5‑Aminosalicylic Acid Azo-Linked to Procainamide Acts as an Anticolitic Mutual Prodrug via Additive Inhibition of Nuclear Factor kappaB

To improve the anticolitic efficacy of 5-aminosalicylic acid (5-ASA), a colon-specific mutual prodrug of 5-ASA was designed. 5-ASA was coupled to procainamide (PA), a local anesthetic, via an azo bond to prepare 5-(4-{[2-(diethylamino)­ethyl]­carbamoyl}­phenylazo)­salicylic acid (5-ASA-azo-PA). 5-ASA-azo-PA was cleaved to 5-ASA and PA up to about 76% at 10 h in the cecal contents while remaining stable in the small intestinal contents. Oral gavage of 5-ASA-azo-PA and sulfasalazine, a colon-specific prodrug currently used in clinic, to rats showed similar efficiency in delivery of 5-ASA to the large intestine, and PA was not detectable in the blood after 5-ASA-azo-PA administration. Oral gavage of 5-ASA-azo-PA alleviated 2,4,6-trinitrobenzenesulfonic acid-induced rat colitis. Moreover, combined intracolonic treatment with 5-ASA and PA elicited an additive ameliorative effect. Furthermore, combined treatment with 5-ASA and PA additively inhibited nuclear factor-kappaB (NFκB) activity in human colon carcinoma cells and inflamed colonic tissues. Finally, 5-ASA-azo-PA administered orally was able to reduce inflammatory mediators, NFκB target gene products, in the inflamed colon. 5-ASA-azo-PA may be a colon-specific mutual prodrug acting against colitis, and the mutual anticolitic effects occurred at least partly through the cooperative inhibition of NFκB activity

Epithelial–Mesenchymal Transition Enhances Nanoscale Actin Filament Dynamics of Ovarian Cancer Cells

Epithelial ovarian cancer cells enhance their ability to migrate and invade through the epithelial–mesenchymal transition (EMT), resulting in cell seeding and metastasis in the peritoneal cavity and onto adjacent organ surfaces. It has been speculated that cytoskeletal dynamics, such as those of the actin filament, play a role in enhanced cell motility; however, direct evidence has not been provided. Herein, we have directly measured pico- to nanonewton-scale mechanical forces generated by actin dynamics of ovarian cancer SKOV-3 cells upon binding of integrin α5β1 to fibronectin (FN), i.e., formation of a focal adhesion, using real-time atomic force microscopy (AFM) in a force spectroscopy mode. The dendrimer surface chemistry through which FN was immobilized on the AFM probe surfaces further enhanced the sensitivity of the force measurement by 1.5-fold. Post-EMT SKOV-3 cells, induced by transforming growth factor-β, generated larger focal adhesion mechanical forces (17 and 41 nN before and after EMT, respectively) with migration faster than that of pre-EMT cells. Importantly, 22% of the forces transmitted through a single FN–integrin α5β1 pair from post-EMT cells were shown to be sufficient to rupture the binding between FN and integrin α5β1 on the cells, a result which is not observed on pre-EMT cells. This implies that post-EMT cells, by generating forces strong enough to break the FN–integrin binding, migrate and metastasize beyond the ovary, whereas pre-EMT cancer cells are confined in the ovary without such force generation. These results demonstrate quantitative and direct evidence for the role of actin dynamics in the enhanced motility of post-EMT ovarian cancer cells, providing a fundamental insight into the mechanism of ovarian cancer metastasis

Co-catalytic Effects of CoS₂ on the Activity of the MoS₂ Catalyst for Electrochemical Hydrogen Evolution

MoS₂ is a promising material to replace the Pt catalyst in the electrochemical hydrogen evolution reaction (HER). It is well known that the activity of the MoS₂ catalyst in the HER is significantly promoted by doping cobalt atoms. Recently, the Co–Mo–S phase, in which cobalt atoms decorate the edge positions of the MoS₂ slabs, has been identified as a co-catalytic phase in the Co-doped MoS₂ (Co-MoS_<i>x</i>) with low Co content. Here, we report the effect of the incorporation of cobalt atoms in the chemical state of the Co-MoS_<i>x</i> catalyst, which gives rise to the co-catalytic effect. Co-MoS_<i>x</i> catalysts with various Co contents were prepared on carbon fiber paper by a simple hydrothermal process. On the Co-MoS_<i>x</i> catalyst with high Co content (Co/Mo ≈ 2.3), a dramatically higher catalytic activity was observed compared to that for the catalyst with low Co content (Co/Mo ≈ 0.36). Furthermore, the co-catalytic phase in the Co-MoS_<i>x</i> catalyst with the high Co content was found not to be the Co–Mo–S phase but was identified as CoS₂ by Raman spectroscopy, X-ray photoelectron spectroscopy, X-ray diffraction, and transmission electron microscopy. It is believed that CoS₂ is an alternative choice to co-catalyze HER on MoS₂-based catalysts

High-Mobility Pyrene-Based Semiconductor for Organic Thin-Film Transistors

Numerous conjugated oligoacenes and polythiophenes are being heavily studied in the search for high-mobility organic semiconductors. Although many researchers have designed fused aromatic compounds as organic semiconductors for organic thin-film transistors (OTFTs), pyrene-based organic semiconductors with high mobilities and on–off current ratios have not yet been reported. Here, we introduce a new pyrene-based p-type organic semiconductor showing liquid crystal behavior. The thin film characteristics of this material are investigated by varying the substrate temperature during the deposition and the gate dielectric condition using the surface modification with a self-assembled monolayer, and systematically studied in correlation with the performances of transistor devices with this compound. OTFT fabricated under the optimum deposition conditions of this compound, namely, 1,6-bis­(5′-octyl-2,2′-bithiophen-5-yl)­pyrene (BOBTP) shows a high-performance transistor behavior with a field-effect mobility of 2.1 cm² V^–1 s^–1 and an on–off current ratio of 7.6 × 10⁶ and enhanced long-term stability compared to the pentacene thin-film transistor

Náhrada hematitových otěruvzdorných desek pro kontilití minihuť pásová NH, a.s. deskami s návarem

Import 20/04/2006Prezenční výpůjčkaVŠB - Technická univerzita Ostrava. Fakulta strojní. Katedra (344) výrobních strojů a konstruován

Dextran-5-(4-ethoxycarbonylphenylazo)salicylic acid ester, a polymeric colon-specific prodrug releasing 5-aminosalicylic acid and benzocaine, ameliorates TNBS-induced rat colitis

<p>Local anesthetics have beneficial effects on colitis. Dextran-5-(4-ethoxycarbonylphenylazo)salicylic acid ester (Dex-5-ESA), designed as a polymeric colon-specific prodrug liberating 5-ASA and benzocaine in the large intestine, was prepared and its therapeutic activity against colitis was evaluated using a TNBS-induced rat colitis model. Dex-5-ESA liberated 5-ASA and benzocaine in the cecal contents while (bio)chemically stable in the small intestinal contents and mucosa. Oral administration of Dex-5-ESA (equivalent to 10 mg 5-ASA/kg, twice a day) alleviated colonic injury and reduced MPO activity in the inflamed colon. In parallel, pro-inflammatory mediators, COX-2, iNOS and CINC-3, elevated by TNBS-induced colitis, were substantially diminished in the inflamed colon. Dex-5-ESA was much more effective for the treatment of colitis than 5-(4-ethoxycarbonylphenylazo)salicylic acid (5-ESA) that may not deliver benzocaine to the large intestine. Our data suggest that Dex-5-ESA is a polymeric colon-specific prodrug, liberating 5-ASA and benzocaine in the target site (large intestine), probably exerting anti-colitic effects by combined action of 5-ASA and benzocaine.</p

Cellulose Nanocrystals and Polyanionic Cellulose as Additives in Bentonite Water-Based Drilling Fluids: Rheological Modeling and Filtration Mechanisms

This research aims to develop low cost, sustainable, environmentally friendly, and high performance water-based drilling fluids (WDFs) using bentonite (BT), polyanionic cellulose (PAC), and cellulose nanocrystals (CNCs). The effect of concentration of BT, PAC, and CNCs on the rheological and filtration properties of PAC/CNC/BT-WDFs was investigated. Eight empirical rheological models were applied to fit quantitatively the fluid properties. Results showed that the presence of PAC, CNCs, and BT improved the rheological and filtration properties of the WDFs. Among the eight empirical rheological models, the Sisko model performed the best in simulating the rheological behavior of the fluids. At the same concentration level of PAC and CNCs, CNCs had more impact on the rheological properties, whereas PAC had more influence on the filtration property. The incorporation of PAC resulted in very low permeable filter cakes, leading to the excellent filtration property. The combined use of PAC and CNCs yielded better rheological and filtration properties

High-Power Hybrid Solid-State Lithium–Metal Batteries Enabled by Preferred Directional Lithium Growth Mechanism

Solid electrolytes are revolutionizing the field of lithium–metal batteries; however, their practical implementation has been impeded by the interfacial instability between lithium metal electrodes and solid electrolytes. While various interlayers have been suggested to address this issue in recent years, long-term stability with repeated lithium deposition/stripping has been challenging to attain. Herein, we successfully operate a high-power lithium–metal battery by inducing the preferred directional lithium growth with a rationally designed interlayer, which employs (i) crystalline-direction-controlled carbon material providing isotropic lithium transports, with (ii) prelithium deposits that guide the lithium nucleation direction toward the current collector. This combination ensures that the morphology of the interlayer is mechanically robust while regulating the preferred lithium growth underneath the interlayer without disrupting the initial interlayer/electrolyte interface, enhancing the durability of the interface. We illustrate how these material/geometric optimizations are conducted from the thermodynamic considerations, and its applicability is demonstrated for the garnet-type Li7–xLa3–aZr2–bO12 (LLZO) solid electrolytes paired with the capacity cathode. It is shown that a lithium–metal cell with the optimized amorphous carbon interlayer with prelithium deposits exhibits outstanding room-temperature cycling performance (99. 6% capacity retention after 250 cycles), delivering 4.0 mAh cm–2 at 2.5 mA cm–2 without significant degradation of the capacity. The successful long-term operation of the hybrid solid-state cell at room temperature (approximately a cumulative deliverable capacity of over 1000 mAh cm–2) is unprecedented and records the highest performance reported for lithium–metal batteries with LLZO electrolytes until date

HIF-1α is upregulated in LCC2 and LCC9 cells.

<p>(A) HIF-1α activity in MCF7S, LCC2 and LCC9 cells was measured by EMSA. (B) Endogenous HIF-1α and LDHA protein levels were measured by western blotting. β-Actin was used as a loading control. (C) The mRNA level of HIF-1α was measured by quantitative RT-PCR using the β-actin gene as an internal control. (D) LDHA was downregulated in MCF7S, LCC2, and LCC9 cells transfected with HIF-1α siRNA. siRNA (20nM) was treated in three cell lines for 48 h. C, control siRNA; H, HIF-1α siRNA (E) HIF-1α was overexpressed by treatment of CoCl₂ (50 μM, 24 h) in each cell line. Elevation of HIF-1α induced increase in LDHA expression levels. The data shown are representative results of 3 independent experiments. Band density of each immunoblot was quantified using MultiGauge. *, <i>P</i> < 0.05; **, <i>P</i> < 0.01; ***, <i>P</i> < 0.001.</p

Increased Akt/mTOR signaling induces HIF-1α activity and aerobic glycolysis.

<p>(A) VHL protein levels, as well as the activity of Akt/mTOR and its downstream targets measured by western blotting using β-actin as a loading control. (B) After treatment with specific inhibitors of Akt (LY294,002, 40 μM) and mTOR (rapamycin, 30 nM) for 4 and 16 h, respectively, HIF-1α and Akt/mTOR protein expressions were measured by western blotting in LCC2 cells. β-Actin was used as a loading control. Band density of each immunoblot with triplicate was quantified using MultiGauge. (C) Rapamycin at 30 nM was used to treat LCC2 cells for 16 h. HIF-1α activity was measured using EMSA in LCC2 cells. The data represent results of 3 independent experiments. (D) Lactate accumulation was measured by ¹H NMR quantification after treatment of rapamycin (30 nM, 16 h). *, <i>P</i> < 0.05.</p