Hypoxia activates macrophage-NLRP3 inflammasome promoting atherosclerosis via PFKFB3-driven glycolysis.

The onset and progression of atherosclerosis are closely linked to the involvement of macrophages. While the contribution of NLRP3 inflammasome activation to the creation of a local highly inflammatory microenvironment is well recognized, the precise triggers remain unclear. In this study, we aimed to investigate the regulatory mechanism of NLRP3 inflammasome activation in response to hypoxia-induced glycolysis involving PFKFB3 in the development of atherosclerosis. To develop an atherosclerosis model, we selected ApoE knockout mice treated with a high-fat western diet. We then quantified the expression of HIF-1α, PFKFB3, and NLRP3. In addition, we administered the PFKFB3 inhibitor PFK158 during atherosclerosis modeling. The glycolytic activity was subsequently determined through 18F-FDG micro-PET/CT, ex vivo glucose uptake, and ECAR analysis. Furthermore, we employed lipopolysaccharide (LPS) and TNF-α to induce the differentiation of bone marrow-derived macrophages (BMDMs) into M1-like phenotypes under both hypoxic and normoxic conditions. Our histological analyses revealed the accumulation of PFKFB3 in human atherosclerotic plaques, demonstrating colocalization with NLRP3 expression and macrophages. Treatment with PFK158 reduced glycolytic activity and NLRP3 inflammasome activation, thereby mitigating the occurrence of atherosclerosis. Mechanistically, hypoxia promoted glycolytic reprogramming and NLRP3 inflammasome activation in BMDMs. Subsequent blocking of either HIF-1α or PFKFB3 downregulated the NLRP3/Caspase-1/IL-1ß pathway in hypoxic BMDMs. Our study demonstrated that the HIF-1α/PFKFB3/NLRP3 axis serves as a crucial mechanism for macrophage inflammation activation in the emergence of atherosclerosis. The therapeutic potential of PFKFB3 inhibition may represent a promising strategy for atheroprotection.

Study on heat transfer law of moving temperature variable gas in thermoacoustic plate stack.

Taking gas and the heat transfer process between gas and plate as the research object, the mathematical model of heat transfer in one working cycle by moving variable temperature air mass under the action of sound field is established, which provides a new idea for understanding thermoacoustic effect. The influence factors in the model are analyzed and it is found that the amplitude of the air mass has a significant influence on the heat transfer, and the heat transfer of the air mass in one working cycle is proportional to the square of the amplitude. In a certain working environment, the thermoacoustic refrigerator has a critical operating frequency, and only when the operating frequency is greater than the critical frequency can refrigeration be realized. The critical operating frequency is independent of the amplitude and increases with the increase of the stack temperature gradient. With the pressure belly point as the reference position, the greater the distance from the reference position, the greater the critical operating frequency. On this basis, the idea of short plate overlapping is put forward and the formation mechanism of temperature difference between two ends of plate overlapping is explained.

Research on the development strategy selection of the new energy vehicle industry from the perspective of green credit-Based on the foursquare evolutionary game analysis.

Developing new energy vehicles is vital to promote green development and the harmonious coexistence of humans and nature. It is also the only way to help China move from a significant automobile country to a powerful automobile country. Based on the background of the "recession" of government subsidies and considering the importance of green credit in promoting green and low-carbon transformation, this paper constructs a four-party evolutionary game model that includes government, automotive companies, banks, and consumers to analyze the stability of the strategic choices of various parties in the development process of the new energy vehicle industry. It uses MATLAB simulation tools to analyze the impact of relevant factors on system stability. The research shows that: (1) The government's subsidy mechanism significantly promotes the development of the new energy vehicle industry. Still, there is a subsidy threshold, beyond which the effect will weaken and quickly bring financial pressure. (2) With the gradual decline of government subsidies, the bank's green credit policy has a specific policy complementary effect on the decline of government subsidies. (3) Considering that costs and benefits are the main influencing factors for automotive companies and consumers' strategic choices, the impact of factors such as the punishment of violations, adjustment of subsidy policies, and consumers' environmental awareness must also be paid attention to.