The dysfunction of glymphatic system suggested why a history of depression may be a strong risk factor for AD in anhedonic mice. We hope our study will contribute to an understanding of the risk mechanism of depressive disorder in the development of AD and the mechanisms of antidepressant therapies in AD.

It is well known that sleep disorders are harmful to people's health and performance, and growing evidence suggests that sleep deprivation (SD) can trigger neuroinflammation in the brain. The nucleotide-binding domain and leucine-rich repeat protein-3 (NLRP3) inflammasome is reported to be relevant to the neuroinflammation induced by SD, but the regulatory signaling that governs the NLRP3 inflammasome in SD is still unknown. Meanwhile, whether the regulatory action of antidepressants in astrocytes could affect the neuroinflammation induced by SD also remains obscure. In this study, we were the first to discover that the antidepressant fluoxetine, a type of specific serotonin reuptake inhibitor widely used in clinical practice, could suppress the neuroinflammation and neuronal apoptosis induced by SD. The main findings from this study are as follows: (i) SD stimulated the expression of activated NLRP3 inflammasomes and the maturation of IL-1β/18 via suppressing the phosphorylation of STAT3 in astrocytes; (ii) SD decreased the activation of AKT and stimulated the phosphorylation of GSK-3β, which inhibited the phosphorylation of STAT3; (iii) the NLRP3 inflammasome expression stimulated by SD was partly mediated by the P2X7 receptor; (iv) an agonist of STAT3 could significantly abolish the expression of NLRP3 inflammasomes induced by an agonist of the P2X7 receptor in primary cultured astrocytes; (v) the administration of fluoxetine could reverse the stimulation of NLRP3 inflammasome expression and function by SD through elevating the activation of STAT3. In conclusion, our present research suggests the promising possibility that fluoxetine could ameliorate the neuronal impairment induced by SD.

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Spinal cord injury (SCI) causes long-term disability and has no clinically effective treatment. After SCI, adenosine triphosphate (ATP) may be released from neuronal cells and astrocytes in large amounts. Our previous studies have shown that the extracellular release of ATP increases the phosphorylation of cytosolic phospholipase A2 (cPLA2 ) and triggers the rapid release of arachidonic acid (AA) and prostaglandin E2 (PGE2) via the stimulation of epidermal growth factor receptor (EGFR) and the downstream phosphorylation of extracellular-regulated protein kinases 1 and 2. Leptin, a glycoprotein, induces the activation of the Janus kinase (JAK2)/signal transducers and activators of transcription-3 (Stat3) pathway via the leptin receptor. In this study, we found that 1) prolonged leptin treatment suppressed the ATP-stimulated release of AA and PGE2 from cultured spinal cord astrocytes; 2) leptin elevated the expression of caveolin-1 (Cav-1) via the JAK2/Stat3 signaling pathway; 3) Cav-1 blocked the interaction between Src and EGFR, thereby inhibiting the phosphorylation of EGFR and cPLA2 and attenuating the release of AA or PGE2; 4) pretreatment with leptin decreased ;he level of apoptosis and the release of interleukin-6 from cocultured neurons and astrocytes; and 5) leptin improved the recovery of locomotion in mice after SCI. Our results highlight leptin as a promising therapeutic agent for SCI. © 2016 Wiley Periodicals, Inc.

Effective fractionation and utilization of the three main components (cellulose, hemicellulose, and lignin) in lignocellulosic biomass give a significant opportunity for commercial operation of a lignocellulosic biorefinery. Herein, we proposed a one-pot method for lignocellulosic biomass (poplar) fractionation by acidic water/phenol pretreatment at mild temperature (120 °C). By this approach, three phases were obtained: water phase containing hemicellulose-derived sugars, phenol phase containing lignin, and cellulose-enriched solid phase. Up to 90% of original lignin was removed with over 96% original cellulose retained in the solid under the optimized conditions (3.5% acid based on biomass weight, 40% phenol content in water/phenol system, 120 °C, and 1 h). Additionally, 77% of original xylan was recovered from the water phase in the form of xylose, while negligible amounts of byproducts (e.g., furfural) formed due to the mild conditions. The pretreated substrate was enzymatically hydrolyzed to glucose, whose digestibility was 2–3 times higher than those obtained using ethanol and dioxane. The lignin, together with the phenol solvent without further separation, was used to prepare lignin-based phenolic foam with satisfactory mechanical and thermal insulation properties. The work highlights a mild one-pot acid-catalyzed pretreatment strategy to separate three main components of lignocellulose, with enhanced processability, so that value-added products can be made, thus providing an effective route for a lignocellulosic biorefinery.

In this work, a mild and efficient process for acid-catalyzed depolymerization of lignin to improve its antioxidant activity was proposed using lignin monomer, p-hydroxybenzyl alcohol (HBA), as a novel capping agent. High molecular weight lignin (HMWL) with high β-O-4 linkage content was used as the feedstock for depolymerization, and the products were further extracted by ethyl acetate to obtain the depolymerized ethyl acetate soluble lignin (DESL) with high antioxidant capacity. Moreover, the mechanism of the promoted depolymerization through the utilization of the capping agent was proposed and verified using a lignin dimer model with a β-O-4 linkage. The results showed that the HBA substantially suppressed lignin condensation and increased the DESL yield. When the HBA dosage was 3 mmol/g lignin, the DESL yield obtained at 150 °C was 51.88%, which was 2.7 times and 1.9 times those obtained at 150 and 210 °C without HBA addition, respectively. Besides, the DPPH· scavenging capacity (IC50, 65.2 μg/mL) of DESL obtained at 150 °C with HBA addition was significantly higher than that obtained without HBA addition (125.7 μg/mL) and was close to that of commercial antioxidant BHT (57.3 μg/mL). Accordingly, this work demonstrates that the acid catalysis process using lignin monomer as a capping agent is effective to produce depolymerized lignin with high antioxidant activity. Furthermore, this study provides new insights for the efficient acid-catalyzed depolymerization of lignin through condensation suppression using lignin monomer as a capping agent.

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