Higher disease burden and lower utilization in mongolian with breast cancer: a 9-year retrospective cohort study of 18.19 million adults in China.

BACKGROUND: Whether health inequalities of disease burden and medical utilization exist by ethnicity in Asian breast cancer (BC) patients remains unclear. We aim to measure ethnic disparities in disease burden and utilization among Mongolian and Han female breast cancer patients in China. MATERIALS AND METHODS: Based on data extracted from Inner Mongolia Regional Health Information Platform, a retrospective cohort study was established during 2012-2021. Disease burden including incidence, 5-year prevalence, mortality, survival rate, and medical cost were analyzed and compared between Han and Mongolian patients. RESULTS: A total of 34,878 female patients (mean [SD] age, 52.34 [10.93] years) were included among 18.19 million Chinese, and 4,315 [12.03%] participants were Mongolian. Age-standardized rates of incidence are 32.68 (95% CI: 20.39-44.98) per 100,000. Higher age-specific incidence and 5-year prevalence were observed in Mongolian than in Han. The cost of breast cancer annually per capita was significantly lower for Mongolian than Han in FBC ($1,948.43 [590.11-4 776.42] vs. $2,227.35 [686.65-5,929.59], P<0.001). Mongolian females showed higher all-cause mortality (30.92, [95% CI: 28.15-33.89] vs. 27.78, [95% CI: 26.77-28.83] per 1,000, P=0.036) and breast cancer-specific mortality (18.78, [95% CI: 16.64-21.13] vs. 15.22, [95% CI: 14.47-16.00] per 1,000, P=0.002) than Han females. After adjusting covariates, Mongolian were associated with increased all-cause mortality (HR, 1.21, [95% CI, 1.09-1.34]; P<0.001) and breast cancer-specific mortality (HR, 1.31, [95% CI, 1.14-1.49]; P<0.001). CONCLUSION: The findings of this cohort study highlight a higher level of disease burden with unmet medical demand in Mongolian patients, suggesting that more practical efforts should be made for the minority. Further research is needed to explore the concrete mechanisms of the disparities as well as eliminate health disproportion.

Four Markers Useful for the Distinction of Intrauterine Growth Restriction in Sheep.

Intrauterine growth restriction (IUGR) is a common perinatal complication in animal reproduction, with long-lasting negative effects on neonates and postnatal animals, which seriously negatively affects livestock production. In this study, we aimed to identify potential genes associated with the diagnosis of IUGR through bioinformatics analysis. Based on the 73 differentially expressed related genes obtained by differential analysis and weighted gene co-expression network analysis, we used three machine learning algorithms to identify 4 IUGR-related hub genes (IUGR-HGs), namely, ADAM9, CRYL1, NDP52, and SERPINA7, whose ROC curves showed that they are a good diagnostic target for IUGR. Next, we identified two molecular subtypes of IUGR through consensus clustering analysis and constructed a gene scoring system based on the IUGR-HGs. The results showed that the IUGR score was positively correlated with the risk of IUGR. The AUC value of IUGR scoring accuracy was 0.970. Finally, we constructed a new artificial neural network model based on the four IUGR-HGs to diagnose sheep IUGR, and its accuracy reached 0.956. In conclusion, the IUGR-HGs we identified provide new potential molecular markers and models for the diagnosis of IUGR in sheep; they can better diagnose whether sheep have IUGR. The present findings provide new perspectives on the diagnosis of IUGR.

miR-136 Regulates the Proliferation and Adipogenic Differentiation of Adipose-Derived Stromal Vascular Fractions by Targeting HSD17B12.

Fat deposition involves the continuous differentiation of adipocytes and lipid accumulation. Studies have shown that microRNA miR-136 and 17ß-hydroxysteroid dehydrogenase type 12 (HSD17B12) play important roles in lipid accumulation. However, the regulatory mechanism through which miR-136 targets HSD17B12 during ovine adipogenesis remains unclear. This study aimed to elucidate the role of miR-136 and HSD17B12 in adipogenesis and their relationship in ovine adipose-derived stromal vascular fractions (SVFs). The target relationship between miR-136 and HSD17B12 was predicted and confirmed using bioinformatics and a dual-luciferase reporter assay. The results showed that miR-136 promoted proliferation and inhibited adipogenic differentiation of ovine SVFs. We also found that HSD17B12 inhibited proliferation and promoted adipogenic differentiation of ovine SVFs. Collectively, our results indicate that miR-136 facilitates proliferation and attenuates adipogenic differentiation of ovine SVFs by targeting HSD17B12. These findings provide a theoretical foundation for further elucidation of the regulatory mechanisms of lipid deposition in sheep.

Primary malignant bone tumors incidence, mortality, and trends in China from 2000 to 2015.

BACKGROUND: Primary malignant bone tumors are uncommon, and their epidemiological features are rarely reported. We aimed to study the incidence and death characteristics of bone tumors from 2000 to 2015. METHODS: Population-based cancer registries submitted registry data to National Central Cancer Registry of China (NCCRC). The data collected from 501 local cancer registries in China were assessed using NCCRC screening methods and criteria. Incidence and mortality rates of primary bone tumor were stratified by age group, gender, and area. Age-standardized incidence and mortality rates were adjusted using the Chinese standard population in 2000 and Segi's world population. The annual percentage change (APC) in rate was calculated using the Joinpoint Regression Program. RESULTS: Data from 368 registries met quality control criteria, of which 134 and 234 were from urban and rural areas, respectively. The data covered 309,553,499 persons. The crude incidence, age-standardized incidence, and crude mortality rates were 1.77, 1.35, and 1.31 per 100,000, respectively. Incidence and mortality rates were higher in males than those in females; they showed downward trends, with declines of 2.2% and 4.8% per year, respectively, and the rates in urban areas were lower than those in rural areas. Significant declining trends were observed in urban areas. Stable trends were seen in rural areas during 2000 to 2007, followed by downward trends. Age-specific incidence and mortality rates showed stable trends in the age group of 0 to 19 years, and downward trends in the age group elder than 19 years. CONCLUSIONS: The incidence and mortality rates of primary malignant bone tumors in rural areas were higher compared to those in urban areas. Targeted prevention measures are required to monitor and control bone tumor incidence and improve the quality of life of affected patients. This research can provide a scientific basis for the prevention and control of bone tumors, as well as basic information for follow-up research.

Integrated database-based Screening Cohort for Asian Nomadic descendants in China (Scan-China): Insights on prospective ethnicity-focused cancer screening.

Established in 2017, the Screening Cohort for Asian Nomadic descendants in China (Scan-China) has benefited over 180,000 members of a multi-ethnic population, particularly individuals of Mongolian descent compared with the general population (Han ethnicity), in the Inner Mongolia Autonomous Region, China. This cohort study aims to evaluate the effectiveness of cancer screening and serve as a real-world data platform for cancer studies. The 6 most prevalent cancers in China are considered-namely, breast, lung, colorectal, gastric, liver and esophageal cancer. After baseline cancer risk assessments and screening tests, both active and passive follow-up (based on the healthcare insurance database, cancer registry, the front page of hospital medical records, and death certificates) will be conducted to trace participants' onset and progression of cancers and other prevalent chronic diseases. Scan-China has preliminarily found a disproportionately lower screening participation rate and higher incidence/mortality rates of esophageal and breast cancer among the Mongolian population than among their Han counterparts. Further research will explore the cancer burden, natural history, treatment patterns, and risk factors of the target cancers.

circITGB1 Regulates Adipocyte Proliferation and Differentiation via the miR-23a/ARRB1 Pathway.

Adipose tissues represent an important energy storage organ in animals and are the largest endocrine organ. It plays an important regulatory role in the pathogenesis of insulin resistance, cardiovascular disease, and metabolic syndrome. Adipose development is a complex biological process involving multiple key genes, signaling pathways, and non-coding RNAs, including microRNAs and circular RNAs. In this study, we characterized circITGB1 and named its host gene ITGB1, which is differentially expressed in sheep of different months based on sequencing data. We collated and analyzed the sequencing data to select miRNA-23a with strong binding to ARRB1. We found that miRNA-23a regulates the development and differentiation of sheep adipocytes by targeting ARRB1. As a competing endogenous RNA, circITGB1 overexpression effectively alleviated the inhibitory effect of miR-23a on ARRB1. Conclusively, we provide evidence that circITGB1 regulates the proliferation and differentiation of sheep adipocytes via the miR-23a/ARRB1 pathway. This study provides a scientific basis for further studies on adipose tissue development at the circRNA level.

circINSR Inhibits Adipogenic Differentiation of Adipose-Derived Stromal Vascular Fractions through the miR-152/MEOX2 Axis in Sheep.

Adipose tissue plays a crucial role in energy metabolism. Several studies have shown that circular RNA (circRNA) is involved in the regulation of fat development and lipid metabolism. However, little is known about their involvement in the adipogenic differentiation of ovine stromal vascular fractions (SVFs). Here, based on previous sequencing data and bioinformatics analysis, a novel circINSR was identified in sheep, which acts as a sponge to promote miR-152 in inhibiting the adipogenic differentiation of ovine SVFs. The interactions between circINSR and miR-152 were examined using bioinformatics, luciferase assays, and RNA immunoprecipitation. Of note, we found that circINSR was involved in adipogenic differentiation via the miR-152/mesenchyme homeobox 2 (MEOX2) pathway. MEOX2 inhibited adipogenic differentiation of ovine SVFs and miR-152 inhibited the expression of MEOX2. In other words, circINSR directly isolates miR-152 in the cytoplasm and inhibits its ability to promote adipogenic differentiation of ovine SVFs. In summary, this study revealed the role of circINSR in the adipogenic differentiation of ovine SVFs and its regulatory mechanisms, providing a reference for further interpretation of the development of ovine fat and its regulatory mechanisms.

Effects of 17α-Methyltestosterone on the Transcriptome and Sex Hormones in the Brain of Gobiocypris rarus.

17α-Methyltestosterone (MT), a synthetic environmental endocrine disruptor with androgenic effects, has been shown to disrupt the reproductive system and inhibit germ cell maturation in Gobiocypris rarus. To further investigate the regulation of gonadal development by MT through the hypothalamic-pituitary-gonadal (HPG) axis, G. rarus were exposed to 0, 25, 50, and 100 ng/L of MT for 7, 14, and 21 days. We analyzed its biological indicators, gonadotropin-releasing hormone (GnRH), gonadotropins, reproduction-related gene expression, and brain tissue transcriptome profiles. We found a significant decrease in the gonadosomatic index (GSI) in G. rarus males exposed to MT for 21 days compared to the control group. GnRH, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) levels, as well as the expressions of the gnrh3, gnrhr1, gnrhr3, fshß, and cyp19a1b genes, were significantly reduced in the brains of both male and female fish when exposed to 100 ng/L MT for 14 days compared to the controls. Therefore, we further constructed four RNA-seq libraries from 100 ng/L MT-treated groups of male and female fish, obtaining 2412 and 2509 DEGs in male and female brain tissue, respectively. Three common pathways were observed to be affected in both sexes after exposure to MT, namely, nicotinate and nicotinamide metabolism, focal adhesion, and cell adhesion molecules. Furthermore, we found that MT affected the PI3K/Akt/FoxO3a signaling pathway through the upregulation of foxo3 and ccnd2, and the downregulation of pik3c3 and ccnd1. Therefore, we hypothesize that MT interferes with the levels of gonadotropin-releasing hormone (GnRH, FSH, and LH) in G. rarus brains through the PI3K/Akt/FoxO3a signaling pathway, and affects the expression of key genes in the hormone production pathway (gnrh3, gnrhr1 and cyp19a1b) to interfere with the stability of the HPG axis, thus leading to abnormal gonadal development. This study provides a multidimensional perspective on the damaging effects of MT on fish and confirms that G. rarus is a suitable model animal for aquatic toxicology.

Overexpression of the QKI Gene Promotes Differentiation of Goat Myoblasts into Myotubes.

The QKI genes encode RNA-binding proteins regulating cell proliferation, differentiation, and apoptosis. The Goat QKI has six isoforms, but their roles in myogenesis are unclear. In this study, the six isoforms of the QKI gene were overexpressed in goat myoblast. Immunofluorescence, qPCR and Western blot were used to evaluate the effect of QKI on the differentiation of goat myoblast. An RNA-Seq was performed on the cells with the gain of the function from the major isoforms to screen differentially expressed genes (DEGs). The results show that six isoforms had different degrees of deletion in exons 6 and 7, and caused the appearance of different types of encoded amino acids. The expression levels of the QKI-1 and QKI-5 groups were upregulated in the biceps femoris and latissimus dorsi muscle tissues compared with those of the QKI-4, QKI-7, QKI-3 and QKI-6 groups. After 6 d of myoblast differentiation, QKI-5 and the myogenic differentiators MyoG, MyoD, and MyHC were upregulated. Compared to the negative control group, QKI promoted myotube differentiation and the myoblasts overexpressing QKI-5 formed large, abundant myotubes. In summary, we identified that the overexpression of the QKI gene promotes goat-myoblast differentiation and that QKI-5 is the major isoform, with a key role. The RNA-Seq screened 76 upregulated and 123 downregulated DEGs between the negative control and the QKI-5-overexpressing goat myoblasts after d 6 of differentiation. The GO and KEGG analyses associated the downregulated DEGs with muscle-related biological functions. Only the pathways related to muscle growth and development were enriched. This study provides a theoretical basis for further exploring the regulatory mechanism of QKI in skeletal-muscle development in goats.

Full-Length Transcriptome and Gene Expression Analysis of Different Ovis aries Adipose Tissues Reveals Transcript Variants Involved in Lipid Biosynthesis.

Sheep have historically been bred globally as a vital food source. To explore the transcriptome of adipose tissue and investigate key genes regulating adipose metabolism in sheep, adipose tissue samples were obtained from F1 Dorper × Hu sheep. High-throughput sequencing libraries for second- and third-generation sequencing were constructed using extracted total RNA. Functional annotation of differentially expressed genes and isoforms facilitated the identification of key regulatory genes and isoforms associated with sheep fat metabolism. SMRT-seq generated 919,259 high-accuracy cDNA sequences after filtering. Full-length sequences were corrected using RNA-seq sequences, and 699,680 high-quality full-length non-chimeric (FLNC) reads were obtained. Upon evaluating the ratio of total lengths based on FLNC sequencing, it was determined that 36,909 out of 56,316 multiple-exon isoforms met the criteria for full-length status. This indicates the identification of 330,375 full-length FLNC transcripts among the 370,114 multiple-exon FLNC transcripts. By comparing the reference genomes, 60,276 loci and 111,302 isoforms were identified. In addition, 43,423 new genes and 44,563 new isoforms were identified. The results identified 185 (3198), 394 (3592), and 83 (3286) differentially expressed genes (transcripts) between tail and subcutaneous, tail and visceral, and subcutaneous and visceral adipose tissues, respectively. Functional annotation and pathway analysis revealed the following observations. (1) Among the differentially expressed genes (DEGs) of TF and SF tissues, the downregulation of ACADL, ACSL6, and NC_056060.1.2536 was observed in SF, while FFAR4 exhibited upregulation. (2) Among the DEGs of TF and VF tissues, expressions of ACADL, ACSL6, COL1A1, COL1A2, and SCD were downregulated in VF, with upregulation of FFAR4. (3) Among SF and VF expressions of COL1A1, COL1A2, and NC_056060.1.2536 were downregulated in VF. Specific differentially expressed genes (ACADL, ACSL6, COL1A1, COL1A2, FFAR4, NC_056060.1.2536, and SCD) and transcripts (NC_056066.1.1866.16 and NC_056066.1.1866.22) were identified as relevant to fat metabolism. These results provide a dataset for further verification of the regulatory pathway associated with fat metabolism in sheep.

Association of Ethnicity, Sex, and Age With Cancer Diagnoses and Health Care Utilization Among Children in Inner Mongolia, China.

Importance: China is experiencing a sustained increase in childhood cancer. However, whether differences exist in disease burden by ethnicity remains unclear. Objective: To compare differences in cancer diagnoses and health care utilization in Inner Mongolia among children subgrouped by ethnicity (Han vs Mongolian), sex, and age. Design, Setting, and Participants: This retrospective cohort study in Inner Mongolia, China, used data on children aged 0 to 14 years with cancer from the Inner Mongolia Regional Health Information Platform, which comprises the National Basic Medical Insurance database and the Inner Mongolia cause-of-death reporting system, from January 1, 2013, to December 31, 2019. Ethnicities analyzed included Han and Mongolian; patients of other ethnicities were not included in the analysis because of the small sample size. Cancer was broadly defined as a primary malignant tumor or hematologic cancer; benign central nervous system tumors were also included. A 2-year washout period was used to exclude prevalent cases. After diagnosis, the patients were followed up until the date of death or the end of the insured status, whichever came first. Exposures: Ethnicity (Han vs Mongolian), sex (male vs female), and age (0-4, 5-9, and 10-14 years). Main Outcomes and Measures: Crude incidence, 5-year prevalence, and survival rates at 1 year and 3 years after diagnosis; health care utilization, represented by medical costs during the first year and first 3 years after diagnosis; and hospital attendance with level (tertiary vs secondary and lower-level hospitals) and location of each unique visit. Results: From 2013 to 2019, 1 106 684 (2013), 1 330 242 (2014), 1 763 746 (2015), 2 400 343 (2016), 2 245 963 (2017), 2 901 088 (2018), and 2 996 580 (2019) children aged 0 to 14 years were registered in the NBMI database. Among the 2 996 580 children enrolled in 2019, the mean (SD) age was 6.8 (4.3) years, of whom 1 572 096 (52.5%) were male, 2 572 091 (85.8%) were Han, and 369 400 (12.3%) were Mongolian. A total of 1910 patients with cancer were identified (1048 were male [54.9%]; 1559 were Han [81.6%], and 300 were Mongolian [15.7%]). There were 764 hematologic cancers (40.0%) and 1146 solid tumors (60.0%). The overall crude incidence of cancer from 2015 to 2019 was 129.85 per million children (95% CI, 123.63-136.06), with a higher incidence among Mongolian than among Han children (155.12 [95% CI, 136.81-173.43] vs 134.39 [95% CI, 127.46-141.32]). The 5-year prevalence was 428.97 per million (95% CI, 405.52-452.42) in 2020, with a higher prevalence among Mongolian than among Han children (568.49 [95% CI, 91.62-645.36] vs 404.34 [95% CI, 379.77-428.91]). The combined 1-year (2015-2019) and 3-year (2015-2017) survival rates were 72.5% (95% CI, 67.5%-77.5%) and 66.8% (95% CI, 61.6%-71.9%), respectively. The 1-year (median [IQR], $1991 [$912-$10 181] vs $3991 [$1171-$15 425]) and 3-year (median [IQR], $2704 [$954-$13 909] vs $5375 [$1283-$22 466]) postdiagnosis costs were lower among Mongolian than among Han children. A higher proportion of Mongolian patients attended low-level hospitals (45.9% vs 17.4%). Conclusions and Relevance: In this cohort study, Mongolian children had a higher incidence and prevalence of cancer but a lower demand for medical care, suggesting that further investigations are needed to identify mechanisms underlying ethnic disparities and ensure that care is equitable.

Differences in the Association Between Modifiable Lifestyle Factors and Gastric Precancerous Lesions Among Mongolians and Han Chinese.

Background: There has been a paucity of evidence examining whether preventable behavioral risk factors led to ethnic differences of gastric precancerous lesions (GPL). We aimed to investigate the ethnic disparity of associations between GPL and lifestyle factors in Mongolian and Han Chinese populations. Methods: The study included participants aged 36-75 years enrolled in the Cancer Screening Program during 2016-2017 in Hohhot and Tongliao City, Inner Mongolia. GPL was defined as the gross cascading events (i.e., gastric ulcer, atrophic gastritis, intestinal metaplasia, and dysplasia) that preceded gastric cancer. Results: A total of 61638 participants were included, of whom 6863(11·1%) were Mongolians. Alcohol consumption was positively associated with GPL risk in both ethnic groups, but the magnitude was greater in Mongolians (odds ratio (OR) 6·91, 95%CI 5·82-8·28) than in Han Chinese (OR 5·64, 95%CI 5·27-6·04), corresponding to a higher population attributable fraction (PAF) for Mongolians (53·18% vs 43·71%). Besides, the strength of the positive association between physical inactivity and GPL risk was greater among Mongolians (OR 2·02, 95%CI 1·70-2·41; OR 1·09, 95%CI 1·02-1·17 among Han Chinese) with a higher PAF. Smoking was strongly associated with GPL risk in both ethnic groups as well, but the association was more prominent among Han Chinese (OR 5·24 (1·70-2·41) for <10 cigarettes/d, 8·19 (7·48-8·97) for 11-20 cigarettes/d, 7·07 (6·40-7·81) for ≥21 cigarettes/d; the corresponding ORs were 2·96 (2·19-4·00), 6·22 (5·04-7·68), and 7·03 (5·45-9·08) among Mongolians). Lastly, our findings revealed that a significant correlation between insufficient fruits and vegetable consumption and GPL risk was only found among Mongolians (OR 1·27, 95%CI 1·04-1·56). Conclusions: Our result suggested that high-risk lifestyle factors should be reduced, particularly in Mongolians. Further studies are needed to elucidate the underlying mechanisms and to reduce health disparities in underserved ethnic groups.

MiR-128-1-5p regulates differentiation of ovine stromal vascular fraction by targeting the KLF11 5'-UTR.

Fat content is an important index to evaluate the individual performance of livestock animals such as sheep for meat production purposes. Reducing the subcutaneous and visceral fat while increasing the intramuscular fat is a valuable goal to achieve for the meat production industry. Here, we investigated the effect of miR-128-1-5p on adipogenesis of subcutaneous fat by targeting 5'-UTR in KLF11, a rare mechanism where most miRNAs bind the 3'-UTR of mRNAs. A dual fluorescence reporter assay was conducted to validate the binding sites of miR-128-1-5p on 5'-UTR of KLF11 mRNA. Roles of miR-128-1-5p in KLF11 expression were measured through co-transfecting miRNA mimics with KLF11-expressing vectors (CDSs together with or without the 5'-UTR) into ovine stromal vascular fractions (SVF). Additionally, functional roles of miR-128-1-5p, and KLF11 in adipogenesis of ovine subcutaneous fat were investigated. Results showed that miR-128-1-5p targeted KLF11 5'-UTR, reduced the fluorescence activity of the dual fluorescent reporter vector, as well as KLF11 mRNA, and protein expression levels. During the differentiation of SVF, disturbing the expression of miR-128-1-5p and KLF11 changed the adipogenic differentiation of SVF as observed in the lipid formation, and adipogenic marker genes. This study indicates that miR-128-1-5p promotes the expression of lipogenic marker genes and the formation of lipid droplets by targeting KLF11 5'-UTR. Furthermore, overexpression, and inhibition of KLF11 indicate that KLF11 inhibited SVF differentiation. In summary, the 5'-UTR binding mechanism discovered in this study extends the understanding of miRNA functions. Key roles of miR-128-1-5p and KLF11 in the adipogenesis of sheep subcutaneous fat have potential values for improving the meat and/or fat ratio of domestic animals.

miR-301a inhibits adipogenic differentiation of adipose-derived stromal vascular fractions by targeting HOXC8 in sheep.

MicroRNAs (miRNAs) regulate adipogenic differentiation in stromal vascular fractions (SVFs) through post-transcriptional regulation of transcription factors and other functional genes. miR-301 and the homeobox C8 (HOXC8) gene are involved in lipid homeostasis; however, their roles in the adipogenic differentiation of ovine SVFs are unknown. Here, we explored the effects of miR-301 and HOXC8 on adipogenic differentiation in ovine SVFs and the regulatory role of miR-301a in HOXC8 expression. Additionally, we evaluated the effect of miR-301a and HOXC8 on the mRNA abundance of adipogenic markers and the ability of ovine SVFs to accumulate lipids. We found that miR-301a regulates adipogenic differentiation in ovine SVFs by directly targeting the 3'-untranslated region of HOXC8, resulting in significant downregulation of the HOXC8 mRNA and protein. Moreover, miR-301a overexpression suppressed adipogenic differentiation in ovine SVFs and significantly inhibited the expression of adipogenesis-related genes-including adiponectin, C/EBPα, PPARγ, and FABP4. Conversely, HOXC8 overexpression in ovine SVFs increased the accumulation of lipid droplets and remarkably promoted the expression of adipogenic markers. Taken together, our results indicate that miR-301a attenuates the adipogenic differentiation of ovine SVFs by targeting HOXC8. These findings improve our understanding of the mechanism of lipid accumulation and metabolism in sheep.

Hybrid Sequencing in Different Types of Goat Skeletal Muscles Reveals Genes Regulating Muscle Development and Meat Quality.

Domestic goats are commonly reared for meat and milk production in several regions of the world. However, the genetic mechanism underlying muscle development and meat quality of goats is limited. Therefore, the aim of this study was to identify known and novel genes regulating muscle development and meat quality of goats using second- and third-generation sequencing technologies. To achieve this, the meat quality and transcriptomes of longissimus dorsi (LD) and biceps femoris (BF) muscle tissues of Lingqiu Greyback goats were examined and compared. Differentially expressed genes (DEGs) and isoforms (DEIs) were functionally annotated. Results showed that 45,574 full-length transcripts covering 18,491 loci were characterized, and 12,566 genes were co-expressed in all samples. Differential expression analysis identified 231 DEGs, including 45 novel genes in the LD and BF muscles of the goats. Additionally, 1173 DEIs were found, in which 642 novel isoforms were identified in this study. Functional annotation and pathway analysis of the DEGs and DEIs revealed that some of them were associated with muscle growth and lipid metabolism. Overall, the findings of this study contribute to the understanding of the transcriptomic diversity underlying meat quality and muscle development of goat.

Prevalence and treatment of high cardiovascular disease risk in Inner Mongolia, China.

Early identification of individuals with high risk is crucial to preventing cardiovascular disease (CVD). We aimed to determine the prevalence of high CVD risk in Inner Mongolia and to analyze the treatment of major risk factors among individuals with high CVD risk. We selected 70,380 participants aged 35-75 years in Inner Mongolia between 2015 and 2017 using multistage stratified sampling. All participants completed a questionnaire and their blood pressure, blood glucose and lipid levels, height, weight and waist circumference were measured. Participants without a history of CVD were defined as high CVD risk if the predicted 10-year risk for CVD exceeded 10%. We assessed rates of high CVD risk and the prevalence and treatment of major risk factors among individuals with high CVD risk. After excluding participants with previous CVD, 68,083 participants remained. The overall prevalence of high CVD risk was 24.96%. The age- and sex-standardized rate of high CVD risk was 22.92%. Among high-risk participants, the prevalence of risk factors was hypertension (91.9%), dyslipidemia (54.1%), obesity (34.6%), diabetes (27.6%), and smoking (24.5%); clustering of these risk factors was common. The percentage of high-risk individuals taking antihypertensive drugs was 45.94% in those with hypertension; 27.99% of those with diabetes took hypoglycemic drugs and only 5.01% of those with dyslipidemia took lipid-lowering drugs. Control rates of hypertension, diabetes, and dyslipidemia were 1.20%, 4.43%, and 2.78%, respectively. Therefore, the prevalence of high CVD risk was elevated in Inner Mongolia, and treatment and control rates were low.

Efficient weighting methods for genomic best linear-unbiased prediction (BLUP) adapted to the genetic architectures of quantitative traits.

Genomic best linear-unbiased prediction (GBLUP) assumes equal variance for all marker effects, which is suitable for traits that conform to the infinitesimal model. For traits controlled by major genes, Bayesian methods with shrinkage priors or genome-wide association study (GWAS) methods can be used to identify causal variants effectively. The information from Bayesian/GWAS methods can be used to construct the weighted genomic relationship matrix (G). However, it remains unclear which methods perform best for traits varying in genetic architecture. Therefore, we developed several methods to optimize the performance of weighted GBLUP and compare them with other available methods using simulated and real data sets. First, two types of methods (marker effects with local shrinkage or normal prior) were used to obtain test statistics and estimates for each marker effect. Second, three weighted G matrices were constructed based on the marker information from the first step: (1) the genomic-feature-weighted G, (2) the estimated marker-variance-weighted G, and (3) the absolute value of the estimated marker-effect-weighted G. Following the above process, six different weighted GBLUP methods (local shrinkage/normal-prior GF/EV/AEWGBLUP) were proposed for genomic prediction. Analyses with both simulated and real data demonstrated that these options offer flexibility for optimizing the weighted GBLUP for traits with a broad spectrum of genetic architectures. The advantage of weighting methods over GBLUP in terms of accuracy was trait dependant, ranging from 14.8% to marginal for simulated traits and from 44% to marginal for real traits. Local-shrinkage prior EVWGBLUP is superior for traits mainly controlled by loci of a large effect. Normal-prior AEWGBLUP performs well for traits mainly controlled by loci of moderate effect. For traits controlled by some loci with large effects (explain 25-50% genetic variance) and a range of loci with small effects, GFWGBLUP has advantages. In conclusion, the optimal weighted GBLUP method for genomic selection should take both the genetic architecture and number of QTLs of traits into consideration carefully.

miR-340-5p inhibits sheep adipocyte differentiation by targeting ATF7.

Several microRNAs (miRNAs) have been identified to play roles in adipocyte differentiation. However, little is known about their involvement in the differentiation of ovine intramuscular adipocytes. Here, the role of one such miRNA, miR-340-5p, in ovine adipocyte differentiation was investigated. Stromal vascular (SV) cells were isolated from skeletal muscle tissues of 1-month-old lambs and induced to differentiate into mature adipocytes. miRNA mimics and inhibitors were used for miR-340-5p overexpression and knockdown assays. For overexpression and knockdown of activating transcription factor 7 (ATF7), lentivirus infection was performed. Luciferase reporter assay was performed to determine the relationship between miR-340-5p and ATF7. The expression of adipogenesis marker genes, PPARγ, C/EBPα, FABP4, ADIPOQ, and ACC, and formation of lipid droplets were detected after the overexpression and inhibition of miR-340-5p, or upon overexpression or knockdown of ATF7. miR-340-5p inhibited the expression of the marker genes and the formation of lipid droplets. ATF7 positively regulated the expression of the marker genes and the formation of lipids. Thus, ATF7 is the target of miR-340-5p in sheep. Overall, these findings indicate that miR-340-5p acts as an inhibitor of the differentiation of intramuscular adipocytes by targeting ATF7. Our study provides a new theoretical basis for improving sheep meat quality.

Regulatory Roles of SREBF1 and SREBF2 in Lipid Metabolism and Deposition in Two Chinese Representative Fat-Tailed Sheep Breeds.

Sterol regulatory element binding proteins (SREBPs) can regulate the lipid homeostasis by regulating its target genes, which are crucial for the cholesterol and fatty acid metabolism. However, the transcriptional regulation role of SREBPs in fat-tailed sheep is unclear. In this study, two Chinese representative breeds of total 80 fat-tailed sheep were employed, serum triglyceride, total cholesterol (TC), non-esterified fatty acid (NEFA), high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and mRNA expressions of SREBF1 and SREBF2 in seven different adipose tissues and liver were examined in sheep at the ages of 4, 6, 8, 10, and 12 months, respectively. The subcellular localization and function of SREBP1/2 were predicted through bioinformatics approaches. The results demonstrated that serum TC and NEFA levels among breeds were significantly different, and most serum indices were dynamically altered in an age-dependent manner. The mRNA expression profiling of SREBF1 and SREBF2 are breed-specific with temporal and spatial expressions differences. Further analysis shows that SREBF1/2 transcriptional levels and tail traits are closely related. All investigations simplify that SREBF1/2 play a crucial role in lipid metabolism and deposition during growth and development of the fat-tailed sheep, which also provides a novel insight for revealing the genetic mechanism of different tail type and meat quality.