Mitochondrial fission is important for the development and progression of pancreatic cancer (PC). However, little is known regarding its role in pancreatic cancer apoptosis, metabolism and migration. In the current study, the mechanism by which mitochondrial fission modifies the biological characteristics of PC was explored. MicroRNA-125a (miR-125a) had the ability to inhibit mitochondrial fission and contributed to cellular survival. Suppressed mitochondrial fission led to a reduction in mitochondrial debris, preserved the mitochondrial membrane potential, inhibited mitochondrial permeability transition pore opening, ablated cytochrome c leakage into the cytoplasm and reduced the pro-apoptotic protein contents, finally blocking mitochondria related apoptosis pathways. Furthermore, defective mitochondrial fission induced by miR-125a enhanced mitochondria-dependent energy metabolism by promoting activity of electron transport chain complexes. Furthermore, suppressed mitochondrial fission also contributed to PANC-1 cell migration by preserving the F-actin balance. Furthermore, mitofusin 2 (Mfn2), the key defender of mitochondrial fission, is involved in inhibition of miR125a-mediated mitochondrial fission. Low contents of miR-125a upregulated Mfn2 transcription and expression, leading to inactivation of mitochondrial fission. Ultimately, the current study determined that miR-125a and Mfn2 are regulated by hypoxia-inducible factor 1 (HIF1). Knockdown of HIF1 reversed miR-125a expression, and therefore, inhibited Mfn2 expression, leading to activation of mitochondrial fission. Collectively, the present study demonstrated mitochondrial fission as a tumor suppression process that is regulated by the HIF/miR-125a/Mfn2 pathways, acting to restrict PANC-1 cell survival, energy metabolism and migration, with potential implications for novel approaches for PC therapy.
Mimicking biological locomotion strategies offers important possibilities and motivations for robot design and control methods. Among bioinspired microrobots, flexible microrobots exhibit remarkable efficiency and agility. These microrobots traditionally rely on soft material components to achieve undulatory propulsion, which may encounter challenges in design and manufacture including the complex fabrication processes and the interfacing of rigid and soft components. Herein, a bioinspired magnetically driven microswimmer that mimics the undulatory propulsive mechanism is proposed. The designed microswimmer consists of four rigid segments, and each segment is connected to the succeeding segment by joints. The microswimmer is fabricated integrally by 3D laser lithography without further assembly, thereby simplifying microrobot fabrication while enhancing structural integrity. Experimental results show that the microswimmer can successfully swim forward along guided directions via undulatory locomotion in the low Reynolds number (Re) regime. This work demonstrates for the first time that the flexible characteristic of microswimmers can be emulated by 3D structures with multiple rigid segments, which broadens possibilities in microrobot design. The proposed magnetically driven microswimmer can potentially be used in biomedical applications, such as medical diagnosis and treatment in precision medicine.
The cells in conventional packaging foams have random size and orientation, and the energyabsorbing behaviour of these foams is determined by the collective contribution of different sizes of cells. In contrast to the random nature of stochastic foams, 3D printing technologies allow engineers to design and produce foams having engineered cellular structures. In this study, engineered cellular structures based on the classic Kelvin 1887 model were 3D printed in 30 × 30 × 30 mm thermoplastic polyurethane cubes with a repeating size of 216 unit cells.One hundred consecutive cyclic compression tests were performed to assess the 3D printed foam's resilience and energy absorption characteristics. The stress-strain curve of the 3D printed thermoplastic polyurethane foam indicated viscoelastic behaviour and a Mullins effect indicative of resilient rubber. A long wave buckling mode was observed during cyclic compression cycles due to the Kelvin structure. The cushion factor computed from the stress-strain curve was close to that of a metal spring with linear elasticity. The combination of the 3D printed foam's resilience, its much lower density than rubber, and the complete geometric freedom of the engineered cellular structures offer designers the potential to create high-performance cushion materials tailored for packaging applications.
Flying insects and swimming fishes have high efficiency and high maneuverability in air and water, respectively. Their wings and fins have evolved for many ages to adapt to propelling in the complex environment. In the paper, an integrative biomimetic robotic fish is proposed and developed, which combines the advantages of insect wings and fish fins to achieve a high agility underwater. In the robotic fish, two caudal fins were equipped at the tail of the robotic fish in parallel as the main propulsion mechanism, the opposite flapping of the two caudal fins generates mutually opposing lateral forces during cruising, which leads to a stable and high-performance swimming. In addition, two pectoral fins that mimic the function of insect wings were equipped at two sides of the robotic fish, which enhances the robotic fish maneuverability in vertical plane. Moreover, a central pattern generator (CPG) model was designed to achieve the versatile maneuvering motions, motion switching, and autonomous swimming with an obstacle avoiding ability. The experiments have demonstrated that the robotic fish can swim more stably and efficiently with versatile maneuver motions by taking advantage of the integrative propulsion mechanism. The developed robotic fish have many potential applications for its agility, stable swimming, and low-cost structure.
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