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BACKGROUND: Recurrent preimplantation embryo developmental arrest (RPEA) is the most common phenotype in assisted reproductive technology treatment failure associated with identified genetic abnormalities. Currently known maternal genetic variants explain only a limited number of cases. Variants of the ß-tubulin subunit gene, TUBB8, cause oocyte meiotic arrest and RPEA through a broad spectrum of spindle defects. In contrast, α-tubulin subunit genes are poorly studied in the context of preimplantation embryonic development. METHODS: Whole exome sequencing was performed on the PREA cohort. Functional characterisations of the identified candidate disease-causing variants were validated using Sanger sequencing, bioinformatics, in vitro functional analyses and single-cell RNA-sequencing of arrested embryos. RESULTS: Four homozygous variants were identified in the PREA cohort: two of TUBA1C (p.Gln358Ter and p.Asp444Metfs*42) and two of TUBA4A (p.Arg339Cys and p.Tyr440Ter). These variants cause varying degrees of spindle assembly defects. Additionally, we characterised changes in the human arrested embryo transcriptome carrying TUBA4A variants, with a particular focus on spindle organisation, chromosome segregation and mRNA decay. CONCLUSION: Our findings identified TUBA1C as a novel genetic marker and expanded the genetic and phenotypic spectrum of TUBA4A in female infertility and RPEA, which altogether highlighted the importance of α-tubulin isotypes in preimplantation embryonic development.
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ZnSeTe quantum dots (QDs) attract growing interest owing to their low threats to health and the environment. They are widely applied as emitters in displays and lighting devices. Previous findings have indicated that inorganic halides are excellent candidates for surface ligands on QDs. By incorporating inorganic halides during the synthesis process, the photoluminescence (PL) intensity and quantum yield (QY) of QDs can be significantly enhanced. However, the alteration of surface states in QDs induced by zinc halide modification and the mechanism of formation of trap-state radiative recombination processes have been less discussed. Herein, we proposed a synthesis strategy for ZnSeTe/ZnSe/ZnSeS/ZnS core/shell/shell/shell QDs modified with ZnCl2, and by comparing the morphology and elemental composition of QDs with different amounts of ZnCl2 added, we revealed the regulatory mechanism of nanocrystal growth in the presence of ZnCl2. QDs with modification of ZnCl2 exhibited broad yellow fluorescence, distinct from the intrinsic blue emission. Through spectroscopic and surface ligand analyses, we attributed this yellow emission to the intermediate state energy levels caused by the defects on the surface. Finally, we used the QDs with broad linewidth emission to fabricate a simple white-light-emitting diode (WLED). This work provided new insights into the role of inorganic ligands and the use of a single emitting material in solid-state lighting devices.
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PURPOSE: To explore the pathogenesis of oocyte maturation defects. METHODS: Whole exome sequencing was conducted to identify potential variants, which were then confirmed within the pedigree through Sanger sequencing. The functional characterization of the identified variants responsible for the disease, including their subcellular localization, protein levels, and interactions with other proteins, was verified through transient transfection in HeLa cells in vitro. Additionally, we employed real-time RT-PCR and single-cell RNA sequencing to examine the impact of ZFP36L2 pathogenic variants on mRNA metabolism in both HeLa cells and mouse or human oocytes. RESULTS: A novel compound heterozygous variant in ZFP36L2 (c.186T > G, p.His62Gln and c.869 C > T, p.Pro290Leu) was discovered in a patient with oocyte maturation defects. Our findings indicate that these variants lead to compromised binding capacity of the ZFP36L2-CONT6L complex and impaired mRNA degradation in HeLa cells and mouse oocytes. Furthermore, we characterized the changes in the human oocyte transcriptome associated with ZFP36L2 variants, with a particular emphasis on cell division, mitochondrial function, and ribosome metabolism. CONCLUSIONS: This study broadens the mutation spectrum of ZFP36L2 and constitutes the first report of human oocyte transcriptome alterations linked to ZFP36L2 variants. In conjunction with existing knowledge of ZFP36L2, our research lays the groundwork for genetic counseling aimed at addressing female infertility.
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Infertilidade Feminina , Oócitos , Humanos , Feminino , Oócitos/crescimento & desenvolvimento , Oócitos/metabolismo , Oócitos/patologia , Camundongos , Células HeLa , Infertilidade Feminina/genética , Infertilidade Feminina/patologia , Animais , Sequenciamento do Exoma , Linhagem , Heterozigoto , Oogênese/genética , Tristetraprolina/genética , Tristetraprolina/metabolismo , Mutação/genética , AdultoRESUMO
Dendrobium nobile is a traditional Chinese herb with anti-inflammatory, antioxidant, and neuroprotective properties. However, its antiaging effects are unclear. Herein, we studied the aging-related functions and the mechanism of action of the alcohol extract of Dendrobium nobile (DnAE) in the model organism Caenorhabditis elegans. The results indicated that 1 mg/mL DnAE slowed lipofuscin accumulation, decreased the levels of reactive oxygen species, elevated superoxide dismutase activity, enhanced oxidative and heat stress resistance, extended the lifespan of nematodes, protected their dopamine neurons from 6-hydroxydopamine-induced neurodegeneration, and reduced Aß-induced neurotoxicity. DnAE upregulated the mRNA expression of the transcription factors DAF-16 and HSF-1, promoted the nuclear localization of DAF-16, and enhanced the fluorescence intensity of HSP-16.2. However, it had no effect on the lifespan of DAF-16 mutants. Thus, DnAE can significantly extend lifespan, enhance heat stress tolerance, and delay age-related diseases through a DAF-16-dependent pathway.
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Proteínas de Caenorhabditis elegans , Dendrobium , Animais , Longevidade , Caenorhabditis elegans , Dendrobium/metabolismo , Estresse Oxidativo , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Fatores de Transcrição de Choque Térmico/metabolismo , Etanol/metabolismo , Fatores de Transcrição Forkhead/metabolismoRESUMO
BACKGROUND: Microglia play a pivotal role in neuroinflammation, while obesity triggers hypothalamic microglia activation and inflammation. Sirt6 is an important regulator of energy metabolism in many peripheral tissues and hypothalamic anorexic neurons. However, the exact mechanism for microglia Sirt6 in controlling high-fat diet-induced obesity remain unknown. METHODS: Microglia Sirt6 expression levels under various nutritional conditions were measured in the hypothalamus of mice. Also, microglia Sirt6-deficient mice were provided various diets to monitor metabolic changes and hypothalamic inflammatory response. Besides, RNA-seq and Co-IP of microglia with Sirt6 alterations were conducted to further investigate the detailed mechanism by which Sirt6 modulated microglia activity. RESULTS: We found that Sirt6 was downregulated in hypothalamic microglia in mice given a high-fat diet (HFD). Additionally, knockout of microglia Sirt6 exacerbated high-fat diet-induced hypothalamic microglial activation and inflammation. As a result, mice were more prone to obesity, exhibiting a decrease in energy expenditure, impaired glucose tolerance, insulin and leptin resistance, and increased food intake. In vitro, Sirt6 overexpression in BV2 cells displayed protective effects against oleic acid and palmitic acid treatment-derived inflammatory response. Mechanically, Sirt6 deacetylated and stabilised NRF2 to increase the expression of anti-oxidative genes and defend against reactive oxygen species overload. Pharmacological inhibition of NRF2 eliminated the beneficial modulating effects of Sirt6 on microglial activity. CONCLUSION: Collectively, our results revealed that microglial Sirt6 was a primary contributor of microglial activation in the central regulation of obesity. Thus, microglial Sirt6 may be an important therapeutic target for obesity.
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Microglia , Sirtuínas , Camundongos , Animais , Microglia/metabolismo , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Dieta Hiperlipídica/efeitos adversos , Obesidade/genética , Obesidade/metabolismo , Hipotálamo , Inflamação/metabolismo , Camundongos Endogâmicos C57BL , Sirtuínas/genética , Sirtuínas/metabolismoRESUMO
BACKGROUND: The myeloblastosis (MYB) superfamily is the largest transcription factor family in plants that play diverse roles during stress responses. However, the biotic stress-responsive MYB transcription factors of the grapevine have not been systematically studied. In China, grapevine berries are often infected with the grapevine berry inner necrosis virus (GINV), which eventually reduces the nutritional quality and commodity value. RESULTS: The present study identified and characterized 265 VvMYB or VvMYB-related genes of the "Crimson seedless" grapevine. Based on DNA-binding domain analysis, these VvMYB proteins were classified into four subfamilies, including MYB-related, 2R-MYB, 3R-MYB, and 4R-MYB. Phylogenetic analysis divided the MYB transcription factors into 26 subgroups. Overexpression of VvMYB58 suppressed GINV abundance in the grapevine. Further qPCR indicated that among 41 randomly selected VvMYB genes, 12 were induced during GINV infection, while 28 were downregulated. These findings suggest that VvMYB genes actively regulate defense response in the grapevine. CONCLUSION: A deeper understanding of the MYB TFs engaged in GINV defense response will help devise better management strategies. The present study also provides a foundation for further research on the functions of the MYB transcription factors.
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Fatores de Transcrição , Vitis , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Frutas/genética , Frutas/metabolismo , Vitis/metabolismo , Filogenia , Necrose/metabolismo , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismoRESUMO
Grapevine downy mildew, caused by the oomycete Plasmopara viticola, is one of the most significant production challenges for the grape and wine industry. P. viticola injects a plethora of effectors into its host cells to disrupt immune processes, but the mechanisms by which these effectors act at the molecular level have not been well characterized. Herein, we show that a candidate P. viticola avirulence homolog (Avh) RxLR effector gene, designated PvAvh77, was strongly up-regulated during the initial stages of P. viticola infection in Vitis vinifera. Further experiments demonstrated that PvAvh77 could trigger non-specific cell death when expressed in the wild grapevine Vitis riparia and in tobacco (Nicotiana benthamiana and Nicotiana tabacum). In addition, a truncated form of PvAvh77, designated PvAvh77-M2, was more active in inducing cell death in N. benthamiana and V. riparia than full-length PvAvh77. Ectopic expression of PvAvh77 in V. vinifera 'Thompson Seedless' leaves neutralized host immunity and enhanced colonization by P. viticola, and the immune-inhibiting activity of PvAvh77 on susceptible Eurasian grapevine depended on its nuclear localization. Using a yeast signal sequence trap approach, we showed that the signal peptide of PvAvh77 is functional in yeast. Moreover, PvAvh77 with a signal peptide stimulated plant immune responses in the apoplast. Notably, application of exogenous purified PvAvh77-M2 effectively initiated defence responses in grapevine extracellularly, as evidenced by increased accumulation of salicylic acid and H2O2, and reduced infection of inoculated P. viticola. In summary, we identified a novel effector, PvAvh77, from P. viticola, which has the potential to serve as an inducer of plant immunity.
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Oomicetos , Phytophthora infestans , Vitis , Saccharomyces cerevisiae , Peróxido de Hidrogênio/metabolismo , Doenças das Plantas , Nicotiana/genética , Vitis/genética , Vitis/metabolismo , Morte Celular , Sinais Direcionadores de Proteínas , Resistência à DoençaRESUMO
An elevation of pathologic intraocular pressure (IOP) is the greatest risk factor for glaucoma. CD154 has been reported to bind to CD40 expressed by orbital fibroblasts and be involved in immune and inflammatory responses. However, the function and mechanism of CD154 in ocular hypertensive glaucoma (OHG) are not fully understood. We isolated and characterized Müller cells and subsequently examined the effect of CD154 on ATP release from those cells. After being cocultured with CD154-pretreated Müller cells, retinal ganglion cells (RGCs) were treated with P2X7 siRNAs or a P2X7 inhibitor. Furthermore, mouse models of glaucoma (GC) were injected with P2X7 shRNA. p21, p53, and P2X7 expression were examined, and cellular senescence and apoptosis were detected by ß-Gal and TUNEL staining, retinal pathology was examined by H&E staining, and CD154 and ß-Gal expression were detected by ELISA. CD154 induced ATP release from Müller cells and accelerated the senescence and apoptosis of RGCs that had been cocultured with Müller cells. We also found that treatment with P2X7 could attenuate the senescence and apoptosis of RGCs mediated by Müller cells pretreated with CD154. In vivo studies in GC model mice verified that P2X7 silencing attenuated pathological damage and prevented the senescence and apoptosis of retinal tissue. The study demonstrates how CD154 accelerates the aging and apoptosis of RGCs by co-cultivating Müller cells pretreated with CD154 in OHG. The research implies that CD154 has the potential to become a new therapeutic target for ocular hypertension glaucoma, providing a new research direction for its treatment.
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Glaucoma , Neuroproteção , Camundongos , Animais , Células Ependimogliais/metabolismo , Células Ependimogliais/patologia , Retina/metabolismo , Glaucoma/tratamento farmacológico , Glaucoma/metabolismo , Glaucoma/patologia , Modelos Animais de Doenças , Ligante de CD40/metabolismo , Trifosfato de Adenosina/metabolismoRESUMO
InP quantum dots (QDs) attract growing interest in recent years, owing to their environmental advantages upon applications in display and lighting. However, compared to Cd-based QDs and Pb-based perovskites, the synthesis of InP QDs with high optical quality is relatively more difficult. Here, we established a mid-synthetic modification approach to improve the optical properties of InP-based QDs. Tris(dimethylamino)phosphine ((DMA)3P) and indium iodide were used to prepare InP QDs with a green emission (â¼527 nm). By introducing zinc halides (ZnX2) during the mid-synthetic process, the photoluminescence quantum yield (PLQY) of the resulting InP/ZnSeS/ZnS core/shell/shell QDs was increased to >70%, and the full-width-at-half-maximum (FWHM) could be narrowed to â¼40 nm. Transmission electron microscopy clearly showed the improvement of the QDs particle size distribution after introducing ZnX2. It was speculated that ZnX2 was bound to the surface of QDs as a Z-type ligand, which not only passivated surface defects and suppressed the emission of defect states but also prevented Ostwald ripening. The InP cores were also activated by ZnX2, which made the growth of the ZnSeS shell more favorable. The photoluminescence properties started to be improved significantly only when the amount of ZnX2 exceeded 0.5 mmol. As the amount increased, more ZnX2 was distributed around the QDs to form a ligand layer, which prevented the shell precursor from crossing the ligand layer to the surface of the InP core, thus reducing the size of the InP/ZnSeS/ZnS QDs. This work revealed a new role of ZnX2 and found a method for InP QDs with high brightness and low FWHM by the mid-synthetic modification, which would inspire the synthesis of even better InP QDs.
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BACKGROUND: Recurrent preimplantation embryo developmental arrest (RPEA) is the most common cause of assisted reproductive technology treatment failure associated with identified genetic abnormalities. Variants in known maternal genes can only account for 20%-30% of these cases. The underlying genetic causes for the other affected individuals remain unknown. METHODS: Whole exome sequencing was performed for 100 independent infertile females that experienced RPEA. Functional characterisations of the identified candidate disease-causative variants were validated by Sanger sequencing, bioinformatics and in vitro functional analyses, and single-cell RNA sequencing of zygotes. RESULTS: Biallelic variants in ZFP36L2 were associated with RPEA and the recurrent variant (p.Ser308_Ser310del) prevented maternal mRNA decay in zygotes and HeLa cells. CONCLUSION: These findings emphasise the relevance of the relationship between maternal mRNA decay and human preimplantation embryo development and highlight a novel gene potentially responsible for RPEA, which may facilitate genetic diagnoses.
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Infertilidade Feminina , Blastocisto , Feminino , Células HeLa , Humanos , Infertilidade Feminina/diagnóstico , Infertilidade Feminina/genética , Gravidez , RNA Mensageiro Estocado , Fatores de Transcrição/genética , Sequenciamento do ExomaRESUMO
BACKGROUND: The main aim of this systematic review was to determine the effectiveness of postoperative rehabilitation interventions that include breathing exercises as a component to prevent atelectasis in lung cancer resection patients. METHODS: In this review, we systematically and comprehensively searched the Cochrane Library, PubMed, EMBASE, and Web of Science in English and CNKI and Wanfang in Chinese from 2012 to 2022. The review included any randomized controlled trials focusing on the effectiveness of postoperative rehabilitation interventions that include breathing exercises to prevent pulmonary atelectasis in lung cancer patients. Participants who underwent anatomic pulmonary resection and received postoperative rehabilitation interventions that included breathing exercises as a component were included in this review. The study quality and risks of bias were measured with the GRADE and Cochrane Collaboration tools, and statistical analysis was performed utilizing RevMan 5.3 software. RESULTS: The incidence of atelectasis was significantly lower in the postoperative rehabilitation intervention group (OR = 0.35; 95% CI, 0.18 to 0.67; I2 = 0%; P = 0.67) than in the control group. The patients who underwent the postoperative rehabilitation program that included breathing exercises (intervention group) had higher forced vital capacity (FVC) scores (MD = 0.24; 95% CI, 0.07 to 0.41; I2 = 73%; P = 0.02), forced expiratory volume in one second (FEV1) scores (MD = 0.31; 95% CI, 0.03 to 0.60; I2 = 98%; P < 0.01) and FEV1/FVC ratios (MD = 9.09; 95% CI, 1.50 to 16.67; I2 = 94%; P < 0.01). CONCLUSION: Postoperative rehabilitation interventions that included breathing exercises decreased the incidence rate of atelectasis and improved lung function by increasing the FVC, FEV1, and FEV1/FVC ratio.
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Neoplasias Pulmonares , Atelectasia Pulmonar , Humanos , Neoplasias Pulmonares/cirurgia , Neoplasias Pulmonares/reabilitação , Pulmão , Terapia por Exercício , Exercícios Respiratórios , Atelectasia Pulmonar/prevenção & controle , Qualidade de VidaRESUMO
Microglia are resident immune cells in the brain and are closely associated with central nervous system inflammation and neurodegenerative diseases. It is known that mammalian target of rapamycin (mTOR) pathway plays an important role in the polarization of microglia. Castor1 has been identified as the cytosolic arginine sensor for the mTOR complex 1 (mTORC1) pathway, but the role of Castor1 in microglial polarization is still unknown. The purpose of this study was to explore the regulatory effect of Castor1 on microglial polarization and the underlying mechanism. The results demonstrated that Castor1 expression was significantly decreased in lipopolysaccharides (LPS) and interferon (IFN)-γ treated microglia. Castor1 overexpression inhibited the microglia M1 polarization by reducing the expression of M1 related markers. However, the expression of M2-related genes was promoted when Castor1 was overexpressed in IL-4 treated microglia. Mechanistically, Castor1 overexpression inhibited the activation of mTOR signaling pathway. In addition, after treatment with the mTOR activator MHY1485, the inhibitory effect of Castor1 overexpression on M1 polarization was attenuated, indicating that the regulation effects of Castor1 on M1 polarization was dependent on its inhibition of mTOR pathway. We propose that Castor1-mTOR signaling pathway could be considered as a potential target for treatment and intervention of central nervous system-related diseases by regulating microglia polarization.
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Microglia , Serina-Treonina Quinases TOR , Humanos , Microglia/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Transdução de Sinais , Inflamação/metabolismo , Alvo Mecanístico do Complexo 1 de Rapamicina , Peptídeos e Proteínas de Sinalização Intracelular/metabolismoRESUMO
AIM: To explore the effects of different types of interference on nurses' working memory, and the role of attention control. DESIGN: A repeated measures design. METHODS: A single-factor, four-level within-subjects design was adopted. Thirty-one nurses completed a delay-recognition task with four blocks in September 2020: Interrupting Stimulus (stimuli requiring attention), Distracting Stimulus (stimuli to-be-ignored), No Interference and Passively View. Behavioural responses of the participants and EEG data were recorded. MATLAB 21b and EEGLAB 21b were used for electroencephalogram data preprocessing and data extraction. RESULTS: Firstly, when nursing information system was used as task material, the accuracy rate and false alarm rate of primary tasks under interruption condition was statistically significantly different with that of distraction and no interference condition. There is a statistically significant difference in electroencephalogram measurement between correct and wrong response under interruption. Secondly, the role of attention control was different under interruption and distraction. There was a statistically significant positive correlation between the average amplitude distraction attention control index and task accuracy, and statistically significant negative correlation between the latency interruption attention control index and the accuracy of working memory task. CONCLUSIONS: There were different effects of interruptions and distractions on nurses' working memory and the role of attention control were also different. Measures can be designed according to these results to reduce the negative impact of interference on nurses, so as to improve work efficiency and reduce patient risk. IMPACT: This study has implications for clinical nursing during human-computer interaction. Resumption of the speed of the target information after an interruption affected task performance. Therefore, interventions should be designed to reduce the time needed for nurses to extract task information after an interruption, such as providing key clues in the information system interface. PATIENT OR PUBLIC CONTRIBUTION: Registered nurses participated in the study as subjects.
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Introduction: Although telemedicine is widely used in the field of rheumatoid arthritis (RA), many systematic reviews have evaluated telemedicine, but we still have no clear effect on RA and no evidence summary. Our aim is to determine the effectiveness of telemedicine on different health outcomes of RA. Methods: The following sources were used: PubMed, Cochrane, Web of Science, Cumulative Index to Nursing and Allied Health Literature, and Embase. The publication period was from the establishment of the database to May 12, 2022. Methodological and reporting qualities were assessed using A Measurement Tool to Assess Systematic Reviews 2 and Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Each intervention's evidence of effect was graded in accordance with the Grades of Recommendations Assessment, Development and Evaluation standards. The comparison of systematic reviews and the investigation of the impact of telemedicine on various outcomes were carried out through a meta-analysis of original studies. Results: Eight systematic reviews were included. The results showed that telemedicine imparted significant improvements in patients with RA in terms of disease activity, function, physical activity, self-efficacy, and knowledge. Conclusions: Telemedicine can improve the overall standard of care for patients with RA. In the future, standardized telemedicine processes should be developed to protect patients.
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Artrite Reumatoide , Telemedicina , Humanos , Artrite Reumatoide/terapia , Telemedicina/métodosRESUMO
As a subclass of the biopharmaceutical classification system (BCS) class II, basic drugs (BCS IIB) exhibit pH-dependent solubility and tend to generate supersaturation in the gastrointestinal tract, leading to less qualified in vitro-in vivo correlation (IVIVC). This study aims to develop a physiologically based multi-cup dissolution approach to improve the evaluation of the supersaturation for a higher quality of IVIVC and preliminarily explores the molecular mechanism of supersaturation and precipitation of ketoconazole affected by Polyvinylpyrrolidone-vinyl acetate copolymer (PVPVA) and hydroxypropyl methyl-cellulose (HPMC). The concentration of ketoconazole in each cup of the dynamic gastrointestinal model (DGIM) was measured using fiber optical probes. Molecular interactions between ketoconazole and PVPVA or HPMC were simulated by Materials Studio. The results demonstrated that PVPVA and HPMC improved and maintained the supersaturation of ketoconazole. PVPVA exhibited superior precipitation inhibitory effect on ketoconazole molecule aggregation due to slightly stronger van der Waals forces as well as unique electrostatic forces, thereby further enhancing in vitro drug absorption, which correlated well with in vivo drug absorption. Compared with a conventional dissolution apparatus paddle method, the DGIM improved the mean prediction error through the IVIVC from 19.30% to 9.96%, reaching the qualification criteria. In conclusion, the physiologically based multi-cup dissolution approach enables improved evaluation of supersaturation in gastrointestinal transportation of BCS IIB drug ketoconazole, enabling screening screen precipitation inhibitors and achieving qualified IVIVC for drug formulation studies.
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Produtos Biológicos , Cetoconazol , Solubilidade , Cetoconazol/farmacologia , Simulação de Dinâmica Molecular , Produtos Biológicos/farmacologia , Absorção Intestinal , Administração OralRESUMO
BACKGROUND: Psychological stress is one of the most important factors that trigger emotional disorders, such as depression and anxiety. Emerging evidence suggests that neuroinflammation exacerbated by bidirectional communication between the peripheral immune system and the central nervous system facilitates abnormal psychiatric symptoms. This study aimed to investigate the hippocampal migration of bone marrow (BM)-derived monocytes and its role in regulating depressive-like behaviors using the chronic psychological stress (CPS) mouse model. More importantly, whether the central migration of these peripheral BM-derived cells depend on the disruption of the blood-brain barrier (BBB) was also investigated. METHODS AND FINDINGS: Green fluorescent protein-positive (GFP+) BM chimeric mice were used to distinguish BM-derived monocytes within the brain. A CPS mouse model was established to explore the effect of CPS on hippocampal migration of BM-derived monocytes and its role in the regulation of depressive-like behaviors. The results revealed that BM-derived GFP+ cells accumulated in the hippocampus and differentiated into microglia-like cells after exposure to CPS. Interestingly, this migration was not associated with BBB disruption. Furthermore, treatment with C-C chemokine receptor 2 (CCR2) antagonist (RS102895) suppressed the recruitment of BM-derived monocytes to the hippocampus and alleviated depressive-like symptoms. CONCLUSION: These findings indicate that monocyte recruitment to the hippocampus in response to psychological stress may represent a novel cellular mechanism that contributes to the development of depression.
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Medula Óssea , Monócitos , Animais , Barreira Hematoencefálica/metabolismo , Células da Medula Óssea/metabolismo , Modelos Animais de Doenças , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Hipocampo/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Monócitos/metabolismo , Estresse PsicológicoRESUMO
Neural precursor cell-expressed developmentally downregulated gene 4 (NEDD4) was a member of HECT E3 ubiquitin ligases, which participated in various biological processes. In this study, a NEDD4 was identified and analyzed in Nile tilapia, Oreochromis niloticus (OnNEDD4) and its open reading frame was 2781 bp, encoding 926 amino acids. Three conserved structure features were found in OnNEDD4, including C2 domain, WW domains and HECT domain. OnNEDD4 was constitutively expressed in all examined tissues and the highest expression level was observed in thymus. After Streptococcus agalactiae stimulation, OnNEDD4 was significantly induced in several tissues, including thymus, intestine, blood and gill. Moreover, yeast two-hybrid assay shown OnNEDD4 could interact with extracellular region of OnCD40, but this interaction didn't affect the phagocytosis of monocytes/macrophages (MO/MΦ) to S. agalactiae and A. hydrophila. Taken together, the present study suggested that OnNEDD4 participate in CD40-mediated immune response excluding phagocytosis.
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Ciclídeos , Doenças dos Peixes , Infecções Estreptocócicas , Animais , Proteínas de Peixes/química , Regulação da Expressão Gênica , Sequência de Aminoácidos , Streptococcus agalactiae/fisiologia , Clonagem Molecular , Imunidade Inata/genéticaRESUMO
Mammals TRAF2 played a dual role in several immune signaling transduction processes. In this study, TRAF2 was cloned from Nile tilapia, Oreochromis niloticus, which named OnTRAF2. The open reading frame was 1797 bp, encoding 598 amino acids. Amino acid alignment and phylogenetic analysis indicated that OnTRAF2 showed relatively low identify with other teleost TRAF2 proteins, with the exception of TRAF2s from Epinephelus coioides. In healthy tilapia, OnTRAF2 was expressed widely in all the examined tissues, which had highest expression level in the brain. After Streptococcus agalactiae infection, the expression level of OnTRAF2 was increased significantly at different times in several organs, implying that OnTRAF2 may be involved in host defense against S. agalactiae infection. The result of subcellular localization showed that OnTRAF2 presented in cytoplasm and nucleus of HEK293T cells. Additionally, overexpression of OnTRAF2 significantly decreased the transcriptional activity of the NF-κB reporter in HEK293T cells, yeast two-hybrid results revealed that OnTRAF2 had no interaction with E3 ubiquitin ligase OnNEDD4. These results indicated that OnTRAF2 played important function during bacterial infection, and negatively mediated the immune signaling transduction in Nile tilapia, while the mechanism need further study.
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Ciclídeos , Doenças dos Peixes , Infecções Estreptocócicas , Animais , Proteínas de Peixes , Regulação da Expressão Gênica , Células HEK293 , Humanos , Mamíferos/metabolismo , NF-kappa B/genética , NF-kappa B/metabolismo , Filogenia , Infecções Estreptocócicas/genética , Infecções Estreptocócicas/veterinária , Streptococcus agalactiae , Fator 2 Associado a Receptor de TNF/genética , Fator 2 Associado a Receptor de TNF/metabolismo , Ubiquitina-Proteína Ligases/metabolismoRESUMO
The high-resolution space camera needs to image the fringe target that meets the sampling frequency in the modulation transfer function test. However, blurry regions often appear in the target image, which seriously affects the visual effect and test efficiency. In this paper, by analyzing the imaging process of the rectangle striated target by a complementary metal-oxide-semiconductor transistor detector, a moiré fringe blurry degradation model of the target image is proposed. According to the degradation model, it is concluded that there are low blurry degradation regions in the image. Taking the low blurry degradation region as the reference information and the region similarity as the weight, the weighted spatial filtering and mean filtering are carried out to eliminate the blurry band in the target image. The experimental results show that compared with bilinear interpolation and guidance filter, this algorithm can effectively remove the image blur caused by the target periodic error and the angle error. The work in this paper provides a practical tool and theoretical support for subsequent space camera tests.
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BACKGROUND: Although oocyte quality is the dominant factor determining embryo quality, few studies have been conducted to evaluate embryo quality based on the metabolites related to the oocyte. With quantification of the follicular fluid (FF) metabolites, in assisted reproductive technology (ART), this study sought to evaluate the embryo or oocyte quality through an informative approach. RESULTS: An evaluation model consisting of 17 features was generated to distinguish the embryo quality on day 3 post-fertilization, and phosphatidylcholines (PCs) were the key contributors to the evaluation. The model was extended to the patients under different ages and hyperstimulations, and the features were further enriched to facilitate the evaluation of the embryo quality. The metabolites were clustered through pathway analysis, leading to a hypothesis that accumulation of arachidonic acid induced by PCs might weaken embryo quality on day 3 post-fertilization. CONCLUSIONS: A discriminating model with metabolic features elicited from follicular fluid was established, which enabled the evaluation of the embryo or oocyte quality even under certain clinical conditions, and the increase of PCs in follicular fluid implies the attenuation of embryo quality on day 3 post-fertilization.