Cancer associated fibroblasts (CAFs) are key stroma cells that play dominant roles in tumor progression. However, the CAFs-derived molecular determinants that regulate colorectal cancer (CRC) ...metastasis and chemoresistance have not been fully characterized.
CAFs and NFs were obtained from fresh CRC and adjacent normal tissues. Exosomes were isolated from conditioned medium and serum of CRC patients using ultracentrifugation method and ExoQuick Exosome Precipitation Solution kit, and characterized by transmission electronic microscopy, nanosight and western blot. MicroRNA microarray was employed to identify differentially expressed miRNAs in exosomes secreted by CAFs or NFs. The internalization of exosomes, transfer of miR-92a-3p was observed by immunofluorescence. Boyden chamber migration and invasion, cell counting kit-8, flow cytometry, plate colony formation, sphere formation assays, tail vein injection and primary colon cancer liver metastasis assays were employed to explore the effect of NFs, CAFs and exosomes secreted by them on epithelial-mesenchymal transition, stemness, metastasis and chemotherapy resistance of CRC. Luciferase report assay, real-time qPCR, western blot, immunofluorescence, and immunohistochemistry staining were employed to explore the regulation of CRC metastasis and chemotherapy resistance by miR-92a-3p, FBXW7 and MOAP1.
CAFs promote the stemness, epithelial-mesenchymal transition (EMT), metastasis and chemotherapy resistance of CRC cells. Importantly, CAFs exert their roles by directly transferring exosomes to CRC cells, leading to a significant increase of miR-92a-3p level in CRC cells. Mechanically, increased expression of miR-92a-3p activates Wnt/β-catenin pathway and inhibits mitochondrial apoptosis by directly inhibiting FBXW7 and MOAP1, contributing to cell stemness, EMT, metastasis and 5-FU/L-OHP resistance in CRC. Clinically, miR-92a-3p expression is significantly increased in CRC tissues and negatively correlated with the levels of FBXW7 and MOAP1 in CRC specimens, and high expression of exosomal miR-92a-3p in serum was highly linked with metastasis and chemotherapy resistance in CRC patients.
CAFs secreted exosomes promote metastasis and chemotherapy resistance of CRC. Inhibiting exosomal miR-92a-3p provides an alternative modality for the prediction and treatment of metastasis and chemotherapy resistance in CRC.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Visualizing individual molecules with chemical recognition is a longstanding target in catalysis, molecular nanotechnology and biotechnology. Molecular vibrations provide a valuable 'fingerprint' for ...such identification. Vibrational spectroscopy based on tip-enhanced Raman scattering allows us to access the spectral signals of molecular species very efficiently via the strong localized plasmonic fields produced at the tip apex. However, the best spatial resolution of the tip-enhanced Raman scattering imaging is still limited to 3-15 nanometres, which is not adequate for resolving a single molecule chemically. Here we demonstrate Raman spectral imaging with spatial resolution below one nanometre, resolving the inner structure and surface configuration of a single molecule. This is achieved by spectrally matching the resonance of the nanocavity plasmon to the molecular vibronic transitions, particularly the downward transition responsible for the emission of Raman photons. This matching is made possible by the extremely precise tuning capability provided by scanning tunnelling microscopy. Experimental evidence suggests that the highly confined and broadband nature of the nanocavity plasmon field in the tunnelling gap is essential for ultrahigh-resolution imaging through the generation of an efficient double-resonance enhancement for both Raman excitation and Raman emission. Our technique not only allows for chemical imaging at the single-molecule level, but also offers a new way to study the optical processes and photochemistry of a single molecule.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Dislocation interaction with and accumulation at twin boundaries have been reported to significantly improve the strength and ductility of nanostructured face-centered cubic (fcc) metals and alloys. ...Here we systematically describe plausible dislocation interactions at twin boundaries. Depending on the characteristics of the dislocations and the driving stress, possible dislocation reactions at twin boundaries include cross-slip into the twinning plane to cause twin growth or de-twinning, formation of a sessile stair-rod dislocation at the twin boundary, and transmission across the twin boundary. The energy barriers for these dislocation reactions are described and compared.
Alkaline conditioning of the amidoxime based adsorbents is a significant step in the preparation of the adsorbent for uranium uptake from seawater. The effects of various alkaline conditioning ...parameters such as the type of alkaline reagent, reaction temperature, and reaction time were investigated with respect to uranium adsorption capacity from simulated seawater (spiked with 8 ppm uranium) and natural seawater (from Sequim Bay, WA). An adsorbent (AF1) was prepared at the Oak Ridge National Laboratory by radiation-induced graft polymerization (RIGP) with acrylonitrile and itaconic acid onto high-surface-area polyethylene fibers. For the AF1 adsorbent, sodium hydroxide emerged as a better reagent for alkaline conditioning over potassium hydroxide, which has typically been used in previous studies, because of higher uranium uptake capacity and lower cost over the other candidate alkaline reagents investigated in this study. Use of sodium hydroxide in place of potassium hydroxide is shown to result in a 21–30% decrease in the cost of uranium recovery.
ABSTRACT
Using the precise times of mid‐egress of the eclipsing polar HU Aqr, we discovered that this polar is orbited by two or more giant planets. The two planets detected so far have masses of at ...least 5.9 and 4.5MJup. Their respective distances from the polar are 3.6 and 5.4 au with periods of 6.54 and 11.96 yr, respectively. The observed rate of decrease of period derived from the downward parabolic change in the observed − calculated (O − C) curve is a factor of 15 larger than the value expected for gravitational radiation. This indicates that it may be only a part of a long‐period cyclic variation, revealing the presence of one more planet. It is interesting to note that the two detected circumbinary planets follow the Titus–Bode law of solar planets with n= 5 and 6. We estimate that another 10 yr of observations will reveal the presence of the predicted third planet.
Isoprene emitted by vegetation is an important precursor of secondary organic aerosol (SOA), but the mechanism and yields are uncertain. Aerosol is prevailingly aqueous under the humid conditions ...typical of isoprene-emitting regions. Here we develop an aqueous-phase mechanism for isoprene SOA formation coupled to a detailed gas-phase isoprene oxidation scheme. The mechanism is based on aerosol reactive uptake coefficients (γ) for water-soluble isoprene oxidation products, including sensitivity to aerosol acidity and nucleophile concentrations. We apply this mechanism to simulation of aircraft (SEAC4RS) and ground-based (SOAS) observations over the southeast US in summer 2013 using the GEOS-Chem chemical transport model. Emissions of nitrogen oxides (NOx ≡ NO + NO2) over the southeast US are such that the peroxy radicals produced from isoprene oxidation (ISOPO2) react significantly with both NO (high-NOx pathway) and HO2 (low-NOx pathway), leading to different suites of isoprene SOA precursors. We find a mean SOA mass yield of 3.3 % from isoprene oxidation, consistent with the observed relationship of total fine organic aerosol (OA) and formaldehyde (a product of isoprene oxidation). Isoprene SOA production is mainly contributed by two immediate gas-phase precursors, isoprene epoxydiols (IEPOX, 58 % of isoprene SOA) from the low-NOx pathway and glyoxal (28 %) from both low- and high-NOx pathways. This speciation is consistent with observations of IEPOX SOA from SOAS and SEAC4RS. Observations show a strong relationship between IEPOX SOA and sulfate aerosol that we explain as due to the effect of sulfate on aerosol acidity and volume. Isoprene SOA concentrations increase as NOx emissions decrease (favoring the low-NOx pathway for isoprene oxidation), but decrease more strongly as SO2 emissions decrease (due to the effect of sulfate on aerosol acidity and volume). The US Environmental Protection Agency (EPA) projects 2013–2025 decreases in anthropogenic emissions of 34 % for NOx (leading to a 7 % increase in isoprene SOA) and 48 % for SO2 (35 % decrease in isoprene SOA). Reducing SO2 emissions decreases sulfate and isoprene SOA by a similar magnitude, representing a factor of 2 co-benefit for PM2.5 from SO2 emission controls.
Abstract
V410 Aur is a known deep and low-mass-ratio contact binary with a spectroscopically tertiary component and a visual companion. However, the physical and orbital properties of the tertiary ...are unknown. We constructed (
O
−
C
) curve with 117 new eclipse times and those collected from the literature, which shows a cyclical variation with a period of 25.44 (±1.17) yr and a projected semimajor axis of 0.0348 (±0.0021) days while it undergoes a long-term period decrease at a rate of
dP
/
dt
= −1.58 × 10
−7
daysyr
−1
. The cyclical variation is analyzed for the light-travel time effect. The minimum mass of the third body is determined as 1.39 (±0.13)
M
⊙
that is much larger than the inferred value (0.97
M
⊙
) of spectroscopic investigation, which indicates that the spectroscopically tertiary is a single-lined spectroscopic binary with an unseen component. The maximum orbital semimajor axis 6.19 (±0.67) au of the third body is determined. Gaia detected a visual companion to V410 Aur at practically the same distance from the Sun nicely confirming the physical bond. These results reveal that V410 Aur contains a single-lined spectroscopic binary with a visual companion in a quintuple stellar system. TESS photometric solutions confirmed that V410 Aur is a deep overcontact binary with a fill-out factor of 73.83(88)% where the additional light contribution is about 24.80(18)%. The continuous variations of light curves are explained by the evolution of a dark spot on the more massive component. The parabolic variation in the (
O
−
C
) curve may be caused by the mass transfer from the massive component to the less massive one in the deep overcontact binary.
Powerful terahertz (THz) radiation is observed from large-scale underdense preplasmas in front of a solid target irradiated obliquely with picosecond relativistic intense laser pulses. The radiation ...covers an extremely broad spectrum with about 70% of its energy located in the high frequency regime over 10 THz. The pulse energy of the radiation is found to be above 100 μJ per steradian in the laser specular direction at an optimal preplasma scale length around 40-50 μm. Particle-in-cell simulations indicate that the radiation is mainly produced by linear mode conversion from electron plasma waves, which are excited successively via stimulated Raman scattering instability and self-modulated laser wakefields during the laser propagation in the preplasma. This radiation can be used not only as a powerful source for applications, but also as a unique diagnostic of parametric instabilities of laser propagation in plasmas.
In this paper, we report on the discovery of an optical flare observed in the R band from the red-dwarf eclipsing binary CU Cancri, whose component stars are at the upper boundary of full convection ...(M
1= 0.43 M⊙ and M
2= 0.4 M⊙, where M⊙ is the solar mass). The amplitude of the flare is the largest among those detected in the R band (∼0.52 mag) and the duration time is about 73 min. Like flares observed on the Sun, quasi-periodic oscillations were seen during and after the flare. Three more R-band flares were found by follow-up monitoring. In total, this binary was monitored photometrically by using an R filter for 79.9 h, which has revealed an R-band flare rate of about 0.05 flares per hour. Together with other strong chromospheric and coronal activities (i.e. very strong Hα and Hβ emission features and an extreme ultraviolet and X-ray source), these detections indicate that it has very strong magnetic activity. Therefore, the apparent faintness (∼1.4 mag in the V band) of CU Cnc, compared with other single red dwarfs of the same mass, can be plausibly explained by the high coverage of dark spots.
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