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BACKGROUND: Placental exosomes are a kind of intercellular communication media secreted by placental cells during pregnancy, exosomogenesis and release are regulated by many secretory glycoproteins. CREG1 is a kind of secreted glycoprotein widely expressed in various organs and tissues of the body, which inhibits cell proliferation and enhances cell differentiation. The aim of this study was to explore the role of CREG1 in regulating exosomogenesis during the proliferation and differentiation of placental trophoblast cells in early pregnant dairy cows by targeting IGF2R and participating in regulating organoid differentiation via exosomes transport. METHODS: Molecular biological methods were firstly used to investigate the expression patterns of CREG1, IGF2R and exosomal marker proteins in early placental development of pregnant dairy cows. Subsequently, the effects of CREG1 on the formation and release of bovine placental trophoblast (BTCs) derived exosomes by targeting IGF2R were investigated. Further, the effects of CREG1 on the change of gene expression patterns along with the transport of exosomes to recipient cells and participate in regulating the differentiation of organoids were explored. RESULTS: The expression of CREG1, IGF2R and exosomal marker proteins increased with the increase of pregnancy months during the early evolution of placental trophoblast cells in dairy cows. Overexpression of Creg1 enhanced the genesis and release of exosomes derived from BTCs, while knocking down the expression of Igf2r gene not only inhibited the genesis of exosomes, but also inhibited the genesis and release of exosomes induced by overexpression of CREG1 protein. Interestingly, IGF2R can regulate the expression of CREG1 through reverse secretion. What's more, the occurrence and release of trophoblast-derived exosomes are regulated by CREG1 binding to IGF2R, which subsequently binds to Rab11. CREG1 can not only promote the formation and release of exosomes in donor cells, but also regulate the change of gene expression patterns along with the transport of exosomes to recipient cells and participate in regulating the early development of placenta. CONCLUSIONS: Our study confirmed that CREG1 is involved in the exosomogenesis and release of exosomes during the proliferation and differentiation of placental trophoblast cells in early pregnant dairy cows by targeting IGF2R, and is involved in the regulation of organoid differentiation through exosome transport.
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Diferenciação Celular , Exossomos , Placenta , Receptor IGF Tipo 2 , Trofoblastos , Animais , Exossomos/metabolismo , Bovinos , Trofoblastos/metabolismo , Trofoblastos/citologia , Feminino , Gravidez , Receptor IGF Tipo 2/metabolismo , Receptor IGF Tipo 2/genética , Placenta/metabolismo , Placenta/citologia , Organoides/metabolismo , Organoides/citologia , Proliferação de CélulasRESUMO
Bovine viral diarrhoea virus (BVDV) can infect cows on days 30-110 of gestation and crossing the placental barrier, resulting in persistently infected (PI) and causing significant economic losses to dairy farming. Bovine placental trophoblast cells (BTCs) are the major cells in the early chorionic tissue of the placenta and play important roles in placental resistance to viral transmission. In this study, we have confirmed that BTCs is among a groups of cell types those could be infected by BVDV in vivo, and BVDV infection stimulates the autophagic responses in BTCs and promotes the release of exosomes. Meanwhile, the exosomes derived from BTCs can be used by BVDV to spread between placental trophoblast cells, and this mode of transmission cannot be blocked by antibodies against the BVDV E2 protein, whereas the replication and spread of BVDV in BTCs can be blocked by inhibiting autophagy and exosomogenesis. Our study provides a theoretical and practical basis for scientific prediction and intervention of reproductive disorders caused by BVDV infection in cows of different gestation periods from a novel perspective.
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Autofagia , Doença das Mucosas por Vírus da Diarreia Viral Bovina , Vírus da Diarreia Viral Bovina , Exossomos , Trofoblastos , Animais , Bovinos , Feminino , Trofoblastos/virologia , Trofoblastos/imunologia , Exossomos/metabolismo , Exossomos/virologia , Doença das Mucosas por Vírus da Diarreia Viral Bovina/transmissão , Doença das Mucosas por Vírus da Diarreia Viral Bovina/virologia , Doença das Mucosas por Vírus da Diarreia Viral Bovina/imunologia , Gravidez , Vírus da Diarreia Viral Bovina/fisiologia , Vírus da Diarreia Viral Bovina/imunologia , Placenta/virologia , Placenta/imunologia , Células Cultivadas , Replicação ViralRESUMO
The development of scalable and passive coatings that can adapt to seasonal temperature changes while maintaining superhydrophobic self-cleaning functions is crucial for their practical applications. However, the incorporation of passive cooling and heating functions with conflicting optical properties in a superhydrophobic coating is still challenging. Herein, an all-in-one coating inspired by the hierarchical structure of a lotus leaf that combines surface wettability, optical structure, and temperature self-adaptation is obtained through a simple one-step phase separation process. This coating exhibits an asymmetrical gradient structure with surface-embedded hydrophobic SiO2 particles and subsurface thermochromic microcapsules within vertically distributed hierarchical porous structures. Moreover, the coating imparts superhydrophobicity, high infrared emission, and thermo-switchable sunlight reflectivity, enabling autonomous transitions between radiative cooling and solar warming. The all-in-one coating prevents contamination and over-cooling caused by traditional radiative cooling materials, opening up new prospects for the large-scale manufacturing of intelligent thermoregulatory coatings.
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As a pivotal player in spermatogenesis, the blood-testis barrier (BTB) made from junction apparatus coexisting in Sertoli cells (SCs) is impaired with an increase in age and ultimately induces spermatogenic dysfunction or even infertility. It has been corroborated that bone marrow mesenchymal stem cell (BMSC) transplantation can efficiently repair and regenerate the testicular function. As vital mediators of cell-to-cell communication, MSC-derived exosomes (Exos) can directly serve as therapeutic agents for tissue repair and regeneration. However, the therapeutic value of BMSC-Exos in aging-induced BTB damage remains to be confirmed. In this study, we explored that the old porcine testes had defective autophagy, which aggravated BTB disruption in SCs. BMSC-Exos could decrease ROS production and NLRP3 inflammasome activation but enhanced autophagy and tight junction (TJ) function in D-gal-triggered aging porcine SCs and mouse model testes, according to in vitro and in vivo experiments. Furthermore, rapamycin, NAC, MCC950, and IL-1Ra restored the TJ function in D-gal-stimulated aging porcine SCs, while BMSC-Exos' stimulatory effect on TJ function was inhibited by chloroquine. Moreover, the treatment with BMSC-Exos enhanced autophagy in D-gal-induced aging porcine SCs by means of the AMPK/mTOR signal transduction pathway. These findings uncovered through the present study that BMSC-Exos can enhance the BTB function in aging testes by improving autophagy via the AMPK/mTOR signaling pathway, thereby suppressing ROS production and NLRP3 inflammasome activation.
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Abnormal function and fibrosis of endometrium caused by cows' endometritis pose difficult implantation of embryos and uterine cavity adhesions. 17ß-Estradiol (E2) serves as the most effective aromatized estrogen, and its synthetase and receptors have been detected in the endometrium. Studies have demonstrated the positive role of estrogen in combating pathological fibrosis in diverse diseases. However, it is still unknown whether E2 regulates endometrium fibrosis in bovine endometritis. Herein, we evaluated the expression patterns of transforming growth factor-ß1 (TGF-ß1), epithelial-mesenchymal transformation (EMT)-related proteins (α-SMA, vimentin N-cadherin and E-cadherin), cytochrome P450 19A1 (CYP19A1), and G protein-coupled estrogen receptor (GPER) in bovine healthy endometrium and Inflammatory endometrium. Our data showed that the inflamed endometrium presented low CYP19A1 and GPER expression, and significantly higher EMT process versus the normal tissue. Moreover, we established a TGF-ß1-induced fibrosis model in BEND cells, and found that E2 inhibited the EMT process of BEND cells in a dose-dependent manner. The anti-fibrotic effect of E2 was blocked by the GPER inhibitor G15, but not the estrogen nuclear receptors (ERs) inhibitor ICI182780. Moreover, the GPER agonist G1 inhibited fibrosis and Smad2/3 phosphorylation but increased the expression of TGFBR3 in BEND cells. Transfection with TGFBR3 small interfering RNA blocked the effect of G1 on fibrosis of BEND cells and upregulated the expression of P-Smad2/3. Our in vivo data also showed that E2 and G1 affected uterus fibrosis in mice endometritis model caused by LPS, which was associated with the inhibition of TGFBR3/Smad2/3 signaling. In conclusion, our data implied that E2 alleviates the fibrosis of TGF-ß1-induced BEND cells, which is associated with the GPER mediation of TGFBR3/Smad2/3 signaling.
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Endometrite , Estradiol , Proteoglicanas , Receptores de Fatores de Crescimento Transformadores beta , Fator de Crescimento Transformador beta1 , Animais , Bovinos , Feminino , Camundongos , Endometrite/metabolismo , Endométrio/metabolismo , Células Epiteliais/metabolismo , Transição Epitelial-Mesenquimal , Estradiol/farmacologia , Estrogênios/metabolismo , Fibrose , Receptores Acoplados a Proteínas G/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Proteínas Smad/metabolismoRESUMO
Solar interfacial steam power generation is a prospective method for seawater desalination. In this work, a salt-blocking three-dimensional (3D) Janus evaporator with a superhydrophobic to superhydrophilic gradient was fabricated by spraying a composite dispersion of multi-walled carbon nanotubes/polydimethylsiloxane (CNTs/PDMS) onto the top side of a polyurethane (PU) foam and polyvinyl alcohol (PVA) solution onto the bottom side. The CNTs/PDMS composite dispersion with nanostructured CNTs and low surface energy PDMS combined with the porous structure of the PU foam rendered the top side superhydrophobic. Therefore, a layer suitable for photothermal conversion was obtained. The hydrophilic PVA combined with the porous structure of the foam rendered the bottom side superhydrophilic, facilitating water absorption and transportation. The asymmetric wettability gradient of the CNTs/PDMS-PU-PVA as a 3D evaporator caused the evaporation rate and transportation speed of water to reach a balance, and the salt was quickly dissolved at the superhydrophilic interface. This 3D salt-resistant Janus evaporator achieved an evaporation rate of 2.26 kg m-2 h-1 under 1 kW m-2 illumination.
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The mechanical durability of superhydrophobic surfaces is of significance for their practical applications. However, few reports about superhydrophobic coating on certain substrates took into consideration both the mechanical stability of the superhydrophobic coating and adhesion stability between the coating and the substrate. Herein, we put forward a facile and efficient strategy to construct robust superhydrophobic coatings by simply spray-coating a composite suspension of SiO2 nanoparticles, polydimethylsiloxane (PDMS), and epoxy resin (EP) on substrates pretreated with an EP base-coating. The as-obtained coating exhibited excellent superhydrophobicity with water contact angle of 163° and sliding angle of 3.5°, which could endure UV irradiation of 180 h, immersion in acidic or basic solutions for 168 h, and outdoor exposure for over 30 days. Notably, the coating surface retained superhydrophobicity after being successively impacted with faucet water for 1 h, impinged with 360 g sand grains, and abraded with sandpaper of 120 grid under a load of 500 g for 5 m distance. The outstanding mechanical stability was mainly attributed to the cross-linking of EP and the elastic nature of PDMS which ensured strong cohesion inside the whole coating and to the substrate. Additionally, the coating showed self-healing capacity against O2 plasma etching. The method is simple with the materials commercially available and is expected to be widely applied in outdoor applications.
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Passive daytime radiative cooling (PDRC) technology provides an eco-friendly cooling strategy by reflecting sunlight reaching the surface and radiating heat underneath to the outer space through the atmospheric transparency window. However, PDRC materials face challenges in cooling performance degradation caused by outdoor contamination and requirements of easy fabrication approaches for scale-up and high cooling efficiency. Herein, a polymer composite coating of polystyrene, polydimethylsiloxane and poly(ethyl cyanoacrylate) (PS/PDMS/PECA) with superhydrophobicity and radiative cooling performance was fabricated and demonstrated to have sustained radiative cooling capability, utilizing the superhydrophobic self-cleaning property to maintain the optical properties of the coating surface. The prepared coating is hierarchically porous which exhibits an average solar reflectance of 96% with an average emissivity of 95% and superhydrophobicity with a contact angle of 160°. The coating realized a subambient radiative cooling of 12.9 °C in sealed air and 7.5 °C in open air. The self-cleaning property of the PS/PDMS/PECA coating helped sustain the cooling capacity for long-term outdoor applications. Moreover, the coating exhibited chemical resistance, UV resistance, and mechanical durability, which has promising applications in wider fields.
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Many individual herbs and herbal formulae have been demonstrated to provide safe and effective treatment for pancreatic ductal adenocarcinoma (PDAC); however, the therapeutic mechanisms underlying their effects have not been fully elucidated. A total of 114 herbal formulae comprising 216 single herbal medicines used to treat PDAC were identified. Cluster analysis revealed a core prescription including four herbs [Glycyrrhizae Radix et Rhizome (Gan Cao), Codonopsis Radix (Dang Shen), Citri Reticulatae Pericarpium (Chen Pi), and Pinelliae Rhizoma (Ban Xia)] in combination to treat PDAC, and 295, 256, 141, and 365 potential targets were screened for each of these four herbs, respectively. PDAC-related proteins (n = 2940) were identified from the DisGeNET database. Finally, 44 overlapping targets of herbs and PDAC were obtained, representing potential targets of the herbal medicines for PDAC treatment. GO enrichment analysis indicated that targets common to herbs and PDAC primarily functioned in response to steroid hormones. KEGG pathway enrichment analysis indicated that the herbs may prevent PDAC by influencing apoptotic, p53, and PI3K/Akt signaling pathways. Further, molecular docking analysis indicated that of identified bioactive compounds, stigmasterol, phaseol, perlolyrine, shinpterocarpin, and licopyranocoumarin have good binding ability with proteins involved in responses to steroid hormones, while stigmasterol, phaseol, perlolyrine, and DIOP have good binding ability with PTGS2(also known as COX-2), ESR1, ESR2, AR, and PGR. The anti-PDAC activity of herbal medicines may be mediated via regulation of proteins with roles in responses to steroid hormones. This study provides further evidence supporting the potential for use of herbal medicines to treat PDAC.
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Adenocarcinoma , Medicamentos de Ervas Chinesas , Plantas Medicinais , Adenocarcinoma/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Hormônios , Humanos , Simulação de Acoplamento Molecular , Fosfatidilinositol 3-Quinases , Esteroides , EstigmasterolRESUMO
Traditional electric cooling in summer and coal heating in winter consume a huge amount of energy and lead to a greenhouse effect. Herein, we developed an energy-free dual-mode superhydrophobic film, which consists of a white side with porous coating of styrene-ethylene-butylene-styrene/SiO2 for radiative cooling and a black side with nanocomposite coating of carbon nanotubes/polydimethylsiloxane for solar heating. In the cooling mode with the white side, the film achieved a high sunlight reflection of 94% and a strong long-wave infrared emission of 92% in the range of 8-13 µm to contribute to a temperature drop of â¼11 °C. In the heating mode with the black side, the film achieved a high solar absorption of 98% to induce heating to raise the air temperature beneath by ΔT of â¼35.6 °C. Importantly, both sides of the film are superhydrophobic with a contact angle over 165° and a sliding angle near 0°, showing typical self-cleaning effects, which defend the surfaces from outdoor contamination, thus conducive to long-term cooling and heating. This dual-mode film shows great potential in outdoor applications as coverings for both cooling in hot summer and heating in winter without an energy input.
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This study evaluated quality attributes and in vivo antioxidant activity of Auricularia cornea var. Li polysaccharide (ACP)-fortified set yogurt during 21 days of storage (4 °C). Set yogurt was manufactured using a commercial yogurt culture, and 3% (w/v) ACP was added. Physicochemical (pH, titratable acidity, and water-holding capacity), textural, rheological, microstructural, flavor, and antioxidant properties of set yogurt were investigated. The results showed that the addition of ACP significantly enhanced WHC, viscosity, firmness, and cohesiveness, while inhibiting post-acidification of set yogurt during storage. The yogurt supplemented with ACP showed a larger hysteresis area and higher G' and Gâ³ values, formed a porous, dense, mesh-like structure and exhibited a unique mushroom flavor. Antioxidant results showed that administration of ACP-fortified yogurt significantly decreased serum alanine aminotransferase and aspartate aminotransferase enzyme activities and malondialdehyde levels, while increasing superoxide dismutase, catalase, phospholipid hydroperoxide glutathione peroxidase, and total antioxidant capacity in the liver and hippocampus of the mice. ACP-fortified yogurt might alleviate hepatic damage and hippocampal neuroinflammation induced by d-galactose. Additionally, ACP-fortified yogurt downregulated the expression of Keap1 and upregulated the expression of Nrf2 and HO-1 in the liver. In conclusion, ACP may be used as an ingredient to produce yogurt with desired properties.
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Antioxidantes , Iogurte , Animais , Antioxidantes/farmacologia , Auricularia , Proteína 1 Associada a ECH Semelhante a Kelch , Camundongos , Fator 2 Relacionado a NF-E2 , Polissacarídeos/química , Polissacarídeos/farmacologiaRESUMO
Nanobodies, or VHHs, refer to the antigen-binding domain of heavy-chain antibodies (HCAbs) from camelids. They have been widely used as research tools for protein purification and structure determination due to their small size, high specificity, and high stability, overcoming limitations with conventional antibody fragments. However, animal immunization and subsequent retrieval of antigen-specific nanobodies are expensive and complicated. Construction of synthetic nanobody libraries using DNA oligonucleotides is a cost-effective alternative for immunization libraries and shows great potential in identifying antigen-specific or even conformation-specific nanobodies. This review summarizes and analyses synthetic nanobody libraries in the current literature, including library design and biopanning methods, and further discusses applications of antigen-specific nanobodies obtained from synthetic libraries to research.
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Cadeias Pesadas de Imunoglobulinas/química , Biblioteca de Peptídeos , Anticorpos de Domínio Único/química , Animais , Antígenos/química , Antígenos/genética , Antígenos/imunologia , Camelus , Cromatografia de Afinidade , Cadeias Pesadas de Imunoglobulinas/genética , Cadeias Pesadas de Imunoglobulinas/imunologia , Anticorpos de Domínio Único/genética , Anticorpos de Domínio Único/imunologiaRESUMO
Daytime passive radiative cooling is a promising electricity-free pathway for cooling terrestrial buildings. Current research interest in this cooling strategy mainly lies in tailoring the optical spectra of materials for strong thermal emission and high solar reflection. However, environmental heat gain poses a crucial challenge to building cooling at subambient temperatures. Herein, we devise a scalable thermal insulating cooler (TIC) consisting of hierarchically hollow microfibers as the building envelope that simultaneously achieves passive daytime radiative cooling and thermal insulation to reduce environmental heat gain. The TIC demonstrates efficient solar reflection (94%) and long-wave infrared emission (94%), yielding a temperature drop of about 9 °C under sunlight of 900 W/m2. Notably, the thermal conductivity of the TIC is lower than that of air, thus preventing heat flow from external environments to indoor space in the summer, an additional benefit that does not sacrifice the radiative cooling performance. A building energy simulation shows that 48.5% of cooling energy could be saved if the TIC is widely deployed in China.
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Chlorella sorokiniana is one of the most productive microalgal species with a high potential for the production of biofuels and other high value-added molecules. Many studies have focused on its capability of mixotrophic growth using reduced organic carbon and growth pattern shift between autotrophic and mixotrophic conditions. In this study, we investigated growth patterns of a novel isolate, C. sorokiniana G32, under mixotrophic growth conditions supplemented with a low level (1.25 g L-1) and a high level (5 g L-1) of glucose. Physiological, transcriptomic (i.e., RNA-seq), and metabolomic (i.e., LC-MS/MS) methods were used. We showed that peak growth based on OD680nm absorbance is â¼4-fold higher with high glucose vs. low glucose supplementation. Photosynthetic efficiency (Fv/Fm) in G32 mixotrophic cultures with high or low glucose supplementation remains identical to that of G32 phototrophic growth. We also found that the conversion rate between absorbance-based cell density and cell dry weight with high glucose supplementation was lower than with low glucose. This suggests that more cell biomass is produced under high glucose treatment than with low glucose. The result was confirmed via sucrose density gradient centrifugation. It is likely that accumulation of high concentration of starch may account for this effect. Transcriptomic analysis of G32 cultures (i.e., via RNA-seq) in response to reciprocal change of glucose levels reveals that expression of a subset of differentially expressed genes (DEGs) is correlated with the amount of glucose supplementation. These DEGs are designated as glucose-specific responsive (GSR) genes. GSR genes are enriched for a number of energy metabolic pathways. Together with metabolomics data (i.e., LC-MS/MS), we show that under high-level supplementation, glucose is preferentially oxidized through an oxidative pentose phosphate pathway. Collectively, our results indicate the mechanism of regulation of glucose assimilation and energy metabolism in G32 under mixotrophic conditions with different levels of glucose supplementation revealed by transcriptomic and metabolomic analyses. We propose that C. sorokiniana G32 has the potential for the production of high value-added molecules.
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Background: Endometrial carcinoma (EC) is the most common cancer of female reproductive system, thus requiring for new effective biomarkers which could predict the onset of EC and worse prognosis. Cell Division Cycle Associated (CDCA) family plays indispensable roles in cell cycle process. However, no study has been focused on the role of CDCAs in EC. Our study aims to investigate the clinical relevance, potential biologic functions and molecular mechanisms of CDCAs in EC. Methods: GEPIA, cBioPortal, GeneMANIA, Networkanalyst, TCGA-UCEC cohort were utilized in this study. Results: NUF2 and CDCA2/3/4/5/7/8 were significantly highly expressed in EC compared with normal tissues. The patients with high NUF2 and CDCA2/3/4/5/8 expression tended to develop to advanced FIGO stages, poor differentiation and worse prognosis(in both OS and RFS analyses) than those with low expression. By contrast, elevated CDCA7 was significantly associated with better prognosis. CBX2 exerted no significant prognostic impact on EC patients. Distinct patterns of the genetic alterations of CDCAs were observed in various histological subtypes of EC. The biological functions of NUF2 and CDCA2/3/4/5/8 were mainly related with the activation of the following pathway: cell cycle, DNA replication, base excision repair, mismatch repair, nucleotide excision repair, cellular senescence and p53 signaling pathway. Conclusions: Our study provides new insight into the onset and progression of EC and proposes NUF2 and CDCA2/3/4/5/8 could act as oncogenes and have shown great diagnostic and prognostic promise in improving EC patient detection and survival prediction with accuracy.
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Establishment of the primordial follicle (PF) pool is pivotal for the female reproductive lifespan; however, the mechanism of primordial folliculogenesis is poorly understood. Here, the transcription factor SP1 was shown to be essential for PF formation in mice. Our results showed that SP1 is present in both oocytes and somatic cells during PF formation in the ovary. Knockdown of Sp1 expression, especially in pregranulosa cells, significantly suppressed nest breakdown, oocyte apoptosis, and PF formation, suggesting that SP1 expressed by somatic cells functions in the process of primordial folliculogenesis. We further demonstrated that SP1 governs the recruitment and maintenance of Forkhead box L2-positive (FOXL2+) pregranulosa cells using an Lgr5-EGFP-IRES-CreERT2 (Lgr5-KI) reporter mouse model and a FOXL2+ cell-specific knockdown model. At the molecular level, SP1 functioned mainly through manipulation of NOTCH2 expression by binding directly to the promoter of the Notch2 gene. Finally, consistent with the critical role of granulosa cells in follicle survival in vitro, massive loss of oocytes in Sp1 knockdown ovaries was evidenced before puberty after the ovaries were transplanted under the renal capsules. Conclusively, our results reveal that SP1 controls the establishment of the ovarian reserve by regulating pregranulosa cell development in the mammalian ovary.
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Células da Granulosa/citologia , Células da Granulosa/metabolismo , Fator 1-alfa Nuclear de Hepatócito/metabolismo , Folículo Ovariano/metabolismo , Animais , Apoptose/genética , Biomarcadores , Suscetibilidade a Doenças , Feminino , Imunofluorescência , Proteína Forkhead Box L2/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Técnicas de Silenciamento de Genes , Camundongos , Oócitos/metabolismo , Folículo Ovariano/crescimento & desenvolvimento , Insuficiência Ovariana Primária/etiologia , Insuficiência Ovariana Primária/metabolismo , Regiões Promotoras Genéticas , Receptor Notch2/genética , Receptor Notch2/metabolismo , Maturidade Sexual/genética , Transdução de SinaisRESUMO
It is known that granulosa cells (GCs) mediate gonadotropin-induced oocyte meiosis resumption by releasing EGF-like factors in mammals, however, the detailed molecular mechanisms remain unclear. Here, we demonstrate that luteinizing hormone (LH) surge-induced histone deacetylase 3 (HDAC3) downregulation in GCs is essential for oocyte maturation. Before the LH surge, HDAC3 is highly expressed in GCs. Transcription factors, such as FOXO1, mediate recruitment of HDAC3 to the amphiregulin (Areg) promoter, which suppresses AREG expression. With the LH surge, decreased HDAC3 in GCs enables histone H3K14 acetylation and binding of the SP1 transcription factor to the Areg promoter to initiate AREG transcription and oocyte maturation. Conditional knockout of Hdac3 in granulosa cells in vivo or inhibition of HDAC3 activity in vitro promotes the maturation of oocytes independent of LH. Taking together, HDAC3 in GCs within ovarian follicles acts as a negative regulator of EGF-like growth factor expression before the LH surge.
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Anfirregulina/genética , Regulação da Expressão Gênica no Desenvolvimento , Histona Desacetilases/metabolismo , Meiose/genética , Oócitos/crescimento & desenvolvimento , Oogênese/genética , Acetilação , Animais , Células Cultivadas , Feminino , Proteína Forkhead Box O1/metabolismo , Técnicas de Inativação de Genes , Células da Granulosa/metabolismo , Inibidores de Histona Desacetilases/farmacologia , Histona Desacetilases/genética , Histonas/metabolismo , Hormônio Luteinizante/metabolismo , Camundongos , Oogênese/efeitos dos fármacos , Cultura Primária de Células , Regiões Promotoras Genéticas/genética , Fator de Transcrição Sp1/metabolismoRESUMO
Robustness of superhydrophobic materials has been gradually taken into consideration for practical applications; however, little attention has been paid to the impact resistance of the superhydrophobicity of the materials. The present study demonstrated a new route for improving the mechanical durability, especially the impact resistance, of the superhydrophobic materials. First, poly(styrene-co-butadiene)/poly(ethylene-vinyl acetate) (SBR/EVA) composite monoliths with microscale cellular structures were manufactured by vulcanization-foaming processes. Then the composite monoliths were treated with sandpaper to create nanostructures above the revealed micropores after removing the uppermost skin, forming micro/nanotextured surfaces and giving improvements in superhydrophobicity. Due to the elastomeric nature of SBR and EVA, the superhydrophobicity of the monoliths can be maintained even while the material is mechanically impacted or compressed, and wearing helps improvement or recovery of the superhydrophobicity because of the self-similarity of the cellular structure inside the monoliths. Additionally, the obtained superhydrophobic materials are resistant to acidic, alkali, and salt liquors as well as organic solvents and have easy healing capacity of superhydrophobicity with a simple sanding treatment when destroyed by exposure to oxygen plasma.
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Gap junctions (GJs) are indispensable for communication between cumulus cells (CCs) and oocytes in coordinating the gonadotropin-induced meiotic maturation of oocytes. Of all proteins that constitute GJs, phosphorylated connexin43 (pCx43) is vital for mediating the actions of gonadotropins. In this study, the mechanism of Cx43 phosphorylation in response to follicle stimulating hormone (FSH) stimulation was examined using an in vitro model of mouse cumulus-oocyte complexes (COCs). The results confirmed that Cx43 phosphorylation occurred twice during FSH treatment. Importantly, the second Cx43 phosphorylation was closely related to cAMP level reduction within oocytes, which initiated oocyte maturation. Exploration of the underlying mechanism revealed that the CC-specific protein kinase C ε (PKCε) level was upregulated by FSH stimulation. PKCε was a kinase downstream from mitogen-activated protein kinase (MAPK) and was responsible for Cx43 phosphorylation. Interestingly, MAPK was involved in both Cx43 phosphorylation processes, while PKCε was only involved in the second. In conclusion, PKCε-mediated MAPK signals might contribute to Cx43 phosphorylation in CCs during FSH-induced oocyte meiotic resumption. Our findings contribute to a better understanding of the molecular regulation mechanism of oocyte maturation in response to FSH in vitro.
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Augmenter of liver regeneration (ALR), produced and released by hepatocytes, has cytoprotective and immunoregulatory effects on liver injury, and has been used in many experimental applications. However, little attention has been paid to the effects of ALR on concanavalin A (Con A)-induced hepatitis. The purpose of this paper is to explore the protective effect of ALR on Con A-induced hepatitis and elucidate potential mechanisms. We found that the ALR pretreatment evidently reduced the amount of ALT and AST in serum. In addition, pro-inflammatory cytokines, chemokines and iNOS were suppressed. ALR pretreatment also decreased CD4(+), CD8(+) T cell infiltration in liver. Besides, we observed that ALR pretreatment was capable of suppressing the activation of several signaling pathways in Con A-induced hepatitis. These findings suggest that ALR can obviously weaken Con A-induced hepatitis and ALR has some certain immune regulation function.