Fast Imaging of Mitochondrial Thioredoxin Reductase Using a Styrylpyridinium-Based Two-Photon Ratiometric Fluorescent Probe.

Thioredoxin reductase (TrxR) is a pivotal antioxidant enzyme, but there remains a challenge for its fast imaging. This work describes the combination of a hydroxyl styrylpyridinium scaffold as the push-pull fluorophore with a carbonate-bridged 1,2-dithiolane unit as the reaction site to develop a fast mitochondrial TrxR2 probe, DSMP. It manifested a plethora of excellent properties including a rapid specific response (12 min), large Stokes shift (170 nm), ratiometric two-photon imaging, favorable binding with TrxR (Km = 12.5 ± 0.2 µM), and the ability to cross the blood-brain barrier. With the aid of DSMP, we visualized the increased mitochondrial TrxR2 activity in cancer cells compared to normal cells. This offers the direct imaging evidence of the connection between the increased TrxR2 activity and the development of cancer. Additionally, the probe allowed the visualization of the loss in TrxR2 activity in a cellular Parkinson's disease model and, more importantly, in mouse brain tissues of a middle cerebral artery occlusion model for ischemic stroke.

Developing Push-Pull Hydroxylphenylpolyenylpyridinium Chromophores as Ratiometric Two-Photon Fluorescent Probes for Cellular and Intravital Imaging of Mitochondrial NQO1.

This work highlights the use of push-pull hydroxylphenylpolyenylpyridinium fluorophores coupled with trimethyl lock quinone to engineer the ratiometric two-photon probes for cellular and intravital imaging of mitochondrial NAD(P)H:quinone oxidoreductase 1 (NQO1), a critical antioxidant enzyme responsible for detoxifying quinones. As a typical representative, QBMP showed favorable binding with NQO1 with a Michaelis constant of 12.74 µM and exhibited a suite of superior properties, including rapid response (4 min), large Stokes shift (162 nm), ultralow detection limit (0.9 nM), favorable two-photon cross section for the released fluorophore (70.5 GM), and deep tissue penetration (225 µm) in fixed brain tissues. More importantly, this probe was successfully applied for distinguishing different NQO1-expressing cancer and normal cells, revealing decreased NQO1 activity in a cellular Parkinson's disease model, screening NQO1 inducers as neuroprotective agents, and imaging of NQO1 in live mouse brain.

[Sources, Distribution of Main Controlling Factors, and Potential Ecological Risk Assessment for Heavy Metals in the Surface Sediment of Hainan Island North Bay, South China].

The distribution characteristics of the content of As, Cr, Cu, Hg, Pb, Zn, and Cd were researched based on the geochemical analysis of 159 surface sediment samples in Haikou Bay, Puqian Bay, Dongzhai Harbor, and Mulan Bay Mathematical statistics methods were used to interpret the sources of heavy metals, and the main controlling factors for heavy metal distribution were confirmed, having been analyzed qualitatively and semi-quantitatively. The results showed that the average contents of As, Cd, Cr, Cu, Hg, Pb, and Zn were 8.40, 0.06, 32.50, 8.32, 0.02, 18.77, and 35.87 µg·g-1, respectively. High contents of Cr, Cu, Hg, Pb, and Zn are mainly distributed in estuaries and harbors. The content of As increased gradually from south to north in the research area, while Cd gathered mainly in Haikou Bay. The source of Cu, Zn, Hg, Pb, Cr, and Cd in sediment was terrestrial input, which was controlled by anthropogenic pollution and migration of weathered products from mother rock. The source of As could be overseas material input. The grain size of sediment was the main factor controlling the contents of Cu, Zn, Hg, Pb, and Cr, and it was found that sediments with a finer grain size have more heavy metals adsorbed. The high As content was controlled mainly by the natural geological background factor, while the content of Cd reflected the difference in regional pollution caused by differing development in cities. Three surface sediment samples were evaluated as class Ⅱ of the National Marine Sediment Standard due to the content of As, while six surface sediment samples were evaluated as class Ⅱ due to the content of Cr, of which the pollution degree was moderate. The concentrations of Cd, Cu, Hg, Pb, and Zn in all of the 159 sediment samples fall in the Ⅰ class, of which the pollution degree is low. The degree of pollution for seven heavy metals were arranged in the following order:As > Cr > Pb > Zn > Cu > Cd > Hg. The potential ecological risk assessment results indicated that all heavy metals in surface sediment caused low levels of pollution generally, and that each heavy metal element was at a low ecological risk level. The order for the ecological risk of the seven heavy metals was:As > Hg > Cd > Pb > Cu > Cr > Zn; therefore, As was the main ecological risk factor. In general, the potential ecological risk for heavy metals was low, which illustrated that the marine environment in the study area was excellent.

Prognostic role of the pre-treatment platelet-lymphocyte ratio in pancreatic cancer: a meta-analysis.

BACKGROUND AND AIMS: Recently, the pre-treatment platelet-lymphocyte ratio (PLR), which is based on blood parameters, was accepted as a prognostic factor for patients with various cancers. Numerous studies have investigated the prognostic role of the PLR in pancreatic cancer; however, it remains unclear. Therefore, we conducted this meta-analysis to evaluate the relationship between the pre-treatment PLR and overall survival (OS) in pancreatic cancer. MATERIALS AND METHODS: We performed a systematic literature search of the PubMed, Embase and Web of Science databases for relevant studies that explored the prognostic role of the pre-treatment PLR in pancreatic cancer. The hazard ratios (HRs) and 95% confidence intervals (CIs) related to OS were pooled using a random effects model. RESULTS: Fourteen retrospective cohort studies involving 2,260 patients were included in this meta-analysis. Compared with low PLR, high PLR was a predictor of shorter OS (HR = 1.24, 95% CI: 1.10-1.39, I2 = 74%). CONCLUSIONS: In this meta-analysis, high pre-treatment PLR was a bio-predictor of short OS in patients with pancreatic cancer, suggesting that PLR could be used to predict prognosis of patients with pancreatic cancer before treatment. However, additional well-designed and large-scale studies are necessary.