Single-cell transcriptome and metagenome profiling reveals the genetic basis of rumen functions and convergent developmental patterns in ruminants.

The rumen undergoes developmental changes during maturation. To characterize this understudied dynamic process, we profiled single-cell transcriptomes of about 308,000 cells from the rumen tissues of sheep and goats at 17 time points. We built comprehensive transcriptome and metagenome atlases from early embryonic to rumination stages, and recapitulated histomorphometric and transcriptional features of the rumen, revealing key transitional signatures associated with the development of ruminal cells, microbiota, and core transcriptional regulatory networks. In addition, we identified and validated potential cross-talk between host cells and microbiomes and revealed their roles in modulating the spatiotemporal expression of key genes in ruminal cells. Cross-species analyses revealed convergent developmental patterns of cellular heterogeneity, gene expression, and cell-cell and microbiome-cell interactions. Finally, we uncovered how the interactions can act upon the symbiotic rumen system to modify the processes of fermentation, fiber digestion, and immune defense. These results significantly enhance understanding of the genetic basis of the unique roles of rumen.

Role of circPAPD7 in regulating proliferation and differentiation of goat skeletal muscle satellite cells.

The circular RNA (circRNA) plays a crucial role in various biological processes, particularly posttranscriptional regulation. However, the role of circRNA in the development of goat skeletal muscle has not been thoroughly explored. Here, we identified circPAPD7, which is a novel circular RNA that is preferentially expressed in the skeletal muscle. Functional assays demonstrated that circPAPD7 promoted proliferation and inhibited differentiation in goat skeletal muscle satellite cells (MuSCs). Mechanistically, it was discovered that circPAPD7 interacts with miR-26a-5p. Moreover, the rescue experiments indicated that the overexpression of circPAPD7 may reverse the inhibitory impact of miR-26a-5p on myoblast proliferation and the accelerated effects on differentiation. Furthermore, we provided evidence that circPAPD7 functions as a sponge for miR-26a-5p, thereby facilitating the upregulation of EZH2 expression in goat MuSCs. Together, the results revealed that circPAPD7 promote proliferation and inhibit differentiation of goat MuSCs via the miR-26a-5p/EZH2 pathway.

Comparative whole-genome resequencing to uncover selection signatures linked to litter size in Hu Sheep and five other breeds.

Hu sheep (HS), a breed of sheep carrying the FecB mutation gene, is known for its "year-round estrus and multiple births" and is an ideal model for studying the high fecundity mechanisms of livestock. Through analyzing and comparing the genomic selection features of Hu sheep and other sheep breeds, we identified a series of candidate genes that may play a role in Hu sheep's high fecundity mechanisms. In this study, we conducted whole-genome resequencing on six breeds and screened key mutations significantly correlated with high reproductive traits in sheep. Notably, the CC2D1B gene was selected by the fixation index (FST) and the cross-population composite likelihood ratio (XP-CLR) methods in HS and other five breeds. It was worth noting that the CC2D1B gene in HS was different from that in other sheep breeds, and seven missense mutations have been identified. Furthermore, the linkage disequilibrium (LD) analysis revealed a strong linkage disequilibrium in this specific gene region. Subsequently, by performing different grouping based on FecB genotypes in Hu sheep, genome-wide selective signal analysis screened several genes related to reproduction, such as BMPR1B and PPM1K. Besides, FST analysis identified functional genes related to reproductive traits, including RHEB, HSPA2, PPP1CC, HVCN1, and CCDC63. Additionally, a missense mutation was found in the CCDC63 gene and the haplotype was different between the high reproduction (HR) group and low reproduction (LR) group in HS. In summary, we discovered genetic differentiation among six distinct breeding sheep breeds at the whole genome level. Additionally, we identified a set of genes which were associated with reproductive performance in Hu sheep and visualized how these genes differed in different breeds. These findings laid a theoretical foundation for understanding genetic mechanisms behind high prolific traits in sheep.

Electroreduction of CO2 on Cu, Fe, or Ni-doped Diamane Sheets: A DFT Study.

Poor mass transfer behavior and inherent activity limit the efficiency of traditional catalysts in electrocatalyzing carbon dioxide reduction reactions. However, the development of novel nanomaterials provides new strategies to solve the above problems. Herein, we propose novel single-metal atom catalysts, namely diamane-based electrocatalysts doped with Cu, Fe, and Ni, explored through density functional theory (DFT) calculations. We thoroughly investigated the doping pattern and energetics for different dopants. Furthermore, we systematically investigated the conversion process of CO2 to C1 or C2+ products, utilizing the free energy analysis of reaction pathways. Our results reveal that dopants could only be introduced into diamane following a specific pattern. Dopants significantly enhance the CO2 adsorption ability of diamane, with Fe and Ni proving notably more effective than Cu. After CO2 adsorption, Cu- and Fe-doped diamane prefer to catalyze CO2RR, while Ni-doped diamane favors hydrogen evolution reaction (HER). The C-C coupling reaction on Cu-hollow diamane, Cu-bridge diamane, and Fe-hollow diamane tends to be from C2+ products. Among all examined catalysts, Cu-hollow diamane shows better electro-catalytic performance. Our study demonstrates the feasibility of and contributes to the development of diamane-based electro-catalysts for CO2RR.

Associations between 25 hydroxyvitamin D concentration and spontaneous abortion.

BACKGROUND: Spontaneous abortion is a common complication of pregnancy that can lead to adverse physical and psychological outcomes for women. Vitamin D is reported to be associated with reproductive functions, whereas its casual effects on abortion remains unclear. MATERIALS AND METHODS: In this study, a two-sample Mendelian randomization (MR) analysis was performed to systematically assess the causal relationships between serum 25 hydroxyvitamin D [25(OH)D] concentration and the risk of spontaneous abortion. GWAS summary data of 25(OH)D were used as exposure, and data of spontaneous abortion was considered as outcome. A retrospective study was additionally conducted to verify the MR results. RESULTS: MR estimates showed that a higher 25(OH)D level was potentially associated with decreased risk of spontaneous abortion (IVW, OR = 0.98, 95%CI = 0.90-1.06; MR Egger, OR = 0.94, 95%CI = 0.84-1.05; Weighted median, OR = 0.93, 95%CI = 0.82-1.06; Weighted mode, OR = 0.93, 95%CI = 0.84-1.03), though the P-value was not statistically significant. The retrospective study also produced consistent result of Vitamin D's protective role to spontaneous abortion. The P-value was very close to statistical significance (P = 0.053). CONCLUSIONS: This study reports the potential protective role of serum 25(OH)D concentration to spontaneous abortion, suggesting that increased vitamin D levels may decrease the risk of abortion. Further larger prospective studies and/or even randomized controlled trials are needed to confirm causal relationship between vitamin D and abortion.

Fat Mass- and Obesity-Associated Protein (FTO) Promotes the Proliferation of Goat Skeletal Muscle Satellite Cells by Stabilizing DAG1 mRNA in an IGF2BP1-Related m6A Manner.

Skeletal muscle development is spotlighted in mammals since it closely relates to animal health and economic benefits to the breeding industry. Researchers have successfully unveiled many regulatory factors and mechanisms involving myogenesis. However, the effect of N6-methyladenosine (m6A) modification, especially demethylase and its regulated genes, on muscle development remains to be further explored. Here, we found that the typical demethylase FTO (fat mass- and obesity-associated protein) was highly enriched in goats' longissimus dorsi (LD) muscles. In addition, the level of m6A modification on transcripts was negatively regulated by FTO during the proliferation of goat skeletal muscle satellite cells (MuSCs). Moreover, a deficiency of FTO in MuSCs significantly retarded their proliferation and promoted the expression of dystrophin-associated protein 1 (DAG1). m6A modifications of DAG1 mRNA were efficiently altered by FTO. Intriguingly, the results of DAG1 levels and its m6A enrichment from FB23-2 (FTO demethylase inhibitor)-treated cells were consistent with those of the FTO knockdown, indicating that the regulation of FTO on DAG1 depended on m6A modification. Further experiments showed that interfering FTO improved m6A modification at site DAG1-122, recognized by Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) and consequently stabilized DAG1 transcripts. Our study suggests that FTO promotes the proliferation of MuSCs by regulating the expression of DAG1 through m6A modification. This will extend our knowledge of the m6A-related mechanism of skeletal muscle development in animals.

Transcriptomic and Metabolomic Analyses Reveal Molecular Regulatory Networks for Pigmentation Deposition in Sheep.

Domestic animals have multiple phenotypes of skin and coat color, which arise from different genes and their products, such as proteins and metabolites responsible with melanin deposition. However, the complex regulatory network of melanin synthesis remains to be fully unraveled. Here, the skin and tongue tissues of Liangshan black sheep (black group) and Liangshan semi-fine-wool sheep (pink group) were collected, stained with hematoxylin-eosin (HE) and Masson-Fontana, and the transcriptomic and metabolomic data were further analyzed. We found a large deposit of melanin granules in the epidermis of the black skin and tongue. Transcriptome and metabolome analysis identified 744 differentially expressed genes (DEGs) and 443 differentially expressed metabolites (DEMs) between the pink and black groups. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analyses revealed the DEGs and DEMs were mainly enriched in the pathways of secondary metabolic processes, melanin biosynthesis processes, melanin metabolism processes, melanosome membranes, pigment granule membranes, melanosome, tyrosine metabolism, and melanogenesis. Notably, we revealed the gene ENSARG00020006042 may be a family member of YWHAs and involved in regulating melanin deposition. Furthermore, several essential genes (TYR, TYRP1, DCT, PMEL, MLANA, SLC45A2) were significantly associated with metabolite prostaglandins and compounds involved in sheep pigmentation. These findings provide new evidence of the strong correlation between prostaglandins and related compounds and key genes that regulate sheep melanin synthesis, furthering our understanding of the regulatory mechanisms and molecular breeding of pigmentation in sheep.

Maternal L-carnitine supplementation promotes brown adipose tissue thermogenesis of newborn goats after cold exposure.

Brown adipose tissue (BAT) is an important component of energy expenditure and necessary to maintain body temperature for newborn mammals. In the previous study, we found that L-carnitine was enriched in BAT and promoted BAT adipogenesis and thermogenesis in goat brown adipocytes. However, whether dietary L-carnitine regulates BAT heat production and energy expenditure in lambs remains unclear. In this study, maternal L-carnitine supplementation elevated the rectal temperature, as well as the expression of UCP1 and mitochondrial DNA content to promote BAT thermogenesis in newborn goats. Moreover, maternal L-carnitine supplementation increased the levels of triglycerides (TG), non-esterified fatty acids (NEFA), and lactate in plasma, as well as the content of lipid droplet and glycogen in BAT of newborn goats. Lipidomic analysis showed that maternal L-carnitine supplementation remodeled the lipid composition of BAT in newborn goats. L-carnitine significantly increased the levels of TG and diglyceride (DG) and decreased the levels of glycerophospholipids and sphingolipids in BAT. Further studies showed that L-carnitine promoted TG and glycogen deposition in brown adipocytes through AMPKα. Our results indicate that maternal L-carnitine supplementation promotes BAT development and thermogenesis in newborn goats and provides new evidence for newborn goats to maintain body temperature in response to cold exposure.

Porous Hydrogel Photothermal Conversion Membrane to Facilitate Water Purification.

Solar water purification technology is one of the most potent methods to obtain freshwater due to its low cost and non-polluting characteristics. However, the purification efficiency is limited by the high ion concentration, organic pollution, and biological pollution during the actual water purification process. Here, we report a porous hydrogel membrane (Fe/TA-TPAM) for the purification of high ion concentration and contaminated water. The hydrogel membrane exhibits good light absorption and photothermal conversion ability, which shows high evaporation rates (1.4 kg m-2 h-1) and high solar efficiency for seawater. Furthermore, with the introduction of tannic acid (TA) and Ti3C2 MXenes, the Fe/TA-TPAM hydrogel membrane exhibits satisfied purification properties for organic-contaminated and biologically contaminated water. The excellent purification effect of Fe/TA-TPAM under light not only confirms the rationality of the hydrogel porous design and in situ generation of photosensitizer in improving the photothermal performance but also provides a novel strategy for designing advanced photothermal conversion membranes for water purification.

Association of Fine Particulate Matter and Its Components with Macrosomia: A Nationwide Birth Cohort Study of 336 Chinese Cities.

To examine the associations between macrosomia risk and exposure to fine particulate matter (PM2.5) and its chemical components during pregnancy, we collected birth records between 2010 and 2015 in mainland China from the National Free Preconception Health Examination Project and used satellite-based models to estimate concentrations of PM2.5 mass and five main components, namely, black carbon (BC), organic carbon (OC), nitrate (NO3-), sulfate (SO42-), and ammonium (NH4+). Associations between macrosomia risk and prenatal exposure to PM2.5 were examined by logistic regression analysis, and the sensitive subgroups were explored by stratified analyses. Of the 3,248,263 singleton newborns from 336 cities, 165,119 (5.1%) had macrosomia. Each interquartile range increase in concentration of PM2.5 during the entire pregnancy was associated with increased risk of macrosomia (odds ratio (OR) = 1.18; 95% confidence interval (CI), 1.17-1.20). Among specific components, the largest effect estimates were found on NO3- (OR = 1.36; 95% CI, 1.35-1.38) followed by OC (OR = 1.23; 95% CI, 1.22-1.24), NH4+ (OR = 1.22; 95% CI, 1.21-1.23), and BC (OR = 1.21; 95% CI, 1.20-1.22). We also that found boys, women with a normal or lower prepregnancy body mass index, and women with irregular or no folic acid supplementation experienced higher risk of macrosomia associated with PM2.5 exposure.

Evaluating the Impact of Maternal Exposure to Ozone on Twin Fetal Growth in China.

Unlike singletons, twins require attention not only to the birth weight of the fetuses but also to discordance (i.e., the differences between weights) because twin growth discordance is a significant factor contributing to perinatal mortality and morbidity in twin pregnancies. However, the impact of maternal air pollution exposure on twin growth discordance has rarely been investigated. We examined the association of long-term ozone exposure during preconception and pregnancy with the birth weight of twins and twin growth discordance among 35,795 twins from the National Free Preconception Health Examination Project between January 2010 and December 2019. Linear mixed-effect models and random-effect logistic regression models were used to examine the associations of ozone exposure with the birth weight-related outcomes (i.e., birth weight of twins and within-pair birth weight difference) and risk of twin growth discordance, respectively, after adjustment for demographic characteristics and lifestyle. We found that an interquartile range (IQR) increase (15 µg/m3) in ozone exposure during the entire pregnancy was associated with a reduction (-28.96g, 95% confidence interval [CI]: -46.37, -11.56) in the total birth weight of twins, and ozone had a more pronounced impact on the birth weight of the smaller fetuses (-18.28 g, 95% CI: -27.22, -9.34) compared to the larger fetuses (-9.88 g, 95% CI: -18.84, -0.92) in twin pregnancies. An IQR increase in ozone exposure during the entire pregnancy was associated with a significant increase (8.41 g, 95% CI: 4.13, 12.69) in the within-pair birth weight difference; the odds ratio (OR) of twin growth discordance related to ozone exposure increased by 9% (OR = 1.09, 95% CI: 1.01, 1.18). However, no consistently significant associations were observed for ozone exposure during prepregnancy. Male-male twin pairs and those who were born prematurely appeared to be more susceptible to ozone exposure than their counterparts. Long-term ozone exposure during pregnancy was associated with twin growth discordance, and our findings provide reference data for future studies.

BTEX sensing potential of elemental-doped graphene: a DFT study.

Elementally-doped graphene demonstrates remarkable gas sensing capabilities as a novel 2D sensor material. In this study, we employed density functional theory calculations, we investigated the impact of various dopants on the BTEX (benzene, toluene, ethylbenzene, and xylene) sensing performance of graphene. Through the systematic analysis of electronic structures and sensitivity, we observed that both the doping method and dopant type significantly influence the interactions between graphene and BTEX molecules. Out of the 22 different elemental doped graphenes studied, N-, O-, and Pd-doped graphenes emerged as promising candidates for BTEX sensor materials. Graphene with N-doping exhibited relatively higher sensitivity towards toluene, ethylbenzene, and xylene compared to O- and Pd-doped graphenes. However, it demonstrated low sensitivity towards benzene. On the other hand, O-doped graphene displayed excellent selectivity for ethylbenzene over the other three gas molecules (benzene, toluene, and xylene). Similarly, Pd-doped graphene also exhibited significant selectivity for ethylbenzene and possessed higher sensitivity than the O-doped graphene. Their distinct characteristics and sensitivities make them potential candidates for future applications in gas sensing technology.

Temporal trends and projections of gynecological cancers in China, 2007-2030.

BACKGROUND: Gynecological cancer will become a more important public health problem in future years but limited evidence on gynecological cancer burden in China. METHODS: We extracted age-specific rate of cancer cases and deaths during 2007-2016 from the Chinese Cancer Registry Annual Report, and estimated age-specific population size using the data released by National Bureau of Statistics of China. Cancer burden were calculated by multiplying the rates with the population size. Temporal trends of the cancer cases, incidence, deaths, and mortality during 2007-2016 were calculated by JoinPoint Regression Program, and from 2017 to 2030 were projected by grey prediction model GM (1,1). RESULTS: In China, total gynecological cancer cases increased from 177,839 to 241,800, with the average annual percentage change of 3.5% (95% CI: 2.7-4.3%) during 2007-2016. Cervical, uterine, ovarian, vulva, and other gynecological cancer cases increased by 4.1% (95% CI: 3.3-4.9%), 3.3% (95% CI: 2.6-4.1%), 2.4% (95% CI: 1.4-3.5%), 4.4% (95% CI: 2.5-6.4%), and 3.6% (95% CI: 1.4-5.9%) respectively. From 2017 to 2030, projected gynecological cancer cases are changing from 246,581 to 408,314. Cervical, vulva and vaginal cancers showed evident upward trend, while uterine and ovarian cancer cases are slightly increasing. The increases for age-standardized incidence rates were similar with that of cancer cases. Temporal trends of cancer deaths and mortality were similar with that of cancer cases and incidence during 2007-2030, except that uterine cancer deaths and mortality were declined. CONCLUSIONS: With the aging of population and other increased risk factors, the burden of gynecological cancers in China is likely to be grew rapidly in the future, comprehensive gynecological cancer control should be concerned.

Expression patterns and DNA methylation profile of GTL2 gene in goats.

Gene trap locus 2 (GTL2), a long non-coding paternal imprinting gene, participates in various biological processes, including cell proliferation, differentiation, and apoptosis, by regulating the transcription of target mRNA, which is tightly related to the growth of the organic and maintenance of function. In this study, DNA methylation patterns of CpG islands (CGI) of GTL2 were explored, and its expression level was quantified in six tissues, rumen epithelium cells, and skeletal muscle cells in goats. GTL2 expression levels were measured by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), and the methylation model was confirmed by bisulfite-sequencing PCR (BSP). CGI methylation of GTL2 indicated a moderate methylation (ranging from 81.42 to 86.83%) in the brain, heart, liver, kidney, lung, and longissimus dorsi. GTL2 is most highly expressed in brain tissues, but there is no significant difference in the other five tissues. In addition, in the rumen epithelium cell proliferation, GTL2 expression was highest at 60 h, followed by 72 h, and almost unchanged at 12-48 h. In the skeletal muscle cell differentiation, GTL2 expression was highest at 0 and 24 h, significantly decreasing at 72 and 128 h. Pearson correlation analysis did not indicate a clear relationship between methylation and GTL2 expression levels, suggesting that other regulatory factors may modulate GTL2 expression. This study will provide a better understanding of the expression regulation mechanism of genes in the delta-like homolog 1 gene (DLK1)-GTL2 domain.

A Google Trends analysis revealed global public interest and awareness of nasal polyps.

INTRODUCTION: Nasal polyps (NPs) is a common upper airway inflammatory disorder with a huge negative burden on both the quality of life and costs to patients. However, NPs patients remain undiagnosed and untreated in a timely, which may be due to a lack of disease-related awareness. Google Trends (GT) is an online and open tool, which can provide real-world data on health informatics worldwide. OBJECTIVES: This study aimed to explore global public interest and awareness in nasal polyps (NPs) by performing a GT analysis. METHODS: Data on relative search volume (RSV) for NPs globally were collected by the public website Google Trends from January 2007 to December 2021. Top-related topics, rising-related topics, and regions were extracted for further analysis. Seasonal variation analysis, the latitude difference analysis, and the rising-related topics between the developed countries and the developing countries were analyzed. A P value less than 0.05 was considered statistically significant. RESULTS: The average searching strength showed an overall increasing trend, although with slight fluctuation. The public interest of NPs focuses on the symptoms and treatment for NPs and changes with time. For seasonal variation countries, the peak for the RSV occurred in winter and the bottom in summer. A region in higher latitudes may yield more RSV than that in lower latitudes. The rising-related topics in the recent 5 years reflected the significant differences in treatment and public interest of NPs between the developed and developing countries. CONCLUSIONS: Google Trends analysis revealed global public interest and awareness of the evolution of trends and related topics in nasal polyps over time. Geographic distribution and seasonal variation may be potential trigger factors for NPs, and the public's interest in treatment especially biologics is rising.

Transcriptome analysis reveals long non-coding natural antisense transcripts involved in muscle development in fetal goat (Capra hircus).

Non-coding RNAs have been shown to play vital roles in muscle development. However, the biological roles of long non-coding natural antisense transcripts, antisense lncRNAs (ASlncRNAs), are largely unknown in embryonic muscle development. Here, we identified a total of 466 ASlncRNAs in the longissimus dorsi muscle. And 48 differentially expressed ASlncRNAs were identified based on pairwise comparisons (P < 0.05), sixteen of which were validated by qPCR. Additionally, 466 ASlncRNAs were predicted to target 335 protein coding genes based on complementary base-pairing. Enrichment analysis suggests that ASlncRNAs may be involved in muscle development by negatively regulating the expression of target genes. Furthermore, 170 ASlncRNAs were identified as potential miRNA precursors, suggesting that these ASlncRNAs may be involved in the regulation of muscle development by producing miRNA precursors. Our results provide a catalog of goat muscle-related ASlncRNAs, and will contribute to a fuller understanding of the roles of ASlncRNAs in muscle development.

HuR Promotes the Differentiation of Goat Skeletal Muscle Satellite Cells by Regulating Myomaker mRNA Stability.

Human antigen R (HuR) is an RNA-binding protein that contributes to a wide variety of biological processes and diseases. HuR has been demonstrated to regulate muscle growth and development, but its regulatory mechanisms are not well understood, especially in goats. In this study, we found that HuR was highly expressed in the skeletal muscle of goats, and its expression levels changed during longissimus dorsi muscle development in goats. The effects of HuR on goat skeletal muscle development were explored using skeletal muscle satellite cells (MuSCs) as a model. The overexpression of HuR accelerated the expression of myogenic differentiation 1 (MyoD), Myogenin (MyoG), myosin heavy chain (MyHC), and the formation of myotubes, while the knockdown of HuR showed opposite effects in MuSCs. In addition, the inhibition of HuR expression significantly reduced the mRNA stability of MyoD and MyoG. To determine the downstream genes affected by HuR at the differentiation stage, we conducted RNA-Seq using MuSCs treated with small interfering RNA, targeting HuR. The RNA-Seq screened 31 upregulated and 113 downregulated differentially expressed genes (DEGs) in which 11 DEGs related to muscle differentiation were screened for quantitative real-time PCR (qRT-PCR) detection. Compared to the control group, the expression of three DEGs (Myomaker, CHRNA1, and CAPN6) was significantly reduced in the siRNA-HuR group (p < 0.01). In this mechanism, HuR bound to Myomaker and increased the mRNA stability of Myomaker. It then positively regulated the expression of Myomaker. Moreover, the rescue experiments indicated that the overexpression of HuR may reverse the inhibitory impact of Myomaker on myoblast differentiation. Together, our findings reveal a novel role for HuR in promoting muscle differentiation in goats by increasing the stability of Myomaker mRNA.

The Profiles and Functions of RNA Editing Sites Associated with High-Altitude Adaptation in Goats.

High-altitude environments dramatically influenced the genetic evolution of vertebrates. However, little is known about the role of RNA editing on high-altitude adaptation in non-model species. Here, we profiled the RNA editing sites (RESs) of heart, lung, kidney, and longissimus dorsi muscle from Tibetan cashmere goats (TBG, 4500 m) and Inner Mongolia cashmere goats (IMG, 1200 m) to reveal RNA editing-related functions of high-altitude adaptation in goats. We identified 84,132 high-quality RESs that were unevenly distributed across the autosomes in TBG and IMG, and more than half of the 10,842 non-redundant editing sites were clustered. The majority (62.61%) were adenosine-to-inosine (A-to-I) sites, followed by cytidine-to-uridine (C-to-U) sites (19.26%), and 32.5% of them had a significant correlation with the expression of catalytic genes. Moreover, A-to-I and C-to-U RNA editing sites had different flanking sequences, amino acid mutations, and alternative splicing activity. TBG had higher editing levels of A-to-I and C-to-U than IMG in the kidney, whereas a lower level was found in the longissimus dorsi muscle. Furthermore, we identified 29 IMG and 41 TBG population-specific editing sites (pSESs) and 53 population-differential editing sites (pDESs) that were functionally involved in altering RNA splicing or recoding protein products. It is worth noting that 73.3% population-differential, 73.2% TBG-specific, and 80% IMG-specific A-to-I sites were nonsynonymous sites. Moreover, the pSESs and pDESs editing-related genes play critical functions in energy metabolisms such as ATP binding molecular function, translation, and adaptive immune response, which may be linked to goat high-altitude adaptation. Our results provide valuable information for understanding the adaptive evolution of goats and studying plateau-related diseases.

Transcriptome Analysis Reveals the Profile of Long Non-Coding RNAs during Myogenic Differentiation in Goats.

The long non-coding RNAs (lncRNAs) are emerging as essential regulators of the growth and development of skeletal muscles. However, little is known about the expression profiles of lncRNAs during the proliferation and differentiation of skeletal muscle satellite cells (MuSCs) in goats. In this study, we investigate potential regulatory lncRNAs that govern muscle development by performing lncRNA expression profiling analysis during the proliferation (cultured in the growth medium, GM) and differentiation (cultured in the differentiation medium, DM1/DM5) of MuSCs. In total, 1001 lncRNAs were identified in MuSC samples, and 314 differentially expressed (DE) (FDR < 0.05, |log2FC| > 1) lncRNAs were screened by pairwise comparisons from three comparison groups (GM-vs-DM1, GM-vs-DM5, DM1-vs-DM5). Moreover, we identified the cis-, trans-, and antisense-regulatory target genes of DE lncRNAs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses showed that these target genes were significantly enriched in muscle development-related GO terms and KEGG pathways. In addition, the network of interactions between DE lncRNAs and their target genes was identified, which included well-known myogenesis regulators such as Myogenic differentiation 1 (MyoD), Myogenin (MyoG), and Myosin heavy chain (MyHC). Meanwhile, competing endogenous RNA (ceRNA) network analysis showed that 237 DE lncRNAs could bind to 329 microRNAs (miRNAs), while miRNAs could target 564 mRNAs. Together, our results provide a genome-wide resource of lncRNAs that may contribute to myogenic differentiation in goats and lay the groundwork for future investigation into their functions during skeletal muscle development.

Combining 16S rRNA Sequencing and Metabolomics Data to Decipher the Interactions between Gut Microbiota, Host Immunity, and Metabolites in Diarrheic Young Small Ruminants.

Diarrhea is associated with gut microbiota, immunity, and metabolic alterations in goat kids and lambs. This study used 28 lambs (11 healthy and 17 diarrheic) and 20 goat kids (10 healthy and 10 diarrheic) to investigate the association between diarrhea occurrence and changes in gut microbiota, metabolism, and immunity in goat kids and lambs. The results revealed that Firmicutes, Proteobacteria, and Bacteroidetes were the dominant phyla in goat kids and lambs. In addition, Enterobacteriaceae and Lachnospiraceae families were identified in both diarrheic goat kids and lambs. Furthermore, functional prediction of microbiota showed that it was involved in cell motility and cancer pathways. The identified differential metabolites were implicated in the bile secretion pathway. Lambs had significant differences in immunoglobulin G (IgG), immunoglobulin M (IgM), interleukin-1ß (IL-1ß), and tumor necrosis factor-alpha (TNF-α) compared to goat kids. IgG and IL-1ß were positively correlated to Patescibacteria, Clostridiaceae, and unclassified_Muribaculaceae in both diarrheic goat kids and lambs. In addition, weighted gene co-expression network analysis (WGCNA) revealed that the MEgreen module was positively associated with IgG, IgM, IL-1ß, TNF-α, and triglyceride (TG). In conclusion, our results characterized the gut microbiota, metabolism, and immune status of lambs and goat kids suffering from diarrhea.