed different body parameters in a diabetic rat model treated with various concentrations of melatonin. Dynamic biomechanicalmeasurements, bone organization hard slice dyeing and micro-CT were used to observe the rat bone microstructure, and immunohistochemistry was used to determine levels of autophagy biomarkers. We also performed in vitro experiments on human fetal osteoblastic (hFOB1.19) cells cultured with high glucose, different concentrations of melatonin, and ERK pathway inhibitors. And we used Western blotting and immunofluorescence to measure the extent of osteogenesis and autophagy. We found that melatonin improved the bone microstructure in our rat diabetes model and reduced the level of autophagy(50 mg/kg was better than 100 mg/kg). Melatonin also enhanced osteogenesis and suppressed autophagy in osteoblasts cultured at high glucose levels (10 µM was better than 1 mM). This suggests melatonin may reduce the level of autophagy in osteoblasts and delay diabetes-induced osteoporosis by inhibiting the ERK signaling pathway.