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In this study, the thermodynamic simulation model and system of the copper side-blown smelting process were established using the chemical equilibrium constant method, based on the process reaction mechanism, multiphase equilibrium principle, and MetCal software platform (MetCal v7.81). Under typical production conditions, the composition of the product and the distribution behavior of impurity elements were simulated. The results indicate that the average relative error between the calculated mass fractions of major elements such as Cu, S, Fe, SiO2, CaO, MgO, and Al2O3 in copper matte and smelting slag, and the actual production values, is 4.25%. Additionally, the average relative error between the calculated distribution ratios of impurity elements such as Pb, Zn, As, Bi, Mo, Au, and Ag in copper matte and smelting slag, and the actual production data, is 6.74%. Therefore, this model and calculation system accurately reflects the actual production situation of the copper side-blown smelting process well and has potential to predict process output accurately while optimizing process parameters, effectively guiding production practice. [ABSTRACT FROM AUTHOR]

Background: Angiogenesis is essential for various physiological and pathological processes, such as embryonic development and cancer cell proliferation, migration, and invasion. Long noncoding RNAs (lncRNAs) play pivotal roles in normal homeostasis and disease processes by regulating gene expression through various mechanisms, including competing endogenous RNAs (ceRNAs) of target microRNAs (miRNAs). The lncRNA MYU is known to promote prostate cancer proliferation via the miR-184/c-Myc regulatory axis and to be upregulated in vascular endothelial cells under hypoxic conditions, which often occurs in solid tumors. In the present study, we investigated whether MYU might affect cancer growth by regulating angiogenesis in vascular endothelial cells under hypoxia. Methods: The expression of MYU-regulated miR-23a-3p and interleukin-8 (IL-8) in HUVEC cell lines was examined using qRT-PCR. The CCK-8 assay, EdU assay, wound-healing assay, and tube-formation assay were used to assess the effects of MYU on cell proliferation, migration, and tube formation of HUVEC cells in vitro. The dual-luciferase reporter assay was performed to examine the effects of miR-23a-3p on MYU and IL-8 expression. Results: We found that the overexpression of MYU and knockdown of miR-23a-3p in human umbilical vein endothelial cells (HUVECs) under hypoxia promoted cell proliferation, migration, and tube formation. Mechanistically, MYU was shown to bind competitively to miR-23a-3p, thereby preventing miR-23a-3p binding to the 3′ untranslated region of IL-8 mRNA. In turn, increased production of pro-angiogenic IL-8 promoted HUVEC proliferation, migration, and tube formation under hypoxia. Conclusion: This study identified a new role for lncRNA MYU as a ceRNA for miR-23a-3p and uncovered a novel MYU–miR-23a-3p–IL-8 regulatory axis for angiogenesis. MYU and/or miR-23a-3p may thus represent new targets for the treatment of hypoxia-related diseases by promoting angiogenesis. [ABSTRACT FROM AUTHOR]

Accurately capturing human movements is a crucial element of health status monitoring and a necessary precondition for realizing future virtual reality/augmented reality applications. Flexible motion sensors with exceptional sensitivity are capable of detecting physical activities by converting them into resistance fluctuations. Silver nanowires (AgNWs) have become a preferred choice for the development of various types of sensors due to their outstanding electrical conductivity, transparency, and flexibility within polymer composites. Herein, we present the design and fabrication of a flexible strain sensor based on silver nanowires. Suitable substrate materials were selected, and the sensor's sensitivity and fatigue properties were characterized and tested, with the sensor maintaining reliability after 5000 deformation cycles. Different sensors were prepared by controlling the concentration of silver nanowires to achieve the collection of motion signals from various parts of the human body. Additionally, we explored potential applications of these sensors in fields such as health monitoring and virtual reality. In summary, this work integrated the acquisition of different human motion signals, demonstrating great potential for future multifunctional wearable electronic devices. [ABSTRACT FROM AUTHOR]

In this study, we investigated the correlation between the composition and function of the gut microbiota and the semen quality of Rongchang boars. Significant differences in gut microbial composition between boars with high (group H) and low (group L) semen utilization rates were identified through 16S rRNA gene sequencing, with 18 differential microbes observed at the genus level. Boars with lower semen utilization rates exhibited a higher relative abundance of Treponema, suggesting its potential role in reducing semen quality. Conversely, boars with higher semen utilization rates showed increased relative abundances of Terrisporobacter, Turicibacter, Stenotrophomonas, Clostridium sensu stricto 3, and Bifidobacterium, with Stenotrophomonas and Clostridium sensu stricto 3 showing a significant positive correlation with semen utilization rates. The metabolomic analyses revealed higher levels of gluconolactone, D-ribose, and 4-pyridoxic acid in the H group, with 4 pyridoxic acid and D-ribose showing a significant positive correlation with Terrisporobacter and Clostridium sensu stricto 3, respectively. In contrast, the L group showed elevated levels of D-erythrose-4-phosphate, which correlated negatively with Bifidobacterium and Clostridium sensu stricto 3. These differential metabolites were enriched in the pentose phosphate pathway, vitamin B6 metabolism, and antifolate resistance, potentially influencing semen quality. These findings provide new insights into the complex interplay between the gut microbiota and boar reproductive health and may offer important information for the discovery of disease biomarkers and reproductive health management. [ABSTRACT FROM AUTHOR]

Long non-coding RNAs (lncRNAs) have been extensively studied, and their crucial roles in adipogenesis, lipid metabolism, and gene expression have been revealed. However, the exact regulatory or other mechanisms by which lncRNAs influence the functioning of mesenteric adipose tissue (MAT) remain largely unknown. In this paper, we report the identification of a new lncRNA, named G8110, from the MAT of Bama pigs. The coordinated expression levels of lncRNA G8110 and NFE2L1 were significantly decreased in the MAT of obese Bama pigs compared with those in the MAT of lean pigs. Using a bone mesenchymal stem cell adipogenic differentiation model, we found that lncRNA G8110 played a role in adipocyte differentiation by positively regulating NFE2L1. We also found that lncRNA G8110 inhibited the formation of intracellular lipid synthesis, promoted lipid metabolism, and inhibited the expression of inflammatory cytokines. Our findings regarding lipid synthesis may further promote the role of lncRNAs in driving adipose tissue remodeling and maintaining metabolic health. [ABSTRACT FROM AUTHOR]

With the increasingly complicated sources of lead smelting materials, it is becoming more difficult to optimize process parameters during the bottom-blowing lead oxidation smelting process. Building a bottom-blowing lead smelting thermodynamic model has significant importance for the green production of the lead smelting process. In this study, we built a multi-phase equilibrium thermodynamic model and simulation system for the oxygen-enriched bottom-blowing lead oxidation smelting process using the MetCal software platform (MetCal v7.81) according to the chemical equilibrium constant method. The equilibrium products composition and important technical indicators were calculated under factory operating conditions. Compared with the industrial data, the calculation results demonstrated that the average relative error of the calculation value of the mass fraction in the crude lead, lead-rich slag, and dust was 3.76%. The average relative error of important technical indicators, including dust rate, crude lead yield, lead-rich slag temperature, slag iron–silica ratio (RFe/SiO2), and slag calcium–silica ratio (RCaO/SiO2), was 6.39%. As a result, the developed modeling and simulation system was able to reflect the current state of the oxygen-enriched bottom-blowing lead smelting. It also demonstrated the potential to enhance the smelting process and optimize the process parameters. Therefore, it is expected to provide a useful tool for thermodynamic analysis. [ABSTRACT FROM AUTHOR]

The performances of algorithms for Hi-C data preprocessing, the identification of topologically associating domains, and the detection of chromatin interactions and promoter–enhancer interactions have been mostly evaluated using semi-quantitative or synthetic data approaches, without utilizing the most recent methods, since 2017. In this study, we comprehensively evaluated 24 popular state-of-the-art methods for the complete end-to-end pipeline of Hi-C data analysis, using manually curated or experimentally validated benchmark datasets, including a CRISPR dataset for promoter–enhancer interaction validation. Our results indicate that, although no single method exhibited superior performance in all situations, HiC-Pro, DomainCaller, and Fit-Hi-C2 showed relatively balanced performances of most evaluation metrics for preprocessing, topologically associating domain identification, and chromatin interaction/promoter–enhancer interaction detection, respectively. The comprehensive comparison presented in this manuscript provides a reference for researchers to choose Hi-C analysis tools that best suit their needs. [ABSTRACT FROM AUTHOR]

The study of chromatin accessibility across tissues and developmental stages is essential for elucidating the transcriptional regulation of various phenotypes and biological processes. However, the chromatin accessibility profiles of multiple tissues in newborn pigs and across porcine liver development remain poorly investigated. Here, we used ATAC-seq and rRNA-depleted RNA-seq to profile open chromatin maps and transcriptional features of heart, kidney, liver, lung, skeletal muscle, and spleen in newborn pigs and porcine liver tissue in the suckling and adult stages, respectively. Specifically, by analyzing a union set of protein-coding genes (PCGs) and two types of transcripts (lncRNAs and TUCPs), we obtained a comprehensive annotation of consensus ATAC-seq peaks for each tissue and developmental stage. As expected, the PCGs with tissue-specific accessible promoters had active transcription and were relevant to tissue-specific functions. In addition, other non-coding tissue-specific peaks were involved in both physical activity and the morphogenesis of neonatal tissues. We also characterized stage-specific peaks and observed a close association between dynamic chromatin accessibility and hepatic function transition during liver postnatal development. Overall, this study expands our current understanding of epigenetic regulation in mammalian tissues and organ development, which can benefit both economic trait improvement and improve the biomedical usage of pigs. [ABSTRACT FROM AUTHOR]

The scaffolding protein Axin is an important regulator of the Wnt signaling pathway, and its dysfunction is closely related to carcinogenesis. Axin could affect the assembly and dissociation of the β-catenin destruction complex. It can be regulated by phosphorylation, poly-ADP-ribosylation, and ubiquitination. The E3 ubiquitin ligase SIAH1 participates in the Wnt pathway by targeting various components for degradation. SIAH1 is also implicated in the regulation of Axin2 degradation, but the specific mechanism remains unclear. Here, we verified that the Axin2-GSK3 binding domain (GBD) was sufficient for SIAH1 binding by the GST pull-down assay. Our crystal structure of the Axin2/SIAH1 complex at 2.53 Å resolution reveals that one Axin2 molecule binds to one SIAH1 molecule via its GBD. These interactions critically depend on a highly conserved peptide 361EMTPVEPA368 within the Axin2-GBD, which forms a loop and binds to a deep groove formed by β1, β2, and β3 of SIAH1 by the N-terminal hydrophilic amino acids Arg361 and Thr363 and the C-terminal VxP motif. The novel binding mode indicates a promising drug-binding site for regulating Wnt/β-catenin signaling. [ABSTRACT FROM AUTHOR]

Simple Summary: Copper sulfate and copper glycinate have been used as additives for copper supplementation and growth promotion in the swine feed industry. However, their effects on the gut microenvironment, especially for the fecal microbiota and metabolites, still remain unclear, which are the important indicators of gut health. As well as the nutrient digestibility and physiological and biochemical indices of pigs, the effects of copper sulfate and copper glycinate on fecal microbial communities and metabolic profiles were investigated to understand it better in the present study. Our results suggested that copper sulfate and copper glycinate could differentially affect fecal microbiota and metabolites, by which dietary copper glycinate exerted more beneficial effects on the gut health of pigs. This study aims to compare the fecal microbiome-metabolome response to copper sulfate (CuSO4) and copper glycinate (Cu-Gly) in pigs. Twelve Meishan gilts were allocated into the CuSO4 group and the Cu-Gly group (fed on a basal diet supplemented with 60 mg/kg copper from CuSO4 or Cu-Gly) paired in litter and body weight. After a two-week feeding trial, the Cu-Gly group had a higher copper digestibility, blood hemoglobin, and platelet volume and higher levels of plasma iron and insulin-like growth factor-1 than the CuSO4 group. The Cu-Gly treatment increased the abundance of the Lachnospiraceae family and the genera Lachnospiraceae XPB1014, Corprococcus_3, Anaerorhabdus_furcosa_group, Lachnospiraceae_FCS020_group, and Lachnospiraceae_NK4B4_group and decreased the abundance of the Synergistetes phylum and Peptostreptococcaceae family compared to the CuSO4 treatment. Moreover, the Cu-Gly group had a lower concentration of 20-Oxo-leukotriene E4 and higher concentrations of butyric acid, pentanoic acid, isopentanoic acid, coumarin, and Nb-p-Coumaroyl-tryptamine than the CuSO4 group. The abundance of Synergistetes was positively correlated with the fecal copper content and negatively correlated with the fecal butyric acid content. The abundance of the Lachnospiraceae_XPB1014_group genus was positively correlated with the plasma iron level and fecal contents of coumarin and butyric acid. In conclusion, Cu-Gly and CuSO4 could differentially affect fecal microbiota and metabolites, which partially contributes to the intestinal health of pigs in different manners. [ABSTRACT FROM AUTHOR]

Background: C-X-C motif chemokine ligand 13 (CXCL13), a member of the CXC subtype in chemokine superfamily, affects numerous biological processes of various types of cells and the progress of a great number of clinical diseases. The purpose of the current study was to reveal the internal mechanism between CXCL13 and benign prostatic hyperplasia (BPH). Methods: Human serum, prostate tissues and human prostate cell lines (BPH-1, WPMY-1) were utilized. The effect of recombinant human CXCL13 (rHuCXCL13) protein and the influences of the knockdown/overexpression of CXCL13 on two cell lines were studied. Rescue experiments by anti-CXCR5 were also conducted. In vivo, rHuCXCL13 was injected into the ventral prostate of rats. Additionally, a tissue microarray of hyperplastic prostate tissues was constructed to analyze the correlations between CXCL13 and clinical parameters. Results: CXCL13 was highly expressed in the prostate tissues and upregulated in the BPH group. It was observed that CXCL13 modulated cell proliferation, apoptosis, and the epithelial–mesenchymal transition (EMT) through CXCR5 via AKT and the ERK1/2 pathway in BPH-1, while it contributed to inflammation and fibrosis through CXCR5 via the STAT3 pathway in WPMY-1. In vivo, rHuCXCL13 induced the development of rat BPH. Additionally, CXCL13 was positively correlated with the prostate volume and total prostate specific antigen. Conclusions: Our novel data demonstrated that CXCL13 modulated cell proliferation, cell cycle, the EMT of epithelial cells, and induced the fibrosis of prostatic stromal cells via a variety of inflammatory factors, suggesting that CXCL13 might be rediscovered as a potential therapeutic target for the treatment of BPH. [ABSTRACT FROM AUTHOR]

Animal fat deposition has a significant impact on meat flavor and texture. However, the molecular mechanisms of fat deposition are not well understood. LncPLAAT3-AS is a naturally occurring transcript that is abundant in porcine adipose tissue. Here, we focus on the regulatory role of lncPLAAT3-AS in promoting preadipocyte proliferation and adipocyte differentiation. By overexpressing or repressing lncPLAAT3 expression, we found that lncPLAAT3-AS promoted the transcription of its host gene PLAAT3, a regulator of adipocyte differentiation. In addition, we predicted the region of lncPLAAT3-AS that binds to miR-503-5p and showed by dual luciferase assay that lncPLAAT3-AS acts as a sponge to absorb miR-503-5p. Interestingly, miR-503-5p also targets and represses PLAAT3 expression and helps regulate porcine preadipocyte proliferation and differentiation. Taken together, these results show that lncPLAAT3-AS upregulates PLAAT3 expression by absorbing miR-503-5p, suggesting a potential regulatory mechanism based on competing endogenous RNAs. Finally, we explored lncPLAAT3-AS and PLAAT3 expression in adipose tissue and found that both molecules were expressed at significantly higher levels in fatty pig breeds compared to lean pig breeds. In summary, we identified the mechanism by which lncPLAAT3-AS regulates porcine preadipocyte proliferation and differentiation, contributing to our understanding of the molecular mechanisms of lipid deposition in pigs. [ABSTRACT FROM AUTHOR]

The breast muscle is essential for flight and determines the meat yield and quality of the meat type in pigeons. At present, studies about long non-coding RNA (lncRNA) expression profiles in skeletal muscles across the postnatal development of pigeons have not been reported. Here, we used transcriptome sequencing to examine the White-King pigeon breast muscle at four different ages (1 day, 14 days, 28 days, and 2 years old). We identified 12,918 mRNAs and 9158 lncRNAs (5492 known lncRNAs and 3666 novel lncRNAs) in the breast muscle, and 7352 mRNAs and 4494 lncRNAs were differentially expressed in the process of development. We found that highly expressed mRNAs were mainly related to cell-basic and muscle-specific functions. Differential expression and time-series analysis showed that differentially expressed genes were primarily associated with muscle development and functions, blood vessel development, cell cycle, and energy metabolism. To further predict the possible role of lncRNAs, we also conducted the WGCNA and trans/cis analyses. We found that differentially expressed lncRNAs such as lncRNA-LOC102093252, lncRNA-G12653, lncRNA-LOC110357465, lncRNA-G14790, and lncRNA-LOC110360188 might respectively target UBE2B, Pax7, AGTR2, HDAC1, Sox8 and participate in the development of the muscle. Our study provides a valuable resource for studying the lncRNAs and mRNAs of pigeon muscles and for improving the understanding of molecular mechanisms in muscle development. [ABSTRACT FROM AUTHOR]

Simple Summary: Functional differences between the various segments of the intestine and differences in the intestines between species have been demonstrated in previous studies. Guinea pigs are commonly used model animals in intestinal-related research. As well as modeling disease states, it is important to study the intestinal tract of guinea pigs to derive basic data for the rational use of guinea pig models. Therefore, we collected six different segments of the intestinal tissue of guinea pigs and analyzed the gene expression profiles and microbial composition of each of these regions. The results revealed the functional regionalization of the intestine, with changes in functional gene expression between different intestinal segments, an association between microbial abundance and gene expression, and differences in intestinal gene expression between different species. Our study provides a reference for future intestinal-related research. The intestine is a tubular organ with multiple functions such as digestion absorption and immunity, but the functions of each intestinal segments are different. Intestinal regionalization is necessary for normal physiological function, but it also means the research results obtained at specific sites may not be applicable to other intestinal segments. In order to comprehensively describe the functional changes in the intestine, different intestinal segments and their contents (duodenum, jejunum, ileum, cecum, colon, and rectum) of guinea pigs were collected for RNA seq and 16S rRNA seq, respectively. The results showed differential genes of each intestinal segment mainly involve mucosa, digestion, absorption, and immunity. The gene sets related to fat, bill salts, vitamins, aggregates, amino acids, and water absorption were highly expressed in the small intestine, and the gene sets related to metal ions, nucleotides, and SCFAs were highly expressed in the large intestine. In terms of immunity, the CD8+ T, Th1, eosinophils, pDCs, and natural killer (NK) T cells in the small intestine showed higher scores than those in the large intestine, while the pattern-recognition receptor signaling pathway-related genes are highly expressed in the large intestine. In terms of microbial composition, Proteobacteria and Actinobacteria are abundant in the small intestine, while Firmicutes and Spirochaete are abundant in large intestine. The correlation analysis showed a high correlation between intestinal microorganisms and gene modules related to digestion and absorption. In addition, cross-species analysis showed the SCFA metabolism gene expression trends in human and rodent intestine were different. In conclusion, we analyzed the changes in substance transport, immune and microbial composition between different intestinal segments of guinea pigs, and explored the relationship between intestinal transcriptome and microorganisms, our research will provides a reference for subsequent intestinal-related research. [ABSTRACT FROM AUTHOR]

Obesity is a major driver of metabolic diseases such as nonalcoholic fatty liver disease, certain cancers, and insulin resistance. However, there are no effective drugs to treat obesity. Betaine is a nontoxic, chemically stable and naturally occurring molecule. This study shows that dietary betaine supplementation significantly inhibits the white fat production in a high-fat diet (HFD)-induced obese mice. This might be due to betaine preventing the formation of new white fat (WAT), and guiding the original WAT to burn through stimulated mitochondrial biogenesis and promoting browning of WAT. Furthermore, dietary betaine supplementation decreases intramyocellular lipid accumulation in HFD-induced obese mice. Further analysis shows that betaine supplementation reduced intramyocellular lipid accumulation might be associated with increasing polyunsaturated fatty acids (PUFA), fatty acid oxidation, and the inhibition of fatty acid synthesis in muscle. Notably, by performing insulin-tolerance tests (ITTs) and glucose-tolerance tests (GTTs), dietary betaine supplementation could be observed for improvement of obesity and non-obesity induced insulin resistance. Together, these findings could suggest that inhibiting WAT production, intramyocellular lipid accumulation and inflammation, betaine supplementation limits HFD-induced obesity and improves insulin resistance. [ABSTRACT FROM AUTHOR]

Simple Summary: The mammalian gut microbiota is an indispensable part of host health. The gut microbiota plays a crucial role in nutrient digestibility, preventing colonization of pathogens and maintaining the host immune system. Host genetics has been conclusively shown to closely related to gut microbiota. Inbreeding can cause a decrease of the host's genetic diversity, however, remarkably little is understood about the gut microbiota of pigs during inbreeding. The Banna minipig inbred is the world's first successful large mammalian experimental animal inbred line since 1980 from full and half-siblings of the Diannan small-ear pig. Now, Banna minipig inbred has been inbred for over 37 generations, and the inbreeding coefficient is more than 99%. This study is the first to characterize and compare the composition and function of gut microbiota between the Diannan small-ear pig and Banna minipig inbred, aiming to better understand the influence of inbreeding on the gut microbiota. The gut microbiota coevolve with the host and can be stably transmitted to the offspring. Host genetics plays a crucial role in the composition and abundance of gut microbiota. Inbreeding can cause a decrease of the host's genetic diversity and the heterozygosity. In this study, we used 16S rRNA gene sequencing to compare the differences of gut microbiota between the Diannan small-ear pig and Banna minipig inbred, aiming to understand the impact of inbreeding on the gut microbiota. Three dominant bacteria (Stenotrophlomonas, Streptococcus, and Lactobacillus) were steadily enriched in both the Diannan small-ear pig and Banna minipig inbred. After inbreeding, the gut microbiota alpha diversity and some potential probiotics (Bifidobacterium, Tricibacter, Ruminocaccae, Christensenellaceae, etc.) were significantly decreased, while the pathogenic Klebsiella bacteria was significantly increased. In addition, the predicted metagenomic analysis (PICRUSt2) indicated that several amino acid metabolisms ("Valine, leucine, and isoleucine metabolism", "Phenylalanine, tyrosine, and tryptophan biosynthesis", "Histidine metabolism") were also markedly decreased after the inbreeding. Altogether our data reveal that host inbreeding altered the composition and the predicted function of the gut microbiome, which provides some data for the gut microbiota during inbreeding. [ABSTRACT FROM AUTHOR]

Skin is the body's largest organ, and the main function of skin is to protect underlying organs from possible external damage. Melanocytes play an important role in skin pigmentation. The Bama pig has a "two-end-black" phenotype with different coat colors across skin regions, e.g., white skin (without melanocytes) and black skin (with melanocytes), which could be a model to investigate skin-related disorders, specifically loss of melanocytes. Here, we generated expression profiles of mRNAs and long noncoding RNAs in Bama pig skins with different coat colors. In total, 14,900 mRNAs and 7549 lncRNAs were expressed. Overall, 2338 mRNAs/113 lncRNAs with FDR-adjusted p-value ≤ 0.05 were considered to be differentially expressed (DE) mRNAs/lncRNAs, with 1305 down-regulated mRNAs and 1033 up-regulated mRNAs in white skin with|log2(fold change)| > 1. The genes down-regulated in white skin were associated with pigmentation, melanocyte–keratinocyte interaction, and keratin, while up-regulated ones were mainly associated with cellular energy metabolisms. Furthermore, those DE lncRNAs were predicted to be implicated in pigmentation, keratin synthesis and cellular energy metabolism. In general, this study provides insight into the transcriptional difference involved in melanocyte-loss-induced keratinocyte changes and promotes the Bama pig as a biomedical model in skin research. [ABSTRACT FROM AUTHOR]

The biochemical and functional differences between oxidative and glycolytic muscles could affect human muscle health and animal meat quality. However, present understanding of the epigenetic regulation with respect to lncRNAs and circRNAs is rudimentary. Here, porcine oxidative and glycolytic skeletal muscles, which were at the growth curve inflection point, were sampled to survey variant global expression of lncRNAs and circRNAs using RNA-seq. A total of 4046 lncRNAs were identified, including 911 differentially expressed lncRNAs (p < 0.05). The cis-regulatory analysis identified target genes that were enriched for specific GO terms and pathways (p < 0.05), including the oxidation-reduction process, glycolytic process, and fatty acid metabolic. All these were closely related to different phenotypes between oxidative and glycolytic muscles. Additionally, 810 circRNAs were identified, of which 137 were differentially expressed (p < 0.05). Interestingly, some circRNA-miRNA-mRNA networks were found, which were closely linked to muscle fiber-type switching and mitochondria biogenesis in muscles. Furthermore, 44.69%, 39.19%, and 54.01% of differentially expressed mRNAs, lncRNAs, and circRNAs respectively were significantly enriched in pig quantitative trait loci (QTL) regions for growth and meat quality traits. This study reveals a mass of candidate lncRNAs and circRNAs involved in muscle physiological functions, which may improve understanding of muscle metabolism and development from an epigenetic perspective. [ABSTRACT FROM AUTHOR]

Acute myocardial infarction (AMI) is an ischemic heart disease with high mortality worldwide. AMI triggers a hypoxic microenvironment and induces extensive myocardial injury, including autophagy and apoptosis. MiRNAs, which are a class of posttranscriptional regulators, have been shown to be involved in the development of ischemic heart diseases. We have previously reported that hypoxia significantly alters the miRNA transcriptome in rat cardiomyoblast cells (H9c2), including miR-27a-5p. In the present study, we further investigated the potential function of miR-27a-5p in the cardiomyocyte response to hypoxia, and showed that miR-27a-5p expression was downregulated in the H9c2 cells at different hypoxia-exposed timepoints and the myocardium of a rat AMI model. Follow-up experiments revealed that miR-27a-5p attenuated hypoxia-induced cardiomyocyte injury by regulating autophagy and apoptosis via Atg7, which partly elucidated the anti-hypoxic injury effects of miR-27a-5p. Taken together, this study shows that miR-27a-5p has a cardioprotective effect on hypoxia-induced H9c2 cell injury, suggesting it may be a novel target for the treatment of hypoxia-related heart diseases. [ABSTRACT FROM AUTHOR]

tRNA-derived fragments (tRFs) are a new class of non-coding RNA that play an important role in regulating cellular RNA processing and protein translation. However, there is currently no study reporting the influence of tRFs on myocardial hypertrophy. In this study, we used an isoproterenol (ISO)-induced myocardial hypertrophy rat model. Small RNA (<40 nts) transcriptome sequencing was used to select differentially expressed tRFs. We also compared the tRFs expression pattern in F0 sperm and the hearts of F1 offspring between the myocardial hypertrophy group (Hyp) and the control group (Con). Isoproterenol successfully induced a typical cardiac hypertrophy model in our study. Small RNA-seq revealed that tRFs were extremely enriched (84%) in the Hyp heart. Overexpression of tRFs1 and tRFs2 both enlarged the surface area of cardiac cells and increased expression of hypertrophic markers (ANF, BNP, and β-MHC). Luciferase reporter assay identified that tRFs1 directly target 3′UTR of Timp3. tRFs1, tRFs2, tRFs3, and tRFs4 were also highly expressed in Hyp F0 sperm and in Hyp F1 offspring hearts, but there was no differential expression of tRFs7, tRFs9, and tRFs10. Compared to Con F1 offspring, Hyp F1 offspring had elevated expression levels of β-MHC and ANP genes, and they had increased fibrosis and apoptosis in their hearts. These results demonstrated that tRFs are involved in regulating the response of myocardial hypertrophy. Besides, tRFs might serve as novel epigenetic factors that contribute to the intergenerational inheritance of cardiac hypertrophy. [ABSTRACT FROM AUTHOR]

Lung tissue plays an important role in the respiratory system of mammals after birth. Early lung development includes six key stages, of which the saccular stage spans the pre- and neonatal periods and prepares the distal lung for alveolarization and gas-exchange. However, little is known about the changes in gene expression between fetal and neonatal lungs. In this study, we performed transcriptomic analysis of messenger RNA (mRNA) and long noncoding RNA (lncRNA) expressed in the lung tissue of fetal and neonatal piglets. A total of 19,310 lncRNAs and 14,579 mRNAs were identified and substantially expressed. Furthermore, 3248 mRNAs were significantly (FDR-adjusted p value ≤ 0.05, FDR: False Discovery Rate) differentially expressed and were mainly enriched in categories related to cell proliferation, immune response, hypoxia response, and mitochondrial activation. For example, CCNA2, an important gene involved in the cell cycle and DNA replication, was upregulated in neonatal lungs. We also identified 452 significantly (FDR-adjusted p value ≤ 0.05) differentially expressed lncRNAs, which might function in cell proliferation, mitochondrial activation, and immune response, similar to the differentially expressed mRNAs. These results suggest that differentially expressed mRNAs and lncRNAs might co-regulate lung development in early postnatal pigs. Notably, the TU64359 lncRNA might promote distal lung development by up-regulating the heparin-binding epidermal growth factor-like (HB-EGF) expression. Our research provides basic lung development datasets and will accelerate clinical researches of newborn lung diseases with pig models. [ABSTRACT FROM AUTHOR]

Guanidinoacetic acid (GAA), an amino acid derivative that is endogenous to animal tissues including muscle and nerve, has been reported to enhance muscular performance. MicroRNA (miRNA) is a post-transcriptional regulator that plays a key role in nutrient-mediated myogenesis. However, the effects of GAA on myogenic differentiation and skeletal muscle growth, and the potential regulatory mechanisms of miRNA in these processes have not been elucidated. In this study, we investigated the effects of GAA on proliferation, differentiation, and growth in C2C12 cells and mice. The results showed that GAA markedly inhibited the proliferation of myoblasts, along with the down-regulation of cyclin D1 (CCND1) and cyclin dependent kinase 4 (CDK4) mRNA expression, and the upregulation of cyclin dependent kinase inhibitor 1A (P21) mRNA expression. We also demonstrated that GAA treatment stimulated myogenic differentiation 1 (MyoD) and myogenin (MyoG) mRNA expression, resulting in an increase in the myotube fusion rate. Meanwhile, GAA supplementation promoted myotube growth through increase in total myosin heavy chain (MyHC) protein level, myotubes thickness and gastrocnemius muscle cross-sectional area. Furthermore, small RNA sequencing revealed that a total of eight miRNAs, including miR-133a-3p and miR-1a-3p cluster, showed differential expression after GAA supplementation. To further study the function of miR-133a-3p and miR-1a-3p in GAA-induced skeletal muscle growth, we transfected miR-133a-3p and miR-1a-3p mimics into myotube, which also induced muscle growth. Through bioinformatics and a dual-luciferase reporter system, the target genes of miR-133a-3p and miR-1a-3p were determined. These two miRNAs were shown to modulate the Akt/mTOR/S6K signaling pathway by restraining target gene expression. Taken together, these findings suggest that GAA supplementation can promote myoblast differentiation and skeletal muscle growth through miR-133a-3p- and miR-1a-3p-induced activation of the AKT/mTOR/S6K signaling pathway. [ABSTRACT FROM AUTHOR]

Macrophages are the foremost controllers of innate and acquired immunity, playing important roles in tissue homeostasis, vasculogenesis, and congenital metabolism. In vitro macrophages are crucial models for understanding the regulatory mechanism of immune responses and the diagnosis or treatment of a variety of diseases. Pigs are the most important agricultural animals and valuable animal models for preclinical studies, but there is no unified method for porcine macrophage isolation and differentiation at present; no systematic study has compared porcine macrophages obtained by different methods. In the current study, we obtained two M1 macrophages (M1&#95;IFNγ + LPS, and M1&#95;GM-CSF) and two M2 macrophages (M2&#95;IL4 + IL10, and M2&#95;M-CSF), and compared the transcriptomic profiles between and within macrophage phenotypes. We observed the transcriptional differences either between or within phenotypes. Porcine M1 and M2 macrophages have consistent gene signatures with human and mouse macrophage phenotypes, respectively. Moreover, we performed GSEA analysis to attribute the prognostic value of our macrophage signatures in discriminating various pathogen infections. Our study provided a framework to guide the interrogation of macrophage phenotypes in the context of health and disease. The approach described here could be used to propose new biomarkers for diagnosis in diverse clinical settings including porcine reproductive and respiratory syndrome virus (PRRSV), African swine fever virus (ASFV), Toxoplasma gondii ( T. gondii ), porcine circovirus type 2 (PCV2), Haemophilus parasuis serovar 4 (HPS4), Mycoplasma hyopneumoniae (Mhp), Streptococcus suis serotype 2 (SS2), and LPS from Salmonella enterica serotype minnesota Re 595 ., Competing Interests: The authors declare no conflict of interest.

Background: C-X-C motif chemokine ligand 13 ( CXCL13 ), a member of the CXC subtype in chemokine superfamily, affects numerous biological processes of various types of cells and the progress of a great number of clinical diseases. The purpose of the current study was to reveal the internal mechanism between CXCL13 and benign prostatic hyperplasia (BPH)., Methods: Human serum, prostate tissues and human prostate cell lines (BPH-1, WPMY-1) were utilized. The effect of recombinant human CXCL13 (rHuCXCL13) protein and the influences of the knockdown/overexpression of CXCL13 on two cell lines were studied. Rescue experiments by anti-CXCR5 were also conducted. In vivo, rHuCXCL13 was injected into the ventral prostate of rats. Additionally, a tissue microarray of hyperplastic prostate tissues was constructed to analyze the correlations between CXCL13 and clinical parameters., Results: CXCL13 was highly expressed in the prostate tissues and upregulated in the BPH group. It was observed that CXCL13 modulated cell proliferation, apoptosis, and the epithelial-mesenchymal transition (EMT) through CXCR5 via AKT and the ERK1/2 pathway in BPH-1, while it contributed to inflammation and fibrosis through CXCR5 via the STAT3 pathway in WPMY-1. In vivo, rHuCXCL13 induced the development of rat BPH. Additionally, CXCL13 was positively correlated with the prostate volume and total prostate specific antigen., Conclusions: Our novel data demonstrated that CXCL13 modulated cell proliferation, cell cycle, the EMT of epithelial cells, and induced the fibrosis of prostatic stromal cells via a variety of inflammatory factors, suggesting that CXCL13 might be rediscovered as a potential therapeutic target for the treatment of BPH.

Skin is the body's largest organ, and the main function of skin is to protect underlying organs from possible external damage. Melanocytes play an important role in skin pigmentation. The Bama pig has a "two-end-black" phenotype with different coat colors across skin regions, e.g., white skin (without melanocytes) and black skin (with melanocytes), which could be a model to investigate skin-related disorders, specifically loss of melanocytes. Here, we generated expression profiles of mRNAs and long noncoding RNAs in Bama pig skins with different coat colors. In total, 14,900 mRNAs and 7549 lncRNAs were expressed. Overall, 2338 mRNAs/113 lncRNAs with FDR-adjusted p -value ≤ 0.05 were considered to be differentially expressed (DE) mRNAs/lncRNAs, with 1305 down-regulated mRNAs and 1033 up-regulated mRNAs in white skin with|log 2 (fold change)| > 1. The genes down-regulated in white skin were associated with pigmentation, melanocyte-keratinocyte interaction, and keratin, while up-regulated ones were mainly associated with cellular energy metabolisms. Furthermore, those DE lncRNAs were predicted to be implicated in pigmentation, keratin synthesis and cellular energy metabolism. In general, this study provides insight into the transcriptional difference involved in melanocyte-loss-induced keratinocyte changes and promotes the Bama pig as a biomedical model in skin research.

Recent evidence suggests that testosterone deficiency can dramatically decrease the quality of sperm. MicroRNAs (miRNAs) are conserved mediators of post-transcriptional gene regulation in eukaryotes. However, the systemic regulation and function of miRNAs in sperm quality decline induced by testosterone deficiency has not been investigated. Here, we found that the sperm apoptosis was significantly enhanced and the sperm motility was dramatically decreased in hemicastrated pigs. We then used small RNA sequencing to detect miRNA profiles of sperm from pigs with prepubertal hemicastration (HC) and compared them with control libraries. We identified 16 differentially expressed (DE) miRNAs between the sperm of prepubertal HC and control (CT) pigs. Functional enrichment analysis indicated that the target genes of these DE miRNAs were mainly enriched in apoptosis-related pathways including the p53, mitogen-activated protein kinase (MAPK), and mammalian target of rapamycin (mTOR) pathways. Furthermore, gain- and loss-of-function analyses demonstrated potential anti-apoptotic effects of the DE miRNAs miR-26a-5p and let-7g-5p on sperm cells. The luciferase reporter assay confirmed that PTEN and PMAIP1 are targets of miR-26a-5p and let-7g-5p, respectively. Spearman&rsquo;s correlation analysis revealed significantly positive correlations between the sperm and its corresponding seminal plasma exosomes regarding the miRNA expression levels. In conclusion, testosterone deficiency-induced changes in the miRNA components of seminal plasma exosomes secreted by the genital tract may partially elucidate sperm miRNAome alterations, which are further responsible for the decline of sperm motility.

Recent evidence suggests that hypoxia caused by acute myocardial infarction can induce cardiomyocyte apoptosis. Exosomes are signalling mediators that contribute to intercellular communication by transporting cytosolic components including miRNAs, mRNAs, and proteins. However, the systemic regulation and function of exosomal miRNAs in hypoxic cardiomyocytes are currently not well understood. Here, we used small RNA sequencing to investigate the effects of hypoxia stress on miRNAome of rat cardiomyoblast cells (H9c2) and corresponding exosomes. We identified 92 and 62 miRNAs in cells and exosomes, respectively, that were differentially expressed between hypoxia and normoxia. Hypoxia strongly modulated expression of hypoxia-associated miRNAs in H9c2 cells, and altered the miRNAome of H9c2 cells-derived exosomes. Functional enrichment analysis revealed extensive roles of differentially expressed exosomal miRNAs in the HIF-1 signalling pathway and in apoptosis-related pathways including the TNF, MAPK, and mTOR pathways. Furthermore, gain- and loss-of-function analysis demonstrated potential anti-apoptotic effects of the hypoxia-induced exosomal miRNAs, including miR-21-5p, miR-378-3p, miR-152-3p, and let-7i-5p; luciferase reporter assay confirmed that Atg12 and Faslg are targets of miR-152-3p and let-7i-5p, respectively. To summarize, this study revealed that hypoxia-induced exosomes derived from H9c2 cells loaded cardioprotective miRNAs, which mitigate hypoxia-induced H9c2 cells apoptosis.

MicroRNAs (miRNAs) are small non-coding RNAs that can regulate their target genes at the post-transcriptional level. Skeletal muscle comprises different fiber types that can be broadly classified as red, intermediate, and white. Recently, a set of miRNAs was found expressed in a fiber type-specific manner in red and white fiber types. However, an in-depth analysis of the miRNA transcriptome differences between all three fiber types has not been undertaken. Herein, we collected 15 porcine skeletal muscles from different anatomical locations, which were then clearly divided into red, white, and intermediate fiber type based on the ratios of myosin heavy chain isoforms. We further illustrated that three muscles, which typically represented each muscle fiber type (i.e., red: peroneal longus (PL), intermediate: psoas major muscle (PMM), white: longissimus dorsi muscle (LDM)), have distinct metabolic patterns of mitochondrial and glycolytic enzyme levels. Furthermore, we constructed small RNA libraries for PL, PMM, and LDM using a deep sequencing approach. Results showed that the differentially expressed miRNAs were mainly enriched in PL and played a vital role in myogenesis and energy metabolism. Overall, this comprehensive analysis will contribute to a better understanding of the miRNA regulatory mechanism that achieves the phenotypic diversity of skeletal muscles.

The gram-negative bacterium Actinobacillus pleuropneumoniae (APP) is an inhabitant of the porcine upper respiratory tract and the causative agent of porcine pleuropneumonia (PP). In recent years, knowledge about the proinflammatory cytokine and chemokine gene expression that occurs in lung and lymph node of the APP-infected swine has been advanced. However, systematic gene expression profiles on hilar nodes from pigs after infection with Actinobacillus pleuropneumoniae have not yet been reported. The transcriptional responses were studied in hilar nodes (HN) from swine experimentally infected with APP and the control groupusing Agilent Porcine Genechip, including 43,603 probe sets. 9,517 transcripts were identified as differentially expressed (DE) at the p ≤ 0.01 level by comparing the log2 (normalized signal) of the two groups named treatment group (TG) and controls (CG). Eight hundred and fifteen of these DE transcripts were annotated as pig genes in the GenBank database (DB). Two hundred and seventy-two biological process categories (BP), 75 cellular components and 171 molecular functions were substantially altered in the TG compared to CG. Many BP were involved in host immune responses (i.e., signaling, signal transmission, signal transduction, response to stimulus, oxidation reduction, response to stress, immune system process, signaling pathway, immune response, cell surface receptor linked signaling pathway). Seven DE gene pathways (VEGF signaling pathway, Long-term potentiation, Ribosome, Asthma, Allograft rejection, Type I diabetes mellitus and Cardiac muscle contraction) and statistically significant associations with host responses were affected. Many cytokines (including NRAS, PI3K, MAPK14, CaM, HSP27, protein phosphatase 3, catalytic subunit and alpha isoform), mediating the proliferation and migration of endothelial cells and promoting survival and vascular permeability, were activated in TG, whilst many immunomodulatory cytokines were suppressed. The significant changes in the expression patterns of the genes, GO terms, and pathways, led to a decrease of antigenic peptides with antigen presenting cells presented to T lymphocytes via the major histocompatibility complex, and alleviated immune response induced APP of HN. The immune response ability of HN in the APP-infected pigs was weakened; however, cell proliferation and migration ability was enhanced.

Porcine pleuropneumonia is a highly contagious respiratory disease that causes great economic losses worldwide. In this study, we aimed to explore the underlying relationship between infection and injury by investigation of the whole porcine genome expression profiles of swine lung tissues post-inoculated with experimentally Actinobacillus pleuropneumoniae. Expression profiling experiments of the control group and the treatment group were conducted using a commercially available Agilent Porcine Genechip including 43,603 probe sets. Microarray analysis was conducted on profiles of lung from challenged versus non-challenged swine. We found 11,929 transcripts, identified as differentially expressed at the p ≤0.01 level. There were 1188 genes annotated as swine genes in the GenBank Data Base. GO term analysis identified a total of 89 biological process categories, 82 cellular components and 182 molecular functions that were significantly affected, and at least 27 biological process categories that were related to the host immune response. Gene set enrichment analysis identified 13 pathways that were significantly associated with host response. Many proinflammatory-inflammatory cytokines were activated and involved in the regulation of the host defense response at the site of inflammation; while the cytokines involved in regulation of the host immune response were suppressed. All changes of genes and pathways of induced or repressed expression not only led to a decrease in antigenic peptides presented to T lymphocytes by APCs via the MHC and alleviated immune response injury induced by infection, but also stimulated stem cells to produce granulocytes (neutrophils, eosinophils, and basophils) and monocyte, and promote neutrophils and macrophages to phagocytose bacterial and foreign antigen at the site of inflammation. The defense function of swine infection with Actinobacillus pleuropneumoniae was improved, while its immune function was decreased.

Intermuscular adipose tissue is located between the muscle fiber bundles in skeletal muscles, and has similar metabolic features to visceral adipose tissue, which has been found to be related to a number of obesity-related diseases. Although various miRNAs are known to play crucial roles in adipose deposition and adipogenesis, the microRNA transcriptome of intermuscular adipose tissue has not, until now, been studied. Here, we sequenced the miRNA transcriptomes of porcine intermuscular adipose tissue by small RNA-sequencing and compared it to a representative subcutaneous adipose tissue. We found that the inflammation- and diabetes-related miRNAs were significantly enriched in the intermuscular rather than in the subcutaneous adipose tissue. A functional enrichment analysis of the genes predicted to be targeted by the enriched miRNAs also indicated that intermuscular adipose tissue was associated mainly with immune and inflammation responses. Our results suggest that the intermuscular adipose tissue should be recognized as a potential metabolic risk factor of obesity.

Adipose tissue is not only a storage organ involved in fuel metabolism, but also an endocrine organ involved in the regulation of insulin sensitivity, thermogenesis, immunity, and inflammation. There are anatomical, cellular, molecular and physiological differences among adipose tissues deposited in different body sites. However, current understanding of the intrinsic differences between the sub-compartments of the subcutaneous adipose tissue remains rudimentary. Here, we analyzed the genome-wide DNA methylation differences between the porcine superficial and deep backfat tissues using methylated DNA immunoprecipitation combined with high-throughput sequencing. We show that the genes with differentially methylated regions in their promoter are mainly involved in the processes of "lipid metabolism" and "regulation of immune-related cytokines". Compared with the deep backfat tissue, the promoters of genes related to the 'positive regulation of cytokine production' were significantly hypermethylated in the superficial backfat tissue, which reflects the intrinsic functional and metabolic differences between the sub-compartments of the subcutaneous adipose tissue. This study provides epigenetic evidence for functionally relevant methylation differences between different layers of porcine backfat tissues.

MicroRNAs (miRNAs) are non-coding small RNAs that play roles in regulating gene expression. Some miRNAs have been classed as epigenetic regulators of metabolism and energy homeostasis. Previous reports indicated that the miRNAs miR-27a and miR-143 were involved in lipid metabolism in human and rodents. To determine the roles of porcine miR-27a and miR-143 in adipocyte lipid metabolism, porcine adipocytes were cultured and allowed to induce differentiation for 10 days. The lipid-filled adipocytes were then transfected with miRNA mimics and inhibitors. We measured how the indicators of adipogenesis and adipolysis in porcine adipocytes were affected by the over-expression and by the inhibition of both miR-27a and miR-143. The results indicated that the over-expression of miR-27a could accelerate adipolysis releasing significantly more glycerol and free fatty acids than the negative control (P < 0.001), while the mimic of miR-143 expression, promoted adipogenesis by accumulating more triglycerides (P < 0.001) in the adipocytes. In addition, we demonstrated that there was good correlation (r > 0.98, P < 0.001) between the indicators of adipolysis in cell lysates and in the culture medium.