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Purpose: To investigate the underlying mechanism of cardiomyocyte protection of carvedilol based on autophagy and apoptosis. Methods: Neonatal rat ventricular myocytes (NRVMs) were exposed to various concentrations of carvedilol before anoxia, and pretreated with 3-MA or compound C for inhibiting autophagy or p-AMPK expression. CCK-8 colorimeter and flow cytometry were used to determine the cell viability and apoptotic rates. The variation of mRNA and protein was measured by RT-PCR and Western blot. The presence of autophagosomes was observed by electron microscopy. Results: First, we found that carvedilol increased autophagic marker levels in a concentration-dependent manner and the number of autophagosomes in NRVMs. Moreover, carvedilol substantially enhanced the viability and noticeably reduced the CK, MDA and LDH levels and cell apoptosis rate compared with the anoxia group. In addition, carvedilol decreased the levels of caspase-3 and Bim in mRNA and protein, but such effect was blocked by the special autophagy inhibitor-3-MA, and the number of autophagosomes was significantly decreased when treated with 3-MA, indicating that carvedilol exhibited anti-apoptotic and anti-injury effects by inducing autophagy in anoxia NRVMs, but these effects can be abolished by adding 3-MA to suppress autophagy. Finally, the carvedilol treatment-induced autophagy by enhancing the activation of p-AMPK and inhibiting p-mTOR. Electron microscopy presented that the number of autophagosomes was significantly decreased when treating with compound C, indicating that carvedilol induced autophagy in anoxia NRVMs partly by the AMPK-mTOR signaling pathway. Conclusions: Carvedilol has cardioprotection by inducing autophagy against apoptosis partly through the AMPK/mTOR pathway during anoxia in NRVMs.

Evodia rutaecarpa has multiple pharmacological effects and is widely used in the prevention and treatment of migraine, diabetes, cardiovascular disease, cancer, and other chronic diseases; however, the pharmacological effects of its active compound evodiamine (Evo) have not been thoroughly investigated. The purpose of this study was to investigate the effects of Evo on antiplatelet activation and thrombosis. We discovered that Evo effectively inhibited collagen-induced platelet activation but had no effect on platelet aggregation caused by activators such as thrombin, ADP, and U46619. Second, we found that Evo effectively inhibited the release of platelet granules induced by collagen. Finally, evodiamine inhibits the transduction of the SFKs/Syk/Akt/PLCγ2 activation pathway in platelets. According to in vivo studies, Evo significantly prolonged the mesenteric thromboembolism induced by ferric chloride and had no discernible effect on the coagulation function of mice. In conclusion, the antiplatelet and thrombotic effects of Evo discovered in this study provide an experimental basis for the investigation of the pharmacological mechanisms of Evo and the development of antiplatelet drugs.

This study aims to trace the context of Christianization and hispanization in Philippine music. The annexation and inclusion of the Philippine Islands into the Spanish Empire, which lasted more than three centuries, resulted in the subsequent remaking of Philippine society through the adoption of Western social and cultural norms. Spain became the dominant force as it intervened and directed the region's political, religious, social, economic, and cultural landscape. This study will use historical research design to identify the widespread propagation of the Catholic faith and the eventual transplantation of predominantly Hispanic culture in most parts of the archipelago, bringing the prevalent cultural and musical traditions of the Western world into this part of the world. Based on the length of the Spanish colonial administration of the Philippines and the success it had in converting the population to Christianity, and given the particular importance of music in Catholic religious life, we might expect to find a treasure trove of music manuscripts, records, biographical information, and musical instruments from the Spanish colonial period, in quantities and conditions proportional to those found in Mexico, Peru, or other large Spanish colonies. The governmental and commercial sectors should continue to collaborate to promote the vocal arts to the Filipino people and ensure that they remain a diamond with a brilliance that will be appreciated forever.

Rationale: Invariant natural killer T (iNKT) cells and Kupffer cells represent major hepatic populations of innate immune cells. However, their roles in steatohepatitis remain poorly understood. To elucidate their functions in steatohepatitis development, real-time, in vivo analysis is necessary to understand the pathophysiological events in the dynamic interactions between them during diet-induced steatohepatitis. Methods: We used a steatohepatitis animal model induced by a methionine-choline-deficient (MCD) diet. Multi-photon confocal live imaging and conventional experimental techniques were employed to investigate the hepatic pathological microenvironment of iNKT and Kupffer cells, interactions between them, and the biological effects of these interactions in steatohepatitis. Results: We found that iNKT cells were recruited and aggregated into small clusters and interacted dynamically with Kupffer cells in the early stage of steatohepatitis. Most significantly, the iNKT cells in the cluster cleared free lipids released by necrotic hepatocytes and presented a non-classical activation state with high IFN-γ expression. Furthermore, the Kupffer cells in the cell cluster were polarized to type M1. The transcriptome sequencing of iNKT cells showed upregulation of genes related to phagocytosis and lipid processing. Adoptive transfer of iNKT cells to Jα18-/- mice showed that iNKT and Kupffer cell clusters were essential for balancing the liver and peripheral lipid levels and inhibiting liver fibrosis development. Conclusions: Our study identified an essential role for dynamic interactions between iNKT cells and Kupffer cells in promoting lipid phagocytosis and clearance by iNKT cells during early liver steatohepatitis. Therefore, modulating iNKT cells is a potential therapeutic strategy for early steatohepatitis.

This study presents an integrated hybrid ground source heat pump (HGSHP) predictive model assisted by liquid dry cooler (LDC). Combining with a new computational component imported to Transient System Simulation Tool (TRNSYS), the long-term simulation results proves that the HGSHP has better performance comparing to conventional ground source heat pump. In Birmingham, USA area, surrounding soil thermal storage is decreasing over time for both hybrid and conventional systems. After 10 years of simulation, the minimum temperature in the target zone is 12.53 °C for the HGHSP, which is 0.63 °C higher than the value of the conventional GSHP. The coefficient of performance (COP) for the hybrid system could stay at 3.33, which is also better than 3.23 for the conventional system. All the collected data shows that HGSHP integrated with liquid dry cooler plays an important role to maintain the soil thermal storage as well as promoting the overall system performance.

Complement component C3, mainly synthesized by hepatocytes, acts as the convergence point of three different pathways in activating the complement cascade. Besides its well-established roles in the extracellular milieu, C3 performs various intracellular functions such as immunomodulation and pathogen recognition. Although C3 is present at extremely high concentrations in hepatocytes, little is known about its intrahepatic function. In this study, we found that C3 knockout (C3-/- ) mice displayed accelerated hepatic triglyceride (TG) accumulation compared with C57BL/6J wild type mice. Mechanistically, C3 deficiency impaired lipophagy in hepatocytes, owing to the disrupted interaction between C3 and autophagy-related 16 like 1, which is essential for autolysosome assembly. Furthermore, lipophagy deficiency affected the function of the endoplasmic reticulum in C3-/- mice, subsequently affecting the expression of protein disulfide isomerase and activity of microsomal TG transfer protein, and ultimately impairing the production of hepatic very-low-density lipoproteins (VLDLs). Rapamycin and thapsigargin treatment accelerated VLDL secretion and alleviated hepatic lipid accumulation in C3-/- mice. Our study demonstrates that C3 promotes lipophagy to facilitate VLDL secretion in hepatocytes, thus playing an essential role in balancing TG levels in the liver.

Polyester-coated fabric has been widely used in membrane structures. However, the mechanical properties of polyester-coated fabric at elevated temperatures have not been well studied, limit...

Background Circulating microRNAs (miRNAs) have emerged as potential biomarkers for cardiovascular diseases. However, few studies have focused on the role of exosomal miRNAs in acute coronary syndrome (ACS). The purpose of this study was to explore weather serum exosomal microRNA-146a (exo-miR-146a) could be used as a novel diagnostic biomarker for ACS and to investigate its relationship with inflammatory response. Methods A total of 63 ACS patients and 25 patients with normal coronary arteries (Control) were enrolled respectively. The serum exosomes were isolated and then identified by transmission electron microscopy (TEM), western blot, and nanoparticle tracking analysis (NTA). The expression levels of exo-miR-146a in serum were detected by real-time quantitative polymerase chain reaction (RT-qPCR) and the expression levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in serum were assessed by enzyme-linked immunosorbent assay (ELISA). Spearman's correlation analysis was used to appraise the potential factors related to serum exo-miR-146a and receiver operating characteristic (ROC) curve analysis was applied for predicting the accuracy of ACS via the area under curve (AUC). Results Exosomes isolated from serum were of typical cup-like shape, with 50-150 nm diameter, and expressed CD9, CD63, CD81, and HSP70. The expression levels of serum exo-miR-146a, IL-1β, IL-6, and TNF-α were significantly increased in ACS patients compared with the control group, Spearman's correlation analysis indicated that exo-miR-146a expression was markedly positively correlated with IL-1β, IL-6, and TNF-α. The ROC curve analyses revealed that exo-miR-146a could distinguish ACS patients from their normal controls. Conclusions The serum exo-miR-146a may be used as a novel diagnostic biomarker for ACS patients, and it is also associated with inflammatory response.

Parkinson’s disease (PD) is characterized by the degeneration of dopaminergic neurons and excessive microglial activation in the substantia nigra pars compacta (SNpc). In the present study, we aimed to demonstrate the therapeutic effectiveness of the potent sphingosine-1-phosphate receptor antagonist fingolimod (FTY720) in an animal model of PD induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), and to identify the potential mechanisms underlying these therapeutic effects. C57BL/6J mice were orally administered FTY720 before subcutaneous injection of MPTP. Open-field and rotarod tests were performed to determine the therapeutic effect of FTY720. The damage to dopaminergic neurons and the production of monoamine neurotransmitters were assessed using immunohistochemistry, high-performance liquid chromatography, and flow cytometry. Immunofluorescence (CD68- positive) and enzyme-linked immunosorbent assay were used to analyze the activation of microglia, and the levels of activated signaling molecules were measured using Western blotting. Our findings indicated that FTY720 significantly attenuated MPTP-induced behavioral deficits, reduced the loss of dopaminergic neurons, and increased dopamine release. FTY720 directly inhibited MPTP-induced microglial activation in the SNpc, suppressed the production of interleukin (IL)-6, IL-1β, and tumor necrosis factor-α in BV-2 microglial cells treated with 1-methyl-4-phenylpyridinium (MPP+), and subsequently decreased apoptosis in SH-SY5Y neuroblastoma cells. Moreover, in MPP+-treated BV-2 cells and primary microglia, FTY720 treatment significantly attenuated the increases in the phosphorylation of PI3K/AKT/GSK-3β, reduced ROS generation and p65 activation, and also inhibited the activation of NLRP3 inflammasome and caspase-1. In conclusion, FTY720 may reduce PD progression by inhibiting NLRP3 inflammasome activation via its effects on ROS generation and p65 activation in microglia. These findings provide novel insights into the mechanisms underlying the therapeutic effects of FTY720, suggesting its potential as a novel therapeutic strategy against PD.

To suppress dendrite formation in lithium metal batteries, high cation transference number electrolytes that reduce electrode polarization are highly desirable, but rarely available using conventional liquid electrolytes. Here, we show that liquid electrolytes increase their cation transference numbers (e.g., ∼0.2 to >0.70) when confined to a structurally rigid polymer host whose pores are on a similar length scale (0.5-2 nm) as the Debye screening length in the electrolyte, which results in a diffuse electrolyte double layer at the polymer-electrolyte interface that retains counterions and reject co-ions from the electrolyte due to their larger size. Lithium anodes coated with ∼1 μm thick overlayers of the polymer host exhibit both a low area-specific resistance and clear dendrite-suppressing character, as evident from their performance in Li-Li and Li-Cu cells as well as in post-mortem analysis of the anode's morphology after cycling. High areal capacity Li-S cells (4.9 mg cm-2; 8.2 mAh cm-2) implementing these high transference number polymer-hosted liquid electrolytes were remarkably stable, considering ∼24 μm of lithium was electroreversibly deposited in each cycle at a C-rate of 0.2. We further identified a scalable manufacturing path for these polymer-coated lithium electrodes, which are drop-in components for lithium metal battery manufacturing.

An inflammasome is an intracellular multiprotein complex that plays important roles in host defense and inflammatory responses. Inflammasomes are typically composed of the adaptor protein apoptosis-associated speck-like protein containing a CARD (ASC), cytoplasmic sensor protein, and the effector protein pro-caspase-1. ASC assembly into a protein complex termed ASC speck is a readout for inflammasome activation. Here, we provide a step-by-step protocol for the detection of ASC speck by confocal microscopy in Bone marrow derived macrophages (BMBDs) triggered by chemical stimuli and bacterial pathogens. We also describe the detailed procedure for the generation of BMDMs, stimulating conditions for inflammasome activation, immunofluorescence cell staining of ASC protein, and microscopic examination. Thus far, this method is a simple and reliable manner to visualize and quantify the intracellular localization of ASC speck. Graphic abstract: Figure 1. Confocal microscopy detection of ASC speck formation in untreated WT BMDMs and WT BMDMs stimulated with LPS and ATP, transfected with dsDNA, and infected with F. novicida or Salmonella as indicated. Arrow indicates the ASC speck. Scale bars: 10 μm.

The mechanism by which inflammasome activation is modulated remains unclear. In this study, we identified an AIM2-interacting protein, the E3 ubiquitin ligase HUWE1, which was also found to interact with NLRP3 and NLRC4 through the HIN domain of AIM2 and the NACHT domains of NLRP3 and NLRC4. The BH3 domain of HUWE1 was important for its interaction with NLRP3, AIM2, and NLRC4. Caspase-1 maturation, IL-1β release, and pyroptosis were reduced in Huwe1-deficient bone marrow-derived macrophages (BMDMs) compared with WT BMDMs in response to stimuli to induce NLRP3, NLRC4, and AIM2 inflammasome activation. Furthermore, the activation of NLRP3, NLRC4, and AIM2 inflammasomes in both mouse and human cells was remarkably reduced by treatment with the HUWE1 inhibitor BI8622. HUWE1 mediated the K27-linked polyubiquitination of AIM2, NLRP3, and NLRC4, which led to inflammasome assembly, ASC speck formation, and sustained caspase-1 activation. Huwe1-deficient mice had an increased bacterial burden and decreased caspase-1 activation and IL-1β production upon Salmonella, Francisella, or Acinetobacter baumannii infection. Our study provides insights into the mechanisms of inflammasome activation as well as a potential therapeutic target against bacterial infection.

Atherosclerosis (AS) is the most common and serious complication in type 2 diabetes mellitus (T2DM). Recent studies have emphasized that inflammation is the main cause of atherosclerosis. Studies have shown that carcinoembryonic antigen-related cellular adhesion molecule 1 (CEACAM1) regulates the expression of matrix metallopeptidase 9 (MMP-9) after ischemic stroke to reduce inflammation. The aim of this study was to elucidate potential molecular mechanism of CEACAM1 on the inflammatory response in atherosclerosis. The serum levels of CEACAM1, MMP-9 and tissue inhibitors of metalloproteinase 1 (TIMP-1) in T2DM patients and healthy control was detected. The results showed that the levels of CEACAM1 and TIMP-1 were significantly decreased, and the levels of MMP-9 were significantly higher than those in the control group. Moreover, we also observed the effect of CEACAM1 on atherosclerosis in T2DM rats. Hematoxylin & eosin (HE) staining and oil red staining showed that CEACAM1 recombinant protein reduced intima-media thickness and the area of atherosclerotic plaques. In order to further explore the molecular mechanism of CEACAM1 regulating MMP-9/TIMP-1, we conducted experiments in rat aorta vascular endothelial cells (RAECs) and rat aorta smooth muscle cells (RASMCs). The result showed that CEACAM1 inhibits inflammatory response via MMP-9/TIMP-1 axis. Taken together, CEACAM1 attenuates diabetic atherosclerosis by inhibition of IκB/NF-κB signal pathway via MMP-9/TIMP-1 axis. Which indicate that CEACAM1 is potentially amenable to therapeutic manipulation for clinical application in atherosclerosis in T2DM.

Batteries assembled with lithium metal anodes and high-capacity cathodes—including air, sulfur, and lithium-rich transition metal oxides—have higher energy density than conventional Li-ion counterparts. Unfortunately, the lifetime of lithium metal cells is typically short, owing to the formation of dendrites on charging, which eventually shorts the cells. Short cycle life is also observed when lithium deposits with a “mossy” morphology; the high surface area of mossy deposits increases the rate of electrolyte degradation, eventually drying out the cells. Here we show that a lithium-ion-conducting, architected macroporous polyelectrolyte (AMP-1) serves as a long-lasting host for uniform and dense lithium–metal electrodeposits. High Coulombic efficiencies indicate the low occurrence of parasitic reactions with the electrolyte. Galvanostatic discharge experiments indicate that AMP-1 suppresses dendrite formation, extending over 2-fold the short-circuit time at high current density. Our success opens new dire...

Acetaminophen (APAP) is the leading cause of drug-induced acute liver failure. Sphingosine-1-phosphate (S1P), whose formation is catalyzed by sphingosine kinase (SPHK)-1 or -2, is a bioactive lipid implicated in human health and disease. Here, we show that APAP-treated sphK1-deficient (sphK1(−/−)) mice exhibited markedly less liver damage and reduced inflammation compared with the wild-type mice. SPHK1 deficiency alleviated APAP-induced endoplasmic reticulum (ER) stress by affecting the phosphorylation of inositol-requiring enzyme 1α (IRE1α) and protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK)-eukaryotic translation initiation factor 2α (eIF2α), levels of activating transcription factor 4 (ATF4), and activation of activating transcription factor 6 (ATF6). SPHK1 deficiency also inhibited mitochondrial permeability transition (MPT), as evidenced by the impaired phosphorylation of JNK, apoptosis signal-regulated kinase 1 (ASK1), and glycogen synthase kinase 3β (GSK3β). In addition, SPHK1 deficiency reduced the levels of histone deacetylase and promoted the acetylation of p65 and STAT1, thereby impairing the transcription of inflammatory genes. Supplementation with exogenous S1P significantly reversed the activation of the PERK-eIF2α-ATF4 pathway and ATF6 during ER stress as well as the activation of GSK3β, ASK1, and JNK during MPT. Both FTY720, a functional S1P receptor antagonist, and PF543, an SPHK1 inhibitor, significantly ameliorated APAP-induced liver injury and improved animal survival. Our study reveals a critical role for SPHK1 in mediating APAP-induced hepatotoxicity by promoting ER stress and MPT.

Background: Xinmailong (XML), a bioactive composite extracted from Periplaneta americana, has been widely used to treat cardiovascular diseases such as congestive heart failure. However, it is unclear whether XML has antiplatelet and antithrombotic effects. Methods: The effects of XML on agonist-induced platelet aggregation, adhesion and spreading, granule secretion, integrin α II bβ3 activation, and thrombus formation were evaluated. Phosphorylation of Syk, PLCγ2, Akt, GSK3β, and MAPK signaling molecules was also studied on agonist-induced platelets. In addition, the antithrombotic effects of XML were observed in vivo using an acute pulmonary thrombosis mouse model. Results: XML dose-dependently inhibited in vitro platelet aggregation and granule secretion induced by thrombin, collagen, and arachidonic acid (AA). XML also greatly reduced platelet adhesion and spreading on both collagen- and fibrinogen-coated surfaces. Biochemical analysis revealed that XML inhibited thrombin-, collagen-, and AA-induced phosphorylation of Syk, PLCγ2, Akt, GSK3β, and MAPK. Additionally, XML significantly inhibited in vivo thrombus formation in a collagen-epinephrine-induced acute pulmonary thrombosis mouse model. Conclusions and General Significance: Here, we provide the first report showing that XML inhibits platelet function and that it possesses antithrombotic activity. This suggests that XML could be a potential therapeutic candidate to prevent or treat platelet-related cardiovascular diseases.

Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) regulates collagen-mediated platelet activation through its cytoplasmic immunoreceptor tyrosine-based inhibition motifs (ITIMs). However, the function of CEACAM1’s extracellular cleavage fragments is currently unknown. In the present study, we used mass spectrometry (MS) to identify 9 cleavage fragments shed by matrix metallopeptidase 12 (MMP-12), and then we synthesized peptides with sequences corresponding to the fragments. QLSNGNRTLT (QLSN), a peptide from the A1-domain of CEACAM1, significantly attenuated collagen-induced platelet aggregation. QLSN also attenuated platelet static adhesion to collagen. Additionally, QLSN reduced human platelet secretion and integrin αIIbβ3 activation in response to glycoprotein VI (GPVI)–selective agonist, convulxin. Correspondingly, QLSN treatment significantly decreased convulxin-mediated phosphorylation of Src, protein kinase B (Akt), spleen tyrosine kinase (Syk) and phospholipase Cγ2 (PLCγ2) in human platelets. These data indicate that the CEACAM1-derived peptide QLSN inhibits GPVI-mediated human platelet activation. QLSN could potentially be developed as a novel antiplatelet agent. QLSN inhibit collagen-induced human platelet activation through glycoprotein VI.

The energy efficiency and cycle life of electrochemical cells with dissolved active materials are inextricably tied to the stability, conductivity, and transport selectivity of the cell's membrane. Membrane design rules have been lacking for such cells operating under harsh conditions, such as high alkalinity, due to the lack of selective, stable membranes. Here, we examined several classes of membranes for three aqueous Zn-based cell chemistries. In doing so, we uncovered a simple relationship between the membrane selectivity and the cell's cycle life, such that it is now possible to predict the lifetime of the cell on the basis of its membrane properties, thus avoiding time- or resource-intensive experimentation in large-format cells. Our work should greatly accelerate the identification of membranes for long-lasting, MW-scale redox-flow, and other low-cost grid batteries, which are required to last 10–20 years., United States. Department of Energy. Office of Basic Energy Sciences (Contract DE-AC02-05CH11231)

An innovative approach based on the variational sparse Bayesian learning method is presented for the optimal design of interleaved linear arrays with a fewer number of subarray elements. In this study, with a consideration of practical array assembling, the acceptable minimum element spacing can be freely adjusted and used to construct the constrained regions for subarray interleaving. The design of interleaved sparse arrays is then recast as a sparse constrained optimisation problem under region constraint, and a fast relevance vector machine is utilised to estimate the sparse weight vectors, with which the number of the selected antenna elements as well as their positions and excitations can be obtained. A set of representative numerical simulations validate the high accuracy and computational efficiency of the proposed method.

The co-pyrolysis of oil shale (a fine-grained and kerogen-rich sedimentary rock) and Chlorella vulgaris (one of microalgae) was carried out in a quartz tube reactor under different temperatures and blending ratios. The product fractional yields, gaseous products and different blending ratios were analyzed in order to obtain the optimal pyrolysis conditions for producing syngas (CO + H 2 ) from oil shale and the synergistic effect of co-pyrolysis. The results indicated that temperature obviously affected the product fractional yields and syngas production from oil shale. High temperature was beneficial to the CO and H 2 emission. And 800 °C was the optimal temperature for oil shale to produce syngas. Under co-pyrolysis, the liquid and gas production from oil shale was promoted by C. vulgaris , but the liquid and gas production from C. vulgaris was inhibited by oil shale. Furthermore, the inhibition of oil shale was stronger than the promotion of C. vulgaris . Meanwhile, blending with oil shale could reduce the total HV e,s and postpone the pyrolysis.

Lithium-sulfur batteries with a high energy density are being considered a promising candidate for next-generation energy storage. However, realization of Li-S batteries is plagued by poor sulfur utilization due to the shuttle of intermediate lithiation products between electrodes and its dynamic redistribution. To optimize the sulfur utilization, an understanding of its redox behavior is essential. Herein, we report a gel cathode consisting of a polysulfide-impregnated O- and N-doped porous carbon and an independent, continuous, and highly conducting 3-dimensional graphite film as the charge-transfer network. This design decouples the function of electron conduction and polysulfide absorption, which is beneficial for understanding the sulfur redox behavior and identifying the dominant factors leading to cell failure when the cells have high sulfur content and insufficient electrolyte. This design also opens up new prospects of tuning the properties of Li-S batteries via separately designing the material functions of electron conduction and polysulfide absorption.

Our previous study together with other investigations have reported that neonatal hypoxia or ischemia induces long-term cognitive impairment, at least in part through brain inflammation and hypomyelination. However, the detailed mechanisms are not fully understood. Here, we used a rodent model of neonatal hypoxia by subjecting postnatal day 0 (P0) rat pups to systemic hypoxia (3.5 h). We found that neonatal hypoxia increased the glutamate content and initiated inflammatory responses at 4 h and 1 day after hypoxia, caused hypomyelination in the corpus callosum, and impaired hippocampus-dependent learning and memory when assessed 30–60 days after hypoxia. Interestingly, much of the hypoxia-induced brain damage was ameliorated by treatment with the ATP analogue 2′,3′-0-(2,4,6-trinitrophenyl)-adenosine 5′-triphosphate (TNP-ATP; blocks all ionotropic P2X1-7 receptors), whereas treatment with pyridoxalphosphate-6-azophenyl-2′,4′-disulphonic acid (PPADS; inhibits P2X1-3 and P2X5-7 receptors) was less neuroprotective. Our data indicated that activation of ionotropic ATP receptors might be partially, if not fully, involved in glutamate deregulation, neuroinflammation, hypomyelination, and cognitive dysfunction after neonatal hypoxia.

Many next-generation batteries, including lithium–sulfur (Li–S) and redox-flow batteries, rely on robust and selective membranes to sustainably block the crossover of active species between the negative and positive electrodes. Preventing membrane degradation is essential for long-term battery operation. Nevertheless, challenges persist in understanding how to minimize the impact of chemical or structural changes in the membrane on its performance. Here we elucidate design rules for understanding and controlling the long-term polysulfide-blocking ability of size-selective polymer membranes cast from polymers of intrinsic microporosity (PIMs). PIM-1 membranes feature electrophilic 1,4-dicyanooxanthrene moieties that are shown to be susceptible to nucleophilic attack by lithium polysulfides, which are endogenous to lithium–sulfur batteries. Once transformed, the polymer chains reconfigure by swelling with additional electrolyte and the size-selective transport ability of the membrane is compromised. These undesirable, chemically-induced changes in membrane structure and selectivity were prevented by controllably cross-linking PIM-1. In doing so, low polysulfide crossover rates were sustained for >95 h, highlighting the critical role of macromolecular membrane design in the development of next-generation battery technologies.

Dye-sensitized solar cells (DSSCs) have attracted world-wide attention due to their low cost, high conversion efficiency, and environmental friendliness. Pt catalyst is usually used as the catalyst in the counter electrode of DSSCs due to its high electrochemical catalytic activity toward tri-iodide reduction. However, the high cost and scarcity of Pt prevent its large-scale application in DSSCs. It is highly desirable to replace Pt with low-cost catalysts made from earth-abundant elements. Here, we report a dual-template synthesis of N-doped macro/mesoporous carbon (macro/meso-NC) with an open-pore structure as the catalyst in the counter electrode of DSSCs. The catalytic activity of macro/meso-NC toward tri-iodide reduction has been tested by cyclic voltammetry (CV) and photocurrent-voltage (J–V) curves. It is found that the macro/meso-NC possesses excellent electrochemical catalytic activity with higher open-circuit voltage and cell efficiency than Pt. A high energy conversion efficiency of 7.27% has been achieved based on the metal-free macro/meso-NC, demonstrating as a promising catalyst for low-cost DSSCs.

The ground source heat pump system is recognized as one of the most significant technologies for building heating/cooling system. The development of hybrid ground source heat pump further solves the conventional system’s problems such as overly depending on conventional energy and soil thermal balance problem. The hybrid system in this research combines a horizontal ground loop and a liquid dry cooler. Both short-term simulations and long-term simulations were carried out in TRNSYS to analyzed energy variation and soil thermal condition with respect to different diverter heating/cooling set temperatures. In order to achieve automatic control of the working fluid direction, a new TRNSYS model was coded in FORTRAN and imported to TRNSYS 18 environment. The results verify diverter heating/cooling set temperatures’ influence to the system overall performance. The recommended operational diverter set temperature range is also given.

Parkinson's disease (PD) is characterized by the degeneration of dopaminergic neurons and excessive microglial activation in the substantia nigra pars compacta (SNpc). In the present study, we aimed to demonstrate the therapeutic effectiveness of the potent sphingosine-1-phosphate receptor antagonist fingolimod (FTY720) in an animal model of PD induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), and to identify the potential mechanisms underlying these therapeutic effects. C57BL/6J mice were orally administered FTY720 before subcutaneous injection of MPTP. Open-field and rotarod tests were performed to determine the therapeutic effect of FTY720. The damage to dopaminergic neurons and the production of monoamine neurotransmitters were assessed using immunohistochemistry, high-performance liquid chromatography, and flow cytometry. Immunofluorescence (CD68- positive) and enzyme-linked immunosorbent assay were used to analyze the activation of microglia, and the levels of activated signaling molecules were measured using Western blotting. Our findings indicated that FTY720 significantly attenuated MPTP-induced behavioral deficits, reduced the loss of dopaminergic neurons, and increased dopamine release. FTY720 directly inhibited MPTP-induced microglial activation in the SNpc, suppressed the production of interleukin (IL)-6, IL-1β, and tumor necrosis factor-α in BV-2 microglial cells treated with 1-methyl-4-phenylpyridinium (MPP

Lithium–sulfur and lithium–air batteries offer theoretical energy densities an order of magnitude higher than that of current lithium-ion batteries and are considered as promising candidates as the next-generation battery chemistries. For an efficient use of these new battery chemistries, careful selection of suitable electrode materials/structures is critical. Graphene, a unique two-dimensional nanomaterial, with its superior electronic conductivity, mechanical strength, and flexibility has been successfully applied in battery studies. Graphene, even with imperfect layers, will be of great interest to battery industrial applications if the manufacturing cost is reduced. Herein, we demonstrate the application of low-cost graphene sponge/sheets derived from expandable graphite in both lithium–sulfur and hybrid lithium–air batteries, respectively, as a cathode conductive matrix to accommodate the soluble polysulfides and as a catalyst for the oxygen reduction reaction. High utilization of active materials and good cycling stability are realized in lithium–sulfur and hybrid lithium–air batteries by employing this low-cost material, demonstrating its promise for use in next-generation battery chemistries.

Water hyacinth pyrolysis was carried out in a quartz tube reactor. Different particle sizes, pyrolysis temperatures and catalysts were tested. The product fractional yields, gaseous products, surface morphology and crystal structure were analyzed in order to obtain the optimal pyrolysis condition for producing syngas (CO + H2) from water hyacinth. The results indicated that particle size had a significant impact on water hyacinth pyrolysis and among four particle sizes in this paper dp

Expensive Pt-based catalysts are usually required to achieve a high discharge voltage and long operation life for hybrid Li-air batteries. However, the cost of the catalysts needs to be lowered by either reducing the Pt loading in the catalysts or replacing Pt with less expensive catalysts. Here, we report the strong coupling of Co 3 O 4 nanocrystals with an O- and N-doped carbon nanoweb (ON-CNW) as a low-cost, highly-efficient catalyst for hybrid Li-air batteries with an alkaline catholyte. Co 3 O 4 /ON-CNW greatly reduces the discharge overpotential compared to ON-CNW and exhibits longer cycle life, which is even better than that of the best reported N-doped mesoporous carbon (0.016% decrease in efficiency per cycle for 130 cycles compared to 0.017% decrease per cycle for 100 cycles obtained with N-doped mesoporous carbon). Although Pt/C exhibits a slightly higher initial discharge voltage (3.02 V compared to 3.00 V for Co 3 O 4 /ON-CNW), the cycle life of Pt/C is 3 O 4 /ON-CNW as a viable, stable cathode for hybrid Li-air batteries.

While many synthesis methods have been reported for Co3O4–carbon nanocomposites as a bifunctional electrocatalyst for the oxygen reduction reaction (ORR) and the oxygen evolution reaction (OER) in alkaline solutions, the individual contributions of Co3O4 and CNW towards ORR and OER are still not clear. Here, we report the individual functionality of Co3O4 and the N-doped carbon nanoweb (CNW) in ORR and OER. The Co3O4/CNW bifunctional catalysts were synthesized by an in situ growth of Co precursors onto CNW followed by a controlled heat treatment. The specific functions of Co3O4 and CNW were delineated by rotating disk electrode measurements. It was found that Co3O4 alone exhibited poor ORR catalytic activity. However, in the presence of CNW, Co3O4 assisted the selective four-electron oxygen reduction over the two-electron pathway. Analyses of the Tafel slope and reaction order suggested that Co3O4 acted as the primary catalytic site for OER. CNW improved the electronic conduction between Co3O4 and the current collector. CNW underwent serious degradation at the high potential of the OER but its stability improved greatly upon the deposition of Co3O4. Two possible mechanisms for the improved catalytic stability are discussed. The findings demonstrate the specific functions of Co3O4 and CNW in catalyzing the OER and ORR and further establish an understanding of the synergy of the composite in electrocatalysis.

VO2 (B) is an interesting cathode candidate in lithium-ion batteries with a high theoretical capacity and fast charge/mass transfer rate. Most of the studies on this material have focused on the lithium insertion reaction in the range of 4.0–1.0 V. In this paper, VO2/rGO nanocomposite was prepared by a microwave-assisted solvothermal method and investigated in both lithium-ion and sodium-ion batteries as a potential anode. The VO2 (B) nanorods have an average diameter of ∼200 nm, and is encapsulated by reduced graphene oxide (rGO) nanosheets. Electrochemical results reveal that the VO2/rGO electrodes exhibit stable cycling and good rate performance in both Li and Na cells. Reversible capacities of 400 mA h g−1 over 400 cycles (vs. Li/Li+) and 200 mA h g−1 over 200 cycles (vs. Na/Na+) have been achieved, indicating it is potential as an anode candidate either in lithium- or sodium-ion batteries. Nevertheless, the reaction mechanisms seem to be different in Li and Na cells. The crystal structure of VO2 (B) is maintained at a low discharge potential of 0.05 V in lithium-ion cells, while phase amorphization occurs in sodium-ion cells below 0.5 V. This result is consistent with the previous study on TiO2, further confirming that some stable metal oxides may show rather different behaviors in Na cells than expected.

We report here the design of low-cost hierarchical oxygen reduction/evolution reaction (ORR/OER) catalysts that could achieve higher cell efficiency and several times longer cycle life than conventional Pt/C + IrO2 bifunctional catalysts in metal–air batteries (Zn–air and Li–air batteries).

Neuropsychiatric (NP) involvement in systemic lupus erythematosus (SLE) severely impacts patients’ quality of life and leads to a poor prognosis. The current therapeutic protocol, corticosteroid administration, can also induce neuropsychiatric disorders. FTY720 is an immunomodulator that selectively confines lymphocytes in lymph nodes and reduces autoreactive T cell recruitment to the central nervous system (CNS). This study aimed to identify a novel therapeutic strategy for NPSLE. B6.MRL-lpr mice were treated with oral administration of FTY720 (2 mg/kg) three times per week for 12 weeks, to evaluate its efficacy in a model of NPSLE. FTY720 significantly attenuated the impulsive and depression-like behavior of B6.MRL-lpr mice. Neuronal damage was reduced in the cortex, hippocampus, and amygdala of the FTY720-treated B6.MRL-lpr mice, as well as in TNF-α-treated HT22 cells. Additionally, FTY720 downregulated levels of inflammatory cytokines, and reduced the infiltration of T cells and neutrophils in the brain parenchyma. FTY720 also acted directly on cerebral endothelial cells and reduced the permeability of the blood-brain barrier (BBB) in B6.MRL-lpr mice, as evidenced by reduced central IgG and albumin levels. Finally, FTY720 significantly inhibited activation of PI3K/Akt/GSK3β/p65 signaling, which further reduced the expression levels of adhesion molecules in bEND.3 cells treated with B6.MRL-lpr mouse serum. Collectively, our data indicate that oral administration of FTY720 at an early stage has beneficial effects in NPSLE-model B6.MRL-lpr mice, suggesting that it may represent an effective new therapeutic strategy for NPSLE.