Lipid Nanoparticles Outperform Electroporation in Delivering Therapeutic HPV DNA Vaccines.

Therapeutic HPV vaccines that induce potent HPV-specific cellular immunity and eliminate pre-existing infections remain elusive. Among various candidates under development, those based on DNA constructs are considered promising because of their safety profile, stability, and efficacy. However, the use of electroporation (EP) as a main delivery method for such vaccines is notorious for adverse effects like pain and potentially irreversible muscle damage. Moreover, the requirement for specialized equipment adds to the complexity and cost of clinical applications. As an alternative to EP, lipid nanoparticles (LNPs) that are already commercially available for delivering mRNA and siRNA vaccines are likely to be feasible. Here, we have compared three intramuscular delivery systems in a preclinical setting. In terms of HPV-specific cellular immune responses, mice receiving therapeutic HPV DNA vaccines encapsulated with LNP demonstrated superior outcomes when compared to EP administration, while the naked plasmid vaccine showed negligible responses, as expected. In addition, SM-102 LNP M exhibited the most promising results in delivering candidate DNA vaccines. Thus, LNP proves to be a feasible delivery method in vivo, offering improved immunogenicity over traditional approaches.

ß-glucosidase, driven by porcine transthyretin promoter, specific expression in the liver of transgenic mice.

Under the background of food security, using non-grain feed instead of corn-soybean-based feed is an effective measure to alleviate the food-feed competition. While, non-grain feeds are often rich in fiber, which cannot be digested by non-ruminants. Producing heterologous enzymes in non-ruminants to improve cellulose utilization rate is a new research strategy by transgenic technology. In this study, porcine transthyretin (TTR) promoter, signal peptide-coding sequence (CDS), Saccharomycopsis fibuligera ß-glucosidase gene (BGL1)-CDS, 6×His sequences fragments were fused into pGL3-control vector to generate transgenic vector. Then, transgenic mice were generated by pronuclear microinjection of the linearized expression vectors. Transgenic mice and their offspring were examined by PCR-based genotyping and copy number variation. Results showed that BGL1 was successfully integrated into the mouse genome and transmitted stably. Furthermore, reverse transcription-polymerase chain reaction (RT-PCR), Western blotting, and ß-glucosidase activity assay demonstrated that BGL1 was specifically expressed in the liver, and ß-glucosidase activity significantly increased. In addition, liver weight index, cellular morphology, and collagen fiber content of the liver showed that exogenous gene insertion did not cause any lesions to live. Taken together, our findings suggest that ß-glucosidase driven by TTR promoter was specifically expressed in the liver of transgenic mice.

Factors influencing the bone mineral density in Duroc boars.

BACKGROUND: Leg weakness affects animal welfare and is one of the primary reasons for culling of boars. Low bone mineral density (BMD) is one of the primary factors contributing to leg weakness. Low BMD also appeared to be associated with severe bone pain and has the highest risk of skeletal fragility. Surprisingly, few studies have been performed on the factors influencing BMD in pigs. Therefore, the primary aim of this study was to identify the influencing factors on boar BMD. Herein, the BMD data were determined through the use of ultrasonography from 893 Duroc boars. Logistic regression model was utilized in the analysis of BMD, in which the explanatory variables in the model were lines, ages, body weights, backfat thicknesses and serum mineral element concentrations (Ca, P, Mg, Cu, Fe, Zn, Mn, Se, Pb and Cd). RESULTS: Results showed that factors significantly influencing BMD included serum Ca, P concentrations, ages and backfat thicknesses (P < 0.05), in which serum Ca concentrations were positively correlated with BMD (P < 0.01), whereas increasing concentrations of serum P decreased BMD (P < 0.01). The serum Ca/P ratio showed significant quadratic effects on BMD (r = 0.28, P < 0.01), and the Ca/P ratio to achieve the best BMD was determined to be 3.7. Furthermore, BMD also changed with age quadratically (r = 0.40, P < 0.01), and reached a peak value around 47 months. Interestingly, a quadratic (r = 0.26, P < 0.01) increase in the BMD was observed as backfat thickness increased, and the inflection point was calculated at around 17 mm. CONCLUSION: In conclusion, BMD characteristics of boars could be detected by ultrasonic method, and serum Ca, serum P, age, and backfat thickness contributed to the greatest effect on BMD.

Effect of humic acid-modified attapulgite on polycyclic aromatic hydrocarbon adsorption and release from paddy soil into the overlying water in a rice-crab coculture paddy ecosystem and the underlying process.

Phenanthrene (Phe), a typical polycyclic aromatic hydrocarbon (PAH) pollutant, poses an enormous safety risk to rice-crab coculture (RC) paddy ecosystems. In this study, humic acid-modified purified attapulgite (HA-ATP) with a composite structure was successfully fabricated to adsorb PAHs released from paddy soil to overlying water in RC paddy ecosystems in Northeast China. The maximum crab bioturbation intensities for dissolved Phe and particulate Phe were 64.83nullng/L·(cm2·d) and 214.29nullng/L·(cm2·d), respectively. The highest concentration of dissolved Phe released from paddy soil to overlying water due to crab bioturbation reached 80.89nullng/L, while the corresponding concentration of particulate Phe reached 267.36nullng/L. The dissolved organic carbon (DOC) and total suspended solid (TSS) concentrations in overlying water increased correspondingly and were strongly correlated with dissolved Phe and particulate Phe concentrations, respectively (P < 0.05). When 6% HA-ATP was added to the surface layer of paddy soil, the efficiency of the adsorption of Phe release was 24.00%-36.38% for particulate Phe and 89.99%-91.91% for dissolved Phe. Because HA-ATP has a large adsorption pore size (11.33 nm) and surface area (82.41nullm2/g) as well as many HA functional groups, it provided multiple hydrophobic adsorption sites for dissolved Phe, which was conducive to competitive adsorption with DOC in the overlying water. In contrast to that adsorbed by DOC, the average proportion of dissolved Phe adsorbed by HA-ATP reached 90.55%, which reduced the dissolved Phe concentration in the overlying water. Furthermore, even though the particulate Phe was resuspended by crab bioturbation, HA-ATP immobilized particulate Phe due to its capacity to inhibit desorption, which achieved the goal of reducing the Phe concentration in the overlying water. This result was confirmed by research on the adsorption-desorption characteristics of HA-ATP. This research provides an environmentally friendly in situ remediation method for reducing agricultural environmental risks and improving rice crop quality.

Irrigation Scheduling for Maize under Different Hydrological Years in Heilongjiang Province, China.

Appropriate irrigation schedules could minimize the existing imbalance between agricultural water supply and crop water requirements (ETc), which is severely impacted by climate change. In this study, different hydrological years (a wet year, normal year, dry year, and an extremely dry year) in Heilongjiang Province were calculated by hydrological frequency methods. Then, the single crop coefficient method was used to calculate the maize ETc, based on the daily meteorological data of 26 meteorological stations in Heilongjiang Province from 1960 to 2020. Afterward, the CROPWAT model was used to calculate the effective precipitation (Pe) and irrigation water requirement (Ir), and formulate the irrigation schedules of maize in Heilongjiang Province under different hydrological years. The results showed that ETc and Ir decreased first and then increased from west to east. The Pe and crop water surplus deficit index increased first and then decreased from west to east in Heilongjiang Province. Meanwhile, the average values of the Ir in were 171.14 mm, 232.79 mm, 279.08 mm, and 334.47 mm in the wet year, normal year, dry year, and extremely dry year, respectively. Heilongjiang Province was divided into four irrigation zones according to the Ir of different hydrological years. Last, the irrigation quotas for the wet year, normal year, dry year, and extremely dry year were 0~180 mm, 20~240 mm, 60~300 mm, and 80~430 mm, respectively. This study provides reliable support for maize irrigation practices in Heilongjiang Province, China.

Cluster analysis and potential influencing factors of boars with different fertility.

The fertility of boars is intimately tied to the pig farm's economic benefits. This study aimed to rapidly categorize boars of different fertility and investigate the factors influencing the categorization using the production data in a large pig farm in northern China, including 11,163 semen collection records of Yorkshire boars (215), 11,163 breeding records and 8770 records of farrowing performance of Yorkshire sows (4505), as well as 4720 records of selection indices (sire line index and dam line index) for boars and sows (215 and 4505) between 2017 and 2020. The boar population was classified by two-step cluster analysis, followed by factor analysis to minimize the dimensionality of data variables and eliminate multicollinearity, and then using ordinal logistic regression model to investigate the risk variables impacting boar fertility categorization. Results showed that the two-step clustering divided the 215 boars into three subgroups: high-fertility (n = 61, 28.4%), medium-fertility (n = 127, 59.1%) and low-fertility (n = 27, 12.6%). The high-fertility boars were shown to be substantially greater than the medium-fertility or low-fertility boars (p < 0.05) in average total litter size, number of born alive, and number of healthy piglets of mated sows. Compared with low-fertility boars, the high-fertility boars were also significantly higher (p < 0.05) in the pregnancy rate and farrowing rate of mated sows. However, the three boar subgroups showed no difference (p > 0.05) in semen quality information (average sperm motility, average sperm density, and average sperm volume). Collinearity diagnosis indicated severe multicollinearity among the 20 data variables, which were reduced to 8 factor variables (factors 1-8) by factor analysis, and further collinearity diagnosis exhibited no multicollinearity among the 8 factor variables. Ordered logistic regression analysis revealed a significant and positive correlation (p < 0.05) of boar fertility with factor 2 (average total litter size, number of born alive, number of healthy piglets), factor 4 (average number of weak piglets and average weak piglet rate), factor 6 (sire line index of boars and dam line index of boars), factor 8 (pregnancy rate and farrowing rate), highlighting factor 2 as the most important factor influencing the classification of boar fertility. Our results indicate that the two-step cluster analysis can be used as a simple and effective method to screen boars with different fertility and that farm producers should pay attention to the recording of the reproductive performance of the mated sows due to its role as the risk factor for classification of boar fertility.

Optimizing feeding regimen of replacement gilts to improve their reproductive performance and retention rate of their first 2 parities.

The effects of age, body weight (BW), and backfat thickness (BF) of replacement gilts at first estrus and first mating on their subsequent reproductive performance and retention of their first 2 parities as sows was evaluated. A total of 3,025 Danish replacement gilts were categorized by farm (allocated to 4 farms), cross combination, age, BW and BF at first estrus and first mating, estrous cycle number at first mating, and flush feeding before first mating. The result shows that all the factors mentioned above were significantly associated with reproductive performance and retention rates of the first 2 parities. Farm 3 had more piglets born alive per litter (BA) (P < 0.05). Farms 3 and 4 had more healthy piglets per litter (HP) (P < 0.05). Farm 4 had the most piglets weaned per litter (PW) (P < 0.05). Landrace × Landrace × Yorkshire (L × L × Y) replacement gilts had the most total piglets born per litter (TB), BA, HP, PW and a higher retention rate of the 2 parities than Landrace × Yorkshire (L × Y) replacement gilts (P < 0.05). In addition, flush feeding before first mating had the most TB, BA, HP, PW, and a higher retention rate of the 2 parities than no flush feeding (P < 0.05). Because the effects of replacement gilts rearing parameters on reproductive performance traits differed, we used 100 replacement gilts as a unit and the total number of weaned piglets from the first 2 parities as a new index. Replacement gilts undergoing their first estrus between 180 and 210 d of age at 115 to 124.9 kg BW and 14 to 15 mm BF had significantly higher reproductive indexes for their first 2 parities per 100 replacement gilts. Replacement gilts that mated between 210 and 230 d of age at 140 to 149.9 kg BW and 15 to 16 mm BF had optimal reproductive indexes. These results provide a new insight into the complex relationships among these reproductive performance traits and may help guide successful management of replacement gilts as a pivotal starting point for future fertility and longevity of rearing herds.

Effect of Enrichment Items on the Physiology and Behavior of Sows in the Third Trimester of Pregnancy.

Modern intensive pig breeding harms animal welfare, which is especially noticeable for pregnant sows kept in confinement stalls. This study aimed to evaluate the effects of enrichment items on the movement and physiological parameters of sows in the third trimester of pregnancy. A total of 30 large white pregnant sows were randomly divided into three equal treatment groups (n = 10): control, pine wood, and scented wood groups. Interestingly, compared with the control group, the sows in the pine wood or scented wood groups showed less ventral lying and more lateral lying behavior (p < 0.01), coupled with significant reduction in the frequency of scratching and sham-chewing (p < 0.01), but with no significant difference in the degree of preference for these enrichment items (p > 0.05). Additionally, the sows in the pine wood or scented wood groups also decreased significantly in the concentration of immunoglobulin A (IgA) (p < 0.01) and the concentration of tumor necrosis factor-α (TNF-α) (p < 0.05) throughout the late pregnancy period. Overall, adding enrichment items to confinement stalls can alleviate the chronic stress and the stereotypic behavior of sows, suggesting their potential to reduce welfare compromise.

Identifying Candidate Genes for Short Gestation Length Trait in Chinese Qingping Pigs by Whole-Genome Resequencing and RNA Sequencing.

Gestation length is a complex polygenic trait that affects pig fetal development. The Qingping (QP) pig, a Chinese native black pig breed, is characterized by short gestation length. However, the genetic architecture of short gestation length is still not clear. The present study aimed to explore the genetic architecture of short gestation length in QP pigs. In this study, selective sweep analyses were performed to detect selective sweep signatures for short gestation length traits between 100 QP pigs and 219 pigs from 15 other breeds. In addition, differentially expressed genes for the short gestation length between QP pigs and Large White pigs were detected by RNA sequencing. Comparing candidate genes from these methods with known genes for preterm birth in the database, we obtained 111 candidate genes that were known preterm birth genes. Prioritizing other candidate genes, 839 novel prioritized candidate genes were found to have significant functional similarity to preterm birth genes. In particular, we highlighted EGFR, which was the most prioritized novel candidate relative to preterm birth genes. Experimental validations in placental and porcine trophectoderm cells suggest that EGFR is highly expressed in the QP pigs with short gestation length and could regulate the NF-κΒ pathway and downstream expression of PTGS2. These findings comprehensively identified candidate genes for short gestation length trait at the genomic and transcriptomic levels. These candidate genes provide an important new resource for further investigation and genetic improvement of gestation length.

A Whole Genome Sequencing-Based Genome-Wide Association Study Reveals the Potential Associations of Teat Number in Qingping Pigs.

Teat number plays an important role in the reproductive performance of sows and the growth of piglets. However, the quantitative trait loci (QTLs) and candidate genes for the teat number-related traits in Qingping pigs remain unknown. In this study, we performed GWAS based on whole-genome single-nucleotide polymorphisms (SNPs) and insertions/deletions (Indels) for the total number of teats and five other related traits in 100 Qingping pigs. SNPs and Indels of all 100 pigs were genotyped using 10× whole genome resequencing. GWAS using General Linear Models (GLM) detected a total of 28 SNPs and 45 Indels as peak markers for these six traits. We also performed GWAS for the absolute difference between left and right teat number (ADIFF) using Fixed and random model Circulating Probability Unification (FarmCPU). The most strongly associated SNP and Indel with a distance of 562,788 bp were significantly associated with ADIFF in both GLM and FarmCPU models. In the 1-Mb regions of the most strongly associated SNP and Indel, there were five annotated genes, including TRIML1, TRIML2, ZFP42, FAT1 and MTNR1A. We also highlighted TBX3 as an interesting candidate gene for SSC14. Enrichment analysis of candidate genes suggested the Wnt signaling pathway may contribute to teat number-related traits. This study expanded significant marker-trait associations for teat number and provided useful molecular markers and candidate genes for teat number improvement in the breeding of sows.

miR-132-3p Modulates DUSP9-Dependent p38/JNK Signaling Pathways to Enhance Inflammation in the Amnion Leading to Labor.

Labor is a process of inflammation and hormonal changes involving both fetal and maternal compartments. MicroRNA-132-3p (miR-132-3p) has been reported to be involved in the development of inflammation-related diseases. However, little is known about its potential role in labor onset. This study aimed to explore the mechanism of miR-132-3p in amnion for labor initiation. In the mouse amnion membranes, the expression of miR-132-3p was found to increase gradually during late gestation. In human amniotic epithelial cell line (WISH), upregulation of miR-132-3p was found to increase proinflammatory cytokines and cyclooxygenase 2 (COX2) as well as prostaglandin E2 (PGE2), which was suppressed by miR-132-3p inhibitor. Dual-specificity phosphatase 9 (DUSP9) was identified as a novel target gene of miR-132-3p, which could be negatively regulated by miR-132-3p. DUSP9 was present in the mouse amnion epithelial cells, with a decrease in its abundance at 18.5 days post coitum (dpc) relative to 15.5 dpc. Silencing DUSP9 was found to facilitate the expression of proinflammatory cytokines and COX2 as well as PGE2 secretion in WISH cells, which could be attenuated by p38 inhibitor SB203580 or JNK inhibitor SP600125. Additionally, intraperitoneal injection of pregnant mice with miR-132-3p agomir not only caused preterm birth, but also promoted the abundance of COX2 as well as phosphorylated JNK and p38 levels, and decreased DUSP9 level in mouse amnion membranes. Collectively, miR-132-3p might participate in inflammation and PGE2 release via targeting DUSP9-dependent p38 and JNK signaling pathways to cause preterm birth.

Glucocorticoid Regulates the Synthesis of Porcine Muscle Protein through m6A Modified Amino Acid Transporter SLC7A7.

The occurrence of stress is unavoidable in the process of livestock production, and prolonged stress will cause the decrease of livestock productivity. The stress response is mainly regulated by the hypothalamic-pituitary-adrenal axis (HPA axis), which produces a large amount of stress hormones, namely glucocorticoids (GCs), and generates a severe impact on the energy metabolism of the animal body. It is reported that m6A modification plays an important role in the regulation of stress response and also participates in the process of muscle growth and development. In this study, we explored the effect of GCs on the protein synthesis procession of porcine skeletal muscle cells (PSCs). We prove that dexamethasone affects the expression of SLC7A7, a main amino acid transporter for protein synthesis by affecting the level of m6A modification in PSCs. In addition, we find that SLC7A7 affects the level of PSC protein synthesis by regulating the conduction of the mTOR signaling pathway, which indicates that the reduction of SLC7A7 expression may alleviate the level of protein synthesis under stress conditions.

Circulating Exosomal miR-221 from Maternal Obesity Inhibits Angiogenesis via Targeting Angptl2.

Maternal obesity disrupts both placental angiogenesis and fetus development. However, the links between adipocytes and endothelial cells in maternal obesity are not fully understood. The aim of this study was to characterize exosome-enriched miRNA from obese sow's adipose tissue and evaluate the effect on angiogenesis of endothelial cells. Plasma exosomes were isolated and analyzed by nanoparticle tracking analysis (NTA), electron morphological analysis, and protein marker expression. The number of exosomes was increased as the gestation of the sows progressed. In addition, we found that exosomes derived from obese sows inhibited endothelial cell migration and angiogenesis. miRNA detection showed that miR-221, one of the miRNAs, was significantly enriched in exosomes from obese sows. Further study demonstrated that exosomal miR-221 inhibited the proliferation and angiogenesis of endothelial cells through repressing the expression of Angptl2 by targeting its 3' untranslated region. In summary, miR-221 was a key component of the adipocyte-secreted exosomal vesicles that mediate angiogenesis. Our study may be a novel mechanism showing the secretion of "harmful" exosomes from obesity adipose tissues causes placental dysplasia during gestation.

Insights into the Interaction of Lysosomal Amino Acid Transporters SLC38A9 and SLC36A1 Involved in mTORC1 Signaling in C2C12 Cells.

Amino acids are critical for mammalian target of rapamycin complex 1 (mTORC1) activation on the lysosomal surface. Amino acid transporters SLC38A9 and SLC36A1 are the members of the lysosomal amino acid sensing machinery that activates mTORC1. The current study aims to clarify the interaction of SLC38A9 and SLC36A1. Here, we discovered that leucine increased expressions of SLC38A9 and SLC36A1, leading to mTORC1 activation. SLC38A9 interacted with SLC36A1 and they enhanced each other's expression levels and locations on the lysosomal surface. Additionally, the interacting proteins of SLC38A9 in C2C12 cells were identified to participate in amino acid sensing mechanism, mTORC1 signaling pathway, and protein synthesis, which provided a resource for future investigations of skeletal muscle mass.

Identification of amino acid response element of SLC38A9 as an ATF4-binding site in porcine skeletal muscle cells.

Amino acids can affect protein synthesis by activating mammalian target of rapamycin complex 1 (mTORC1) signaling pathway. Amino acid transporters SLC38A9 on the lysosomal membrane not only transport amino acids, but also can sense amino acids and activate mTORC1 signaling pathway. Activating transcription factor 4 (ATF4) can promote the expression of amino acid transporters by binding with amino acid response element (AARE). In this study, two AAREs were found in the SLC38A9 promoter region of pig, and both of them bound to ATF4. The AARE in the first intron was located in the core promoter region of SLC38A9. ATF4 regulated mRNA expression level of SLC38A9 in porcine skeletal muscle cells. In the absence of amino acids, the expression of ATF4 decreased and the expression of SLC38A9 increased. After leucine addition, the expression levels of ATF4 and SLC38A9 increased. It suggested that in the absence of amino acids, the expression of SLC38A9 was increased via binding of ATF4 to AARE binding factors in SLC38A9 promoter fragment; after the addition of leucine, ATF4 was activated, resulting in the increase of SLC38A9 expression.

Partial Deficiency of Zfp217 Resists High-Fat Diet-Induced Obesity by Increasing Energy Metabolism in Mice.

Obesity-induced adipose tissue dysfunction and disorders of glycolipid metabolism have become a worldwide research priority. Zfp217 plays a crucial role in adipogenesis of 3T3-L1 preadipocytes, but about its functions in animal models are not yet clear. To explore the role of Zfp217 in high-fat diet (HFD)-induced obese mice, global Zfp217 heterozygous knockout (Zfp217+/-) mice were constructed. Zfp217+/- mice and Zfp217+/+ mice fed a normal chow diet (NC) did not differ significantly in weight gain, percent body fat mass, glucose tolerance, or insulin sensitivity. When challenged with HFD, Zfp217+/- mice had less weight gain than Zfp217+/+ mice. Histological observations revealed that Zfp217+/- mice fed a high-fat diet had much smaller white adipocytes in inguinal white adipose tissue (iWAT). Zfp217+/- mice had improved metabolic profiles, including improved glucose tolerance, enhanced insulin sensitivity, and increased energy expenditure compared to the Zfp217+/+ mice under HFD. We found that adipogenesis-related genes were increased and metabolic thermogenesis-related genes were decreased in the iWAT of HFD-fed Zfp217+/+ mice compared to Zfp217+/- mice. In addition, adipogenesis was markedly reduced in mouse embryonic fibroblasts (MEFs) from Zfp217-deleted mice. Together, these data indicate that Zfp217 is a regulator of energy metabolism and it is likely to provide novel insight into treatment for obesity.

Glucocorticoid Receptor Alpha Targets SLC2A4 to Regulate Protein Synthesis and Breakdown in Porcine Skeletal Muscle Cells.

In the presence of stress, the hypothalamic-pituitary-adrenal (HPA) axis activity can be enhanced to promote the secretion of a large amount of glucocorticoids (GCs), which play an important role in the anabolism and catabolism of skeletal muscle. When the endogenous and exogenous glucocorticoids are deficient or excessive, the body will produce stress-related resistance and change the protein metabolism. In this study, we investigated the effect of GC receptor GRα on protein breakdown and synthesis in porcine skeletal muscle cells (PSCs). Overexpression of GRα was shown to increase the expression of protein degradation-related genes, while knockdown of GRα decreased the expression of these genes. Additionally, we found a relationship between GRα and solute carrier family 2 member 4 (SLC2A4), SLC2A4 expression level increases when stress occurs, suggesting that increasing SLC2A4 expression can partially alleviate stress-induced damage, and we found that there is a combination between them via luciferase reporter assays, which still needs to be confirmed in further studies.

Gut Microbiological Disorders Reduce Semen Utilization Rate in Duroc Boars.

Although rising evidence suggests that the gut microbiota is closely related to host health, the effects of gut microbiota on male fertility are still rarely explored. This study was to investigate the gut microbiota composition and function, fecal short-chain fatty acids (SCFA), intestinal permeability, and systemic inflammatory status of Duroc boar with high (H group, 100%) and low (L group, <80%) semen utilization rate. Fecal samples, analyzed by 16S ribosomal RNA gene sequencing, displayed taxonomic and functional changes between boars with high and low semen utilization rates. For the gut microbiota composition of the boars, four genera were different between the two groups. The [Ruminococcus] and Sphingobium were enriched in L group boars, then negatively correlated with the semen utilization rate. While RFN20 and Paludibacter were enhanced in the H group, only RFN20 showed a significantly positive correlation with the semen utilization rate of boars. In addition, changes in the metabolic function of the gut microbiota of the two groups were found, including altered branched-chain fatty acid (BCFA) production. Significant increases in plasma endotoxin, zonulin, diamine oxidase, and lipocalin-2 levels were observed in boars with low semen utilization, and also, a similar trend in IL-6 and TNF-α was found. However, the concentration of IL-10 in plasma of boars with high semen utilization rate showed an increasing tendency. These results indicated increased intestinal permeability and systemic inflammation in boars with low semen utilization. Data showed that the composition and functions of gut microbiota varied between boars with high or low semen utilization rates, while the semen utilization rate is notably correlated with the gut microbiota composition, intestinal permeability, and inflammatory status of the boar.

Novel Insights into Adipogenesis from the Perspective of Transcriptional and RNA N6-Methyladenosine-Mediated Post-Transcriptional Regulation.

Obesity is a critical risk factor causing the development of metabolic diseases and cancers. Its increasing prevalence worldwide has aroused great concerns of the researchers on adipose development and metabolic function. During adipose expansion, adipogenesis is a way to store lipids as well as to avoid lipotoxicity in other tissues, and may be an approach to offset the negative metabolic effects of obesity. In this Review, the transcriptional regulation of adipogenesis is outlined to characterize numerous biological processes in research on the determination of adipocyte fate and regulation of adipogenic differentiation. Notably, one of the post-transcriptional modifications of mRNA, namely, N6-methyladenosine (m6A), has been recently found to play a role in adipogenesis. Here, the roles of m6A-related enzymes and proteins in adipogenesis, with a particular focus on how these m6A-related proteins function at different stages of adipogenesis, are mainly discussed. The Review also highlights the coordination role of the transcriptional and post-transcriptional (RNA m6A methylation) regulation in adipogenesis and related biological processes. In this context, a better understanding of adipogenesis at both the transcriptional and post-transcriptional levels may facilitate the development of novel strategies to improve metabolic health in obesity.

The transcriptomes from two adipocyte progenitor cell types provide insight into the differential functions of MSTN.

Myostatin (MSTN) was previously shown to differentially regulate the adipogenesis of adipose-derived stem cells (ADSCs) and muscle satellite cells (MSCs), both of which can serve as progenitor cells for intramuscular adipocytes. We previously showed that MSTN mediates the differential regulation of MyoD and PPARγ in ADSCs and MSCs. Here, we analyzed the effects of MSTN on whole-transcriptome expression profiles of ADSCs and MSCs, revealing that MSTN differentially regulates ADSCs and MSCs, with MSCs being more responsive to MSTN treatment. More genes and pathways were altered in MSCs than in ADSCs. These changes may be responsible for the differences in the adipogenesis potential of ADSCs and MSCs after MSTN treatment. Analysis of the functions of genes that are differentially expressed in ADSCs and MSCs showed that KLF6 is a positive regulator of adipogenesis. In conclusion, the results provide important molecular insights into the regulatory mechanisms of MSTN in ADSCs and MSCs.