Randomized, Double-Blind, and Placebo-Controlled Trial of Clenbuterol in Denervated Muscle Atrophy

Objectives. β2-adrenergic agonists, such as clenbuterol, have been shown to promote the hypertrophy of healthy skeletal muscles and to ameliorate muscle wasting in a few pathological conditions in both animals and humans. We intended to investigate the clinical efficacy of clenbuterol on attenuating denervation-induced muscle atrophy. Methods. A double-blind, placebo-controlled, parallel, and randomized trial was employed. 71 patients, suffering from brachial plexus injuries, were given either clenbuterol (60 μg, bid) or placebo for 3 months. Before and at the end of the study, patients were given physical examinations, biopsies of biceps brachii, electromyograms (EMGs), and other laboratory tests. Results. Compared with placebo treatment, clenbuterol significantly mitigated the decreases in cross-sectional areas of type I and II muscle fibers and alleviated the reduction in fibrillation potential amplitudes, without any adverse effects. Conclusions. Clenbuterol safely ameliorated denervated muscle atrophy in this cohort; thus larger clinical studies are encouraged for this or other β2 agonists on denervation-induced muscle atrophy

Molecular Dynamic Simulation to Explore the Molecular Basis of Btk-PH Domain Interaction with Ins(1,3,4,5)P4

Bruton’s tyrosine kinase contains a pleckstrin homology domain, and it specifically binds inositol 1,3,4,5-tetrakisphosphate (Ins(1,3,4,5)P4), which is involved in the maturation of B cells. In this paper, we studied 12 systems including the wild type and 11 mutants, K12R, S14F, K19E, R28C/H, E41K, L11P, F25S, Y40N, and K12R-R28C/H, to investigate any change in the ligand binding site of each mutant. Molecular dynamics simulations combined with the method of molecular mechanics/Poisson-Boltzmann solvent-accessible surface area have been applied to the twelve systems, and reasonable mutant structures and their binding free energies have been obtained as criteria in the final classification. As a result, five structures, K12R, K19E, R28C/H, and E41K mutants, were classified as “functional mutations,” whereas L11P, S14F, F25S, and Y40N were grouped into “folding mutations.” This rigorous study of the binding affinity of each of the mutants and their classification provides some new insights into the biological function of the Btk-PH domain and related mutation-causing diseases

User-Centered Software Design: User Interface Redesign for Blockly–Electron, Artificial Intelligence Educational Software for Primary and Secondary Schools

According to the 2021 and 2022 Horizon Report, AI is emerging in all areas of education, in various forms of educational aids with various applications, and is carving out a similarly ubiquitous presence across campuses and classrooms. This study explores a user-centered approach used in the design of the AI educational software by taking the redesign of the user interface of AI educational software Blockly–Electron as an example. Moreover, by analyzing the relationship between the four variables of software usability, the abstract usability is further certified so as to provide ideas for future improvements to the usability of AI educational software. User-centered design methods and attribution analysis are the main research methods used in this study. The user-centered approach was structured around four phases. Overall, seventy-three middle school students and five teachers participated in the study. The USE scale will be used to measure the usability of Blockly–Electron. Five design deliverables and an attribution model were created and discovered in the linear relationship between Ease of Learning, Ease of Use, Usefulness and Satisfaction, and Ease of use as a mediator variable, which is significantly different from the results of previous regression analysis for the USE scale. This study provides a structural user-centered design methodology with quantitative research. The deliverables and the attribution model can be used in the AI educational software design. Furthermore, this study found that usefulness and ease of learning significantly affect the ease of use, and ease of use significantly affects satisfaction. Based on this, the usability will be further concretized to facilitate the production of software with greater usability

Induction of lncRNA MALAT1 by hypoxia promotes bone formation by regulating the miR-22-3p/CEBPD axis

Adaptation to hypoxia promotes fracture healing. However, the underlying molecular mechanism remains unknown. Increasing evidence has indicated that long non-coding RNAs (lncRNAs) play crucial roles in several diseases, including fracture healing. In the present study, lncRNA microarray analysis was performed to assess the expression levels of different lncRNAs in MC3T3-E1 cells cultured under hypoxic conditions. A total of 42 lncRNAs exhibited significant differences in their expression, including metastasis associated lung adenocarcinoma transcript 1 (MALAT1), maternally expressed 3, AK046686, AK033442, small nucleolar RNA host gene 2 and distal-less homeobox 1 splice variant 2. Furthermore, overexpression of MALAT1 promoted osteoblast differentiation, alkaline phosphatase (ALP) activity and matrix mineralization of MC3T3-E1 cells, whereas its knockdown diminished hypoxia-induced cell differentiation, ALP activity and matrix mineralization in these cells. Moreover, functional analysis indicated that MALAT1 regulated the mRNA and protein expression levels of CCAAT/ enhancer binding protein δ by competitively binding to microRNA-22-3p. Adenoviral-mediated MALAT1 knockdown inhibited fracture healing in a mouse model. Taken together, the results indicated that MALAT1 may serve a role in hypoxia-mediated osteogenesis and bone formation