BACKGROUND Advances in diagnostic imaging techniques make it possible to detect tuberculosis (TB) lesions earlier, when only bone destruction or inflammatory infiltration is demonstrated. These techniques provide doctors with more opportunities to treat TB in the early stages of the disease. Traditional aggressive debridement surgery increases the risk of surgical complications. Therefore, we aimed to determine whether using percutaneous pedicle screw (PPS) fixation alone for the treatment of early spinal TB was a valid and less invasive surgical technique. MATERIAL AND METHODS We retrospectively reviewed the clinical and radiographic outcomes in cases with thoracic or lumbar TB treated with PPS surgery or hybrid surgery between January 2010 and January 2017. The operative time, blood loss, length of hospital stay, and hospitalization costs in the 2 groups were recorded and compared. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) before and at 18 months after surgery were tested to evaluate TB progress. Back pain was measured using the visual analog scale (VAS) before the operation and at the final follow-up. Radiological outcomes were evaluated at 1, 6, 12, and 18 months after surgery. A paired t-test was used to evaluate preoperative and postoperative clinical outcomes using SPSS 19.0 software. P values less than 0.05 were considered to be significant. RESULTS A total of 42 patients were involved in this retrospective study. In both groups, the average preoperative ESR, CRP level, and VAS score for back pain significantly decreased after surgery. In the PPS group, the operative time, blood loss, hospital stay, and hospitalization costs were all significantly lower than those in the hybrid group. X-ray and CT images showed satisfactory bone fusion and good maintenance of spinal alignment in both groups at the final follow-up. CONCLUSIONS PPS fixation alone was a valid and less invasive surgery for the treatment of early spinal TB. Furthermore, the recovery process of spinal TB can be facilitated using a "simple" internal fixation procedure, and bone fusion can be achieved without aggressive debridement and bone graft surgery.

Rationale: Atherosclerosis is a chronic inflammatory and epigenetic disease that is influenced by different patterns of blood flow. However, the epigenetic mechanism whereby atheroprotective flow controls endothelial gene programming remains elusive. Here, we investigated the possibility that flow alters endothelial gene expression through epigenetic mechanisms. Methods: En face staining and western blot were used to detect protein expression. Real-time PCR was used to determine relative gene expression. RNA-sequencing of human umbilical vein endothelial cells treated with siRNA of enhancer of zeste homolog 2 (EZH2) or laminar flow was used for transcriptional profiling. Results: We found that trimethylation of histone 3 lysine 27 (H3K27me3), a repressive epigenetic mark that orchestrates gene repression, was reduced in laminar flow areas of mouse aorta and flow-treated human endothelial cells. The decrease of H3K27me3 paralleled a reduction in the epigenetic "writer"-EZH2, the catalytic subunit of the polycomb repressive complex 2 (PRC2). Moreover, laminar flow decreased expression of EZH2 via mechanosensitive miR101. Genome-wide transcriptome profiling studies in endothelial cells treated with EZH2 siRNA and flow revealed the upregulation of novel mechanosensitive gene IGFBP5 (insulin-like growth factor-binding protein 5), which is epigenetically silenced by H3K27me3. Functionally, inhibition of H3K27me3 by EZH2 siRNA or GSK126 (a specific EZH2 inhibitor) reduced H3K27me3 levels and monocyte adhesion to endothelial cells. Adenoviral overexpression of IGFBP5 also recapitulated the anti-inflammatory effects of H3K27me3 inhibition. More importantly, we observed EZH2 upregulation, and IGFBP5 downregulation, in advanced atherosclerotic plaques from human patients. Conclusion: Taken together, our findings reveal that atheroprotective flow reduces H3K27me3 as a chromatin-based mechanism to augment the expression of genes that confer an anti-inflammatory response in the endothelium. Our study exemplifies flow-dependent epigenetic regulation of endothelial gene expression, and also suggests that targeting the EZH2/H3K27me3/IGFBP5 pathway may offer novel therapeutics for inflammatory disorders such as atherosclerosis.

Retinopathy of prematurity (ROP) remains a major cause of childhood blindness and current laser photocoagulation and anti-VEGF antibody treatments are associated with reduced peripheral vision and possible delayed development of retinal vasculatures and neurons. In this study, we advanced the translational potential of adenosine A2A receptor (A2AR) antagonists as a novel therapeutic strategy for selectively controlling pathological retinal neovascularization in oxygen-induced retinopathy (OIR) model of ROP.

Metacaspases (MCs) are cysteine proteases that are important for programmed cell death (PCD) in plants. In this study, we identified 89 MC genes in the genomes of four Gossypium species (Gossypium raimondii, Gossypium barbadense, Gossypium hirsutum, and Gossypium arboreum), and classified them as type-I or type-II genes. All of the type-I and type-II MC genes contain a sequence encoding the peptidase C14 domain. During developmentally regulated PCD, type-II MC genes may play an important role related to fiber elongation, while type-I genes may affect the thickening of the secondary wall. Additionally, 13 genes were observed to be differentially expressed between two cotton lines with differing fiber strengths, and four genes (GhMC02, GhMC04, GhMC07, and GhMC08) were predominantly expressed in cotton fibers at 5-30 days post-anthesis (DPA). During environmentally induced PCD, the expression levels of four genes were affected in the root, stem, and leaf tissues within 6 h of an abiotic stress treatment. In general, the MC gene family affects the development of cotton fibers, including fiber elongation and fiber thickening while four prominent fiber- expressed genes were identified. The effects of the abiotic stress and hormone treatments imply that the cotton MC gene family may be important for fiber development. The data presented herein may form the foundation for future investigations of the MC gene family in Gossypium species.

Liver fibrosis is a common consequence of various chronic hepatitis and liver injuries. The myofibroblasts, through the accumulation of extracellular matrix (ECM) proteins, are closely associated with the progression of liver fibrosis. However, the molecular mechanisms underlying transcriptional regulation of fibrogenic genes and ECM proteins in myofibroblasts remain largely unknown. Using tamoxifen inducible myofibroblast-specific Cre-expressing mouse lines with selective deletion of the transcription factor Yin Yang 1 (YY1), here we show that YY1 deletion in myofibroblasts mitigates carbon tetrachloride-induced liver fibrosis. This protective effect of YY1 ablation on liver fibrosis was accompanied with reduced expression of profibrogenic genes and ECM proteins, including TNF-α, TGF-β, PDGF, IL-6, α-SMA and Col1α1 in liver tissues from YY1 mutant mice. Moreover, using the human hepatic stellate cell (HSC) line LX-2, we found that knockdown of YY1 in myofibroblasts by siRNA treatment diminished myofibroblast proliferation, α-SMA expression, and collagen deposition. Collectively, our findings reveal a specific role of YY1 in hepatic myofibroblasts and suggest a new therapeutic strategy for hepatic fibrosis-associated liver diseases.

Gynostemma pentaphyllum (GP), known as "southern ginseng", can reduce the blood pressure and blood lipid levels. In this study, 300 layer chicks of one day old were divided randomly into three groups (control group (base diet), high addition group (base diet with 1% GP), and low addition group (base diet with 0.5% GP)). After 29 weeks, the growth performance, egg quality, and serum index were determined. Additionally, liver mRNA was identified using RNA-seq to investigate the molecular mechanisms. The results indicated that the serum total cholesterol and triglycerides decreased significantly in the GP addition group. The addition of GP increased the egg weight, Haugh unit and redness (a*) of the egg yolk color, and reduced the yolk cholesterol concentration. Moreover, 95 differentially expressed genes (DEGs) were screened between the control and GP addition group. GO and the KEGG analysis showed that the PPAR pathway was significantly enriched. Five fatty acid metabolism-related genes (FABP3, CYP7A1, ANKRD22, SCD1, and PCK1) were validated by qRT-PCR analysis, which confirmed the tendency of the expression. These DEGs in the PPAR pathway may be the key factors of GP affecting fatty acid metabolism. These results may provide a theoretical basis for further research and new insights into GP as a feed additive.

Limited circulating tumor cells (CTCs) capturing efficiency and lack of regulation capability on CTC-supportive metastatic niches (MNs) are two main obstacles hampering the clinical translation of conventional liposomes for the treatment of metastatic breast cancers. Traditional delivery strategies, such as ligand modification and immune modulator co-encapsulation for nanocarriers, are inefficient and laborious. Here, a multifunctional Rg3 liposome loading with docetaxel (Rg3-Lp/DTX) was developed, in which Rg3 was proved to intersperse in the phospholipid bilayer and exposed its glycosyl on the liposome surface. Therefore, it exhibited much higher CTC-capturing efficiency via interaction with glucose transporter 1 (Glut1) overexpressed on CTCs. After reaching the lungs with CTCs, Rg3 inhibited the formation of MNs by reversing the immunosuppressive microenvironment. Together, Rg3-Lp/DTX exhibited excellent metastasis inhibition capacity by CTC ("seeds") neutralization and MN ("soil") inhibition. The strategy has great clinical translation prospects for antimetastasis treatment with enhanced therapeutic efficacy and simple preparation process.

Development of abdominal aortic aneurysms (AAA) enhances lesion group-2 innate lymphoid cell (ILC2) accumulation and blood IL5. ILC2 deficiency in Rorafl/fl Il7rCre/+ mice or induced ILC2 depletion in Icosfl-DTR-fl/+ Cd4Cre/+ mice expedites AAA growth, increases lesion inflammation, but leads to systemic IL5 and eosinophil (EOS) deficiency. Mechanistic studies show that ILC2 protect mice from AAA formation via IL5 and EOS. IL5 or ILC2 from wild-type (WT) mice, but not ILC2 from Il5-/- mice induces EOS differentiation in bone-marrow cells from Rorafl/fl Il7rCre/+ mice. IL5, IL13, and EOS or ILC2 from WT mice, but not ILC2 from Il5-/- and Il13-/- mice block SMC apoptosis and promote SMC proliferation. EOS but not ILC2 from WT or Il5-/- mice block endothelial cell (EC) adhesion molecule expression, angiogenesis, dendritic cell differentiation, and Ly6Chi monocyte polarization. Reconstitution of WT EOS and ILC2 but not Il5-/- ILC2 slows AAA growth in Rorafl/fl Il7rCre/+ mice by increasing systemic EOS. Besides regulating SMC pathobiology, ILC2 play an indirect role in AAA protection via the IL5 and EOS mechanism.

Microtubules (MTs) are of importance to fiber development. The Xklp2 (TPX2) proteins as a class of microtubule-associated proteins (MAPs) play a key role in plant growth and development by regulating the dynamic changes of microtubules (MTs). However, the mechanism underlying this is unknown. The interactions between TPX2 proteins and tubulin protein, which are the main structural components, have not been studied in fiber development of upland cotton. Therefore, a genome-wide analysis of the TPX2 family was firstly performed in Gossypiumhirsutum L. This study identified 41 GhTPX2 sequences in the assembled G. hirsutum genome by a series of bioinformatic methods. Generally, this gene family is phylogenetically grouped into six subfamilies, and 41 G. hirsutum TPX2 genes (GhTPX2s) are distributed across 21 chromosomes. A heatmap of the TPX2 gene family showed that homologous GhTPX2 genes, GhWDLA2/7 and GhWDLA4/9, have large differences in expression levels between two upland cotton recombinant inbred lines (69307 and 69362) that are different in fiber quality at 15 and 20 days post anthesis. The relative data indicate that these four genes are down-regulated under oryzalin, which causes microtubule depolymerization, as determined via qRT-PCR. A subcellular localization experiment suggested that GhWDLA2 and GhWDLA7 are localized to the microtubule cytoskeleton, and GhWDLA4 and GhWDLA9 are only localized to the nucleus. However, only GhWDLA7 between GhWDLA2 and GhWDLA7 interacted with GhTUA2 in the yeast two-hybrid assay. These results lay the foundation for further function study of the TPX2 gene family.

The chemotherapy effect of docetaxel (DTX) against triple-negative breast cancer (TNBC) remains mediocre and limited when encapsulated in conventional cholesterol liposomes, mainly ascribed to poor penetration and immunosuppressive tumor microenvironment (TME) caused by tumor stroma cells, especially cancer-associated fibroblasts (CAFs). Many studies have attempted to address these problems but trapped into the common dilemma of excessively complicated formulation strategies at the expense of druggability as well as clinical translational feasibility. To better address the discrepancy, ginsenoside Rg3 was utilized to substitute cholesterol to develop a multifunctional DTX-loaded Rg3 liposome (Rg3-Lp/DTX). The obtained Rg3-Lp/DTX was proved to be preferentially uptake by 4T1 cells and accumulate more at tumor site via the interaction between the glycosyl moiety of Rg3 exposed on liposome surface and glucose transporter1 (Glut1) overexpressed on tumor cells. After reaching tumor site, Rg3 was shown to reverse the activated CAFs to the resting stage and attenuate the dense stroma barrier by suppressing secretion of TGF-β from tumor cells and regulating TGF-β/Smad signaling. Therefore, reduced levels of CAFs and collagens were found in TME after incorporation of Rg3, inducing enhanced penetration of Rg3-Lp/DTX in the tumor and reversed immune system which can detect and neutralize tumor cells. Compared with wooden cholesterol liposomes, the smart and versatile Rg3-Lp/DTX could significantly improve the anti-tumor effect of DTX, providing a promising approach for TNBC therapy with excellent therapeutic efficacy and simple preparation process.

Retinopathy of prematurity (ROP) remains one of the major causes of blindness in children worldwide. While current ROP treatments are mostly disruptive to reduce proliferative neovascularization by targeting the hypoxic phase, protection against early hyperoxia-induced retinal vascular loss represents an effective therapeutic window, but no such therapeutic strategy is available. Built upon our recent demonstration that the protection against oxygen-induced retinopathy by adenosine A2A receptor (A2A R) antagonists is most effective when administered at the hyperoxia (not hypoxic) phase, we here uncovered the cellular mechanism underlying the A2A R-mediated protection against early hyperoxia-induced retinal vascular loss by reversing the inhibition of cellular proliferation via possibly multiple signaling pathways. Specifically, we revealed two distinct stages of the hyperoxia phase with greater cellular proliferation and apoptosis activities and upregulation of adenosine signaling at postnatal 9 day (P9) but reduced cellular activities and adenosine-A2A R signaling at P12. Importantly, the A2A R-mediated protection at P9 was associated with the reversal of hyperoxia-induced inhibition of progenitor cells at the peripheral retina at P9 and of retinal endothelial proliferation at P9 and P12. The critical role of cellular proliferation in the hyperoxia-induced retinal vascular loss was validated by the increased avascular areas by siRNA knockdown of the multiple signaling molecules involved in modulation of cellular proliferation, including activin receptor-like kinase 1, DNA-binding protein inhibitor 1, and vascular endothelial growth factor-A.

Trehalose, a naturally occurring non-toxic disaccharide, has attracted considerable attention for its potential in alleviating oxidative stress in skeletal muscle. In this study, our aim was to elucidate the metabolic mechanisms underlying the protective effects of trehalose against hydrogen peroxide (H2O2)-induced oxidative stress in C2C12 myoblasts. Our results show that both trehalose treatment and pretreatment effectively alleviate the H2O2-induced decrease in cell viability, reduce intracellular reactive oxygen species (ROS), and attenuate lipid peroxidation. Furthermore, using NMR-based metabolomics analysis, we observed that trehalose treatment and pretreatment modulate the metabolic profile of myoblasts, specifically regulating oxidant metabolism and amino acid metabolism, contributing to their protective effects against oxidative stress. Importantly, our results reveal that trehalose treatment and pretreatment upregulate the expression levels of P62 and Nrf2 proteins, thereby activating the Nrf2-NQO1 axis and effectively reducing oxidative stress. These significant findings highlight the potential of trehalose supplementation as a promising and effective strategy for alleviating oxidative stress in skeletal muscle and provide valuable insights into its potential therapeutic applications.

The transcription factors CDX1 and CDX2 are homeobox genes that regulate development of the epithelium of the small and large intestine. A few studies have shown that Cdx2 protein expression is useful in the diagnosis of adenocarcinomas as well as neuroendocrine tumors of the small and large intestine. To examine the utility of Cdx2 in recognizing neuroendocrine tumors of unknown primary sites, we analyzed 224 primary and metastatic neuroendocrine tumors by immunohistochemistry. The specificity of the antibody reaction was confirmed by Western blotting. Cdx2 antibody stained all primary and most metastatic midgut carcinoid tumors. A few rectal and pulmonary carcinoids were positive, while gastric carcinoids were negative for Cdx2. One of five small cell carcinomas (20%) of the colon was positive for Cdx2, while all pulmonary small cell carcinomas were negative. Neuroendocrine tumors of the pituitary, parathyroid, medullary thyroid carcinomas, paragangliomas, pheochromocytomas and Merkel cell carcinomas were all negative for Cdx2. Western blot analysis of seven cases showed a 40 kDa band in both primary and metastatic midgut carcinoid tumors. These results indicate that Cdx2 can be very useful in recognizing metastatic neuroendocrine carcinomas of unknown primary sites, especially when they are derived from the small intestine.

RhoE/Rnd3 is an atypical member of the Rho superfamily of proteins, However, the global biological function profile of this protein remains unsolved. In the present study, a RhoE‑knockout H9C2 cardiomyocyte cell line was established using CRISPR/Cas9 technology, following which differentially expressed genes (DEGs) between the knockout and wild‑type cell lines were screened using whole genome expression gene chips. A total of 829 DEGs, including 417 upregulated and 412 downregulated, were identified using the threshold of fold changes ≥1.2 and P<0.05. Using the ingenuity pathways analysis system with a threshold of ‑Log (P‑value)>2, 67 canonical pathways were found to be enriched. Many of the detected signaling pathways, including that of oncostatin M signaling, were found to be associated with the inflammatory response. Subsequent disease and function analysis indicated that apart from cardiovascular disease and development function, RhoE may also be involved in other diseases and function, including organismal survival, cancer, organismal injury and abnormalities, cell‑to‑cell signaling and interaction, and molecular transport. In addition, 885 upstream regulators were enriched, including 59 molecules that were predicated to be strongly activated (Z‑score >2) and 60 molecules that were predicated to be significantly inhibited (Z‑scores <‑2). In particular, 33 regulatory effects and 25 networks were revealed to be associated with the DEGs. Among them, the most significant regulatory effects were 'adhesion of endothelial cells' and 'recruitment of myeloid cells' and the top network was 'neurological disease', 'hereditary disorder, organismal injury and abnormalities'. In conclusion, the present study successfully edited the RhoE gene in H9C2 cells using CRISPR/Cas9 technology and subsequently analyzed the enriched DEGs along with their associated canonical signaling pathways, diseases and functions classification, upstream regulatory molecules, regulatory effects and interaction networks. The results of the present study should facilitate the discovery of the global biological and functional properties of RhoE and provide new insights into role of RhoE in human diseases, especially those in the cardiovascular system.

The transition from meiotic spermatocytes to postmeiotic haploid germ cells constitutes an essential step in spermatogenesis. The epigenomic regulatory mechanisms underlying this transition remain unclear. Here, we find a prominent transcriptomic switch from the late spermatocytes to the early round spermatids during the meiotic-to-postmeiotic transition, which is associated with robust histone acetylation changes across the genome. Among histone deacetylases (HDACs) and acetyltransferases, we find that HDAC3 is selectively expressed in the late meiotic and early haploid stages. Three independent mouse lines with the testis-specific knockout of HDAC3 show infertility and defects in meiotic exit with an arrest at the late stage of meiosis or early stage of round spermatids. Stage-specific RNA-seq and histone acetylation ChIP-seq analyses reveal that HDAC3 represses meiotic/spermatogonial genes and activates postmeiotic haploid gene programs during meiotic exit, with associated histone acetylation alterations. Unexpectedly, abolishing HDAC3 catalytic activity by missense mutations in the nuclear receptor corepressor (NCOR or SMRT) does not cause infertility, despite causing histone hyperacetylation as HDAC3 knockout, demonstrating that HDAC3 enzyme activity is not required for spermatogenesis. Motif analysis of the HDAC3 cistrome in the testes identified SOX30, which has a similar spatiotemporal expression pattern as HDAC3 during spermatogenesis. Depletion of SOX30 in the testes abolishes the genomic recruitment of the HDAC3 to the binding sites. Collectively, these results establish the SOX30/HDAC3 signaling as a key regulator of the transcriptional program in a deacetylase-independent manner during the meiotic-to-postmeiotic transition in spermatogenesis.

Idiopathic pulmonary fibrosis (IPF) is a lethal human disease with short survival time and few treatment options. Herein, we demonstrated that discoidin domain receptor 2 (DDR2), a receptor tyrosine kinase that predominantly transduces signals from fibrillar collagens, plays a critical role in the induction of fibrosis and angiogenesis in the lung. In vitro cell studies showed that DDR2 can synergize the actions of both transforming growth factor (TGF)-β and fibrillar collagen to stimulate lung fibroblasts to undergo myofibroblastic changes and vascular endothelial growth factor (VEGF) expression. In addition, we confirmed that late treatment of the injured mice with specific siRNA against DDR2 or its kinase inhibitor exhibited therapeutic efficacy against lung fibrosis. Thus, this study not only elucidated novel mechanisms by which DDR2 controls the development of pulmonary fibrosis, but also provided candidate target for the intervention of this stubborn disease.

The cellulose synthase gene superfamily, which includes the cellulose synthase (Ces) and cellulose synthase-like (Csl) families, is involved in the synthesis of cellulose and hemicellulose. This superfamily is critical for cotton fiber development in Gossypium species. Applying a series of bioinformatic methods, we identified 228 Ces/Csl genes from four Gossypium species (G. hirsutum, G. barbadense, G. arboreum, and G. raimondii). These genes were then grouped into 11 subfamilies based on phylogenetic relationships. A subsequent analysis of gene evolution revealed sites in CSLG and CSLJ genes that were under long-term positive selection pressure, with a posterior probability >0.95. Moreover, the dN:dS value for the CSLJ clade was 1.305, suggesting this subfamily was under positive selection pressure. Our data indicated that the dN:dS value ranged from 0.0084 to 0.9693 among the homologous Ces/Csl genes, implying they were under purifying selection pressure. Our transcriptome and qRT-PCR analyses revealed that CesA genes were more highly expressed in tetraploids than in diploids. However, the Csl expression levels exhibited the opposite trend. Furthermore, changes to promoter sequences may have influenced the expression of homologous Ces/Csl genes. Our findings may provide novel insights into the evolutionary relationships and expression patterns of the Ces/Csl genes in Gossypium species.

Mechanistic target of rapamycin (mTOR) controls cell growth and metabolism in response to environmental and metabolic signals. Rapamycin robustly extends the lifespan in mammals and has clinical relevance in organ transplantation and cancer therapy but side effects include male infertility. Here, we report that chronic rapamycin treatment causes spermatogenic arrest in adult male mice due to defects in sex body formation and meiotic sex chromosome inactivation (MSCI). Many sex chromosome-linked genes were up-regulated in isolated pachytene spermatocytes from rapamycin-treated mice. RNA-Seq analysis also identified mRNAs encoding the core piRNA pathway components were decreased. Furthermore, rapamycin treatment was associated with a drastic reduction in pachytene piRNA populations. The inhibitory effects of rapamycin on spermatogenesis were partially reversible, with restoration of testis mass and sperm motility within 2 months of treatment cessation. Collectively, we have defined an essential role of mTOR in MSCI and identified a novel function as a regulator of small RNA homeostasis in male germ cells.

The egg-laying rate is an important indicator for evaluating fertility of poultry. In order to better understand the laying mechanism of Muscovy ducks, gene expression profiles and pathways of ovarian tissues in high- and low-laying black (BH and BL) and white Muscovy ducks (WH and WL) during the peak production period were performed by using RNA-seq. The total number of reads produced for each ovarian sample ranged from 44,344,070 to 47,963,328. A total of 113, 619 and 87 differentially expressed genes (DEGs) were identified in BH-vs-WH, BL-vs-BH and BL-vs-WL, respectively. Among them, 54, 356 and 49 genes were up regulated and 59, 263 and 38 genes were down regulated. In addition, there were only 10 up-regulated genes in WL-vs-WH. In the comparison of DEGs in black and white Muscovy ducks, two co-expressed DEG genes were detected between BH-vs-WH and BL-vs-WL and seven DEGs were co-expressed between BL-vs-BH and WL-vs-WH. The RNA-Seq data were confirmed to be reliable by qPCR. Numerous DEGs known to be involved in ovarian development were identified, including TGFβ2, NGFR, CEBPD, CPEB2, POSTN, SMOC1, FGF18, EFNA5 and SDC4. Gene Ontology (GO) annotations indicated that DEGs related to ovarian development were mainly enriched in biological processes of "circadian sleep/wake cycle process," "negative regulation of transforming growth factor-β secretion," "positive regulation of calcium ion transport" in BH-vs-WH and "cell surface receptor signaling pathway," "Notch signaling pathway" and "calcium ion transport" in BL-vs-BH. Besides, "steroid biosynthetic process," "granulosa cell development" and "egg coat formation" were mainly enriched in BL-vs-WL and "reproduction," "MAPK cascade" and "mitotic cell cycle" were mainly enriched in WL-vs-WH. KEGG pathway analysis showed that the PI3K-Akt signaling pathway and ovarian steroidogenesis were the most enriched in Muscovy duck ovary transcriptome data. This work highlights potential genes and pathways that may affect ovarian development in Muscovy duck.

Angiogenesis is a physiological process for the formation of new blood vessels from the pre-existing vessels and it has a vital role in the survival and growth of neoplasms. During tumor angiogenesis, the activation of the gene transcriptions in vascular endothelial cells (ECs) plays an essential role in the promotion of EC proliferation, migration, and vascular network development. However, the molecular mechanisms underlying transcriptional regulation of EC and tumor angiogenesis remains to be fully elucidated. Here we report that the transcription factor Yin Yang 1 (YY1) in ECs is critically involved in tumor angiogenesis. First, we utilized a tamoxifen-inducible EC-specific YY1 deficient mouse model and showed that YY1 deletion in ECs inhibited the tumor growth and tumor angiogenesis. Using the in vivo matrigel plug assay, we then found that EC-specific YY1 ablation inhibited growth factor-induced angiogenesis. Furthermore, vascular endothelial growth factor (VEGF)-induced EC migration was diminished in YY1-depleted human umbilical vein endothelial cells (HUVECs). Finally, a rescue experiment revealed that YY1-regulated BMP6 expression in ECs was involved in EC migration. Collectively, our results demonstrate that endothelial YY1 has a crucial role in tumor angiogenesis and suggest that targeting endothelial YY1 could be a potential therapeutic strategy for cancer treatment.