Romidepsin exhibits anti-esophageal squamous cell carcinoma activity through the DDIT4-mTORC1 pathway.

Esophageal squamous cell carcinoma (ESCC) is one of the most common human malignancies worldwide and is associated with high morbidity and mortality. Current treatment options are limited, highlighting the need for development of novel effective agents. Here, a high-throughput drug screening (HTS) was performed using ESCC cell lines in both two- and three-dimensional culture systems to screen compounds that have anti-ESCC activity. Our screen identified romidepsin, a histone deactylase inhibitor, as a potential anti-ESCC agent. Romidepsin treatment decreased cell viability, induced apoptosis and cell cycle arrest in ESCC cell lines, and these findings were confirmed in ESCC cell line-derived xenografted (CDX) mouse models. Mechanically, romidepsin induced transcriptional upregulation of DNA damage-inducible transcript 4 (DDIT4) gene by histone hyperacetylation at its promoter region, leading to the inhibition of mammalian target of rapamycin complex 1 (mTORC1) pathway. Furthermore, romidepsin exhibited better efficacy and safety compared to the conventional therapeutic drugs in ESCC patient-derived xenografted (PDX) mouse models. These data indicate that romidepsin may be a novel option for anti-ESCC therapy.

Development of Fluorescence In Situ Hybridization as a Rapid, Accurate Method for Detecting Coliforms in Water Samples.

Coliform bacteria are indicators of water quality; however, most detection methods for coliform bacteria are time-consuming and nonspecific. Here, we developed a fluorescence in situ hybridization (FISH) approach to detect four types of coliform bacteria, including Escherichia coli, Klebsiella pneumoniae, Enterobacter aerogenes, and Citrobacter freundii, simultaneously in water samples using specific probes for 16S rRNA. This FISH method was applied to detect coliform bacteria in simulated water and domestic wastewater samples and compared with traditional detection methods (e.g., plate counting, multiple-tube fermentation (MTF) technique, and membrane filter (MF) technique). Optimal FISH conditions for detecting the four types of coliforms were found to be fixation in 3% paraformaldehyde at 4 °C for 2 h and hybridization at 50 °C for 1.5 h. By comparing FISH with plate counting, MTF, MF, and a commercial detection kit, we found that FISH had the shortest detection time and highest accuracy for the identification of coliform bacteria in simulated water and domestic wastewater samples. Moreover, the developed method could simultaneously detect individual species and concentrations of coliform bacteria. Overall, our findings indicated that FISH could be used as a rapid, accurate biosensor system for simultaneously detecting four types of coliform bacteria to ensure water safety.

The effectiveness of a pay for performance program on diabetes care in Taiwan: A nationwide population-based longitudinal study.

Over the past two decades, studies have widely examined the effectiveness of pay-for-performance (P4P) programs by conducting biochemical tests and assessing complications; however, the reported effectiveness of such programs among participants selected through purposeful sampling is controversial. Therefore, the objective of the current study was to analyze the effectiveness of a P4P program on patients' prognoses, including hospitalization for chronic diabetic complications, and all-cause mortality during specific follow-up years by using a nationwide population-based database in Taiwan. Based on 125,315 newly diagnosed type 2 diabetes patient cohort during 2002-2006, two control sets were designed by propensity-score-matching strategy according to participation of P4P program and followed up to 2012. The results indicated that full participants demonstrated the lowest risks of developing complications and all-cause mortality compared with nonparticipants. These findings confirm the long-term effect of P4P programs on full participants and reveal that this effect is not due to confounding variables. The results indicate the importance of performance management and adherence to interventions for patients with chronic diseases in a long-term observation. Comprehensive and continuous care is suggested to improve patient prognosis and quality of care.

Functional Supramolecular Polymers: A Fluorescent Microfibrous Network in a Supramolecular Hydrogel for High-Contrast Live Cell-Material Imaging in 3D Environments.

A new bottom-up strategy based on aromatic peptide amphiphile is developed for a high-contrast visualization of 3D live cell-material imaging-something that has been difficult to achieve previously because of the problems associated with the diffraction of light by the nanosized peptide materials and the aggregation-caused quenching of aggregated π-conjugated fluorophores in the nanostructures. This study reports an example of a novel supramolecular hydrogelator, naphthaleneimide-phenylalanine (NI-Phe), which forms a self-supporting hydrogel displaying a unique microfibrous network and promising aggregation-induced emission characteristics at pH 7.4. The storage modulus of the NI-Phe gel supports the mass of a cell for 3D cell culturing. This work illustrates a new dopant-free supramolecular approach, complementary to well-established doping procedures that should facilitate the development of live cell imaging in 3D scaffolding materials.

A novel nanostructured supramolecular hydrogel self-assembled from tetraphenylethylene-capped dipeptides.

Herein, we report a tetraphenylethylene-diglycine (TPE-GG) hydrogelator from a systematic study of TPE-capped dipeptides with various amphiphilic properties. From a chemical design, we found that the hydrogelation of TPE-GG molecules can be utilized to generate supramolecular nanostructures with a large TPE-based nanobelt width (∼300 nm) and lateral dimension ratio (>30 fold). In addition, TPE-GG has the lowest molecular weight and minimum number of atoms compared to any TPE-capped peptide hydrogelator reported to date. This minimal self-assembled hydrogelator can fundamentally achieve the gel features compared with other TPE-capped peptides. A combined experimental and computational study indicates the π-π interactions, electrostatic interactions and hydrogen-bonding interactions are the major driving forces behind the formation of self-assembled nanobelts. This study demonstrates the importance of structure-property relationships and provides new insights into the design of supramolecular nanomaterials.

Biological decolorization of dye solution containing malachite green by Pandoraea pulmonicola YC32 using a batch and continuous system.

In our study, we have isolated a relatively newly identified bacteria species, Pandoraea pulmonicola YC32, and first assessed its capability to treat malachite green (MG). The effects of various factors on decolorization efficiency were investigated in a batch system. The decolorization efficiency was found to be optimal within a pH of 7-10 and it increased, with increasing initial MG concentration up to 100 mg/l. The relationship between the decolorization rate and MG concentration agreed with Lineweaver-Burk equation. The apparent kinetic parameters, R(MG,max) and K(m), were 6.23 mg-MG/g-cell/h and 153.4 mg/l, respectively. The initial step in the biodegradation pathway of MG by P. pulmonicola YC32 was a reduction or N-demethylation reaction. We achieved a decolorization efficiency of 85.2% with 50mg/l MG in the immobilized P. pulmonicola YC32 continuous column system. This is the first report on the application of a continuous column system to decolorize MG using a microorganism.