Rapid and visual detection of dichloroacetonitrile in water.

Dichloroacetonitrile (DCAN) is a common biotoxic disinfection by-product (DBP) of chlorine. The current methods used for detecting DCAN are tedious and heavily instrument-dependent, and are not suitable for on-site detection. In the present study, we developed a colorimetric assay for rapid detection of DCAN. DCAN in water acted as a complexing agent that formed a complex with cuprous species. The cuprous species was then extracted by chloroform and visualized using dithizone. The visual detection limit for DCAN was 20 ng mL-1, while fluorescence quantification could detect DCAN at a concentration as low as 8.75 ng mL-1. Moreover, haloacetonitriles (HANs) derived from chlorine disinfection and structurally similar to DCAN, including TCAN, BCAN, and DBAN, could also be detected using this method. Other DBPs at concentrations as high as 200 ng mL-1 did not affect the detection process. The low cost and instrument-independence characteristic of the present method enables its routine determination of the concentration of DCAN in water.

DNA dendrimer-templated copper nanoparticles: self-assembly, aggregation-induced emission enhancement and sensing of lead ions.

Copper nanomaterials based on DNA scaffold (DNA-Cu NMs) are becoming a novel fluorescent material, but it is still challenging to obtain highly fluorescent DNA-Cu NMs with excellent stability. In this work, we report a kind of copper nano-assemblies (Cu NASs) with aggregation-induced emission enhancement (AIEE) property using DNA dendrimers with sticky end as template. The sticky end of the DNA dendrimers induced the formation of much bigger Cu NASs with average size ranging from 131 to 264 nm, depending on the length of the DNA dendrimer sticky end from 6 bases to 27 bases. Compared with complete complementary DNA dendrimer, nearly 6-fold fluorescence enhancement was achieved using DNA dendrimer with 27 bases sticky end. Moreover, the DNA dendrimer-Cu NASs demonstrated excellent stability in serum and could be rapidly quenched by Pb2+ ions. Based on the above property, highly sensitive and selective fluorescent detection of Pb2+ ions was possible with a linear range of 2.0-100 nM and a detection limit of 0.75 nM. Due to the sensitive and rapid response to Pb2+ as well as excellent stability in complex matrix, the proposed fluorescent Cu NASs demonstrated high potential as an excellent fluorescent probe for Pb2+ in complex matrix.

Highly Sensitive and Selective Fluorescence "Turn-On" Detection of Pb (II) Based on Fe3O4@Au-FITC Nanocomposite.

New nanocomposites, Fe3O4@Au-FITC, were prepared and explored to develop a fluorescent detection of Pb2+. The Fe3O4@AuNPs-FITC nanocomposites could be etched by Pb2+ in the presence of Na2S2O3, leading to fluorescence recovery of FITC quenched by Fe3O4@Au nanocomposites. With the increase of Pb2+ concentration, the fluorescence recovery of Fe3O4@AuNPs-FITC increased gradually. Under optimized conditions, a detection limit of 5.2 nmol/L of Pb2+ with a linear range of 0.02-2.0 µmol/L were obtained. The assay demonstrated negligible response to common metal ions. Recoveries of 98.2-106.4% were obtained when this fluorescent method was applied in detecting Pb2+ spiked in a lake-water sample. The above results demonstrated the high potential of ion-induced nanomaterial etching in developing robust fluorescent assays.

Preclinical development and characterisation of 99mTc-NM-01 for SPECT/CT imaging of human PD-L1.

The level of expression of programmed cell death-1 (PD-1)/programmed death ligand-1 (PD-L1) is a predictive biomarker for cancer immunotherapy, however, its detection remains challenging due to tumour heterogeneity and the influence from the binding of therapeutic agents. We recently developed [99mTc]-NM-01 as a companion diagnostic imaging agent for non-invasive molecular imaging of PD-L1 by single-photon emission computed tomography (SPECT). The aim of the study was to evaluate the [99mTc] radiolabelling of GMP graded NM-01 and its pharmacology, pharmacokinetics and toxicology. NM-01 bound specifically to human PD-L1 (Kd=0.8 nM) and did not interfere with the binding of the anti-PD-L1 antibody atezolizumab. NM-01 can bind various PD-L1-positive cancer cell lines and only interact with PD-L1 expressed on the cell surface. In SPECT/CT imaging, high [99mTc]-NM-01 accumulation was observed in the HCC827 mouse xenografted tumour model (30-min: 1.50 ± 0.27 %ID/g; 90-min: 1.23 ± 0.18 %ID/g), demonstrated a predominantly renal elimination (high uptake in bladder and kidney), while activity in the blood pool and other major organs remained low. The tumour-to-muscle and tumour-to-blood ratios were comparable with/without atezolizumab (P<0.04) but were significantly lowered when co-injected with excess NM-01 (P=0.04 and P=0.01, respectively.) The blood clearance of [99mTc]-NM-01 is bi-phasic; consisting of an initial fast washout phase with half-life of 2.1 min and a slower clearance phase with half-life of 25.4 min. In an intravenous extended single-dose toxicity study, no treatment-related changes were observed and the maximum tolerated dose of [99mTc]-NM-01 was 2.58 mg/kg. [99mTc]-NM-01 has suitable properties as a potential candidate for SPECT/CT imaging of PD-L1 assessment in cancer patients.

Curcuma oil ameliorates benign prostatic hyperplasia through suppression of the nuclear factor-kappa B signaling pathway in rats.

ETHNO PHARMACOLOGICAL RELEVANCE: Curcuma longa L is traditionally used as an anti-inflammatory remedy in Chinese traditional medicine. Curcuma oil (CO), a lipophilic fraction from Curcuma longa L. has been reported to have anti-proliferative, anti-inflammatory and anti-oxidant activities. However, CO has never been investigated for its possible therapeutic effects on benign prostatic hyperplasia (BPH). AIMS OF THE STUDY: The study is thus to determine the therapeutic effects of curcuma oil on BPH and also the possible mechanism (s) of action. MATERIALS &METHODS: A BPH-1 cell line and Sprague Dawley (SD) rats were used to establish BPH models in vitro and in vivo, respectively. Rats were treated by CO (2.4, 7.2 mg/kg/i.g.) and finasteride (5 mg/kg/i.g.), respectively. Histological changes were examined by hematoxylin and eosin (H&E) staining. Protein expression was analyzed for 5α-reductase (5AR), dihydrotestosterone (DHT), interleukin (IL)-1ß, IL-6 and tumor necrosis factor (TNF)-α by ELISA. Ki-67, Caspase-8,-9 and -3 expressions were evaluated via immunohistochemistry (IHC). RESULTS: CO effectively induced apoptosis in BPH-1 cells. BPH was successfully established by administration of testosterone propionate (TP) in rats, which upregulated both 5α-reductase expression and DHT production. Importantly, TP establishment significantly stimulated the phosphorylation of p65, one subunit of NF-κB, thus led to activation of the NF-κB signaling pathway in prostatic tissues of rats. In turn, the activation of NF-κB pathway induced concomitant upregulation of proinflammatory factors IL-1ß, IL-6, TNF-α, and COX-2 and significant increase of the Bcl2/Bax expression ratio for enhanced cell survival, contributing to the initiation and progression of BPH in rats. Notably, CO therapy significantly decreased prostate weight and hyperplasia in BPH-induced animals. Also CO was found to suppress the expression of 5α-reductase and thus the production of DHT, which is essential for the amelioration of BPH. More importantly, CO was shown to suppress the activation of NF-κB pathway through decreasing the expression of phosphorylated p65 and consequently reduced the inflammatory responses and cell survival in prostatic tissues, leading to the inhibition of BPH development in rats. CONCLUSION: Curcuma oil is very effective for ameliorating BPH in rats. The underlying mechanisms involve in reduced inflammatory responses and cell survival through suppression of the NF-κB signaling pathway by CO in prostatic tissues.