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Focusing on the demand of energy and heavy machinery for high efficiency and high output capacity of transmission equipment, this research studies the multi-objective optimization of the NN type small tooth difference transmission with the highest efficiency and maximum output capacity. Firstly, traverse all tooth number combinations in the optimization space under different tooth number difference, different staggered tooth difference in a certain range of teeth, and get the tooth combinations table. Then, the multi-objective optimization model of the NN type small tooth difference transmission is established, taking the number of teeth combination, standard pressure angle, meshing angle, addendum height coefficient and displacement coefficient as the optimization design variables and considering the overlap ratio, tooth profile overlap interference and addendum thickness constraints. The multi-objective differential evolution algorithm based on Pareto is used to solve the optimization model, and the distribution of Pareto optimal solution set is obtained. The results obtained in this study are compared with those in the standard design manual. The comparison results show that the results in this study are better than those in the standard design manual, which can provide reference for the design of NN type small tooth difference transmission.

Objective: To summarize the research progress on the role of macrophage-mediated osteoimmune in osteonecrosis of the femoral head (ONFH) and its mechanisms., Methods: Recent studies on the role and mechanism of macrophage-mediated osteoimmune in ONFH at home and abroad were extensively reviewed. The classification and function of macrophages were summarized, the osteoimmune regulation of macrophages on chronic inflammation in ONFH was summarized, and the pathophysiological mechanism of osteonecrosis was expounded from the perspective of osteoimmune, which provided new ideas for the treatment of ONFH., Results: Macrophages are important immune cells involved in inflammatory response, which can differentiate into classically activated type (M1) and alternatively activated type (M2), and play specific functions to participate in and regulate the physiological and pathological processes of the body. Studies have shown that bone immune imbalance mediated by macrophages can cause local chronic inflammation and lead to the occurrence and development of ONFH. Therefore, regulating macrophage polarization is a potential ONFH treatment strategy. In chronic inflammatory microenvironment, inhibiting macrophage polarization to M1 can promote local inflammatory dissipation and effectively delay the progression of ONFH; regulating macrophage polarization to M2 can build a local osteoimmune microenvironment conducive to bone repair, which is helpful to necrotic tissue regeneration and repair to a certain extent., Conclusion: At present, it has been confirmed that macrophage-mediated chronic inflammatory immune microenvironment is an important mechanism for the occurrence and development of ONFH. It is necessary to study the subtypes of immune cells in ONFH, the interaction between immune cells and macrophages, and the interaction between various immune cells and macrophages, which is beneficial to the development of potential therapeutic methods for ONFH.

The combination of osteogenesis and angiogenesis dual-delivery trace element-carrying bioactive scaffolds and stem cells is a promising method for bone regeneration and repair. Canonical Wnt and HIF-1 α signaling pathways are vital for BMSCs' osteogenic differentiation and secretion of osteogenic factors, respectively. Simultaneously, lithium (Li) and copper (Cu) can activate the canonical Wnt and HIF-1 α signaling pathway, respectively. Moreover, emerging evidence has shown that the canonical Wnt and HIF signaling pathways are related to coupling osteogenesis and angiogenesis. However, it is still unclear whether the lithium- and copper-doped bioactive scaffold can induce the coupling of the osteogenesis and angiogenesis in BMSCs and the underlying mechanism. So, we fabricated a lithium- (Li + -) and copper- (Cu 2+ -) doped organic/inorganic (Li 2.5-Cu 1.0-HA/Col) scaffold to evaluate the coupling osteogenesis and angiogenesis effects of lithium and copper on BMSCs and further explore its mechanism. We investigated that the sustained release of lithium and copper from the Li 2.5-Cu 1.0-HA/Col scaffold could couple the osteogenesis- and angiogenesis-related factor secretion in BMSCs seeding on it. Moreover, our results showed that 500  μ M Li + could activate the canonical Wnt signaling pathway and rescue the XAV-939 inhibition on it. In addition, we demonstrated that the 25  μ M Cu 2+ was similar to 1% oxygen environment in terms of the effectiveness of activating the HIF-1 α signaling pathway. More importantly, the combination stimuli of Li + and Cu 2+ could couple the osteogenesis and angiogenesis process and further upregulate the osteogenesis- and angiogenesis-related gene expression via crosstalk between the canonical Wnt and HIF-1 α signaling pathway. In conclusion, this study revealed that lithium and copper could crosstalk between the canonical Wnt and HIF-1 α signaling pathways to couple the osteogenesis and angiogenesis in BMSCs when they are sustainably released from the Li-Cu-HA/Col scaffold., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2021 Zhen Tan et al.)