Search

Background: Hyperglycemia‐induced neuroinflammation significantly contributes to diabetic neuropathic pain (DNP), but the underlying mechanisms remain unclear. Objective: To investigate the role of Sirt3, a mitochondrial deacetylase, in hyperglycemia‐induced neuroinflammation and DNP and to explore potential therapeutic interventions. Method and Results: Here, we found that Sirt3 was downregulated in spinal dorsal horn (SDH) of diabetic mice by RNA‐sequencing, which was further confirmed at the mRNA and protein level. Sirt3 deficiency exacerbated hyperglycemia‐induced neuroinflammation and DNP by enhancing microglial aerobic glycolysis in vivo and in vitro. Overexpression of Sirt3 in microglia alleviated inflammation by reducing aerobic glycolysis. Mechanistically, high‐glucose stimulation activated Akt, which phosphorylates and inactivates FoxO1. The inactivation of FoxO1 diminished the transcription of Sirt3. Besides that, we also found that hyperglycemia induced Sirt3 degradation via the mitophagy‐lysosomal pathway. Blocking Akt activation by GSK69093 or metformin rescued the degradation of Sirt3 protein and transcription inhibition of Sirt3 mRNA, which substantially diminished hyperglycemia‐induced inflammation. Metformin in vivo treatment alleviated neuroinflammation and diabetic neuropathic pain by rescuing hyperglycemia‐induced Sirt3 downregulation. Conclusion: Hyperglycemia induces metabolic reprogramming and inflammatory activation in microglia through the regulation of Sirt3 transcription and degradation. This novel mechanism identifies Sirt3 as a potential drug target for treating DNP. [ABSTRACT FROM AUTHOR]

Summary: This paper investigates the event‐triggered output feedback control problem for the two‐time‐scale systems with structured uncertainty. Due to the non‐ignorable problem in applications such as equipment aging or parameter drifting, the robustness of the designed controller is worth discussing. A dynamic event‐triggered scheme is proposed to reduce the computational cost of the control signal. The results indicate that with the proposed event‐triggered controller, the system can achieve asymptotic stability without some common restrictions on the fast system rather than practical stability. Moreover, the Zeno behavior is excluded. Simulation examples with comparison studies illustrate the effectiveness of the proposed method. [ABSTRACT FROM AUTHOR]

The pro‐inflammatory phenotype of microglia usually induces neuroinflammatory reactions in neuropathic pain. Glycometabolism shift to glycolysis can promote the pro‐inflammatory phenotype transition of microglia. The omics data analysis suggest a critical role for Lyn dysregulation in neuropathic pain. The present study aimed at exploring the mechanism of Lyn‐mediated glycolysis enhancement of microglia in neuropathic pain. Neuropathic pain model was established by chronic constriction injury (CCI), then pain thresholds and Lyn expression were measured. Lyn inhibitor Bafetinib and siRNA‐lyn knockdown were administrated intrathecally to evaluate the effects of Lyn on pain thresholds, glycolysis and interferon regulatory factor 5 (IRF5) nuclear translocation of microglia in vivo and in vitro. ChIP was carried out to observe the binding of transcription factors SP1, PU.1 to glycolytic gene promoters by IRF5 knockdown. Finally, the relationship between glycolysis and pro‐inflammatory phenotype transition of microglia was evaluated. CCI led to the upregulation of Lyn expression and glycolysis enhancement in microglia of spinal dorsal horn. Bafetinib or siRNA‐lyn knockdown intrathecally alleviated pain hyperalgesia, suppressed glycolysis enhancement and inhibited nuclear translocation of IRF5 in CCI mice. Also, IRF5 promoted the binding of transcription factors SP1, PU.1 to glycolytic gene promoters, and then the enhanced glycolysis facilitated the proliferation and pro‐inflammatory phenotype transition of microglia and contributed to neuropathic pain. Lyn‐mediated glycolysis enhancement of microglia contributes to neuropathic pain through facilitating IRF5 nuclear translocation in spinal dorsal horn. [ABSTRACT FROM AUTHOR]

In this paper, we consider event‐triggered control for linear singularly perturbed systems. A composite event‐triggered controller is proposed based on the decoupled slow and fast subsystems which are triggered simultaneously. Two internal dynamic variables are introduced in the event‐triggered mechanism. The results indicate that the systems can achieve asymptotic stability with the proposed event‐triggered control. In addition, the triggering time intervals have a finite lower bound independent of the initial states, thus Zeno phenomenon is excluded. The efficiency of the approach is illustrated through simulation examples. [ABSTRACT FROM AUTHOR]

Glycerophospholipids (GPs) and sphingolipids (SPs) are important lipid components in the body and play biological functions. Omega‐3 polyunsaturated fatty acids (n‐3 PUFAs) are important nutrients, and their supplements are commonly used for preventing some diseases. However, the effect of n‐3 PUFAs on the human glycerophospholipidome and sphingolipidome is unclear. We used targeted lipidomics to study the GP and SP profile of healthy individuals after supplementation with n‐3 PUFAs for 3, 7, 14 and 21 days. Fuzzy c‐means clustering was used to cluster the lipid species into six classes reflecting different changed‐content patterns after n‐3 PUFA supplementation. Among the species with significantly changed content, lysophospholipids were the most sensitive; their content started to increase on day 3. The content of phosphatidylserines increased at a later stage. The content of most of the phosphatidylcholines and alkylphosphatidylcholines decreased on day 21. A correlation network analysis of lipid species suggested that some enzymes involved in the metabolism of lysophospholipids and phosphatidylserines were regulated by n‐3 PUFAs. Levels of creatine kinase‐MB (CK‐MB), urea, glucose, triglycerides and total bilirubin were altered by n‐3 PUFA at 21 days. Correlation analysis revealed that the level of CK‐MB was negatively correlated with those of species in lysophosphatidic acid, lysophosphatidylcholine, lysophosphatidylethanolamine and phosphatidylserine classes, which were increased by n‐3 PUFA supplementation. With the analysis in this work, we demonstrated the regular pattern of n‐3 PUFAs on GP and SP metabolism, which provides a pharmacological basis for n‐3 PUFAs for clinical application. [ABSTRACT FROM AUTHOR]

Pre‐eclampsia (PE) is considered a leading cause of mortality and morbidity in pregnant women worldwide. Eicosanoids derived from polyunsaturated fatty acids (PUFAs) might play an important role in the occurrence and development of PE. Omega‐3 PUFAs are nutrients that are popular supplements for pregnant women and can reduce blood pressure. However, the levels of eicosanoids derived from omega‐3 PUFAs in women with PE is not clear. The purpose of this study was to investigate the eicosanoid metabolic signature of PE. We performed a case–control study using data for pregnant women (n = 10) with PE and normotensive pregnant women (n = 10). We investigated the difference in eicosanoid profile between the groups by LC‐MS/MS‐based metabolomics. The plasma levels of arachidonic acid metabolites and some of the lipoxygenase metabolites of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) showed an increasing trend, and those of the cytochrome P450 metabolites of EPA and DHA were decreased in women with PE. Levels of leukotriene B4, 14,15‐dihydroxy‐eicosatetraenoate, 16‐hydroxydocosahexaenoic acid and 8,9‐epoxy eicosatetraenoic acid were significantly correlated with PE occurrence. These eicosanoids might take part in the progression of PE in pregnant women. [ABSTRACT FROM AUTHOR]

The article discusses a study which investigated a novel integration process of a microbial fuel cell (MFC) into a sequencing batch reactor (SBR) to determine the energy production and the removal of the chemical oxygen demand (COD) for energy-saving wastewater treatment. It provides an overview of the use of activated sludge process for biological wastewater treatment. The development of membrane-less MFC is described using non-woven cloth. Also determined is the generation of electricity of the biocathode MFC.

The bimetallic title complex, [CuFe(CN)5(C12H30N6O2)(NO)] or [Cu(L)Fe(CN)5(NO)] [where L is 1,8-bis(2-hydroxyethyl)1,3,6,8,10,13-hexaazacyclotetradecane], has a one-dimensional zigzag polymeric -Cu(L)-NC-Fe(NO)(CN)3-CN-Cu(L)-chain, in which the CuII and FeII centres are linked by two CN groups. In the complex, the CuII ion is coordinated by four N atoms from the L ligand [Cu-N(L) = 1.999 (2)2.016 (2) Å] and two cyanide N atoms [Cu-N = 2.383 (2) and 2.902 (3) Å], and has an elongated octahedral geometry. The FeII centre is in a distorted octahedral environment, with Fe-N(nitroso) = 1.656 (2) Å and Fe-C(CN) = 1.938 (3)1.948 (3) Å. The one-dimensional zigzag chains are linked to form a three-dimensional network via N-H···N and OH···N hydrogen bonds. [ABSTRACT FROM AUTHOR]

The title binuclear complex, [CuFe(CN)5(C8H21N5O2)(NO)]·2H2O or [CuFe(nelin)(CN)5(NO)]·2H2O (nelin is 5-methyl-5-nitro-3,7-di­aza­nonane-1,9-di­amine) consists of discrete binuclear mixed-metal species, with a Cu centre linked to an Fe centre through a cyano bridge, and two water mol­ecules of crystallization. In the complex, the CuII ion is coordinated by five N atoms and has a distorted square-pyramidal geometry. The FeII centre is in a distorted octahedral environment. [ABSTRACT FROM AUTHOR]

The bimetallic title complex, [CuFe(CN)(5)(C(12)H(30)N(6)O(2))(NO)] or [Cu(L)Fe(CN)(5)(NO)] [where L is 1,8-bis(2-hydroxyethyl)-1,3,6,8,10,13-hexaazacyclotetradecane], has a one-dimensional zigzag polymeric -Cu(L)-NC-Fe(NO)(CN)(3)-CN-Cu(L)- chain, in which the Cu(II) and Fe(II) centres are linked by two CN groups. In the complex, the Cu(II) ion is coordinated by four N atoms from the L ligand [Cu-N(L) = 1.999 (2)-2.016 (2) A] and two cyanide N atoms [Cu-N = 2.383 (2) and 2.902 (3) A], and has an elongated octahedral geometry. The Fe(II) centre is in a distorted octahedral environment, with Fe-N(nitroso) = 1.656 (2) A and Fe-C(CN) = 1.938 (3)-1.948 (3) A. The one-dimensional zigzag chains are linked to form a three-dimensional network via N-H.N and O-H.N hydrogen bonds.

The title binuclear complex, [CuFe(CN)(5)(C(8)H(21)N(5)O(2))(NO)] x 2H(2)O or [CuFe(nelin)(CN)(5)(NO)] x 2H(2)O (nelin is 5-methyl-5-nitro-3,7-diazanonane-1,9-diamine) consists of discrete binuclear mixed-metal species, with a Cu centre linked to an Fe centre through a cyano bridge, and two water molecules of crystallization. In the complex, the Cu(II) ion is coordinated by five N atoms and has a distorted square-pyramidal geometry. The Fe(II) centre is in a distorted octahedral environment.