Integrated analysis of intestinal microbial community and muscle transcriptome profile in rabbits.

Intestinal microbial community plays an important part in maintaining health and skeletal muscle development in livestock. This study is the first of its kind in the world. In order to better understand the relationship between gut microbiota and gene expression in skeletal muscle of rabbits, caecum contents and longissimus dorsi tissues of rabbits at 0 d (S1), 35 d (S2) and 70d (S3) were collected and subjected for 16S rRNA sequencing and transcriptome sequencing. Our results showed that, among three groups of rabbits, Firmicutes and Bacteroidetes were the dominant phyla at the phylum level, while Akmansia, Bacteroides and Ruminobacter were the dominant genera at the genus level, and the relative abundance of Akmansia and Bacteroides increased firstly and then decreased from 0 d to 70 d. By analyzing the transcriptome sequencing data, we identified 2866, 2446 and 4541 differentially expressed genes (DEGs) in S1 vs S2, S2 vs S3 and S1 vs S3 groups, respectively. Finally, we performed correlation analysis between gut microbiota and the expression levels of muscle development-related genes of rabbits at 0 d and 70 d. Compared with 0 day old rabbits, in 70 day old rabbits Acinetobacter and Cronbacter with decreased abundance, and Ruminococcaceae_UCG-014 and Ruminococcus_1 with increase abundance is beneficial to caecum health in rabbits. These results will lay a foundation for further re-searches about the relationship between caecum microflora and muscle development in rabbits.

NEDD8 enhances Hippo signaling by mediating YAP1 neddylation.

The Hippo-YAP signaling pathway plays a central role in many biological processes such as regulating cell fate, organ size, and tissue growth, and its key components are spatiotemporally expressed and posttranslationally modified during these processes. Neddylation is a posttranslational modification that involves the covalent attachment of NEDD8 to target proteins by NEDD8-specific E1-E2-E3 enzymes. Whether neddylation is involved in Hippo-YAP signaling remains poorly understood. Here, we provide evidence supporting the critical role of NEDD8 in facilitating the Hippo-YAP signaling pathway by mediating neddylation of the transcriptional coactivator yes-associated protein 1 (YAP1). Overexpression of NEDD8 induces YAP1 neddylation and enhances YAP1 transactivity, but inhibition of neddylation suppresses YAP1 transactivity and attenuates YAP1 nuclear accumulation. Furthermore, inhibition of YAP1 signaling promotes MLN4924-induced ovarian granulosa cells apoptosis and disruption of nedd8 in zebrafish results in downregulation of yap1-activated genes and upregulation of yap1-repressed genes. Further assays show that the xiap ligase promotes nedd8 conjugates to yap1 and that yap1 neddylation. In addition, we identify lysine 159 as a major neddylation site on YAP1. These findings reveal a novel mechanism for neddylation in the regulation of Hippo-YAP signaling.

Double-Sided Bonding Process Enables X-ray Flat Panel Detectors.

Metal halide perovskites have demonstrated superior sensitivity, lower detection limits, stability, and exceptional photoelectric properties in comparison to existing commercially available X-ray detector materials, showing their potential for shaping the next generation of X-ray detectors. Nevertheless, significant challenges persist in the seamless integration of these materials into pixelated array sensors for large-area X-ray direct detection imaging. In this article, we propose a strategy for fabricating large-scale array devices using a double-sided bonding process. The approach involves depositing a wet film on the surface of a thin-film transistor substrate to establish a robust bond between the substrate and δ-CsPbI3 wafer via van der Waals force, thereby facilitating area-array imaging. Additionally, the freestanding polycrystalline δ-CsPbI3 wafer demonstrated a competitive ultralow detection limit of 3.46 nGyair s-1 under 50 kVP X-ray irradiation, and the δ-CsPbI3 wafer still maintains a stable signal output (signal current drift is 3.5 × 10-5 pA cm-1 s-1 V-1) under the accumulated radiation dose of 234.9 mGyair. This strategy provides a novel perspective for the industrial production of large-area X-ray flat panel detectors utilizing perovskites and their derivatives.

Supplementation of sodium acetate improves the growth performance and intestinal health of rabbits through Wnt/ß-catenin signaling pathway.

Acetic acid, which is one of the most abundant short-chain fatty acids (SCFA) in rabbits' cecum, has been reported to play an important function during various physiological metabolic processes. The present study was conducted to elucidate the effects of sodium acetate on growth performance and intestinal health by evaluating feed intake and efficiency, diarrhea score, serum and cecum metabolites, cecal pH and SCFA, histological staining, nutritional composition of meat and gene expression profile of cecum in rabbits. As a result of sodium acetate supplement, the feed conversion ratio, diarrhea score, and diameter of muscle fiber were significantly decreased (P < 0.05). Additionally, dietary sodium acetate significantly increased in total area of muscle fibers and content of crude ash (P < 0.05). Dietary sodium acetate significantly increased serum glucose, total bile acid, and total cholesterol levels and decreased amylase, lipase, and tCO2 content (P < 0.05). Further examination suggested that sodium acetate supplementation enhanced the micro-environment of cecum, evidenced by significantly increased levels of total antioxidant capacity, total superoxide dismutase, and glutathione peroxidase, and decreased pH and amylase levels (P < 0.05). According to transcriptome sequencing of cecal tissues, differentially expressed genes were predominantly enriched in cell cycle, ABC transporters, and chemokine signaling pathways. Sodium acetate was further suggested to stimulate the proliferation and migration of rabbits' cecum epithelial cells by activating Wnt/ß-catenin pathway both in vivo and in vitro. In conclusion, dietary sodium acetate supplementation improved growth performance and intestinal health in rabbits.

Acetate plays a significant role in modulating production performance of animals. This study shows that sodium acetate supplementation in diet enhances rabbit growth performance by improving intestinal health and stimulating cecum epithelial cell proliferation. The supporting evidence suggests that sodium acetate significantly reduced the feed conversion ratio and diarrhea score in rabbits, while also enhancing the cecum's resistance to oxidative stress. Sodium acetate improves meat quality to some extent, as reflected in an increase total area of muscle fibers and content of crude ash. Sodium acetate was further suggested to stimulate the proliferation and migration of rabbits' cecum epithelial cells by activating Wnt/ß-catenin pathways both in vivo and in vitro. In conclusion, these findings suggest dietary sodium acetate is a useful additive for rabbit production.

Comparative Genome-Wide Alternative Splicing Analysis between Preadipocytes and Adipocytes.

Alternative splicing is a ubiquitous regulatory mechanism in gene expression that allows a single gene to generate multiple messenger RNAs (mRNAs). Adipocyte development is regulated by many processes, and recent studies have found that splicing factors also play an important role in adipogenic development. In the present study, we further investigated the differences in selective shearing during different periods of adipocyte differentiation. We identified five alternative splicing types including skipped exon, mutually exclusive exon, Alternative 5' splice site, Alternative 3' splice site, and Retained intron, with skipped exons being the most abundant type of selective shearing. In total, 641 differentially expressed selective shearing genes were obtained, enriched in 279 pathways, from which we selected and verified the accuracy of the sequencing results. Overall, RNA-seq revealed changes in the splicing and expression levels of these new candidate genes between precursor adipocytes and adipocytes, suggesting that they may be involved in adipocyte generation and differentiation.

SOX6 AU controls myogenesis by cis-modulation of SOX6 in cattle.

Long non-coding RNAs (lncRNAs) have been shown to be involved in the regulation of skeletal muscle development through multiple mechanisms. The present study revealed that the lncRNA SOX6 AU (SRY-box transcription factor 6 antisense upstream) is reverse transcribed from upstream of the bovine sex-determining region Y (SRY)-related high-mobility-group box 6 (SOX6) gene. SOX6 AU was significantly differentially expressed in muscle tissue among different developmental stages in Xianan cattle. Subsequently, knockdown and overexpression experiments discovered that SOX6 AU promoted primary skeletal muscle cells proliferation, apoptosis, and differentiation in bovine. The overexpression of SOX6 AU in bovine primary skeletal muscle cells resulted in 483 differentially expressed genes (DEGs), including 224 upregulated DEGs and 259 downregulated DEGs. GO functional annotation analysis showed that muscle development-related biological processes such as muscle structure development and muscle cell proliferation were significantly enriched. KEGG pathway analysis revealed that the PI3K/AKT and MAPK signaling pathways were important pathways for DEG enrichment. Notably, we found that SOX6 AU inhibited the mRNA and protein expression levels of the SOX6 gene. Moreover, knockdown of the SOX6 gene promoted the proliferation and apoptosis of bovine primary skeletal muscle cells. Finally, we showed that SOX6 AU promoted the proliferation and apoptosis of bovine primary skeletal muscle cells by cis-modulation of SOX6 in cattle. This work illustrates our discovery of the molecular mechanisms underlying the regulation of SOX6 AU in the development of beef.

Designing Surface Passivators Through Intramolecular Potential Manipulation for Efficient and Stable Perovskite Solar Cells.

The conjugation of terminal ammonium salt groups with perovskite surfaces is a frequently employed technique that aims to enhance the overall performance of perovskite materials, encompassing both bulk and surface properties. Particularly, it exhibits heightened efficacy when applied to surface modification, due to its ability to mitigate defect accumulation and facilitate facile binding with the receptive sites inherent to the perovskite structure. However, the interaction of the bulk ammonium group with PbI2 has the potential to form a low-dimensional phase of perovskite, which may obstruct carrier extraction at the interface. Therefore, the surface passivators (MeO-PFACl) are designed through intramolecular potential manipulation. The combinations of the electron-donating methoxy group and π-π conjugation of the phenyl ring reduce the local potential at the reactive site of formamidinium group, making it less likely to form a low-dimension phase with perovskite. This surface passivation strategy effectively suppresses the surface nonradiative recombination and promotes the interface carrier extraction. The devices treated with MeO-PFACl have demonstrated exceptional performance, achieving a peak power conversion efficiency (PCE) of 25.88%, with an average PCE of 25.37%. These works offer a novel principle for enhancing both the efficiency and stability of PSCs using ammonium-incorporated molecules without the induction of an additional phase layer.

LncRNA BlncAD1 Modulates Bovine Adipogenesis by Binding to MYH10, PI3K/Akt Signaling Pathway, and miR-27a-5p/CDK6 Axis.

Research on adipogenesis will help to improve the meat quality of livestock. Long noncoding RNAs (lncRNAs) are involved in mammalian adipogenesis as epigenetic modulators. In this study, we analyzed lncRNA expression during bovine adipogenesis and detected 195 differentially expressed lncRNAs, including lncRNA BlncAD1, which was significantly upregulated in mature bovine adipocytes. Gain- and loss-of-function experiments confirmed that BlncAD1 promoted the proliferation, apoptosis, and differentiation of bovine preadipocytes. RNA pull-down revealed that the nonmuscle myosin 10 (MYH10) is a potential binding protein of BlncAD1. Then, we elucidated that loss of BlncAD1 caused increased ubiquitination of MYH10, which confirmed that BlncAD1 regulates adipogenesis by enhancing the stability of the MYH10 protein. Western blotting was used to demonstrate that BlncAD1 activated the PI3K/Akt signaling pathway. Bioinformatic analysis and dual-luciferase reporter assays indicated that BlncAD1 competitively absorbed miR-27a-5p. The overexpression and interference of miR-27a-5p in bovine preadipocytes displayed that miR-27a-5p inhibited proliferation, apoptosis, and differentiation. Further results suggested that miR-27a-5p targeted the CDK6 gene and that BlncAD1 controlled the proliferation of bovine preadipocytes by modulating the miR-27a-5p/CDK6 axis. This study revealed the complex mechanisms of BlncAD1 underlying bovine adipogenesis for the first time, which would provide useful information for genetics and breeding improvement of Chinese beef cattle.

Novel mechanism of Clostridium butyricum alleviated coprophagy prevention-induced intestinal inflammation in rabbit.

As bacteria synthesize nutrients primarily in the cecum, coprophagy is indispensable for supplying rabbits with essential nutrients. Recent research has demonstrated its pivotal role in maintaining intestinal microbiota homeostasis and immune regulation in rabbits, although the specific mechanism remains unknown. Here, we used coprophagy prevention (CP) to investigate the effects of coprophagy on the cecum homeostasis and microbiota in New Zealand white rabbits. Furthermore, whether supplementation of Clostridium butyricum (C. butyricum) may alleviate the cecum inflammation and apoptosis caused by CP was also explored. Four groups were randomly assigned: control (Con), sham-coprophagy prevention (SCP), coprophagy prevention (CP), and CP and C. butyricum addition (CPCB). Compared to Con and SCP, CP augmented cecum inflammation and apoptosis, as well as bacterial adhesion to the cecal epithelial mucosa, while decreasing the expression of tight junction proteins (ZO-1, occluding, and claudin-1). The relative abundance of short-chain fatty acids (SCFAs)-producing bacteria was significantly decreased in the CP group. Inversely, there was an increase in the Firmicutes/Bacteroidetes ratio and the relative abundance of Christensenellaceae_R-7_group. Additionally, CP increased the levels of Flagellin, IFN-γ, TNF-a, and IL-1ß in cecum contents and promoted the expression of TLR5/MyD88/NF-κB pathway in cecum tissues. However, the CPCB group showed significant improvements in all parameters compared to the CP group. Dietary C. butyricum supplementation significantly increased the production of SCFAs, particularly butyric acid, triggering anti-inflammatory, tissue repairing, and barrier-protective responses. Notably, CPCB effectively mitigated CP-induced apoptosis and inflammation. In summary, CP disrupts the cecum epithelial barrier and induces inflammation in New Zealand white rabbits, but these effects can be alleviated by C. butyricum supplementation. This process appears to be largely associated with the TLR5/MyD88/NF-κB signaling pathway.

Copy number variations within fibroblast growth factor 13 gene influence growth traits and alternative splicing in cattle.

Previous researches revealed a copy number variation (CNV) region in the bovine fibroblast growth factor 13 (FGF13) gene. However, its effects remain unknown. This study detected the various copy number types in seven Chinese cattle breeds and analysed their population genetic characteristics and effects on growth traits and transcription levels. Copy number Loss was more frequent in Caoyuan Red cattle and Xianan cattle than in the other breeds. Association analysis between CNV and growth traits of Qinchuan indicated that the CNV was significantly related to chest depth, hip width and hucklebone width (P < 0.05). Additionally, the growth traits of individuals with copy number Loss were significantly inferior to those with copy number Gain or Median (P < 0.05). Besides, we found two splicing isoforms, AS1 and AS2, in FGF13 gene, which resulted from alternative 5' splicing sites of intron 1. These isoforms showed varied expression levels in various tissues. Moreover, CNV was significantly and negatively associated with the mRNA expression of AS1 (r = -0.525, P < 0.05). The CNVs in bovine FGF13 gene negatively regulated growth traits and gene transcription. These observations provide new insights into bovine FGF13 gene, delivering potentially useful information for future Chinese cattle breeding programs.

Integrated analysis reveals the regulatory mechanism of the neddylation inhibitor MLN4924 on the metabolic dysregulation in rabbit granulosa cells.

BACKGROUND: Neddylation, an important post-translational modification (PTM) of proteins, plays a crucial role in follicular development. MLN4924 is a small-molecule inhibitor of the neddylation-activating enzyme (NAE) that regulates various biological processes. However, the regulatory mechanisms of neddylation in rabbit ovarian cells have not been emphasized. Here, the transcriptome and metabolome profiles in granulosa cells (GCs) treated with MLN4924 were utilized to identify differentially expressed genes, followed by pathway analysis to precisely define the altered metabolisms. RESULTS: The results showed that 563 upregulated and 910 downregulated differentially expressed genes (DEGs) were mainly enriched in pathways related to cancer, cell cycle, PI3K-AKT, progesterone-mediated oocyte maturation, and PPAR signaling pathway. Furthermore, we characterized that MLN4924 inhibits PPAR-mediated lipid metabolism, and disrupts the cell cycle by promoting the apoptosis and proliferation of GCs. Importantly, we found the reduction of several metabolites in the MLN4924 treated GCs, including glycerophosphocholine, arachidic acid, and palmitic acid, which was consistent with the deregulation of PPAR signaling pathways. Furthermore, the increased metabolites included 6-Deoxy-6-sulfo-D-glucono-1,5-lactone and N-Acetyl-D-glucosaminyldiphosphodolichol. Combined with transcriptome data analyses, we identified genes that strongly correlate with metabolic dysregulation, particularly those related to glucose and lipid metabolism. Therefore, neddylation inhibition may disrupt the energy metabolism of GCs. CONCLUSIONS: These results provide a foundation for in-depth research into the role and molecular mechanism of neddylation in ovary development.

Clostridium butyricum Ameliorates the Effect of Coprophagy Prevention on Hepatic Lipid Synthesis in Rabbits via the Gut-Liver Axis.

Coprophagy prevention (CP) affects the growth performance, hepatic lipid synthesis, and gut microbiota in rabbits. Supplementation with Clostridium butyricum (C. butyricum, Strain number: CCTCC M 2019962) has been found to improve growth performance in rabbits. However, it remains unknown whether C. butyricum can ameliorate the effects of CP on hepatic lipid synthesis and the underlying mechanisms are yet to be elucidated. Therefore, this study aimed to investigate the impact of CP on hepatic lipid synthesis and the underlying mechanism based on the gut-liver axis. The findings revealed that supplementation with C. butyricum could reverse CP-related growth performance, lipid accumulation, bile acid synthesis, and inflammation. Furthermore, C. butyricum exerted protective effects on the gut by preserving intestinal barrier integrity and modulating gut microbiota composition; these factors may represent potential mechanisms through which C. butyricum improves CP-related outcomes. Specifically, C. butyricum reshaped the microbiota by increasing butyric acid levels, thereby maintaining secondary bile acid (deoxycholic acid, chenodeoxycholic acid) balance and attenuating the inhibitory effects of the FXR/SHP pathway on lipid synthesis (SREBP1c/ApoA1). Moreover, the activation of butyrate/GPR43pathway by C. butyricum reduced damage to the intestinal barrier (ZO-1/Occludin/Claudin1) and restored the gut immune microenvironment in CP rabbits. In summary, supplementation with C. butyricum can alleviate the adverse effects of CP on growth performance and hepatic lipid synthesis by modulating the gut-liver axis.

Homogenizing out-of-plane cation composition in perovskite solar cells.

Perovskite solar cells with the formula FA1-xCsxPbI3, where FA is formamidinium, provide an attractive option for integrating high efficiency, durable stability and compatibility with scaled-up fabrication. Despite the incorporation of Cs cations, which could potentially enable a perfect perovskite lattice1,2, the compositional inhomogeneity caused by A-site cation segregation is likely to be detrimental to the photovoltaic performance of the solar cells3,4. Here we visualized the out-of-plane compositional inhomogeneity along the vertical direction across perovskite films and identified the underlying reasons for the inhomogeneity and its potential impact for devices. We devised a strategy using 1-(phenylsulfonyl)pyrrole to homogenize the distribution of cation composition in perovskite films. The resultant p-i-n devices yielded a certified steady-state photon-to-electron conversion efficiency of 25.2% and durable stability.

Accelerated Apoptosis and Down-Regulated FMRP in Human Neuroblastoma Cells with CRISPR/Cas9 Genome Editing.

Background: Fragile X syndrome (FXS) is a genetic disease with intellectual disabilities. FXS is often caused by the CGG-repeat expansion mutation in the FMR1 gene with suppressed FMR1 transcription and decreased protein levels in the brain of the patients. The RNA-guided CRISPR/Cas9 system is a promising targeted genomic editing tool in gene therapy of FXS. In order to evaluate its feasibility, the present study used CRISPR/Cas9 system to target the FMR1 5'-UTR sites in cultured human neuroblastoma cells. Methods: PCR and DNA clone were used to construct plasmids. CRISPR function was tested by Western blot and flow cytometry. Data were analyzed by a two-tailed unpaired Student's t-test using GraphPad software. This research was conducted from 2020 to 2022 in the Second Affiliated Hospital of Soochow University, Suzhou, China. Results: Cell cycle analysis showed significant differences in G1, S and G2/M phases between the two groups (P<0.05). In the knockout cells, apoptosis was accelerated (P<0.05) with a significantly down-regulated (P<0.05) expression of FMRP as compared with the control group. Conclusion: This study provides further understanding about the FMRP function and molecular mechanism of FMR1 gene in nerve cells, and suggests the feasibility of gene therapy in FXS by CRISPR/Cas9 gene editing system.

Supple Formamidinium-Based Low-Dimension Perovskite Derivative for Sensitive and Ultrastable X-ray Detection.

Halide perovskite materials possess excellent optoelectronic properties and have shown great potential for direct X-ray detection. Perovskite wafers are particularly attractive among various detection structures due to their scalability and ease of preparation, making them the most promising candidates for X-ray detection and array imaging applications. However, device instability and current drift caused by ionic migration are persistent challenges for perovskite detectors, especially in polycrystalline wafers with numerous grain boundaries. In this study, we examined the potential of one-dimensional (1D) δ-phase (yellow phase) formamidinium lead iodide (δ-FAPbI3) as an X-ray detection material. This material possesses a suitable band gap of 2.43 eV, which makes it highly promising for X-ray detection and imaging using compact wafers. Moreover, we found that δ-FAPbI3 has low ionic migration, low Young's modulus, and excellent long-term stability, making it an ideal candidate for high-performance X-ray detection. Notably, the yellow phase perovskite derivative exhibits exceptional long-term atmospheric stability (RH of ≈70 ± 5%) over six months, as well as an extremely low dark current drift (3.43 × 10-4 pA cm-1 s-1 V-1), which is comparable to that of single-crystal devices. An X-ray imager with a large-size δ-FAPbI3 wafer integrated on a thin film transistor (TFT) backplane was further fabricated. Direct 2D multipixel radiographic imaging was successfully performed, demonstrating the feasibility of δ-FAPbI3 wafer detectors for sensitive and ultrastable imaging applications.

Impact of coprophagy prevention on the growth performance, serum biochemistry, and intestinal microbiome of rabbits.

BACKGROUND: Coprophagy plays a vital role in maintaining growth and development in many small herbivores. Here, we constructed a coprophagy model by dividing rabbits into three groups, namely, control group (CON), sham-coprophagy prevention group (SCP), and coprophagy prevention group (CP), to explore the effects of coprophagy prevention on growth performance and cecal microecology in rabbits. RESULTS: Results showed that CP treatment decreased the feed utilization and growth performance of rabbits. Serum total cholesterol and total triglyceride in the CP group were remarkably lower than those in the other two groups. Furthermore, CP treatment destroyed cecum villi and reduced the content of short-chain fatty acids (SCFAs) in cecum contents. Gut microbiota profiling showed significant differences in the phylum and genus composition of cecal microorganisms among the three groups. At the genus level, the abundance of Oscillospira and Ruminococcus decreased significantly in the CP group. Enrichment analysis of metabolic pathways showed a significantly up-regulated differential metabolic pathway (PWY-7315, dTDP-N-acetylthomosamine biosynthesis) in the CP group compared with that in the CON group. Correlation analysis showed that the serum biochemical parameters were positively correlated with the abundance of Oscillospira, Sutterella, and Butyricimonas but negatively correlated with the abundance of Oxalobacte and Desulfovibrio. Meanwhile, the abundance of Butyricimonas and Parabacteroidesde was positively correlated with the concentration of butyric acid in the cecum. CONCLUSIONS: In summary, coprophagy prevention had negative effects on serum biochemistry and gut microbiota, ultimately decreasing the growth performance of rabbits. The findings provide evidence for further revealing the biological significance of coprophagy in small herbivorous mammals.

Bidirectional Anions Gathering Strategy Afford Efficient Mixed PbSn Perovskite Solar Cells.

Mixed lead-tin (PbSn) perovskite solar cells (PSCs) possess low toxicity and adjustable bandgap for both single-junction and all-perovskite tandem solar cells. However, the performance of mixed PbSn PSCs still lags behind the theoretical efficiency. The uncontrollable crystallization and the resulting structural defect are important reasons. Here, the bidirectional anions gathering strategy (BAG) is reported by using Methylammonium acetate (MAAc) and Methylammonium thiocyanate (MASCN) as perovskite bulk additives, which Ac- escapes from the perovskite film top surface while SCN- gathers at the perovskite film bottom in the crystallization process. After the optoelectronic techniques, the bidirectional anions movement caused by the top-down gradient crystallization is demonstrated. The layer-by-layer crystallization can collect anions in the next layer and gather at the broader, enabling a controllable crystallization process, thus getting a high-quality perovskite film with better phase crystallinity and lower defect concentration. As a result, PSCs treated by the BAG strategy exhibit outstanding photovoltaic and electroluminescent performance with a champion efficiency of 22.14%. Additionally, it demonstrates excellent long-term stability, which retains ≈92.8% of its initial efficiency after 4000 h aging test in the N2 glove box.

Hyperphosphorylation of EGFR/ERK signaling facilitates long-term arsenite-induced hepatocytes epithelial-mesenchymal transition and liver fibrosis in sprague-dawley rats.

Arsenic is a well known environmental hazardous material, chronic arsenic exposure results in different types of liver damage. Among them, liver fibrosis has become a research hotspot because of its reversibility, while the underlying mechanism is still unclear. Previous studies revealed that EGFR/ERK signaling appears to play an important role in fibrosis diseases. In this study, sprague-dawley rats were exposed to different doses of arsenite for 36 weeks to investigate the roles of EGFR/ERK signaling on arsenite-induced liver fibrogenesis. Our results showed that long-term arsenite exposure induced liver fibrosis, accompanied by hepatic stellate cells (HSCs) activation, excessive serum secretion of extracellular matrix (ECM), and hepatocytes epithelial-mesenchymal transformation (EMT). In addition, arsenite exposure caused hyperphosphorylation of EGFR/ERK signaling in liver tissue of rats, indicating that EGFR/ERK signaling may be involved in arsenite-induced liver fibrosis. Indeed, erlotinib (a specific phosphorylation inhibitor of EGFR) intervention significantly decreased arsenite induced hyperphosphorylation of EGFR/ERK signaling, thereby suppressed hepatocytes EMT process and alleviated liver fibrogenesis in arsenite exposed rats. In summary, the present study provides evidences showing that hyperphosphorylation of EGFR/ERK signaling facilitates long-term arsenite-induced hepatocytes EMT and liver fibrosis in rats, which brings new insights into the pathogenesis of arsenic-induced liver injury.

Overexpression of ATGL impairs lipid droplet accumulation by accelerating lipolysis in goat mammary epithelial cells.

Adipose triglyceride lipase (ATGL) is the key enzyme for the degradation of triacylglycerols (TAGs). It functions in concert with other enzymes to mobilize TAG and supply fatty acids (FAs) for energy production. Dysregulated lipolysis leads to excess concentrations of circulating FAs, which may lead to destructive and lipotoxic effects to the organism. To understand the role of ATGL in mammary lipid metabolism, ATGL was overexpressed in goat mammary epithelial cells (GMECs) by using a recombinant adenovirus system. ATGL overexpression decreased lipid droplet (LD) accumulation and cellular TG content (p < 0.05) along with a decrease in the expression of the key enzyme that catalyzes the final step of TG synthesis (DGAT). Significant increases were observed in the expression of genes related to lipolysis (hormone-sensitive lipase [HSL]) and FA desaturation (SCD) by ATGL overexpression. Genes responsible for FA oxidation (PPARα), LD formation and secretion (ADRP and BTN1A1), and long-chain FA uptake (CD36) were all decreased by ATGL overexpression (p < 0.05). The primary products of TAG lipolysis, free FAs (FFAs), were notably increased in the ATGL-overexpressing cells. Taken together, our results demonstrated that ATGL activation impairs lipid formation partially through accelerating lipolysis in GMECs.

Microbiome-Metabolome Analysis of the Immune Microenvironment of the Cecal Contents, Soft Feces, and Hard Feces of Hyplus Rabbits.

The intestinal microbiota and its metabolites play vital roles in host growth, development, and immune regulation. This study analyzed the microbial community distribution and the cytokine and short-chain fatty acid (SCFA) content of cecal contents (Con group), soft feces (SF group), and hard feces (HF group) of 60-day-old Hyplus rabbits and verified the effect of soft feces on the cecal immune microenvironment by coprophagy prevention (CP). The results showed that there were significant differences in the levels of phylum and genus composition, cytokines, and SCFAs among the Con group, SF group, and HF group. The correlation analysis of cytokines and SCFAs with differential microbial communities showed that Muribaculaceae, Ruminococcaceae_UCG-014, Ruminococcaceae_NK4A214_group, and Christensenellaceae_R-7_Group are closely related to cytokines and SCFAs. After CP treatment, the contents of propionic acid, butyric acid, IL-4, and IL-10 in cecum decreased significantly, whereas TNF-α and IL-1ß increased significantly. Moreover, the inhibition of coprophagy led to the downregulation of the expression levels of tight junction proteins (Claudin-1, Occludin, and ZO-1) related to intestinal inflammation and intestinal barrier function, and the ring-like structure of ZO-1 was disrupted. In conclusion, coprophagy can not only help rabbits obtain more probiotics and SCFAs but also play an essential role in improving the immune microenvironment of cecum.