RÉSUMÉ
Polycyclic heteroaromatics (PHAs) are a highly versatile class of functional materials, especially applicable as efficient luminophores in organic light-emitting diodes (OLEDs). Those constructed by tethered phenyl surrounding the main group center attract extensive attention due to their excellent OLED device performance. However, the development of such a class of emitters is often limited to boron, nitrogen-doped π-conjugated heterocycles. Herein, we proposed a novel kind of blue emitter by constructing a donor-acceptor molecular configuration, utilizing a dual sulfone-bridged triphenylamine (BTPO) core and mono/di-diphenylamine (DPA) substituents. The twisted D-A molecular structures and appropriate donor strength facilitate the effective separation of natural transition orbitals, endowing the emitters with charge-transfer dominant hybridized local and charge-transfer characteristics for the excited states. Both BTPO-DPA and BTPO-2DPA own small S1-T1 splitting energy, thus demonstrating blue thermally activated delayed fluorescence. The more symmetrical structure and enhanced CT features brought by additional DPA moiety confer BTPO-2DPA with a shorter delayed fluorescence lifetime, a higher fluorescence quantum yield and narrower emission. Therefore, BTPO-2DPA based OLED devices exhibit superior blue electroluminescence performance, with external quantum efficiencies reaching 12.31%.
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Ginsenoside Compound K (GCK) is the main metabolite of natural protopanaxadiol ginsenosides with diverse pharmacological effects. Gut microbiota contributes to the biotransformation of GCK, while the effect of gut microbiota on the pharmacokinetics of GCK in vivo remains unclear. To illustrate the role of gut microbiota in GCK metabolism in vivo, a systematic investigation of the pharmacokinetics of GCK in specific pathogen free (SPF) and pseudo-germ-free (pseudo-GF) rats were conducted. Pseudo-GF rats were treated with non-absorbable antibiotics. Liquid chromatography tandem mass spectrometry (LC-MS/MS) was validated for the quantification of GCK in rat plasma. Compared with SPF rats, the plasma concentration of GCK significantly increased after the gut microbiota depleted. The results showed that GCK absorption slowed down, Tmax delayed by 3.5 h, AUC0-11 increased by 1.3 times, CLz/F decreased by 0.6 times in pseudo-GF rats, and Cmax was 1.6 times higher than that of normal rats. The data indicated that gut microbiota played an important role in the pharmacokinetics of GCK in vivo.
Sujet(s)
Microbiome gastro-intestinal , Ginsénosides , Ginsénosides/pharmacocinétique , Animaux , Microbiome gastro-intestinal/effets des médicaments et des substances chimiques , Rats , Mâle , Spectrométrie de masse en tandem , Rat Sprague-Dawley , Chromatographie en phase liquide , Organismes exempts d'organismes pathogènes spécifiquesRÉSUMÉ
BACKGROUND: Osteoporosis, characterized by reduced bone mass and deterioration of bone quality, is a significant health concern for postmenopausal women. Considering that the specific role of circRNAs in osteoporosis and osteoclast differentiation remains poorly understood, this study aims to shed light on their involvement in these processes to enhance our understanding and potentially contribute to improved treatment strategies for osteoporosis. METHODS: An osteoporotic model was constructed in vivo in ovariectomized mouse. In vitro, we induced osteoclast formation in bone marrow-derived macrophages (BMDMs) using M-CSF + RANKL. To assess osteoporosis in mice, we conducted HE staining. We used MTT and TRAP staining to measure cell viability and osteoclast formation, respectively, and also evaluated their mRNA and protein expression levels. In addition, RNA pull-down, RIP and luciferase reporter assays were performed to investigate interactions, and ChIP assay was used to examine the impact of circZNF367 knockdown on the binding between FUS and CRY2. RESULTS: We observed increased expression of CircZNF367, FUS and CRY2 in osteoporotic mice and M-CSF + RANKL-induced BMDMs. Functionally, knocking down circZNF367 inhibited osteoporosis in vivo. Furthermore, interference with circZNF367 suppressed osteoclast proliferation and the expression of TRAP, NFATc1, and c-FOS. Mechanistically, circZNF367 interacted with FUS to maintain CRY2 mRNA stability. Additionally, knocking down CRY2 rescued M-CSF + RANKL-induced osteoclast differentiation in BMDMs promoted by circZNF367 and FUS. CONCLUSION: This study reveals that the circZNF367/FUS axis may accelerate osteoclasts differentiation by upregulating CRY2 in osteoporosis and suggests that targeting circZNF367 may have potential therapeutic effects on osteoporosis.
Sujet(s)
Ostéoporose , ARN circulaire , Animaux , Femelle , Souris , Différenciation cellulaire/génétique , Facteur de stimulation des colonies de macrophages , Ostéoclastes , Ostéoporose/génétique , Stabilité de l'ARN/génétique , ARN circulaire/génétiqueRÉSUMÉ
Excessive bone resorption by osteoclasts results in the development of multiple bone disorders including osteoporosis. This study aimed to explore the biological function of methyltransferase-like14 (METTL14) in osteoclast formation, as well as its related mechanisms. Expression levels of METTL14, GPX4 and osteoclast-related proteins TRAP, NFATc1, c-Fos were detected by qRT-PCR and Western blotting. The osteoporosis model was established in mice by bilateral ovariectomy (OVX). Bone histomorphology was determined by micro-CT and H&E staining. NFATc1 expression in bone tissues was determined by immunohistochemical staining. Proliferation of primary bone marrow macrophages cells (BMMs) was assessed by MTT assay. Osteoclast formation was observed by TRAP staining. The regulatory mechanism was evaluated by RNA methylation quantification assay, MeRIP-qPCR, dual luciferase reporter assay, and RIP, respectively. METTL14 was down-regulated in the serum samples of postmenopausal osteoporotic women, which was positively associated with bone mineral density (BMD). Osteoclast formation was promoted in OVX-treated METTL14+/- mice as compared with wild-type littermates. Conversely, METTL14 overexpression repressed RANKL-induced osteoclast differentiation of BMMs. Mechanistically, METTL14-mediated m6A modification post-transcriptionally stabilized glutathione peroxidase 4 (GPX4), with the assistance of Hu-Antigen R (HuR). Finally, GPX4 depletion-mediated osteoclast formation in BMMs could be counteracted by METTL14 or HuR overexpression. Collectively, METTL14 inhibits osteoclastogenesis and bone resorption via enhancing GPX4 stability through an m6A-HuR dependent mechanism. Therefore, targeting METTL14 might be a novel promising treatment strategy for osteoporosis.
Sujet(s)
Résorption osseuse , Ostéoporose , Humains , Femelle , Souris , Animaux , Ostéoclastes/métabolisme , Methyltransferases/génétique , Methyltransferases/métabolisme , Différenciation cellulaire , Ostéoporose/génétique , Ostéoporose/métabolisme , Résorption osseuse/génétique , Résorption osseuse/métabolisme , Facteurs de transcription/métabolisme , Ovariectomie , Facteurs de transcription NFATCRÉSUMÉ
Immunoglobulins are key humoral immune molecules produced and secreted by B lymphocytes at various stages of differentiation. No research has reported whether immunoglobulins are present in the non-proliferative female germ cells-oocytes-and whether they are functionally important for oocyte quality, self-protection, and survival. Herein, we found that IgG was present in the oocytes of immunodeficient mice; the IgG-VDJ regions were highly variable between different oocytes, and H3K27Ac bound and regulated the IgG promoter region. Next, IgG mRNA and protein levels increased in response to LPS, and this increment was mediated by CR2 on the oocyte membrane. Finally, we revealed three aspects of the functional relevance of oocyte IgG: first, oocytes could upregulate IgG to counteract the increased ROS level induced by CSF1; second, oocytes could upregulate IgG in response to injected virus ssRNA to maintain mitochondrial integrity; third, upon bacterial infection, oocytes could secrete IgG, subsequently encompassing the bacteria, thus increasing survival compared to somatic cells. This study reveals for the first time that the female germ cells, oocytes, can independently adjust intrinsic IgG production to survive in adverse environments.
Sujet(s)
Cellules germinales , Ovocytes , Femelle , Souris , Animaux , Ovocytes/métabolisme , Différenciation cellulaire , ARN messager/métabolisme , Immunoglobuline G/métabolismeRÉSUMÉ
Osseointegration between implants and bone tissue lays the foundation for the long-term stability of implants. The incorporation of a porous structure and local slow release of siRNA to silence casein kinase-2 interacting protein-1 (CKIP-1), a downregulator of bone formation, is expected to promote osseointegration. Here, porous implants with a porous outer layer and dense inner core were prepared by metal coinjection molding (MIM). Mg-doped calcium phosphate nanoparticles (CaPNPs)-grafted arginine-glycine-aspartate cell adhesion sequence (RGD) and transcribed activator (TAT) (MCPRT)/CKIP-1 siRNA complex and polylysine (PLL) were coated onto the surface of the porous implants by layer-by-layer (LBL) self-deposition. The in vitro results showed that the MCPRT-siRNA coating promoted MG63 cell adhesion and proliferation, enhanced the protein expressions (ALP and OC) and bone formation-related gene expression (OPN, OC and COL-1α) in vitro. The in vivo results demonstrated that the porous structure enhanced bone ingrowth and that the local slow release of MCPRT-siRNA accelerated new bone formation at the early stage. The porous structure coupled with local CKIP-1 siRNA delivery constitutes a promising approach to achieve faster and stronger osseointegration for dental implants.
Sujet(s)
Ostéo-intégration , Titane , Matériaux revêtus, biocompatibles/pharmacologie , Porosité , Petit ARN interférent/génétique , Titane/pharmacologieRÉSUMÉ
Many integral membrane proteins might act as indispensable coordinators in specific functional microdomains to maintain the normal operation of known receptors, such as Notch. Gm364 is a multi-pass transmembrane protein that has been screened as a potential female fertility factor. However, there have been no reports to date about its function in female fertility. Here, we found that global knockout of Gm364 decreased the numbers of primordial follicles and growing follicles, impaired oocyte quality as indicated by increased ROS and γ-H2AX, decreased mitochondrial membrane potential, decreased oocyte maturation, and increased aneuploidy. Mechanistically, Gm364 directly binds and anchors MIB2, a ubiquitin ligase, on the membrane. Subsequently, membrane MIB2 ubiquitinates and activates DLL3. Next, the activated DLL3 binds and activates Notch2, which is subsequently cleaved within the cytoplasm to produce NICD2, the intracellular active domain of Notch2. Finally, NICD2 can directly activate AKT within the cytoplasm to regulate oocyte meiosis and quality.
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Protéines proto-oncogènes c-akt , Transduction du signal , Animaux , Femelle , Fécondité , Protéines membranaires/métabolisme , Follicule ovarique/métabolisme , Protéines proto-oncogènes c-akt/métabolisme , Transduction du signal/physiologie , Ubiquitine/métabolismeRÉSUMÉ
Objective. Chronic stress (CS)-induced abnormal metabolism and other subsequent aspects of abnormality are threatening human health. Little is known regarding whether and how protein post-translational-modifications (PTMs) correlate with abnormal metabolism under CS. The aim of this study was to address this issue and also identify novel key protein PTM. Methods. First, we screened which pan-PTM had significant change between control and CS female mice and whether clinical CS females had similar pan-PTM change. Second, we performed quantitative PTM-omics and metabolomics to verify the correlation between abnormal protein PTMs and atypical metabolism. Third, we performed quantitative phospho-omics to identify the key PTM-regulating enzyme and investigate the interaction between PTM protein and PTM-regulating enzyme. Fourth, we attempted to rectify the abnormal metabolism by correcting the activity of the PTM-regulating enzyme. Finally, we examined whether the selected key protein was also correlated with stress scores and atypical metabolism in clinical women. Results. We initially found that multiple tissues of CS female mice have downregulated pan-crotonylation, and verified that the plasma of clinical CS females also had downregulated pan-crotonylation. Then we determined that ATP5O-K51 crotonylation decreased the most and also caused gross ATP5O decrement, whereas the plasma of CS mice had downregulated phospholipids. Next, downregulating ATP5O crotonylation partially recapitulated the downregulated phospholipid metabolism in CS mice. Next, we verified that HDAC2-S424 phosphorylation determined its decrotonylation activity on ATP5O-K51. Furthermore, correcting HDAC2 hyper-phosphorylation recovered the gross ATP5O level and partially rescued the downregulated phospholipid metabolism in CS mice. Finally, the ATP5O level was also significantly lower and correlated with high stress scores and downregulated phospholipid metabolism in clinical female plasma. Conclusion. This study discovered a novel PTM mechanism involving two distinct types of PTM in CS and provided a novel reference for the clinical precautions and treatments of CS.
RÉSUMÉ
Chewing areca nut (betel quid) is strongly associated with oral submucous fibrosis (OSF), a pre-cancerous lesion. Among the areca alkaloids, arecoline is the main agent responsible for fibroblast proliferation; however, the specific molecular mechanism of arecoline affecting the OSF remains unclear. The present study revealed that arecoline treatment significantly enhanced Transforming growth factor-ß (TGF-ß)-induced buccal mucosal fibroblast (BMF) activation and fibrotic changes. Arecoline interacts with phosphodiesterase 4A (PDE4A) to exert its effects through modulating PDE4A activity but not PDE4A expression. PDE4A silence reversed the effects of arecoline on TGF-ß-induced BMFs activation and fibrotic changes. Moreover, the exchange protein directly activated by cAMP 1 (Epac1)-selective Cyclic adenosine 3',5'-monophosphate (cAMP) analog (8-Me-cAMP) but not the protein kinase A (PKA)-selective cAMP analog (N6-cAMP) remarkably suppressed α-smooth muscle actin(α-SMA) and Collagen Type I Alpha 1 Chain (Col1A1) protein levels in response to TGF-ß1 and arecoline co-treatment, indicating that cAMP-Epac1 but not cAMP-PKA signaling is involved in arecoline functions on TGF-ß1-induced BMFs activation. In conclusion, arecoline promotes TGF-ß1-induced BMFs activation through enhancing PDE4A activity and the cAMP-Epac1 signaling pathway during OSF. This novel mechanism might provide more powerful strategies for OSF treatment, requiring further in vivo and clinical investigation.
RÉSUMÉ
Manipulating the molecular orbital properties of excited states and the subsequent relaxation processes can greatly alter the emission behaviors of luminophores. Herein we report a vivid example of this, with luminescence conversion from thermally activated delayed fluorescence (TADF) to ultralong room-temperature phosphorescence (URTP) via a facile substituent effect on a rigid benzothiazino phenothiazine tetraoxide (BTPO) core. Pristine BTPO with multiple heteroatoms shows obvious intramolecular charge transfer (ICT) excited states with small exchange energy, featuring TADF. Via delicately functionalizing the BTPO core with peripheral moieties, the excited states of the BTPO derivatives become a hybridized local and charge transfer (HLCT) state in the S1 state and a local excitation (LE) dominated HLCT state in the T1 state, with enlarged energy bandgaps. Upon dispersion in a polymer matrix, the BTPO derivatives exhibit a persistent bright green afterglow with long lifetimes of up to 822 ms and decent quantum yields of up to 11.6%.
RÉSUMÉ
Background: Compared to commonly-used green space indicators from downward-facing satellite imagery, street view-based green space may capture different types of green space and represent how environments are perceived and experienced by people on the ground, which is important to elucidate the underlying mechanisms linking green space and health. Objectives: This study aimed to evaluate machine learning models that can classify the type of vegetation (i.e., tree, low-lying vegetation, grass) from street view images; and to investigate the associations between street green space and socioeconomic (SES) factors, in Los Angeles County, California. Methods: SES variables were obtained from the CalEnviroScreen3.0 dataset. Microsoft Bing Maps images in conjunction with deep learning were used to measure total and types of street view green space, which were compared to normalized difference vegetation index (NDVI) as commonly-used satellite-based green space measure. Generalized linear mixed model was used to examine associations between green space and census tract SES, adjusting for population density and rural/urban status. Results: The accuracy of the deep learning model was high with 92.5% mean intersection over union. NDVI were moderately correlated with total street view-based green space and tree, and weakly correlated with low-lying vegetation and grass. Total and three types of green space showed significant negative associations with neighborhood SES. The percentage of total green space decreased by 2.62 [95% confidence interval (CI): -3.02, -2.21, p < 0.001] with each interquartile range increase in CalEnviroScreen3.0 score. Disadvantaged communities contained approximately 5% less average street green space than other communities. Conclusion: Street view imagery coupled with deep learning approach can accurately and efficiently measure eye-level street green space and distinguish vegetation types. In Los Angeles County, disadvantaged communities had substantively less street green space. Governments and urban planners need to consider the type and visibility of street green space from pedestrian's perspective.
Sujet(s)
Parcs de loisirs , Caractéristiques de l'habitat , Humains , Los Angeles , Apprentissage machine , Poaceae , Facteurs socioéconomiques , ArbresRÉSUMÉ
Polycystic ovarian syndrome (PCOS) is a major severe ovary disorder affecting 5-10% of reproductive women around the world. PCOS can be considered a metabolic disease because it is often accompanied by obesity and diabetes. Brown adipose tissue (BAT) contains abundant mitochondria and adipokines and has been proven to be effective for treating various metabolic diseases. Recently, allotransplanted BAT successfully recovered the ovarian function of PCOS rat. However, BAT allotransplantation could not be applied to human PCOS; the most potent BAT is from infants, so voluntary donors are almost inaccessible. We recently reported that single BAT xenotransplantation significantly prolonged the fertility of aging mice and did not cause obvious immunorejection. However, PCOS individuals have distinct physiologies from aging mice; thus, it remains essential to study whether xenotransplanted rat BAT can be used for treating PCOS mice. In this study, rat-to-mouse BAT xenotransplantation, fortunately, did not cause severe rejection reaction, and significantly recovered ovarian functions, indicated by the recovery of fertility, oocyte quality, and the levels of multiple essential genes and kinases. Besides, the blood biochemical index, glucose resistance, and insulin resistance were improved. Moreover, transcriptome analysis showed that the recovered PCOS F0 mother following BAT xenotransplantation could also benefit the F1 generation. Finally, BAT xenotransplantation corrected characteristic gene expression abnormalities found in the ovaries of human PCOS patients. These findings suggest that BAT xenotransplantation could be a novel therapeutic strategy for treating PCOS patients.
Sujet(s)
Tissu adipeux brun/transplantation , Infertilité féminine/chirurgie , Ovaire/métabolisme , Syndrome des ovaires polykystiques/chirurgie , Animaux , Femelle , Fécondité , Humains , Infertilité féminine/sang , Souris de lignée BALB C , Ovocytes/cytologie , Syndrome des ovaires polykystiques/sang , Rat Sprague-Dawley , Transcriptome , Transplantation hétérologueRÉSUMÉ
Osteosarcoma is the most common primary malignant tumor, especially in children and adolescents. Circular RNAs (circRNAs) are found to play roles in the progression of osteosarcoma. However, the exact functions of circRNAs in osteosarcoma development still need to be clarified. We obtained differentially expressed circRNAs and miRNAs from a GSE99671 data set (GEO database). The gene co-expression network of ceRNAs and osteosarcoma-related genes was analyzed using the STRING database. qRT-PCR was used to detect the expression of circ-03955 and miR-3662. Transwell assays and flow cytometry were performed to detect phenotypic changes in cell function. A xenograft tumor model was established using BALB/c nude mice. Dual luciferase activity and RNA immunoprecipitation assays were performed to assess the relationship between circ-03955, miR-3662, and metadherin (MTDH). Immunohistochemistry, immunofluorescence, and Western blotting were used to assess protein expression levels. Circ-03955 was significantly upregulated, and miR-3662 was downregulated in osteosarcoma. Circ-03955 silencing inhibited the growth and metastasis of osteosarcoma. Mechanism analysis revealed that circ-03955 could bind to miR-3662, and the latter could target MTDH, leading to its suppressed expression and facilitating epithelial-mesenchymal transition (EMT). All these findings demonstrate that the presence of circ-03955 promotes EMT in osteosarcoma by acting as miR-3662 sponge-mediated MTDH expression.
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Prolonging the ovarian lifespan is attractive and challenging. An optimal clinical strategy must be safe, long-acting, simple, and economical. Allotransplantation of brown adipose tissue (BAT), which is most abundant and robust in infants, has been utilized to treat various mouse models of human disease. Could we use BAT to prolong the ovarian lifespan of aging mice? Could we try BAT xenotransplantation to alleviate the clinical need for allogeneic BAT due to the lack of voluntary infant donors? In the current study, we found that a single rat-to-mouse (RTM) BAT xenotransplantation did not cause systemic immune rejection but did significantly increase the fertility of mice and was effective for more than 5 months (equivalent to 10 years in humans). Next, we did a series of analysis including follicle counting; AMH level; estrous cycle; mTOR activity; GDF9, BMP15, LHR, Sirt1, and Cyp19a level; ROS and annexin V level; IL6 and adiponectin level; biochemical blood indices; body temperature; transcriptome; and DNA methylation studies. From these, we proposed that rat BAT xenotransplantation rescued multiple indices indicative of follicle and oocyte quality; rat BAT also improved the metabolism and general health of the aging mice; and transcriptional and epigenetic (DNA methylation) improvement in F0 mice could benefit F1 mice; and multiple KEGG pathways and GO classified biological processes the differentially expressed genes (DEGs) or differentially methylated regions (DMRs) involved were identical between F0 and F1. This study could be a helpful reference for clinical BAT xenotransplantation from close human relatives to the woman.
Sujet(s)
Tissu adipeux brun/métabolisme , Vieillissement de la cellule , Longévité , Follicule ovarique/métabolisme , Ovaire/métabolisme , Animaux , Femelle , Mâle , Souris , Rats , Rat Sprague-Dawley , Transplantation hétérologueRÉSUMÉ
In order to develop a biodegradable guided bone regeneration membrane with the required mechanical properties and high corrosion resistance, Zn-0.8%Li(wt), Zn-0.8%Li-0.2%Mg(wt), and Zn-0.8%Li-0.2%Ag(wt) alloys were cast and hot rolled into 0.1-mm thick sheets. The main secondary phase in Zn-0.8%Li-(Mg, Ag) alloys was the LiZn4 nanoprecipitate. Following the addition of minimal amounts of Mg, the tensile strength of the Zn-0.8%Li-0.2%Mg alloy improved, albeit with a greatly reduced elongation and corrosion resistance. The addition of minimal amounts of Ag refined the microstructure, producing fine equiaxed grains (2.3⯵m) in the Zn-0.8%Li-0.2%Ag alloy, and promoted a uniform distribution of LiZn4 nanoprecipitates with increased density and refined size. Therefore, the Zn-0.8%Li-0.2%Ag alloy exhibited optimal tensile strength and the highest corrosion resistance, with its elongation reaching 97.9⯱â¯8.7%. The corrosion products of Zn-0.8%Li-(Mg, Ag) alloys immersed in Ringer's solution for 35â¯days mainly consisted of zinc oxide and zinc carbonate. In addition, the cytotoxicity test using L929 cells and the evaluation of bone marrow mesenchymal stem cell proliferation indicated that the Zn-0.8%Li-0.2%Ag alloy had good biocompatibility.
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Alliages/pharmacologie , Matériaux biocompatibles/pharmacologie , Régénération osseuse/effets des médicaments et des substances chimiques , Régénération tissulaire guidée , Lithium/pharmacologie , Phénomènes mécaniques , Argent/pharmacologie , Zinc/pharmacologie , Animaux , Mort cellulaire/effets des médicaments et des substances chimiques , Lignée cellulaire , Prolifération cellulaire/effets des médicaments et des substances chimiques , Survie cellulaire/effets des médicaments et des substances chimiques , Corrosion , Techniques électrochimiques , Concentration en ions d'hydrogène , Cellules souches mésenchymateuses/cytologie , Cellules souches mésenchymateuses/effets des médicaments et des substances chimiques , Souris , Spectroscopie infrarouge à transformée de Fourier , Contrainte mécanique , Propriétés de surface , Résistance à la traction , Diffraction des rayons XRÉSUMÉ
Tight control of energy metabolism is essential for normal cell function and organism survival. PKM (pyruvate kinase, muscle) isoforms 1 and 2 originate from alternative splicing of PKM pre-mRNA. They are key enzymes in oxidative phosphorylation and aerobic glycolysis, respectively, and are essential for ATP generation. The PKM1:PKM2 expression ratio changes with development and differentiation, and may also vary under metabolic stress and other conditions. Until now, there have been no reports about the function and regulation of PKM isozymes in oocytes. Here, we demonstrate that PKM1 or PKM2 depletion significantly disrupts ATP levels and mitochondrial integrity, and exacerbates free-radical generation and apoptosis in mouse oocytes. We also show that KBTBD8, a female fertility factor in the KBTBD ubiquitin ligase family, selectively regulates PKM1 levels through a signaling cascade that includes Erk1/2 and Aurora A kinases as intermediates. Finally, using RNA sequencing and protein network analysis, we identify several regulatory proteins that may be govern generation of mature PKM1 mRNA. These results suggest KBTBD8 affects PKM1 levels in oocytes via a KBTBD8âErk1/2âAurora A axis, and may also affect other essential processes involved in maintaining oocyte quality.
Sujet(s)
Protéines adaptatrices de la transduction du signal/physiologie , Aurora kinase A/métabolisme , Protéines de transport/métabolisme , Système de signalisation des MAP kinases/physiologie , Protéines membranaires/métabolisme , Ovocytes/physiologie , Pyruvate kinase/métabolisme , Hormones thyroïdiennes/métabolisme , Protéines adaptatrices de la transduction du signal/génétique , Animaux , Aurora kinase A/génétique , Protéines de transport/génétique , Extracellular Signal-Regulated MAP Kinases/génétique , Extracellular Signal-Regulated MAP Kinases/métabolisme , Régulation de l'expression des gènes , Techniques de maturation in vitro des ovocytes , Méiose , Protéines membranaires/génétique , Souris , Hormones thyroïdiennes/génétique ,RÉSUMÉ
The development of an efficient, robust, and low-cost catalyst for water electrolysis is critically important for renewable energy conversion. Herein, we achieve a significant improvement in electrocatalytic activity for both the oxygen-evolution reaction (OER) and the hydrogen-evolution reaction (HER) by constructing a novel hierarchical PrBa0.5Sr0.5Co2O5+δ (PBSC)@FeOOH catalyst. The optimized PBSC@FeOOH-20 catalyst consisted of layered perovskite PBSC nanorods and 20 nm thick amorphous FeOOH nanoflakes exhibiting an excellent electrocatalytic activity for the OER and the HER in 0.1 M KOH media, delivering a current density of 10 mA cm-2 at overpotentials of 390 mV for the OER and 280 mV for the HER, respectively. The substantially enhanced performance is probably attributed to the hierarchical nanostructure, the good charge-transfer capability, and the strong electronic interactions of FeOOH and PBSC. Importantly, an alkaline electrolyzer-integrated PBSC@FeOOH-20 catalyst as both the anode and cathode shows a highly active overall water splitting with a low voltage of 1.638 V at 10 mA cm-2 and high stability during continuous operation. This study provides new insights into exploring efficient bifunctional catalysts for overall water splitting, and it suggests that the rational design of the oxyhydroxide/perovskite heterostructure shows great potential as a promising type of electrocatalysts.
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Placenta-specific 1 (Plac1) has been found to be essential for placentation, and abnormal Plac1 expression and distribution is highly correlated with preeclampsia and implantation failure; however, its function in mammalian oocytes has not been elucidated. Here, we report that Plac1 was more prominent in mouse oocytes and enriched at the membrane region throughout meiosis. On the one hand, Plac1 knockdown severely disrupted microvillus organization; however, on the other hand, Plac1 significantly decreased oocyte maturation and increased aneuploidy, consequently disrupting normal fertilization. On the basis of immunoprecipitate matrix-assisted laser desorption/ionization, we established a working model, then verified and suggested that, at the germinal vesicle stage, Plac1 enriches the membrane to activate furin, and active furin subsequently activates IGF-1 receptor to maintain regular microvillus organization. Upon meiosis onset, active furin/IGF-1 receptor relocates into the cytoplasm to activate (phosphorylate) Akt to promote meiosis. In summary, our finding suggests that Plac1, a protein that is crucial for placentation, is also essential for oocyte meiosis and fertilization.-Shi, L.-Y., Ma, Y., Zhu, G.-Y., Liu, J.-W., Zhou, C.-X., Chen, L.-J., Wang, Y., Li, R.-C., Yang, Z.-X., Zhang, D. Placenta-specific 1 regulates oocyte meiosis and fertilization through furin.
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Fécondation/physiologie , Furine/métabolisme , Méiose/physiologie , Ovocytes/métabolisme , Protéines de la grossesse/métabolisme , Animaux , Activation enzymatique/physiologie , Femelle , Furine/génétique , Souris , Souris de lignée ICR , Ovocytes/cytologie , Protéines de la grossesse/génétique , Transport des protéines/physiologie , Protéines proto-oncogènes c-akt/génétique , Protéines proto-oncogènes c-akt/métabolisme , Récepteur IGF de type 1/génétique , Récepteur IGF de type 1/métabolismeRÉSUMÉ
Design of prosthetic implants to ensure rapid and stable osseointegration remains a significant challenge, and continuous efforts have been directed to new implant materials, structures and morphology. This paper aims to develop and characterise a porous titanium dental implant fabricated by metallic powder injection-moulding. The surface morphology of the specimens was first examined with a scanning electron microscope (SEM), followed by microscopic computerised tomography (µ-CT) scanning to capture its 3D microscopic features non-destructively. The nature of porosity and pore sizes were determined statistically. A homogenisation technique based on the Hills-energy theorem was adopted to evaluate its directional elastic moduli, and the conservation of mass theorem was employed to quantify the oxygen diffusivity for bio-transportation feature. This porous medium was found to have pore sizes varying from 50 to 400 µm and the average porosity of 46.90 ± 1.83%. The anisotropic principal elastic moduli were found fairly close to the upper range of cortical bone, and the directional diffusivities could potentially enable radial osseous tissue ingrowth and vascularisation. This porous titanium successfully reduces the elastic modulus mismatch between implant and bone for dental and orthopaedic applications, and provides improved capacity for transporting oxygen, nutrient and waste for pre-vascular network formation. Copyright © 2016 John Wiley & Sons, Ltd.
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Implants dentaires , Titane , Microtomographie aux rayons X/méthodes , Diffusion , Module d'élasticité , Humains , Test de matériaux , Microscopie électronique à balayage , Ostéo-intégration , Oxygène/métabolisme , Porosité , Propriétés de surfaceRÉSUMÉ
Osteoblasts growing into bone substitute is an important step of bone regeneration. This study prepared porous hydroxyapatite (HA)/BaTiO3 piezoelectric composites with porosity of 40%, 50% and 60% by ice-templating method. Effects of HA/BaTiO3 composites with different porosities, with and without polarizing treatment on adhesion, proliferation and differentiation of osteoblasts were investigated in vitro. Results revealed that cell densities of the porous groups were significantly higher than those of the dense group (p<0.05), so did the alkaline phosphate (ALP) and bone gla protein (BGP) activities. Porosity of 50% group exhibited higher ALP activity and BGP activity than those of the 40% and 60% groups. Scanning electron microscopy (SEM) observations revealed that osteoblasts adhered and stretched better on porous HA/BaTiO3 than on the dense one, especially HA/BaTiO3 with porosity of 50% and 60%. However, there was no significant difference in the cell morphology, cell densities, ALP and BGP activities between the polarized group and the non-polarized group (p>0.05). The absence of mechanical loading on the polarized samples may account for this. The results indicated that hierarchically porous HA/BaTiO3 played a favorable part in osteoblasts proliferation, differentiation and adhesion process and is a promising bone substitute material.