New tricks for old drugs- praziquantel ameliorates bleomycin-induced pulmonary fibrosis in mice.

BACKGROUND: Pulmonary fibrosis is a chronic progressive disease with complex pathogenesis, short median survival time, and high mortality. There are few effective drugs approved for pulmonary fibrosis treatment. This study aimed to evaluate the effect of praziquantel (PZQ) on bleomycin (BLM)-induced pulmonary fibrosis. METHODS: In this study, we investigated the role and mechanisms of PZQ in pulmonary fibrosis in a murine model induced by BLM. Parameters investigated included survival rate, lung histopathology, pulmonary collagen deposition, mRNA expression of key genes involved in pulmonary fibrosis pathogenesis, the activity of fibroblast, and M2/M1 macrophage ratio. RESULTS: We found that PZQ improved the survival rate of mice and reduced the body weight loss induced by BLM. Histological examination showed that PZQ significantly inhibited the infiltration of inflammatory cells, collagen deposition, and hydroxyproline content in BLM-induced mice. Besides, PZQ reduced the expression of TGF-ß and MMP-12 in vivo and inhibited the proliferation of fibroblast induced by TGF-ß in vitro. Furthermore, PZQ affected the balance of M2/M1 macrophages. CONCLUSIONS: Our study demonstrated that PZQ could ameliorate BLM-induced pulmonary fibrosis in mice by affecting the balance of M2/M1 macrophages and suppressing the expression of TGF-ß and MMP-12. These findings suggest that PZQ may act as an effective anti-fibrotic agent for preventing the progression of pulmonary fibrosis.

Over-activation of NMDA receptors promotes ABCA1 degradation and foam cell formation.

ATP-binding cassette transporter A1 (ABCA1) is an essential regulator of intracellular cholesterol efflux. Secreted cholesterol binds to lipid-free apolipoprotein A-I (apoA-I) in peripheral blood to constitute high-density lipoprotein cholesterol (HDL) complexes. ABCA1 protein on the surface of macrophages acts as a crucial controller in preventing cholesterol accumulation. Importantly, ABCA1 is unstable and easily degraded via a series of biochemical activities, including but not limited to calpain-mediated and ubiquitin-proteasome system-mediated processes. How accelerated ABCA1 degradation impacts disordered lipid metabolism in macrophages and foam cell formation is unclear. N-methyl d-aspartate receptors (NMDARs) are ionotropic glutamate receptors with high calcium permeability. Calcium influx via NMDARs activates downstream signaling pathways. Over-activation of NMDARs stimulated by NMDA contributes to dysfunctional lipid metabolism in macrophages and foam cell formation via promotion of calpain-mediated ABCA1 proteolysis. However, increased NMDAR activity does not affect liver X receptor expression or ABCA1 mRNA levels. Following NMDA receptor silencing or calpain inhibition, NMDA treatment did not reduce ABCA1 protein levels, nor caused lipid accumulation in macrophages. In addition, NMDAR over-activation activates NF-κB signaling to promote IL-1ß and IL-6 macrophage marker expression. However, NMDAR silencing and calpain inhibition reduce inflammatory macrophage responses. In summary, our study suggests that NMDAR activation reduces surface ABCA1 protein, promotes lipid accumulation, and induces the production and secretion of many inflammatory mediators in macrophages, possibly through enhanced calpain-mediated ABCA1 protein degradation. Thus, the NMDAR receptor may be a novel pharmacologic target for atherosclerosis therapy.

Ozone therapy promotes the differentiation of basal keratinocytes via increasing Tp63-mediated transcription of KRT10 to improve psoriasis.

Psoriasis is a chronic immune-mediated inflammatory dermatosis. Recently, ozone therapy has been applicated to psoriasis treatment; however, the mechanism by which ozone therapy improves psoriasis remains unclear. The excessive proliferation and the differentiation of basal keratinocytes have been considered critical issues during pathological psoriasis process, in which keratin 6 (KRT6) and KRT10 might be involved. In the present study, KRT6, IL-17 and IL-22 protein within psoriasis lesions was decreased, while KRT10 and Tp63 protein in psoriasis lesions was increased by ozone treatment in both patient and IMQ mice psoriatic tissues. In the meantime, ozone treatment down-regulated KRT6 mRNA and protein expression while up-regulated KRT10 mRNA and protein expression within IL-22 treated primary KCs; the cell viability of KCs was suppressed by ozone treatment. Moreover, Tp63 bound to KRT10 promoter region to activate its transcription in basal keratinocytes; the promotive effects of ozone on Tp63 and KRT10 were significantly reversed by Tp63 silence. Both TP63 and KRT10 mRNA expression were significantly increased by ozone treatment in psoriasis lesions; there was a positive correlation between Tp63 and KRT10 expression within tissue samples, suggesting that ozone induces the expression of Tp63 to enhance the expression of KRT10 and the differentiation of keratinocytes, therefore improving the psoriasis. In conclusion, the application of ozonated oil could be an efficient and safe treatment for psoriasis; ozone promotes the differentiation of keratinocytes via increasing Tp63-mediated transcription of KRT10, therefore improving psoriasis.

Megakaryocytes participate in the occurrence of bleomycin-induced pulmonary fibrosis.

Pulmonary fibrosis is characterized by the remodeling of fibrotic tissue and collagen deposition, which mainly results from aberrant fibroblasts proliferation and trans-differentiation to myofibroblasts. Patients with chronic myelogenous leukemia, myeloproliferative disorder, and scleroderma with pulmonary fibrosis complications show megakaryocyte infiltration in the lung. In this study, we demonstrated that the number of CD41+ megakaryocytes increased in bleomycin (BLM)-induced lung fibrosis tissues through the Chemokine (CXCmotif) ligand 12/Chemokine receptor 4 (CXCL12/CXCR4) axis. Pharmacological inhibition of the CXCL12/CXCR4 axis with WZ811 prevented migration of CD41+ megakaryocytes induced by BLM-injured lung tissue ex vivo and in vivo. In addition, WZ811 significantly attenuated lung fibrosis after BLM challenge. Moreover, megakaryocytes directly promoted fibroblast proliferation and trans-differentiation to myofibroblasts. We conclude that thrombopoietin (TPO) activated megakaryocytes through transforming growth factor ß (TGF-ß) pathway to promote fibroblast proliferation and trans-differentiation to myofibroblasts, which is abolished by treatment with selective TGF-ßR-1/ALK5 inhibitors. Therefore, CD41+ megakaryocytes migrate to injured lung tissue partially through the CXCL12/CXCR4 axis to promote the proliferation and trans-differentiation of fibroblasts through direct contact and the TGF-ß1 pathway.

Cigarette smoke exposure combined with lipopolysaccharides induced pulmonary fibrosis in mice.

Cigarette smoke (CS) is a risk factor for pulmonary fibrosis and lipopolysaccharides (LPS) are associated with human occupational lung diseases; however, their combined role in pulmonary fibrosis remains unknown. Therefore, we investigated whether CS combined with LPS induces pulmonary fibrosis in mice. C57BL/6 mice were exposed to CS or normal air for 21 or 35 days, followed by LPS or saline instillation on day 14, 21, and 28. Lung function was tested, and lung tissues were harvested for histological and molecular analyses. Compared to the control, CS and LPS groups, the CS + LPS group showed reduced body weight and survival rate, increased respiratory resistance, decreased lung compliance, marked alveolar structure destruction, and fibrotic lesion formation. Lung tissues showed a considerable increase in IL-6, TNF-α, IL-1ß, α-SMA, and TGF-ß levels and collagen content. Our results indicate that cigarette smoke exposure followed by LPS in mice induces pulmonary fibrosis with pathophysiology consistent with that of human pulmonary fibrosis.

Memantine ameliorates pulmonary inflammation in a mice model of COPD induced by cigarette smoke combined with LPS.

An enhanced chronic inflammatory response in the airways has been regarded as a critical characteristic of chronic obstructive pulmonary disease (COPD). Memantine, an N-methyl-d-aspartate (NMDA) receptors antagonist, has been reported to alleviate lung inflammation. In this study, we investigated the effect and mechanism of memantine on the COPD model induced by cigarette smoke (CS) combined with LPS. Mice and RAW264.7 cells were treated with LPS in the presence or absence of CS. We performed H&E staining to analysis the lung histopathological characteristics. Cytokines (IL-6, TNF-α, and IFN-γ) levels in bronchoalveolar lavage fluid (BALF), lung tissue homogenates and RAW264.7 cell culture medium were determined. Glutamate levels in plasma and culture medium of RAW264.7 were determined. The intracellular Ca2+ flux in RAW264.7 cells was measured by fluo-3 AM staining. The protein levels of NR-1, xCT, ERK1/2, and AKT signaling in the lung tissue and cells were investigated. The result showed that CS and LPS stimulation caused inflammation response, a significant increase in the release of cytokines, including TNF-α, IL-6, and IFN-γ, the elevated release of glutamate and protein levels of NR-1 and xCT, increased Ca2+ influx, and the activation of the ERK1/2 pathway in vitro and in vivo. The above effects of CS and LPS stimulation could be significantly attenuated by memantine treatment. In conclusion, memantine can effectively ameliorate pulmonary inflammation in CS + LPS-induced COPD in mice via reducing NR-1 and xCT expression, glutamate release, Ca2+ influx, and the phosphorylation of Erk1/2. We provided a possible mechanism by which memantine ameliorates COPD in mice.

[LIMR is involved in the inhibitory effect of antiflammin-1 on epithelial-mesenchymal transition in A549 cells].

Epithelial-mesenchymal transition (EMT) occurring in alveolar epithelial cells plays an important role in the development and progression of pulmonary fibrosis. Previous studies showed that antiflammin-1 (the active fragment of uteroglobin) effectively inhibited bleomycin-induced pulmonary fibrosis. However, its mechanism is still far from being clarified. In this study, we investigated the effects of antiflammin-1 on EMT in A549 cells induced by transforming growth factor-ß1 (TGF-ß1) and the underlying mechanism by using morphological observation and Western blot. The results showed that the expression of α-smooth muscle actin (α-SMA) increased significantly while the expression of E-cadherin decreased significantly in A549 cells following treatment with TGF-ß1 concomitant with morphological change of A549 cells from pebble-like shape epithelial cells to spindle-like mesenchymal shape. This process of EMT in A549 cells induced by TGF-ß1 was significantly inhibited when A549 cells were co-incubated with TGF-ß1 and antiflammin-1. Furthermore, the anti-lipocalin interacting membrane receptor (LIMR) antibody and PD98059 (an ERK signaling pathway blocker) attenuated the inhibitory effect of antiflammin-1 on TGF-ß1-induced EMT, respectively. Our findings indicate that antiflammin-1 can inhibit EMT in A549 cells induced by TGF-ß1, which is related to LIMR and its downstream ERK signaling pathway.

NMDA receptor activation inhibits the antifibrotic effect of BM-MSCs on bleomycin-induced pulmonary fibrosis.

Endogenous glutamate (Glu) release and N-methyl-d-aspartate (NMDA) receptor (NMDAR) activation are associated with lung injury in different animal models. However, the underlying mechanism is unclear. Bone marrow-derived mesenchymal stem cells (BM-MSCs), which show potential use for immunomodulation and tissue protection, play a protective role in pulmonary fibrosis (PF) process. Here, we found the increased Glu release from the BM cells of bleomycin (BLM)-induced PF mice in vivo. BLM stimulation also increased the extracellular Glu in BM-MSCs via the antiporter system xc- in vitro. The gene expression of each subunit of NMDAR was detected in BM-MSCs. NMDAR activation inhibited the proliferation, migration, and paracrine function of BM-MSCs in vitro. BM-MSCs were derived from male C57BL/6 mice, transfected with lentiviral vectors carrying the enhanced green fluorescence protein gene, pretreated with NMDA, and transplanted into the female recipient mice that were intratracheally injected with BLM to induce PF. Transplantation of NMDA-pretreated BM-MSCs significantly aggravated PF as compared with that in the normal BM-MSCs transplantation group. The sex determination gene Y chromosome and green fluorescence protein genes of BM-MSCs were detected to observe BM-MSCs homing in the fibrotic lungs. Moreover, NMDAR activation inhibited BM-MSC migration by downregulating the stromal cell-derived factor-1/C-X-C chemokine receptor type 4 signaling axis. NMDAR activation aggravated the transforming growth factor-ß1-induced extracellular matrix production in alveolar epithelial cells and fibroblasts through the paracrine effects of BM-MSCs. In summary, these findings suggested that NMDAR activation-mediated Glu excitotoxicity induced by BLM in BM-MSCs abolished the therapeutic effects of normal BM-MSCs transplantation on BLM-induced PF.

Controlling AOX1 promoter strength in Pichia pastoris by manipulating poly (dA:dT) tracts.

Alcohol oxidase I (AOX1) promoter is the most popular but strictly-regulated methanol inducible promoter for heterologous protein expression in Pichia pastoris. In recent years, AOX1 promoter libraries have been developed with deletion or insertion methods. The present research manipulated poly (dA:dT) tracts in this promoter to control promoter strength, which hadn't been tried before. There were 34 variants derived from the native AOX1 promoter constructed. And variants were integrated into the same genomic location and upstream of the same reporter gene porcine growth hormone (pGH). To test the transferability of the results obtained from reporter gene pGH, the variants were connected to reporter gene Lac Z. The resulted promoter library spanned an activity range between 0.25 and 3.5 fold of the wild-type promoter activity. In addition, activities of variants correlated with their predicted nucleosome architecture, which were directed by poly (dA:dT) tracts. The cumulative sum of predicted nucleosome affinity across the region (-820 to -540) was related to promoters strength in single deletion variants on a proportional basis. Overall, the research promotes understanding of the regulatory patterns for AOX1 promoter and suggested that varying promoter expression of engineering nucleosome architecture was also a feasible approach in P. pastoris.

Epicutaneous sensitization with ovalbumin, staphylococcal enterotoxin B and vitamin D analogue induces atopic dermatitis in mice.

OBJECTIVE: To illuminate a method for establishment of a cost-efficient atopic dermatitis (AD) mouse model by topical application of ovalbumin (OVA), super-antigen staphylococcal enterotoxin B (SEB), and calcipotriene ointment (CO) on the back of BALB/c mice.
 Methods: Experimental mice were topically treated with OVA/SEB or OVA/SEB/CO every other day during 15 days of induction. Clinical alterations on the skin area were monitored every other day. Epidermal thickness were measured by reflectance confocal microscope (RCM) before harvest. Inflammatory cells in skin biopsies were marked by hematoxylin-eosin (HE) staining. Blood sample and skin biopsies were measured by ELISA and quantitative real-time PCR to detect the expression of IL-2, IL-4, IL-31, interferon (IFN)-γ, tumor necrosis factor (TNF)-α pruritus-associated nerve growth factor (NGF), and serum IgE.
 Results: Human AD-like cutaneous local inflammatory reaction was characterized by the accumulation of inflammatory cells, increased epidermal thickness and serum IgE levels as well as Th1 cell-associated cytokines (IFN-γ, TNF-α), Th2 cell-associated cytokines (IL-4, IL-31), and NGF in the OVA/SEB/CO group compared with that in the normal control group or the OVA/SEB group.
 Conclusion: OVA/SEB/CO can induce an AD-like mouse model with lower economic and time consumption.

A Sustained Activation of Pancreatic NMDARs Is a Novel Factor of ß-Cell Apoptosis and Dysfunction.

Type 2 diabetes, which features ß-cell failure, is caused by the decrease of ß-cell mass and insulin secretory function. Current treatments fail to halt the decrease of functional ß-cell mass. Strategies to prevent ß-cell apoptosis and dysfunction are highly desirable. Recently, our group and others have reported that blockade of N-methyl-d-aspartate receptors (NMDARs) in the islets has been proposed to prevent the progress of type 2 diabetes through improving ß-cell function. It suggests that a sustained activation of the NMDARs may exhibit deleterious effect on ß-cells. However, the exact functional impact and mechanism of the sustained NMDAR stimulation on islet ß-cells remains unclear. Here, we identify a sustained activation of pancreatic NMDARs as a novel factor of apoptotic ß-cell death and function. The sustained treatment with NMDA results in an increase of intracellular [Ca2+] and reactive oxygen species, subsequently induces mitochondrial membrane potential depolarization and a decrease of oxidative phosphorylation expression, and then impairs the mitochondrial function of ß-cells. NMDA specifically induces the mitochondrial-dependent pathway of apoptosis in ß-cells through upregulation of the proapoptotic Bim and Bax, and downregulation of antiapoptotic Bcl-2. Furthermore, a sustained stimulation of NMDARs impairs ß-cell insulin secretion through decrease of pancreatic duodenal homeobox-1 (Pdx-1) and adenosine triphosphate synthesis. The activation of nuclear factor-κB partly contributes to the reduction of Pdx-1 expression induced by overstimulation of NMDARs. In conclusion, we show that the sustained stimulation of NMDARs is a novel mediator of apoptotic signaling and ß-cell dysfunction, providing a mechanistic insight into the pathological role of NMDARs activation in diabetes.

Photorechargeable High Voltage Redox Battery Enabled by Ta3 N5 and GaN/Si Dual-Photoelectrode.

Solar rechargeable battery combines the advantages of photoelectrochemical devices and batteries and has emerged as an attractive alternative to artificial photosynthesis for large-scale solar energy harvesting and storage. Due to the low photovoltages by the photoelectrodes, however, most previous demonstrations of unassisted photocharge have been realized on systems with low open circuit potentials (<0.8 V). In response to this critical challenge, here it is shown that the combined photovoltages exceeding 1.4 V can be obtained using a Ta3 N5 nanotube photoanode and a GaN nanowire/Si photocathode with high photocurrents (>5 mA cm-2 ). The photoelectrode system makes it possible to operate a 1.2 V alkaline anthraquinone/ferrocyanide redox battery with a high ideal solar-to-chemical conversion efficiency of 3.0% without externally applied potentials. Importantly, the photocharged battery is successfully discharged with a high voltage output.

An excessive increase in glutamate contributes to glucose-toxicity in ß-cells via activation of pancreatic NMDA receptors in rodent diabetes.

In the nervous system, excessive activation of NMDA receptors causes neuronal injury. Although activation of NMDARs has been proposed to contribute to the progress of diabetes, little is known about the effect of excessive long-term activation of NMDARs on ß-cells, especially under the challenge of hyperglycemia. Here we thoroughly investigated whether endogenous glutamate aggravated ß-cell dysfunction under chronic exposure to high-glucose via activation of NMDARs. The glutamate level was increased in plasma of diabetic mice or patients and in the supernatant of ß-cell lines after treatment with high-glucose for 72 h. Decomposing the released glutamate improved GSIS of ß-cells under chronic high-glucose exposure. Long-term treatment of ß-cells with NMDA inhibited cell viability and decreased GSIS. These effects were eliminated by GluN1 knockout. The NMDAR antagonist MK-801 or GluN1 knockout prevented high-glucose-induced dysfunction in ß-cells. MK-801 also decreased the expression of pro-inflammatory cytokines, and inhibited I-κB degradation, ROS generation and NLRP3 inflammasome expression in ß-cells exposed to high-glucose. Furthermore, another NMDAR antagonist, Memantine, improved ß-cells function in diabetic mice. Taken together, these findings indicate that an increase of glutamate may contribute to the development of diabetes through excessive activation of NMDARs in ß-cells, accelerating ß-cells dysfunction and apoptosis induced by hyperglycemia.

CRIP1, a novel immune-related protein, activated by Enterococcus faecalis in porcine gastrointestinal epithelial cells.

Cysteine-rich intestinal protein 1 (CRIP1) is an important transcriptional regulation factor during the tumor development. Although it was largely studied in the human or mouse, no report has provided functional evidence for it in the swine. To date, the real sequence of porcine CRIP1 (poCRIP1) was also still unknown. In this study, clear characteristics for the poCRIP1 were represented. A 552bp poCRIP1 cDNA was obtained from porcine brain tissue using real time reverse transcriptase PCR. The poCRIP1 showed 89% and 93% homologous with human and cattle, respectively. And it also contained one conserved domain, LIM-CRIP domain. Meanwhile, the genomic structure and promoter map was done and several conserved transcriptional regulatory sites were also predicted in this study. The expression pattern of poCRIP1 indicated that poCRIP1 is expressed in mucosal tissue. An infection experiment about the gut was designed to analyze whether or not poCRIP1 was functional in gut immunity, and an interesting result was that poCRIP1 was only activated by an opportunistic pathogen, Enterococcus faecalis FA2-2. It was the first report to identify the full-length sequence of poCRIP1 gene, represent a clear characteristic and immunologic role of CRIP1 in domestic animal until now.

Why Do Lithium-Oxygen Batteries Fail: Parasitic Chemical Reactions and Their Synergistic Effect.

As an electrochemical energy-storage technology with the highest theoretical capacity, lithium-oxygen batteries face critical challenges in terms of poor stabilities and low charge/discharge round-trip efficiencies. It is generally recognized that these issues are connected to the parasitic chemical reactions at the anode, electrolyte, and cathode. While the detailed mechanisms of these reactions have been studied separately, the possible synergistic effects between these reactions remain poorly understood. To fill in the knowledge gap, this Minireview examines literature reports on the parasitic chemical reactions and finds the reactive oxygen species a key chemical mediator that participates in or facilitates nearly all parasitic chemical reactions. Given the ubiquitous presence of oxygen in all test cells, this finding is important. It offers new insights into how to stabilize various components of lithium-oxygen batteries for high-performance operations and how to eventually materialize the full potentials of this promising technology.

Effect of cooperation of chaperones and gene dosage on the expression of porcine PGLYRP-1 in Pichia pastoris.

Mammalian peptidoglycan recognition proteins (PGLYRPs) are highly conserved pattern-recognition molecules of the innate immune system with considerable bactericidal activity, which manifest their potential values for the application to food and pharmaceutical industry. However, the effective expression of porcine PGLYRP-1 in Pichia pastoris has not been reported so far. In this study, expression in P. pastoris was explored as an efficient way to produce functional porcine PGLYRP-1. Cooperation of chaperones co-expression and gene dosage (including protein disulfide isomerase (PDI)/binding protein (BiP) and pglyrp-1) were used to enhance functional expression of antimicrobial protein in P. pastoris. Overexpression of PDI was certainly able to increase secretion level of PGLYRP-1 protein because the increase in secreted PGLYRP-1 secretion was correlated with the copy numbers of PDI in high copy pglyrp-1 clones. However, co-expression of BiP was proved to be detrimental to PGLYRP-1 secretion. In addition, we also found that excessive expression of PDI and/or BiP could decrease the mRNA expression of pglyrp-1 gene. This showed that PDI and BiP as the target genes of unfolded protein response (UPR) might regulate the transcription of the target protein. These data demonstrated for the first time that the combination of chaperones and gene dosages could improve the yield of PGLYRP-1, which could facilitate the application to food and pharmaceutical industry.

Achieving Low Overpotential Li-O2 Battery Operations by Li2O2 Decomposition through One-Electron Processes.

As a promising high-capacity energy storage technology, Li-O2 batteries face two critical challenges, poor cycle lifetime and low round-trip efficiencies, both of which are connected to the high overpotentials. The problem is particularly acute during recharge, where the reactions typically follow two-electron mechanisms that are inherently slow. Here we present a strategy that can significantly reduce recharge overpotentials. Our approach seeks to promote Li2O2 decomposition by one-electron processes, and the key is to stabilize the important intermediate of superoxide species. With the introduction of a highly polarizing electrolyte, we observe that recharge processes are successfully switched from a two-electron pathway to a single-electron one. While a similar one-electron route has been reported for the discharge processes, it has rarely been described for recharge except for the initial stage due to the poor mobilities of surface bound superoxide ions (O2(-)), a necessary intermediate for the mechanism. Key to our observation is the solvation of O2(-) by an ionic liquid electrolyte (PYR14TFSI). Recharge overpotentials as low as 0.19 V at 100 mA/g(carbon) are measured.

Functionalizing Titanium Disilicide Nanonets with Cobalt Oxide and Palladium for Stable Li Oxygen Battery Operations.

Li oxygen (Li-O2) batteries promise high energy densities but suffer from challenges such as poor cycling lifetime and low round-trip efficiencies. Recently, the instability of carbon cathode support has been recognized to contribute significantly to the problems faced by Li-O2 batteries. One strategy to address the challenge is to replace carbon materials with carbon-free ones. Here, we present titanium silicide nanonets (TiSi2) as such a new material platform for this purpose. Because TiSi2 exhibits no oxygen reduction reaction (ORR) or oxygen evolution reaction (OER) activities, catalysts are required to promote discharge and recharge reactions at reduced overpotentials. Pd nanoparticles grown by atomic layer deposition (ALD) were observed to provide the bifunctionalities of ORR and OER. Their adhesion to TiSi2 nanonets, however, was found to be poor, leading to drastic performance decay due to Pd detachments and aggregation. The problem was solved by adding another layer of Co3O4, also prepared by ALD. Together, the Pd/Co3O4/TiSi2 combination affords the desired functionalities and stability. Li-O2 test cells that lasted more than 126 cycles were achieved. The reversible formation and decomposition of Li2O2 was verified by Raman spectroscopy, X-ray photoelectron spectroscopy (XPS), ferrocenium back-titration, and gas-chromatography and mass spectrometry (GC-MS). Our results provide a new material platform for detailed studies of Li-O2 operations for better understanding of the chemistries involved, which is expected to help pave the way toward practical Li-O2 battery realizations.

NMDA Receptor Antagonist Attenuates Bleomycin-Induced Acute Lung Injury.

BACKGROUND: Glutamate is a major neurotransmitter in the central nervous system (CNS). Large amount of glutamate can overstimulate N-methyl-D-aspartate receptor (NMDAR), causing neuronal injury and death. Recently, NMDAR has been reported to be found in the lungs. The aim of this study is to examine the effects of memantine, a NMDAR channel blocker, on bleomycin-induced lung injury mice. METHODS: C57BL/6 mice were intratracheally injected with bleomycin (BLM) to induce lung injury. Mice were randomized to receive saline, memantine (Me), BLM, BLM plus Me. Lungs and BALF were harvested on day 3 or 7 for further evaluation. RESULTS: BLM caused leukocyte infiltration, pulmonary edema and increase in cytokines, and imposed significant oxidative stress (MDA as a marker) in lungs. Memantine significantly mitigated the oxidative stress, lung inflammatory response and acute lung injury caused by BLM. Moreover, activation of NMDAR enhances CD11b expression on neutrophils. CONCLUSIONS: Memantine mitigates oxidative stress, lung inflammatory response and acute lung injury in BLM challenged mice.

Three dimensionally ordered mesoporous carbon as a stable, high-performance Li-O2 battery cathode.

Enabled by the reversible conversion between Li2O2 and O2, Li-O2 batteries promise theoretical gravimetric capacities significantly greater than Li-ion batteries. The poor cycling performance, however, has greatly hindered the development of this technology. At the heart of the problem is the reactivity exhibited by the carbon cathode support under cell operation conditions. One strategy is to conceal the carbon surface from reactive intermediates. Herein, we show that long cyclability can be achieved on three dimensionally ordered mesoporous (3DOm) carbon by growing a thin layer of FeO(x) using atomic layer deposition (ALD). 3DOm carbon distinguishes itself from other carbon materials with well-defined pore structures, providing a unique material to gain insight into processes key to the operations of Li-O2 batteries. When decorated with Pd nanoparticle catalysts, the new cathode exhibits a capacity greater than 6000 mAh g(carbon) (-1) and cyclability of more than 68 cycles.