Energy harvesting from water streaming at charged surface.

Water flowing at a charged surface may produce electricity, known as streaming current/potentials, which may be traced back to the 19th century. However, due to the low gained power and efficiencies, the energy conversion from streaming current was far from usable. The emergence of micro/nanofluidic technology and nanomaterials significantly increases the power (density) and energy conversion efficiency. In this review, we conclude the fundamentals and recent progress in electrical double layers at the charged surface. We estimate the generated power by hydrodynamic energy dissipation in multi-scaling flows considering the viscous systems with slipping boundary and inertia systems. Then, we review the coupling of volume flow and current flow by the Onsager relation, as well as the figure of merits and efficiency. We summarize the state-of-the-art of electrokinetic energy conversions, including critical performance metrics such as efficiencies, power densities, and generated voltages in various systems. We discuss the advantages and possible constraints by the figure of merits, including single-phase flow and flying droplets.

Lentinan has a beneficial effect on cognitive deficits induced by chronic Toxoplasma gondii infection in mice.

BACKGROUND: Toxoplasma gondii (T. gondii) is increasingly considered a risk factor for neurodegenerative diseases. However, there is only limited information on the development of drugs for T. gondii infection. Lentinan from Lentinula edodes is a bioactive ingredient with the potential to enhance anti-infective immunity. The present study aimed to investigate the neuroprotective effect of lentinan on T. gondii-associated cognitive deficits in mice. METHODS: A chronic T. gondii infection mouse model was established by administering 10 cysts of T. gondii by gavage. Lentinan was intraperitoneally administered 2 weeks before infection. Behavioral tests, RNA sequencing, immunofluorescence, transmission electron microscopy and Golgi-Cox staining were performed to assess the effect of lentinan on cognitive deficits and neuropathology in vivo. In vitro, the direct and indirect effects of lentinan on the proliferation of T. gondii tachyzoites were evaluated in the absence and presence of BV-2 cells, respectively. RESULTS: Lentinan prevented T. gondii-induced cognitive deficits and altered the transcriptome profile of genes related to neuroinflammation, microglial activation, synaptic function, neural development and cognitive behavior in the hippocampus of infected mice. Moreover, lentinan reduced the infection-induced accumulation of microglia and downregulated the mRNA expression of proinflammatory cytokines. In addition, the neurite and synaptic ultrastructural damage in the hippocampal CA1 region due to infection was ameliorated by lentinan administration. Lentinan decreased the cyst burden in the brains of infected mice, which was correlated with behavioral performance. In line with this finding, lentinan could significantly inhibit the proliferation of T. gondii tachyzoites in the microglial cell line BV2, although lentinan had no direct inhibitory effect on parasite growth. CONCLUSIONS: Lentinan prevents cognitive deficits via the improvement of neurite impairment and synaptic loss induced by T. gondii infection, which may be associated with decreased cyst burden in the brain. Overall, our findings indicate that lentinan can ameliorate T. gondii-related neurodegenerative diseases.

Dimethyl itaconate ameliorates the deficits of goal-directed behavior in Toxoplasma gondii infected mice.

BACKGROUND: The neurotrophic parasite Toxoplasma gondii (T. gondii) has been implicated as a risk factor for neurodegenerative diseases. However, there is only limited information concerning its underlying mechanism and therapeutic strategy. Here, we investigated the effects of T. gondii chronic infection on the goal-directed cognitive behavior in mice. Moreover, we evaluated the preventive and therapeutic effect of dimethyl itaconate on the behavior deficits induced by the parasite. METHODS: The infection model was established by orally infecting the cysts of T. gondii. Dimethyl itaconate was intraperitoneally administered before or after the infection. Y-maze and temporal order memory (TOM) tests were used to evaluate the prefrontal cortex-dependent behavior performance. Golgi staining, transmission electron microscopy, indirect immunofluorescence, western blot, and RNA sequencing were utilized to determine the pathological changes in the prefrontal cortex of mice. RESULTS: We showed that T. gondii infection impaired the prefrontal cortex-dependent goal-directed behavior. The infection significantly downregulated the expression of the genes associated with synaptic transmission, plasticity, and cognitive behavior in the prefrontal cortex of mice. On the contrary, the infection robustly upregulated the expression of activation makers of microglia and astrocytes. In addition, the metabolic phenotype of the prefrontal cortex post infection was characterized by the enhancement of glycolysis and fatty acid oxidation, the blockage of the Krebs cycle, and the disorder of aconitate decarboxylase 1 (ACOD1)-itaconate axis. Notably, the administration of dimethyl itaconate significantly prevented and treated the cognitive impairment induced by T. gondii, which was evidenced by the improvement of behavioral deficits, synaptic ultrastructure lesion and neuroinflammation. CONCLUSION: The present study demonstrates that T. gondii infection induces the deficits of the goal-directed behavior, which is associated with neuroinflammation, the impairment of synaptic ultrastructure, and the metabolic shifts in the prefrontal cortex of mice. Moreover, we report that dimethyl itaconate has the potential to prevent and treat the behavior deficits.

Dimethyl itaconate ameliorates cognitive impairment induced by a high-fat diet via the gut-brain axis in mice.

BACKGROUND: Gut homeostasis, including intestinal immunity and microbiome, is essential for cognitive function via the gut-brain axis. This axis is altered in high-fat diet (HFD)-induced cognitive impairment and is closely associated with neurodegenerative diseases. Dimethyl itaconate (DI) is an itaconate derivative and has recently attracted extensive interest due to its anti-inflammatory effect. This study investigated whether intraperitoneal administration of DI improves the gut-brain axis and prevents cognitive deficits in HF diet-fed mice. RESULTS: DI effectively attenuated HFD-induced cognitive decline in behavioral tests of object location, novel object recognition, and nesting building, concurrent with the improvement of hippocampal RNA transcription profiles of genes associated with cognition and synaptic plasticity. In agreement, DI reduced the damage of synaptic ultrastructure and deficit of proteins (BDNF, SYN, and PSD95), the microglial activation, and neuroinflammation in the HFD-fed mice. In the colon, DI significantly lowered macrophage infiltration and the expression of pro-inflammatory cytokines (TNF-α, IL-1ß, IL-6) in mice on the HF diet, while upregulating the expression of immune homeostasis-related cytokines (IL-22, IL-23) and antimicrobial peptide Reg3γ. Moreover, DI alleviated HFD-induced gut barrier impairments, including elevation of colonic mucus thickness and expression of tight junction proteins (zonula occludens-1, occludin). Notably, HFD-induced microbiome alteration was improved by DI supplementation, characterized by the increase of propionate- and butyrate-producing bacteria. Correspondingly, DI increased the levels of propionate and butyrate in the serum of HFD mice. Intriguingly, fecal microbiome transplantation from DI-treated HF mice facilitated cognitive variables compared with HF mice, including higher cognitive indexes in behavior tests and optimization of hippocampal synaptic ultrastructure. These results highlight the gut microbiota is necessary for the effects of DI in improving cognitive impairment. CONCLUSIONS: The present study provides the first evidence that DI improves cognition and brain function with significant beneficial effects via the gut-brain axis, suggesting that DI may serve as a novel drug for treating obesity-associated neurodegenerative diseases. Video Abstract.

Polyene phosphatidylcholine ameliorates synovial inflammation: involvement of PTEN elevation and glycolysis suppression.

BACKGROUND: Synovial inflammation, characterized by the activation of synovial fibroblasts (SFs), is a crucial factor to drive the progression of rheumatoid arthritis (RA). Polyene phosphatidylcholine (PPC), the classic hepatoprotective drug, has been reported to ameliorate arthritis in animals. However, the molecular mechanism remains poorly understood. METHODS AND RESULTS: Using in vitro primary synovial fibroblast (SFs) culture system, we revealed that phosphatase and tension homolog deleted on chromosome 10 (PTEN), a tumor suppressor, mediates the anti-inflammatory effect of PPC in lipopolysaccharide (LPS)-stimulated primary SFs. PPC decreased the production of TNF-α and IL-6 production while elevating the level of IL-10 and TGF-ß. Furthermore, PPC up-regulated the expression of PTEN, but inhibited the expression of p-AKT (ser473) and PI3K-p85α. Moreover, pre-treatment of SF1670 (the inhibitor of PTEN) or 740Y-P (the agonist of AKT/PI3K pathways) partially abrogated the anti-inflammatory effect of PPC. In addition, PPC could inhibit the expression of GLUT4, a key transporter of glucose that fuels the glycolysis, which is accompanied by the expression downregualtion of glycolytic enzymes PFKFB3 and PKM2. Furthermore, PPC could reduce ROS production and mitochondrial membrane potential in LPS-stimulated SFs and MH7A cell line. CONCLUSION: The present study supported that PPC can alleviate synovial inflammation, which involves in the elevation of PTEN and blockage of glycolysis.

ß-Glucan ameliorates anxiety-like behavior in mice chronically infected with the Toxoplasma gondii Wh6 strain.

Chronic Toxoplasma gondii (T. gondii) infection has been revealed to be a risk factor for neuropsychiatric diseases, including anxiety. However, there is no intervention strategy. The present study aimed to investigate the protective effect of ß-glucan on T. gondii Wh6 strain-induced anxiety-like behavior in mice. The anxiety mouse model was established by infection with 10 cysts of the T. gondii Wh6 strain. ß-Glucan was intraperitoneally administered 2 weeks before infection. Open field and elevated plus maze tests were performed to assess anxiety-like behavior. In the open field test, Wh6-infected mice spent less time in the central zone and had fewer entries into the central zone. In the elevated plus maze test, the infection reduced the frequency and time of head entries in the open arms. These results showed that Wh6 causes anxiety-like behavior in mice. Interestingly, the administration of ß-glucan significantly ameliorated anxiety-like behavioral performance. The present study shows that ß-glucan can alleviate the anxiety-like behavior induced by chronic T. gondii infection in mice, which indicates that ß-glucan may be a potential drug candidate for treating T. gondii-related mental disorders, including anxiety.

Polyene Phosphatidylcholine Ameliorates High Fat Diet-Induced Non-alcoholic Fatty Liver Disease via Remodeling Metabolism and Inflammation.

Recent years have witnessed a rise in the morbidity of non-alcoholic fatty liver disease (NAFLD), in line with the global outbreak of obesity. However, effective intervention strategy against NAFLD is still unavailable. The present study sought to investigate the effect and mechanism of polyene phosphatidylcholine (PPC), a classic hepatoprotective drug, on NAFLD induced by high fat diet (HFD). We found that PPC intervention reduced the mass of liver, subcutaneous, epididymal, and brown fats in HFD mice. Furthermore, PPC supplementation significantly mitigated liver steatosis and improved glucose tolerance and insulin sensitivity in HFD mice, which was accompanied by declined levels of hepatic triglyceride, serum triglyceride, low density lipoprotein, aspartate aminotransferase, and alanine aminotransferase. Using transcriptome analysis, there were 1,789 differentially expressed genes (| fold change | ≥ 2, P < 0.05) including 893 upregulated genes and 896 downregulated genes in the HFD group compared to LC group. A total of 1,114 upregulated genes and 1,337 downregulated genes in HFD + PPC group were identified in comparison to HFD group. With the help of Gene Ontology (GO) analysis, these differentially expressed genes between HFD+PPC and HFD group were discovered related to "lipid metabolic process (GO: 0006629)," "lipid modification (GO: 0030258)," and "lipid homeostasis (GO: 0055088)". Though Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, we found pathways associated with hepatic homeostasis of metabolism and inflammation. Notably, the pathway "Non-alcoholic fatty liver disease (mmu04932)" (P-value = 0.00698) was authenticated in the study, which may inspire the potential mechanism of PPC to ameliorate NAFLD. The study also found that lipolysis, fatty acid oxidation, and lipid export associated genes were upregulated, while the genes in uptake of lipids and cholesterol synthesis were downregulated in the liver of HFD mice after PPC supplementation. Interestingly, PPC attenuated the metabolic inflammation via inhibiting pro-inflammatory macrophage in the livers of mice fed by HFD. In summary, this study demonstrates that PPC can ameliorate HFD-induced liver steatosis via reprogramming metabolic and inflammatory processes, which inspire clues for further clarifying the intervention mechanism of PPC against NAFLD.

Polyene Phosphatidylcholine Interacting with TLR-2 Prevents the Synovial Inflammation via Inactivation of MAPK and NF-κB Pathways.

Rheumatoid arthritis (RA) is a chronic autoimmune joint disease that causes cartilage and bone damage or even disability, seriously endangering human health. Chronic synovial inflammation has been shown to play a vital role in disease sustainability. Therefore, downregulation of synovial inflammation is considered to be an effective discipline for RA therapy. Polyene phosphatidylcholine (PPC) is a hepatoprotective agent, which was observed to inhibit inflammation in macrophages and prevent collagen-induced arthritis (CIA) of rats in our previous study. However, the underlying mechanism remains unclear. The present study further reported that PPC can inhibit synovial inflammation. In lipopolysaccharide (LPS)-stimulated primary synovial fibroblasts (SFs) of mice, PPC significantly decreased pro-inflammatory cytokines production while increasing anti-inflammatory cytokines level. In this process, PPC downregulated the expression of TLR-2 and their downstream signaling molecules such as MyD88, p-ERK1/2, p-JNK1/2, and p-P38 in MAPK pathway and p-IκBα and NF-κB-p65 in NF-κB pathway. Moreover, the inhibitory effect of PPC on the above molecules and cytokines was weakened after pre-treatment with TLR-2 agonist Pam3CSK4. In addition, PPC lost its anti-inflammatory effect and its suppressing capability on MAPK and NF-κB pathways in TLR-2-/- primary SFs after exposure to LPS. Collectively, this study demonstrated that PPC can alleviate synovial inflammation through TLR-2-mediated MAPK and NF-κB pathways, which can be proposed to be a potential drug candidate for RA prevention.

A metabolite attenuates neuroinflammation, synaptic loss and cognitive deficits induced by chronic infection of Toxoplasma gondii.

Background: Neurodegenerative diseases including AD is currently one of intractable problems globally due to the insufficiency of intervention strategies. Long-term infection of Toxoplasma gondii (T. gondii) can induce cognitive impairment in hosts, which is closely implicated in the pathogenesis of neurodegenerative diseases. Aconitate decarboxylase 1 (Acod1) and its produced metabolite itaconate (termed Acod1/itaconate axis), have recently attracted extensive interests due to its anti-inflammatory role in macrophages. However, whether the axis can influence cognitive function remains unknown. Methods: A chronic T. gondii-infected mice (C57BL/6J) model was established via administration of cysts by gavage. Novel location (NL), novel object recognition (NOR), Y-maze spatial memory and nest building tests were used to evaluate the behavior performance. Transmission electron microscopy, immunofluorescence, RT-PCR, western-blotting and RNA sequencing were utilized to determine the pathological changes, neuroinflammation and transcription profile in hippocampus tissues post infection, respectively. Moreover, the protective effect of Acod1/itaconate axis in T. gondii-induced cognitive deficits was evaluated. Results: We found that the latent infection of the parasite impaired the cognitive function, which was assessed behaviorally by novel location (NL), novel object recognition (NOR), Y-maze spatial memory and nest building tests. RNA sequencing of hippocampus showed that the infection downregulated the expression of genes related to synaptic plasticity, transmission and cognitive behavior. To our attention, the infection robustly upregulated the expression of genes associated with pro-inflammatory responses, which was characterized by microglia activation and disorder of Acod1/itaconate axis. Interestingly, administration of dimethyl itaconate (DI, an itaconate derivative with cell membrane permeability) could significantly ameliorate the cognitive deficits induced by T. gondii, which was proved by improvement of behavior performance and synaptic ultrastructure impairment, and lower accumulation of pro-inflammatory microglia. Notably, DI administration had a potential therapeutic effect on the cognitive deficits and synaptic impairment induced by the parasitic infection. Conclusions: Overall, these findings provide a novel insight for the pathogenesis of T. gondii-related cognitive deficits in hosts, and also provide a novel clue for the potential therapeutic strategies.

Metabolomics Analysis of Splenic CD19+ B Cells in Mice Chronically Infected With Echinococcus granulosus sensu lato Protoscoleces.

Background: The larval stages of Echinococcus granulosus sensu lato (E. granulosus s.l) infection can alter B cell function and affect host anti-infective immunity, but the underlying mechanism remains unclear. The newly emerging immunometabolism highlights that several metabolites are key factors in determining the fate of immune cells, which provides a new insight for exploring how larval E. granulosus s.l. infection remodels B cell function. This study investigated the metabolomic profiles of B cells in mice infected with E. granulosus s.l. protoscoleces (PSC). Results:Total CD19+ B cells, purified from the spleen of infected mice, showed significantly increased production of IL-6, TNF-α, and IL-10 after exposure to LPS in vitro. Moreover, the mRNA expression of metabolism related enzymes in B cells was remarkably disordered post infection. In addition, differential metabolites were identified in B cells after infection. There were 340 differential metabolites (83 upregulated and 257 downregulated metabolites) identified in the positive ion model, and 216 differential metabolites (97 upregulated and 119 downregulated metabolites) identified in the negative ion mode. Among these, 64 differential metabolites were annotated and involved in 68 metabolic pathways, including thyroid hormone synthesis, the metabolic processes of glutathione, fructose, mannose, and glycerophospholipid. Furthermore, several differential metabolites such as glutathione, taurine, and inosine were validated to regulate the cytokine production in LPS stimulated B cells. Conclusion:Infection with the larval E. granulosus s.l. causes metabolic reprogramming in the intrinsic B cells of mice, which provides the first evidence for understanding the role and mechanism of B cells in parasite anti-infective immunity from the viewpoint of immunometabolism.