A simple and efficient ratiometric fluorescent probe 1 for hypochlorite has been rationally constructed based on a novel hypochlorite promoted oxidation of N-alkylpyridinium reaction. Notably, this oxidation reaction was first employed for developing fluorescent hypochlorite probe. Upon addition of hypochlorite, probe 1 presented a ratiometric response, with the emission wavelength displaying a remarkable blue shift (up to 143 nm). Probe 1 also provided highly selective and sensitive response to hypochlorite. The detection limit was measured to be 0.093 μM. The sensing reaction product, compound 2, was isolated and confirmed by NMR spectra and mass spectrometry. TD-DFT calculation demonstrated that the intramolecular charge transfer process in compound 2 was significantly inhibited, which result in the large blue shift of emission. Probe 1 has been successfully applied for hypochlorite detection in natural water samples. Living cell imaging experiments established that probe 1 could detect not only artificially loaded but also endogenous hypochlorite in living cells.
Immersed boundary-lattice Boltzmann method (IB-LBM) has become a popular method for studying fluid-structure interaction (FSI) problems. However, the performance issues of the IB-LBM have to be considered when simulating the practical problems. The Graphics Processing Units (GPUs) from NVIDIA offer a possible solution for the parallel computing, while the CPU is a multicore processor that can also improve the parallel performance. This paper proposes a parallel algorithm for IB-LBM on a CPU-GPU heterogeneous platform, in which the CPU not only controls the launch of the kernel function but also performs calculations. According to the relatively local calculation characteristics of IB-LBM and the features of the heterogeneous platform, the flow field is divided into two parts: GPU computing domain and CPU computing domain. CUDA and OpenMP are used for parallel computing on the two computing domains, respectively. Since the calculation time is less than the data transmission time, a buffer is set at the junction of two computational domains. The size of the buffer determines the number of the evolution of the flow field before the data exchange. Therefore, the number of communications can be reduced by increasing buffer size. The performance of the method was investigated and analyzed using the traditional metric MFLUPS. The new algorithm is applied to the computational simulation of red blood cells (RBCs) in Poiseuille flow and through a microchannel.
The normal electrophysiologic behavior of the heart is determined by the integrated activity of specific cardiac ionic currents. Mutations in genes encoding the molecular components of individual cardiac ion currents have been shown to result in multiple cardiac arrhythmia syndromes. Presently, 12 genes associated with inherited long QT syndrome (LQTS) have been identified, and the most common mutations are in the hKCNQ1 (LQT1, Jervell and Lange-Nielson syndrome), hKCNH2 (LQT2), and hSCN5A (LQT3, Brugada syndrome) genes. Several drugs have been withdrawn from the market or received black box labeling due to clinical cases of QT interval prolongation, ventricular arrhythmias, and sudden death. Other drugs have been denied regulatory approval owing to their potential for QT interval prolongation. Further, off-target activity of drugs on cardiac ion channels has been shown to be associated with increased mortality in patients with underlying cardiovascular diseases. Since clinical arrhythmia risk is a major cause for compound termination, preclinical profiling for off-target cardiac ion channel interactions early in the drug discovery process has become common practice in the pharmaceutical industry. In the present study, we report assay development for three cardiac ion channels (hKCNQ1/minK, hCav1.2, and hNav1.5) on the IonWorks Quattro™ system. We demonstrate that these assays can be used as reliable pharmacological profiling tools for cardiac ion channel inhibition to assess compounds for cardiac liability during drug discovery.
In the title coumarin derivative, C 28 H 26 N 2 O 2 , the coumarin unit is approximately planar, with a maximum deviation of 0.048 (3) Å. The central benzene ring is oriented at dihedral angles of 30.15 (14) and 10.51 (11)°, respectively, to the pyridine ring and coumarin ring system. In the crystal, weak C—H...O and C—H...N hydrogen bonds and weak C—H...π interactions link the molecules into a three-dimensional supramolecular architecture.
Monascus, a traditional Chinese fermentation fungus, is used as a natural dietary supplement. As a metabolite of Monascus, g-aminobutyric acid (GABA) had been proven to be a hypotensive agent. In this study, the ability of Monascus pilosus to produce GABA was investigated under solid-state fermentation. Plackett-Burman design (PBD) was applied to seek for the crucial parameters that affect the production of GABA. In addition, central composite design (CCD) was used to optimize each crucial variable. As a result, the maximum GABA production predicted by the CCD was 937.61 mg/kg using 60 g sterilized rice and 0.5% ethanol; optimum values of those crucial coefficients were determined to be monosodium glutamate (MSG) 0.714 (37.14 gkg-1), CaCl22H2O -0.025 (4.4625 gkg-1), and time of anaerobic treatment with CO2 (CO2 Time) -0.1947 (43.327 h). Under the theoretical optimal conditions, the actual GABA production was 884.32 mg/kg, approximately 4.9 times than that before optimization.
A type of sorafenib- (SOR-) loaded long-circulating nanoliposome was constructed, and the targeting performance and antitumor effects of the prepared liposome were evaluated in the present study. Polyethylene glycol- (PEG-) modified long-circulating nanoliposomes (LC-NPs) were designed and prepared using reverse evaporation, and the LC-NPs were used for delivering sorafenib (LC-PEG-SOR-NPs). Then, the anti-VEGFR antibody as a targeting moiety was chemically coupled with LC-PEG-SOR-NPs to form liver cancer-targeted nanoliposomes (anti-VEGFR-LC-PEG-SOR-NPs). The drug entrapment and loading efficiency were measured. And the cancer-targeting performance and therapeutic efficiency were evaluated both in vitro and in vivo . The anti-VEGFR-LC-PEG-SOR-NPs with an average of 119.8±4.2nm showed a uniform spherical structure. The drug entrapment and loading efficiency were 92.5% and 18.5%, respectively. The killing efficiency of anti-VEGFR-LC-PEG-SOR-NPs was up to 18% after incubating with liver cancer cells for 72 h. Furthermore, the anti-VEGFR-LC-PEG-SOR-NPs could actively target at the tumor region and could efficiently inhibit tumor growth with negligible side effects. This newly designed nanoliposomes had desirable dispersibility, high drug entrapment efficiency, tumor targeting and therapeutic efficiency, and good safety. As a biocompatible nanocomposite, it was promising to become a novel and useful tumor-targeting nanodrug for liver cancer therapy.
'/%3e%3cuse xlink:href='%23a' transform='rotate(23.036 .093 25.536)'/%3e%3cuse xlink:href='%23a' transform='rotate(45.87 1.273 16.18)'/%3e%3cuse xlink:href='%23a' transform='rotate(69.945 .996 12.078)'/%3e%3cuse xlink:href='%23a' transform='rotate(20.66 -19.689 31.932)'/%3e%3c/svg%3e)
