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Abstract Acute myeloid leukemia (AML) comprises a multifarious and heterogeneous array of illnesses characterized by the anomalous proliferation of myeloid cells in the bone marrow microenvironment (BMM). The BMM plays a pivotal role in promoting AML progression, angiogenesis, and metastasis. The immune checkpoints (ICs) and metabolic processes are the key players in this process. In this review, we delineate the metabolic and immune checkpoint characteristics of the AML BMM, with a focus on the roles of BMM cells e.g. tumor-associated macrophages, natural killer cells, dendritic cells, metabolic profiles and related signaling pathways. We also discuss the signaling pathways stimulated in AML cells by BMM factors that lead to AML progression. We then delve into the roles of immune checkpoints in AML angiogenesis, metastasis, and cell proliferation, including co-stimulatory and inhibitory ICs. Lastly, we discuss the potential therapeutic approaches and future directions for AML treatment, emphasizing the potential of targeting metabolic and immune checkpoints in AML BMM as prognostic and therapeutic targets. In conclusion, the modulation of these processes through the use of directed drugs opens up new promising avenues in combating AML. Thereby, a comprehensive elucidation of the significance of these AML BMM cells' metabolic and immune checkpoints and signaling pathways on leukemic cells can be undertaken in the future investigations. Additionally, these checkpoints and cells should be considered plausible multi-targeted therapies for AML in combination with other conventional treatments in AML. Video Abstract

Background: The production of recombinant proteins in Escherichia coli is one of the most valuable achievements in biotechnology, with many therapeutic and diagnostic applications; however, the aggregation and misfolding of proteins that result in the formation of insoluble inclusion bodies is a disruptive factor in this process. Various solubilization and refolding methods can be used to improve recombinant protein conformation. In this study, we applied a dilution method with a refolding buffer to produce a native form of soluble immature mouse TGF-β1. Materials and Methods: The TGF-β1 cDNA which encodes the protein without the signal peptide, was cloned into the pET21-b (+) vector. The target protein was expressed by the transformation of E. coli BL21 cells with the plasmid. The resulting inclusion bodies were solubilized and then diluted in the refolding buffer to make a protein with native structure. Results: Following PCR of the recombinant plasmid with T7 primers, electrophoresis and sequencing of the amplified product indicated 100% identity of the target sequence with the murine TGF-β1 gene. Finally, the protein solubility and immuno-reactivity were confirmed a 44 kDa protein which conducted with the anti-TGF-β1-specific polyclonal antibody on a western blot. Conclusion: Our dilution method and refolding buffer effectively converted aggregated immature mouse TGF-β1 to a soluble and immuno-reactive form.

Backgrounds and Objectives: Assessing the educational services provided for students and determining the gap between the current status and the expected status can pave the way for developing programs to promote the quality of educational services. This study was performed aiming at determining the quality of educational services in Shahroud University of Medical Sciences in 2010.Methods: In this cross-sectional study, 274 students of Shahroud University of Medical Sciences were selected by random sampling method. The data were collected using SERVQUAL standard questionnaire. The 27-question questionnaire included two sections of demographic data and five-dimension educational services quality, which was completed as self-administered. The data were analyzed through independent samples t-test, paired samples t-test, and one-way ANOVA.Results: There were quality gaps in all dimensions of educational services quality and the statements to assess them. The biggest quality gap was in the responsiveness dimension (-1.45), and the lowest gap was in the reliability dimension (-1.14). The mean gap scores in female students were higher than male students in all five dimensions of educational services quality, and this difference were statistically significant (p

Introduction: Green spaces support people mentally in their everyday life. Perceived restorativeness and Perceived Sensory Dimension (PSD) have been addressed as optimal environmental related characteristics with regards to psychological restoration. However, relatively little research has investigated how the perception of these characteristics, directly and indirectly, affects restoration experience, particularly in a sample of university students within the area of green outdoor campus landscapes.Methods: This study hypothesizes these associations through application of partial least squares structural equation modeling (PLS-SEM), inputting data from a sample of university students in Malaysia. In the hypothesized model, we examine the degree of restoration that is enjoyed by subjects within landscapes through the effects of these characteristics. Indirect effects of perceived restorativeness via evaluation of mediation effects associated with perception of landscape characteristics and restoration experience are also investigated.Results: Through validation of the measurement model, we find significant positive coefficient paths with adequate predictive abilities in the hypothesized model. Findings suggest the effect of PSD on perceived restorativeness leads to a better explanation of restoration experience. In addition, perceived landscape characteristics of PSD enhance restoration experience in alignment with perceived restorativeness characteristics.Conclusions: Greater effects on restoration experience come through perceived restorativeness that is affected by PSD, which itself is capable of promoting favorable experiences of restorativeness in a green space and facilitating psychological restorative outcomes. The mechanistic effect of emotional regulation implies a distinct role of green spaces in maintaining good mental health and has relevance to public health models that promote independence and well-being through preventative approaches. The work paves the way for further studies that examine which dimensions of PSD support perceived restorativeness and restoration experience more than others, and the wider psycho-social value of green spaces through the application of mediation effects and personal sensory dimensions in the development of mental health.