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Li Yansong,Jiang Tao,Du Mengyu,He Shuxuan,Ning Huang,Cheng Bo,Yan Chaoying,Tang Wenxin,Gao Wei,Guo Hongyan,Li Qiao,Wang Qiang 생화학분자생물학회 2023 Experimental and molecular medicine Vol.55 No.-
Dementia, as an advanced diabetes-associated cognitive dysfunction (DACD), has become the second leading cause of death among diabetes patients. Given that little guidance is currently available to address the DACD process, it is imperative to understand the underlying mechanisms and screen out specific therapeutic targets. The excessive endogenous fructose produced under high glucose conditions can lead to metabolic syndrome and peripheral organ damage. Although generated by the brain, the role of endogenous fructose in the exacerbation of cognitive dysfunction is still unclear. Here, we performed a comprehensive study on leptin receptor-deficient T2DM mice and their littermate m/m mice and revealed that 24-week-old db/db mice had cognitive dysfunction and excessive endogenous fructose metabolism in the hippocampus by multiomics analysis and further experimental validation. We found that the rate-limiting enzyme of fructose metabolism, ketohexokinase, is primarily localized in microglia. It is upregulated in the hippocampus of db/db mice, which enhances mitochondrial damage and reactive oxygen species production by promoting nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) expression and mitochondrial translocation. Inhibiting fructose metabolism via ketohexokinase depletion reduces microglial activation, leading to the restoration of mitochondrial homeostasis, recovery of structural synaptic plasticity, improvement of CA1 pyramidal neuron electrophysiology and alleviation of cognitive dysfunction. Our findings demonstrated that enhanced endogenous fructose metabolism in microglia plays a dominant role in diabetes-associated cognitive dysfunction and could become a potential target for DACD.
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Fuxi Li,Junzhao Ye,Yanhong Sun,Yansong Lin,Tingfeng Wu,Congxiang Shao,Qianqian Ma,Xianhua Liao,Shiting Feng,Bihui Zhong 대한당뇨병학회 2021 Diabetes and Metabolism Journal Vol.45 No.3
Background: Excessive delivery of free fatty acids (FFAs) to the liver promotes steatosis and insulin resistance (IR), with IR defined as reduced glucose uptake, glycogen synthesis and anti-lipolysis stimulated by normal insulin levels. Whether the associations between FFAs and diabetes development differ between patients with and without nonalcoholic fatty liver disease (NAFLD) remains unclear. Methods: Consecutive subjects (2,220 NAFLD subjects and 1,790 non-NAFLD subjects according to ultrasound imaging) were enrolled from the First Affiliated Hospital of Sun Yat-sen University between 2009 and 2019. The homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. Results: There was an approximate J-shaped relationship between FFA levels and HOMA-IR in the NAFLD group. Higher FFA concentration quartiles were associated with higher risks of IR (odds ratio [OR], 9.24; 95% confidence interval [CI], 6.43 to 13.36), prediabetes (OR, 10.48; 95% CI, 5.66 to 19.39), and type 2 diabetes mellitus (T2DM; OR, 19.43; 95% CI, 12.75 to 29.81) in the NAFLD group but not in the non-NAFLD group. The cut-off points for the FFA levels increased in a stepwise manner in discriminating IR, prediabetes and T2DM (573, 697, and 715 μmol/L) in the NAFLD group but not in non-NAFLD individuals. Conclusion: A distinct dose-dependent relationship of FFA levels was found with IR, prediabetes and T2DM in NAFLD patients. Screening serum FFA levels in NAFLD patients would be valuable in preventing diabetes development.
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Feng, Wenjie,Li, Yansong,Ren, DeLiang Techno-Press 2006 Structural Engineering and Mechanics, An Int'l Jou Vol.23 No.2
In this paper, the dynamic response of a piezoelectric layer with a penny-shaped crack is investigated. The piezoelectric layer is subjected to an axisymmetrical action of both mechanical and electrical impacts. Two kinds of crack surface conditions, i.e., electrically impermeable and electrically permeable, are adopted. Based upon integral transform technique, the crack boundary value problem is reduced to a system of Fredholm integral equations in the Laplace transform domain. By making use of numerical Laplace inversion the time-dependent dynamic stress and electric displacement intensity factors are obtained, and the dynamic energy release rate is further derived. Numerical results are plotted to show the effects of both the piezoelectric layer thickness and the electrical impact loadings on the dynamic fracture behaviors of the crack tips.
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Xinbo Wang,Mingyu Tang,Yuming Zhang,Yansong Li,Jingdong Mao,Qinghua Deng,Shusen Li,Zhenwei Jia,Liyin Du 대한수의학회 2022 Journal of Veterinary Science Vol.23 No.5
Background: Clinical dexamethasone (DEX) treatment or stress in bovines results in extensive physiological changes with prominent hyperglycemia and neutrophils dysfunction. Objectives: To elucidate the effects of DEX treatment in vivo on cellular energy status and the underlying mechanism in circulating neutrophils. Methods: We selected eight-month-old male bovines and injected DEX for 3 consecutive days (1 time/d). The levels of glucose, total protein (TP), total cholesterol (TC), and the proinflammatory cytokines interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α in blood were examined, and we then detected glycogen and adenosine triphosphate (ATP) content, phosphofructosekinase-1 (PFK1) and glucose-6-phosphate dehydrogenase (G6PDH) activity, glucose transporter (GLUT)1, GLUT4, sodium/glucose cotransporter (SGLT)1 and citrate synthase (CS) protein expression and autophagy levels in circulating neutrophils. Results: DEX injection markedly increased blood glucose, TP and TC levels, the Ca2+/P5+ ratio and the neutrophil/lymphocyte ratio and significantly decreased blood IL-1β, IL-6 and TNF-α levels. Particularly in neutrophils, DEX injection inhibited p65-NFκB activation and elevated glycogen and ATP contents and SGLT1, GLUT1 and GR expression while inhibiting PFK1 activity, enhancing G6PDH activity and CS expression and lowering cell autophagy levels. Conclusions: DEX induced neutrophils glucose uptake by enhancing SGLT1 and GLUT1 expression and the transformation of energy metabolism from glycolysis to pentose phosphate pathway (PPP)-tricarboxylic acid (TCA) cycle. This finding gives us a new perspective on deeper understanding of clinical anti-inflammatory effects of DEX on bovine.
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Yan Song,Jingcheng Wang,Yuanhao Shi,Chuang Li 제어·로봇·시스템학회 2011 International Journal of Control, Automation, and Vol.9 No.5
This paper is concerned with H_∞ control of networked control systems (NCSs) with both network-induced delay and packet disordering taken into account. A switching-based method depends on different cases of prediction numbers is presented to model the NCSs as a switched system. With the application of an improved prediciton-based method to compensate for the time delay and packet disordering, H_∞ controller is designed by solving the linear matrix inequalities (LMIs). The proposed method can be applied variously due to all kinds of prediciton numbers of the consective disordering packet have been considered, which means that our techniques are less conservative than existing lit-eratures. Finally numerical examples and simulations are used to illustrate the effectiveness and valid-ity of the proposed switching-based method and the improved prediction-based H∞ controller design synthesis.
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