Cyclic Peptide Mimotopes for the Detection of Serum Anti–ATIC Autoantibody Biomarker in Hepato-Cellular Carcinoma

Tumor-associated (TA) autoantibodies have been identified at the early tumor stage before developing clinical symptoms, which holds hope for early cancer diagnosis. We identified a TA autoantibody from HBx-transgenic (HBx-tg) hepatocellular carcinoma (HCC) model mouse, characterized its target antigen, and examined its relationship to human HCC. The mimotopes corresponding to the antigenic epitope of TA autoantibody were screened from a random cyclic peptide library and used for the detection of serum TA autoantibody. The target antigen of the TA autoantibody was identified as an oncogenic bi-functional purine biosynthesis protein, ATIC. It was upregulated in liver cancer tissues of HBx-tg mouse as well as human HCC tissues. Over-expressed ATIC was also secreted extracellularly via the cancer-derived exosomes, which might cause auto-immune responses. The cyclic peptide mimotope with a high affinity to anti-ATIC autoantibody, CLPSWFHRC, distinguishes between serum samples from HCC patients and healthy subjects with 70.83% sensitivity, 90.68% specificity (AUC = 0.87). However, the recombinant human ATIC protein showed a low affinity to anti-ATIC autoantibody, which may be incompatible as a capture antigen for serum TA autoantibody. This study indicates that anti-ATIC autoantibody can be a potential HCC-associated serum biomarker and suggests that autoantibody biomarker’s efficiency can be improved by using antigenic mimicry to native antigens present in vivo.     

A New Potent and Selective Monoamine Oxidase-B Inhibitor with Extended Conjugation in a Chalcone Framework: 1-[4-(Morpholin-4-yl)phenyl]-5-phenylpenta-2,4-dien-1-one

The general blueprint for the design of monoamine oxidase-B (MAO-B) inhibitors has been based on two phenyl or heteronuclei linked via a spacer of appropriate length. In this study, 1-[4-(morpholin-4-yl)phenyl]-5-phenylpenta-2,4-dien-1-one (MO10) was prepared by the condensation of 4′-morpholinoacetophenone and cinnamaldehyde in basic alcoholic medium. MO10 was assessed for inhibitory activity against two human MAO isoforms, MAO-A and MAO-B. Interestingly, MO10 showed a remarkable inhibition against MAO-B with an IC₅₀ value of 0.044 μM along with a selectivity index of 366.13. The IC₅₀ value was better than that of lazabemide (IC₅₀ value of 0.063 μM), which was used as a reference. Kinetics studies revealed that MO10 acted as a competitive inhibitor of MAO-B, with a K_i value of 0.0080 μM. The observation of recovery of MAO-B inhibition, compared to reference levels showed MO10 to be a reversible inhibitor. MTT assays showed that MO10 was nontoxic to normal VERO cells with an IC₅₀ value of 195.44 μg/mL. SwissADME predicted that MO10 provided advantageous pharmacokinetics profiles for developing agents acting on the central nervous system, that is, high passive human gastrointestinal absorption and blood–brain barrier permeability. Molecular docking simulations showed that MO10 properly entered the aromatic cage formed by Y435, Y398, and FAD of the active site of MAO-B. On the basis of these results, MO10 can be considered a promising starting compound in development of agents for the treatment of various neurodegenerative disorders.     

Quantitative analysis of microbial community structure in two-phase anaerobic digesters treating food wastewater

An acidogenic reactor with a 0.5-L working volume and a methanogenic digester with a 5-L of working volume were operated for 150 days on a continuous mode to investigate the structure of a microbial community during food wastewater treatment. During the steady state of anaerobic digestion, volatile solids (VS) removal efficiency in the pilot plant was approximately 65%. The bacterial population was higher than any other methanogens detected during the entire anaerobic process and treatment of raw food wastewater. Methanomicrobiales (MMB), Methanosarcinales (MSL), and Methanobacteriales (MBT) were detected during digestion. The methanogenic population present in the acidogenic reactor was directly affected by the archaeal community in raw food wastewater. However, the shift of microbial community in the methanogenic digester was relatively gradual. The performance of methanogenic digester might be more related to the change of microbial metabolism affected by the physicochemical properties of the input substrate.     

Simvastatin Attenuates the Oxidative Stress,Endothelial Thrombogenicity and the Inducibility of Atrial Fibrillation in a Rat Model of Ischemic Heart Failure

Increased atrial oxidative stress has an important role in inducing and maintaining atrial fibrillation (AF), and the activation of the small GTPase Rac1 contributes to the oxidative stress. We investigated the relationship of Rac1, atrial endothelial thromboprotective markers and AF inducibility and if simvastatin has a potential beneficial effect on a myocardial infarction (MI)-induced heart failure (HF) rat model. Rats were randomized into three groups (shams, MI group and simvastatin treatment group) and underwent echocardiography, AF induction studies and left atrial (LA) fibrosis analysis. Atrial Rac 1, sodium calcium exchanger (I_NCX), sarcoplasmic reticulum calcium ATPase (SERCA), endothelial nitric oxide synthase (eNOS) and induced nitric oxide synthase (iNOS) were measured. AF inducibility, AF duration and LA fibrosis were significantly higher in the MI group (p < 0.001 vs. sham), which were significantly reduced by simvastatin (p < 0.05 vs. MI). The reduced expressions of atrial eNOS, SERCA, thrombomodulin, tissue factor pathway inhibitor and tissue plasminogen activator in the MI group were significantly improved by simvastatin. Furthermore, the increased expression of atrial iNOS, I_NCX and Rac1 activity were significantly decreased by the simvastatin. Oxidative stress, endothelial dysfunction and thrombogenicity are associated with the promotion of AF in a rat model of ischemic HF. These were associated with increased Rac1 activity, and simvastatin treatment prevents these changes.     

Phosphorous retention capacity of filter media for estimating the longevity of constructed wetland

The filter medium could be selected and the longevity of the filter medium by the phosphorus saturation could be predicted in the constructed wetland system, accordingly proposing the scheme to remove the phosphorus for a long period. The phosphorus adsorption capacities of various filter media were investigated in relation to the size and types of filter media to screen the optimal condition. The objective of this study was to evaluate the constructed wetland longevity by improving P adsorption capacity. The maximum P adsorption capacities of filter media A (4--10 mm), B (2--4 mm), and C (0.1--2 mm) were 7.7, 11.6, and 22.5 mg/kg, respectively, showing that they increased as the filter media size decreased. Among the experimental media, the optimal filter media size was 0.1--2 mm. When Ca, Mg, Al and Fe were added to the filter medium C, which is the optimal filter medium, the addition of Ca improved mostly the P adsorption capacity. In the alternative proposal to use these facts, the oyster shell was added to the filter medium and the P adsorption capacity was examined: adding 2% oyster shell increased the P adsorption capacity from 23 to 36 mg/kg. In the column where the oyster shell was mixed, when the oyster shell content was 5%, 10%, 20%, 40%, 60%, 80%, and 100% in the filter medium C, the respective saturation times of the P adsorption were about 6, 9, 17, 30, 43, 56, and 70 days. When the oyster shell content was 0%, 5%, 10%, 20%, 40%, 60%, 80%, and 100% after 1 month in the column, the P adsorption amount was about 180, 600, 1560, 4280, 6157, 7089, 7519, and 7925 mg/kg, respectively. The increment of the P adsorption amount was small if the oyster shell content was 60% or more, because the filter medium with more than 60% oyster shell content did not approach the saturation time by the P adsorption yet. The P adsorption amount for 60%, 80%, and 100% could be predicted as about 9702, 12,879, and 16,056 mg/kg, respectively. The largest amount of extracted P in the filter media with oyster shell after 30 days of P solution application was bound to Ca, followed by water soluble-P, Al--P, and Fe--P. Therefore, it was concluded that the adsorption amount of the phosphorus could be increased by adding the oyster shell to the filter medium. Also, it was concluded that adding the oyster shell to the filter medium in the constructed wetland was the scheme to extend the longevity of the constructed wetland by the phosphorus saturation, and using the oyster shell would be useful in aspect of economical efficiency and easiness. Especially, it would be the alternative proposal to reduce the environmental pollution in aspect of recycling wastes.     

Impacts of climate and land‐cover changes on water resources in a humid subtropical watershed: a case study from East Texas,USA

This study investigates the response of water resources regarding the climate and land‐cover changes in a humid subtropical watershed during the period 1970–2009. A 0.7°C increase in temperature and a 16.3% increase in precipitation were observed. Temperature had a lower increase trend, and precipitation showed definite increasing trend compared to previous studies. The main trend of land‐cover change was conversion of vegetation and barren lands to developed and crop lands affected by human intervention, and forest and grass to bush/shrub which considered to be caused by natural climate system. Hydrologic responses to climate and land‐cover changes resulted in increases of surface run‐off (15.0%), soil water content (2.7%), evapotranspiration (20.1%) and a decrease in groundwater discharge (9.2%). We found that surface run‐off is relatively stable with precipitation, whereas groundwater discharge and soil water content are sensitive to changes in land cover, especially land cover brought about by human intervention.     

Recent Progress of Innovative Perovskite Hybrid Solar Cells

Recently, innovative perovskite hybrid solar cells have attracted great interest in solar cell research fields, such as dye-sensitized solar cells, organic photovoltaics, thin-film solar cells, and silicon solar cells, because their device efficiencies are gradually approaching those of crystalline Si solar cells, and they can be fabricated by cheap low-temperature solution processes. Here, we review the recent progress of innovative perovskite hybrid solar cells. The introduction includes the general concerns about solar cells and why we need innovative solar cells. The second part explains the structure and the material properties of hybrid perovskite materials. We focus on why the hybrid perovskite materials can exhibit excellent solar cell properties, such as high open-circuit voltage. The third part introduces recent progress in innovative perovskite hybrid solar cells, in terms of device architecture and deposition methods for dense perovskite thin films with full surface coverage. The device architecture is important in attaining high power conversion efficiency; the device operating mechanism is dependent on the device structure; and the pinhole-free dense perovskite thin films with full surface coverage are crucial for achieving high efficiency. Finally, we summarize the recent progress in perovskite hybrid solar cells, and the issues to be solved, in the summary and outlook section.     

Effects of Heat Treatment on the Microstructures and High Temperature Mechanical Properties of Hypereutectic Al–14Si–Cu–Mg Alloy Manufactured by Liquid Phase Sintering Process

Hypereutectic Al–Si alloy is an aluminum alloy containing at least 12.6 wt.% Si. It is necessary to evenly control the primary Si particle size and distribution in hypereutectic Al–Si alloy. In order to achieve this, there have been attempts to manufacture hypereutectic Al–Si alloy through a liquid phase sintering. This study investigated the microstructures and high temperature mechanical properties of hypereutectic Al–14Si–Cu–Mg alloy manufactured by liquid phase sintering process and changes in them after T6 heat treatment. Microstructural observation identified large amounts of small primary Si particles evenly distributed in the matrix, and small amounts of various precipitation phases were found in grain interiors and grain boundaries. After T6 heat treatment, the primary Si particle size and shape did not change significantly, but the size and distribution of CuAl₂ (θ) and AlCuMgSi (Q) changed. Hardness tests measured 97.36 HV after sintering and 142.5 HV after heat treatment. Compression tests were performed from room temperature to 300 °C. The results represented that yield strength was greater after heat treatment (RT?~?300 °C: 351?~?93 MPa) than after sintering (RT?~?300 °C: 210?~?89 MPa). Fracture surface analysis identified cracks developing mostly along the interface between the primary Si particles and the matrix with some differences among temperature conditions. In addition, brittle fracture mode was found after T6 heat treatment.     

Microstructure,Tensile and Fatigue Properties of Al–5 wt.%Mg Alloy Manufactured by Twin Roll Strip Casting

This study investigated the microstructure, tensile and fatigue properties of Al–5 wt.%Mg alloy manufactured by twin roll strip casting. Strips cast as a fabricated (F) specimen and a specimen heat treated (O) at 400 °C/5 h were produced and compared. In the F specimen, microstructural observation discovered clustered precipitates in the center area, while in the O specimen precipitates were relatively more evenly distributed. Al, Al₆(Mn, Fe), Mg₂Al₃ and Mg₂Si phases were observed. However, most of the Mg₂Al₃ phase in the heat-treated O specimen was dissolved. A room temperature tensile test measured yield strength of 177.7 MPa, ultimate tensile strength of 286.1 MPa and elongation of 11.1% in the F specimen and 167.7 MPa (YS), 301.5 MPa (UTS) and 24.6% (EL) in the O specimen. A high cycle fatigue test measured a fatigue limit of 145 MPa in the F specimen and 165 MPa in the O specimen, and the O specimen achieved greater fatigue properties in all fatigue stress conditions. The tensile and fatigue fracture surfaces of the above-mentioned specimens were observed, and this study attempted to investigate the tensile and fatigue deformation behavior of strip cast Al–5 wt.%Mg based on the findings.