Design, Synthesis and Biological Evaluation of Novel PEG-Rakicidin B1 Hybrid as Clostridium difficile (CD) Targeted Anti-Bacterial Agent.

Rakicidin B1 was isolated and purified from the culture broth of a marine Streptomyces sp. as a potent anti-cancer agent, and lately the compound and its derivatives have firstly been found to possess anti-Clostridium difficile (CD) activity but with high cytotoxicity. Herein, following our previous discovery on anti-CD activity of Rakicidin B1, structure modification was performed at the OH position of Rakicidin B1 and a new Rakicidin B1-PEG hybrids FIMP2 was facilely designed and synthesized by conjugating the PEG2000 with the scaffolds of Rakicidin B1 via the linkage of carbamate. The cytotoxicity of the FIMP2 was first evaluated against three different cancer cell lines, including HCT-8 cells, PANC-1, and Caco-2, with IC50 values at 0.519 µM, 0.815 µM, and 0.586 µM, respectively. Obviously, as compared with a positive control group treated with Rakicidin B1, the IC50 value of FIMP2 increased by nearly 91-fold, 50-fold, and 67-fold, suggesting that the PEGylation strategy significantly reduced the cytotoxicity of FIMP2. Thus, this preliminary result may be beneficial to increase its safety index (SI) value due to the decreased cytotoxicity of FIMP2. In addition, this decreased cytotoxicity of FIMP2 was further confirmed based on a zebrafish screening model in vivo. Thereafter, the anti-CD activity of FIMP2 was evaluated in vivo, and its efficacy to treat CDI was found to be better than that of vancomycin. The mortality and recurrence rate of FIMP2 is not as low compared with that of vancomycin; these results demonstrated that compound FIMP2 is a new, promising anti-CD agent with significant efficacy against CD recurrence with low cytotoxicity towards bodies.

Facile Transformation from Rofecoxib to a New Near-Infrared Lipid Droplet Fluorescent Probe and Its Investigations on AIE Property, Solvatochromism and Mechanochromism.

Lipid-related cancers cause a large number of deaths worldwide. Therefore, development of highly efficient Lipid droplets (LDs) fluorescent imaging probes will be beneficial to our understanding of lipid-related cancers by allowing us to track the metabolic process of LDs. In this work, a LDs-specific NIR (λmax = 698 nm) probe, namely BY1, was rationally designed and synthesized via a one-step reaction by integrating triphenylamine (electron-donor group) unit into the structure of rofecoxib. This integration strategy enabled the target BY1 to form a strong Donor-Acceptor (D-A) system and endowed BY1 with obvious aggregation-induced emission (AIE) effect. Meanwhile, BY1 also showed observable solvent effect and reversible mechanochromatic luminescent property, which could be interpreted clearly via density functional theory (DFT) calculations, differential scanning calorimetry (DSC), powder X-ray diffraction (XPRD), and single crystal X-ray data analysis. More importantly, BY1 exhibited highly specific fluorescent imaging ability (Pearson's correlation = 0.97) towards lipid droplets in living HeLa cells with low cytotoxicity. These results demonstrated that BY1 is a new promising fluorescent probe for lipid droplets imaging, and it might be beneficial to facilitate biological research of lipid-related cancers.

One-Step Transformations from ACQ Luminogens to DSEgens via the Boc Protection Process.

Dual-state emission luminogens (DSEgens), as a new type of luminescent materials that can effectively emit light in solution and solid state, have attracted tremendous attention due to their potential application in chemical sensing, biological imaging, organic electronic devices, etc. In this study, two new rofecoxib derivatives ROIN and ROIN-B have been synthesized, and their photophysical properties are fully investigated by experimental studies and theoretical calculations. The key intermediate ROIN, resulting from one-step conjugation of rofecoxib with an indole unit, shows the classical aggregation-caused quenching (ACQ) effect. Meanwhile, by introducing a tert-butoxycarbonyl (Boc) group on the basis of ROIN without enlarging the π conjugation system, ROIN-B was successfully developed with an obvious DSE property. In addition, both fluorescent behaviors and their transformation from ACQ to DSE were elucidated clearly by going through the analysis of their single X-ray data. Moreover, the target ROIN-B, as a new DSEgens, also displays reversible mechanofluorochromism and lipid droplet-specific imaging ability in HeLa cells. Taken together, this work proposes a precise molecular design strategy to afford a new DSEgens, which may provide guidance for the future exploration of new DSEgens.

A portable low-power integrated current and temperature laser controller for high-sensitivity gas sensor applications.

A low-noise, low power, high modulation-bandwidth design integrated laser current and temperature driver with excellent long-term stability is described. The current driver circuit is based on the Hall-Libbrecht design. A high sensitivity and a stable driver current were obtained using a differential amplifier and an integral amplifier. The set-point voltage for the current driver came from an ultra-compact, ultra-low temperature coefficient voltage reference chip or the digital to analog convertor output of a microcontroller or a modulation signal. An integral temperature chip, referred to as ADN8834, was used to drive the thermoelectric cooler controller of the distributed feedback (DFB) laser. The internal amplifier acquired the feedback current of the temperature sensor. The proportional-integral-derivative parameters such as proportion, integration, and derivative were set by external resistors. The short- and long-term stability and linearity of the developed laser driver were tested using a DFB laser with a central wavelength of 6991 cm-1. The laser driver was validated for high-sensitivity gas sensing of CO2 and C2H2 via a laser absorption spectroscopy experiment. The limits of detection were less than 11.5 ppm and 0.124 ppm for CO2 and C2H2, respectively. Direct absorption measurements and the 1-f and 2-f demodulation signals confirmed the capabilities of the proposed laser driver system in high-sensitivity gas sensing applications. The driver unit can readily be accommodated into many portable laser sensing devices for industrial applications.

Quantum speed limit and a signal of quantum criticality.

We study the quantum speed limit time (QSLT) of a coupled system consisting of a central spin and its surrounding environment, and the environment is described by a general XY spin-chain model. For initial pure state, we find that the local anomalous enhancement of the QSLT occurs near the critical point. In addition, we investigate the QSLT for arbitrary time-evolution state in the whole dynamics process and find that the QSLT will decay monotonously and rapidly at a large size of environment near the quantum critical point. These anomalous behaviors in the critical vicinity of XY spin-chain environment can be used to indicate the quantum phase transition point. Especially for the XX spin-chain environment, we find that the QSLT displays a sudden transition from discontinuous segmented values to a steady value at the critical point. In this case, the non-Makovianity and the Loschmidt echo are incapable of signaling the critical value of the transverse field, while the QSLT can still witness the quantum phase transition. So, the QSLT provides a further insight and sharper identification of quantum criticality.