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Germinated plants grow in darkness until they emerge above the soil. To help the seedling penetrate the soil, most dicot seedlings develop an etiolated apical structure consisting of an apical hook and folded, unexpanded cotyledons atop a rapidly elongating hypocotyl. Brassinosteroids (BRs) are necessary for etiolated apical development, but their precise role and mechanisms remain unclear. Arabidopsis thaliana SMALL AUXIN UP RNA17 (SAUR17) is an apical-organ-specific regulator that promotes production of an apical hook and closed cotyledons. In darkness, ethylene and BRs stimulate SAUR17 expression by transcription factor complexes containing PHYTOCHROME-INTERACTING FACTORs (PIFs), ETHYLENE INSENSITIVE 3 (EIN3), and its homolog EIN3-LIKE 1 (EIL1), and BRASSINAZOLE RESISTANT1 (BZR1). BZR1 requires EIN3 and PIFs for enhanced DNA-binding and transcriptional activation of the SAUR17 promoter; while EIN3, PIF3, and PIF4 stability depends on BR signaling. BZR1 transcriptionally downregulates EIN3-BINDING F-BOX 1 and 2 (EBF1 and EBF2), which encode ubiquitin ligases mediating EIN3 and PIF3 protein degradation. By modulating the EBF-EIN3/PIF protein-stability circuit, BRs induce EIN3 and PIF3 accumulation, which underlies BR-responsive expression of SAUR17 and HOOKLESS1 and ultimately apical hook development. We suggest that in the etiolated development of apical structures, BRs primarily modulate plant sensitivity to darkness and ethylene.
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Proteínas de Arabidopsis , Arabidopsis , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Escuridão , Brassinosteroides/farmacologia , Brassinosteroides/metabolismo , Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Etilenos/metabolismo , Plântula/genética , Plântula/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismoRESUMO
Featured with the attractive properties such as large surface area, unique atomic layer thickness, excellent electronic conductivity, and superior catalytic activity, layered metal chalcogenides (LMCs) have received considerable research attention in electrocatalytic applications. In this review, the approaches developed to synthesize LMCs-based electrocatalysts are summarized. Recent progress in LMCs-based composites for electrochemical energy conversion applications including oxygen reduction reaction, carbon dioxide reduction reaction, oxygen evolution reaction, hydrogen evolution reaction, overall water splitting, and nitrogen reduction reaction is reviewed, and the potential opportunities and practical obstacles for the development of LMCs-based composites as high-performing active substances for electrocatalytic applications are also discussed. This review may provide an inspiring guidance for developing high-performance LMCs for electrochemical energy conversion applications.
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BACKGROUND: Ethanol elicits a rapid stimulatory effect and a subsequent, prolonged sedative response, which are potential predictors of EtOH consumption by decreasing adenosine signaling; this phenomenon also reflects the obvious sex difference. cAMP-PKA signaling pathway modulation can influence the stimulatory and sedative effects induced by EtOH in mice. This study's objective is to clarify the role of phosphodiesterase (PDE) in mediating the observed sex differences in ethanol responsiveness between male and female animals. METHODS: EtOH was administered intraperitoneally (i.p.) for 7 days to identify the changes in PDE isoforms in response to EtOH treatment. Additionally, EtOH consumption and preference of male and female C57BL/6J mice were assessed using the drinking-in-the-dark (DID) and two-bottle choice (2BC) tests. Further, pharmacological inhibition of PDE7A heterozygote knockout mice was performed to investigate its effects on ethanol-induced stimulation and sedation in both male and female mice. Finally, Western blotting analysis was performed to evaluate the alterations in cAMP-PKA/Epac2 pathways. RESULTS: Ethanol administration resulted in an immediate upregulation in PDE7A expression in female mice, indicating a strong association between PDE7A and ethanol stimulation. Through the pharmacological inhibition of PDE7A KD mice, we have demonstrated, for the first time, that PDE7A selectively attenuates ethanol responsiveness and consumption exclusively in female mice may be associated with the cAMP-PKA/Epac2 pathway and downstream phosphorylation of CREB and ERK1/2. CONCLUSIONS: PDE7A inhibition or knockdown attenuates EtOH responsiveness and consumption exclusively in female mice associated the change of cAMP-PKA/Epac2 signaling pathways, thereby highlighting its potential as a novel therapeutic target for alcohol use disorder.
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Phosphodiesterase 8 (PDE8), as a member of PDE superfamily, specifically promotes the hydrolysis and degradation of intracellular cyclic adenosine monophosphate (cAMP), which may be associated with pathogenesis of Alzheimer's disease (AD). However, little is currently known about potential role in the central nervous system (CNS). Here we investigated the distribution and expression of PDE8 in brain of mouse, which we believe can provide evidence for studying the role of PDE8 in CNS and the relationship between PDE8 and AD. Here, C57BL/6J mice were used to observe the distribution patterns of two subtypes of PDE8, PDE8A and PDE8B, in different sexes in vivo by western blot (WB). Meanwhile, C57BL/6J mice were also used to demonstrate the distribution pattern of PDE8 in selected brain regions and localization in neural cells by WB and multiplex immunofluorescence staining. Furthermore, the triple transgenic (3×Tg-AD) mice and wild type (WT) mice of different ages were used to investigate the changes of PDE8 expression in the hippocampus and cerebral cortex during the progression of AD. PDE8 was found to be widely expressed in multiple tissues and organs including heart, kidney, stomach, brain, and liver, spleen, intestines, and uterus, with differences in expression levels between the two subtypes of PDE8A and PDE8B, as well as two sexes. Meanwhile, PDE8 was widely distributed in the brain, especially in areas closely related to cognitive function such as cerebellum, striatum, amygdala, cerebral cortex, and hippocampus, without differences between sexes. Furthermore, PDE8A was found to be expressed in neuronal cells, microglia and astrocytes, while PDE8B is only expressed in neuronal cells and microglia. PDE8A expression in the hippocampus of both female and male 3×Tg-AD mice was gradually increased with ages and PDE8B expression was upregulated only in cerebral cortex of female 3×Tg-AD mice with ages. However, the expression of PDE8A and PDE8B was apparently increased in both cerebral cortex and hippocampus in both female and male 10-month-old 3×Tg-AD mice compared WT mice. These results suggest that PDE8 may be associated with the progression of AD and is a potential target for its prevention and treatment in the future.
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3',5'-AMP Cíclico Fosfodiesterases , Doença de Alzheimer , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Animais , Feminino , Masculino , Camundongos , 3',5'-AMP Cíclico Fosfodiesterases/metabolismo , 3',5'-AMP Cíclico Fosfodiesterases/genética , Doença de Alzheimer/metabolismo , Encéfalo/metabolismo , Hipocampo/metabolismoRESUMO
BACKGROUND: Hirschsprung disease (HSCR) is a congenital intestinal disease characterised by functional obstruction of the colon. Herein, we investigated the role and mechanism of the gene GFRA4 in HSCR. METHODS: GFRA4 expression in the ganglionic and aganglionic segment tissues in patients with HSCR and healthy colon tissues were detected using qRT-PCR, western blot, and immunohistochemistry. Cell proliferation, cycle distribution, apoptosis, changes in mitochondrial membrane potential, and differentiation were assessed in mouse enteric neural crest stem cells (ENCSCs) using the CCK-8 assay, EdU staining, flow cytometry, JC-1 probe, and immunofluorescence, respectively. GSEA analysis was performed to screen the signaling pathways regulated by GFRA4. RESULTS: GFRA4 was downregulated in aganglionic segment tissues compared to control and ganglionic segment tissues. GFRA4 overexpression promoted proliferation and differentiation, and inhibited apoptosis in ENCSCs, while GFRA4 down-regulation had the opposite result. GFRA4 activated the hedgehog pathway. GFRA4 overexpression enhanced the expression of key factors of the hedgehog pathway, including SMO, SHH, and GLI1. However, GFRA4 down-regulation reduced their expression. An antagonist of hedgehog pathway, cyclopamine, attenuated the effect of GFRA4 overexpression on proliferation, differentiation, and apoptosis of ENCSCs. CONCLUSION: GFRA4 promotes proliferation and differentiation but inhibits apoptosis of ENCSCs via the hedgehog pathway in HSCR. IMPACT: This study confirms that GFRA4 improves the proliferation and differentiation of ENCSCs via modulation of the hedgehog pathway. This study for the first time revealed the role and the mechanism of the action of GFRA4 in HSCR, which indicates that GFRA4 may play a role in the pathological development of HSCR. Our findings may lay the foundation for further investigation of the mechanisms underlying HSCR development and into targets of HSCR treatment.
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BACKGROUND: Based on research, c.609G>A (p.W203X) is a universal mutation site for MMACHC in methylmalonic acidemia (MMA) combined with homocystinuria, cblC type (cblC disease), and c.467G>A (p.G156D) mutation in families with such disease have not yet been reported. To conduct clinical and molecular genetic analysis of a family with cblC disease. METHODS: This work followed the Declaration of Helsinki. All testing methods were performed under the informed consent of our children patients' parents. A second-generation cblC family with 5 members, was selected as the research subject, including sick siblings and parents and an older sister with normal phenotype, given newborn screening for acylcarnitine spectrum via liquid chromatography tandem mass spectrometry (LC-MS/MS), and diagnosed through combining urine organic acid with homocysteine detection via gas chromatography-mass spectrometry (GC-MS) with second-generation gene sequencing technology. The peripheral blood of five family members was collected for genomic DNA extraction, and the changes were screened in disease-related MMACHC sequence via PCR and direct DNA sequencing. RESULTS: The family conformed to the autosomal recessive inheritance, the proband and younger sister were cblC patients, diagnosed in February and at 22d given relevant treatment. The proband died, whereas the younger sister received follow-up treatment. Their parents and sister had normal phenotype. In 2 cases, there was compound heterozygous mutation in MMACHC called c.609G>A (p.W203X) nonsense mutation and c.467G>A (p.G156D) missense mutation in exon 4, while the father with normal phenotype had heterozygous mutation c.609G>A in exon 4 coding area. In its protein, the 203rd amino acid changed from tryptophan to a stop codon (p.W203 x). The normal mother and sister had a heterozygous mutation c.467G>A in exon 4 coding area. In its protein, the 156th amino acid changed from glycine to aspartic acid (p.G156D). CONCLUSIONS: The cblC family results from c.609G>A (p.W203X) and c.467G>A (p.G156D) compound heterozygous mutations in MMACHC, which has a pathogenic impact.
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Erros Inatos do Metabolismo dos Aminoácidos , Homocistinúria , Recém-Nascido , Criança , Humanos , Homocistinúria/complicações , Homocistinúria/diagnóstico , Homocistinúria/genética , Cromatografia Líquida , Espectrometria de Massas em Tandem , Erros Inatos do Metabolismo dos Aminoácidos/diagnóstico , Erros Inatos do Metabolismo dos Aminoácidos/genética , Mutação , Aminoácidos , Biologia Molecular , Vitamina B 12 , Ácido Metilmalônico , OxirredutasesRESUMO
BACKGROUND: MRI has been widely used to predict the preoperative proliferative potential of pituitary adenoma (PA). However, the relationship between the cyst/tumor volume ratio (C/T ratio) and the proliferative potential of PA has not been reported. Herein, we determined the predictive value of the C/T ratio of PA for tumor cell proliferation. METHODS: The clinical data of 72 patients with PA and cystic change on MRI were retrospectively analyzed. PA volume, cyst volume, and C/T ratio were calculated. The corresponding intraoperative specimens were collected. Immunohistochemistry and hematoxylin-eosin staining were performed to evaluate the Ki67 index and nuclear atypia. Patients were categorized according to the Ki67 index (< 3% and ≥ 3%) and nuclear atypia (absence and presence). Univariate and multivariate analyses were used to identify the significant predictors of the Ki67 index and nuclear atypia. The receiver operating characteristic curve assessed the prediction ability of the significant predictors. RESULTS: Larger tumor volumes, smaller cyst volumes, and lower C/T ratios were found in patients with higher Ki67 indexes and those with nuclear atypia (P < 0.05). C/T ratio was an independent predictor of the Ki67 index (odds ratio = 0.010, 95% confidence interval = 0.000-0.462) and nuclear atypia (odds ratio = 0.010, 95% confidence interval = 0.000-0.250). The predictive value of the C/T ratio did not differ significantly from that of tumor volume (P > 0.05) but was better than that of cyst volume (P < 0.05). The area under the curve of the C/T ratio for predicting the Ki67 index and nuclear atypia was larger than that for predicting cyst volume and tumor volume. CONCLUSIONS: C/T ratios can be used to predict PA tumor proliferation preoperatively. Our findings may facilitate the selection of surgery timing and the efficacy evaluation of surgery.
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Adenoma , Cistos , Neoplasias Hipofisárias , Humanos , Neoplasias Hipofisárias/diagnóstico por imagem , Neoplasias Hipofisárias/cirurgia , Antígeno Ki-67/análise , Estudos Retrospectivos , Carga Tumoral , Adenoma/diagnóstico por imagem , Adenoma/cirurgia , Proliferação de CélulasRESUMO
Fibroblast growth factor (FGF)/extracellular signal-regulated kinase (ERK) signaling plays a crucial role in anterior-posterior (A-P) axial patterning of vertebrate embryos by promoting posterior development. In our screens for novel developmental regulators in Xenopus embryos, we identified Fam3b as a secreted factor regulated in ectodermal explants. Family with sequence similarity 3 member B (FAM3B)/PANDER (pancreatic-derived factor) is a cytokine involved in glucose metabolism, type 2 diabetes, and cancer in mammals. However, the molecular mechanism of FAM3B action in these processes remains poorly understood, largely because its receptor is still unidentified. Here we uncover an unexpected role of FAM3B acting as a FGF receptor (FGFR) ligand in Xenopus embryos. fam3b messenger RNA (mRNA) is initially expressed maternally and uniformly in the early Xenopus embryo and then in the epidermis at neurula stages. Overexpression of Xenopus fam3b mRNA inhibited cephalic structures and induced ectopic tail-like structures. Recombinant human FAM3B protein was purified readily from transfected tissue culture cells and, when injected into the blastocoele cavity, also caused outgrowth of tail-like structures at the expense of anterior structures, indicating FGF-like activity. Depletion of fam3b by specific antisense morpholino oligonucleotides in Xenopus resulted in macrocephaly in tailbud tadpoles, rescuable by FAM3B protein. Mechanistically, FAM3B protein bound to FGFR and activated the downstream ERK signaling in an FGFR-dependent manner. In Xenopus embryos, FGFR activity was required epistatically downstream of Fam3b to mediate its promotion of posterior cell fates. Our findings define a FAM3B/FGFR/ERK-signaling pathway that is required for axial patterning in Xenopus embryos and may provide molecular insights into FAM3B-associated human diseases.
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Citocinas/fisiologia , Desenvolvimento Embrionário/fisiologia , Receptores de Fatores de Crescimento de Fibroblastos/metabolismo , Proteínas de Xenopus/fisiologia , Xenopus laevis/embriologia , Animais , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Células HEK293 , HumanosRESUMO
In order to realize the economic dispatch and safety stability of offshore wind farms, and to address the problems of strong randomness and strong time correlation in offshore wind power forecasting, this paper proposes a combined model of principal component analysis (PCA), sparrow algorithm (SSA), variational modal decomposition (VMD), and bidirectional long- and short-term memory neural network (BiLSTM). Firstly, the multivariate time series data were screened using the principal component analysis algorithm (PCA) to reduce the data dimensionality. Secondly, the variable modal decomposition (VMD) optimized by the SSA algorithm was applied to adaptively decompose the wind power time series data into a collection of different frequency components to eliminate the noise signals in the original data; on this basis, the hyperparameters of the BiLSTM model were optimized by integrating SSA algorithm, and the final power prediction value was obtained. Ultimately, the verification was conducted through simulation experiments; the results show that the model proposed in this paper effectively improves the prediction accuracy and verifies the effectiveness of the prediction model.
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Ridge-furrow with full ï¬lm mulching has been widely applied to increase crop yield and water productivity on the Loess Plateau, but it may stimulate carbon (C) mineralization. How to integrate other technological benefits based on this technology for long-term maintenance of high yield and soil fertility is a pressing issue. With the local farmers' practice (FP) as a control, three integrated soil-crop system management (ISSM) practices integrating fertilizer rates, fertilizer types and planting densities (ISSM-N1, ISSM-N2 and ISSM-MN) were established to improve maize yield and soil quality. Compared with the FP, the maize yield increased by 13.34%, 21.83% and 30.24%, and the soil quality index (SQI) increased by 9.66%, 14.91% and 38.38% for ISSM-N1, ISSM-N2 and ISSM-MN, respectively. However, ISSM-N1 did not significantly increase yield, and ISSM-N2 increased residual soil nitrate and decreased nitrogen (N) partial factor productivity significantly. Compared to the FP, ISSM practices increased soil organic carbon (SOC), labile organic C fractions (LOCFs) and potassium permanganate organic C fractions in the topsoil to varying degrees, but only ISSM-MN reached significant levels for most C fractions. The sensitivity index indicated very easily oxidizable C (24.6%), easily oxidizable C (24.7%), hot-water extractable C (30.8%), labile organic C (24.7%) and particulate organic C (57.3%) were more sensitive than SOC (22.7%). ISSM-MN sequestered significantly higher C than the other treatments. The results of the relative importance analysis and the structural equation model indicated that LOCFs were the direct contributors to yield, while recalcitrant C (CO) was the indirect contributor, revealing the underlying mechanism that CO decomposed to replenish LOCFs and the total N pool with the water soluble C pool as the transit station. Overall, ISSM-MN is the most promising strategy to improve crop yield and soil fertility in the long term on the Loess Plateau.
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Agricultura , Solo , Solo/química , Agricultura/métodos , Carbono/análise , Fertilizantes/análise , Zea mays , Nitrogênio/análise , Água/análise , ChinaRESUMO
Following germination in the dark, Arabidopsis (Arabidopsis thaliana) seedlings undergo etiolation and develop apical hooks, closed cotyledons, and rapidly elongating hypocotyls. Upon light perception, the seedlings de-etiolate, which includes the opening of apical hooks and cotyledons. Here, we identify Arabidopsis Small Auxin Up RNA17 (SAUR17) as a downstream effector of etiolation, which serves to bring about apical hook formation and closed cotyledons. SAUR17 is highly expressed in apical hooks and cotyledons and is repressed by light. The apical organs also express a group of light-inducing SAURs, as represented by SAUR50, which promote hook and cotyledon opening. The development of etiolated or de-etiolated apical structures requires asymmetric differential cell growth. We present evidence that the opposing actions of SAUR17 and SAUR50 on apical development largely result from their antagonistic regulation of Protein Phosphatase 2C D-clade 1 (PP2C-D1), a phosphatase that suppresses cell expansion and promotes apical hook development in the dark. SAUR50 inhibits PP2C-D1, whereas SAUR17 has a higher affinity for PP2C-D1 without inhibiting its activity. PP2C-D1 predominantly associates with SAUR17 in etiolated seedlings, which shields it from inhibitory SAURs such as SAUR50. Light signals turn off SAUR17 and upregulate a subgroup of SAURs including SAUR50 at the inner side of the hook and cotyledon cells, leading to cell expansion and unfolding of the hook and cotyledons.
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Proteínas de Arabidopsis/metabolismo , Arabidopsis/genética , Regulação da Expressão Gênica de Plantas , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Transdução de Sinal Luminoso , Reguladores de Crescimento de Plantas/metabolismo , Arabidopsis/crescimento & desenvolvimento , Arabidopsis/fisiologia , Arabidopsis/efeitos da radiação , Proteínas de Arabidopsis/genética , Cotilédone/genética , Cotilédone/crescimento & desenvolvimento , Cotilédone/fisiologia , Etilenos/metabolismo , Estiolamento , Genes Reporter , Ácidos Indolacéticos/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/genética , Luz , Proteína Fosfatase 2C/genética , Proteína Fosfatase 2C/metabolismo , Plântula/genética , Plântula/crescimento & desenvolvimento , Plântula/fisiologia , Regulação para CimaRESUMO
The polarization modulation of deep-UV light is an important process that incorporates functionality to selectively respond to light-mater interaction. Typically, optical anisotropy is foremost to the use efficiency of deep-UV birefringent crystals. Herein, a new congruently melting polyborate with extremely large birefringence (Δn(001) =0.14@589.3â nm) and band gap (6.89â eV) is discovered as a high performance birefringent crystal, which breaks the current deadlock of deep-UV polyborates that usually show small birefringence. The rigid tetrahedra, including [ZnO4 ] and edge-sharing [BO4 ] tetrahedra, make all the planar [BO3 ] triangles in the lattice adopt preferential arrangement and thereby lead to an extraordinary large birefringence that is larger than all the deep-UV borates with experimentally measured values. Structural analyses with the additional theoretical calculations were used to study the origin of strong optical anisotropy in BaZnB4 O8 .
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RESEARCH QUESTION: What are the different features of the vaginal microbiome (VMB) between patients with polycystic ovary syndrome (PCOS) and healthy women? DESIGN: A cross-sectional study was conducted at a single academic university-affiliated centre. A total of 1446 participants were recruited (PCOS group, n =713, control group, nâ¯=â¯733). Vaginal swabs were analysed using 16S rRNA gene sequencing. The diversity and composition of the microbiome were compared between the PCOS group and the control group. Microbial interaction networks and functional prediction were investigated. RESULTS: The PCOS group had a higher alpha diversity than the control group (Shannon Pâ¯=â¯0.03, Simpson Pâ¯=â¯0.02), and higher intra-group variability was observed in PCOS group (P < 2.2E-16). At the genus level, the proportion of Lactobacillus decreased (85.1% versus 89.3%, false discovery rate [FDR]â¯=â¯0.02), whereas the proportion of Gardnerella vaginalis and Ureaplasma increased in the PCOS group (5.1% versus 3.3%, FDRâ¯=â¯0.006; 1.2% versus 0.6%, FDRâ¯=â¯0.002, respectively). Lactobacillus acidophilus, Prevotella buccalis and G. vaginalis were identified as the main differential species. L. acidophilus was positively correlated with serum levels of anti-Müllerian hormone (AMH), and triglyceride (Pâ¯=â¯2.01E-05, Pâ¯=â¯0.004, respectively). P. buccalis was negatively correlated with serum levels of AMH and testosterone (Pâ¯=â¯0.002, Pâ¯=â¯0.003, respectively). G. vaginalis was positively correlated with serum levels of AMH, oestradiol and progesterone (Pâ¯=â¯0.004, Pâ¯=â¯0.005, Pâ¯=â¯0.03, respectively). The VMB interaction network indicated that Lactobacillus crispus, Prevotella timonensis, and P. buccalis could be key drivers in the PCOS group. Overall, 55 predicted genes were found to be differentially abundant between PCOS and the control (FDRs < 0.25). CONCLUSIONS: The PCOS group had a higher diversity of vaginal microbiome and showed an enhanced level of heterogeneity. The proportion of Lactobacillus in the PCOS group decreased, whereas the proportions of Gardnerella and Ureaplasma increased. These results warrant further research that can validate the correlation between PCOS and VMB.
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Microbiota , Síndrome do Ovário Policístico , Feminino , Humanos , Estudos Transversais , RNA Ribossômico 16S/genética , Hormônio AntimüllerianoRESUMO
Circulating tumor cells (CTCs) play a vital role in the metastasis and recurrence of breast cancer. CTCs are highly heterogeneous at the stage of Epithelial-to-Mesenchymal Transition (EMT), but the phenotypic and biological characteristics in different EMT stages remain poorly defined. We conducted an orthotopic mouse (4T1) model of breast cancer to isolate CTCs and identified two phenotypes of CTCs: intermediate E/M and mesenchymal CTCs. MTT, Colony formation, Transwell migration and invasion assays were utilized to examined cell proliferation, colony forming, migration and invasion ability. Both the intermediate E/M and mesenchymal CTCs exhibited lower rates of proliferation, colony formation and invasion, as compared to primary tumor cells. The mesenchymal CTCs had a higher rate of invasion but lower rates of proliferation and colony formation than the intermediate E/M CTCs. They also exhibited lower rates of growth and metastasis than the primary tumor cells in vivo, but the mesenchymal CTCs had a higher rate of metastasis than the intermediate E/M CTCs. Fluid shear stress induced the EMT transition of CTCs. The comprehensive analysis of CTCs proteomics discovered proteins that differentially expressed in the two types of CTCs and their primary tumor cells.
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Células Neoplásicas Circulantes , Camundongos , Animais , Células Neoplásicas Circulantes/patologia , Biomarcadores Tumorais/metabolismo , Transição Epitelial-Mesenquimal/genética , Contagem de Células , Metástase NeoplásicaRESUMO
Depression is among the most frequent psychiatric comorbid conditions in Alzheimer disease (AD). However, pharmacotherapy for depressive disorders in AD is still a big challenge, and the data on the efffcacy of current antidepressants used clinically for depressive symptoms in patients with AD remain inconclusive. Here we investigated the mechanism of the interactions between depression and AD, which we believe would aid in the development of pharmacological therapeutics for the comorbidity of depression and AD. Female APP/PS1/Tau triple transgenic (3×Tg-AD) mice at 24 months of age and age- and sex-matched wild-type (WT) mice were used. The shuttle-box passive avoidance test (PAT) were implemented to assess the abilities of learning and memory, and the open field test (OFT) and the tail suspension test (TST) were used to assess depression-like behavior. High-performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS) was used to detect the level of neurotransmitters related to depression in the hippocampus of mice. The data was identified by orthogonal projections to latent structures discriminant analysis (OPLS-DA). Most neurotransmitters exert their effects by binding to the corresponding receptor, so the expression of relative receptors in the hippocampus of mice was detected using Western blot. Compared to WT mice, 3×Tg-AD mice displayed significant cognitive impairment in the PAT and depression-like behavior in the OFT and TST. They also showed significant decreases in the levels of L-tyrosine, norepinephrine, vanillylmandelic acid, 5-hydroxytryptamine, and acetylcholine, in contrast to significant increases in 5-hydroxyindoleacetic acid, L-histidine, L-glutamine, and L-arginine in the hippocampus. Moreover, the expression of the alpha 1a adrenergic receptor (ADRA1A), serotonin 1 A receptor (5HT1A), and γ-aminobutyric acid A receptor subunit alpha-2 (GABRA2) was significantly downregulated in the hippocampus of 3×Tg-AD mice, while histamine H3 receptor (H3R) expression was significantly upregulated. In addition, the ratio of phosphorylated cAMP-response element-binding protein (pCREB) and CREB was significantly decreased in the hippocampus of 3×Tg-AD mice than WT mice. We demonstrated in the present study that aged female 3×Tg-AD mice showed depression-like behavior accompanied with cognitive dysfunction. The complex and diverse mechanism appears not only relevant to the imbalance of multiple neurotransmitter pathways, including the transmitters and receptors of the monoaminergic, GABAergic, histaminergic, and cholinergic systems, but also related to the changes in L-arginine and CREB signaling molecules.
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Doença de Alzheimer , Disfunção Cognitiva , Camundongos , Feminino , Animais , Doença de Alzheimer/complicações , Doença de Alzheimer/genética , Doença de Alzheimer/tratamento farmacológico , Camundongos Transgênicos , Espectrometria de Massas em Tandem , Depressão/tratamento farmacológico , Disfunção Cognitiva/metabolismo , Hipocampo/metabolismo , Neurotransmissores/metabolismo , Modelos Animais de Doenças , Peptídeos beta-Amiloides/farmacologia , Proteínas tau/metabolismoRESUMO
Myxogastrea is a group of eukaryotic microorganisms included in Amoebozoa. Its life cycle includes two trophic stages: plasmodia and myxamoeflagellates. However, only about 102 species have their complete life cycle known in literature and only about 18 species have their plasmodial axenic culture accomplished in laboratory conditions. The research presented herein involved culturing of Physarum galbeum on the water agar medium. The events that transpired during its life cycle including spore germination, plasmodia formation, and sporocarp development were documented especially the subglobose or discoid sporotheca and the stalk formation. The spores germinated by the V-shape split method to release a single protoplasm. Yellow-green pigmented phaneroplasmodia developed into sporocarps by subhypothallic type. The present article gives details of the sporocarp development of P. galbeum and its plasmodial axenic culture on solid and liquid mediums.
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Physarum , Animais , Cultura Axênica , Meios de Cultura , Estágios do Ciclo de VidaRESUMO
OBJECTIVE: We aim to study the MRI features of pituitary adenoma (PA) apoplexy and their relationship with hypoxia, proliferation, and pathology. METHODS: Sixty-seven patients with MRI signs of PA apoplexy were selected. According to the MRI signs, they were divided into the parenchymal group and the cystic group. The parenchymal group had a low signal area on T2WI without cyst >2 mm and this area was not significantly enhanced on the corresponding TW1 enhancement. The cystic group had a cyst >2 mm on T2WI, and the cyst showed liquid stratification on T2WI or high signal on T1WI. The relative T1WI (rT1WI) enhancement value and relative T2WI (rT2WI) value of non-apoplexy areas were measured. Protein levels of hypoxia-inducible factor-1 (HIF-1α), pyruvate dehydrogenase kinase 1 (PDK1), and Ki67 were detected with immunohistochemistry and Western blot. Nuclear morphology was observed with HE staining. RESULTS: The rT1WI enhancement average value, rT2WI average value, Ki67 protein expression level, and the number of abnormal nuclear morphology of non-apoplexy lesions in the parenchymal group were significantly lower than those in the cystic group. The protein expression levels of HIF-1α and PDK1 in the parenchymal group were significantly higher than those in the cystic group. HIF-1α protein was positively correlated with PDK1 but negatively correlated with Ki67. CONCLUSION: When there is PA apoplexy, the ischemia and hypoxia of the cystic group are lesser than those of the parenchymal group, but the proliferation is stronger.
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Cistos , Neoplasias Hipofisárias , Humanos , Neoplasias Hipofisárias/complicações , Neoplasias Hipofisárias/diagnóstico por imagem , Antígeno Ki-67 , Imageamento por Ressonância Magnética , Hipóxia , Proliferação de CélulasRESUMO
The conversion of nitrogen-oxygen-rich biomass wastes into heteroatomic co-doped nanostructured carbons used as energy storage materials has received widespread attention. In this study, an in situ nitrogen-oxygen co-doped porous carbon was prepared for supercapacitor applications via a two-step method of pre-carbonization and pyrolytic activation using mixed egg yolk/white and rice waste. The optimal sample (YPAC-1) was found to have a 3D honeycomb structure composed of abundant micropores and mesopores with a high specific surface area of 1572.1 m2 g-1, which provided abundant storage space and a wide transport path for electrolyte ions. Notably, the specific capacitance of the constructed three-electrode system was as high as 446.22 F g-1 at a current density of 1 A g-1 and remained above 50% at 10 A g-1. The capacitance retention was 82.26% after up to 10,000 cycles. The symmetrical capacitor based on YPAC-1 with a two-electrode structure exhibited an energy density of 8.3 Wh kg-1 when the power density was 136 W kg-1. These results indicate that porous carbon materials prepared from mixed protein and carbohydrate waste have promising applications in the field of supercapacitors.
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To evaluate the efficacy and safety of wet dressing combined with chitosan wound dressing for deep II degree burn wounds, and provide the basis for clinical application. From October 2019 to October 2021, 80 patients with second-degree deep burn treated in the Department of burn and plastic surgery of our hospital were selected as the research objects. Patients were randomly divided into two groups. The control group (40n) was treated with wet compress, and the study group (40n) was treated with wet compress combined with chitosan wound dressing. The wound healing time, wound healing percentage and pain score were used as the effectiveness indexes, and the incidence of adverse events and serious adverse events and the detection rate of bacterial culture of wound exudates were used as the safety indexes. The efficacy and safety of the two groups were compared. The wound healing time of the study group (19.53 ± 2.74 days) was shorter than that of the control group (24.78 ± 4.86 days), the difference was significant (t = 3.571, P = 0.015). The percentage of wound healing at the 14th after treatment in the study group was higher than that in the control group (65.00% versus 37.50%) (X2 = 6.054, P = 0.014). There was no significant difference in pain scores between the two groups at each time point. The scar growth was observed 3 months after wound healing. The scar score of the study group (6.00 ± 0.98) was lower than that of the control group (8.77 ± 1.19) (t = 2.571, P = 0.031). The positive rate of wound secretion culture on the 7th and 14th day was statistically significant (X2 = 4.528, P = 0.033; X2 = 6.646, P = 0.010), and the study group was lower than the control group (29.03% versus 81.82%; 8.11% versus 42.86%). There was no significant difference in treatment cost between the study group and the control group (1258.7 ± 223.6 versus 1248.9 ± 182.3) (t = 1.571, P = 0.071). No adverse events or serious adverse events occurred in both groups. Chitosan wound dressing can significantly shorten the time of wound healing and reduce wound pain and wound infection in patients with deep second-degree burns. And it can effectively improve the situation of scar hyperplasia, which is worthy of clinical application.
Assuntos
Queimaduras , Quitosana , Humanos , Cicatriz , Quitosana/uso terapêutico , Estudos Prospectivos , Método Simples-Cego , Resultado do Tratamento , Bandagens , Queimaduras/tratamento farmacológico , DorRESUMO
Suspended particulate matter (SPM) affects the optical properties of water, which can be used as a marker of water quality. The water quality of Lake Taihu has changed immensely since the 1980's. However, despite the link between water quality and SPM, long-term systematic studies on SPM have not been conducted in this lake. Here, we used Landsat-5 TM and Landsat-8 OLI data to model changes in the SPM concentration of Lake Taihu from 1984 to 2020. Various models were generated, calibrated, and finally validated using in situ SPM, remote sensing reflectance (Rrs) data, and synchronous satellite data. After comparing various commonly used models, it was found that the exponential model based on band combination [Rrs(red) + Rrs(NIR)/Rrs(green)] had the highest accuracy, with an average unbiased relative error greater than 35%. Subsequently, the SPM products of Lake Taihu during 1984-2020 were generated. Overall, the SPM concentration showed a downward trend over the study period, which might be primarily attributable to a decline in wind speed. These findings may assist in the conservation of Lake Taihu and its associated water resources.