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BackgroundChina has the largest number of patients with Type 2 Diabetes Mellitus (T2DM), and it tends to increasingly grow in the future, putting an enormous burden on disease control and prevention in China. While glycemic variability (GV) came to be an important indicator of blood glucose control in diabetic patients, studies suggested that premeal snacks may help blood glucose control, but there are still some problems to be researched. Therefore, we designed this trial to evaluate which kind of premeal snacks would lead to better effects on GV under two diet patterns in pre-diabetes subjects and to evaluate assessments of acceptability and compliance, behavior, and metabolism changes in individuals will be described.Methods and analysisThe study is a single-center, open-label, multiparallel group, randomized controlled trial. A total of 32 male and female volunteers will be randomized into 4 groups in a single allocated ratio of soy milk (powder) snack, milk (powder) snack, almonds snack, and placebo control with 250 ml of water taken 30 min before lunch, respectively. The study consists of two intervention periods over 11 days. The first intervention period under habitual diet conditions from D3 to D6 (4 days), during which all subjects are asked to maintain their habitual eating and daily activities similar to the run-in period. The second intervention consists of prelunch snacks with standard meals. We will examine both the effect of GV and various metabolic and behavioral outcomes potentially associated with the interventions. At the end of this study, we will assess the acceptability and maintainability of the intervention through interviews.Clinical trial registrationChinese Clinical Trial Registry, identifier ChiCTR2200058935.

Protein homeostasis serves as an important step in regulating diverse cellular processes underlying the function and development of the nervous system. In particular, the ubiquitination proteasome system (UPS), a universal pathway mediating protein degradation, contributes to the development of numerous synaptic structures, including the Drosophila olfactory-associative learning center mushroom body (MB), thereby affecting associated function. Here, we describe the function of a newly characterized Drosophila F-box protein CG5003, an adaptor for the RING-domain type E3 ligase (SCF complex), in MB development. Lacking CG5003 ubiquitously causes MB γ axon pruning defects and selective CG5003 expression in pan-neurons leads to both γ axon and α/β lobe abnormalities. Interestingly, change in CG5003 expression in MB neurons does not cause any abnormalities in axons, suggesting that CG5003 functions in cells extrinsic to MB to regulate its development. Mass spectrum analysis indicates that silencing CG5003 expression in all neurons affects expression levels of proteins in the cell and structural morphogenesis, transcription regulator activity, and catalytic activity. Our findings reinforce the importance of UPS and identify a new factor in regulating neuronal development as exemplified by the synaptic structure MB.