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Accurate segmentation of retinal vessels is an essential prerequisite for the subsequent analysis of fundus images. Recently, a number of methods based on deep learning have been proposed and shown to demonstrate promising segmentation performance, especially U-Net and its variants. However, tiny vessels and low-contrast vessels are hard to detect due to the issues of a loss of spatial details caused by consecutive down-sample operations and inadequate fusion of multi-level features caused by vanilla skip connections. To address these issues and enhance the segmentation precision of retinal vessels, we propose a novel high-resolution network with strip attention. Instead of the U-Net-shaped architecture, the proposed network follows an HRNet-shaped architecture as the basic network, learning high-resolution representations throughout the training process. In addition, a strip attention module including a horizontal attention mechanism and a vertical attention mechanism is designed to obtain long-range dependencies in the horizontal and vertical directions by calculating the similarity between each pixel and all pixels in the same row and the same column, respectively. For effective multi-layer feature fusion, we incorporate the strip attention module into the basic network to dynamically guide adjacent hierarchical features. Experimental results on the DRIVE and STARE datasets show that the proposed method can extract more tiny vessels and low-contrast vessels compared with existing mainstream methods, achieving accuracies of 96.16% and 97.08% and sensitivities of 82.68% and 89.36%, respectively. The proposed method has the potential to aid in the analysis of fundus images.
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Vasos Retinianos , Vanilla , Animais , Vasos Retinianos/diagnóstico por imagem , Abomaso , Fundo de Olho , Processamento de Imagem Assistida por Computador , AlgoritmosRESUMO
Multiple disease resistance (MDR) in maize has attracted increasing attention. However, the interplay between cell death and metabolite changes and their contributions to MDR remains elusive in maize. In this study, we identified a mutant named as lesion mimic 30 (les30) that showed 'suicidal' lesion formation in the absence of disease and had enhanced resistance to the fungal pathogen Curvularia lunata. Using map-based cloning, we identified the causal gene encoding pheophorbide a oxidase (PAO), which is known to be involved in chlorophyll degradation and MDR, and is encoded by LETHAL LEAF SPOT1 (LLS1). LLS1 was found to be induced by both biotic and abiotic stresses. Transcriptomics analysis showed that genes involved in defense responses and secondary metabolite biosynthesis were mildly activated in leaves of the les30 mutant without lesions, whilst they were strongly activated in leaves with lesions. In addition, in les30 leaves with lesions, there was overaccumulation of defense-associated phytohormones including jasmonic acid and salicylic acid, and of phytoalexins including phenylpropanoids, lignin, and flavonoids, suggesting that their biosynthesis was activated in a lesion-dependent manner. Taken together, our study implies the existence of an interactive amplification loop of interrupted chlorophyll degradation, cell death, expression of defense-related genes, and metabolite changes that results in suicidal lesion formation and MDR, and this has the potential to be exploited by genetic manipulation to improve maize disease resistance.
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Resistência à Doença , Zea mays , Alelos , Morte Celular/fisiologia , Clorofila/metabolismo , Resistência à Doença/genética , Humanos , Oxilipinas/metabolismo , Doenças das Plantas/genética , Doenças das Plantas/microbiologia , Folhas de Planta/genética , Folhas de Planta/metabolismo , Proteínas de Plantas/genética , Zea mays/metabolismoRESUMO
Right ventricular (RV) failure has become a deadly complication of left ventricular assist device (LVAD) implantation, for which desynchrony in bi-ventricular pulse resulting from a LVAD is among the important factor. This paper investigated how different control modes affect the synchronization of pulse between LV (left ventricular) and RV by numerical method. The numerical results showed that the systolic duration between LV and RV did not significantly differ at baseline (LVAD off and cannula clamped) (48.52% vs. 51.77%, respectively). The systolic period was significantly shorter than the RV systolic period in the continuous-flow mode (LV vs. RV: 24.38% vs. 49.16%) and the LV systolic period at baseline. The LV systolic duration was significantly shorter than the RV systolic duration in the pulse mode (LV vs. RV: 28.38% vs. 50.41%), but longer than the LV systolic duration in the continuous-flow mode. There was no significant difference between the LV and RV systolic periods in the counter-pulse mode (LV vs. RV: 43.13% vs. 49.23%). However, the LV systolic periods was shorter than the no-pump mode and much longer than the continuous-flow mode. Compared with continuous-flow and pulse mode, the reduction in rotational speed (RS) brought out by counter-pulse mode significantly corrected the duration of LV systolic phase. The shortened duration of systolic phase in the continuous-flow mode was corrected as re-synchronization in the counter-pulse mode between LV and RV. Hence, we postulated that the beneficial effects on RV function were due to re-synchronizing of RV and LV contraction. In conclusion, decreased RS delivered during the systolic phase using the counter-pulse mode holds promise for the clinical correction of desynchrony in bi-ventricular pulse resulting from a LVAD and confers a benefit on RV function.
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Insuficiência Cardíaca , Coração Auxiliar , Disfunção Ventricular Direita , Insuficiência Cardíaca/terapia , Humanos , Sístole , Função Ventricular DireitaRESUMO
OBJECTIVES: The aim of this study was to investigate variations in the interaction between enamel, that is, the acquired enamel pellicle (AEP) and citric or hydrochloric acid. MATERIALS AND METHODS: A 24-h AEP was formed on natural enamel specimens (n = 40) from pooled whole mouth human saliva. Samples were randomly allocated to citric (0.3%, pH 3.2) or hydrochloric (HCl) acid (0.01 M, pH 2.38) exposure for 30 or 300 s. The total protein concentration (TPC), and phosphorous and calcium concentrations of the pellicle were determined before and after acid exposure, and again after re-immersion in saliva. Surface roughness and tandem scanning confocal microscopy imaging were used to assess enamel changes. RESULTS: After 300 s of citric acid exposure, the mean ± SD TPC reduced from 5.1 ± 1.1 to 3.5 ± 1.1 mg/mL (p < 0.05). In contrast, after 300 s of HCl exposure, the mean TPC did not reduce significantly from baseline (6.6 ± 1.1 to 5.7 ± 0.7 mg/mL) but was significantly reduced in the reformed pellicle to 4.9 ± 1.2 mg/mL (p < 0.001). This reduction occurred after significant release of calcium and phosphorous from the enamel surface (p < 0.001). Thirty seconds of exposure to either acid had no obvious effect on the AEP. The surface roughness of the enamel decreased after acid exposure but no differences between groups was observed. CONCLUSIONS: These findings indicate that citric acid interacted with proteins in the AEP upon contact, offering enamel protection. In contrast, HCl appeared to bypass the pellicle, and reduced protein was observed only after changes in the enamel chemical composition.
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Película Dentária , Esmalte Dentário , Humanos , Ácido Clorídrico/efeitos adversos , Saliva , Erosão Dentária/induzido quimicamenteRESUMO
Regurgitation is an abnormal condition happens when left ventricular assist devices (LVADs) operated at a low speed, which causes LVAD to fail to assist natural blood-pumping by heart and thus affects patients' health. According to the degree of regurgitation, three LVAD's regurgitation states were identified in this paper: no regurgitation, slight regurgitation and severe regurgitation. Regurgitation index ( RI), which is presented based on the theory of dynamic closed cavity, is used to grade the regurgitation of LVAD. Numerical results showed that when patients are in exercising, resting and sleeping state, the critical speed between slight regurgitation and no regurgitation are 6 650 r/min, 7 000 r/min and 7 250 r/min, respectively, with corresponding RI of 0.401, 0.300 and 0.238, respectively. And the critical speed between slight regurgitation and severe regurgitation are 5 500 r/min, 6 000 r/min and 6 450 r/min, with corresponding RI of 0.488, 0.359 and 0.284 respectively. In addition, there is a negative relation correction between RI and rotational speed, so that grading the LVAD's regurgitation can be achieved by determining the corresponding critical speed. Therefore, the detective parameter RI based on the signal of flow is proved to be able to grade LVAD's regurgitation states effectively and contribute to the detection of LVAD's regurgitation, which provides theoretical basis and technology support for developing a LVADs controlling system with high reliability.
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The implantable miniaturized axial blood pump works at a high rotational speed,which increases the risk of blood damage.In this article,we aimed to reduce the possibility of hemolysis and thrombosis by designing a twostage axial blood pump.Under the operation conditions of flow rate 5L/min and outlet pressure of 100 mm Hg,we carried out the numerical simulation on the two-stage and single-stage blood pumps to compare the hemolysis and platelet activation state.The results turned out that the hemolysis index of two-stage axial blood pump was better while the platelet activation state was worse than those of single stage design.On the index of hemolysis level and platelet activation state,the design of the two-stage pump with the low and high-head impeller combination was better than the two-stage pump with the equal heads,or the high and low-head impeller combination.In terms of reducing the risk of blood damage for implantable miniaturized axial blood pump,the research result can provide some theoretical basis and new design ideas.
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Coração Auxiliar , Hemólise , Ativação Plaquetária , Trombose/prevenção & controle , Humanos , PressãoRESUMO
Objectives: The increased utilization of Artificial intelligence (AI) in healthcare changes practice and introduces ethical implications for AI adoption in medicine. We assess medical doctors' ethical stance in situations that arise in adopting an AI-enabled Clinical Decision Support System (AI-CDSS) for antibiotic prescribing decision support in a healthcare institution in Singapore. Methods: We conducted in-depth interviews with 30 doctors of varying medical specialties and designations between October 2022 and January 2023. Our interview guide was anchored on the four pillars of medical ethics. We used clinical vignettes with the following hypothetical scenarios: (1) Using an antibiotic AI-enabled CDSS's recommendations for a tourist, (2) Uncertainty about the AI-CDSS's recommendation of a narrow-spectrum antibiotic vs. concerns about antimicrobial resistance, (3) Patient refusing the "best treatment" recommended by the AI-CDSS, (4) Data breach. Results: More than half of the participants only realized that the AI-enabled CDSS could have misrepresented non-local populations after being probed to think about the AI-CDSS's data source. Regarding prescribing a broad- or narrow-spectrum antibiotic, most participants preferred to exercise their clinical judgment over the AI-enabled CDSS's recommendations in their patients' best interest. Two-thirds of participants prioritized beneficence over patient autonomy by convincing patients who refused the best practice treatment to accept it. Many were unaware of the implications of data breaches. Conclusion: The current position on the legal liability concerning the use of AI-enabled CDSS is unclear in relation to doctors, hospitals and CDSS providers. Having a comprehensive ethical legal and regulatory framework, perceived organizational support, and adequate knowledge of AI and ethics are essential for successfully implementing AI in healthcare.
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Antibacterianos , Inteligência Artificial , Sistemas de Apoio a Decisões Clínicas , Médicos , Humanos , Singapura , Antibacterianos/uso terapêutico , Masculino , Feminino , Padrões de Prática Médica , Adulto , Atitude do Pessoal de Saúde , Pessoa de Meia-Idade , Entrevistas como Assunto , Pesquisa QualitativaRESUMO
Copine proteins are highly conserved and ubiquitously found in eukaryotes, and their indispensable roles in different species were proposed. However, their exact function remains unclear. The phytohormone brassinosteroids (BRs) play vital roles in plant growth, development and environmental responses. A key event in effective BR signaling is the formation of functional BRI1-SERK receptor complex and subsequent transphosphorylation upon ligand binding. Here, we demonstrate that BONZAI (BON) proteins, which are plasma membrane-associated copine proteins, are critical components of BR signaling in both the monocot maize and the dicot Arabidopsis. Biochemical and molecular analyses reveal that BON proteins directly interact with SERK kinases, thereby ensuring effective BRI1-SERK interaction and transphosphorylation. This study advances the knowledge on BR signaling and provides an important target for optimizing valuable agronomic traits, it also opens a way to study steroid hormone signaling and copine proteins of eukaryotes in a broader perspective.
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Proteínas de Arabidopsis , Arabidopsis , Proteínas de Transporte , Arabidopsis/metabolismo , Brassinosteroides/metabolismo , Zea mays/genética , Zea mays/metabolismo , Proteínas Quinases/metabolismo , Proteínas de Arabidopsis/metabolismo , Proteínas de Membrana/metabolismoRESUMO
The centrifugal blood pump is a commonly used ventricular assist device. It can replace part of the heart function, pumping blood throughout the body in order to maintain normal function. However, the high shear stress caused by the impeller rotating at high speeds can lead to hemolysis and, as a consequence, to stroke and other syndromes. Therefore, reducing the hemolysis level while ensuring adequate pressure generation is key to the optimization of centrifugal blood pumps. In this study, a screw centrifugal blood pump was used as the research object. In addition, pressure generation and the hemolysis level were optimized simultaneously using a coupled algorithm composed of random forest (RF) and multi-objective gray wolf optimization (MOGWO). After verifying the prediction accuracy of the algorithm, three optimized models were selected and compared with the baseline model in terms of pressure cloud, 2D streamline, SSS distribution, HI distribution, and vortex distribution. Finally, via a comprehensive evaluation, the optimized model was selected as the final optimization design, in which the pressure generation increased by 24% and the hemolysis value decreased by 48%.
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Background: The uncertainties surrounding the COVID-19 pandemic led to a surge in non-urgent emergency department (ED) attendance among people presenting with upper respiratory tract infection (URTI) symptoms. These non-urgent visits, often manageable in primary care, exacerbated ED overcrowding, which could compromise the quality of ED services. Understanding patients' expectations and the reasons for these ED visits is imperative to mitigate the problem of ED overcrowding. Hence, we assessed the factors influencing patients' expectations for diagnostic tests during their ED visits for uncomplicated URTI during different phases of the pandemic. Methods: We conducted a cross-sectional study on adults with URTI symptoms seeking care at four public EDs in Singapore between March 2021 and March 2022. We segmented the study period into three COVID-19 pandemic phases-containment, transition, and mitigation. The outcome variables are whether patients expected (1) a COVID-19-specific diagnostic test, (2) a non-COVID-19-specific diagnostic test, (3) both COVID-19-specific and non-COVID-19-specific diagnostic tests, or (4) no diagnostic test. We built a multinomial regression model with backward stepwise selection and classified the findings according to Andersen's healthcare utilization model. Results: The mean age of participants was 34.5 (12.7) years. Factors (adjusted odds ratio [95% confidence interval]) influencing expectations for a COVID-19-specific diagnostic test in the ED include younger age {21-40 years: (2.98 [1.04-8.55])}, no prior clinical consultation (2.10 [1.13-3.89]), adherence to employer's health policy (3.70 [1.79-7.67]), perceived non-severity of illness (2.50 [1.39-4.55]), being worried about contracting COVID-19 (2.29 [1.11-4.69]), and during the transition phase of the pandemic (2.29 [1.15-4.56]). Being non-employed influenced the expectation for non-COVID-19-specific diagnostic tests (3.83 [1.26-11.66]). Factors influencing expectations for both COVID-19-specific and non-COVID-19-specific tests include younger age {21-40 years: (3.61 [1.26-10.38]); 41-60 years: (4.49 [1.43-14.13])}, adherence to employer's health policy (2.94 [1.41-6.14]), being worried about contracting COVID-19 (2.95 [1.45- 5.99]), and during the transition (2.03 [1.02-4.06]) and mitigation (2.02 [1.03-3.97]) phases of the pandemic. Conclusion: Patients' expectations for diagnostic tests during ED visits for uncomplicated URTI were dynamic across the COVID-19 pandemic phases. Expectations for COVID-19-specific diagnostic tests for ED visits for uncomplicated URTI were higher among younger individuals and those worried about contracting COVID-19 during the COVID-19 pandemic. Future studies are required to enhance public communications on the availability of diagnostic services in primary care and public education on self-management of emerging infectious diseases such as COVID-19.
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COVID-19 , Adulto , Humanos , Adulto Jovem , COVID-19/diagnóstico , COVID-19/epidemiologia , Pandemias , Motivação , Estudos Transversais , Serviço Hospitalar de Emergência , Aceitação pelo Paciente de Cuidados de Saúde , Testes Diagnósticos de Rotina , Teste para COVID-19RESUMO
Based on the nonlinear relationship between heart rate and stroke volume, a flow model of left ventricular circulation was improved, and a variable-speed blood-pump control strategy based on heart-rate feedback was proposed. The control strategy was implemented on a system combining the rotary blood pump and blood circulation models of heart failure. The aortic flow of a healthy heart at different heart rates was the desired control goal. Changes in heart rate were monitored and pump speed was adjusted so that the output flow and aortic pressure of the system would match a normal heart in real time to achieve the best auxiliary state. After simulation with MATLAB, the cardiac output satisfied the ideal perfusion requirements at different heart rates, and aortic pressure demonstrated lifting and had good pulsatile performance when a variable-speed blood pump was used. The coupled model reflected the relationship between hemodynamic parameters at different heart rates with the use of the variable-speed blood pump, providing a theoretical basis for the blood-pump-assisted treatment of heart failure and the design of physiological control strategies.
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Implanting rotary blood pumps (RBPs) has become the principal treatment for patients suffering from severe heart failure. There are still many challenges to address for RBP control systems. These problems include meeting the patient's physiological perfusion, eliminating postoperative complications, as well as debugging the patient's physiological control system (automatically and indiscriminately). This paper proposes a non-invasive adaptive control system based on the Frank-Starling-like mechanism (NAC-FSL) to solve these problems. This control system uses the motor speed of the rotary blood pump as the only input variable, and the pump flow was estimated by the motor speed for achieving non-invasive detection. Simultaneously, a cardiovascular reference model was developed to provide an appropriate real-time preload for heart failure patients. The Frank-Starling-like control baseline was tracked to obtain the desired reference average pump flow by using the preload. Avoiding suction was done by adopting the control baseline (CLn), which included a flat slope under a high preload. Moreover, the NAC-FSL system could potentially unload the left ventricle and provide a higher pump flow with a smaller error during the exercise state, as compared to the CSC system. Finally, the K value indicating the preload sensitivity in the NAC-FSL controller was optimized to meet the perfusion needs according to the hemodynamic parameters.
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MiR396s play important roles in regulating plant growth and stress response, and great potential for crop yield promotion was anticipated. For more comprehensive and precise understanding of miR396s in Poaceae, we analyzed the phylogenetic linkage, gene expression, and chromosomal distribution of miR396s in this study. Although the mature miR396s' sequences were mostly conserved, differential expression patterns and chromosomal distribution were found among Poaceae species including the major cereal crops rice, wheat, and maize. Consistently, in comparison with rice, wheat and maize plants transformed with the target mimicry construct of miR396 (MIM396) exhibited differential effects on grain size and disease resistance. While the TaMIM396 plants showed increased grain size, panicle length and sensitivity to B. graminis, the ZmMIM396 plants didn't show obvious changes in grain size and disease resistance. In Addition, several GROWTH-REGULATING FACTOR (GRF) genes in wheat and maize were repressed by miR396s, which could be reversed by MIM396, confirming the conserved regulatory roles of miR396 on GRFs. While providing new solution to enhance grain yield in wheat and revealing potential regulatory variations of miR396s in controlling grain size and disease resistance in different crops, this study gives clues to further explore miR396s' functions in other Poaceae species.
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MicroRNAs , Oryza , Triticum/genética , Triticum/metabolismo , Poaceae/genética , Zea mays/genética , Zea mays/metabolismo , Regulação da Expressão Gênica de Plantas , Filogenia , Resistência à Doença , Plantas Geneticamente Modificadas/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Grão Comestível/genética , Oryza/genéticaRESUMO
Disease lesion mimic (Les/les) mutants display disease-like spontaneous lesions in the absence of pathogen infection, implying the constitutive activation of defense responses. However, the genetic and biochemical bases underlying the activated defense responses in those mutants remain largely unknown. Here, we performed integrated transcriptomics and metabolomics analysis on three typical maize Les mutants Les4, Les10, and Les17 with large, medium, and small lesion size, respectively, thereby dissecting the activated defense responses at the transcriptional and metabolomic level. A total of 1,714, 4,887, and 1,625 differentially expressed genes (DEGs) were identified in Les4, Les10, and Les17, respectively. Among them, 570, 3,299, and 447 specific differentially expressed genes (SGs) were identified, implying a specific function of each LES gene. In addition, 480 common differentially expressed genes (CGs) and 42 common differentially accumulated metabolites (CMs) were identified in all Les mutants, suggesting the robust activation of shared signaling pathways. Intriguingly, substantial analysis of the CGs indicated that genes involved in the programmed cell death, defense responses, and phenylpropanoid and terpenoid biosynthesis were most commonly activated. Genes involved in photosynthetic biosynthesis, however, were generally repressed. Consistently, the dominant CMs identified were phenylpropanoids and flavonoids. In particular, lignin, the phenylpropanoid-based polymer, was significantly increased in all three mutants. These data collectively imply that transcriptional activation of defense-related gene expression; increase of phenylpropanoid, lignin, flavonoid, and terpenoid biosynthesis; and inhibition of photosynthesis are generalnatures associated with the lesion formation and constitutively activated defense responses in those mutants. Further studies on the identified SGs and CGs will shed new light on the function of each LES gene as well as the regulatory network of defense responses in maize.
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A novel transapical coaptation plate (TCP) device was developed and anchored by sutures in the mitral valve to treat functional mitral regurgitation. The objective of this study was to test efficacy of the TCP in an in vitro model. Eight fresh porcine mitral valves were mounted in a left heart simulator to simulate functional mitral regurgitation by means of annular dilatation and asymmetrical or symmetrical papillary muscle (PM) displacement. Six polyurethane TCPs in thickness of 6.4(#1), 4.8(#2), 3.2(#3) mm and hardness of durometer 30 A (H) and 30 OO(S),were fabricated and labeled as H1, H2, H3 and S1, S2, S3, respectively. These TCPs were anchored by the sutures in the mitral annulus and left ventricle apex, and tested. Steady backward flow leakage in a hydrostatic condition and regurgitant volume in a pulsatile flow were measured before and after implantation of the TCPs. Mean regurgitant volume fractions in the asymmetric PM displacement were reduced significantly from 59.1 to 37.2% for H1, 43.2% for H2, 35.9% for S1 and 34.2% for S2 (p < 0.021), after implantation of the TCPs. No significant reduction in mitral regurgitation was seen for H3 and S3 (p > 0.067). Mitral regurgitation was mild in the symmetric PM displacement, and was not significantly reduced after implantation of the TCPs. In conclusion, the TCP anchored by the sutures in the mitral annulus and left ventricle apex functions successfully as a plug in the mitral valve leaflet gap. The TCP with thickness equal to or greater than 4.8 mm is effective to reduce functional mitral regurgitation. The TCP hardness has no effect on difference in reduction of functional mitral regurgitation.
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Implante de Prótese de Valva Cardíaca , Próteses Valvulares Cardíacas , Modelos Cardiovasculares , Fluxo Pulsátil , Animais , Implante de Prótese de Valva Cardíaca/instrumentação , Implante de Prótese de Valva Cardíaca/métodos , Insuficiência da Valva Mitral/fisiopatologia , Insuficiência da Valva Mitral/cirurgia , SuínosRESUMO
The mitogen-activated protein kinase (MAPK) cascades, which play crucial roles in plant development processes, are universal modules of signal transduction in eukaryotes and consist of a core module of three sequentially phosphorylated kinases: MAPK, MAPK kinase (MAPKK), and MAPKK kinase (MAPKKK). This is the first report on the identification and analysis of MAPK cascades in Eucommia ulmoides. We conducted a genome-wide screening and identified 13 EuMAPKs, five EuMAPKKs, and 57 EuMAPKKKs. The construction of phylogenetic trees revealed that EuMAPKs and EuMAPKKs were divided into four groups (A, B, C, and D), and EuMAPKKKs were divided into three subfamilies (MEKK, RAF, and ZIK). These subfamilies were further confirmed by conserved domain/motif analysis and gene structure analysis. Based on the expression profiles of all identified EuMAPK cascades in various organs at different developmental stages, three genes (EuRAF22-2, EuRAF34-1, and EuRAF33-2) with stable expression patterns at all stages of fruit or leaf development, three genes (EuRAF2-3, EuMPK11, and EuMEKK21) with differential expression patterns, and two highly expressed genes (EuZIK1 and EuMKK2) were screened and validated by qRT-PCR. Overall, our results could be used for further research on the precise role of MAPK cascades during organ development in E. ulmoides.
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Eucommiaceae/genética , Proteínas Quinases Ativadas por Mitógeno/genética , Organogênese Vegetal/genética , Sequência de Aminoácidos , Mapeamento Cromossômico , Cromossomos de Plantas/metabolismo , Sequência Conservada , Eucommiaceae/crescimento & desenvolvimento , Perfilação da Expressão Gênica/métodos , Regulação da Expressão Gênica de Plantas/genética , Genoma de Planta/genética , Estudo de Associação Genômica Ampla , MAP Quinase Quinase Quinases/metabolismo , Sistema de Sinalização das MAP Quinases/genética , Sistema de Sinalização das MAP Quinases/fisiologia , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Proteínas Quinases Ativadas por Mitógeno/fisiologia , Filogenia , Proteínas de Plantas/genética , Alinhamento de SequênciaRESUMO
Asiatic acid (AA) derivatives 4 and 5 modified at the C-11 and C-28 positions were designed and synthesized, their structures were confirmed using HRMS, (1)H NMR and (13)C NMR. In vitro antitumor activities of all compounds against MGC-803, NCI-H460, HepG2, Hela and 7404 cancer cell lines were evaluated and compared with commercial anticancer drug 5-fluorouracil (5-FU), employing standard MTT assay. The new compounds 5a-5t showed stronger anti-proliferative activity than AA, especially compound 5b was found to be the best inhibition activity on HepG2 cell line. In addition, the mechanism of compound 5b was preliminarily investigated by acridine orange/ethidium bromide staining, Hoechst 33258 staining, JC-1 mitochondrial membrane potential staining, flow cytometric, qRT-PCR (quantitative real-time PCR) and Western blot. Compound 5b induced the productions of ROS, and altered anti- and pro-apoptotic proteins, leading to mitochondrial dysfunction and activations of caspase-9 and caspase-3 for causing cell apoptosis. Moreover, the cell cycle analysis showed that compound 5b mainly arrested HepG2 cells in G1 stage.
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Compostos de Anilina/química , Antineoplásicos/farmacologia , Triterpenos Pentacíclicos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Células HeLa , Células Hep G2 , Humanos , Modelos Moleculares , Estrutura Molecular , Triterpenos Pentacíclicos/síntese química , Triterpenos Pentacíclicos/química , Relação Estrutura-AtividadeRESUMO
In order to explore the genetic mutations of the H9N2 subtype avian influenza viruses isolated in Shandong, sixteen avian influenza virus subtype H9N2 were isolated from different areas of Shandong Province. The complete HA fragments of the viruses were amplified by RT-PCR and the sequences were analyzed on homology and heredity evolution after the cloning and sequencing of the products. The results showed that the amino acid motif of cleavage sites for all the sixteen virus in the HA gene were RSSR decrease GLF, which was consistent with the characterization of the LPAIV. Seven to nine potential glycosylation sites were found during the analysis and the receptor binding sites were relatively conservative except the 198 site. The Leucine(L) at the amino acid position 234 in the HA genes of all isolates indicated the potential of binding with SAalpha,2-6 receptor of mammals. Homology analysis showed that the homology of HA nucleotide and amino acid sequences was 96.3%-99.9% and 97.1%-99.6% for different strains. They belonged to a branch of the A/Duck/Hong Kong/Y280/97 in the phylogenetic tree.
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Variação Genética , Glicoproteínas de Hemaglutininação de Vírus da Influenza/genética , Vírus da Influenza A Subtipo H9N2/isolamento & purificação , Influenza Aviária/virologia , Sequência de Aminoácidos , Animais , Aves , China , Glicoproteínas de Hemaglutininação de Vírus da Influenza/química , Vírus da Influenza A Subtipo H9N2/química , Vírus da Influenza A Subtipo H9N2/classificação , Vírus da Influenza A Subtipo H9N2/genética , Dados de Sequência Molecular , Filogenia , Homologia de Sequência de AminoácidosRESUMO
The implantability and durability have been for decades the focus of artificial heart R&D. A mini axial and a maglev radial pump have been developed to meet with such requirements.The mini axial pump weighing 27g (incl.5g rotor) has an outer diameter of 21mm and a length of 10mm in its largest point, but can produce a maximal blood flow of 6l/min with 50mmHg pressure increase. Therefore, it is suitable for the patients of 40-60kg body weight. For other patients of 60-80kg or 80-100kg body weight, the mini axial pumps of 23mm and 25mm outer diameter had been developed before, these devices were acknowledged to be the world smallest LVADs by Guinness World Record Center in 2004.The permanent maglev radial pump weighing 150g is a shaft-less centrifugal pump with permanent magnetic bearings developed by the author. It needs no second coil for suspension of the rotor except the motor coil, different from all other maglev pumps developed in USA, Japan, European, etc. Thus no detecting and controlling systems as well as no additional power supply for maglev are necessary. The pump can produce a blood flow up to as large as 10l/min against 100mmHg pressure.An implantable and durable blood pump will be a viable alternative to natural donor heart for transplantation.