Revealing the role of hydrogen bond coupling structure for enhanced performance of the solid-state electrolyte.

Achieving practical applications of PEO-based composite solid electrolyte (CPE) batteries requires the precise design of filler structures at the molecular level to form stable composite interfacial phases, which in turn improve the conductivity of Li+ and inhibit the nucleation growth of lithium dendrites. Some functional fillers suffer from severe agglomeration due to poor compatibility with the polymer base or grain boundary migration, resulting in limited improvement in cell performance. In this paper, ILs@KAP1 is reported as a filler to enhance the performance of PEO-based batteries. Thereinto, the hypercrosslinked phosphorus ligand polymer-containing KAP1, designed at the molecular level, has an abundant porous structure, hydrogen bonding network, and a rigid skeleton structure of benzene rings. These can be used both to improve the flammability with PEO-based and to reduce the crystallinity of the polymer electrolyte. Ionic liquids (ILs) are encapsulated in the nanochannels of KAP1, and thus a 3D Li+ conducting framework could be formed. In this case, it could not only facilitate the wettability of the contact interface with the electrode, significantly promoting its compatibility and providing a fast Li+ transport path, but also facilitate the formation of LiF, Li3N and Li2O rich SEI components, further fostering the uniform deposition/exfoliation of lithium. The LFP||CPE||Li battery assembled with ILs@KAP1-PEO-CPE has a high initial discharge specific capacity about 156 mAh/g at 1C and a remaining capacity about 121.8 mAh/g after 300 cycles (capacity retention of 78.07%).

LPA1 receptors in the lateral habenula regulate negative affective states associated with alcohol withdrawal.

The role of lysophosphatidic acid (LPA) signaling in psychiatric disorders and drug abuse is significant. LPA receptors are widely expressed in the central nervous system, including the lateral habenula (LHb). Recent studies suggest that LHb is involved in a negative emotional state during alcohol withdrawal, which can lead to relapse. The current study examines the role of LHb LPA signaling in the negative affective state associated with alcohol withdrawal. Adult male Long-Evans rats were trained to consume either alcohol or water for eight weeks. At 48 h of withdrawal, alcohol-drinking rats showed anxiety- and depression-like symptoms, along with a significant increase in LPA signaling and related neuronal activation molecules, including autotaxin (ATX, Enpp2), LPA receptor 1/3 (LPA1/3), ßCaMKII, and c-Fos. However, there was a decrease in lipid phosphate phosphatase-related protein type 4 (LPPR4) in the LHb. Intra-LHb infusion of the LPA1/3 receptor antagonist ki-16425 or PKC-γ inhibitor Go-6983 reduced the abnormal behaviors and elevated relapse-like ethanol drinking. It also normalized high LPA1/3 receptors and enhanced AMPA GluA1 phosphorylation in Ser831 and GluA1/GluA2 ratio. Conversely, selective activation of LPA1/3 receptors by intra-LHb infusion of 18:1 LPA induced negative affective states and upregulated ßCaMKII-AMPA receptor phosphorylation in Naive rats, which were reversed by pretreatment with intra-LHb Go-6983. Our findings suggest that disturbances in LPA signaling contribute to adverse affective disorders during alcohol withdrawal, likely through PKC-γ/ßCaMKII-linked glutamate signaling. Targeting LPA may therefore be beneficial for individuals suffering from alcohol use disorders.

Rostromedial tegmental nucleus nociceptin/orphanin FQ (N/OFQ) signaling regulates anxiety- and depression-like behaviors in alcohol withdrawn rats.

Recent studies indicate that stimulation of the rostromedial tegmental nucleus (RMTg) can drive a negative affective state and that nociceptin/orphanin FQ (N/OFQ) may play a role in affective disorders and drug addiction. The N/OFQ precursor prepronociceptin encoding genes Pnoc are situated in RMTg neurons. To determine whether N/OFQ signaling contributes to the changes in both behavior phenotypes and RMTg activity of alcohol withdrawn (Post-EtOH) rats, we trained adult male Long-Evans rats, randomly assigned into the ethanol and Naïve groups to consume either 20% ethanol or water-only under an intermittent-access procedure. Using the fluorescence in situ hybridization technique combined with retrograde tracing, we show that the ventral tegmental area projecting RMTg neurons express Pnoc and nociceptin opioid peptide (NOP) receptors encoding gene Oprl1. Also, using the laser capture microdissection technique combined with RT-qPCR, we detected a substantial decrease in Pnoc but an increase in Oprl1 mRNA levels in the RMTg of Post-EtOH rats. Moreover, RMTg cFos expression is increased in Post-EtOH rats, which display anxiety- and depression-like behaviors. Intra-RMTg infusion of the endogenous NOP agonist nociceptin attenuates the aversive behaviors in Post-EtOH rats without causing any notable change in Naïve rats. Conversely, intra-RMTg infusion of the NOP selective antagonist [Nphe1]nociceptin(1-13)NH2 elicits anxiety- and depression-like behaviors in Naïve but not Post-EtOH rats. Furthermore, intra-RMTg infusion of nociceptin significantly reduces alcohol consumption. Thus, our results show that the deficiency of RMTg NOP signaling during alcohol withdrawal mediates anxiety- and depression-like behaviors. The intervention of NOP may help those individuals suffering from alcohol use disorders.

Efficient capture and conversion of polysulfides by zinc protoporphyrin framework-embedded triple-layer nanofiber separator for advanced Li-S batteries.

The practical application of Lithium-sulfur (Li-S) batteries is significantly inhibited by (i) the notable 'shuttle effect' of lithium polysulfides (LiPS), (ii) the corrosion of the lithium interface, and (iii) the sluggish redox reaction kinetics. The functional separator in the Li-S battery has the potential to provide the perfect solution to these problems. Herein a triple-layer multifunctional PVDF-based nanofiber separator, which contains GoTiN/PVDF layer on the top and bottom and ZnTPP/PVDF layer on the middle, is designed. The polarity and porous structure of this multifunctional separator can greatly improve the wettability of electrolytes and enhance the transportation of Li+. With the zinc-based porphyrin framework (ZnTPP) structure, this separator has a strong chemisorption and LiPS conversion ability, which greatly prevent the 'shuttle effect'. Consequently, the designed multilayer separator showed excellent electrochemical performance. As a result, the cell with GoTiN@ZnTPP@GoTiN nanofiber membrane displayed an initial discharge capacity of 1180 mAh/g with a benign capacity retention of 65.9% at 0.5C and high coulombic efficiency of more than 98.5% after 100 cycles. Even at 2C, it can still release a capacity of 798 mAh/g. Moreover, the remarkable capacity of 591 mAh/g could be achieved with a high sulfur load of 5.76 mg/cm2 under a current density of 0.1C. Based on these merits, this novel and scalable multifunctional separator is a promising candidate to replace the conventional PP separator for advanced Li-S batteries to deal with various challenges.

Inhibition of heat shock protein family A member 8 attenuates spinal cord ischemia-reperfusion injury via astrocyte NF-κB/NLRP3 inflammasome pathway : HSPA8 inhibition protects spinal ischemia-reperfusion injury.

BACKGROUND: Astrocyte over-activation and extensive neuron loss are the main characteristic pathological features of spinal cord ischemia-reperfusion injury (SCII). Prior studies have placed substantial emphasis on the role of heat shock protein family A member 8 (HSPA8) on postischemic myocardial inflammation and cardiac dysfunction. However, it has never been determined whether HSPA8 participates in astrocyte activation and thus mediated neuroinflammation associated with SCII. METHODS: The left renal artery ligation-induced SCII rat models and oxygen-glucose deprivation and reoxygenation (OGD/R)-induced rat primary cultured astrocytes were established. The lentiviral vector encoding short hairpin RNA targeting HSPA8 was delivered to the spinal cord by intrathecal administration or to culture astrocytes. Then, the spinal neuron survival, gliosis, and nod-like receptor pyrin domain-containing 3 (NLRP3) inflammasome and its related pro-inflammatory cytokines were analyzed. RESULTS: SCII significantly enhanced the GFAP and HSPA8 expression in the spinal cord, resulting in blood-brain barrier breakdown and the dramatical loss of spinal neuron and motor function. Moreover, injury also increased spinal nuclear factor-kappa B (NF-κB) p65 phosphorylation, NLRP3 inflammasome-mediated caspase-1 activation, and subsequent interleukin (IL)-1ß as well as IL-18 secretion. Silencing the HSPA8 expression efficiently ameliorated the spinal cord tissue damage and promoted motor function recovery after SCII, through blockade of the astrocyte activation and levels of phosphorylated NF-κB, NLRP3, caspase-1, IL-1ß, and IL-18. Further in vitro studies confirmed that HSPA8 knockdown protected astrocytes from OGD/R-induced injury via the blockade of NF-κB and NLRP3 inflammasome activation. CONCLUSION: Our findings indicate that knockdown of HSPA8 inhibits spinal astrocytic damage after SCII, which may provide a promising therapeutic strategy for SCII treatment.

Endocannabinoid signaling in the lateral habenula regulates pain and alcohol consumption.

Hyperalgesia, which often occurs in people suffering from alcohol use disorder, may drive excessive drinking and relapse. Emerging evidence suggests that the lateral habenula (LHb) may play a significant role in this condition. Previous research suggests that endocannabinoid signaling (eCBs) is involved in drug addiction and pain, and that the LHb contains core components of the eCBs machinery. We report here our findings in rats subjected to chronic ethanol vapor exposure. We detected a substantial increase in endocannabinoid-related genes, including Mgll and Daglb mRNA levels, as well as monoacylglycerol lipase (MAGL) protein levels, as well as a decrease in Cnr1 mRNA and type-1 cannabinoid receptor (CB1R) protein levels, in the LHb of ethanol-exposed rats. Also, rats withdrawing from ethanol exposure displayed hypersensitivity to mechanical and thermal nociceptive stimuli. Conversely, intra-LHb injection of the MAGL inhibitor JZL184, the fatty acid amide hydrolase inhibitor URB597, or the CB1R agonist WIN55,212-2 produced an analgesic effect, regardless of ethanol or air exposure history, implying that alcohol exposure does not change eCB pain responses. Intra-LHb infusion of the CB1R inverse agonist rimonabant eliminated the analgesic effect of these chemicals. Rimonabant alone elicited hyperalgesia in the air-, but not ethanol-exposed animals. Moreover, intra-LHb JZL184, URB597, or WIN55,212-2 reduced ethanol consumption in both homecages and operant chambers in rats exposed to ethanol vapor but not air. These findings suggest that LHb eCBs play a pivotal role in nociception and facilitating LHb eCBs may attenuate pain in drinkers.

Curcumin Affects Gastric Cancer Cell Migration, Invasion and Cytoskeletal Remodeling Through Gli1-ß-Catenin.

PURPOSE: The function of curcumin on the gastric cancer cell line, SGC-7901 is unknown. The present study aimed to observe the effects of curcumin on gastric cancer cells through the Shh and Wnt signaling pathways. METHODS: SGC-7901 cells were transfected with si-Gli1 and si-ß-catenin siRNA, then cells were stimulated with curcumin and its effects on cell migration, invasion, cytoskeleton remodeling, EMT, apoptosis and cell cycle were investigated by transwell assays, immunofluorescence and flow cytometry assays. The interaction between Gli1 and ß-catenin was observed by co-immunoprecipitation. RESULTS: We show that curcumin suppressed the expression of Shh, Gli1 and Foxm1 in the Shh signaling pathway, and the expression of ß-catenin in the Wnt signaling pathway in SGC-7901 cells, both in mRNA and protein. As a result, cellular migration, invasion and cytoskeletal remodeling ability decreased. Our results revealed that when stimulated with curcumin, cells showed decreased cellular migration and invasion, while enhanced apoptosis. In addition, curcumin induced cytoskeletal remodeling and S phase cell cycle arrest. The inhibition of Shh and Wnt signaling pathway and the addition of curcumin also inhibited the epithelial-mesenchymal transition process. Furthermore, a physical interaction was observed between Gli1 of the Shh signaling and ß-catenin of the Wnt signaling in these cells, but curcumin inhibited the interaction of these two proteins. CONCLUSION: The present study indicated that curcumin plays an anti-tumor role through Gli1-ß-catenin pathway in gastric cancer SGC-7901 cells.

Highly active Ce, Y, La-modified Cu/SiO2 catalysts for hydrogenation of methyl acetate to ethanol.

Rare earth element (Ce, Y, and La) modified Cu/SiO2 catalysts via hydrolysis precipitation and impregnation method were fabricated for the vapor-phase hydrogenation of methyl acetate to ethanol. LaO x showed the most pronounced promotion in the catalytic tests. After detailed characterizations, via N2 adsorption-desorption, XRD, N2O chemisorption, FTIR, H2-TPR, H2-TPD, TEM, XPS, and TG/DTA, we found that the addition of promoter LaO x can decrease the particle size while in turn, it can increase the dispersion of copper species. The strong interactions between copper and lanthanum atoms alter the surface chemical states of the copper species. This results in the generation of more Cu+ species and high S Cu + values, which are responsible for the excellent activity and stability during hydrogenation. In addition, the content of additive LaO x and reaction conditions (reaction temperature and LHSV) were optimized. Then, the long-term stability performance was evaluated over the selected catalyst in contrast with Cu/SiO2.

Lysophosphatidic acid induces the migration and invasion of SGC-7901 gastric cancer cells through the LPA2 and Notch signaling pathways.

Lysophosphatidic acid (LPA), a simple water­soluble glycerophospholipid with growth factor­like activity, regulates certain behaviors of multiple cancer types by binding to its receptor, LPA receptor 2 (LPA2). Notch1 is a key mediator in multiple human cancer cell types. The association between LPA2 and Notch1 in gastric cancer cells is not well known. The present study aimed to investigate the function of LPA2 and Notch1 in controlling the migration and invasion activities of SGC­7901 gastric cancer cells following stimulation with LPA. It was revealed that LPA may stimulate the expression of Notch1 and Hes family bHLH transcription factor 1, and the phosphorylation of protein kinase B which belongs to the Notch pathway. Furthermore, by performing transwell migration and invasion assays, immunofluorescent staining, analyzing the expression of markers for the epithelial­mesenchymal transition (EMT) and downregulating LPA2 and Notch1 expression, it was verified that LPA2 and Notch1 mediated the metastasis, invasion, EMT and rebuilding of the cytoskeleton of SGC­7901 cells upon LPA treatment. An immunoprecipitation assay revealed that LPA2 interacted with Notch1 in SGC­7901 cells. The present study may provide novel ideas and an experimental basis for identifying the factors that affect the functions of SGC­7901 cells.

C-Phycocyanin inhibits hepatic gluconeogenesis and increases glycogen synthesis via activating Akt and AMPK in insulin resistance hepatocytes.

C-Phycocyanin (C-PC), a kind of blue protein isolated from Spirulina platensis, can ameliorate hyperglycemia, but its effects on gluconeogenesis and glycogenesis are unknown. In the present study, we investigated the effects and underlying mechanisms of C-PC on gluconeogenesis and glycogenesis in insulin resistant hepatocytes. Insulin resistance was induced by high glucose (HG) in human hepatocellular carcinoma (HepG2) cells. C-PC ameliorated glucose production and phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) expression in HG-induced insulin resistant HepG2 cells. It also increased glucose uptake, glycogen content and glycogen synthase (GS) activation in HG-induced insulin resistant HepG2 cells. The data revealed the mechanism of C-PC in improving glucose homoeostasis via activating the IRS/PI3 K/Akt and SIRT1/LKB1/AMPK signaling pathway in insulin resistant hepatocytes. C-PC could be a promising leading compound for the development of a hypoglycemic agent.

Phycocyanin ameliorates alloxan-induced diabetes mellitus in mice: Involved in insulin signaling pathway and GK expression.

The therapeutic potential and molecular mechanism of phycocyanin from Spirulina on alloxan-induced diabetes mice was investigated. In the experiment, 4-week treatment of phycocyanin at the dose of 100 and 200 mg/kg body weight in alloxan-induced diabetes mice resulted in improved metrics in comparison with alloxan-induced diabetes group. These metrics include blood glucose levels, glycosylated serum protein (GSP), glycosylated hemoglobin (GHb) and fasting serum insulin (FINS) levels. As its molecular mode of action, phycocyanin leads to the increase of IRS-1 tyrosine phosphorylation and the decrease of IRS-1 serine phosphorylation, also accompany with increased level of Akt phosphorylation on Ser473 in the liver and pancreas in diabetic mice. In addition, phycocyanin treatment enhanced the glucokinase (GK) level in the liver and pancreas, and the glucokinase regulatory protein (GKRP) level in the liver in diabetic mice. The results suggest that phycocyanin ameliorates alloxan-induced diabetes mellitus in mice by activating insulin signaling pathway and GK expression in pancreas and liver in diabetic mice.