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This study investigated the protective effect of aplysin on the liver and its influence on inflammation and the gut microbiota in rats with ethanol-induced liver injury.Male Sprague-Dawley rats were randomly assigned to an alcohol-containing liquid diet, control liquid diet or treatment with aplysin for 8 weeks. Hepatic and intestinal histopathological analysis was performed, and cytokine levels and the intestinal mucosal barrier were assessed. Enterobacterial repetitive intergenic consensus polymerase chain reaction (ERIC-PCR) and 16S rDNA high-throughput sequencing were performed to provide an overview of the gut microbiota composition.Chronic alcohol exposure caused liver damage in rats. Serum aspartate aminotransferase (AST), aminotransferase (ALT), alkaline phosphatase (ALP) and triglyceride (TG) activities in liver tissue were higher than in the control group. Alcohol administration elevated the levels of serum transforming growth factor-β (TGF-β) and tumor necrosis factor-α (TNF-α) and reduced interleukin-10 (IL-10) levels compared with those of control rats. In addition, the levels of plasma endotoxin, diamine oxidase (DAO), and fatty acid-binding protein 2 (FABP2) in the alcohol group were higher than in the control group. The results of ERIC-PCR indicated that aplysin treatment shifted the overall structure of the ethanol-disrupted gut microbiota toward that of the control group. One hundred twenty to 190 genera of bacteria were detected by high throughput sequencing. Alcohol-induced changes in the gut microbial composition were detected at the genus level. These alcohol-induced effects could be reversed with aplysin treatment.These results suggest that aplysin exerts a protective effect on ethanol-induced hepatic injury in rats by normalizing fecal microbiota composition and repairing intestinal barrier function.

This paper proposes a data-driven diagnostic approach for Polymer Electrolyte Membrane Fuel Cell (PEMFC) systems. Fault detection and isolation (FDI) is realized by analyzing individual cell voltages. A feature extraction method Fisher Discriminant Analysis (FDA) and a multi-class classification method Directed Acyclic Graph Support Vector Machine (DAGSVM) are utilized successively to extract the useful features from raw data and classify the extracted features into various classes related to health states. Experimental data of two different stacks are used to validate the proposed approach. The results show that five concerned faults can be detected and isolated with a high accuracy. Moreover, the light computational cost of the approach enhances the possibility of its online implementation.

Abstract Li[Ni 1/3 Mn 1/3 Co 1/3 ]O 2 /graphite, Li[Ni 0.5 Mn 0.3 Co 0.2 ]O 2 /graphite and Li[Ni 0.6 Mn 0.2 Co 0.2 O 2 ]/graphite pouch cells were examined with and without electrolyte additives using the ultra high precision charger at Dalhousie University, electrochemical impedance spectroscopy, gas evolution measurements and “cycle-store” tests. The electrolyte additives tested were vinylene carbonate (VC), prop-1-ene-1,3-sultone (PES), pyridine-boron trifluoride (PBF), 2% PES + 1% methylene methanedisulfonate (MMDS) + 1% tris(trimethylsilyl) phosphite (TTSPi) and 0.5% pyrazine di-boron trifluoride (PRZ) + 1% MMDS. The charge end-point capacity slippage, capacity fade, coulombic efficiency, impedance change during cycling, gas evolution and voltage drop during “cycle-store” testing were compared to gain an understanding of the effects of these promising electrolyte additives or additive combinations on the different types of pouch cells. It is hoped that this report can be used as a guide or reference for the wise choice of electrolyte additives in Li[Ni 1/3 Mn 1/3 Co 1/3 ]O 2 /graphite, Li[Ni 0.5 Mn 0.3 Co 0.2 ]O 2 /graphite and Li[Ni 0.6 Mn 0.2 Co 0.2 O 2 ]/graphite pouch cells and also to show the shortcomings of particular positive electrode compositions.

The continual spread of novel coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), posing a severe threat to the health worldwide. The main protease (Mpro, alias 3CLpro) of SARS-CoV-2 is a crucial enzyme for the maturation of viral particles and is a very attractive target for designing drugs to treat COVID-19. Here, we propose a multiple conformation-based virtual screening strategy to discover inhibitors that can target SARS-CoV-2 Mpro. Based on this strategy, nine Mpro structures and a protein mimetics library with 8960 commercially available compounds were prepared to carry out ensemble docking for the first time. Five of the nine structures are apo forms presented in different conformations, whereas the other four structures are holo forms complexed with different ligands. The surface plasmon resonance assay revealed that 6 out of 49 compounds had the ability to bind to SARS-CoV-2 Mpro. The fluorescence resonance energy transfer experiment showed that the biochemical half-maximal inhibitory concentration (IC50) values of the six compounds could hamper Mpro activities ranged from 0.69 ± 0.05 to 2.05 ± 0.92 μM. Evaluation of antiviral activity using the cell-based assay indicated that two compounds (Z1244904919 and Z1759961356) could strongly inhibit the cytopathic effect and reduce replication of the living virus in Vero E6 cells with the half-maximal effective concentrations (EC50) of 4.98 ± 1.83 and 8.52 ± 0.92 μM, respectively. The mechanism of the action for the two inhibitors were further elucidated at the molecular level by molecular dynamics simulation and subsequent binding free energy analysis. As a result, the discovered noncovalent reversible inhibitors with novel scaffolds are promising antiviral drug candidates, which may be used to develop the treatment of COVID-19.

Proton conducting ceramics (PCC) cells are promising energy conversion devices that enable high efficiency energy conversion at lower temperature range, solving the challenge of conventional solid oxide cells (SOCs) due to the high operating temperature. Electrochemical performance and chemical stability of PCC electrolyte has been investigated in recent studies, suggesting that rare-earth doped Ba(Zr,Ce)O3 perovskite-type ceramics are optimal materials exhibiting high proton conductivity and chemical stability during operations. On the contrary, mechanical stability of these PCC electrolyte materials has not been evaluated despite the fact that the mechanical properties are critically important for achieving long-term stable operation as fuel cells or electrolyser cells. For the development of conventional SOCs, mechanical stability during high temperature operation was one of the most significant challenges to deal with, which was attained as a result of detailed studies on in-situ elastic properties of composing materials such as oxygen ion conducting electrolytes and residual stresses. Similarly, for PCC cells, mechanical properties of cells and composing materials have been of significant interest in order to achieve mechanically stable long-term operation, even though PCC cells operate at lower temperature than SOCs. Furthermore, the metal-supported (MS) structure which provides superior mechanical robustness compared to anode-supported (AS) structure is expected to be applied effectively to PCC cells, which are called proton conducting ceramics – metal-supported cells (PCC-MSCs), leading to greater necessity of the mechanical evaluation of the cells and composing materials. Electrolyte is the most crucial component in an electrochemical cell and must be mechanically stable because ion transport and gas tightness made by electrolyte determines electrical performance. However, there has been important concern that larger thermal stresses might be introduced in PCC cells compared to SOCs, resulting from the thermal expansion coefficient (TEC) mismatch between the electrode and electrolyte and from the chemical expansion by the hydration that occurs in a certain temperature range. The PCC electrolyte is highly in need of investigation on in-situ mechanical properties, especially on elastic properties. In this study, elastic properties of electrochemically promising PCC, Y-doped Ba(Zr,Ce)O3 perovskite-type ceramics, were investigated under high temperature conditions. Elastic moduli such as Young’s modulus and Poisson’s ratio were measured by the method that we previously developed for elastic investigation in high temperature conditions using ultrasonic waves. This method enables highly accurate and repetitive examination of elastic properties at high temperatures in materials with poor sinterability including PCC by measuring ultrasonic sound velocities in pellets typically fabricated for electrochemical tests. Pellets of BaZr1-xYxO3-δ (BZY) with different concentrations of doped yttrium, BaZr0.9Y0.1O3-δ (BZY10), BaZr0.85Y0.15O3-δ (BZY15), and BaZr0.8Y0.2O3-δ (BZY20), were fabricated. Additionally, pellets of BaZryCe1-yY0.1O3-δ (BZCY) with different ratio of Ce to Zr, BaZr0.7Ce0.2Y0.1O3-δ (BZCY721) and BaZr0.8Ce0.1Y0.1O3-δ (BZCY811) were fabricated. Powders of PCCs above were consolidated to be thick rounded shape and sintered in air. Each prepared sample was set in an electric furnace in laboratory air atmosphere and sound velocities were measured with the sample slowly heated up to 700 °C and subsequently cooled down to room temperature to calculate elastic moduli at each measuring point. In the first series of heating and cooling measurements for as-sintered samples, hysteresis on elastic moduli in intermediate temperature range was observed. We repeatedly conducted a series of heating and cooling measurements several times, and then the hysteresis was not observed any further. Fig.1 shows final state Young’s modulus of BZCY721, BZCY811, and BZY10 (BZCY901) without hysteresis. Elastic moduli at room temperature have not changed through multiple heating and cooling measurements, and crystal structures and lattice parameters were also confirmed to remain constant by x-ray diffraction (XRD) analysis. The hysteresis found in a specific temperature range suggests that elastic moduli were influenced presumably by a change in defect structure of PCC caused by hydration or defect association of oxygen vacancies and dopants. At room temperature, Young’s modulus decreased with the increment of Ce concentration by 16 % from BZY10 to BZCY721. When materials have the same crystalline structure, Young’s modulus generally decreases as mean atomic volume of the base crystal increases. Because BaCeO3 has larger mean atomic volume than BaZrO3, this observation is qualitatively reasonable. However, in high temperatures, the difference became significant only for BZCY721, Young’s modulus decreased by 30 % from that at room temperature in BZCY721. These results suggest that Ce substitution causes different high temperature dependences. Figure 1

Diseases related to ethanol abuse, especially binge drinking, are becoming one of the most costly health problems in the world. Ethanol-induced DNA damage plays a key role in the etiology of these diseases. New compounds are expected to offer new options against ethanol-induced genotoxicity. It was found, for the first time, that resveratrol and three analogues with 3,5-dimethoxyl groups in the A-ring, such as (E)-4-(3,5-dimethoxystyryl)phenol (RV32), or with a quinolyl in the B-ring, such as (E)-5-[2-(quinolin-4-yl)vinyl]benzene-1,3-diol (RV01) and (E)-4-(3,5-dimethoxystyryl)quinoline (RV02), strongly inhibited ethanol-induced oxidative DNA damage in human peripheral lymphocytes in vitro. Resveratrol and RV32 with more hydroxyl groups in structures showed stronger direct scavenging activity of hydroxyl radicals than RV01 and RV02. Moreover, all compounds reduced hydroxyl radical generation by regulating the mRNA expression of alcohol dehydrogenase 1B and acetaldehyde dehydrogenase 2. Further studies proved resveratrol and three analogues activated the base excision repair system in transcriptional and protein levels in DNA repair process. Both 3,5-dimethoxyl groups and quinolyl modification may enhance such activity. In summary, resveratrol and its three analogues revealed significant protective activity against ethanol-induced oxidative DNA damage in human peripheral lymphocytes, which demonstrates their potential for use in prevention and treatment of the diseases related to ethanol abuse.

Chemotherapy is a conventional treatment for glioma, but its efficacy is greatly limited due to low blood-brain barrier (BBB) permeability and lack of specificity. Herein, intelligent and tumor microenvironment (TME)-responsive folic acid (FA) derivatives and mitochondria-targeting berberine (BBR) derivatives co-modified liposome coated with Tween 80 loading paclitaxel (PTX-Tween 80-BBR + FA-Lip) was constructed. Specifically speaking, liposomes modified by FA can be effectively target ed to glioma cells. BBR, due to its delocalized positive electricity and lipophilicity, can be attracted by mitochondrial membrane potential and concentrate on mitochondria to achieve mitochondrial targeting and induce cell apoptosis. By simultaneously modifying the liposome with FA and BBR to deliver drugs, leads to a good therapeutic effect of glioma through FA-based glioma targeting and BBR-based mitochondrial targeting. In addition, the surface of the liposome was coated with Tween 80 to further improve BBB penetration. All results exhibited that PTX-Tween 80-BBR + FA-Lip can observably improve the chemotherapy therapeutic efficacy through the highly specific tumor targeting and mitochondrial targeting, which can provide new ideas and methods for the targeted therapy of glioma.

Data collected in a large epidemiologic study were analyzed to examine respiratory health effects of residential coal use in 7058 school children living in the four Chinese cities of Chongqing, Guangzhou, Lanzhou, and Wuhan. A Scenario Evaluation Approach was used to develop two exposure variables, heating coal smoke and cooking coal smoke. Estimated lifetime exposures to heating coal smoke and cooking coal smoke were both classified into four-level ordinal scales, as follows: no reported exposure (control); lightly exposed; moderately exposed; and heavily exposed. Zero-one dummy variables were constructed for each exposure level other than the control level (total six variables). These variables were entered into the analytical model. We tested for exposure-response relationships using logistic regression models, while controlling for other relevant covariates, including an indicator variable of ambient air pollution levels. We observed monotonic and positive exposure-response relationships of exposure to heating coal smoke with modeled odds ratios (ORs) of phlegm, cough with phlegm, and bronchitis. Other health outcomes were not associated with such exposure in a monotonic exposure-response pattern. However, ORs for cough, wheeze, and asthma were all higher in the exposed groups than in the control group. We observed no consistent associations between cooking coal smoke and the examined health outcomes. We conclude that exposure to heating coal smoke could have adverse effects on children's respiratory symptoms and illnesses in these four Chinese cities.