A simulated colorimetric INHIBIT logic gate based on 2-(2-thiazolylazo)-<i>p</i>-cresol

<p>2-(2-Thiazolylazo)-<i>p</i>-cresol system achieved distinct optical output signal by controlling pH and mercury-ion complexation. The 2-(2-thiazolylazo)-<i>p</i>-cresol with mercury ion existed as an equilibrium mixture of both an azo and hydrazone tautomeric forms at 372 and 425 nm, respectively, along with the appearance of a new absorption peak at 610 nm (visual color of green), which was attributed to the binding of mercury ion with 2-(2-thiazolylazo)-<i>p</i>-cresol. Furthermore, the addition of proton led to the perturbation of the conjugation between 2-(2-thiazolylazo)-<i>p</i>-cresol and mercury ion and absence of absorption at 610 nm (visual color of yellow). 2-(2-thiazolylazo)-<i>p</i>-cresol could thus be applied to develop an effective simulated colorimetric INHIBIT logic gate with mercury ion and proton as inputs. Consequently, green color with the absorption peak at 610 nm was outputted from yellow color of 2-(2-thiazolylazo)-<i>p</i>-cresol in the presence of mercury ion as an input signal at pH 7.0.</p

The intersection among results in our study.

<p>According to the TNM staging and origin of tissues, CRC patients were divided into stages II, III, or IV colon or rectal cancer. There were 17 dysregulated miRNAs with a similar expression pattern in all 7 groups (II, III, IV, G1, G2, C, and R); 28 dysregulated miRNAs were found only in stage II and 51 only in stage III, but stage IV had 12 dysregulated miRNAs.</p

Identification of miRNAs Differentially Expressed in Clinical Stages of Human Colorectal Carcinoma—An Investigation in Guangzhou, China

<div><p>Aberrant expression of microRNAs (miRNAs) has been implicated in human cancer, including colorectal cancer (CRC). Such dysregulated miRNAs may have potential as diagnostic markers or therapeutic targets. However, the nature of an association between these miRNAs and clinical stages of CRC is still not clear. To this end, we performed a miRNA profiling of 1547 distinct human miRNAs using 31 samples of tumor and paired normal mucosa obtained from 31 CRC patients. Based on statistical analyses of profiling data, we identified 569 miRNAs that were significantly dysregulated in CRC relative to normal tissues (<i>P</i><0.05). Among the 569 dysregulated miRNAs, downregulation of 17 was associated with stages II, III, and IV colon and rectal cancers (separate or combined), according to our criteria. We also assessed the potential of these dysregulated miRNAs as diagnostic biomarkers for CRC patients who were without metastasis, and the value of the dysregulated miRNAs for predicting metastasis, lymph node and distant. Their distinct expression patterns in colon and rectal cancers were also examined. Although our findings cannot be immediately applied toward clinical diagnosis, our new study model for determining and assessing the biomarker potential of dysregulated miRNAs should be useful in further research in detection of human CRC.</p></div

Evaluation of the potential of miR-374a, miR-4634, miR-516a-5p as diagnostic biomarkers in clinical application.

<p>Among them, miR-374a was dysregulated in stage II, miR-4634 was related to lymph node metastasis in stage III, and miR-516a-5p might be associated with distant metastasis.</p

Expression levels of dysregulated miRNAs.

<p>Box plots of expression levels of six miRNAs in both tumors and paired normal tissues. The relative level of the six miRNAs was normalized to internal control gene and was showed as normalized CT. The line represents the median value—the higher the value, the lower the expression level. Paired t-tests were performed to examine the differences in miRNAs between tumors and the paired normal tissues.</p

Clinical and histopathological characteristics of patients.

<p>* Information not available.</p

Expression levels of miR-145*, -30e*, -378*, -125a-5p, -3195, and -4770 in an independent sample test.

<p>Expression levels of miR-145*, -30e*, -378*, -125a-5p, -3195, and -4770 in an independent sample test.</p

ROC curve analysis of 17 dysregulated miRNAs.

<p>Analysis of data implied that most of the dysregulated miRNAs have potential as diagnostic biomarkers for CRC detection, with high sensitivity and specificity.</p

DataSheet1_Antifungal activity of the repurposed drug disulfiram against Cryptococcus neoformans.doc

Fungal infections have become clinically challenging owing to the emergence of drug resistance in invasive fungi and the rapid increase in the number of novel pathogens. The development of drug resistance further restricts the use of antifungal agents. Therefore, there is an urgent need to identify alternative treatments for Cryptococcus neoformans (C. neoformans). Disulfiram (DSF) has a good human safety profile and promising applications as an antiviral, antifungal, antiparasitic, and anticancer agent. However, the effect of DSF on Cryptococcus is yet to be thoroughly investigated. This study investigated the antifungal effects and the mechanism of action of DSF against C. neoformans to provide a new theoretical foundation for the treatment of Cryptococcal infections. In vitro studies demonstrated that DSF inhibited Cryptococcus growth at minimum inhibitory concentrations (MICs) ranging from 1.0 to 8.0 μg/mL. Combined antifungal effects have been observed for DSF with 5-fluorocytosine, amphotericin B, terbinafine, or ketoconazole. DSF exerts significant protective effects and synergistic effects combined with 5-FU for Galleria mellonella infected with C. neoformans. Mechanistic investigations showed that DSF dose-dependently inhibited melanin, urease, acetaldehyde dehydrogenase, capsule and biofilm viability of C. neoformans. Further studies indicated that DSF affected C. neoformans by interfering with multiple biological pathways, including replication, metabolism, membrane transport, and biological enzyme activity. Potentially essential targets of these pathways include acetaldehyde dehydrogenase, catalase, ATP-binding cassette transporter (ABC transporter), and iron-sulfur cluster transporter. These findings provide novel insights into the application of DSF and contribute to the understanding of its mechanisms of action in C. neoformans.</p