Search

Objective·Transcriptomic and lipidomic analysis techniques were used to investigate the role of transient receptor potential vanilloid type 1 (TRPV1) channel activation in the regulation of high-fat diet-induced microglial metabolism.Methods·Eight-week-old C57BL/6J mice (WT) and Trpv1-/- (KO) mice were used as experimental animals, and fed high-fat diet (HFD) for 3 days, 7 days, and 8 weeks to induce modelling (WT and KO groups, n = 3; WT-HFD and KO-HFD groups, n = 4). TRPV1 channel expression and cellular localisation were measured by immunofluorescence in the brains of mice in the WT-HFD and KO-HFD group. RNA sequencing and liquid chromatography-mass spectrometry were performed to determine the brain phenotype of mice in the WT-HFD and KO-HFD groups.Results·The expression level of Trpv1 mRNA in microglia was significantly increased in mice in the WT-HFD group compared to mice in the WT group. The expression levels of genes related to brain lipid metabolism, mitochondrial function, glucose transfer, and glycolysis were down-regulated in the KO-HFD group of mice compared with the WT-HFD group of mice. Lipidomic analysis showed that although lipids accumulated in the brain tissue of mice in the KO-HFD group, Trpv1 knockdown attenuated HFD-induced microglia activation, and in addition the TRPV1 agonist capsaicin attenuated palmitate-induced depolarisation of mitochondrial membrane potential in vitro.Conclusion·Together, these findings suggest that TRPV1 regulates lipid and glucose metabolism in microglia via fuel availability driven by a mitochondrial mechanism.

The assessment findings are given too much weight in the current system of evaluation for physical education instruction at higher education institutions. In contrast, the method of teaching and students’ basic health literacy are given insufficient weight. To address this phenomenon, this paper utilizes educational evaluation theory, fuzzy comprehensive evaluation theory, and multiple evaluation theory as the basis for setting up the higher education institution’s physical education teaching assessment system. Three first-level indexes comprise the entire index system, namely, “condition quality,” “process quality,” and “result quality.” Through fuzzy comprehensive evaluation, hierarchical analysis, and genetic algorithm, it is determined that the “process quality” is the most important factor. The “process quality” has the highest weight coefficient of 0.4419, which enhances the importance of the physical education teaching process in higher education institutions. After determining the evaluation index system, the average physical education scores of X physical education classes in University H were calculated by conventional teaching evaluation means and the evaluation means established in this paper, respectively, and compared and analyzed. The difference between the two final average scores was 2.9, which was attributed to the fact that the multivariate evaluation means paying more attention to the core literacy of students’ health. The standard deviation of the statistical results is 2.3, and the skewness, kurtosis, and S-W test values meet the statistical requirements and satisfy the normal distribution, which is thorough and scientific and can encourage academic institutions to pay more focus on how they teach and students’ fundamental physical literacy. These institutions can enhance their instruction by implementing the evaluation system established in this paper, which will improve the quality of instruction and learning in higher education sports.

The microenvironment mediated by the microglia (MG) M1/M2 phenotypic switch plays a decisive role in the neuronal fate and cognitive function of Alzheimer's disease (AD). However, the impact of metabolic reprogramming on microglial polarization and its underlying mechanism remains elusive. This study reveals that cordycepin improved cognitive function and memory in APP/PS1 mice, as well as attenuated neuronal damage by triggering MG‐M2 polarization and metabolic reprogramming characterized by increased OXPHOS and glycolysis, rather than directly protecting neurons. Simultaneously, cordycepin partially alleviates mitochondrial damage in microglia induced by inhibitors of OXPHOS and glycolysis, further promoting MG‐M2 transformation and increasing neuronal survival. Through confirmation of cordycepin distribution in the microglial mitochondria via mitochondrial isolation followed by HPLC‐MS/MS techniques, HKII and PDK2 are further identified as potential targets of cordycepin. By investigating the effects of HKII and PDK2 inhibitors, the mechanism through which cordycepin targeted HKII to elevate ECAR levels in the glycolysis pathway while targeting PDK2 to enhance OCR levels in PDH‐mediated OXPHOS pathway, thereby inducing MG‐M2 polarization, promoting neuronal survival and exerting an anti‐AD role is elucidated. [ABSTRACT FROM AUTHOR]

One medical challenge in studying the amyloid-β (Aβ) peptide mechanism for Alzheimer's disease (AD) is exploring the law of beta toxic oligomers' diffusion in human brains in vivo. One beneficial means of solving this problem is brain network analysis based on graph theory. In this study, the characteristics of Aβ functional brain networks of Healthy Control (HC), Mild Cognitive Impairment (MCI), and AD groups were compared by applying graph theoretical analyses to Carbon 11-labeled Pittsburgh compound B positron emission tomography (11C PiB-PET) data. 120 groups of PiB-PET images from the ADNI database were analyzed. The results showed that the small-world property of MCI and AD were lost as compared to HC. Furthermore, the local clustering of networks was higher in both MCI and AD as compared to HC, whereas the path length was similar among the three groups. The results also showed that there could be four potential Aβ toxic oligomer seeds: Frontal_Sup_Medial_L, Parietal_Inf_L, Frontal_Med_Orb_R, and Parietal_Inf_R. These four seeds are corresponding to Regions of Interests referred by physicians to clinically diagnose AD.

Research on the mechanical properties of structure–soil interfaces is of great significance to engineering construction in the South China Sea. In this work, an interfacial cyclic shear test between steel and calcareous sand was carried out using self-developed shear equipment, and the macroscopic shear characteristics and particle breakage characteristics were analysed. The results showed that the interfacial peak shear stress under constant stiffness showed more significant weakening characteristics than under constant stress. The calcareous sand showed regular shear shrinkage and dilatancy in a single cycle and was continuously compressed with the number of cycles. The position of the shear stress–normal stress curve moved in the direction of low normal stress with the number of cycles. Under the condition of constant stiffness, the interfacial friction angle at 200kPa increased with the number of cycles, but showed the opposite rule at 1100kPa. The interface shear stiffness under constant stress first decreased and then increased with the number of cycles, while it always decreased under constant stiffness. The relative crushing value increased with the number of cycles; however, the increasing range gradually decreased, and obvious fracture was observed on the surfaces of the broken particles. [ABSTRACT FROM AUTHOR]