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In order to study the influence of load change on the meshing characteristics of cycloid pinwheel of RV reducer, considering the modification of cycloid tooth profile, the three-dimensional model of cycloid pinwheel mechanism was established by UG. The changes of meshing tooth pairs and meshing stress of cycloid pinwheel in a meshing transmission cycle were analyzed by using the transient dynamics module of Ansys, and the simulation was compared with the theoretical contact stress. Results show that the overall trend of contact stress between simulation and theory is consistent, the number of meshing teeth and meshing stress of cycloid pinwheel show a periodic law, and increase with the increase of load. The change trend of contact stress and equivalent stress is opposite to the number of meshing teeth, the more the number of meshing teeth, the smaller the meshing stress. The equivalent stress of the needle tooth in the length direction increases with the increase of load, and the stress has a trend of uniform distribution, but the change is small. The finite element analysis has certain reference significance for the design, analysis and manufacture of RV reducer.

[INLINE:1] Fidgetin, a microtubule-severing enzyme, regulates neurite outgrowth, axonal regeneration, and cell migration by trimming off the labile domain of microtubule polymers. Because maintenance of the microtubule labile domain is essential for axon initiation, elongation, and navigation, it is of interest to determine whether augmenting the microtubule labile domain via depletion of fidgetin serves as a therapeutic approach to promote axonal regrowth in spinal cord injury. In this study, we constructed rat models of spinal cord injury and sciatic nerve injury. Compared with spinal cord injury, we found that expression level of tyrosinated microtubules in the labile portion of microtubules continuously increased, whereas fidgetin decreased after peripheral nerve injury. Depletion of fidgetin enhanced axon regeneration after spinal cord injury, whereas expression level of end binding protein 3 (EB3) markedly increased. Next, we performed RNA interference to knockdown EB3 or fidgetin. We found that deletion of EB3 did not change fidgetin expression. Conversely, deletion of fidgetin markedly increased expression of tyrosinated microtubules and EB3. Deletion of fidgetin increased the amount of EB3 at the end of neurites and thereby increased the level of tyrosinated microtubules. Finally, we deleted EB3 and overexpressed fidgetin. We found that fidgetin trimmed tyrosinated tubulins by interacting with EB3. When fidgetin was deleted, the labile portion of microtubules was elongated, and as a result the length of axons and number of axon branches were increased. These findings suggest that fidgetin can be used as a novel therapeutic target to promote axonal regeneration after spinal cord injury. Furthermore, they reveal an innovative mechanism by which fidgetin preferentially severs labile microtubules.

Approximately 30% of the veterans who fought in the 1991 Gulf War (GW) suffer from a disease called Gulf War Illness (GWI), which encompasses a constellation of symptoms including cognitive deficits. A coalescence of evidence indicates that GWI was caused by low-level exposure to organophosphate pesticides and nerve agents in combination with physical stressors of the battlefield. Until recently, progress on mechanisms and therapy had been limited to rodent-based models. Using peripheral blood mononuclear cells from veterans with or without GWI, we recently developed a bank of human induced pluripotent stem cells that can be differentiated into a variety of cellular fates. With these cells, we have now generated cerebral organoids, which are three-dimensional multicellular structures that resemble the human brain. We established organoid cultures from two GW veterans, one with GWI and one without. Immunohistochemical analyses indicate that these organoids, when treated with a GW toxicant regimen consisting of the organophosphate diisopropyl fluorophosphate (a sarin analog) and cortisol (to mimic battlefield stress), display multiple indicators consistent with cognitive deficits, including increased astrocytic reactivity, enhanced phosphorylation of tau proteins, decreased microtubule stability, and impaired neurogenesis. Interestingly, some of these phenotypes were more pronounced in the organoids derived from the veteran with GWI, potentially reflecting a stronger response to the toxicants in some individuals compared to others. These results suggest that veteran-derived human cerebral organoids not only can be used as an innovative human model to uncover the cellular responses to GW toxicants but can also serve as a platform for developing personalized medicine approaches for the veterans.

The mechanical properties of the aluminum matrix composite directly affect its application in aerospace, transportation, and other industries. In this study, the effect of TiB2 particles on the comprehensive properties which includes microstructure, thermal deformation behavior, tensile properties, fracture morphology and hardness of Al-Zn-Mg-Cu alloy was analyzed. Furthermore, the microstructures of these alloys were analyzed using energy-dispersive X-ray spectroscopy, X-ray diffraction, scanning electron microscopy, and a metallography microscope. The stress–strain curves and dynamic softening of the two alloys were studied using the thermal compression test. Furthermore, a thermal processing diagram was constructed for comparing the safety and instability processing zones of the alloys. The Vickers hardness test and the tensile test were performed to compare their hardness, tensile properties, and fracture morphologies. The results demonstrated that TiB2 was contributing to the refinement of the grain size. When the deformation temperature and the stress–strain rate were 300–450 °C and 0.01–10 s−1, the alloy exhibited the same stress-strain variation trend during the thermal compression process before and after adding TiB2 particles. But the deformation resistance of the alloy was improved and processing instability zones were reduced from 300–320 °C/2.5–10 s−1 and 430–450 °C/0.2–0.5 s−1 to 420–450 °C/0.2–1 s−1 because of the addition of TiB2 particles. TiB2 particles could also increase the hardness of the alloy by 71.96% and improve the plastic properties and the fracture stress compared with before adding. [ABSTRACT FROM AUTHOR]

Engineered three-dimensional (3D) in vitro and ex vivo neural tissues, also known as “mini brains and spinal cords in a dish,” can be derived from different types of human stem cells via several differentiation protocols. In general, human mini brains are micro-scale physiological systems consisting of mixed populations of neural progenitor cells, glial cells, and neurons that may represent key features of human brain anatomy and function. To date, these specialized 3D tissue structures can be characterized into spheroids, organoids, assembloids, organ-on-a-chip and their various combinations based on generation procedures and cellular components. These 3D CNS models incorporate complex cell-cell interactions and play an essential role in bridging the gap between two-dimensional human neuroglial cultures and animal models. Indeed, they provide an innovative platform for disease modeling and therapeutic cell replacement, especially shedding light on the potential to realize personalized medicine for neurological disorders when combined with the revolutionary human induced pluripotent stem cell technology. In this review, we highlight human 3D CNS models developed from a variety of experimental strategies, emphasize their advances and remaining challenges, evaluate their state-of-the-art applications in recapitulating crucial phenotypic aspects of many CNS diseases, and discuss the role of contemporary technologies in the prospective improvement of their composition, consistency, complexity, and maturation.