Ontogeny of myeloperoxidase (MPO) positive cells in flounder (Paralichthys olivaceus).

Neutrophils represent an important asset of innate immunity. Neutrophils express myeloperoxidase (MPO) which is a heme-containing peroxidase involved in microbial killing. In this study, by using real-time quantitative PCR and Western blot analysis, the flounder MPO (PoMPO) was observed to be highly expressed in the head kidney, followed by spleen, gill, and intestine during ontogeny - during developmental stages from larvae to adults. Furthermore, PoMPO positive cells were present in major immune organs of flounder at all developmental stages, and the number of neutrophils was generally higher as the fish grew to a juvenile stage. In addition, flow cytometry analysis revealed that the proportion of PoMPO positive cells relative to leukocytes, in the peritoneal cavity, head kidney, and peripheral blood of flounder juvenile stage was 18.3 %, 34.8 %, and 6.0 %, respectively, which is similar to the adult stage in flounder as previously reported. The presence and tissue distribution of PoMPO during ontogeny suggests that PoMPO positive cells are indeed a player of the innate immunity at all developmental stages of flounder.

Interaction of ubiquitin-like protein SILENCING DEFECTIVE 2 with LIKE HETEROCHROMATIN PROTEIN 1 is required for regulation of anthocyanin biosynthesis in Arabidopsis thaliana in response to sucrose.

The regulatory mechanisms of anthocyanin biosynthesis have been well documented at the transcriptional and translational levels. By contrast, how anthocyanin biosynthesis is epigenetically regulated remains largely unknown. In this study, we employed genetic, molecular biology, and chromatin immunoprecipitation-quantitative polymerase chain reaction assays to identify a regulatory module essential for repressing the expression of genes involved in anthocyanin biosynthesis through chromatin remodeling. We found that SILENCING DEFECTIVE 2 (SDE2), which was previously identified as a negative regulator for sucrose-induced anthocyanin accumulation in Arabidopsis, is cleaved into N-terminal SDE2-UBL and C-terminal SDE2-C fragments at the first diglycine motif, and the cleaved SDE2-C, which can fully complement the sde2 mutant, is localized in the nucleus and physically interacts with LIKE HETEROCHROMATIN PROTEIN 1 (LHP1) in vitro and in vivo. Genetic analyses showed that both SDE2 and LHP1 act as negative factors for anthocyanin biosynthesis. Consistently, immunoblot analysis revealed that the level of LHP1-bound histone H3 lysine 27 trimethylation (H3K27me3) significantly decreases in sde2 and lhp1 mutants, compared to wild-type (WT). In addition, we found that sugar can induce expression of SDE2 and LHP1, and enhance the level of the nucleus-localized SDE2-C. Taken together, our data suggest that the SDE2-C-LHP1 module is required for repression of gene expression through H3K27me3 modification during sugar-induced anthocyanin biosynthesis in Arabidopsis thaliana.

Zishen Yutai Pills Promote Angiogenesis at the Maternal-Fetal Interface in Recurrent Spontaneous Abortion Mice by Regulating miR-187/VEGF Axis.

Ethnopharmacological Relevance: Zishen Yutai pills (ZYP), a traditional Chinese patent medicine, was listed in China in 1981. It is composed of 15 traditional Chinese medicines and has the effects of regulating menstruation, helping pregnancy, and preventing abortion. In clinical practice, it is effective in preventing habitual and threatened miscarriages, and continuing to explore its mechanism of action is very meaningful research. Aim of the Study: To explore the possible mechanism of ZYP promoting angiogenesis at the maternal-fetal interface in recurrent spontaneous abortion (RSA). Materials and Methods: In vitro experiments, placental trophoblast cells (PTCs) were isolated from the placental tissue of RSA mice and divided into six groups: Control group, Model group, ZYP group, miR-187 inhibitor NC group, miR-18 7 inhibitor group, and miR-187 inhibitor+ZYP group. Cell viability and cell cycle were measured using CCK8 and flow cytometry, respectively. The expression levels of miR-187, VEGF, VEGF-R1, and VEGF-R2 were measured using RT-qPCR, WB, and IF staining. Animal experiments first establish an RSA mice model (CBA/J × DBA/2) and then randomly divide the mice into four groups (n=10): normal pregnancy group, RSA model group, ZYP group, and progesterone capsule group. Observed the changes in embryo absorption rate, pathological morphology of decidual tissue, and ultrastructure of vascular endothelial cells in each group of mice. RT-qPCR, WB, and IF staining methods were used to determine the expression of miR-187, VEGF, VEGF-R1, and VEGF-R2. Results: In vitro, ZYP promoted the viability of PTCs and regulated their cell cycle, and ZYP down-regulated miR-187, up-regulated VEGF, VEGF-R1 and VEGF-R2 levels. miR-187 inhibitor showed the same effects, and further ZYP intervention enhanced the effects. In vivo, ZYP remarkably reduced embryo resorption rates, and improved the pathological morphology of decidual tissues and ultrastructure of vascular endothelial cells. Moreover, ZYP down-regulated miR-187, up-regulated VEGF, VEGF-R1 and VEGF-R2. Conclusion: In summary, ZYP can regulate the expression of VEGF via miR-187, then promote the angiogenesis at the maternal-fetal interface, and playing a therapeutic role in RSA.

MAPK family genes' influences on myogenesis in cattle: Genome-wide analysis and identification.

The mitogen-activated protein kinase (MAPK) family is highly conserved in mammals, and is involved in a variety of physiological phenomena like regeneration, development, cell proliferation, and differentiation. In this study, 13 MAPK genes were identified in cattle and their corresponding protein properties were characterized using genome-wide identification and analysis. Phylogenetic analysis showed that the 13 BtMAPKs were cluster grouped into eight major evolutionary branches, which were segmented into three large subfamilies: ERK, p38 and JNK MAPK. BtMAPKs from the same subfamily had similar protein motif compositions, but considerably different exon-intron patterns. The heatmap analysis of transcriptome sequencing data showed that the expression of BtMAPKs was tissue-specific, with BtMAPK6 and BtMAPK12 highly expressed in muscle tissues. Furthermore, knockdown of BtMAPK6 and BtMAPK12 revealed that BtMAPK6 had no effect on myogenic cell proliferation, but negatively affected the differentiation of myogenic cells. In contrast, BtMAPK12 improved both the cell proliferation and differentiation. Taken together, these results provide novel insights into the functions of MAPK families in cattle, which could serve as a basis for further studies on the specific mechanisms of the genes in myogenesis.

Discovery of Quinacrine as a Potent Topo II and Hsp90 Dual-Target Inhibitor, Repurposing for Cancer Therapy.

Topo II and Hsp90 are promising targets. In this study, we first verified the structural similarities between Topo IIα ATPase and Hsp90α N-ATPase. Subsequently, 720 compounds from the Food and Drug Administration (FDA) drug library and kinase library were screened using the malachite green phosphate combination with the Topo II-mediated DNA relaxation and MTT assays. Subsequently, the antimalarial drug quinacrine was found to be a potential dual-target inhibitor of Topo II and Hsp90. Mechanistic studies showed that quinacrine could specifically bind to the Topo IIα ATPase domain and inhibit the activity of Topo IIα ATPase without impacting DNA cleavage. Furthermore, our study revealed that quinacrine could bind Hsp90 N-ATPase and inhibit Hsp90 activity. Significantly, quinacrine has broad antiproliferation activity and remains sensitive to the multidrug-resistant cell line MCF-7/ADR and the atypical drug-resistant tumor cell line HL-60/MX2. Our study identified quinacrine as a potential dual-target inhibitor of Topo II and Hsp90, depending on the ATP-binding domain, positioning it as a hit compound for further structural modification.

Integration of RNA-seq and ATAC-seq identifies muscle-regulated hub genes in cattle.

As the main product of livestock, muscle itself plays an irreplaceable role in maintaining animal body movement and regulating metabolism. Therefore, it is of great significance to explore its growth, development and regeneration to improve the meat yield and quality of livestock. In this study, we attempted to use RNA-seq and ATAC-seq techniques to identify differentially expressed genes (DEGs) specifically expressed in bovine skeletal muscle as potential candidates for studying the regulatory mechanisms of muscle development. Microarray data from 8 tissue samples were selected from the GEO database for analysis. First, we obtained gene modules related to each tissue through WGCNA analysis. Through Gene Ontology (GO) functional annotation, the module of lightyellow (MElightyellow) was closely related to muscle development, and 213 hub genes were screened as follow-up research targets. Further, the difference analysis showed that, except for PREB, all other candidate hub genes were up-regulated (muscle group vs. other-group). ATAC-seq analysis showed that muscle-specific accessible chromatin regions were mainly located in promoter of genes related to muscle structure development (GO:0061061), muscle cell development (GO:0055001) and muscle system process (GO:0003012), which were involved in cAMP, CGMP-PKG, MAPK, and other signaling pathways. Next, we integrated the results of RNA-seq and ATAC-seq analysis, and 54 of the 212 candidate hub genes were identified as key regulatory genes in skeletal muscle development. Finally, through motif analysis, 22 of the 54 key genes were found to be potential target genes of transcription factor MEF2C. Including CAPN3, ACTN2, MB, MYOM3, SRL, CKM, ALPK3, MAP3K20, UBE2G1, NEURL2, CAND2, DOT1L, HRC, MAMSTR, FSD2, LRRC2, LSMEM1, SLC29A2, FHL3, KLHL41, ATXN7L2, and PDRG1. This provides a potential reference for studying the molecular mechanism of skeletal muscle development in mammals.

RNA-Seq and lipidomics reveal different adipogenic processes between bovine perirenal and intramuscular adipocytes.

Adipogenesis involves complex interactions between transcription and metabolic signalling. Exploration of the developmental characteristics of intramuscular adipocyte will provide targets for enhancing beef cattle marbling without increasing obesity. Few reports have compared bovine perirenal and intramuscular adipocyte transcriptomes using the combined analysis of transcriptomes and lipid metabolism to explore differences in adipogenic characteristics. We identified perirenal preadipocytes (PRA) and intramuscular preadipocytes (IMA) in Qinchuan cattle. We found that IMA were highly prolific in the early stages of adipogenesis, while PRA shows a stronger adipogenic ability in the terminal differentiation. Bovine perirenal and intramuscular adipocytes were detected through the combined analysis of the transcriptome and metabolome. More triglyceride was found to be upregulated in perirenal adipocytes; however, more types and amounts of unsaturated fatty acids were detected in intramuscular adipocytes, including eicosapentaenoic acid (20:5 n-3; EPA) and docosahexaenoic acid (22:6 n-3; DHA). Furthermore, differentially expressed genes in perirenal and intramuscular adipocytes were positively correlated with the eicosanoid, phosphatidylcholine (PC), phosphatidyl ethanolamine (PE), and sphingomyelin contents. Associated differential metabolic pathways included the glycerolipid and glycerophospholipid metabolisms. Our research findings provide a basis for the screening of key metabolic pathways or genes and metabolites involved in intramuscular fat production in cattle.

CREB1 promotes proliferation and differentiation by mediating the transcription of CCNA2 and MYOG in bovine myoblasts.

The cAMP response element binding protein 1 (CREB1) is an important nuclear transcription factor in eukaryotes. To explore the potential role of CREB1 on Qinchuan bovine skeletal myoblasts, we investigated the function of CREB1 on proliferation and differentiation. In this study, we found that CREB1 promoted cell proliferation by promoting DNA synthesis in S phase and cell division in G2 phase and promoted myogenic differentiation process in bovine myoblasts. Through dual luciferase experiments, we found that CREB1 can bind to the proximal promoter regions of CCNA2 and MyoG, indicating that CREB1 can play a positive regulatory role in the proliferation and differentiation of myoblasts by mediating the transcription of CCNA2 and MyoG. In addition, through downstream target gene analysis and transcriptome sequencing, we found that CREB1 plays a role in cell proliferation, myogenic differentiation, skeletal muscle repair and other related pathways.

Genomic Variation-Mediating Fluconazole Resistance in Yeast.

Fungal infections pose a serious and growing threat to public health. These infections can be treated with antifungal drugs by killing hazardous fungi in the body. However, the resistance can develop over time when fungi are exposed to antifungal drugs by generating genomic variations, including mutation, aneuploidy, and loss of heterozygosity. The variations could reduce the binding affinity of a drug to its target or block the pathway through which drugs exert their activity. Here, we review genomic variation-mediating fluconazole resistance in the yeast Candida, with the hope of highlighting the functional consequences of genomic variations for the antifungal resistance.

Analysis of stability of reference genes for qPCR in bovine preadipocytes during proliferation and differentiation in vitro.

The stability of internal reference genes is crucial to the reliability of gene expression results using real-time fluorescence quantitative PCR (qRT-PCR). Inappropriate reference genes may lead to inaccurate results or even wrong conclusions. This study aims to identify stable reference genes for analyzing the expression of proliferation-related and differentiation-inducing genes in bovine primary preadipocytes (BPPs) in vitro. In this study, the stability of 16 candidate internal reference genes (GAPDH, ACTB, PPIA, LRP10, HPRT1, YWHAZ, B2M, TBP, EIF3K, RPS9, UXT, 18S rRNA, RPLP0, MARVELD, EMD and RPS15A) for qRT-PCR at proliferation and differentiation stages of BPPs was investigated by three different algorithms (geNorm, NormFinder and BestKeeper). The expression of two marker genes, PCNA and LPL, was used to determine the validity of the candidate reference genes (RGs) at the proliferation and differentiation stages, respectively. The results showed that GAPDH and RPS15A were the most stable RGs in the proliferation of bovine primary preadipocyte, while PPIA was the least stable internal reference gene. RPLP0 and EIF3K were the most stable RGs in the differentiation induction of bovine primary preadipocyte, while GAPDH was the least stable internal reference gene. This study of RGs laid the foundation for subsequent research into the mechanism of proliferation and differentiation of BPPs in vitro using qRT-PCR.

Genetic variants in the serum amyloid A2 (SAA2) gene as a potential marker for milk production traits in Chinese Holstein cows.

BACKGROUND: This study was conducted to detect potential polymorphisms of the serum amyloid A2 (SAA2) gene and explore their relationships with milk production traits in Chinese Holstein cows. OBJECTIVES: THIS STUDY USED: sequencing technology conducted in 532 Chinese Holstein cows. METHODS: Three single nucleotide polymorphisms (SNPs) were identified within intron 1, named g.14061A>G, g.14072G>C and g.14819C>T. Eight estimated haplotypes were identified, of which three major haplotypes had a frequency of Hap3 (-ACC-), Hap5 (-GCC-) and Hap2 (-AGT-), with 17.9%, 12.30% and 8.10%, respectively. RESULTS: The association analysis of single markers (g.14061A>G and g.14819C>T) and combined genotypes (Hap1/5) revealed prominent effects on milk production traits in Chinese Holstein cows (p < 0.05). CONCLUSIONS: Our results suggest that the SAA2 gene is associated with economic traits in Chinese Holstein cows and may be used as candidate gene for marker-assisted selection and management in breeding programs.

Screening and validation of reference genes for qRT-PCR of bovine skeletal muscle-derived satellite cells.

The accuracy of sixteen commonly used internal reference genes was assessed in skeletal muscle-derived satellite cells of Qinchuan cattle at different stages of proliferation and induction of differentiation to determine the most suitable ones. Quantitative real-time PCR and three commonly used algorithmic programs, GeNorm, NormFinder and BestKeeper, were used to evaluate the stability of expression of the candidate internal reference genes (GAPDH, ACTB, PPIA, LRP10, HPRT1, YWHAZ, B2M, TBP, EIF3K , RPS9, UXT, 18S rRNA, RPLP0, MARVELD, EMD and RPS15A) in skeletal muscle-derived satellite cells at 0, 12, 24, 36 and 48 h of growth and after differentiation for 0, 2, 4, 6 and 8 days. The expression of two satellite cell marker genes, CCNA2 and MYF5, was used for validation analysis. The results of the software analyses showed that GAPDH and RPS15A were the most stable reference gene combinations during in vitro proliferation of bovine skeletal muscle-derived satellite cells, RPS15A and RPS9 were the most stable reference gene combinations during in vitro induction of differentiation of the cells, and PPIA was the least stable reference gene during proliferation and differentiation and was not recommended. This study lays the foundation for the selection of reference genes for qRT-PCR during the proliferation and induction of differentiation of bovine skeletal muscle-derived satellite cells.

Structural characteristics and mucosal immune response of the interbranchial lymphoid tissue in the gills of flounder (Paralichthys olivaceus).

A specialized lymphoepithelial tissue termed the interbranchial lymphoid tissue (ILT) is recently identified in several fish species. However, the structural variation and mucosal immune functions of the ILT remain largely unknown. In this study, the anti-Zap-70 MAb was firstly determined to specifically recognize ZAP-70 protein, and CD4-1+, CD4-2+ and CD8ß+ T-cells, but not IgM+ B cells, in peripheral blood leucocytes of flounder (Paralichthys olivaceus). Then we found that aggregates of Zap-70+ cells were located in the epithelium covering the bottom of the interbranchial cleft and along the afferent and efferent edges of the filaments in a cross view, where a meshwork of epithelial cells containing diffused lymphoid cells was exhibited, confirming these structures as the ILT; In a sagittal view, Zap-70+ cells were situated at the base of the filaments (here named as proximal ILT, pILT) and in the interlamellar epithelium (named as distal ILT, dILT). Also, a few IgM+ B cells were distributed at these sites. The lymphoepithelium within pILT and dILT was very thin with a low number of Zap-70+ cells in premetamorphosis and postclimax larvae of flounder, and got thicker containing much more Zap-70+ cells in juvenile and adult individuals. The aggregates of CD4-1+/Zap-70+, CD4-2+/Zap-70+, and CD8ß+/Zap-70+ T-cell subsets were identified in the ILT. Post bath vaccination with inactivated Edwardsiella tarda and then intraperitoneal injection of EdU, the amounts of EdU+ and Zap-70+ cells obviously increased at 3 d and 7 d, and co-localization of EdU+/Zap-70+ cells identified the presence of proliferative T cells; meanwhile, MHC class II-expressing cells were increased. These findings indicated that the ILT in gills of flounder was an important site for the induction of local T cell-mediated immunity, which would lead to a better understanding of mucosal immunity and defense mechanisms of teleost fish.

Construction of Adipogenic ceRNA Network Based on lncRNA Expression Profile of Adipogenic Differentiation of Human MSC Cells.

The Long non-coding RNA (lncRNA) expression profile data of ten samples including human Mesenchymal Stem Cell (MSC) adipogenic differentiation 0, 3, and 6 days from the GEO database, and then perform gene ID conversion, BLAST comparison, and annotation marking. Finally, group A (treatment group on day 3 of differentiation and control group on day 0 of differentiation) obtained a total of 1180 mRNA and 185 lncRNA; group B (treatment group on day 6 of differentiation and control group on day 0 of differentiation). A total of 1376 mRNA and 206 lncRNA were obtained. Finally, we processed the differential lncRNAs and mRNAs obtained in the two groups, and obtained 113 shared differential lncRNAs to further predict the targeted miRNA, a total of 815 lncRNA-miRNA pairs. The targeted mRNA was further predicted, and the grouped differential mRNAs were combined to obtain 64 differential mRNAs. In the end, we obtained 216 ceRNAs containing 26 lncRNAs, 27 miRNAs and 64 mRNAs. We found that the mRNAs in the ceRNA network were mainly enriched with 45 Gene Ontology (GO) terms, mainly including glucose homeostasis mechanism and insulin stimulation response. 69 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were mainly enriched. It mainly includes many pathways related to lipid metabolism such as Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK), Rap1, cAMP, mitogen-activated protein kinase (MAPK), Ras, hypoxia inducible factor-1 (HIF-1), PI3K-Akt, insulin signaling and so on. In the end, we identified 216 ceRNA regulatory relationships related to obesity research. Our research provides a clearer direction for understanding the molecular mechanism of obesity, the screening and determination of drug targets biomarkers in the future.

Screening and Identification of Muscle-Specific Candidate Genes via Mouse Microarray Data Analysis.

Muscle tissue is involved with every stage of life activities and has roles in biological processes. For example, the blood circulation system needs the heart muscle to transport blood to all parts, and the movement cannot be separated from the participation of skeletal muscle. However, the process of muscle development and the regulatory mechanisms of muscle development are not clear at present. In this study, we used bioinformatics techniques to identify differentially expressed genes specifically expressed in multiple muscle tissues of mice as potential candidate genes for studying the regulatory mechanisms of muscle development. Mouse tissue microarray data from 18 tissue samples was selected from the GEO database for analysis. Muscle tissue as the treatment group, and the other 17 tissues as the control group. Genes expressed in the muscle tissue were different to those in the other 17 tissues and identified 272 differential genes with highly specific expression in muscle tissue, including 260 up-regulated genes and 12 down regulated genes. is the genes were associated with the myofibril, contractile fibers, and sarcomere, cytoskeletal protein binding, and actin binding. KEGG pathway analysis showed that the differentially expressed genes in muscle tissue were mainly concentrated in pathways for AMPK signaling, cGMP PKG signaling calcium signaling, glycolysis, and, arginine and proline metabolism. A PPI protein interaction network was constructed for the selected differential genes, and the MCODE module used for modular analysis. Five modules with Score > 3.0 are selected. Then the Cytoscape software was used to analyze the tissue specificity of differential genes, and the genes with high degree scores collected, and some common genes selected for quantitative PCR verification. The conclusion is that we have screened the differentially expressed gene set specific to mouse muscle to provide potential candidate genes for the study of the important mechanisms of muscle development.

Synthesis of anisotropic colloids with concave and convex structures.

Anisotropic colloidal particles with concave and convex structures are useful in both theoretical studies and applications. In this work, we mass-produced polystyrene (PS) colloidal particles with multiple concavities through dispersion polymerization techniques. By increasing the delayed feeding time td of the cross-linker divinylbenzene (DVB), the morphological evolution of particles can be classified into two stages, during which the formation of different concavities is consistent with either the buckling mechanism or phase separation mechanism. By varying the DVB dosage, we found that the size of the big chamber formed on the particle surfaces decreases as the DVB dosage increases. Then, using these concave particles as seeds, 2-5 µm anisotropic colloids with various shapes, including spherical, ellipsoidal, snowman and multi-protrusion, were synthesized by seeded emulsion polymerization. Moreover, our results show that both the chambers and long narrow ditches on the surface of seeds can be the active sites for monomers to gather and polymerize, but monomers in the big chamber have a priority to polymerize first when big and small concavities both exist on seeds. The results of this study could mean great potential in synthesizing a variety of anisotropic particles with well-controlled concave morphologies.

FAM13A promotes proliferation of bovine preadipocytes by targeting Hypoxia-Inducible factor-1 signaling pathway.

The family with sequence similarity 13 member A (FAM13A) gene has been discovered in recent years and is related to metabolism. In this study, the function of FAM13A in precursor adipocyte proliferation in Qinchuan cattle was investigated using fluorescence quantitative polymerase chain reaction (PCR), western blotting, 5-ethynyl-2'-deoxyuridine staining, and other tests. FAM13A promoted precursor adipocyte proliferation. To determine the pathway FAM13A was involved in, transcriptome sequencing, fluorescence quantitative PCR, western blotting, and other tests were used, which identified the hypoxia inducible factor-1 (HIF-1) signalling pathway. Finally, cobalt chloride, a chemical mimic of hypoxia, was used to treat precursor adipocytes. mRNA and protein levels of FAM13A were significantly increased after hypoxia. Thus, FAM13A promoted bovine precursor adipocyte proliferation by inhibiting the HIF-1 signalling pathway, whereas chemically induced hypoxia negatively regulated FAM13A expression, regulating cell proliferation.

UHPLC-MS-MS analysis of oxylipins metabolomics components of follicular fluid in infertile individuals with diminished ovarian reserve.

BACKGROUND: Diminished ovarian reserve (DOR) refers to a decrease in the number and quality of oocytes in the ovary, which results in a lack of sex hormones and a decline of fertility in women. DOR can potentially progress to premature ovarian failure (POF), which has a negative impact on women's quality of life and is a major cause of female infertility. Oxidative stress is a major contributor to fertility decrease in DOR patients, affecting the follicular microenvironment, oocyte maturation, fertilization, and embryo development. Understanding intracellular signal transduction can be achieved by defining specific oxidized lipid components in follicular fluid (FF) of DOR infertile patients. METHODS: The oxylipins metabolic signatures in the FF of DOR patients and females with normal ovarian reserve (NOR) enrolled for the in vitro fertilization (IVF) cycle were analyzed using UHPLC-MS-MS technology. Principal component analysis (PCA) and orthogonal projections to latent structure discriminant analysis (OPLS-DA) were used to analyze the derived metabolomic profiles. Pathway enrichment analysis was carried out using the Kyoto Encyclopedia of Genes and Genomes (KEGG) and MetaboAnalyst databases. Furthermore, the Spearman rank correlation coefficient was used to determine the correlation between age, FSH, AMH, AFC, oocytes retrieved, MII oocytes, fertilization, high-quality embryos, and the concentration of differential oxidized lipid metabolites in FF. RESULTS: Fifteen oxylipins metabolites were found to be lower in the FF of DOR patients than those in the NOR group, including ±20-HDoHE, ±5-iso PGF2α-VI, 12S-HHTrE, 15-deoxy-Δ12,14-PGJ2, 1a,1b-dihomo PGE2, 1a,1b-dihomo PGF2α, 20-COOH-AA, 20-HETE, 8S,15S-DiHETE, PGA2, PGD2, PGE1, PGF1α, PGF2α, and PGJ2. The pathway enrichment analysis revealed that the 15 differentially oxidized lipid metabolites were closely related to the arachidonic acid metabolic pathway. Correlation analysis revealed that the concentration of 8 different oxidized lipid metabolites in FF was negatively correlated to FSH and positively correlated with AFC. AMH, the number of oocytes retrieved, MII oocytes and fertilization, were all positively correlated with 9 different oxidized lipid metabolites, but only one metabolite was positively correlated with the number of high-quality embryos. CONCLUSIONS: Metabolomic analysis of FF revealed that oxylipins metabolism disorders were closely related to ovarian reserve function. Among these oxylipins metabolites, arachidonic acid metabolism undergoes significant changes that may be related to oocyte development, resulting in decreased fertility in DOR patients. TRIAL REGISTRATION: ChiCTR, ChiCTR2000038182 , Registered 12 September 2020-Retrospectively registered.

9-Bromo-2,3-diethylbenzo[de]chromene-7,8-dione (MSN54): A novel non-intercalative topoisomerase II catalytic inhibitor.

Novel mansonone F derivative MSN54 (9-bromo-2,3-diethylbenzo[de]chromene-7,8-dione) exhibited significant cytotoxicity against twelve human tumor cell lines in vitro, with particularly strong potency against HL-60/MX2 cell line resistant to Topo II poisons. MSN54 was found to have IC50 of 0.69 and 1.43 µM against HL-60 and HL-60/MX2 cells, respectively. The resistance index is 10 times lower than that of the positive control VP-16 (etoposide). Various biological assays confirmed that MSN54 acted as a Topo IIα specific non-intercalative catalytic inhibitor. Furthermore, MSN54 exhibited good antitumor efficacy and low toxicity at a dose of 5 mg/kg in A549 tumor xenograft models. Thus, compound MSN54 is a promising candidate for the development of novel antitumor agents.

Corrigendum: Bovine Pre-adipocyte Adipogenesis Is Regulated by bta-miR-150 Through mTOR Signaling.

[This corrects the article DOI: 10.3389/fgene.2021.636550.].