The Marine-Derived Oligosaccharide Sulfate (MdOS), a Novel Multiple Tyrosine Kinase Inhibitor, Combats Tumor Angiogenesis both In Vitro and In Vivo

Despite the emerging success of multi-targeted protein tyrosine kinase (PTK) inhibitors in cancer therapy, significant side effects and resistance concerns seems to be avoided unlikely. The aim of the present study was to identify novel multi-targeting PTK inhibitors. The kinase enzymatic activities were measured by enzyme-linked immunosorbent assay (ELISA). The antiproliferative activities in human microvascular endothelial cells (HMECs) were evaluated by sulforhodamine (SRB) assay. The phosphorylation of kinases and their downstream molecules was probed by western blot analysis. The binding mode between MdOS and PTKs was profiled by surface plasmon resonance (SPR) approach and molecular simulation. Tube formation assay, rat aortic ring method and chicken chorioallantoic membrane assay were combined to illustrate the in vitro and in vivo anti-angiogenic effects. Results indicated that MdOS, a novel marine-derived oligosaccharide sulfate, exhibited a broad-spectrum PTK inhibitory action. At an enzymatic level, MdOS inhibited HER2, EGFR, VEGFR, PDGFR, c-Kit, FGFR1 and c-Src, with little impact on FGFR2. In cellular settings, MdOS inhibited phosphorylation of PTKs, exemplified by HER2, EGFR and VEGFR2, and downstream molecules of Erk1/2 and AKT. Further studies demonstrated that MdOS acted as an ATP-competitive inhibitor via directly binding to the residues of entrance rather than those of the ATP-binding pocket. Furthermore, MdOS inhibited proliferation and tube formation of HMECs, arrested microvessel outgrowth of rat aortic rings and hindered the neovascularization of chick allantoic membrane. Taken together, results presented here indicated that MdOS exhibited anti-angiogenic activity in a PTK-dependent manner and make it a promising agent for further evaluation in PTK-associated cancer therapy

Black Phosphorus Q-Switched Large-Mode-Area Tm-Doped Fiber Laser

We report on a passively Q-switched fiber laser with black phosphorus as saturable absorber. By employing the sol-gel fabricated large-mode-area Tm-doped fiber as gain medium, a high-energy Q-switched fiber laser has been demonstrated which delivers the maximum pulse energy of 11.72 μJ with the pulse width of 660 ns at the wavelength of 1954 nm. Our experimental results indicate that BP Q-switched large-mode-area Tm-doped fiber laser is an effective and reliable approach to generate high-energy pulses at 2 μm

Simultaneously Wavelength- and Temperature-Insensitive Mid-Infrared Optical Parametric Amplification with LiGaS₂ Crystal

Ultrafast mid-infrared (mid-IR) lasers with a high pulse repetition rate are in great demand in various fields, including attosecond science and strong-field physics. Due to the lack of suitable mid-IR laser gain medium, optical parametric amplifiers (OPAs) are used to generate an ultrafast mid-IR laser. However, the efficiency of OPA is sensitive to phase mismatches induced by wavelength and temperature deviations from the preset points, which thus limits the pulse duration and the average power of the mid-IR laser. Here, we exploited a noncollinear phase-matching configuration to achieve simultaneously wavelength- and temperature-insensitive mid-IR OPA with a LiGaS2 crystal. The noncollinearity can cancel the first-order dependence of phase matching on both wavelength and temperature. Benefitting from the thermal property of the LiGaS2 crystal, some collinear phase-matching solutions derived from the first-order and even third-order wavelength insensitivity have comparatively large temperature bandwidths and can be regarded as approximate solutions with simultaneous wavelength and temperature insensitivity. These simultaneously wavelength- and temperature-insensitive phase-matching designs are verified through numerical simulations in order to generate few-cycle, high-power mid-IR pulses

Synthesis and Properties of Macrocyclic Butanoic Acid Conjugates as a Promising Delivery Formulation for the Nutrition of Colon

Butanoic acid plays a significant role in the maintenance of mucosal health and is the preferred energy substrate for the cells in the colon. Here, butanoic acid was selectively conjugated to the secondary hydroxyl group of β-cyclodextrin through ester bond using sodium hydride as the deprotonation reagent. The preliminary release behaviors of butanoic acid in rat gastrointestinal tract contents were investigated at 37°C within 12 h. In the contents of stomach, the conjugates did seldom release butanoic acid, released butanoic acid only 5.8% in the contents of small intestine, and released butanoic acid significantly up to 38.4% in the contents of colon. These results indicate that the conjugate activation took place site specifically in the rat colonic contents, via the biodegradation by glycosidases and hydrolases in the colon. Therefore, the β-cyclodextrin conjugates of butanoic acid may be of value as an orally administered colon-specific formulation for the nutrition of colon

Deep Transfer Learning Method Based on Automatic Domain Alignment and Moment Matching

Domain discrepancy is a key research problem in the field of deep domain adaptation. Two main strategies are used to reduce the discrepancy: the parametric method and the nonparametric method. Both methods have achieved good results in practical applications. However, research on whether the combination of the two can further reduce domain discrepancy has not been conducted. Therefore, in this paper, a deep transfer learning method based on automatic domain alignment and moment matching (DA-MM) is proposed. First, an automatic domain alignment layer is embedded in the front of each domain-specific layer of a neural network structure to preliminarily align the source and target domains. Then, a moment matching measure (such as MMD distance) is added between every domain-specific layer to map the source and target domain features output by the alignment layer to a common reproduced Hilbert space. The results of an extensive experimental analysis over several public benchmarks show that DA-MM can reduce the distribution discrepancy between the two domains and improve the domain adaptation performance

Loading Nano-CuO on TiO₂ Nanomeshes towards Efficient Photodegradation of Methylene Blue

In order to improve the photocatalytic activity of TiO2, we successfully loaded nano-CuO on the TiO2 nanomeshes as CuO-TiO2 nanocomposites through a facile electrodeposition method. The optimized calcined temperature after Cu electrodeposition is confirmed as 450 °C, which could furthest assist the crystallization of anatase TiO2 and guarantee the high photocatalytic activity of CuO-TiO2 nanocomposites. Comparing with pure TiO2 nanomeshes, CuO-TiO2 nanocomposites showed better degradability of methylene blue, and the degradation efficiency reached to 35% after 120 min irradiation. Additionally, CuO-TiO2 nanocomposites exhibit much stronger absorption intensity within the visible light scope, more than two times than that of pure TiO2 nanomeshes, which indicates that the loading of nano-CuO could promote photocatalytic efficiency by the strong visible light absorption. Additionally, CuO-TiO2 nanocomposites show faster photocurrent response and lower charge transfer resistance than that of pure TiO2 nanomeshes, which implies that the recombination rate of photogenerated electron-hole pairs was reduced after nano-CuO loading

Loading Nano-CuO on TiO2 Nanomeshes towards Efficient Photodegradation of Methylene Blue

In order to improve the photocatalytic activity of TiO2, we successfully loaded nano-CuO on the TiO2 nanomeshes as CuO-TiO2 nanocomposites through a facile electrodeposition method. The optimized calcined temperature after Cu electrodeposition is confirmed as 450 °C, which could furthest assist the crystallization of anatase TiO2 and guarantee the high photocatalytic activity of CuO-TiO2 nanocomposites. Comparing with pure TiO2 nanomeshes, CuO-TiO2 nanocomposites showed better degradability of methylene blue, and the degradation efficiency reached to 35% after 120 min irradiation. Additionally, CuO-TiO2 nanocomposites exhibit much stronger absorption intensity within the visible light scope, more than two times than that of pure TiO2 nanomeshes, which indicates that the loading of nano-CuO could promote photocatalytic efficiency by the strong visible light absorption. Additionally, CuO-TiO2 nanocomposites show faster photocurrent response and lower charge transfer resistance than that of pure TiO2 nanomeshes, which implies that the recombination rate of photogenerated electron-hole pairs was reduced after nano-CuO loading