Complexing characteristics between Cu(â ¡) ions and dissolved organic matter in combined sewer overflows: Implications for the removal of heavy metals by enhanced coagulation.

Enhanced coagulation has been widely used in storm tanks to remove heavy metal ions (HMs) from combined sewer overflows (CSOs), but faces challenges on removing the HMs bound to dissolved organic matter (DOM) with small molecular weight (MW). DOM ubiquitously existing in CSOs generally contains a large distribution range of MW, which can significantly impact the MW distribution of HMs by complexing reaction, thereby adding uncertainties for the removal efficiency of coagulation. Therefore, realizing the potential MW distribution of the HMs bound to CSO-DOM is greatly important for cost-effectively removing HMs from CSOs in the coagulation process. This paper presents a comprehensive approach of ultrafiltration, fluorescence quenching titration, excitation-emission matrix parallel factor analysis, complexation model, and two-dimensional correlation fluorescence spectroscopy for exploring the MW-based complexing characteristics between Cu(II) ions and CSO-DOM components. Results show that: (1) Cu(II) ions that bound to the CSO-DOM were mainly distributed in the MW range of <5 kDa, which makes them very difficult to be removed from CSOs by coagulation technique. (2) Concentration effect and molecular composition exerted great impacts on the MW distribution of the Cu(II) ions bound to CSO-DOM. (3) The humic-like component of terrestrial origin with the MW range of 100 kDa∼0.45 µm possessed high binding stability, capacity, and priority with Cu(II) ions, and they could be used at a high concentration to promote the removal efficiency of coagulation for Cu(Ⅱ) ions of CSOs by competitive complexation and inter-molecular bridging.

Vitamin A-decorated biocompatible micelles for chemogene therapy of liver fibrosis.

Liver fibrosis refers to excessive accumulation of hepatic collagen, which is primarily produced by activated hepatic stellate cells (HSCs). No effective drugs are clinically available to treat this condition, reflecting the fact that antifibrotic drugs do not specifically target activated HSCs. Here, we report the synthesis and evaluation of poly (lactide-co-glycolide)-polyspermine-poly (ethylene glycol)-vitamin A (PLGA-PSPE-PEG-VA), and activated HSC-targeted, biocompatible amphiphilic polymers for co-delivery of chemical (silibinin) and genetic (siCol1α1) drugs that synergistically suppress collagen I accumulation in fibrogenesis. PLGA-PSPE-PEG-VA self-assembled into core-shell polymeric micelles (PVMs) at low concentrations. After loading with silibinin and siCol1α1, the resulting chemical/genetic drug-loaded PVMs (CGPVMs) exhibited a small particle size and a slightly positive surface. CGPVMs had very low cytotoxicity and hemolytic activity in vitro and were well tolerated in mice, with no liver toxicity or inflammation. Importantly, CGPVMs effectively accumulated in fibrotic livers and specifically targeted activated HSCs. As expected CGPVMs more efficiently decreased collagen I production and ameliorated liver fibrosis compared with chemical drug (silibinin)-loaded PVMs (CPVMs) or genetic drug (siCol1α1)-loaded PVMs (GPVMs) only. These results indicate that CGPVMs are a promising tool for targeted delivery of chemogenes to activated HSCs in the treatment of liver fibrosis.

Circulating tight junction proteins mirror blood-brain barrier integrity in leukaemia central nervous system metastasis.

The aim of this study was to evaluate the clinical significance of circulating tight junction (TJ) proteins as biomarkers reflecting of leukaemia central nervous system (CNS) metastasis. TJs [claudin5 (CLDN5), occludin (OCLN) and ZO-1] concentrations were measured in serum and cerebrospinal fluid (CSF) samples obtained from 45 leukaemia patients. Serum ZO-1 was significantly higher (p < 0.05), but CSF ZO-1 levels were not significantly higher in the CNS leukaemia (CNSL) compared to the non-CNSL. The CNSL patients also had a lower CLDN5/ZO1 ratio in both serum and CSF than in non-CNSL patients (p < 0.05). The TJ index was negatively associated with WBCCSF , ALBCSF and BBB values in leukaemia patients. Among all of the parameters studied, CLDN5CSF had the highest specificity in discriminating between CNSL and non-CNSL patients. Therefore, analysing serum and CSF levels of CLDN5, OCLN and the CLDN5/ZO1 ratio is valuable in evaluating the potential of leukaemia CNS metastasis. Copyright © 2016 John Wiley & Sons, Ltd.