A fluorescent probe for monitoring sulfite in living cells with large Stokes shift and rapid response.

Sulfite (SO32-) is considered as a monitor of a wide range of physiological processes. However, cells and tissues are adversely affected when the body ingests high level of sulfite. Here, we designed and synthesized a "turn on" fluorescent probe ImiSft-1 with 2-cyano-N-methylacetamide as the specific recognition site of SO32-. This probe predominantly achieved high response intensity to SO32- and desirable properties such as large Stokes shift (∼180 nm), fast response time (within 15 s), and high sensitivity (LOD = 0.12 µM). Importantly, the probe was highly selective for sulfite from other bio-species including biological thiols. Other functional properties included broad pH adaptability (5.0-10.0) and low cytotoxicity. Given these advantages and the fluorescence imaging in living MCF-7 cells, it was demonstrated that probe ImiSft-1 could monitor the changes of sulfite concentration in living cells.

Discovery of derivatives from Spartina alterniflora-sourced moiety as xanthine oxidase inhibitors to lower uric acid.

In this work, hit compounds Spartinin F1-F20 sharing the Spartina alterniflora-sourced ferulic acid backbone were synthesized and evaluated on inhibiting xanthine oxidase and lowering uric acid level. The top hit Spartinin F2 exhibited inhibition percentages at 10 µM dosage as high as 84.48 (higher than that of the positive control allopurinol) and low cyto-toxicity. Spartinin F2 inferred potential efficiency in lowering the serum UA level (from 631.6 µM to 295.0 µM), which was comparable with allopurinol (to 309.2 µM). Spartinin F2 was also beneficial for other serum indexes. The bioavailability of Spartinin F2 was 63.71% from the preliminary pharmacokinetics test and the molecular docking simulation indicated that except for retaining the hydrogen bonds with the key residues such as THR 1010 and LYS 771, the introduction of the π-sulfur interactions via the sulfonate might also be beneficial for developing more potent XO inhibitors.

Discovery of novel aminophosphonate derivatives containing pyrazole moiety as potential selective COX-2 inhibitors.

Cyclooxygenase is critical for maintaining physiological functions, whereas overexpression of COX-2 was closely implicated in various cancers. In this study, a series of novel aminophosphonate derivatives containing pyrazole moiety were synthesized with their anti-cancer activity evaluated. In vitro assays of the target compounds showed that Z21 displayed excellent COX-2 inhibitory activity against COX-2 (IC50 = 0.22 ± 0.04 µM) and anti-proliferative activity against MCF-7 cell (IC50 = 4.37 ± 0.49 µM). The apoptosis induction of compound Z21 was confirmed by flow cytometry and polymerase chain reaction. Further investigation demonstrated that compound Z21 induced apoptosis of MCF-7 cells through a mitochondrion-dependent pathway and involved cell-cycle arrest in G2 phase. Overall, these results provided some new insights into the design of therapeutic drugs for COX-2 inhibitors and indicated the connection between selective COX-2 inhibition and the anti-tumor activity.

Demonstration of a fully integrated superconducting receiver with a 2.7 THz quantum cascade laser.

We demonstrate for the first time the integration of a superconducting hot electron bolometer (HEB) mixer and a quantum cascade laser (QCL) on the same 4-K stage of a single cryostat, which is of particular interest for terahertz (THz) HEB/QCL integrated heterodyne receivers for practical applications. Two key issues are addressed. Firstly, a low power consumption QCL is adopted for preventing its heat dissipation from destroying the HEB's superconductivity. Secondly, a simple spherical lens located on the same 4-K stage is introduced to optimize the coupling between the HEB and the QCL, which has relatively limited output power owing to low input direct current (DC) power. Note that simulation techniques are used to design the HEB/QCL integrated heterodyne receiver to avoid the need for mechanical tuning. The integrated HEB/QCL receiver shows an uncorrected noise temperature of 1500 K at 2.7 THz, which is better than the performance of the same receiver with all the components not integrated.

A NIR-triggered multifunctional nanoplatform mediated by Hsp70 siRNA for chemo-hypothermal photothermal synergistic therapy.

Recently, hypothermal photothermal therapy (HPTT) seemed essential for the future clinical transformation of cancer optical therapies. However, at a lower working temperature, heat shock proteins (HSPs) seriously affect the anti-tumor effect of HPTT. This work reports a reasonable design of a dual-responsive nanoplatform for the synergistic treatment of chemotherapy and HPTT. We adopted a one-step method to wrap indocyanine green (ICG) into imidazole skeleton-8 (ZIF-8) and further loaded it with the chemotherapy drug doxorubicin (DOX). Furthermore, we introduced Hsp-70 siRNA to block the affection of HSPs at an upstream node, thereby avoiding the side effects of traditional heat shock protein inhibitors. The prepared ZIF-8@ICG@DOX@siRNA nanoparticles (ZID-Si NPs) could significantly improve the stability of siRNA to effectively down-regulate the expression of HSP70 protein during the photothermal therapy, thus realizing the pH-controlled and NIR-triggered release of the chemotherapeutical drug DOX. Moreover, tumors were also imaged accurately by ICG wrapped in ZID-Si nanoparticles. After the evaluation of the in vitro and in vivo photothermal effect as well as the anti-tumor activity, we found that the added Hsp-70 siRNA enhanced the synergistic anti-cancer activity of HPTT and chemotherapy. In summary, this work holds great potential in cancer treatment, and suggests better efficacy of synergistic chemo/HPTT than the single-agent therapy.

A quasi-optical vector near-field measurement system at terahertz band.

This paper describes a vector near-field measurement system at terahertz band based on a high sensitivity superconducting receiver equipped with a quasi-optical probe for high resolution near-field sensing. A novel single-receiver rather than commonly used dual-receiver configuration is adopted for vector measurement. Performances of the measurement system including stability and dynamic range are studied. Vector near-field measurement of a diagonal feedhorn at 850 GHz is presented and shows good agreement with simulation and direct far-field measurement.