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Ten-eleven translocation (TET) proteins are dioxygenases that convert 5-methylcytosine (5mC) into 5-hydroxylmethylcytosine (5hmC) in DNA and RNA. However, their involvement in adult stem cell regulation remains unclear. Here, we identify a novel enzymatic activity-independent function of Tet in the Drosophila germline stem cell (GSC) niche. Tet activates the expression of Dpp, the fly homologue of BMP, in the ovary stem cell niche, thereby controlling GSC self-renewal. Depletion of Tet disrupts Dpp production, leading to premature GSC loss. Strikingly, both wild-type and enzyme-dead mutant Tet proteins rescue defective BMP signaling and GSC loss when expressed in the niche. Mechanistically, Tet interacts directly with Bap55 and Stat92E, facilitating recruitment of the Polybromo Brahma associated protein (PBAP) complex to the dpp enhancer and activating Dpp expression. Furthermore, human TET3 can effectively substitute for Drosophila Tet in the niche to support BMP signaling and GSC self-renewal. Our findings highlight a conserved novel catalytic activity-independent role of Tet as a scaffold protein in supporting niche signaling for adult stem cell self-renewal.
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Dioxigenases , Proteínas de Drosophila , Drosophila melanogaster , Animais , Feminino , Humanos , Diferenciação Celular/genética , Drosophila/genética , Drosophila melanogaster/genética , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Células Germinativas/metabolismo , Nicho de Células-Tronco/fisiologia , Células-Tronco/metabolismo , Dioxigenases/metabolismoRESUMO
c-FLIP functions as a dual regulator of apoptosis and inflammation, yet its implications in Zika virus (ZIKV) infection remain partially understood, especially in the context of ZIKV-induced congenital Zika syndrome (CZS) where both apoptosis and inflammation play pivotal roles. Our findings demonstrate that c-FLIP promotes ZIKV infection in placental cells and myeloid-derived macrophages, involving inflammation and caspase-8/3-mediated apoptosis. Moreover, our observations reveal that c-FLIP augments ZIKV infection in multiple tissues, including blood cell, spleen, uterus, testis, and the brain of mice. Notably, the partial deficiency of c-FLIP provides protection to embryos against ZIKV-induced CZS, accompanied by a reduction in caspase-3-mediated apoptosis. Additionally, we have found a distinctive parental effect of c-FLIP influencing ZIKV replication in fetal heads. In summary, our study reveals the critical role of c-FLIP as a positive regulator in caspase-8/3-mediated apoptosis during ZIKV infection, significantly contributing to the development of CZS.
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Apoptose , Proteína Reguladora de Apoptosis Semelhante a CASP8 e FADD , Caspase 3 , Caspase 8 , Infecção por Zika virus , Zika virus , Infecção por Zika virus/virologia , Infecção por Zika virus/metabolismo , Infecção por Zika virus/patologia , Proteína Reguladora de Apoptosis Semelhante a CASP8 e FADD/metabolismo , Animais , Camundongos , Caspase 8/metabolismo , Feminino , Humanos , Caspase 3/metabolismo , Gravidez , Placenta/virologia , Placenta/metabolismo , Placenta/patologia , Camundongos Endogâmicos C57BL , Replicação Viral , Camundongos KnockoutRESUMO
BACKGROUND: Flowering at the right time is a very important factor affecting the stable annual yield of longan. However, a lack of knowledge of the regulatory mechanism and key genes of longan flowering restricts healthy development of the longan industry. Therefore, identifying relevant genes and analysing their regulatory mechanism are essential for scientific research and longan industry development. RESULTS: DlLFY (Dimocarpus longan LEAFY) contains a 1167 bp open reading frame and encodes 388 amino acids. The amino acid sequence has a typical LFY/FLO family domain. DlLFY was expressed in all tissues tested, except for the leaf, pericarp, and pulp, with the highest expression occurring in flower buds. Expression of DlLFY was significantly upregulated at the early flower induction stage in "SX" ("Shixia"). The results of subcellular localization and transactivation analysis showed that DlLFY is a typical transcription factor acting as a transcriptional activator. Moreover, overexpression of DlLFY in Arabidopsis promoted early flowering and restrained growth, resulting in reduced plant height and rosette leaf number and area in transgenic plants. DNA affinity purification sequencing (DAP-Seq) analysis showed that 13 flower-related genes corresponding to five homologous genes of Arabidopsis may have binding sites and be putative target genes. Among these five flower-related genes, only AtTFL1 (terminal flower 1) was strongly inhibited in transgenic lines. CONCLUSION: Taken together, these results indicate that DlLFY plays a pivotal role in controlling longan flowering, possibly by interacting with TFL1.
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Arabidopsis , Sapindaceae , Arabidopsis/genética , Arabidopsis/metabolismo , Flores , Folhas de Planta/metabolismo , Sapindaceae/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismoRESUMO
Seawater electrolysis holds tremendous promise for the generation of green hydrogen (H2). However, the system of seawater-to-H2 faces significant hurdles, primarily due to the corrosive effects of chlorine compounds, which can cause severe anodic deterioration. Here, a nickel phosphide nanosheet array with amorphous NiMoO4 layer on Ni foam (Ni2P@NiMoO4/NF) is reported as a highly efficient and stable electrocatalyst for oxygen evolution reaction (OER) in alkaline seawater. Such Ni2P@NiMoO4/NF requires overpotentials of just 343 and 370 mV to achieve industrial-level current densities of 500 and 1000 mA cm-2, respectively, surpassing that of Ni2P/NF (470 and 555 mV). Furthermore, it maintains consistent electrolysis for over 500 h, a significant improvement compared to that of Ni2P/NF (120 h) and Ni(OH)2/NF (65 h). Electrochemical in situ Raman spectroscopy, stability testing, and chloride extraction analysis reveal that is situ formed MoO4 2-/PO4 3- from Ni2P@NiMoO4 during the OER test to the electrode surface, thus effectively repelling Cl- and hindering the formation of harmful ClO-.
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To explore the impacts of cytomegalovirus (CMV) infection and antiviral treatment (AVT) on native liver survival (NLS) in biliary atresia (BA) infants. This retrospective cohort study included infants diagnosed as BA between January 2015 and December 2021 at Hunan Children's Hospital. CMV infection was defined by DNA polymerase chain reaction alone (DNA data set) and combination of DNA and immunoglobulin M (CMV data set). In the DNA data set of 330 patients, 234 patients (70.9%) survived with their native liver in 2 years, with 113 (73.9%) in the DNA- cohort, 70 (65.4%) in the DNA+ and AVT- cohort and 51 (72.9%) in the DNA+ and AVT+ cohort, without significant differences by log-rank tests. In patients administrated between 2015 and March 2019, there were 206 evaluable patients in the DNA data set, with rates of 5-year NLS of 68.3% in the DNA- cohort, similar to that in the DNA+ and AVT+ cohort (62.2%, p = 0.546), but significantly higher than that in the DNA+ and AVT- cohort (51.4%, p = 0.031). Similar trends were also observed in the CMV data set, although statistically insignificant. CMV infection before or on the day of HPE can reduce the rate of 5-year NLS and AVT was recommended for CMV-infected BA infants.
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Antivirais , Atresia Biliar , Infecções por Citomegalovirus , Citomegalovirus , Humanos , Infecções por Citomegalovirus/tratamento farmacológico , Infecções por Citomegalovirus/virologia , Estudos Retrospectivos , Atresia Biliar/tratamento farmacológico , Antivirais/uso terapêutico , Feminino , Masculino , Lactente , Citomegalovirus/genética , Citomegalovirus/efeitos dos fármacos , Prognóstico , DNA Viral , Recém-NascidoRESUMO
Nitroaromatic compounds have a wide range of applications. However, they pose a significant threat to both the environment and human health. Ionic liquid hydrogels (ILs-gels) have emerged as a cost-effective and environmentally friendly option for various applications. However, conventional ILs-gels are known to possess mechanical flaws or defects. The procedure utilized a facile synthesis route that involved the polymerization of acrylamide (AM) and ionic liquids (ILs) to create a novel candidate for nanoparticle absorption. This study resolved this issue by creating toughened hydrophobic combined hydrogels synthesized through the addition of SiO2@poly(butyl acrylate) core-shell inorganic-organic hybrid latex particles (SiO2@PBA) to the AM-ILs mixture. The SiO2@PBA particles were chosen to provide the hydrogels with exceptional stretchability (up to 4050% strain) and high mechanical properties (tensile strength of 126 kPa) by acting as both a nanotoughener and a cross-linking point for hydrophobic linkage. Additionally, the P(AM/ILs)-SiO2@PBA hydrogel served as a template for the in situ and stable formation of palladium (Pd) nanoparticles. By incorporation of these Pd nanoparticles as catalysts into P(AM/ILs)-SiO2@PBA hydrogel carriers, the resulting P(AM/ILs)-SiO2@PBA/Pd hydrogels exhibited the ability to catalyze the degradation of p-nitrophenol. Remarkably, even after 15 applications, the efficiency of the degradation process remained consistently above 90%. Thus, the innovative SiO2@PBA toughened ILs-hydrogel design strategy can be utilized to develop robust and stretchable hydrogel materials for catalytic use in the sewage disposal industry.
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BACKGROUND: IgA nephropathy (IgAN) is a major cause of primary glomerulonephritis characterized by mesangial deposits of galactose-deficient IgA1 (Gd-IgA1). Toll-like receptors (TLRs), particularly TLR4 are involved in the pathogenesis of IgAN. The role of gut microbiota on IgAN patients was recently investigated. However, whether gut microbial modifications of Gd-IgA1 through TLR4 play a role in IgAN remains unclear. METHODS: We recruited subjects into four groups, including 48 patients with untreated IgAN, 22 treated IgAN patients (IgANIT), 22 primary membranous nephropathy (MN), and 31 healthy controls (HCs). Fecal samples were collected to analyze changes in gut microbiome. Gd-IgA1 levels, expression of TLR4, B-cell stimulators, and intestinal barrier function were evaluated in all subjects. C57BL/6 mice were treated with a broad-spectrum antibiotic cocktail to deplete the gut microbiota and then gavaged with fecal microbiota transplanted fromclinical subjects of every group. Gd-IgA1 and TLR4 pathway were detected in peripheral blood mononuclear cells (PBMCs) from IgAN and HCs co-incubated with Lipopolysaccharide (LPS) and TLR4 inhibitor. RESULTS: Compared with other three groups, different compositions and decreased diversity demonstrated gut dysbiosis in un-treated IgAN, especially the enrichment of Escherichia -Shigella. Elevated Gd-IgA1 levels were found in un-treated IgAN patients and correlated with gut dysbiosis, TLR4, B-cell stimulators, indexes of intestinal barrier damage, and proinflammatory cytokines. In vivo, mice colonized with gut microbiota from IgAN and IgANIT patients, copied the IgAN phenotype with the activation of TLR4/MyD88/NF-κB pathway, B-cell stimulators in the intestine, and complied with enhanced proinflammatory cytokines. In vitro, LPS activated TLR4/MyD88/NF-κB pathway, B-cell stimulators and proinflammatory cytokines in the PBMCs from IgAN patients, which resulted in overproduction of Gd-IgA1 and inhibited by TLR4 inhibitor. CONCLUSIONS: Our results illustrated that gut-kidney axis was involved in the pathogenesis of IgAN. Gut dysbiosis could stimulate the overproduction of Gd-IgA1 by TLR4 signaling pathway production and B-cell stimulators.
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The impact of non-Born-Oppenheimer couplings on the isotopic effects in the reaction of the Cl(2P) atom with the HD (v = 0, j = 0) molecule is investigated with our recently developed nonadiabatic time-independent quantum scattering methods, where the full open-shell characteristics are included in the six-state model, and also with the recently developed two-state model solving by time-independent methods, where part of the open-shell characteristic is included. The same reaction is also calculated with the simple adiabatic model using the lowest adiabatic potential energy surface. Compared with the results from different models, it is found that the reactivity of the Cl + HD â HCl + D channel is significantly overestimated in the adiabatic model. In contrast, the reactivity of the other channel agrees well with the nonadiabatic models. This is due to the van der Waals well in the reactant channel being changed a lot by including the nonadiabatic couplings. These quantum dynamics calculations suggest that sometimes the adiabatic model should be used with caution; otherwise, it may result in significant deviations for some reactions.
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BACKGROUND: Increasing evidence suggested that immune abnormalities involved in the pathophysiology of schizophrenia. However, the relationship between immunity and clinical features has not been clarified. The aim of this study was to measure the plasma levels of tumor necrosis factor alpha (TNF-α) and soluble TNF-α receptor 1 (sTNF-α R1) and to investigate their association with agitation in first episode patients with schizophrenia (FEPS). METHODS: The plasma TNF-α and sTNF-α R1 levels were measured using sandwich enzyme-linked immunosorbent assay (ELISA) in the FEPS with (n = 36) and without agitation (n = 49) symptoms, and healthy controls (HCs, n = 54). The psychopathology was assessed by the Positive and Negative Syndrome Scale (PANSS), and the agitation symptoms were evaluated by the PANSS excitatory component (PANSS-EC). RESULTS: The plasma TNF-α levels in patients with and without agitation symptoms were significantly higher than those in HCs. The patients with agitation had significantly higher plasma TNF-α levels compared to the patients without agitation. There were no significant differences in the sTNF-α R1 levels among the three groups. Furthermore, the plasma TNF-α levels were positively correlated with the PANSS total score, Positive and General psychopathological subscores, and PANSS-EC score in the FEPS, but the relationships were not found for the plasma sTNF-α R1 levels. CONCLUSIONS: These results suggested that TNF-α might play an important role in the onset and development of agitation symptoms of schizophrenia.
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Agitação Psicomotora , Receptores Tipo I de Fatores de Necrose Tumoral , Esquizofrenia , Fator de Necrose Tumoral alfa , Humanos , Esquizofrenia/sangue , Esquizofrenia/complicações , Feminino , Masculino , Fator de Necrose Tumoral alfa/sangue , Agitação Psicomotora/sangue , Adulto , Receptores Tipo I de Fatores de Necrose Tumoral/sangue , Adulto Jovem , Escalas de Graduação PsiquiátricaRESUMO
BACKGROUND: Evidence on plasma biomarkers to identify first pass effect (FPE) in patients with acute ischemic stroke (AIS) with large vessel occlusion (LVO) treated with thrombectomy is limited. PURPOSE: To evaluate whether plasma D-dimer could predict FPE. MATERIAL AND METHODS: Consecutive patients with LVO who underwent first-line stent retriever thrombectomy at our center between January 2018 and August 2021 were enrolled. Patients were classified into the FPE (modified Thrombolysis in Cerebral Infarction [mTICI] ≥2c) group or non-FPE (mTICI 0-2b) group based on angiographic outcomes. Logistic regression analysis was performed to determine the predictors of FPE. The overall ability of D-dimer levels in predicting FPE was evaluated using receiver operating characteristic (ROC) curves. RESULTS: In total, 313 patients were included; 88 (28.1%) patients achieved FPE. Compared to those with non-FPE, patients with FPE had more diabetes mellitus history, lower D-dimer levels, higher clot burden score, a higher proportion of M1 middle cerebral artery, and a higher proportion of main stem occlusion pattern (P <0.05). After adjusting for potential variables, D-dimer levels (OR=0.81, 95% CI=0.52-0.96), clot burden score (OR=1.76, 95% CI=1.38-2.87), and main stem occlusion pattern (OR=1.85, 95% CI=1.19-2.62) remained independently associated with FPE. Based on the ROC analysis, the D-dimer as a predictor for predicting FPE presented with a specificity of 79%, a negative predictive value of 87%, and an area under the curve of 0.761. CONCLUSION: Low emergency admission plasma D-dimer level is an independent predictor of FPE in patients with AIS treated with stent retriever thrombectomy.
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Biomarcadores , Produtos de Degradação da Fibrina e do Fibrinogênio , AVC Isquêmico , Stents , Trombectomia , Humanos , Masculino , Feminino , Trombectomia/métodos , Idoso , AVC Isquêmico/sangue , AVC Isquêmico/cirurgia , AVC Isquêmico/diagnóstico por imagem , Pessoa de Meia-Idade , Biomarcadores/sangue , Valor Preditivo dos Testes , Estudos Retrospectivos , Resultado do Tratamento , Idoso de 80 Anos ou maisRESUMO
Objective: To evaluate and compare the efficacy, bleeding events, and inflammation levels of optimized bivalirudin versus ordinary heparin in the context of percutaneous coronary intervention (PCI) for patients with acute myocardial infarction. This approach will underscore the comprehensive scope of the study, addressing multiple dimensions of clinical outcomes. Methods: This study involved 120 acute myocardial infarction patients treated from January 2022 to January 2023, randomly allocated into two groups: the control group received ordinary heparin, and the observation group received bivalirudin. Both groups underwent percutaneous coronary intervention (PCI). The study specifically measured coagulation indexes such as prothrombin time (PT) and activated partial thromboplastin time (aPTT), and inflammatory markers including C-reactive protein (CRP) and interleukin-6 (IL-6). Additionally, the incidence of bleeding events and major adverse cardiovascular events (MACE) within 30 days post-PCI were recorded, with bleeding events categorized according to the Bleeding Academic Research Consortium (BARC) criteria and MACE defined by the occurrence of death, non-fatal myocardial infarction, or stroke. Results: No significant differences were observed in coagulation indexes and pre-operation inflammation levels between the two groups (P > .05). However, at 7 days post-operation, despite both groups showing reduced inflammation-NLR decreased by 25%, hs-CRP by 30%, and IL-10 increased by 20%-the bivalirudin group exhibited notably lower incidence rates of various bleeding events (mucosal 2% vs 6%, gingival 1% vs 4%, puncture site 3% vs 8%, and hematuria 1% vs 5%) within 30 days post-PCI compared to the heparin group. TIMI blood flow grades 3 (indicating normal flow) were achieved in 85% of the bivalirudin group compared to 70% in the heparin group. The incidence of MACE was comparable between groups with both reporting a 5% occurrence rate (P > .05). Conclusion: The study reveals that while both bivalirudin and ordinary heparin effectively prevent MACE post-acute myocardial infarction intervention, bivalirudin significantly reduces postoperative bleeding events and maintains comparable anti-inflammatory effects. This suggests its preferable use in clinical settings, particularly in patient populations at high risk for bleeding. Future research could further explore the specific patient characteristics that optimize bivalirudin's benefits over heparin, enhancing tailored therapeutic approaches. This could potentially include randomized trials focusing on patients with different baseline bleeding risks.
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Soil salinity has a major impact on rice seed germination, severely limiting rice production. Herein, a rice germination defective mutant under salt stress (gdss) was identified by using chemical mutagenesis. The GDSS gene was detected via MutMap and shown to encode potassium transporter OsHAK9. Phenotypic analysis of complementation and mutant lines demonstrated that OsHAK9 was an essential regulator responsible for seed germination under salt stress. OsHAK9 is highly expressed in germinating seed embryos. Ion contents and non-invasive micro-test technology results showed that OsHAK9 restricted K+ efflux in salt-exposed germinating seeds for the balance of K+/Na+. Disruption of OsHAK9 significantly reduced gibberellin 4 (GA4) levels, and the germination defective phenotype of oshak9a was partly rescued by exogenous GA3 treatment under salt stress. RNA sequencing (RNA-seq) and real-time quantitative polymerase chain reaction analysis demonstrated that the disruption of OsHAK9 improved the GA-deactivated gene OsGA2ox7 expression in germinating seeds under salt stress, and the expression of OsGA2ox7 was significantly inhibited by salt stress. Null mutants of OsGA2ox7 created using clustered, regularly interspaced, short palindromic repeat (CRISPR)/CRISPR-associated nuclease 9 approach displayed a dramatically increased seed germination ability under salt stress. Overall, our results highlight that OsHAK9 regulates seed germination performance under salt stress involving preventing GA degradation by mediating OsGA2ox7, which provides a novel clue about the relationship between GA and OsHAKs in rice.
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Giberelinas , Oryza , Giberelinas/farmacologia , Giberelinas/metabolismo , Germinação/fisiologia , Potássio/metabolismo , Oryza/metabolismo , Sementes/metabolismo , Estresse Salino , Proteínas de Membrana Transportadoras/metabolismo , Regulação da Expressão Gênica de PlantasRESUMO
Polyethylene oxide (PEO)-based all solid-state lithium metal batteries (ASSLMBs) are strongly hindered by the fast dendrite growth at the Li metal/electrolyte interface, especially under large rates. The above issue stems from the suboptimal interfacial chemistry and poor Li+ transport kinetics during cycling. Herein, a SnF2-catalyzed lithiophilic-lithiophobic gradient solid electrolyte interphase (SCG-SEI) of LixSny/LiF-Li2O is in-situ formed. The superior ionic LiF-Li2O rich upper layer (17.1 nm) possesses high interfacial energy and fast Li+ diffusion channels, wherein lithiophilic LixSny alloy layer (8.4 nm) could highly reduce the nucleation overpotential with lower diffusion barrier and promote rapid electron transportation for reversible Li+ plating/stripping. Simultaneously, the insoluble SnF2-coordinated PEO promotes the rapid Li+ ion transport in the bulk phase. As a result, an over 46.7 and 3.5 times improvements for lifespan and critical current density of symmetrical cells are achieved, respectively. Furthermore, LiFePO4-based ASSLMBs deliver a recorded cycling performance at 5 C (over 1000 cycles with a capacity retention of 80.0%). More importantly, impressive electrochemical performances and safety tests with LiNi0.8Mn0.1Co0.1O2 and pouch cell with LiFePO4, even under extreme conditions (i.e., 100 â), are also demonstrated, reconfirmed the importance of lithiophilic-lithiophobic gradient interfacial chemistry in the design of high-rate ASSLMBs for safety applications.
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OBJECTIVES: To investigate the effects of different angles of pulmonary surfactant (PS) administration on the incidence of bronchopulmonary dysplasia and intracranial hemorrhage in preterm infants. METHODS: A prospective study was conducted on 146 preterm infants (gestational age <32 weeks) admitted to the Department of Neonatology, Provincial Hospital Affiliated to Anhui Medical University from January 2019 to May 2023. The infants were randomly assigned to different angles for injection of pulmonary surfactant groups: 0° group (34 cases), 30° group (36 cases), 45° group (38 cases), and 60° group (38 cases). Clinical indicators and outcomes were compared among the groups. RESULTS: The oxygenation index was lower in the 60° group compared with the other three groups, with shorter invasive ventilation time and oxygen use time, and a lower incidence of bronchopulmonary dysplasia than the other three groups (P<0.05). The incidence of intracranial hemorrhage was lower in the 60° group compared to the 0° group (P<0.05). The cure rate in the 60° group was higher than that in the 0° group and the 30° group (P<0.05). CONCLUSIONS: The clinical efficacy of injection of pulmonary surfactant at a 60° angle is higher than other angles, reducing the incidence of intracranial hemorrhage and bronchopulmonary dysplasia in preterm infants.
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Displasia Broncopulmonar , Recém-Nascido Prematuro , Hemorragias Intracranianas , Surfactantes Pulmonares , Humanos , Surfactantes Pulmonares/administração & dosagem , Recém-Nascido , Estudos Prospectivos , Displasia Broncopulmonar/prevenção & controle , Displasia Broncopulmonar/tratamento farmacológico , Displasia Broncopulmonar/etiologia , Masculino , Feminino , Hemorragias Intracranianas/prevenção & controle , Hemorragias Intracranianas/induzido quimicamenteRESUMO
The ciliary body, located at the junction of the choroid and iris, is crucial in the development of the embryonic eye. Notch2 signalling, Wnt signalling, transforming growth factor ß (TGF-ß) signalling, and Pax6 signalling are critical for coordinating the ciliary body formation. These signalling pathways are coordinated with each other and participate in the ciliary body development, ensuring the precise formation and optimal functioning of the eye structure. Although rare, ciliary body hypoplasia, ciliary tumours, and genetic-related iritis indicate the intricate nature of ciliary body development. Given the ciliary body's important biological significance and potential medical relevance, we aim to provide a comprehensive overview of the developmental molecular mechanisms governing ciliary body formation and function. Here, we focus on the intricate signalling pathways governing ciliary body development and corresponding genetic ciliary diseases.
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OBJECTIVE: Acyl-CoA thioesterase 13 (ACOT13) is involved in lipid biosynthesis, gene transcription, and signal transduction. We explored the potential of ACOT13 to predict ovarian cancer (OC) prognosis and patient immunotherapy responses. METHODS: The Cancer Genome Atlas and Gene Expression Omnibus databases were used to extract raw data. To investigate the potential of ACOT13 as a prognostic and immunotherapeutic marker for OC, bioinformatic analyses were performed using the TIMER website, LinkedOmics database, and R software. We also explored the effects on the invasive ability of OC cells in vitro using a ACOT13 knockdown. RESULTS: The expression of ACOT13 in OC was high and associated with a better prognosis. The expression of ACOT13 was also linked to immune cell invasion immunity-related gene expression. Additionally, immunotherapy was more effective in patients with high ACOT13 expression levels. Multiple critical signaling pathways were found to be involved in the role of ACOT13 in energy metabolism and cell mobility based on Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. OC cells invaded and migrated significantly more when ACOT13 was knocked down. CONCLUSION: High ACOT13 expression in OC is associated to a better OC outcome.
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Cell-cell interactions are essential components of coordinated cell function in lung homeostasis. Lung diseases involve altered cell-cell interactions and communication between different cell types, as well as between subsets of cells of the same type. The identification and understanding of intercellular signaling in lung fibrosis offer insights into the molecular mechanisms underlying these interactions and their implications in the development and progression of lung fibrosis. A comprehensive cell atlas of the human lung, established with the facilitation of single-cell RNA transcriptomic analysis, has enabled the inference of intercellular communications using ligand-receptor databases. In this review, we provide a comprehensive overview of the modified cell-cell communications in lung fibrosis. We highlight the intricate interactions among the major cell types within the lung and their contributions to fibrogenesis. The insights presented in this review will contribute to a better understanding of the molecular mechanisms underlying lung fibrosis and may guide future research efforts in developing targeted therapies for this debilitating disease.
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Sandy Dolomite is a kind of widely distributed rock. The uniaxial compressive strength (UCS) of Sandy Dolomite is an important metric in the application in civil engineering, geotechnical engineering, and underground engineering. Direct measurement of UCS is costly, time-consuming, and even infeasible in some cases. To address this problem, we establish an indirect measuring method based on the convolutional neural network (CNN) and regression analysis (RA). The new method is straightforward and effective for UCS prediction, and has significant practical implications. To evaluate the performance of the new method, 158 dolomite samples of different sandification grades are collected for testing their UCS along and near the Yuxi section of the Central Yunnan Water Diversion (CYWD) Project in Yunnan Province, Southwest of China. Two regression equations with high correlation coefficients are established according to the RA results, to predict the UCS of Sandy Dolomites. Moreover, the minimum thickness of Sandy Dolomite was determined by the Schmidt hammer rebound test. Results show that CNN outperforms RA in terms of prediction the precision of Sandy Dolomite UCS. In addition, CNN can effectively deal with uncertainty in test results, making it one of the most effective tools for predicting the UCS of Sandy Dolomite.
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AIM: To examine the regulatory role of microRNA-204 (miR-204) on silent information regulator 1 (SIRT1) and vascular endothelial growth factor (VEGF) under high-glucose-induced metabolic memory in human retinal pigment epithelial (hRPE) cells. METHODS: Cells were cultured with either normal (5 mmol/L) or high D-glucose (25 mmol/L) concentrations for 8d to establish control and high-glucose groups, respectively. To induce metabolic memory, cells were cultured with 25 mmol/L D-glucose for 4d followed by culture with 5 mmol/L D-glucose for 4d. In addition, exposed in 25 mmol/L D-glucose for 4d and then transfected with 100 nmol/L miR-204 control, miR-204 inhibitor or miR-204 mimic in 5 mmol/L D-glucose for 4d. Quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was used to detect miR-204 mRNA levels. SIRT1 and VEGF protein levels were assessed by immunohistochemical and Western blot. Flow cytometry was used to investigate apoptosis rate. RESULTS: It was found that high glucose promoted miR-204 and VEGF expression, and inhibited SIRT1 activity, even after the return to normal glucose culture conditions. Upregulation of miR-204 promoted apoptosis inhibiting SIRT1 and increasing VEGF expression. However, downregulation of miR-204 produced the opposite effects. CONCLUSION: The study identifies that miR-204 is the upstream target of SIRT1 and VEGF, and that miR-204 can protect hRPE cells from the damage caused by metabolic memory through increasing SIRT1 and inhibiting VEGF expression.
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Chordin-like 1 (CHRDL1) is a secreted protein that serves as an endogenous antagonist of bone morphogenetic proteins (BMPs). In the developing retina, Bmp4 has been demonstrated to be essential for sustaining the proliferation of progenitor cells and facilitating the differentiation of glial cells. Despite these efforts, the precise effects of Bmp4 inhibition on the developing retina are yet to be fully understood. We sought to address this question by overexpressing Chrdl1 in the developing retina. In this study, we explored the impact of Bmp4 inhibition on the developing mouse retina by conditionally overexpressing the Bmp4 inhibitor Chrdl1. Initially, we characterized the expression patterns of Bmp4 and Chrdl1 in the developing mouse retina from E10.5 to P12.5. Additionally, we utilized various molecular markers to demonstrate that Bmp4 inhibition disrupts both neuronal and Müller glial differentiation in the developing mouse retina. Moreover, through the application of RNA-seq analysis, distinctively expressed retinal genes under the modulation of Bmp4 signaling were discerned, encompassing the upregulation of Id1/2/3/4 and Hes1/5, as well as the downregulation of Neurod1/2/4 and Bhlhe22/23. Lastly, electroretinogram (ERG) and optomotor response (OMR) assays were conducted to illustrate that Bmp4 inhibition impairs the functional connectivity of various cells in the retina and consequently affects visual function. Collectively, this study demonstrates that inhibiting Bmp4 promotes the differentiation of retinal neurons over Müller glia by activating the expression of genes associated with neuron specification. These findings offer molecular insights into the role of Bmp4 signaling in mammalian retinal development.