RESUMO
BACKGROUND: The healing process after a myocardial infarction (MI) in humans involves complex events that replace damaged tissue with a fibrotic scar. The affected cardiac tissue may lose its function permanently. In contrast, zebrafish display a remarkable capacity for scar-free heart regeneration. Previous studies have revealed that syndecan-4 (SDC4) regulates inflammatory response and fibroblast activity following cardiac injury in higher vertebrates. However, whether and how Sdc4 regulates heart regeneration in highly regenerative zebrafish remains unknown. METHODS AND RESULTS: This study showed that sdc4 expression was differentially regulated during zebrafish heart regeneration by transcriptional analysis. Specifically, sdc4 expression increased rapidly and transiently in the early regeneration phase upon ventricular cryoinjury. Moreover, the knockdown of sdc4 led to a significant reduction in extracellular matrix protein deposition, immune cell accumulation, and cell proliferation at the lesion site. The expression of tgfb1a and col1a1a, as well as the protein expression of Fibronectin, were all down-regulated under sdc4 knockdown. In addition, we verified that sdc4 expression was required for cardiac repair in zebrafish via in vivo electrocardiogram analysis. Loss of sdc4 expression caused an apparent pathological Q wave and ST elevation, which are signs of human MI patients. CONCLUSIONS: Our findings support that Sdc4 is required to mediate pleiotropic repair responses in the early stage of zebrafish heart regeneration.
Assuntos
Coração , Regeneração , Sindecana-4 , Peixe-Zebra , Animais , Peixe-Zebra/genética , Peixe-Zebra/metabolismo , Sindecana-4/genética , Sindecana-4/metabolismo , Regeneração/genética , Coração/fisiologia , Coração/fisiopatologia , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismo , Infarto do Miocárdio/genética , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/patologia , Proliferação de Células/genética , Miocárdio/metabolismo , Miocárdio/patologia , Técnicas de Silenciamento de GenesRESUMO
In a randomized controlled trial with time-to-event endpoint, some commonly used statistical tests to test for various aspects of survival differences, such as survival probability at a fixed time point, survival function up to a specific time point, and restricted mean survival time, may not be directly applicable when external data are leveraged to augment an arm (or both arms) of an RCT. In this paper, we propose a propensity score-integrated approach to extend such tests when external data are leveraged. Simulation studies are conducted to evaluate the operating characteristics of three propensity score-integrated statistical tests, and an illustrative example is given to demonstrate how these proposed procedures can be implemented.
RESUMO
Pig farmers in Taiwan tend to overdose copper (Cu) and zinc (Zn) in animal feeds to ensure pig health. The application of Cu- or Zn-rich livestock compost to fields can result in high Cu/Zn residues in surface soil and violate limitations for zinc and copper in land applications. This study aims to extract Cu and Zn from sludge using organic acid or H2O2/organic acids. The livestock bio-sludge was dried and treated with different concentrations of acetic acid (1N, 2N, and 4N). The acid-extracted sludge was then treated with or without adding H2O2 during different periods (4, 24, and 48 h) to investigate the efficiency of acid extraction of Cu and Zn. The supernatant of the acid-extracted product was separated from the residues through centrifugation. Experimental results showed that the treatment set of dried bio-sludge with 2% H2O2 significantly promoted the removal efficiency of Cu and Zn from the bio-sludge (p < 0.01). The best removal efficiency of Cu and Zn from the bio-sludge was 40% and 70%, respectively, using 4N acetic acid in the 48 h group. The study shows a green method for extracting Cu and Zn from livestock sludge, enhancing the sustainability of intensive livestock farming.
RESUMO
In this note, we express our viewpoint regarding power considerations, via simulation studies, in clinical study design using hierarchical composite endpoint and Finkelstein-Schoenfeld test.
Assuntos
Projetos de Pesquisa , Humanos , Ensaios Clínicos como Assunto , Simulação por Computador , Modelos Estatísticos , Determinação de Ponto FinalRESUMO
BACKGROUND: Postmenopausal bone loss and decreased physical performance are commonly presented issues. This study aimed through systematic review and meta-analysis to examine the benefits of adding exercise to medicine/supplements in postmenopausal women. METHODS: A systematic search was conducted of four electronic databases for articles published from inception to December 2023. Clinical controlled trials comparing the effect of additional exercise and medicine/supplements alone in postmenopausal women were included. The outcomes studied were bone mineral density (BMD) and physical performance. The quality of evidence was evaluated by the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE). RESULTS: Nineteen articles with 1249 participants were included in this study for systematic review and meta-analysis. The results showed that additional exercise was not associated with significantly improved BMD at the lumbar spine and hip joint compared with medicine/supplements only. However, results of subgroup analysis of exercise types showed a significant improvement in lumbar spine BMD by combining multiple types of exercise training (SMD = 0.37; 95% confidence interval [CI] = 0.01-0.72; p = .04). Furthermore, additional exercise significantly improved lower extremity muscle strength (Standard Mean Difference [SMD] = 1.77; 95% CI = 0.56-2.98; p = .004), Berg's Balance Scale (SMD = 0.72; 95% CI = 0.12-1.32; p = .02), Timed Up and Go (SMD = -1.07; 95% CI = -1.35--0.78; p < .001), fear of falling (SMD = 1.32; 95% CI = 0.89-1.75; p < .001), and the quality of life (SMD = 1.39; 95% CI = 0.74-2.05; p < .001). The quality level of the evidence was between low to very low. CONCLUSIONS: The significant value of the exercise was demonstrated through enhancing physical performance and quality of life. Moreover, combining various exercise training programs has shown a positive effect on BMD at the lumbar spine. Therefore, for postmenopausal women, combining exercise with medicine/supplements is recommended to further improve physical function and specific areas of BMD. (PROSPERO: CRD42023390633).