Chromatin Remodeling of Colorectal Cancer Liver Metastasis is Mediated by an HGF‐PU.1‐DPP4 Axis

Colorectal cancer (CRC) metastasizes mainly to the liver, which accounts for the majority of CRC-related deaths. Here it is shown that metastatic cells undergo specific chromatin remodeling in the liver. Hepatic growth factor (HGF) induces phosphorylation of PU.1, a pioneer factor, which in turn binds and opens chromatin regions of downstream effector genes. PU.1 increases histone acetylation at the DPP4 locus. Precise epigenetic silencing by CRISPR/dCas9KRAB or CRISPR/dCas9HDAC revealed that individual PU.1-remodeled regulatory elements collectively modulate DPP4 expression and liver metastasis growth. Genetic silencing or pharmacological inhibition of each factor along this chromatin remodeling axis strongly suppressed liver metastasis. Therefore, microenvironment-induced epimutation is an important mechanism for metastatic tumor cells to grow in their new niche. This study presents a potential strategy to target chromatin remodeling in metastatic cancer and the promise of repurposing drugs to treat metastasis

Binding and neutralization of vascular endothelial growth factor (VEGF) and related ligands by VEGF Trap, ranibizumab and bevacizumab

Pharmacological inhibition of VEGF-A has proven to be effective in inhibiting angiogenesis and vascular leak associated with cancers and various eye diseases. However, little information is currently available on the binding kinetics and relative biological activity of various VEGF inhibitors. Therefore, we have evaluated the binding kinetics of two anti-VEGF antibodies, ranibizumab and bevacizumab, and VEGF Trap (also known as aflibercept), a novel type of soluble decoy receptor, with substantially higher affinity than conventional soluble VEGF receptors. VEGF Trap bound to all isoforms of human VEGF-A tested with subpicomolar affinity. Ranibizumab and bevacizumab also bound human VEGF-A, but with markedly lower affinity. The association rate for VEGF Trap binding to VEGF-A was orders of magnitude faster than that measured for bevacizumab and ranibizumab. Similarly, in cell-based bioassays, VEGF Trap inhibited the activation of VEGFR1 and VEGFR2, as well as VEGF-A induced calcium mobilization and migration in human endothelial cells more potently than ranibizumab or bevacizumab. Only VEGF Trap bound human PlGF and VEGF-B, and inhibited VEGFR1 activation and HUVEC migration induced by PlGF. These data differentiate VEGF Trap from ranibizumab and bevacizumab in terms of its markedly higher affinity for VEGF-A, as well as its ability to bind VEGF-B and PlGF

Mild and efficient extraction of fluorescent chlorophyll a from spinach leaves for application as the sustainable emitter in light-emitting electrochemical cells

Natural pigments are sustainable compounds that can be employed as emitters, sensors and sensitisers in optoelectronics. The most abundant pigment, chlorophyll, offers advantages of easily available and plentiful feedstock, biodegradability and non-toxicity. However, strenuous extraction and separation limit its application on larger scale. In this work, a practically mild and scalable extraction and separation method for rapid isolation of chlorophyll a from spinach is presented. Three different stationary phases for column chromatography were evaluated, and a new solvent system was developed for the elution of chlorophyll a on a neutral alumina chromatography column. The purified product was obtained with a yield of 0.98 mg ⋅ g−1 with respect to the dry leaves. A first light-emitting electrochemical cell (LEC) based on chlorophyll a as the emitter is reported, using the extracted chlorophyll a as the guest compound dispersed in a blend-host matrix in a concentration of 2.5 or 5 mass %. The higher-chlorophyll-concentration LEC exhibits emission solely from the chlorophyll emitter, with the main emission peak located at 675 nm. The lower-chlorophyll-concentration LEC features two distinct emission bands, one in the red region that is originating from the chlorophyll guest and one in the blue region (main peak at 430 nm) that stems from the blend host. This combined red:blue emission can be attractive for, e. g., greenhouse applications, since it matches the action spectrum of plant photosynthesis

Mild and Efficient Extraction of Fluorescent Chlorophyll a from Spinach Leaves for Application as the Sustainable Emitter in Light‐Emitting Electrochemical Cells

Abstract Natural pigments are sustainable compounds that can be employed as emitters, sensors and sensitisers in optoelectronics. The most abundant pigment, chlorophyll, offers advantages of easily available and plentiful feedstock, biodegradability and non‐toxicity. However, strenuous extraction and separation limit its application on larger scale. In this work, a practically mild and scalable extraction and separation method for rapid isolation of chlorophyll a from spinach is presented. Three different stationary phases for column chromatography were evaluated, and a new solvent system was developed for the elution of chlorophyll a on a neutral alumina chromatography column. The purified product was obtained with a yield of 0.98 mg ⋅ g−1 with respect to the dry leaves. A first light‐emitting electrochemical cell (LEC) based on chlorophyll a as the emitter is reported, using the extracted chlorophyll a as the guest compound dispersed in a blend‐host matrix in a concentration of 2.5 or 5 mass %. The higher‐chlorophyll‐concentration LEC exhibits emission solely from the chlorophyll emitter, with the main emission peak located at 675 nm. The lower‐chlorophyll‐concentration LEC features two distinct emission bands, one in the red region that is originating from the chlorophyll guest and one in the blue region (main peak at 430 nm) that stems from the blend host. This combined red:blue emission can be attractive for, e. g., greenhouse applications, since it matches the action spectrum of plant photosynthesis

Combining Benzotriazole and Benzodithiophene Host Units in Host-Guest Polymers for Efficient and Stable Near-Infrared Emission from Light-Emitting Electrochemical Cells

A set of host-guest copolymers with alternating benzodithiophene and benzotriazole (BTz) derivatives as host units and 4,7-bis(5-bromothiophen-2-yl)-benzo[c][1,2,5]thiadiazole as the minority guest are synthesized, characterized, and evaluated for applications. A light-emitting electrochemical cell (LEC) comprising such a host-guest copolymer delivers fast-response near-infrared (NIR) emission peaked at 723 nm with a high radiance of 169 mu W cm(-2) at a low drive voltage of 3.6 V. The NIR-LEC also features good stability, as the peak NIR output only drops by 8% after 350 h of continuous operation. It is, however, found that the LEC performance is highly sensitive to the detailed chemical structure of the host backbone, and that the addition of electron-donating thiophene bridging units onto the BTz unit is highly positive while the inclusion of fluorine atoms results in a drastically lowered performance, presumably because of the emergence of hydrogen bonding within the active material

Intense and Stable Near-Infrared Emission from Light-Emitting Electrochemical Cells Comprising a Metal-Free Indacenodithieno[3,2-b]thiophene-Based Copolymer as the Single Emitter

We report on the synthesis, characterization, and application of a series of metal-free near-infrared (NIR) emitting alternating donor/acceptor copolymers based on indacenodithieno[3,2-b]thiophene (IDTT) as the donor unit. A light-emitting electrochemical cell (LEC), comprising a blend of the copolymer poly[indacenodithieno[3,2-b]thiophene-2,8-diyl-alt-2,3-diphenyl-5,8-di(thiophen-2-y1)- quinoxaline-5,5\u27-diy1] and an ionic liquid as the single-layer active material sandwiched between two air-stable electrodes, delivered NIR emission (lambda(peak) = 705 nm) with a high radiance of 129 mu W/cm(2) when driven by a low voltage of 3.4 V. The NIR-LEC also featured good stress stability, as manifested in that the peak NIR output from a nonencapsulated device after 24 h of continuous operation only had dropped by 3% under N-2 atmosphere and by 27% under ambient air. This work accordingly introduces IDTT-based donor/acceptor copolymers as functional metal-free electroluminescent materials in NIR-emitting devices and also provides guidelines for how future NIR emitters should be designed for further improved performance

RZ Pyx: A special short period detached massive binary with two cool stellar companions in a quadruple system

RZ Pyx is one of a small group of short-period B-type eclipsing binaries with an orbital period of 0.656 days. Several new CCD times of light minimum of RZ Pyx were obtained. Together with all available photoelectric and CCD times of light minimum, the changes of the orbital period are investigated for the first time. Meanwhile, previously published light curves are reanalyzed with the Wilson–Devinney code. Based on the analysis of the O–C diagram, two cyclic variations with periods of 37.1 years and 9.7 years are discovered superimposed on a continuous increase at a rate of dP/dt=+0.32×10−7 day yr−1. The light curve solutions suggest that RZ Pyx is a marginal detached binary system where both components do not overfill their respective Roche lobes. The fill-out factors of the primary and the secondary component are 95.5(±0.8)% and 99.1(±1.9)%, respectively, revealing that the secondary is nearly filling its Roche lobe. This may indicate that RZ Pyx has undergone a mass-transferring evolutionary stage and it is on the marginal detached stage temporarily. The long-term increase in the orbital period could be explained by the enhanced mass loss by stellar winds of the two detached massive components. Since the two binary components are early-type stars, the two cyclic oscillations could be plausibly interpreted as the results of the light travel-time effect caused by the presence of two additional companions. It is estimated that the masses of the two additional bodies are no less than 0.36M⊙ and 0.21M⊙, respectively. The two cool stellar companions are orbiting the central binary at orbital separations of 23.1 and 9.5 au in a quadruple stellar system. Both the marginal detached configuration and the presence of two cool stellar companions make RZ Pyx a very interesting binary system for further investigations.Fil: Ergang, Zhao. Chinese Academy of Sciences; República de ChinaFil: Shengbang, Qian. Chinese Academy of Sciences; República de ChinaFil: Linjia, Li. Chinese Academy of Sciences; República de ChinaFil: Fernandez Lajus, Eduardo Eusebio. Universidad Nacional de La Plata; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Astrofísica La Plata. Universidad Nacional de La Plata. Facultad de Ciencias Astronómicas y Geofísicas. Instituto de Astrofísica La Plata; ArgentinaFil: Jia, Zhang. Chinese Academy of Sciences; República de ChinaFil: Xiangdong, Shi. Chinese Academy of Sciences; República de Chin