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Antimicrobial peptides (AMPs) that selectively permeabilize bacterial membranes are promising alternatives to conventional antibiotics. Dimerization of AMP is considered an attractive strategy to enhance antimicrobial and membrane-lytic activity, but it also increases undesired hemolytic and cytotoxic activity. Here, we prepared Lys-linked homodimers of membrane-permeabilizing magainin II and cell-penetrating buforin II. Dimerization did not significantly alter conformational behavior, but it had a substantial impact on antimicrobial properties. We found that while the magainin II dimer showed increased antimicrobial and cytotoxic effects, the buforin II dimer conferred much greater antibacterial potency without exhibiting cytotoxic activity. Interestingly, the buforin II dimer was highly effective against several antibiotic-resistant bacterial isolates. Membrane permeabilization experiments indicated that the magainin II dimer rapidly disrupted both anionic and zwitterionic membranes, whereas the buforin II dimer selectively disrupted anionic membranes. Like the monomeric form, the buforin II dimer was efficiently translocated across lipid bilayers. Therefore, our results suggest that the dimerization of cell-penetrating buforin II not only disrupts the bacterial membrane, but also translocates it across the membrane to target intracellular components, resulting in effective antimicrobial activity. We propose that dimerization of intracellular targeting AMPs may present a superior strategy for therapeutic control of pathogenic bacteria.

Thermochemical heat storage is a promising energy storage method and has received much attention in recent years. To improve the design and application of such systems, a better understanding of the characteristics of thermochemical heat storage is required. In this study, we analyze the heat release characteristics of thermochemical heat storage considering various operating parameters, such as charging temperature, humidity, and material. Three different thermochemical materials are considered herein, namely, zeolite 13X, zeolite 5A, and silica gel. The temperature profile at the inlet and outlet of the storage chamber, and that inside the chamber packed with thermochemical material, were measured. The pressure drop across the chamber was measured as well. The results indicate that the heat release characteristics change with position and time. Furthermore, the temporal curves of released heat are significantly affected by charging temperature and humidity. Zeolite 13X rapidly released a large amount of heat within a short period of time, whereas silica gel gradually released a small amount of heat, over a longer duration of time. The pressure drop across the chamber was found to vary with the bead size of the thermochemical material. Thus, the operating parameters including charging temperature, humidity, and material, have a significant effect on the characteristics of heat release. The data obtained herein can serve as a reference for the design of thermochemical storage systems.

Cross-linking technology has been considered as one of the effective strategies for improving the physicochemical stability of proton-exchange membranes (PEMs) for fuel cell applications. However, ...

End-group cross-linked sulfonated poly(arylene ether sulfone) (SPAES) membranes were prepared using thiol capped SPAES (SH-SPAES) with different amounts of vinyl polysulfone (VPSf) as a polymeric cross-linker. The cross-linked membranes showed remarkably improved physicochemical stabilities compared to the corresponding linear SPAES membrane. Although the proton conductivity of the SPAES membrane composed of SPAES with the degree of sulfonation (DS) as 70 mol% could not be measured due to its low physical stability under the measurement condition, those of the cross-linked membranes were repeatedly evaluated due to the enhanced stability through the formation of cross-linked structures. The obtained proton conductivity values from cross-linked membranes are larger than those of the linear SPAES membrane which composed of SPAES with DS of 50 mol% having the ion exchange capacity (IEC) similar to that of the cross-linked membranes, especially at relative low humidity conditions. Furthermore, the fuel cell performance of the membrane electrode assembly (MEA) prepared with the cross-linked membrane, showing the optimized physicochemical stabilities and proton conductivity exhibited a maximum power density of 692 mW cm−2, which was larger than that with Nafion 212 (603 mW cm−2) at 80 °C under fully humidified H2/Air condition.

Sulfonated poly(arylene ether sulfone) (SPAES) composite membranes were prepared using graphene oxide (GO) and sulfonated poly(arylene thioether sulfone)-grafted graphene oxide (SATS-GO) as fillers for proton exchange membrane fuel cell (PEMFC) applications. When GO and SATS-GO were mixed with SPAES to form the composite membranes, dimensional stability, chemical stability, and mechanical strength were improved. The composite membranes containing SATS-GO especially showed higher proton conductivity than the pristine SPAES and the composite membrane containing GO because of highly sulfonated polymer (SATS) introduced on GO surface. Furthermore, the sulfonic acid groups in SATS-GO can increase the compatibility between the filler and matrix polymer.

Porous nanosheets made of effectively aligned zeolitic imidazolate framework-8 (ZIF-8), dubbed ZPGO, with an exceptionally high surface area (2170 m2 g−1) were demonstrated. This composite was prepared by growing ZIF-8s on highly porous graphene oxide (PGO) and the mixed matrix membrane with such a nanofiller showed drastically improved size-selective CO2 transport even at very low filler concentration (0.02 wt%) especially under mixed gas conditions where both selectivity (CO2/N2 ∼57) and CO2 permeability (∼163 barrer) were significantly enhanced. In addition to this, ZPGO effectively suppressed CO2-plasticization, which indicates great potential in real operations. This new concept of nanofillers is expected to maximize the filler effect in other fields benefitting from a high surface area as well.

We investigated the effect of graphene oxide (GO) and sulfonated polytriazole grafted graphene oxide (SPTA-GO) on sulfonated poly(arylene ether sulfone) (SPAES) based polymer electrolytes for application in proton exchange membrane fuel cells. GO was fabricated by the chemical oxidation of graphite and SPTA-GO was prepared via the click reaction using copper (Ⅰ) catalyzed azide-alkyne 1,3-dipolar cycloaddition between ethynyl-terminated sulfonated polytriazole (E-SPTA) and azide functionalized GO (N3-GO). All the SPAES based composite membranes with GO and SPTA-GO revealed better physical/chemical stabilities and mechanical strength than the pristine SPAES membrane, while noticeable improvement of proton conductivity was only observed in the SPAES composite membrane with SPTA-GO since the SPTA moiety attached on GO has both sulfonic acid and triazole groups that can introduce the additional proton conducting channels into the SPAES matrix. The maximum power density of the membrane electrode assembly employing the SPAES composite membrane with SPTA-GO reached up to 1.58 W cm−2 at 80 °C and 100% RH condition, which is larger than that employing commercial Nafion 212 (1.33 W cm−2).

Cross-linked sulfonated poly (ether ether ketone) (C-SPEEK) membranes for direct methanol fuel cell (DMFC) applications are prepared using SPEEK with chloromethyl side groups (SPEEK-Cl) and poly (2,5-benzimidazole)-grafted graphene oxide (ABPBI-GO) as a cross-linker. The C-SPEEK membranes exhibit remarkably improved physicochemical stability and decreased methanol permeability compared to a pristine SPEEK membrane and SPEEK composite membranes composed of SPEEK and GO based fillers such as GO and ABPBI-GO. Although the proton conductivities of the C-SPEEK membranes are smaller than those of the pristine SPEEK and SPEEK composite (SPEEK/GO and SPEEK/ABPBI-GO) membranes, cell performances of the membrane electrode assemblies (MEAs) using the C-SPEEK membranes with the optimized contents of ABPBI-GO (cross-linker) are better than those using the pristine SPEEK and SPEEK composite membranes due to the well dispersion of ABPBI-GO by forming an effectively covalent bonded network structure with SPEEK-Cl resulting in the decreased methanol permeability. The maximum power density of the MEA with the C-SPEEK membrane (86 mW cm−2) is larger than those with the pristine SPEEK (71 mW cm−2) and SPEEK composite (69 mW cm−2) membranes at 60 °C with 1.5 M methanol/air feed condition.

This article first presented direct applicability of Fenton's oxidation to high-strength wastewater, especially when efficiency of biological treatment for high-strength wastewater is insufficient. Fenton's oxidation was applied both to biologically pretreated molasses wastewater (BMW) and untreated molasses wastewater (MW), and the removal of color and chemical oxygen demand using chromate (CODcr) were compared between the two wastewaters. The optimum reaction time was 20 min for both BMW and MW. Neither the different dosages of Fenton's reagents nor the initial pH affected the removal ratios of CODcr and color from either BMW or MW. The maximum removal ratios of CODcr and color were approximately 90 and 97% for BMW and 88 and 98% for MW, respectively. Although these ratios are similar, the optimum H2O2 dose (g L−1)/initial CODcr (g L−1) ratio and the optimum H2O2/Fe2+ molar ratio for BMW treatment were larger than those for MW treatment. This indicates that direct Fenton treatment of MW uses le...

In batch mesophilic anaerobic digestion of a mixture of iron-rich sludge collected from Fenton treatment of molasses wastewater (MWW) and thickened sewage sludge from a municipal wastewater treatment plant, the methane content in the gas from the mixture was significantly higher than that from thickened sewage sludge only. When minerals in iron-rich sludge obtained by incineration were fed to thickened sewage sludge in semi-continuous experiments, the methane content obtained by digestion of thickened sewage sludge only increased approximately from 53% to 64%. These results suggest that iron-rich sludge can enhance methane production for thickened sewage sludge.

The Fenton method was applied to the removal of chemical oxygen demand using chromate (CODcr) and color from high-strength livestock wastewater in which the initial CODcr was 5000-5700 mg/L. The optimum ratio of H2O2 (mg/L) to the initial CODcr was 1.05 and the optimum molar ratio of H2O2/Fe2+ was 2. The optimum initial pH and the optimum reaction time were 3.5-4 and 30 min, respectively. Under optimal conditions, the removal ratios of CODcr and color of the supernatant after static precipitation of the produced sludge were 88 and 95.4%, respectively. Addition of Fenton's reagents in several aliquots did not affect the efficiencies of CODcr and color removal.

One approach for enhancing intestinal absorption of therapeutic peptides is chemical conjugation to bile acids. In this study, recombinant salmon calcitonin (sCT) was chemically modified by covalent attachment of deoxycholic acid (DOCA). Three different sCT-DOCA conjugates, namely, sCT- mono-DOCA, sCT-di-DOCA, and sCT-tri-DOCA, were prepared and characterized for their structural and biological properties. The permeability of these conjugates in the gastrointestinal tract was evaluated using Caco-2 cell monolayers to determine their potential as an oral dosage form. The conjugates were isolated by reversed-phase fast protein liquid chromatography (FPLC) and confirmed by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. Circular dichroism spectra in 50% trifluoroethanol aqueous condition showed the ordered secondary structure of sCT-DOCA. The biological activities of sCT-DOCA conjugates were evaluated by cyclic AMP assay using T-47D cells, and the mean EC50 values of sCT, sCT-mono-DOCA, and sCT-di-DOCA were 0.034, 0.076, and 0.46 nM, respectively. The transport experiments using the Caco-2 cell monolayer showed that the permeability of sCT-DOCA conjugates in buffer was not altered from the native sCT. However, the permeability of sCT-DOCA conjugates was increased up to 2.5 times that of the native sCT when sCT-DOCA was formulated in 1% dimethylsulfoxide (DMSO) solution. The conjugated DOCA of sCT-DOCA significantly enhanced the absorption of sCT-DOCA in the intestinal membrane when sCT-DOCA conjugates were completely solubilized by DMSO. In conclusion, this study proposes that therapeutic peptides that have poor absorption profiles could potentially be developed into orally active drugs by conjugation with DOCA in the formulation with appropriate solubilizing agents. Drug Dev. Res. 64:129-135, 2005. � c 2005 Wiley-Liss, Inc.

Objective: Angiogenesis has been demonstrated to modulate adipogenesis and obesity. This study was undertaken to determine whether the botanical drug ALS-L1023 (ALS), which exhibits antiangiogenic activity, can regulate adipose tissue growth in high-fat-diet-induced obese mice. Materials and Methods: The effects of ALS on angiogenesis and extracellular matrix remodeling were measured using in vitro assays. The effects of ALS on adipose tissue growth was investigated in nutritionally obese mice. Results: ALS inhibited angiogenesis in a concentration-dependent manner in the tube formation assay and the VEGF-induced proliferation assay using human umbilical vein endothelial cells. ALS also suppressed matrix metalloproteinase (MMP) activity in vitro. ALS administration to high-fat-diet-induced obese mice significantly reduced body weight gain, adipose tissue mass, and adipocyte size compared with the findings in the controls. ALS treatment decreased blood vessel density and MMP activity in adipose tissues. ALS reduced the mRNA levels of angiogenic factors (VEGFs and FGF-2) and MMPs (MMP-2 and MMP-9), whereas it increased the mRNA levels of angiogenic inhibitors (TSP-1 and TIMPs) in adipose tissues. Conclusion: These results suggest that in vivo and in vitro treatment with ALS, which has antiangiogenic and MMP inhibitory activities, reduces adipose tissue mass in nutritionally induced obese mice, providing evidence that adipose tissue growth can be regulated by angiogenesis inhibitors.

Piceatannol (3,4,3',5'-tetrahydroxy-trans-stilbene), derived from the seeds of Euphorbia lagascae, has been reported to have anti-proliferative, anti-inflammatory, and antioxidant properties. However, the mechanisms underlying its chemoprotective effects remain largely unresolved. In the present study, we found that piceatannol treatment (30 microM) significantly upregulated the expression of the antioxidant enzyme heme oxygenase-1 (HO-1) and its mRNA transcript at 6h and 3h, respectively in human breast epithelial (MCF10A) cells. A redox-sensitive transcription factor NF-E2-related factor (Nrf2) plays a pivotal role in induced expression of many cytoprotective enzymes including HO-1. Piceatannol induced translocation of Nrf2 into the nucleus and its transcriptional activities when treated to the MCF10A cells for 6h. Upregulation of HO-1 expression by piceatannol through direct binding of Nrf2 to antioxidant response element (ARE) was verified by the chromatin immunoprecipitation (ChIP) assay. siRNA knock down of Nrf2 gene abolished piceatannol-induced HO-1 expression. In addition, piceatannol-induced activation of Nrf2 and/or HO-1 expression was abrogated by the pharmacological inhibitor (LY294002) as well as the kinase-dead form of Akt. In an attempt to elucidate the molecular mechanisms underlying cytoprotective or chemoprotective activity exerted by piceatannol, we examined its effect on the signaling pathways responsible for induction of HO-1 expression. We hypothesize that an electrophilic quinone formed as a consequence of oxidation of piceatannol bearing the catechol moiety may bind directly to Kelch-like ECH-associated protein 1 (Keap1), an inhibitory protein that sequesters Nrf2 in the cytoplasm. This will diminish the affinity of Keap1 for Nrf2. The thiol reducing agents, dithiothreitol (100 microM) or beta-mercaptoethanol (1.4 microM), attenuated piceatannol-induced Nrf2 activation and HO-1 expression. It is hence likely that piceatannol modifies specific cysteine residues of Keap1, which allows Nrf2 to translocate into the nucleus and bind to ARE, leading to enhancement of the expression of HO-1. The characteristic catechol moiety of piceatannol appears to be critical for induction of Nrf2 activation and subsequent upregulation of HO-1.