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OTULIN coordinates with LUBAC to edit linear polyubiquitin chains in embryonic development, autoimmunity, and inflammatory diseases. However, the mechanism by which angiogenesis, especially that of endothelial cells (ECs), is regulated by linear ubiquitination remains unclear. Here, we reveal that constitutive or EC-specific deletion of Otulin resulted in arteriovenous malformations and embryonic lethality. LUBAC conjugates linear ubiquitin chains onto Activin receptor-like kinase 1 (ALK1), which is responsible for angiogenesis defects, inhibiting ALK1 enzyme activity and Smad1/5 activation. Conversely, OTULIN deubiquitinates ALK1 to promote Smad1/5 activation. Consistently, embryonic survival of Otulin-deficient mice was prolonged by BMP9 pretreatment or EC-specific ALK1Q200D (constitutively active) knockin. Moreover, mutant ALK1 from type 2 hereditary hemorrhagic telangiectasia (HHT2) patients exhibited excessive linear ubiquitination and increased HOIP binding. As such, a HOIP inhibitor restricted the excessive angiogenesis of ECs derived from ALK1G309S-expressing HHT2 patients. These results show that OTULIN and LUBAC govern ALK1 activity to balance EC angiogenesis.
Assuntos
Receptores de Activinas Tipo II/genética , Receptores de Activinas Tipo II/metabolismo , Endopeptidases/genética , Complexos Multiproteicos/metabolismo , Neovascularização Patológica/genética , Poliubiquitina/metabolismo , Adulto , Animais , Endopeptidases/metabolismo , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Feminino , Fator 2 de Diferenciação de Crescimento/farmacologia , Células Endoteliais da Veia Umbilical Humana , Humanos , Masculino , Camundongos Mutantes , Mutação , Neovascularização Patológica/tratamento farmacológico , Neovascularização Patológica/metabolismo , Neovascularização Fisiológica/genética , Proteína Smad1/genética , Proteína Smad1/metabolismo , Proteína Smad5/genética , Proteína Smad5/metabolismo , Telangiectasia Hemorrágica Hereditária , Ubiquitina-Proteína Ligases/metabolismoRESUMO
OBJECTIVES: To investigate the prognostic impact and pathophysiological characteristics of fragmented QRS complex (fQRS) on patients with connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH). METHODS: This was a multicentre retrospective study recruiting 141 patients with CTD-PAH diagnosed by right heart catheterization (114 cases in the discovery cohort and 27 cases in the validation cohort). fQRS and ST-T change were detected on conventional 12-lead electrocardiogram (ECG). Patients were followed up every 3 months to update their status and the primary end point was all-cause death. Clinical information and ECG characteristics were compared between survival and death groups and Kaplan-Meier curve was used for survival analysis. RESULTS: There were significant differences in age, gender, 6-min walk distance, NT-proBNP, WHO class, presence of fQRS and presence of ST-T change in inferior leads between survival group and death group. Inferior fQRS and ST-T change were significantly associated with right ventricular (RV) dilatation and reduced RV ejection fraction (RVEF). Kaplan-Meier curve showed that all-cause mortality was higher in CTD-PAH with fQRS (p= 0.003) and inferior ST-T change (p= 0.012). Low- and intermediate-risk CTD-PAH with inferior ST-T change had higher all-cause mortality (p= 0.005). The prognostic value of fQRS and inferior ST-T change was validated in external validation cohort. CONCLUSION: The presence of inferior fQRS and ST-T change could predict poor prognosis in CTD-PAH. CLINICAL TRIAL REGISTRATION NUMBER: NCT05980728, https://clinicaltrials.gov.
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F-box proteins participate in the regulation of many processes, including cell division, development, and plant hormone responses. Brassinosteroids (BRs) regulate plant growth and development by activating core transcriptional and other multiple factors. In rice, OVATE family proteins (OFPs) participate in BR signalling and regulate grain size. Here we identified an F-box E3 ubiquitin ligase, FBX206, that acts as a negative factor in BR signalling and regulates grain size and yield in rice. Suppressed expression of FBX206 by RNAi leads to promoted plant growth and increased grain yield. Molecular analyses showed that the expression levels of BR biosynthetic genes were up-regulated, whereas those of BR catabolic genes were down-regulated in FBX206-RNAi plants, resulting in the accumulation of 28-homoBL, one of the bioactive BRs. FBX206 interacted with OsOFP8, a positive regulator in BR signalling, and OsOFP19, a negative regulator in BR signalling. SCFFBX206 mediated the degradation of OsOFP8 but suppressed OsOFP19 degradation. OsOFP8 interacted with OsOFP19, and the reciprocal regulation between OsOFP8 and OsOFP19 required the presence of FBX206. FBX206 itself was ubiquitinated and degraded, but interactions of OsOFP8 and OsOFP19 synergistically suppressed the degradation of FBX206. Genetic interactions indicated an additive effect between FBX206 and OsOFP8 and epistatic effects of OsOFP19 on FBX206 and OsOFP8. Our study reveals the regulatory networks of FBX206, OsOFP8, and OsOFP19 in BR signalling that regulate grain size and yield in rice.
Assuntos
Proteínas F-Box , Oryza , Brassinosteroides/metabolismo , Oryza/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Proteínas F-Box/genética , Proteínas F-Box/metabolismo , Reguladores de Crescimento de Plantas/metabolismo , Grão Comestível/genética , Grão Comestível/metabolismo , Regulação da Expressão Gênica de PlantasRESUMO
In recent years, environmental DNA (eDNA) has received attention from biologists due to its sensitivity, convenience, labor and material efficiency, and lack of damage to organisms. The extensive application of eDNA has opened avenues for the monitoring and biodiversity assessment of amphibians, which are frequently small and difficult to observe in the field, in areas such as biodiversity survey assessment and detection of specific, rare and threatened, or alien invasive species. However, the accuracy of eDNA can be influenced by factors such as ambient temperature, pH, and false positives or false negatives, which makes eDNA an adjunctive tool rather than a replacement for traditional surveys. This review provides a concise overview of the eDNA method and its workflow, summarizes the differences between applying eDNA for detecting amphibians and other organisms, reviews the research progress in eDNA technology for amphibian monitoring, identifies factors influencing detection efficiency, and discusses the challenges and prospects of eDNA. It aims to serve as a reference for future research on the application of eDNA in amphibian detection.
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DNA Ambiental , Animais , Ecossistema , Anfíbios/genética , BiodiversidadeRESUMO
The extensive application of pesticides and antibiotics in agricultural production makes it possible for them to coexist in farmland, and the interaction of the two pollutants can lead to changes in environmental behavior and toxicity, creating uncertainty risks to soil and soil organisms. In this study, we explored the environmental behavior and the effects of earthworms under co-exposure to amoxicillin and boscalid and further explored the accumulation and toxic effects on earthworms. The results showed that amoxicillin increased the adsorption of boscalid in soil and inhibited its degradation. In addition, we noticed that the co-exposure of amoxicillin and boscalid caused intestinal barrier damage, which increased the bioaccumulation of earthworms for boscalid and led to more severe oxidative stress and metabolic disorders in earthworms. In summary, our findings indicate that amoxicillin can increase the ecological risk of boscalid in the environment and imply that the encounter between antibiotics and pesticides in the environment can amplify the toxic effects of pesticides, which provides new insights into the ecological risks of antibiotics.
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Amoxicilina , Compostos de Bifenilo , Niacinamida , Oligoquetos , Animais , Oligoquetos/efeitos dos fármacos , Oligoquetos/metabolismo , Amoxicilina/toxicidade , Amoxicilina/farmacologia , Niacinamida/farmacologia , Niacinamida/toxicidade , Niacinamida/análogos & derivados , Poluentes do Solo/toxicidade , Antibacterianos/toxicidade , Antibacterianos/farmacologia , Estresse Oxidativo/efeitos dos fármacosRESUMO
The extensive application of pesticides in agricultural production has raised significant concerns about its impact on human health. Different pesticides, including fungicides, insecticides, and herbicides, cause environmental pollution and health problems for non-target organisms. Infants and young children are so vulnerable to the harmful effects of pesticide exposure that early-life exposure to pesticides deserves focused attention. Recent research lays emphasis on understanding the mechanism between negative health impacts and early-life exposure to various pesticides. Studies have explored the impacts of exposure to these pesticides on model organisms (zebrafish, rats, and mice), as well as the mechanism of negative health effects, based on advanced methodologies like gut microbiota and multi-omics. These methodologies help comprehend the pathogenic mechanisms associated with early-life pesticide exposure. In addition to presenting health problems stemming from early-life exposure to pesticides and their pathogenic mechanisms, this review proposes expectations for future research. These proposals include focusing on identifying biomarkers that indicate early-life pesticide exposure, investigating transgenerational effects, and seeking effective treatments for diseases arising from such exposure. This review emphasizes how to understand the pathogenic mechanisms of early-life pesticide exposure through gut microbiota and multi-omics, as well as the adverse health effects of such exposure.
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Microbioma Gastrointestinal , Inseticidas , Praguicidas , Criança , Humanos , Animais , Ratos , Camundongos , Praguicidas/toxicidade , Multiômica , Peixe-Zebra , Inseticidas/farmacologiaRESUMO
Current models emphasize that membrane voltage (Vm) depolarization-induced Ca2+ influx triggers the fusion of vesicles to the plasma membrane. In sympathetic adrenal chromaffin cells, activation of a variety of G protein coupled receptors (GPCRs) can inhibit quantal size (QS) through the direct interaction of G protein Gißγ subunits with exocytosis fusion proteins. Here we report that, independently from Ca2+, Vm (action potential) per se regulates the amount of catecholamine released from each vesicle, the QS. The Vm regulation of QS was through ATP-activated GPCR-P2Y12 receptors. D76 and D127 in P2Y12 were the voltage-sensing sites. Finally, we revealed the relevance of the Vm dependence of QS for tuning autoinhibition and target cell functions. Together, membrane voltage per se increases the quantal size of dense-core vesicle release of catecholamine via Vm â P2Y12(D76/D127) â Gißγ â QS â myocyte contractility, offering a universal Vm-GPCR signaling pathway for its functions in the nervous system and other systems containing GPCRs.
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Catecolaminas/metabolismo , Células Cromafins/fisiologia , Proteínas Heterotriméricas de Ligação ao GTP/metabolismo , Vesículas Secretórias/fisiologia , Potenciais de Ação , Animais , Feminino , Células HEK293 , Humanos , Masculino , Camundongos Knockout , Cultura Primária de Células , Ratos Sprague-Dawley , Receptores Purinérgicos P2Y12/metabolismo , Transdução de SinaisRESUMO
The ability of knowledge, attitude, and practice of intensive care unit (ICU) nurses to perform medical device-related pressure injuries (MDRPIs) can affect the incidence of MDRPI in ICU patients. Therefore, in order to improve ICU nurses' understanding and nursing ability of MDRPIs, we investigated the non-linear relationship (synergistic and superimposed relationships) between the factors influencing ICU nurses' ability of knowledge, attitude, and practice. A Clinical Nurses' Knowledge, Attitude, and Practice Questionnaire for the Prevention of MDRPI in Critically Ill Patients was administered to 322 ICU nurses from tertiary hospitals in China from January 1, 2022 to June 31, 2022. After the questionnaire was distributed, the data were collected and sorted out, and the corresponding statistical analysis and modelling software was used to analyse the data. IBM SPSS 25.0 software was used to conduct Single factor analysis and Logistic regression analysis on the data, so as to screen the statistically significant influencing factors. IBM SPSS Modeler18.0 software was used to construct a decision tree model of the factors influencing MDRPI knowledge, attitude, and practice of ICU nurses, and ROC curves were plotted to analyse the accuracy of the model. The results showed that the overall passing rate of ICU nurses' knowledge, attitude, and practice score was 72%. The statistically significant predictor variables ranked in importance were education background (0.35), training (0.31), years of working (0.24), and professional title (0.10). AUC = 0.718, model prediction performance is good. There is a synergistic and superimposed relationship between high education background, attended training, high years of working and high professional title. Nurses with the above factors have strong MDRPI knowledge, attitude, and practice ability. Therefore, nursing managers can develop a reasonable and effective scheduling system and MDRPI training program based on the study results. The ultimate goal is to improve the ability of ICU nurses to know and act on MDRPI and to reduce the incidence of MDRPI in ICU patients.
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Enfermeiras e Enfermeiros , Úlcera por Pressão , Humanos , Úlcera por Pressão/etiologia , Úlcera por Pressão/prevenção & controle , Úlcera por Pressão/epidemiologia , Conhecimentos, Atitudes e Prática em Saúde , Competência Clínica , Estudos Transversais , Unidades de Terapia Intensiva , Inquéritos e QuestionáriosRESUMO
AIM: The purpose of this study was to explore the relationships among perceptions of decent work, psychological empowerment, and work immersion among nurses, hypothesizing that psychological empowerment mediates the relationship between perceptions of decent work and work immersion. BACKGROUND: At present, there are many studies on nurses' perceptions of decent labor and work immersion in China, but the relationship between them has not been discussed from a psychological perspective. METHODS: The sample consisted of clinical nurses in Jiangxi, Zhejiang, Hubei, and Guangdong provinces, China, and the nurses' general information, decent labor perception, psychological empowerment, and work immersion scores were assessed using the General Information Scale, Decent Labor Perception Scale, Psychological Empowerment Scale, and Work Immersion Scale, respectively. Pearson correlation analysis and structural equation modeling were used to analyze the data. RESULTS: The total scores of nurses' perceptions of decent work, psychological empowerment, and work immersion were at a moderate level. The total nurse work immersion score and each dimension score were positively correlated with the total nurse decent work perception score and the total psychological empowerment score. Decent work perception and psychological empowerment directly and positively predicted work immersion; decent work perception also indirectly acted on work immersion through psychological empowerment. CONCLUSIONS AND IMPLICATIONS FOR NURSING AND HEALTH POLICY: Nurses' work immersion was moderate, and this study explored the mechanisms by which perceptions of decent work affect nurses' work immersion from a psychological perspective, validating the mediating role of psychological empowerment. This study emphasizes that nursing managers should fully understand the importance of nurses' work immersion, continuously improve nurses' decent labor perceptions, enhance their psychological empowerment level, improve their work immersion, and enhance the quality of nursing services.
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Biosynthesis of D-allulose has been achieved using ketose 3-epimerases (KEases), but its application is limited by poor catalytic performance. In this study, we redesigned a genetically encoded biosensor based on a D-allulose-responsive transcriptional regulator for real-time monitoring of D-allulose. An ultrahigh-throughput droplet-based microfluidic screening platform was further constructed by coupling with this D-allulose-detecting biosensor for the directed evolution of the KEases. Structural analysis of Sinorhizobium fredii D-allulose 3-epimerase (SfDAE) revealed that a highly flexible helix/loop region exposes or occludes the catalytic center as an essential lid conformation regulating substrate recognition. We reprogrammed SfDAE using structure-guided rational design and directed evolution, in which a mutant M3-2 was identified with 17-fold enhanced catalytic efficiency. Our research offers a paradigm for the design and optimization of a biosensor-based microdroplet screening platform.
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Frutose , Racemases e Epimerases , Frutose/químicaRESUMO
Solar-to-fuel conversion followed by secondary utilization in fuel cells provides an appealing approach to alleviating global energy shortages but is largely restricted by the complex design of power systems and the development of functional catalysts. Herein, we presented a biohybrid photoelectrochemical cell (BPEC) to implement sustainable solar-to-fuel-to-electric power conversion in a single compartment, by ingeniously combining reliable photoelectrochemical H2O2 generation with efficient bioelectrochemical H2O2 consumption. Specifically, the BPEC is composed of a Mo-modified BiVO4 (Mo:BiVO4) photoanode and a horseradish peroxidase (HRP)/pyrene-modified 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (bis-Pyr-ABTS)/carbon nanotubes with an encapsulated Co nanoparticle (Co/CNTs) biocathode. Upon photoexcitation, two-electron H2O oxidation can be carried out at the Mo-BiVO4 photoanode to produce H2O2, followed by electroenzymatic reduction of H2O2 to H2O by HRP with the help of a bis-Pyr-ABTS redox mediator at the biocathode. Besides, in response to the insufficient Faradaic efficiency of H2O2 generation at the photoanode, the functional Co/CNTs catalysts, possessing prominent electrocatalytic selectivity toward two-electron O2 reduction (electron transfer number = 2.6), are modified on the biocathode, thus clearly defining effective H2O/H2O2/O2 self-circulation in this device. This developed BPEC obtains an open-circuit potential of 1.03 ± 0.02 V and a maximum power density of 0.18 ± 0.02 mW cm-2. Moreover, inspired by the particular advantage of enzymatic biofuel cells for easy miniaturization, an enclosed "sandwich-like" BPEC of approximately 1 cm3 size is fabricated and delivers a power output of 0.13 ± 0.03 mW cm-2. Our work represents a controllable approach for meaningful solar energy utilization, beyond traditional artificial photosynthesis, and can further provide a significant paradigm shift in building an energy-sustainable society.
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Nanotubos de Carbono , Energia Solar , Peróxido de Hidrogênio , Ácidos SulfônicosRESUMO
Realization of a highly sensitive analysis and sensing platform is important for early-stage tumor diagnosis. In this work, a self-powered biosensor with a novel sandwich graphdiyne (SGDY) combined with an aptamer-specific recognition function was developed to sensitively and accurately detect tumor markers. Results indicated that the detection limits of microRNA (miRNA)-21 and miRNA-141 were 0.15 and 0.30 fM (S/N = 3) in the linear range of 0.05-10000 and 1-10000 fM, respectively. The newly designed platform has great promise for early-stage tumor diagnosis.
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Técnicas Biossensoriais , MicroRNAs , Neoplasias , Humanos , Biomarcadores Tumorais , MicroRNAs/análise , Técnicas Biossensoriais/métodos , Neoplasias/diagnóstico , Limite de Detecção , Técnicas EletroquímicasRESUMO
OBJECTIVE: Myocardial involvement is frequently observed in PM and DM but typically remains subclinical. This study aimed to investigate characteristics of myocardial involvement and compare differences between patients with PM and DM by cardiac MR (CMR) imaging. METHODS: From March 2017 to December 2019, a total of 17 PM and 27 DM patients were enrolled in this retrospective study. In all patients, clinical assessment and CMR examination were performed. CMR parameters, including left ventricular (LV) morphologic and functional parameters, and CMR tissue characterization imaging parameters, such as native T1, T2, extracellular volume (ECV) and late gadolinium enhancement, were analysed. RESULTS: In patients in both PM and DM groups, elevated global native T1 and ECV values were observed. Global ECV values were higher in the PM group when compared with the DM group (33.24 ± 2.97% vs 30.36 ± 4.20%; P = 0.039). Furthermore, patients in the PM and DM groups showed a different positive segment distribution of late gadolinium enhancement, native T1 and ECV, whereas the number of positive segments in PM patients was greater compared with that in DM patients. No significant differences in LV morphological and functional parameters were observed between patients in PM and DM groups, and most were in normal range. CONCLUSION: CMR tissue characterization imaging could detect early myocardial involvement in PM and DM patients without overt LV dysfunction. Furthermore, characteristics of myocardial involvement were different between PM and DM patients with more serious myocardial involvement seen in PM patients.
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Técnicas de Imagem Cardíaca , Dermatomiosite/diagnóstico por imagem , Coração/diagnóstico por imagem , Miocárdio , Polimiosite/diagnóstico por imagem , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
OBJECTIVES: Pulmonary arterial hypertension (PAH) is a severe complication of CTD, being one of the leading causes of mortality for patients with this condition. Soluble suppression of tumorigenicity 2 (sST2) is a novel biomarker associated with adverse clinical outcomes in cardiovascular patients. In this study, we investigated the role of sST2 as a predictor of poor clinical outcome in patients with CTD associated with pulmonary hypertension (CTD-PH). METHODS: This retrospective cohort study enrolled 71 CTD-PH patients diagnosed by echocardiography. Twenty-one CTD patients without PH were selected for a control group. A receiver operating characteristic (ROC) curve assessed the predictive value of sST2 in assessing 3-year clinical worsening. Hazard ratios associated with potential predictors of clinical worsening were estimated using Cox proportional hazard models. The primary end point was clinical worsening. RESULTS: The level of sST2 was significantly elevated in CTD-PH patients compared with the control group. After a mean follow-up of 25.29 (1.88) months, end point events occurred in 26 patients. sST2 was an independent predictor of clinical worsening and all-cause death in patients with CTD-PH. sST2 ≥ 39.99 ng/ml discriminated 3-year clinical worsening with a sensitivity and specificity of 100% and 84.9%, respectively. The patients with both higher levels of sST2 (≥39.99 ng/ml) and N-terminal pro-brain natriuretic peptide (NT-proBNP) (≥300 ng/l) had the worst prognosis. CONCLUSION: sST2 ≥ 39.99 ng/ml predicts higher incidence of clinical worsening events in CTD-PH patients. Furthermore, patients with elevated sST2 had significantly worse prognosis among those with high NT-proBNP.
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Doenças do Tecido Conjuntivo , Hipertensão Pulmonar , Biomarcadores , Humanos , Proteína 1 Semelhante a Receptor de Interleucina-1 , Peptídeo Natriurético Encefálico , Fragmentos de Peptídeos , Prognóstico , Estudos RetrospectivosRESUMO
Autism spectrum disorders (ASDs) are a group of highly inheritable neurodevelopmental disorders. Functional mutations in TRIO, especially in the GEF1 domain, are strongly implicated in ASDs, whereas the underlying neurobiological pathogenesis and molecular mechanisms remain to be clarified. Here we characterize the abnormal morphology and behavior of embryonic migratory interneurons (INs) upon Trio deficiency or GEF1 mutation in mice, which are mediated by the Trio GEF1-Rac1 activation and involved in SDF1α/CXCR4 signaling. In addition, the migration deficits are specifically associated with altered neural microcircuit, decreased inhibitory neurotransmission, and autism-like behaviors, which are reminiscent of some features observed in patients with ASDs. Furthermore, restoring the excitatory/inhibitory (E/I) imbalance via activation of GABA signaling rescues autism-like deficits. Our findings demonstrate a critical role of Trio GEF1 mediated signaling in IN migration and E/I balance, which are related to autism-related behavioral phenotypes.
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Transtorno do Espectro Autista , Transtorno Autístico , Transtornos do Neurodesenvolvimento , Animais , Transtorno do Espectro Autista/genética , Transtorno Autístico/genética , Humanos , Interneurônios , Camundongos , Transtornos do Neurodesenvolvimento/genética , NeurogêneseRESUMO
BACKGROUND: The morphological alterations of small pulmonary vessels measured by computed tomography (CT) is increasingly used in evaluation of suspected pulmonary hypertension (PH). OBJECTIVE: To investigate the significance alterations of quantitative assessment of small pulmonary vessels on chest CT in distinguishing different types of PH and their severity. METHODS: We retrospectively analyzed a dataset of 120 healthy controls (HCs) and 91 PH patients, including 34 patients with connective tissue diseases-related PH (CTD-PH), 26 patients with idiopathic pulmonary arterial hypertension (iPAH), and 31 patients with chronic obstructive pulmonary disease-related PH (COPD-PH). The CTD-PH patients were divided into mild to moderate PH (CTD-LM-PH) group (nâ=â17) and severe PH (CTD-S-PH) group (nâ=â17). A total of 53 CTD patients without PH (CTD-nPH) were enrolled for comparison with the CTD-PH. We measured the cross-sectional area of small pulmonary vessels <â5âmm2 (%CSA <5) and between 5-10âmm2 (%CSA5-10) as a percentage of total lung area among the populations included above and compared %CSA in different types of PH groups and HCs group. The mean pulmonary arterial pressure (mPAP) was measured by right heart catheterization. RESULTS: The %CSA5-10 of COPD-PH, CTD-PH, and iPAH patients increased (0.21±0.09, 0.49±0.20 and 0.61±0.20, pâ<â0.02) sequentially, while the %CSA <5 of CTD-PH, iPAH, and COPD-PH patients decreased (0.79±0.65, 0.65±0.38 and 0.52±0.27, pâ<â0.05) sequentially. The %CSA5-10 was significantly higher in CTD-S-PH patients than CTD-LM-PH patients and CTD-nPH patients (0.51±0.21, 0.31±0.15 and 0.28±0.12, pâ<â0.01). The %CSA5-10 was positively correlated with mPAP in the CTD-PH group. CONCLUSIONS: The quantitative parameters %CSA <5 and %CSA5-10 assessed by chest CT are useful for distinguishing different types of PH. In addition, the %CSA5-10 can provide information for identification of CTD-PH severity.
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Hipertensão Pulmonar , Doença Pulmonar Obstrutiva Crônica , Humanos , Hipertensão Pulmonar/diagnóstico por imagem , Pulmão/irrigação sanguínea , Doença Pulmonar Obstrutiva Crônica/diagnóstico por imagem , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodosRESUMO
BACKGROUND: Cardiac involvement is a serious complication of idiopathic inflammatory myopathy (IIM). GDF-15 can predict the risk and the prognosis of cardiovascular disease, but its value is unclear in IIM. OBJECTIVE: To investigate the diagnostic value of GDF-15 for myocardial involvement in IIM. METHODS: A total of 77 IIM patients from May 2018 to August 2020 were included in this retrospective study. Of these, 43 patients underwent cardiac magnetic resonance (CMR) examination. There were 33 SLE patients and 16 healthy people were used as the control group. The concentration of GDF-15 of these groups was measured by ELISA. RESULTS: There were significant differences in GDF-15 levels in patients with IIM, SLE and healthy controls (H = 45.291, P<0.001). GDF-15 levels were statistically significant different between IIM patients with the myocardial injury [1484.88(809.07 2835.50) pg/ml] and without myocardial injury [593.26(418.61 784.59) pg/ml, P =0.001]. After adjusted for age, renal function, the risk of myocardial injury in IIM patients increased an average of 0.3% by per increased unit of GDF-15 (odds ratio=1.003, 95% CI: 1.000, 1.007). The level of GDF-15 was positively correlated with extra-cellular volume (ECV) (rs = 0.348, P =0.028). GDF-15 ≥ 929.505 pg/ml (area under the curve=0.856, 95% CI: 0.744, 0.968) predicted myocardial injury in IIM with a sensitivity of 0.75 and specificity of 0.90. CONCLUSION: GDF-15 could serve as a potential biomarker to predict myocardial injury in IIM patients.
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Cardiomiopatias/sangue , Fator 15 de Diferenciação de Crescimento/sangue , Miosite/sangue , Adulto , Fatores Etários , Biomarcadores/sangue , Cardiomiopatias/diagnóstico por imagem , Estudos de Casos e Controles , Intervalos de Confiança , Estudos Transversais , Ensaio de Imunoadsorção Enzimática , Feminino , Coração/diagnóstico por imagem , Humanos , Lúpus Eritematoso Sistêmico/sangue , Imageamento por Ressonância Magnética , Masculino , Miosite/diagnóstico por imagem , Razão de Chances , Estudos Retrospectivos , Sensibilidade e EspecificidadeRESUMO
Secondary cell wall not only provides rigidity and mechanical resistance to plants, but also has a large impact on plant growth and adaptation to environments. Biosynthesis of secondary cell wall is regulated by a complicated signaling transduction network; however, it is still unclear how the transcriptional regulation of secondary cell wall biosynthesis works at the molecular level. Here, we report in rice that OVATE family proteins 6 (OsOFP6) is a positive regulator in modulating expression of the genes related to biosynthesis of the secondary cell wall. Transgenic plants with knock-down of OsOFP6 by RNA interference showed increased leaf angle, which resulted from the thinner secondary cell wall with reduced amounts of cellulose and lignin, whilst overexpression of OsOFP6 in rice led to the thinker secondary cell wall with increased lignin content. Protein-protein interaction analysis revealed that OsOFP6 interacts with Oryza sativa homeobox 15 (OSH15), a class I KNOX protein. The interaction of OsOFP6 and OSH15 enhanced the transcriptional activity of OSH15 which binds to the promoter of OsIRX9 (Oryza sativa IRREGULAR XYLEM 9). Taken together, our study provides insights into the function of OsOFP6 in regulating leaf angle and the control of biosynthesis of secondary cell wall.
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Parede Celular/metabolismo , Oryza/metabolismo , Folhas de Planta/metabolismo , Proteínas de Plantas/metabolismo , Proteínas Repressoras/metabolismo , Fatores de Transcrição/metabolismo , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Parede Celular/ultraestrutura , Celulose/metabolismo , Regulação da Expressão Gênica de Plantas , Proteínas de Homeodomínio/metabolismo , Lignina/metabolismo , Oryza/genética , Folhas de Planta/anatomia & histologia , Folhas de Planta/citologia , Proteínas de Plantas/genética , Plantas Geneticamente Modificadas/genética , Regiões Promotoras Genéticas , Domínios e Motivos de Interação entre Proteínas , Interferência de RNA , Proteínas Repressoras/genética , Fatores de Transcrição/genética , Xilema/metabolismoRESUMO
OBJECTIVE: Pulmonary artery enlargement is a common manifestation of chest CT in patients with pulmonary arterial hypertension (PAH). The exact clinical significance of this phenomenon has not been clarified in connective tissue disease (CTD)-associated PAH (CTD-PAH). We aimed to explore the association between the dilatation of pulmonary artery and prognosis of CTD-PAH patients. METHODS: We retrospectively investigated 140 CTD-PAH patients diagnosed by echocardiography from 2009 to 2018. A chest multi-slice CT was performed on all the patients. Main pulmonary artery (MPA), right pulmonary artery (RPA), left pulmonary artery (LPA), ascending aorta (AAo) and descending aorta (DAo) diameters were measured. The ratios MPA/AAo and MPA/DAo were also calculated. The primary end point was all-cause mortality. RESULTS: During the observational period of 3.44 (0.23) years, 36 patients were followed to death. Cox univariate proportional hazard analysis showed that age, gender, MPA diameter, LPA diameter and RPA diameter were related to the risk of 5-year all-cause mortality in patients with CTD-PAH. In Cox multivariate proportional hazard analysis, MPA diameter and gender were predictors of all-cause mortality in CTD-PAH patients. An all-cause mortality risk prediction model revealed that baseline MPA diameter has the ability to predict 5-year all-cause mortality in CTD-PAH patients. Kaplan-Meier analysis showed that the 5-year survival rate was significantly lower in patients with MPA ≥37.70 mm (P ≤ 0.00012) compared with MPA ≤ 37.70 mm. CONCLUSION: MPA diameter ≥37.70 mm measured by chest multi-slice CT was a potential independent risk factor of the poor long-term prognosis in Chinese CTD-PAH patients.
Assuntos
Doenças do Tecido Conjuntivo/mortalidade , Hipertensão Pulmonar/mortalidade , Artéria Pulmonar/diagnóstico por imagem , Adulto , Fatores Etários , Aorta/diagnóstico por imagem , Aorta Torácica/diagnóstico por imagem , Causas de Morte , Doenças do Tecido Conjuntivo/complicações , Dilatação Patológica/diagnóstico por imagem , Dilatação Patológica/etiologia , Dilatação Patológica/mortalidade , Feminino , Humanos , Hipertensão Pulmonar/etiologia , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada Multidetectores , Tamanho do Órgão , Prognóstico , Modelos de Riscos Proporcionais , Artéria Pulmonar/patologia , Radiografia Torácica/métodos , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais , Taxa de Sobrevida , Fatores de TempoRESUMO
The loss-of-function mutation in PARK7/DJ-1 is one of the most common causes of autosomal recessive Parkinson's disease, and patients carrying PARK7 mutations often exhibit both a progressive movement disorder and emotional impairment, such as anxiety. However, the causes of the emotional symptom accompanying PARK7-associated and other forms of Parkinson's disease remain largely unexplored. Using two-photon microscopic Ca2+ imaging in awake PARK7-/- and PARK7+/+ mice, we found that (i) PARK7-/- neurons in the frontal association cortex showed substantially higher circuit activity recorded as spontaneous somatic Ca2+ signals; (ii) both basal and evoked dopamine release remained intact, as determined by both electrochemical dopamine recordings and high performance liquid chromatography in vivo; (iii) D2 receptor expression was significantly decreased in postsynaptic frontal association cortical neurons, and the hyper-neuronal activity were rescued by D2 receptor intervention using either local pharmacology or viral D2 receptor over-expression; and (iv) PARK7-/- mice showed anxiety-like behaviours that were rescued by either local D2 receptor pharmacology or overexpression. Thus, for first time, we demonstrated a robust D2 receptor-dependent phenotype of individual neurons within the prefrontal cortex circuit in awake parkinsonian mice that linked with anxiety. Our work sheds light on early-onset phenotypes and the mechanisms underlying Parkinson's disease by imaging brain circuits in an awake mouse model.