Biochemical pancreatic ß-cell lineage reprogramming: Various cell fate shifts.

The incidence of pancreatic diseases has been continuously rising in recent years. Thus, research on pancreatic regeneration is becoming more popular. Chronic hyperglycemia is detrimental to pancreatic ß-cells, leading to impairment of insulin secretion which is the main hallmark of pancreatic diseases. Obtaining plenty of functional pancreatic ß-cells is the most crucial aspect when studying pancreatic biology and treating diabetes. According to the International Diabetes Federation, diabetes has become a global epidemic, with about 3 million people suffering from diabetes worldwide. Hyperglycemia can lead to many dangerous diseases, including amputation, blindness, neuropathy, stroke, and cardiovascular and kidney diseases. Insulin is widely used in the treatment of diabetes; however, innovative approaches are needed in the academic and preclinical stages. A new approach aims at synthesizing patient-specific functional pancreatic ß-cells. The present article focuses on how cells from different tissues can be transformed into pancreatic ß-cells.

Concurrent Learning-Based Adaptive Control of Underactuated Robotic Systems With Guaranteed Transient Performance for Both Actuated and Unactuated Motions.

With the wide applications of underactuated robotic systems, more complex tasks and higher safety demands are put forward. However, it is still an open issue to utilize "fewer" control inputs to satisfy control accuracy and transient performance with theoretical and practical guarantee, especially for unactuated variables. To this end, for underactuated robotic systems, this article designs an adaptive tracking controller to realize exponential convergence results, rather than only asymptotic stability or boundedness; meanwhile, unactuated states exponentially converge to a small enough bound, which is adjustable by control gains. The maximum motion ranges and convergence speed of all variables both exhibit satisfactory performance with higher safety and efficiency. Here, a data-driven concurrent learning (CL) method is proposed to compensate for unknown dynamics/disturbances and improve the estimate accuracy of parameters/weights, without the need for persistency of excitation or linear parametrization (LP) conditions. Then, a disturbance judgment mechanism is utilized to eliminate the detrimental impacts of external disturbances. As far as we know, for general underactuated systems with uncertainties/disturbances, it is the first time to theoretically and practically ensure transient performance and exponential convergence speed for unactuated states, and simultaneously obtain the exponential tracking result of actuated motions. Both theoretical analysis and hardware experiment results illustrate the effectiveness of the designed controller.

FUNDC2, a mitochondrial outer membrane protein, mediates triple-negative breast cancer progression via the AKT/GSK3ß/GLI1 pathway.

Triple-negative breast cancer (TNBC) lacks effective therapeutic targets and has a poor prognosis, easy recurrence and metastasis. It is urgent and important to explore TNBC treatment targets. Through mass spectrometry combined with qRT-PCR validation in luminal A cells and TNBC cells, high-content screening and clinical sample analysis, FUNDC2 was discovered as a novel target. The function of the outer mitochondrial membrane protein FUNDC2 in breast cancer is still unclear. In this study, we find that FUNDC2 expression in TNBC tissues is significantly higher than that in luminal subtype breast cancer tissues. FUNDC2 silencing in TNBC cells significantly reduces cell proliferation, migration and invasion. As demonstrated in vivo using subcutaneous tumor xenografts in mice, FUNDC2 suppression significantly inhibits tumor growth. The underlying mechanism might be mediated by inactivating its downstream signal AKT/GSK3ß and GLI1, a key factor of the Hedgehog signaling pathway. Therefore, FUNDC2 may promote TNBC progression and provide a therapeutic target for treating TNBC.

Biomedical importance of the ubiquitin-proteasome system in diabetes and metabolic transdifferentiation of pancreatic duct epithelial cells into ß-cells.

The ubiquitin-proteasome system (UPS) is a major pathway for cellular protein degradation. The molecular function of the UPS is the removal of damaged proteins, and this function is applied in many biological processes, including inflammation, proliferation, and apoptosis. Accumulating evidence also suggests that the UPS also has a key role in pancreatic ß-cell transdifferentiation in diabetes and can be targeted for treatment of diabetic diseases. In this review, we summarized the mechanistic roles of the UPS in the biochemical activities of pancreatic ß-cells, including the role of the UPS in insulin synthesis and secretion, as well as ß-cell degradation. Also, we discuss how the UPS mediates the transdifferentiation of pancreatic duct epithelial cells into ß-cells as the experimental basis for the development of new strategies for the treatment of diabetes in regenerative medicine.