Genome-wide profiling of histone acetylation enhancer of fatty liver hemorrhagic syndrome in laying hens.

Objective: Rare study of the non-coding and regulatory regions of the genome limits our ability to decode the mechanisms of fatty liver hemorrhage syndrome (FLHS) in chickens. Method: Herein, we constructed the HFD-induced FLHS chicken model to investigate the genome-wide active enhancers and transcriptome by H3K27ac target chromatin immunoprecipitation sequencing (ChIP-seq) and RNA sequencing (RNA-Seq) profiles of normal and FLHS liver tissues. Concurrently, an integrative analysis combining ChIP-seq with RNA-Seq and a comparative analysis with chicken FLHS, rat Non-alcoholic fatty liver disease (NAFLD) and human NAFLD at the transcriptome level revealed the enhancer target genes and conservative genes involved in metabolic processes. Results: In total, 56 and 199 peak-genes were identified in upregulated peak-genes positively regulated by H3K27ac (Cor (peak-gene correlation) ≥ 0.5 & log2(FoldChange) ≥ 1) (PP) and downregulated peak-genes positively regulated by H3K27ac (Cor (peak-gene correlation) ≥ 0.5 & log2(FoldChange) ≤ -1)(PN), respectively; then we screened key regulatory targets mainly distributing in lipid metabolism (PCK1, APOA4, APOA1, INHBE) and apoptosis (KIT, NTRK2) together with MAPK and PPAR signaling pathway in FLHS. Intriguingly, PCK1 was also significantly covered in up-regulated super-enhancers (SEs), which further implied the vital role of PCK1 during the development of FLHS. Conclusion: Together, our studies provided new insights into the pathogenesis and potential therapy biomarkers of FLHS.

Short-chain fatty acids in nonalcoholic fatty liver disease: New prospects for short-chain fatty acids as therapeutic targets.

Nonalcoholic fatty liver disease (NAFLD) is a stress-induced liver injury related to heredity, environmental exposure and the gut microbiome metabolism. Short-chain fatty acids (SCFAs), the metabolites of gut microbiota (GM), participate in the regulation of hepatic steatosis and inflammation through the gut-liver axis, which play an important role in the alleviation of NAFLD. However, little progress has been made in systematically elucidating the mechanism of how SCFAs improve NAFLD, especially the epigenetic mechanisms and the potential therapeutic application as clinical treatment for NAFLD. Herein, we adopted PubMed and Medline to search relevant keywords such as 'SCFAs', 'NAFLD', 'gut microbiota', 'Epigenetic', 'diet', and 'prebiotic effect' to review the latest research on SCFAs in NAFLD up to November 2023. In this review, firstly, we specifically discussed the production and function of SCFAs, as well as their crosstalk coordination in the gut liver axis. Secondly, we provided an updated summary and intensive discussion of how SCFAs affect hepatic steatosis to alleviate NAFLD from the perspective of genetic and epigenetic. Thirdly, we paid attention to the pharmacological and physiological characteristics of SCFAs, and proposed a promising future direction to adopt SCFAs alone or in combination with prebiotics and related clinical drugs to prevent and treat NAFLD. Together, this review aimed to elucidate the function of SCFAs and provide new insights to the prospects of SCFAs as a therapeutic target for NAFLD.

Compiling and applying atmospheric resource balance sheet in off-office auditing of leading cadres in China.

Atmospheric resources provide important support for human economic and social systems through their unique ecosystem service functions. Implementing the off-office auditing of atmospheric resources for leading cadres holds great strategic significance for fundamentally solve air pollution problems. Exploring the compilation of an atmospheric resource balance sheet is a necessary pre-step in the implementation of outgoing audits. In this paper, atmospheric resources are innovatively divided into atmospheric capacity resources and atmospheric quality resources from the perspective of the ecosystem service functions of atmospheric resources. The value of atmospheric resource assets is calculated by combining the environmental capacity value method and the environmental loss evaluation method. This study evaluates atmospheric ecological achievements based on the atmospheric resources balance sheet and related accounts as the data carrier and opens up the key "blocking point" of the off-office auditing of atmospheric resources. This paper takes Anhui Province as an example and applies the accounting results of the prepared atmospheric resource balance sheet to evaluate the atmospheric resource ecological achievements of leading cadres from 2016 to 2020. The results clearly reflect the ecological achievements and shortcomings of local leading cadres during their tenure.

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.

Is China's Enterprise Employees' Basic Pension Plan Sustainable? Evidence from Two Northeastern Provinces in the Double-Drop Era.

In 2019, the Chinese central government adopted the "double-drop" policy (to reduce both the rate and the base of employers' contributions to employees' basic pension plan) as an attempt to increase overall employment and plan coverage in the national labor market and, in turn, achieve a balance in the plan's annual contributions and benefits at the provincial level. Accordingly, we utilize the cohort element method and actuarial models to explore the policy's effects on the plan's financial sustainability in both the short and long term based on data from Heilongjiang and Liaoning provinces in northeastern China. We further examine the policy's indirect effects (through changes in the compliance rate, enterprises' overall employment rate, coverage rates, or economic growth rates) on the plan's sustainability using the circulation substitution method. We find that, although the policy directly reduces employer contributions, it indirectly improves the plan's balance between contributions and benefits through changes in employment, coverage, compliance, or economic growth rates. Nevertheless, the overall effect of the policy is far weaker than its negative effect. Hence, we provide a portfolio of solutions that includes increases in provincial governments' subsidies (to approximately 8% of total fiscal expenditures), increases in the central government's adjustment proportion (to 11%-15%), and delays in the retirement age (progressively to age 65).

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.

What factors determine the survival of green innovative enterprises in China? -- A method based on fsQCA.

Increasingly serious environmental problems have generated a large number of small and medium-sized green innovative enterprises. Against the background of rapid technological changes and increasingly fierce market competition, survival is the main problem faced by these enterprises. Exploring the mechanisms and core elements that determine the survival of green innovation enterprises is of great practical significance for improving the survival probability of green innovation enterprises and achieving environmental improvement through green innovation. In this paper, twenty-nine enterprises that have won the title of "Top 10 Green Innovative Enterprises" in China are considered the research objects, and the fuzzy set qualitative comparative analysis (fsQCA) method is used to examine the path combinations that affect the survival of enterprises from the perspectives of resource-based and dynamic capabilities. The findings are as follows. First, government support is key to the survival of green innovative enterprises; second, China's green innovative enterprises have a research and development dilemma, and only matching high R&D capacity with product competitiveness can enhance their survival capabilities; and third, the lack of resource base capacity is the key factor affecting the failure of green enterprises, and dynamic capacity is the key factor for the survival of green innovative enterprises. The main contribution of this paper to the field of management is that enterprises must always pay attention to the coordinated development of internal resource-based capability and external dynamic capability. Conversely, the Chinese government should provide high R&D support to enterprises with competitive products so that these enterprises can rapidly grow into leading enterprises through continuous innovation and drive the sustained and rapid development of China's green innovation industry.

Ecological security assessment of Chaohu Lake Basin of China in the context of River Chief System reform.

In the face of the increasingly severe water environment, establishing an effective water environment management mechanism is a major concern of governments around the world. The River Chief System attempts to match water environment management to the performance of the main leaders of the local party and government and represents an institutional innovation to solve the problem of river and lake management in China. However, there is still a lack of systematic research on the performance of the River Chief System and how to promote its overall effectiveness. This paper took Chaohu Lake Basin, with a concentrated and complicated water environment, as the research object and divided it into eastern and western halves. The water ecological security before and after the implementation of the River Chief System was comprehensively evaluated, and the obstacles to ecological security were diagnosed. The implementation effect of the River Chief System and the weak links of the corresponding river chiefs' work performance were analyzed. The results show the following: (1) Since the implementation of the River Chief System in 2013, the overall water ecological security of Chaohu Lake Basin has been raised from the lower limit to the upper limit of the generally healthy category, initially reflecting the effect of the River Chief System. (2) For the eastern half of the lake, the threat to water ecological security mainly comes from the development of industry. Industrial water use intensity is the primary obstacle to the ecological security of the eastern half of the lake in recent years. (3) For the western half of the lake, the threat to water ecological security mainly comes from the process of urbanization. The wetland area, urban domestic water use intensity, and artificial afforestation area are the main factors hindering the ecological security of the western half of the lake. The above analysis results can be used as the basis for future work to improve the performance of the relevant river chiefs in Chaohu Lake Basin.

Functional role of Forskolin and PD166285 in the development of denuded mouse oocytes.

OBJECTIVE: cAMP and mature promoting factor (MPF) play critical roles during the maturation of mammalian oocytes. The aim of this study was to produce the offspring from denuded oocytes (DOs) in mice by regulating cAMP and MPF. METHODS: In this study, we used DOs at the germinal vesicle (GV) stage in mice and regulated levels of cAMP and MPF in DOs by adding Forskolin and PD166285 during in vitro maturation without follicle stimulating hormone and luteinizing hormone, respectively. RESULTS: Combined use of 50 µM Forskolin for 3 h and 2.5 µM PD166285 for additional 21 h enhanced the developmental competence of DOs, maturation rate of DOs was 76.71%± 4.11%, blastocyst rate was 18.33%±4.44% after parthenogenetic activation (PA). The DOs could successfully be fertilized with sperm in vitro, cleavage rate was 17.02%±5.82% and blastocyst rate was 5.65%±3.10%. Besides, 2-cell in vitro fertilization embryos from DOs produced 4 normal live offspring (4/34). CONCLUSION: The results confirmed that the combination of Forskolin and PD166285 can induce DOs to complete meiosis process and produce normal offspring.

Comparative transcriptomic analysis reveals the roles of ROS scavenging genes in response to cadmium in two pak choi cultivars.

To identify key regulatory genes involved in ROS scavenging in response to cadmium (Cd) exposure in pak choi, eight cDNA libraries from Cd-treated and Cd-free roots of two cultivars, Baiyewuyueman (high Cd accumulator) and Kuishan'aijiaoheiye (low Cd accumulator), were firstly performed by RNA-sequencing. Totally 0.443 billion clean reads and 244,190 unigenes were obtained from eight transcriptome. About 797 and 1167 unigenes encoding ROS related proteins and transcription factors were identified. Of them, 11 and 16 ROS scavenging system related DEGs, and 29 and 15 transcription factors related DEGs were found in Baiyewuyueman and Kuishan'aijiaoheiye, respectively. Ten ROS-scavenging genes (Cu/Zn-SOD, GST1, PODs, TrxR2, PrxR, FER3 and NDPK) showed higher expression levels in Cd-exposed seedings of Baiyewuyueman than those of Kuishan'aijiaoheiye. Four genes (GPX, APX, GRX and GST3) specifically expressed in Cd-free roots of Kuishan'aijiaoheiye. For transcription factors, ERF12/13/22 and WRKY31 was up-regulated by Cd in Baiyewuyueman, while in Kuishan'aijiaoheiye, Cd induced down-regulations of bZIP, NAC and ZFP families. The results indicate that the two cultivars differed in the mechanism of ROS scavenging in response to Cd stress. Fe SOD1, POD A2/44/54/62 and GST1 may be responsible for the difference of Cd tolerance between Baiyewuyueman and Kuishan'aijiaoheiye.