Epigenetic regulation of H3K27me3 in laying hens with fatty liver hemorrhagic syndrome induced by high-energy and low-protein diets.

BACKGROUND: Fatty liver hemorrhagic syndrome (FLHS) in the modern poultry industry is primarily caused by nutrition. Despite encouraging progress on FLHS, the mechanism through which nutrition influences susceptibility to FLHS is still lacking in terms of epigenetics. RESULTS: In this study, we analyzed the genome-wide patterns of trimethylated lysine residue 27 of histone H3 (H3K27me3) enrichment by chromatin immunoprecipitation-sequencing (ChIP-seq), and examined its association with transcriptomes in healthy and FLHS hens. The study results indicated that H3K27me3 levels were increased in the FLHS hens on a genome-wide scale. Additionally, H3K27me3 was found to occupy the entire gene and the distant intergenic region, which may function as silencer-like regulatory elements. The analysis of transcription factor (TF) motifs in hypermethylated peaks has demonstrated that 23 TFs are involved in the regulation of liver metabolism and development. Transcriptomic analysis indicated that differentially expressed genes (DEGs) were enriched in fatty acid metabolism, amino acid, and carbohydrate metabolism. The hub gene identified from PPI network is fatty acid synthase (FASN). Combined ChIP-seq and transcriptome analysis revealed that the increased H3K27me3 and down-regulated genes have significant enrichment in the ECM-receptor interaction, tight junction, cell adhesion molecules, adherens junction, and TGF-beta signaling pathways. CONCLUSIONS: Overall, the trimethylation modification of H3K27 has been shown to have significant regulatory function in FLHS, mediating the expression of crucial genes associated with the ECM-receptor interaction pathway. This highlights the epigenetic mechanisms of H3K27me3 and provides insights into exploring core regulatory targets and nutritional regulation strategies in FLHS.

Metabolism and residue differences of Enrofloxacin between the brain and peripheral tissues and the resulting brain damages in crucian carp (Carassius auratus var. Pengze).

This study aimed to explore the metabolism and residue differences of Enrofloxacin (ENR) at two doses between the brain and peripheral tissues (liver, kidney, and muscle) along with the brain damages caused by ENR in crucian carp (Carassius auratus var. Pengze). The concentrations of ENR in tissues were determined using a validated high-performance liquid chromatography (HPLC) analysis. Relying on the hematoxylin-eosin (HE) staining method, brain damages caused by the drug were evaluated by the section of pathological tissue. Metabolism and residue results showed that ENR could be detected in the brain throughout the experiment both at median lethal dose (LD50 at 96 h, 1949.84 mg/kg) and safe dose (SD, 194.98 mg/kg), as well as in the three peripheral tissues. The maximum residue at LD50 followed the decreasing order of liver >kidney > brain > muscle. Although the Cmax of ENR at SD in the brain was significantly lower than that in other peripheral tissues (p < .05), it still reached 41.91 µg/g. The T1/2 of ENR in brain tissue at the same dose was both shorter than that in peripheral tissues. At LD50 , the amount of ENR residues in brain was lower than that in peripheral tissues on the whole, except that it had been higher than in the muscle for the first 3 h. At SD, the drug residue in brain tissue was lower than that in peripheral tissues from 12 h to 960 h, but it exceeded the muscle and kidney at 1 h and 6 h, respectively. At 960 h, the residual amount of ENR at SD in the brain was 0.09 µg/g, while it was up to 0.15 µg/g following the oral administration at LD50 . Demonstrated by the HE staining, there were pathological lesions caused by ENR in the brain at LD50 , which were characterized by sparse neural network and increased staining of glial cells. The present results indicated that metabolism and residue of ENR in crucian carp were affected by the tissue type and drug dosage, and the ENR could also bring about histopathological changes in the brain.

Cryptotanshinone decreases granulosa cell apoptosis and restores ovarian function in mice with premature ovarian failure.

With the increasing incidence of premature ovarian failure (POF) seriously threaten the women's health. Whether cryptotanshinone decreased the granulosa cell apoptosis to improve the POF would be explored. POF mice were conducted with intraperitoneal injection of cyclophosphamide and then treated with cryptotanshinone. The body weight and ovarian weight were recorded. The estrus was detected by vaginal smears. The pathological changes of ovarian were observed with hematoxylin and eosin staining. ELISA assay analyzed the levels of LH, FSH, AMH, E2 and AzpAB in mice serum. The expression of Bcl-2, Bax, KI67 and PCNA in ovarian tissues was detected by Western blot analysis and KI67 expression was also determined by immunohistochemistry. The body weight and ovarian weight were decreased and the pathological results of ovarian were worsen in POF mice. The estrus was decreased in POF mice. The levels of LH, FSH and AzpAB were increased and the levels of AMH and E2 were decreased in POF mice serum. The expression of Bcl-2, KI67 and PCNA was decreased and Bax expression was increased in ovarian tissues of POF mice. Those changes affected by cyclophosphamide could be reversed by cryptotanshinone. Cryptotanshinone could decrease the granulosa cell apoptosis to restore ovarian function.

Effects of two kinds of fishery drugs on the expressions of GAD and GABA-T mRNA in crucian carp (Carassius auratus gibelio).

The objective of this study was to investigate the effects of difloxacin (DIF) and avermectin (AVM) on glutamate decarboxylase (GAD) and GABA-transaminase (GABA-T) in different tissues of crucian carp (Carassius auratus gibelio). After the treatments of DIF and AVM, the mRNA expressions of GAD and GABA-T in different tissues were detected by quantitative real-time PCR (qPCR). The results showed that the mRNA expressions of GAD65, GAD67, and GABA-T in the telencephalon (Tel), mesencephalon (Mes), cerebella (Cer), and medulla oblongata (Med) were downregulated significantly with the safe dose (SD, 20 mg/kg) of DIF (P < 0.05 or P < 0.01). While the expressions of GAD65 and GAD67 in the kidney at 12 h had strikingly upregulated to 13.81 ± 1.06** and 150.67 ± 12.85** times. Treated with the lethal dose of 50% (LD50, 2840 mg/kg b. W.) of DIF, the mRNA expressions of GAD65, GAD67, and GABA-T in all tissues were increased significantly (P < 0.01). The results of AVM group showed that the mRNA expressions of GAD65, GAD67, and GABA-T both in the central and peripheral tissues were all remarkably downregulated at the safe concentration (SC, 0.0039 mg/L) and the lethal concentration of 50% (LC50, 0.039 mg/L), except for the mRNA inhibitions of GAD65, GAD67, and GABA-T in the muscle at 2 h which sharply downregulated to 0.20 ± 0.02ΔΔ × 10-2, 0.57 ± 0.06ΔΔ × 10-1 and 0.44 ± 0.02ΔΔ × 10-1, respectively (P < 0.01).

[Extracts from Testudinis Carapacis et Plastri Regulates Expression of ID1 in Mscs].

OBJECTIVE: To explore BMP4 affecting the Extracts from Testudinis Carapacis et Plastri (PTE) stimulating proliferation of MSCs and the mechanism. METHODS: Cotransfected PGL3-IDI and pEGFP-BMP4 of 0, 0. 1,0. 3, 0. 5 and 1 µg/mL respectively using the calcium phosphate co-precipitation method in rat MSCs. One of transfected cells were divided into control group and PTE group. PTE group was stimulated by PTE of 30 µ/L for 36 h, while control group was not. Collected cells using lucifease activity measurement to detect the activity of ID. Then 0. 3 µg/mL pEGFP-BMP4 was chose to cotransfect. MSCs was divided into control group, PTE group, BMP4 group, BMP4 + PTE group. BMP4 and BMP4 + PTE group were cotransfected with PGL3-ID1 and pEGFP-BMP4 but control or PTE groups were not. PTE and BMP4 + PTE groups were stimulated by PTE of 30 µg/mL for 36 h but the either two groups were not. The activities of ID1, BMP4 and RARα were detected using RT-PCR. RESULTS: The expressions of ID1, BMP4 and RARa rose in PTE group. The expression of BMP4 and RARα rose while IDI decreased in BMP4 groups. BMP4, ID1 and RARα decreased remarkable in BMP4 + PTE group comparing with BMP4 group. CONCLUSION: PTE promotes the proliferation of MSCs, it also regulates the expression of BMP4 to prevent excessive proliferation of MSCs.

tsRNA-3043a intensifies apoptosis and senescence of ovarian granulosa cells to drive premature ovarian failure by targeting FLT1.

Premature ovarian failure (POF) represents the pathological aging of the ovary. The tRNA-derived small fragments (tsRNAs) play significant roles in diseases; however, whether tsRNAs are involved in POF remains unknown. The cell and mice models of POF were established, and the tsRNAs profile in the ovarian tissues of POF mice was revealed through sequencing. The functions of tsRNA-3043a and its target gene FLT1 in POF cells and mice were detected. POF mice were characterized by a decreased number of normal follicles, ovarian weight, SOD level, and serum contents of E2, LH, and FSH. A total of 81 tsRNAs were aberrantly expressed in the ovarian tissue of POF mice. The expression of tsRNA-3043a was up-regulated in POF mice. tsRNA-3043a mimics inhibited the proliferation and promoted apoptosis, lipid accumulation, and cellular senescence of ovarian granulosa KGN cells, as well as altered the transcriptome. tsRNA-3043a inhibitor had the opposite effect. tsRNA-3043a targets and binds to FLT1. Overexpression of FLT1 protected KGN cells from pathological aging. tsRNA-3043a promotes the progression of POF by inhibiting FLT1 in vitro and in vivo. tsRNA-3043a targets FLT1 and promotes apoptosis and senescence of ovarian granulosa cells, leading to the progression of POF. This study provides a new target for pharmacological intervention in POF.

Chicken ovarian follicular atresia: interaction network at organic, cellular, and molecular levels.

Most of follicles undergo a degenerative process called follicular atresia. This process directly affects the egg production of laying hens and is regulated by external and internal factors. External factors primarily include nutrition and environmental factors. In follicular atresia, internal factors are predominantly regulated at 3 levels; organic, cellular and molecular levels. At the organic level, the hypothalamic-pituitary-ovary (HPO) axis plays an essential role in controlling follicular development. At the cellular level, gonadotropins and cytokines, as well as estrogens, bind to their receptors and activate different signaling pathways, thereby suppressing follicular atresia. By contrast, oxidative stress induces follicular atresia by increasing ROS levels. At the molecular level, granulosa cell (GC) apoptosis is not the only factor triggering follicular atresia. Autophagy is also known to give rise to atresia. Epigenetics also plays a pivotal role in regulating gene expression in processes that seem to be related to follicular atresia, such as apoptosis, autophagy, proliferation, and steroidogenesis. Among these processes, the miRNA regulation mechanism is well-studied. The current review focuses on factors that regulate follicular atresia at organic, cellular and molecular levels and evaluates the interaction network among these levels. Additionally, this review summarizes atretic follicle characteristics, in vitro modeling methods, and factors preventing follicular atresia in laying hens.

Functional remodeling of gut microbiota and liver in laying hens as affected by fasting and refeeding after fasting.

Objective: Animals will experience energy deprivation processes such as moulting, clutching, migration and long-distance transportation under natural survival conditions and in production practices, and the body will trigger a series of adaptive metabolic changes during these processes. Fasting and refeeding after fasting can induce remodeling of nutrients and energy metabolism. This study aims to investigate the mechanisms by which the gut microbiota and liver of poultry respond to energy deprivation under specific conditions. Methods: Ninety 252-day-old laying hens were randomly divided into 3 groups: (1) fed ad libitum (control group); (2) fasted from day 13 to day 17 (fasting group); (3) fasted from day 1 to day 5, then refed on a specific feeding way (refeeding group). After that, the serum, liver, jejunum tissues, and cecum contents were sampled and sent for metabolome, transcriptome, morphology, and 16S rDNA sequencing analyses, respectively. Results: Results showed that food deprivation not only observably decreased the body weight, liver index, and the villus height and villus/crypt ratio of jejunum, but also significantly changed the gut microbiota compositions, serum metabolic profiles, and the hepatic gene expression patterns of laying hens, whereas these changes were effectively reversed by the following refeeding operation. At the same time, metabolome combined transcriptome analysis revealed that both serum differential metabolites and hepatic differential expressed genes (DEGs) were consistently enriched in the lipid and amino metabolism pathways, and strong correlations were synchronously found between the differential metabolites and both of the differential gut microbial genera and DEGs, suggesting the crosstalks among gut, liver and their resulting serum metabolic products. Conclusion: The results suggested that the organism might coordinate to maintain metabolic homeostasis under energy deprivation through a combination of changes in gut microbial composition and hepatic gene expression.

Loss of LBP triggers lipid metabolic disorder through H3K27 acetylation-mediated C/EBPß- SCD activation in non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is associated with mutations in lipopolysaccharide-binding protein ( LBP), but the underlying epigenetic mechanisms remain understudied. Herein, LBP -/- rats with NAFLD were established and used to conduct integrative targeting-active enhancer histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation coupled with high-throughput and transcriptomic sequencing analysis to explore the potential epigenetic pathomechanisms of active enhancers of NAFLD exacerbation upon LBP deficiency. Notably, LBP -/- reduced the inflammatory response but markedly aggravated high-fat diet (HFD)-induced NAFLD in rats, with pronounced alterations in the histone acetylome and regulatory transcriptome. In total, 1 128 differential enhancer-target genes significantly enriched in cholesterol and fatty acid metabolism were identified between wild-type (WT) and LBP -/- NAFLD rats. Based on integrative analysis, CCAAT/enhancer-binding protein ß (C/EBPß) was identified as a pivotal transcription factor (TF) and contributor to dysregulated histone acetylome H3K27ac, and the lipid metabolism gene SCD was identified as a downstream effector exacerbating NAFLD. This study not only broadens our understanding of the essential role of LBP in the pathogenesis of NAFLD from an epigenetics perspective but also identifies key TF C/EBPß and functional gene SCD as potential regulators and therapeutic targets.

Characterization, purification of Poncirin from edible citrus Ougan (Citrus reticulate cv. Suavissima) and its growth inhibitory effect on human gastric cancer cells SGC-7901.

Poncirin is a bitter flavanone glycoside with various biological activities. Poncirin was isolated from four different tissues (flavedo, albedo, segment membrane, and juice sac) of Ougan fruit (Citrus reticulate cv. Suavissima). The highest content of poncirin was found in the albedo of Ougan fruit (1.37 mg/g DW). High speed counter-current chromatography (HSCCC) combined with D101 resin chromatography was utilized for the separation and purification of poncirin from the albedo of Ougan fruit. After this two-step purification, poncirin purity increased from 0.14% to 96.56%. The chemical structure of the purified poncirin was identified by both HPLC-PDA and LC-MS. Poncirin showed a significant in vitro inhibitory effect on the growth of the human gastric cancer cells, SGC-7901, in a dose-dependent manner. Thus, poncirin from Ougan fruit, may be beneficial for gastric cancer prevention. The purification method demonstrated here will be useful for further studies on the pharmacological mechanism of poncirin activity, as well as for guiding the consumption of Ougan fruit.

Disruption of sex steroid hormones biosynthesis by short-term enrofloxacin antibiotic exposure in Carassius auratus var. Pengze.

BACKGROUND: It has been reported that antibiotic enrofloxacin can impair reproductive function of mammals, induces multi-generational oscillatory effects on reproduction of Caenorhabditis elegans, and disturbes endocrine system in grass carp. OBJECTIVES: This study aims to explore the effect of short-term enrofloxacin exposure on sex steroid hormones biosynthesis in Carassius auratus var. Pengze through assessing the contents of growth hormone (GH), thyroid hormone 4 (T4), estradiol (E2) and testosterone (T) in plasma, and investigating sex steroid hormones biosynthesis based on targeted metabonomics analysis, and determining expression level of some important genes, gonadotropin-releasing hormone (gnrh), gonadotropin hormone 1-ß (gth1-ß), gonadotropin hormone 2-ß (gth2-ß) and cyp19a1a in hypothalamus-pituitary-ovary axis (HPOA). RESULTS: We found that short-term exposure of enrofloxacin disordered contents of E2 and T in plasma of fish determined by ELISA detection, T content elevation and E2 content decline, which was confirmed by the following data from targeted metabonomics analysis of plasma. The metabonomic results showed that both T and its upstream intermediate products during the process of sex steroid hormones biosynthesis in fish were increased significantly, but E2 content was decreased markedly. At the exposure 24 h of enrofloxacin, expression of gnrh in hypothalamus, gth1-ß and gth2-ß in pituitary were promoted. Meanwhile GH and T4 contents in plasma, two inducers of sex steroid hormones synthesis, were augmented, which indicated that sex steroid hormones biosynthesis was improved. However cyp19a1a expression in ovary was repressed, and content of estriol (E3) was upregulated. These data suggested that enrofloxacin promoted sex steroid hormones biosynthesis and conversion of E2 to estriol (E3), but inhibited the conversion of T to E2. Finally, content of E2 was declined sharply. DISCUSSION: Animal specific antibacterial enrofloxacin is widely detectable in aquatic ecosystem, exposure of the agent can induce adverse effects on plants and animals. This study firstly evidenced induction of disruption of sex steroid hormones by enrofloxacin in fish, which indicates enrofloxacin is an endocrine disruption compound that can induce endocrine disruption of animals, including fish.

Intravascular Ultrasound-Based Fractional Flow Reserve for Predicting Prognosis after Percutaneous Coronary Intervention.

AccuFFRivus is an alternative to fractional flow reserve (FFR) based on intravascular ultrasound (IVUS) images for functional assessment of coronary stenosis. However, its prognostic impact in patients undergoing percutaneous coronary intervention (PCI) is still unclear. This retrospective study aimed to investigate the capability of AccuFFRivus in predicting prognosis. AccuFFRivus was calculated based on postoperative angiographic and IVUS images. Vessel-oriented clinical events (VOCE) at 2 years were recorded and analyzed. A total of 131 participants with 131 vessels were included in the study. VOCE occurred in 15 patients during 2-year follow-up. AccuFFRivus after PCI (post-AccuFFRivus) was significantly higher in the non-VOCE group than in the VOCE group (0.95 ± 0.03 vs. 0.91 ± 0.02, p < 0.001). Multivariate Cox regression showed that AccuFFRivus ≤ 0.94 was a strong independent predictor of VOCE during 2-year follow-up (hazard ratio 23.76, 95% confidence interval: 3.04-185.81, p < 0.001). The left panel displays the Receiver operating characteristics (ROC) curves of postoperative parameters (post-AccuFFRivus and post-MLA) versus vessel-oriented clinical events (VOCE) occurrence within 2-year follow-up. The right panel demonstrates Kaplan-Meier curves of VOCE stratified by the optimal cut-off of post-AccuFFRivus.

Enrofloxacin hydrochloride toxicological effects on crucian carp reflected by serological changes and neurotoxicity.

Due to its water solubility and wide applicability, enrofloxacin hydrochloride (EH) may enter aquatic ecosystems and cause negative effects on aquatic organisms. This study aimed to explore toxicological effects via serological changes and neurotoxicity, which were induced by EH exposure in crucian carp (Carassius auratus var. Pengze). The drug residues in brain tissue and protein content in serum were determined to analyze serological changes. Alterations in brain tissue structure and function, cerebral microvessels permeability, and the expressions of gene and protein regarding blood-brain barrier (BBB) were studied to reflect the neurotoxicity. Employing a validated high-performance liquid chromatography (HPLC) method, EH residues could be detected at various time-points throughout the experiment. Enzyme-linked immunosorbent assay (ELISA) showed that EH increased the levels of S100B, NSE and GFAP proteins in serum. Additionally, there was a significant positive correlation between serum S100B, NSE protein contents and EH residues (P < 0.05). Hematoxylin and eosin (H&E) staining revealed brain damage from EH exposure by the formation of vacuoles in brain glial cells, pyknosis of the nucleus, and a decrease in cell population density. Transmission electron microscope (TEM) revealed morphological changes in microvessels and condensation of astrocyte nucleus. Evans blue (EB) permeability test visualized an obvious increase in cerebral microvessels leakage. The real-time quantitative PCR (qPCR) results indicated that EH up-regulated the mRNA expression levels of S100B, NSE and GFAP, down-regulated the mRNA expression levels of P-gp, ZO-1, Occludin and Claudin-5. The Western blot (WB) results demonstrated increased NSE and GFAP protein expressions, decreased P-gp and Occludin protein expressions following EH exposure in brain, in consistent with the gene expressions, respectively. In conclusion, these findings indicated that EH brought about marked rise in serum biomarker levels and disrupted the central nervous system (CNS) of crucian carp. These data would help elucidate the mechanism underlying EH-induced neurotoxicological effects.

In vitro antibacterial effects of Broussonetia papyrifera leaf extract and its anti-colitis in DSS-treated mice.

Recently, the hybrid Broussonetia papyrifera (BP) has been extensively cultivated and predominantly utilized in ruminants because of its high protein and bioactive compound content. In the present study, the effects of an ethanolic extract of BP leaves (BPE, 200 mg/kg) on mitigating 2% dextran sodium sulfate (DSS)-induced intestinal inflammation in mice were evaluated. BPE is rich in flavonoids, polyphenols, and polysaccharides, and displays potent antioxidant and antibacterial activities against pathogenic strains such as Clostridium perfringens, Salmonella Typhimurium, and Salmonella enterica subsp. enterica in vitro. In a mouse study, oral administration of DSS resulted in weight loss, incidence of diarrhea, enlargement of the liver and spleen, impaired colonic morphology, downregulation of both gene and protein expression related to intestinal antioxidant (Nrf2) and barrier function (ZO-1), decreased diversity of colonic microbiota, and 218 differentially altered colonic metabolites; however, co-treatment with BPE did not restore these modified aspects except for the liver index and colonic bacterial diversity. The singular treatment with BPE did not manifest evident side effects in normal mice but induced a mild occurrence of diarrhea and a notable alteration in the colonic metabolite profile. Moreover, a single BPE administration augmented the abundance of the commensal beneficial bacteria Faecalibaculum and Akkermansia genera. Overall, the extract of BP leaves did not demonstrate the anticipated effectiveness in alleviating DSS-induced intestinal inflammation.

Separation and purification of neohesperidin from the albedo of Citrus reticulata cv. Suavissima by combination of macroporous resin and high-speed counter-current chromatography.

In this article, a simple and efficient protocol for rapid preparation and separation of neohesperidin from the albedo of Citrus reticulata cv. Suavissima was established by the combination of macroporous resin column chromatography and high-speed counter-current chromatography (HSCCC). Six types of resin were investigated by adsorption and desorption tests, and D101 macroporous resin was selected for the first cleaning-up procedure, in which 55% aqueous ethanol was used to elute neohesperidin. After treatment with D101 resin, the neohesperidin purity increased 11.83-fold from 4.92% in the crude extract to 58.22% in the resin-refined sample, with a recovery of 68.97%. The resin-refined sample was directly subjected to HSCCC purification with a two-phase solvent system composed of ethyl acetate-n-butanol-water (4:1:5, v/v), and 23.6 mg neohesperidin with 97.47% purity was obtained from 60 mg sample in only one run. The recovery of neohesperidin in HSCCC separation procedure was 65.85%. The chemical structure of the purified neohesperidin was identified by both HPLC and LC-MS. The established purification process will be helpful for further characterization and utilization of Citrus neohesperidin.

Blood-brain barrier permeability to enrofloxacin in Pengze crucian carp (Carassius auratus var. Pengze).

BACKGROUND: Enrofloxacin (ENR) is a kind of quinolone antibiotic that is most widely used antimicrobials in veterinary practice, and possesses both a broad spectrum antimicrobial activity against a range of bacteria and adverse effects towards plants and animals. OBJECTIVES: This study was conducted to explore the permeability of blood-brain barrier (BBB) to ENR and brain injury based on crucian carp orally administrated with high dose of ENR. METHODS: Juvenile Pengze crucian carp were treated with half lethal dose (LD50 ) or safe dose (SD50 ) of ENR. BBB permeability was determined by evaluating ENR contents detected by HPLC and evens blue contents estimated by confocal laser scanning microscope. Brain damage was evaluated by measuring protein and mRNA contents of related molecules with western blotting and qPCR. RESULTS: Data indicated that ENR destroyed BBB structure of crucian carp and enhanced permeability of the biological barrier, resulting in more ENR crossed BBB and induced brain damage of crucian carp. CONCLUSIONS: This data indicated that ENR can induce brain damage of crucian carp through destroying BBB structure and enhancing permeability.

Eu doped Ti3C2 quantum dots to form a ratiometric fluorescence platform for visual and quantitative point-of-care testing of tetracycline derivatives.

Antibiotic residues have become a public health issues, the fast detection of tetracycline (Tc) in the environment is urgently required. In this work, Ti3C2 quantum dots (Ti3C2 QDs) and Europium ions jointly constructed a ratiometric fluorescence (FL) platform for the detection of Tc, based on synergistic impact of the Foster Resonance Energy Transfer (FRET) from Ti3C2 QDs to Eu3+ ions and the Antenna Effect (AE) between Tc and Eu3+ ions. And we proposed a ratiometric FL platform for detecting Tc with good linear response range (100-1000 uM) and low detection limit (48.79 nM). Meanwhile, we applied this platform to detect a serious of ß-diketone ligands of Eu3+ ions, demonstrating the platform's versatility for this category of chemical. Furthermore, based on the color changes of QDs@Eu3+ from blue to red at 365 nm ultraviolet light, an intelligent detection smart device was built for the visual semi-quantitative detection of Tc in actual samples. We proved the applicability of the device in complicated samples and the potential for rapid, sensitive, intuitive and point-of-care detection in the field of environment, food, pharmaceutical and agriculture.

Construction of a transposase accessible chromatin landscape reveals chromatin state of repeat elements and potential causal variant for complex traits in pigs.

BACKGROUND: A comprehensive landscape of chromatin states for multiple mammalian tissues is essential for elucidating the molecular mechanism underlying regulatory variants on complex traits. However, the genome-wide chromatin accessibility has been only reported in limited tissue types in pigs. RESULTS: Here we report a genome-wide landscape of chromatin accessibility of 20 tissues in two female pigs at ages of 6 months using ATAC-seq, and identified 557,273 merged peaks, which greatly expanded the pig regulatory element repository. We revealed tissue-specific regulatory elements which were associated with tissue-relevant biological functions. We identified both positive and negative significant correlations between the regulatory elements and gene transcripts, which showed distinct distributions in terms of their strength and distances from corresponding genes. We investigated the presence of transposable elements (TEs) in open chromatin regions across all tissues, these included identifications of porcine endogenous retroviruses (PERVs) exhibiting high accessibility in liver and homology of porcine specific virus sequences to universally accessible transposable elements. Furthermore, we prioritized a potential causal variant for polyunsaturated fatty acid in the muscle. CONCLUSIONS: Our data provides a novel multi-tissues accessible chromatin landscape that serve as an important resource for interpreting regulatory sequences in tissue-specific and conserved biological functions, as well as regulatory variants of loci associated with complex traits in pigs.

Epigenetic association study uncovered H3K27 acetylation enhancers and dysregulated genes in high-fat-diet-induced nonalcoholic fatty liver disease in rats.

Aim: To evaluate the regulatory landscape underlying the active enhancer marked by H3K27ac in high-fat diet (HFD)-induced nonalcoholic fatty liver disease (NAFLD) in rats. Materials & methods: H3K27ac chromatin immunoprecipitation and high-throughput RNA sequencing to construct regulatory profiles and transcriptome of liver from NAFLD rat model induced by HFD. De novo motif analysis for differential H3K27ac peaks. Functional enrichment, Kyoto Encyclopedia of Genes and Genomes pathway and protein-protein interaction network were examined for differential peak-genes. The mechanism was further verified by western blot, chromatin immunoprecipitation-quantitative PCR and real-time PCR. Results: A total of 1831 differential H3K27ac peaks were identified significantly correlating with transcription factors and target genes (CYP8B1, PLA2G12B, SLC27A5, CYP7A1 and APOC3) involved in lipid and energy homeostasis. Conclusion: Altered acetylation induced by HFD leads to the dysregulation of gene expression, further elucidating the epigenetic mechanism in the etiology of NAFLD.

What is this summary about? Nonalcoholic fatty liver disease (NAFLD) is a typical metabolic disease, which is becoming the most common liver disease in the world. Despite its high prevalence and morbidity, there is currently no effective diagnostic or approved therapy, and the molecular mechanisms for NAFLD have not been fully clarified, especially for epigenetics. Herein, we focused on histone modification and investigated the impact of active enhancer to explore the epigenetic regulation of NAFLD, seeking new targets for the prevention and treatment of the disease. What were the results? We identified the alteration of H3K27 acetylation and differential gene expression, enriched potential transcription-factor binding motifs and highlighted the hub risk genes of CYP8B1, PLA2G12B, SLC27A5, CYP7A1 and APOC3 in a NAFLD rat model. What do the results mean? This work emphasized the vital roles of histone modification of H3K27ac in a high-fat-diet-induced NAFLD model, which could regulate the expression of key genes and transcription factor binding motifs, and H3K27ac induced the formation of NAFLD. Targeting the H3K27ac modification, dysregulated target genes and enriched pathways may be of great importance for NAFLD prediction and prevention, and serve as a valuable resource for genome-wide studies of epigenomic regulation in lipid metabolic disease.

Effect of JAK-STAT pathway in regulation of fatty liver hemorrhagic syndrome in chickens.

OBJECTIVE: To explore the molecular mechanisms of fatty liver hemorrhagic syndrome (FLHS) in laying hens, an experiment was conducted to reveal the differences in histopathological observation and gene expression between FLHS group and normal group. METHODS: We compared the histopathological difference using hematoxylin and eosin staining and proceeded with RNA sequencing of adipose tissue to search differentially expressed genes and enriched biological processes and pathways. Then we validated the mRNA expression levels by real-time polymerase chain reaction and quantified protein levels in the circulation by enzyme-linked immunosorbent assay. RESULTS: We identified 100 differentially expressed transcripts corresponding to 66 genes (DEGs) were identified between FLHS-affected group and normal group. Seven DEGs were significantly enriched in the immune response process and lipid metabolic process, including phospholipase A2 group V, WAP kunitz and netrin domain containing 2, delta 4-desaturase sphingolipid 2, perilipin 3, interleukin-6 (IL-6), ciliary neurotrophic factor (CNTF), and suppressor of cytokine signaling 3 (SOCS3). And these genes could be the targets of immune response and be involved in metabolic homeostasis during the process of FLHS in laying hens. Based on functional categories of the DEGs, we further proposed a model to explain the etiology and pathogenesis of FLHS. IL-6 and SOCS3 mediate inflammatory responses and the satiety hormone of leptin, induce dysfunction of Jak-STAT signaling pathway, leading to insulin resistance and lipid metabolic disorders. Conversely, CNTF may reduce tissue destruction during inflammatory attacks and confer protection from inflammation-induced insulin resistance in FLHS chickens. CONCLUSION: These findings highlight the therapeutic implications of targeting the JAK-STAT pathway. Inhibition of IL6 and SOCS3 and facilitation of CNTF could serve as a favorable strategy to enhance insulin action and improve glucose homoeostasis, which are of importance for treating obesity-related disorders for chickens.