Search

Objective To analyze problems existing in the management of the transformation of scientificand technological achievement in our hospital, and to realize the continuous improvement of service quality through project management. Methods Based on PDCA cycle management model combined with the project management tools (such as fishbone diagram, brainstorming method, Gantt chart, SMART principle, etc.), we established an innovation mechanism to improve the quality of management by strategies including establishing anachievement transformation system, optimizing approval process, building a professional cooperation platformand providing publicity and training guidance. Results The improved management quality has been achieved inthree aspects including "increased number of patent applications and authorizations", "increased transformationrate of patent" and "shortened transformation cycle". Conclusion The adoption of PDCA cycle management caneffectively improve the quality of scientific and technological achievement transformation in the hospital.

Introduction Myocardial infarction (MI) is the most severe manifestation of coronary heart disease that causes more than 7 million deaths per year (1). Even with advances of reperfusion strategies and [...], Myocardial infarction (MI) is characterized by massive cardiomyocyte (CM) death and cardiac dysfunction, and effective therapies to achieve cardioprotection are greatly needed. Here, we report that flavin-containing monooxygenase 2 (FMO2) levels were markedly increased in CMs in both ex vivo and in vivo models of ischemic injury. Genetic deletion of FMO2 resulted in reduced CM survival and enhanced cardiac dysfunction, whereas CM-specific FMO2 overexpression conferred a protective effect in infarcted rat hearts. Mechanistically, FMO2 inhibited the activation of ER stress-induced apoptotic proteins, including caspase 12 and C/EBP homologous protein (CHOP), by downregulating the unfolded protein response pathway. Furthermore, we identified FMO2 as a chaperone that catalyzes disulfide bond formation in unfolded and misfolded proteins through its GVSG motif. GVSG-mutated FMO2 failed to catalyze disulfide bond formation and lost its protection against ER stress and CM death. Finally, we demonstrated the protective effect of FMO2 in a human induced pluripotent stem cell-derived CM model. Collectively, this study highlights FMO2 as a key modulator of oxidative protein folding in CMs and underscores its therapeutic potential for treating ischemic heart disease.

BACKGROUND: Cardiac fibrosis is a common pathological feature associated with adverse clinical outcome in postinjury remodeling and has no effective therapy. Using an unbiased transcriptome analysis, we identified FMO2 (flavin-containing monooxygenase 2) as a top-ranked gene dynamically expressed following myocardial infarction (MI) in hearts across different species including rodents, nonhuman primates, and human. However, the functional role of FMO2 in cardiac remodeling is largely unknown. METHODS: Single-nuclei transcriptome analysis was performed to identify FMO2 after MI; FMO2 ablation rats were generated both in genetic level using the CRISPR-cas9 (clustered regularly interspaced short palindromic repeats/clustered regularly interspaced short palindromic repeat-associated 9) technology and lentivirus-mediated manner. Gain-of-function experiments were conducted using postn-promoter FMO2, miR1a/miR133a-FMO2 lentivirus, and enzymatic activity mutant FMO2 lentivirus after MI. RESULTS: A significant downregulation of FMO2 was consistently observed in hearts after MI in rodents, nonhuman primates, and patients. Single-nuclei transcriptome analysis showed cardiac expression of FMO2 was enriched in fibroblasts rather than myocytes. Elevated spontaneous tissue fibrosis was observed in the FMO2-null animals without external stress. In contrast, fibroblast-specific expression of FMO2 markedly reduced cardiac fibrosis following MI in rodents and nonhuman primates associated with diminished SMAD2/3 phosphorylation. Unexpectedly, the FMO2-mediated regulation in fibrosis and SMAD2/3 signaling was independent of its enzymatic activity. Rather, FMO2 was detected to interact with CYP2J3 (cytochrome p450 superfamily 2J3). Binding of FMO2 to CYP2J3 disrupted CYP2J3 interaction with SMURF2 (SMAD-specific E3 ubiquitin ligase 2) in cytosol, leading to increased cytoplasm to nuclear translocation of SMURF2 and consequent inhibition of SMAD2/3 signaling. CONCLUSIONS: Loss of FMO2 is a conserved molecular signature in postinjury hearts. FMO2 possesses a previously uncharacterized enzyme-independent antifibrosis activity via the CYP2J3-SMURF2 axis. Restoring FMO2 expression exerts potent ameliorative effect against fibrotic remodeling in postinjury hearts from rodents to nonhuman primates. Therefore, FMO2 is a potential therapeutic target for treating cardiac fibrosis following injury.

Background: In many countries and regions, such as the United States, Europe and China, a trend has emerged in which students' enthusiasm for STEM is declining. This decline may be related to students' lack of science self-efficacy. An accurate examination of students' science self-efficacy can provide a research foundation for how to cultivate it. This paper used mixed methods to develop a valid science self-efficacy scale for high school students, focusing on the perceived competence dimension. A cross-sectional analysis exploring and interpreting differences across grades and genders in science self-efficacy among high school students was conducted. Subsequently, a 1-year longitudinal study was conducted on the development of science self-efficacy in China. Results: This study developed a 24-item science self-efficacy instrument based on the Rasch model, and the validity of the instrument was assessed through multiple aspects, including face, content, construct, and predictive validity. This instrument was used to divide students' science self-efficacy into four different levels. A cross-sectional study examining 1564 high school students in 10th--12th grades revealed that students' science self-efficacy exhibited a complex process of decreasing and then increasing by grade. Most girls' science self-efficacy was higher than that of boys for Levels 1 and 4, while for the intermediate levels, i.e., Levels 2 and 3, most boys had higher science self-efficacy than girls. The quantitative and qualitative results of the longitudinal study through a 1-year follow-up of 233 high school students indicated that students' science self-efficacy significantly improved. We revealed inconsistencies between cross-sectional and longitudinal studies of the change in science self-efficacy from 10 to 11th grade. Conclusion: This study makes many contributions. First, we developed a science self-efficacy measurement instrument for high school students with high reliability and validity based on the Rasch model and characterized four different levels of student science self-efficacy. Second, the gender differences in science self-efficacy and the complex changes among grades were explained from the perspective of science self-efficacy level. Finally, students' science self-efficacy significantly improved in the longitudinal study, which was explained by self-efficacy theory and the Chinese core competency-oriented science curriculum.

Golgi Protein 73 (GP73) is a Golgi-resident protein that is highly expressed in primary tumor tissues. Initially identified as an oncoprotein, GP73 has been shown to promote tumor development, particularly by mediating the transport of proteins related to epithelial-mesenchymal transition (EMT), thus facilitating tumor cell EMT. Though our previous review has summarized the functional roles of GP73 in intracellular signal transduction and its various mechanisms in promoting EMT, recent studies have revealed that GP73 plays a crucial role in regulating the tumor and immune microenvironment. GP73 can modulate intracellular signaling pathways to influence cytokine and chemokine networks, resulting in inflammation caused by viral and bacterial infection or immune diseases, and leading tumor microenvironment deteriorated. Additionally, extracellular GP73 can also regulate signaling pathways of target cells by binding to their cell-surface receptors or entering the acceptor cells, thereby facilitating inflammation or promoting tumor development. In this review, we aim to summarize the findings, providing insights for future investigations on GP73 and its potential as a therapeutic target in ameliorating chronic inflammation in the immune and tumor microenvironment. [ABSTRACT FROM AUTHOR]

Aim: With an aging global population, there has been a growing interest in the subjective well‐being (SWB) of older people. As a positive emotion, gratitude has been found to be significantly and positively associated with SWB. However, the mechanisms underlying the relationship between gratitude and SWB remain poorly understood. This study aimed to examine the mediating effects of social support and self‐efficacy in the relationship between gratitude and SWB among older Chinese adults in nursing homes. Design: A cross‐sectional study. Methods: A sample of 354 older adults in nursing homes aged 60 years and above was recruited across three nursing homes in Guangzhou, China. Participants completed the Gratitude Questionnaire‐Six‐Item Form, the World Health Organization's well‐being index, the General Self‐efficacy questionnaire and the Multidimensional Scale of Perceived Social Support. Structural equation modelling was used to evaluate the relationships between gratitude, self‐efficacy, social support and SWB. A bootstrap test was performed to test mediating roles of self‐efficacy and social support. Results: Gratitude was found to be significantly and positively associated with SWB (β = 0.294, p < 0.001). Self‐efficacy and social support independently mediated the relationship between gratitude and SWB (indirect effect of self‐efficacy: Standardised β = 0.105, 95% CI [0.061, 0.157]; indirect effect of social support: Standardised β = 0.116, 95% CI [0.444, 0.191], all p < 0.001). Additionally, the results indicated that the mediating effect of self‐efficacy was not significantly different from that of social support in the link between gratitude with SWB. Conclusion: These findings presented strong evidence that self‐efficacy and social support provided the underlying mechanisms through which gratitude was associated with SWB in Chinese nursing home residents. This highlighted the need to develop interventions aiming at increasing gratitude, self‐efficacy and social support to promote SWB among elderly people. Patient or Public Contribution: No patient or public contribution. [ABSTRACT FROM AUTHOR]

Introduction: Amyloidosis caused by TTR mutations (ATTRv) is a rare inherited and autosomal dominant disease. More than 150 mutants of TTR have been reported, whereas some of them remain to be investigated. Methods: A 52-year-old male presented with heart failure and clinically diagnosed ATTR cardiac amyloidosis (ATTR-CA) was recruited. Whole-exome sequencing (WES) was performed. Biochemical and biophysical experiments characterized protein stability using urea-mediated tryptophan fluorescence. Drug response was analyzed by fibril formation assay. Finally, tetramer TTR concentration in patient's serum sample was measured by ultra-performance liquid chromatography (UPLC). Results: For the proband, WES revealed a mutation (c.200G>T; p.Gly67Val and referred to as G47V) in TTR gene. Biochemical and biophysical kinetics study showed that the thermodynamic stability of G47V-TTR (Cm = 2.4 m) was significantly lower than that of WT-TTR (Cm = 3.4 m) and comparable to that of L55P-TTR (Cm = 2.3 m), an early age-of-onset mutation. G47V:WT-TTR heterozygous tetramer kinetic stability (t1/2 = 1.4 h) was further compromised compared to that of the homozygous G47V-TTR (t1/2 = 3.1 h). Among three small molecule stabilizers, AG10 exhibited the best inhibition of the fibrillation of G47V-TTR homozygous protein. Using a UPLC assay, nearly 40% of TTR in this patient was calculated to be non-tetrameric. Conclusion: In this work, we reported a patient presented early onset of clinically typical ATTR-CA due to G47V-TTR mutation. Our work for the first time not only characterized the biochemical properties of G47V-TTR mutation, but also provided hints for the pathogenicity of this mutation. [ABSTRACT FROM AUTHOR]